Second-Line Therapy for Advanced NSCLC.

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Weiss, Jared M; Stinchcombe, Thomas E

2013-01-01

Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.

Influence of [18F] fluorodeoxyglucose positron emission tomography on salvage treatment decision making for locally persistent nasopharyngeal carcinoma

International Nuclear Information System (INIS)

Zheng Xiaojang; Chen Longhua; Wang Quanshi; Wu Fubing

2006-01-01

Purpose: The purpose of this study was to evaluate the role of [ 18 F] fluorodeoxyglucose positron emission tomography (FDG-PET) in influencing salvage treatment decision making for locally persistent nasopharyngeal carcinoma (NPC). Methods and Materials: A total of 33 NPC patients with histologic persistence at nasopharynx 1 to 6 weeks after a full course of radiotherapy underwent both computed tomography (CT) and FDG-PET/CT simulation at the same treatment position. The salvage treatment decisions, with regard to the decision to offer salvage treatment and the definition of gross tumor volume (GTV), were made before knowledge of the FDG-PET findings. Subsequently the salvage treatment decisions were made again based on the FDG-PET findings and compared with the pre-FDG-PET decisions. Results: All 33 patients were referred for salvage treatment in the pre-FDG-PET decision. After knowledge of the FDG-PET results, the decision to offer salvage treatment was withdrawn in 4 of 33 patients (12.1%), as no abnormal uptake of FDG was found at nasopharynx. Spontaneous remission was observed in repeat biopsies and no local recurrence was found in these 4 cases. For the remaining 29 patients, GTV based on FDG-PET was smaller than GTV based on CT in 24 (82.8%) cases and was greater in 5 (17.2%) cases, respectively. The target volume had to be significantly modified in 9 of 29 patients (31%), as GTV based on FDG-PET images failed to be enclosed by the treated volume in the salvage treatment plan performed based on GTV based on CT simulation images. Conclusion: Use of FDG-PET was found to influence the salvage treatment decision making for locally persistent NPC by identifying patients who were not likely to benefit from additional treatment and by improving accuracy of GTV definition in salvage treatment planning

Travel distance and use of salvage palliative chemotherapy in patients with metastatic colorectal cancer.

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Ahmed, Shahid; Iqbal, Mahjabeen; Le, Duc; Iqbal, Nayyer; Pahwa, Punam

2018-04-01

Salvage palliative chemotherapy in metastatic colorectal cancer has been associated with significant improvement in survival. However, not all patients receive all available therapies. Travel burden can affect patient access and use of future therapy. The present study aims to determine relationship between travel distance (TD) and salvage palliative chemotherapy in patients with metastatic colorectal cancer. A patient cohort diagnosed with metastatic colorectal cancer during 2006-2010 in the province of Saskatchewan, Canada was studied. Logistic regression analyses were performed to assess relationship between travel distance and subsequent line therapies. The median age of 264 eligible patients was 62 years [interquartile range (IQR): 53-72]. The patients who received salvage systemic therapy had a median distance to travel of 60.0 km (IQR: 4.7-144) compared with 88.1 km (IQR: 4.8-189) if they did not receive second- or third-line therapy (P=0.06). In multivariate analysis distance to the cancer center therapies. Our result revealed that travel distance to the cancer center greater than 100 km was associated less frequent use of second or subsequent line therapies in patients with metastatic colorectal cancer.

Elucidation of salvage laryngectomy pathologic and clinical variables to guide further treatment intensification investigation.

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Scharpf, Joseph; Ward, Matthew; Adelstein, David; Koyfman, Shlomo; Li, Mingsi

2018-04-01

There are limited treatment options beyond surgical salvage for patients who fail nonoperative treatment for laryngeal squamous cell carcinoma. In this study, we examine the failure patterns after surgical salvage and the potential pathologic and clinical prognostic variables that might guide further postoperative intensification investigation. Retrospective analysis at a tertiary academic referral center. From an institutional review board-approved institutional head and neck cancer registry, a consecutive series of 147 patients who underwent salvage laryngectomy for squamous cell cancer recurrence or persistence after radiotherapy with or without chemotherapy between May 1995 and May 2016 were identified. Variables potentially associated with oncologic outcome after surgical salvage were then collected and retrospectively evaluated. The projected 2-year locoregional failure rate was 21.8% (95% confidence interval [CI], 14.6%-29.0%]), and the overall survival 65% (95% CI, 57.5%-74.3%) for the entire cohort after salvage laryngectomy. On multivariable analysis, sarcomatoid/spindle cell pathology (hazard ratio [HR], 3.147; 95% CI, 1.181-8.386; P = 0.022), lymphovascular space invasion (LVSI) (positive vs. negative; HR, 2.31; 95% CI, 1.21-4.42; P = 0.011), and advanced initial American Joint Committee on Cancer 7th Edition grouped stage (stages III-IVB vs. stages I-II; HR, 1.64; 95% CI, 1.04-2.6; P = 0.035) were found to be independently associated with inferior disease-free survival. No other clinical or pathologic variables predicted failure. Salvage laryngectomy after nonoperative treatment failure results in successful locoregional control rates and survival in the majority of patients failing initial therapy. This should temper enthusiasm for routine treatment intensification with postoperative re-irradiation and/or other systemic treatments for the vast majority of patients. Sarcomatoid pathology, LVSI, and an advanced initial stage are associated with inferior

Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

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Pearson, Edward; McGarry, Lisa; Gala, Smeet; Nieset, Christopher; Nanavaty, Merena; Mwamburi, Mkaya; Levy, Yair

2016-04-01

Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

International Nuclear Information System (INIS)

Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett; Scardino, Peter T.; Eastham, James A.; Zelefsky, Michael J.

2012-01-01

Purpose: To review the impact of high–dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases–free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988–2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases–free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p 0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by

Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

Energy Technology Data Exchange (ETDEWEB)

Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

2012-09-01

Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes. Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose {>=}66 Gy, of whom 205 (72%) received doses {>=}70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response. Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score {>=}7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose {>=}70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose {>=}70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07). Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in

Salvage robotic radical prostatectomy

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Samuel D Kaffenberger

2014-01-01

Full Text Available Failure of non-surgical primary treatment for localized prostate cancer is a common occurrence, with rates of disease recurrence ranging from 20% to 60%. In a large proportion of patients, disease recurrence is clinically localized and therefore potentially curable. Unfortunately, due to the complex and potentially morbid nature of salvage treatment, radical salvage surgery is uncommonly performed. In an attempt to decrease the morbidity of salvage therapy without sacrificing oncologic efficacy, a number of experienced centers have utilized robotic assistance to perform minimally invasive salvage radical prostatectomy. Herein, we critically evaluate the existing literature on salvage robotic radical prostatectomy with a focus on patient selection, perioperative complications and functional and early oncologic outcomes. These results are compared with contemporary and historical open salvage radical prostatectomy series and supplemented with insights we have gained from our experience with salvage robotic radical prostatectomy. The body of evidence by which conclusions regarding the efficacy and safety of robotic salvage radical prostatectomy can be drawn comprises fewer than 200 patients with limited follow-up. Preliminary results are promising and some outcomes have been favorable when compared with contemporary open salvage prostatectomy series. Advantages of the robotic platform in the performance of salvage radical prostatectomy include decreased blood loss, short length of stay and improved visualization. Greater experience is required to confirm the long-term oncologic efficacy and functional outcomes as well as the generalizability of results achieved at experienced centers.

Efficacy and Safety of Capecitabine, Irinotecan, Gemcitabine, and Bevacizumab as Second-Line Treatment in Advanced Biliary Tract Cancer

DEFF Research Database (Denmark)

Larsen, Finn Ole; Markussen, Alice; Diness, Laura V

2018-01-01

, there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. METHODS: From November 2013 to January 2016, 50 patients with advanced...

Reduced dose of salvage-line regorafenib monotherapy for metastatic colorectal cancer in Japan.

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Hirano, Gen; Makiyama, Akitaka; Makiyama, Chinatsu; Esaki, Taito; Oda, Hisanobu; Uchino, Keita; Komoda, Masato; Tanaka, Risa; Matsushita, Yuzo; Mitsugi, Kenji; Shibata, Yoshihiro; Kumagai, Hozumi; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Akashi, Koichi; Baba, Eishi

2015-01-01

Salvage-line regorafenib monotherapy exhibited a marked survival benefit for metastatic colorectal cancer (mCRC). However, the toxicity of this regimen has resulted in the clinical use of a reduced dose of regorafenib. Thirty-two Japanese mCRC patients (median age=61 years) who had been treated with regorafenib were retrospectively examined. Best objective response rate was 0% and stable disease (SD) was 31%. Median progression-free survival was 81 days and median overall survival was 233 days. Adverse events of any grade were observed in all patients: 17 (53%) patients suffered grade 3 or 4 adverse events including fatigue (13%), anorexia (13%), hand-foot skin reaction (22%) and elevations of alanine aminotransferase/aspartate aminotransferase (19%/16%). One patient with grade 5 liver dysfunction was identified (3%). Twenty-nine (91%) patients required treatment dose reduction or a delay in treatment. The relative dose intensity was 59%. Regorafenib treatments were terminated because of disease progression (59%) or adverse events (34%). Despite a decrease in the intensity of regorafenib treatment, because of severe adverse events, a fairly favorable efficacy was achieved in Japanese patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Single-Stage Treatment of Osteomyelitis for Digital Salvage by Using an Antibiotic-Eluting, Methylmethacrylate Joint-Spanning Spacer.

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Aimé, Victoria L; Kidwell, John T; Webb, Leland H

2017-06-01

Osteomyelitis of the digit is a challenging problem that can result in amputation. We describe 13 cases of osteomyelitis involving bones of the hand managed with a novel technique. We reviewed records of 12 patients (13 digits) who had joint-spanning, antibiotic-eluting (tobramycin or vancomycin), methylmethacrylate spacers placed as definitive, single-stage treatment for digital osteomyelitis. The primary outcome was digit salvage. Secondary outcomes were infection eradication (no recurrence at 3 months) and spacer removal. Patients were followed up until the infection resolved (ie, no cutaneous signs of infection, including pain, erythema, or swelling). At a mean of 24 months, 10 of 13 infections had successful one-stage treatment. One patient required a second operation to revise a soft tissue flap but the spacer remained in place. Two spacers were removed because of malalignment. An antibiotic-eluting methylmethacrylate spacer is an innovative treatment for digital osteomyelitis. In 12 consecutive patients (13 digits), we successfully salvaged the digit. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Epirubicin plus paclitaxel regimen as second-line treatment of patients with small-cell lung cancer.

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Pasello, Giulia; Carli, Paolo; Canova, Fabio; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Urso, Loredana; Conte, Pierfranco; Favaretto, Adolfo

2015-04-01

Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. The aim of this study was to describe activity and safety of second-line with epirubicin at 70 mg/m(2) followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of six cycles. This is a retrospective review of all patients with SCLC evaluated for second-line treatment between 2003 and 2013 at our Institution. Sixty-eight patients received the study regimen of epirubicin with paclitaxel. We observed partial response in 19 (30%), stable disease in 22 (34%) and total early failure rate in 23 (36%) patients. Median progression free and overall survival were 21.8 and 26.5 weeks, respectively. Haematological toxicities were as follows: grade 3-4 leukopenia and neutropenia in 18 (31%) and 30 (22%) of patients, respectively; grade 3 anaemia and grade 4 thrombocytopenia were reported in 2 (3%) and 5 (9%) of patients, respectively. Epirubicin with paclitaxel is an active and tolerable second-line regimen in patients with SCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Salvage Treatment for Recurrent Intracranial Germinoma After Reduced-Volume Radiotherapy: A Single-Institution Experience and Review of the Literature

International Nuclear Information System (INIS)

Hu, Yu-Wen; Huang, Pin-I; Wong, Tai-Tong; Ho, Donald Ming-Tak; Chang, Kai-Ping; Guo, Wan-Yuo; Chang, Feng-Chi; Shiau, Cheng-Yin; Liang, Muh-Lii; Lee, Yi-Yen

2012-01-01

Purpose: Intracranial germinomas (IGs) are highly curable with radiotherapy (RT). However, recurrence still occurs, especially when limited-field RT is applied, and the optimal salvage therapy remains controversial. Methods and Materials: Between January 1989 and December 2010, 14 patients with clinically or pathologically diagnosed recurrent IGs after RT were reviewed at our institution. Of these, 11 received focal-field RT, and the other 3 received whole-brain irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the respective first course of RT. In addition, we identified from the literature 88 patients with recurrent IGs after reduced-volume RT, in whom the details of salvage therapy were recorded. Results: The median time to recurrence was 30.3 months (range, 3.8–134.9 months). One patient did not receive further treatment and was lost during follow-up. Of the patients, 7 underwent salvage with craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median follow-up time was 105.1 months (range, 24.2–180.9 months). Three patients died without evidence of disease progression: two from second malignancies and one from unknown cause. The others remained disease free. The 3-year survival rate after recurrence was 83.3%. A total of 102 patients from our study and the literature review were analyzed to determine the factors affecting prognosis and outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all patients and for those receiving salvage CSI, respectively. Univariate analysis showed that initial RT volume, initial RT dose, initial CT, and salvage RT type were significant prognostic predictors of survival. On multivariable analysis, salvage CSI was the most significant factor (p = 0.03). Conclusions: Protracted follow-up is recommended because late recurrence is not uncommon. CSI with or without CT is an effective

Qualitative study of patients’ decision-making when accepting second-line treatment after failure of first-line chemotherapy

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Roch, Benoît; Roth, Caroline; Mérel, Jean-Pierre

2018-01-01

Objective Treatment failures in advanced lung cancer are frequent events affecting patients during or after first-line chemotherapy. International guidelines recommend second-line chemotherapy. However, around one half of patients who experience disease progression enter a systemic second-line therapy. In the herein qualitative study, we investigated patients' thoughts and attitudes determining the decision to undergo a second-line chemotherapy. Methods Thirty-three purposively selected patients who recently accepted second-line or palliative chemotherapy were invited to participate in this survey consisting of semi-structured in-depth interviews. Grounded theory was applied to investigate participants’ perceptions of the context that have surrounded their decision to undergo palliative chemotherapy. Results For most patients, tumor burden and reduced quality of life in relation with lung cancer itself were major drivers of the decision-making process. There was a balance between two different attitudes: making a decision to undergo a new line of chemotherapy or starting a psychological process in order to accept end of life. Choosing between these two attitudes allowed the patient to keep the matter of palliative care at a distance. Even in case of low chance of success, many patients who worried about their life partner's future would accept a new chemotherapy line. Some patients experienced ambivalent thoughts regarding social network, particularly about their family as daily function impairment required an increased need for relative's support. The initial "Worrying about others" thoughts left place to in an increasing self-need of care as those provided by relatives; this phenomenon might increase patients' self- perception of being a burden for others. Confidence previously established with formal caregiver support was another major decision driver: some patients with sustained confidence in their medical staff may have privileged this formal support rather

Advanced colorectal cancer, refractory to infusional fluorouracil treatment: efficacy of second line fluorouracil in combination with a different biochemical modulation

NARCIS (Netherlands)

van Halteren, H. K.; Wagener, D. J.; Vreugdenhil, G.; Punt, C. J.

1997-01-01

Currently there is no standard second line treatment for patients with advanced colorectal cancer (ACC). Previous reports have demonstrated that some patients may benefit from second line infusional 5-fluorouracil (5-FU) after failing 5-FU bolus treatment. We retrospectively studied the efficacy and

Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. A comparative analysis

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Romagna, Alexander; Schwartz, Christoph; Tonn, Joerg-Christian; Kreth, Friedrich-Wilhelm [Ludwig-Maximilians-University, Department of Neurosurgery, Munich (Germany); Egensperger, Rupert [Ludwig-Maximilians-University, Center for Neuropathology and Prion Research, Munich (Germany); Watson, Juliana; Belka, Claus; Nachbichler, Silke Birgit [Ludwig-Maximilians-University, Department of Radiation-Oncology, Munich (Germany)

2016-11-15

Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy{sub 3} and 249.6 Gy{sub 3}). No toxicity-related risk factors were identified. SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment. (orig.) [German] Daten zu Risiko und Effizienz ablativer

Effect of post-fire salvage logging treatments on micobiological properties of two different soils in the Povince of Alicante.

Science.gov (United States)

Arcenegui, Victoria

2017-04-01

It is well known that the natural wildfire regime in Mediterranean forests is greatly disturbed by human activities. Fire can induce temporal or permanent changes in the soil (see Certini, 2005) and can retard or compromise the recovery of the ecosystem afterwards. Changes in soil properties and the impact on soil functions depend mainly on the severity of the fires (Neary et al., 1999) and type of soil and weather during and after burning (Robichaud & Hungerford, 2000). Post-fire management can have an additional impact on the ecosystem; in some cases, even more severe than the fire. Post-fire salvage logging treatments are very frequently but its ecological impact is uncertain. Mainly because there are so many variables at play. A research has been done in "Sierra de Mariola Natural Park" in Alcoi (M) and ''Cabo de San Antonio'' in Javea (J), both in the Province of Alicante (E Spain). A big forest fire (>500 has) occurred in July 2012 and in September 2014 respectively. After fire, salvage logging (SL) treatment were done. In the first area (M), with a soil classified as Typic Xerorthent, extraction of the burned wood using heavy machinery was applied. In contrast, in the second area (J), a Rhodoxeralf soil, not heavy machinery was used. Plots for monitoring this effect were installed in both areas and in a similar nearby area where no treatment was done, and then used as control (C) for comparison. Soil samplings were done immediately after treatment and 4 years and two years in M site and J site respectively. We examined the effect of salvage logging on basal soil respiration (BSR), and microbial biomass carbon (Cmic). Our results showed that in site M four years after the treatment, the plots without treatment showed a much better improvement for the properties monitored. And not differences were found in site J after two years of monitoring. The impact of salvage logging was different depending on the soil type and the way to do the treatment.

Proposed salvage treatment strategy for biochemical failure after radical prostatectomy in patients with prostate cancer: a retrospective study

International Nuclear Information System (INIS)

Miyake, Makito; Tanaka, Nobumichi; Asakawa, Isao; Morizawa, Yosuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Hasegawa, Masatoshi; Konishi, Noboru; Fujimoto, Kiyohide

2014-01-01

Treatment options for patients with recurrent disease after radical prostatectomy include salvage radiotherapy of the prostatic bed and/or androgen deprivation therapy. To establish an effective treatment strategy for recurrent disease after radical prostatectomy, we retrospectively analyzed the outcome of salvage radiation monotherapy in such cases. Data from 61 men who had undergone salvage radiation monotherapy for biochemical recurrent disease after radical prostatectomy were retrospectively reviewed. In all patients, salvage radiotherapy consisted of iraradiation to the prostatic bed (70 Gy) using three-dimensional conformal radiotherapy techniques. Treatment outcome was analyzed to identify predictive factors of salvage radiotherapy. The biochemical recurrence-free survival after salvage radiation monotherapy at 2 and 5 years was 55% and 38%, respectively. Cox proportional regression models revealed that the independent predictive factors for biochemical recurrence were Gleason Score ≥ 8, negative surgical margin, and PSA velocity ≥ 0.38 ng/mL/year. Negative surgical margin and PSA velocity ≥ 0.8 ng/mL/year were significantly associated with poor response in the serum PSA levels after salvage radiotherapy. Based on our findings, we propose a treatment strategy for biochemical recurrent disease after radical prostatectomy. Patients with Gleason score ≤ 7, positive surgical margin, and PSA velocity < 0.38 ng/mL/year are categorized the most favorable group, so that eradication by salvage radiation monotherapy could be expected. Other patients could be divided to two groups depending on surgical margin status and PSA velocity: 1) patients who might require combination of SRT and short-term androgen deprivation therapy and 2) patients who should be treated by androgen deprivation monotherapy

Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for malaria in children in Guinea-Bissau

DEFF Research Database (Denmark)

Kofoed, Poul-Erik; Rodrigues, Amabelia; Aaby, Peter

2006-01-01

BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo...... sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later. METHODS: Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine...

Comparison of Efficacy and Safety of Different Therapeutic Regimens as 
Second-line Treatment for Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Zhihua LI

2015-05-01

Full Text Available Background and objective Small-cell lung cancer (SCLC is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress after the first-line therapy. The evidence of a benefit from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the efficacy and safety of different second-line treatment regimens. Methods We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC, and the rest 152 patients received second-line chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. The endpoints were objective response rate (ORR, disease control rate (DCR, progression-free survival (PFS, and overall survival (OS. Results Patients administered second-line chemotherapy lived significantly longer, with a total OS from first-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001, and the ORR, DCR, PFS and OS of the former (including the sensitive disease and resistance/refractory disease patients were obviously better than that of the latter. The ORR and DCR of the patients who received second-line chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second-line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line chemotherapy were divided by types of second-line regimens. The sensitive disease patients were from group A (VP-16-based rechallenge and group B1 (CPT-11-based regimen. The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6% and 58.8%, respectively. There was no statistically significant difference (P=0.264; P=0

Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.

Directory of Open Access Journals (Sweden)

Julie H Levison

Full Text Available We investigated the prevalence of wild-type virus (no major drug resistance and drug resistance mutations at second-line antiretroviral treatment (ART failure in a large HIV treatment program in South Africa.HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%. Mean duration on ART (SD prior to initiation of second-line ART was 23 (17 months, and time from second-line ART initiation to failure was 10 (9 months. Plasma samples were obtained 7(9 months from confirmed failure. At second-line failure, 22 patients (67% had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5 months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

Directory of Open Access Journals (Sweden)

Samsuddin Khan

2014-07-01

Full Text Available Background: There are limited data on the failure of second-line antiretroviral therapy (ART and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective: To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL testing. Design: This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results: A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62% responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0. No serious treatment-related adverse events were recorded. Conclusions: With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL

Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation.

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Trevisani, Franco; Brandi, Giovanni; Garuti, Francesca; Barbera, Maria Aurelia; Tortora, Raffaella; Casadei Gardini, Andrea; Granito, Alessandro; Tovoli, Francesco; De Lorenzo, Stefania; Inghilesi, Andrea Lorenzo; Foschi, Francesco Giuseppe; Bernardi, Mauro; Marra, Fabio; Sacco, Rodolfo; Di Costanzo, Giovan Giuseppe

2018-02-01

Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [PSS: 17.3 (10.5-24.1) vs. 7.8 (5.2-10.1) months, (p = 0.035)]. Treatment toxicity was low and easily manageable with dose modulation. MC may be an efficient and safe second-line systemic therapy for HCC patients who discontinued sorafenib for toxicity or tumor progression.

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

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Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

Role of salvage esophagectomy after definitive chemoradiotherapy

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Tachimori, Yuji

2009-01-01

Chemoradiotherapy has become a popular definitive therapy among many patients and oncologists for potentially resectable esophageal carcinoma. Although the complete response rates are high and short-term survival is favorable after chemoradiotherapy, persistent or recurrent locoregional disease is quite frequent. Salvage surgery is the sole curative intent treatment option for this course. As experience with definitive chemoradiotherapy grows, the number of salvage surgeries may increase. Selected articles about salvage esophagectomy after definitive chemoradiotherapy for esophageal carcinoma are reviewed. The number of salvage surgeries was significantly lower than the number of expected candidates. To identify candidates for salvage surgery, patients undergoing definitive chemoradiotherapy should be followed up carefully. Salvage esophagectomy is difficult when dissecting fibrotic masses from irradiated tissues. Patients who underwent salvage esophagectomy had increased morbidity and mortality. Pulmonary complications such as pneumonia and acute respiratory distress syndrome were common. The anastomotic leak rate was significantly increased because of the effects of the radiation administered to the tissues used as conduits. The most significant factor associated with long-term survival appeared to be complete resection. However, precise evaluation of resectability before operation was difficult. Nevertheless, increased morbidity and mortality will be acceptable in exchange for potential long-term survival after salvage esophagectomy. Such treatment should be considered for carefully selected patients at specialized centers. (author)

Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases.

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Thibault, Isabelle; Campbell, Mikki; Tseng, Chia-Lin; Atenafu, Eshetu G; Letourneau, Daniel; Yu, Eugene; Cho, B C John; Lee, Young K; Fehlings, Michael G; Sahgal, Arjun

2015-10-01

We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (Pinitial SBRT is a feasible and efficacious salvage treatment option. Copyright © 2015 Elsevier Inc. All rights reserved.

Original Article Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage Ill/TV neuroblastoma

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Abdel Rahman, M.; Zekri, W.Z.K.; Moussa, E.A.M.; El Debawy, E.; Mostafa, N.E.; Yones, A.; Ezzat, S.; Rayan, A.

2011-01-01

Neuroblastoma is the most common extracranial and deadly solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at h igh risk o f treatment failure. The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients. Patients and methods: Sixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%). Results: They were 40 males (60.6%) and 26 females (39.4%). Patients' age ranged between 3 months and 12.5 years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%)'died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%). Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy. By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR. Conclusion: Chemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation

Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

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Kongsted, Per; Svane, Inge M; Lindberg, Henriette

2016-01-01

To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

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Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

2012-01-01

Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

Phase II study of biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastro-oesophageal cancer

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Schønnemann, K R; Yilmaz, Mette Karen; Bjerregaard, J K

2012-01-01

The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma.......The purpose of this phase II trial was to evaluate the efficacy and safety of cetuximab and irinotecan as second-line treatment in patients with gastro-oesophageal adenocarcinoma....

A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma.

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Kim, Young Saing; Lee, Soon Il; Park, Se Hoon; Park, Silvia; Hwang, In Gyu; Lee, Sang-Cheol; Sun, Jong-Mu; Lee, Jeeyun; Lim, Ho Yeong

2016-02-01

The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic urothelial carcinoma. Weekly docetaxel was well tolerated but demonstrated modest activity, with a response rate of 6%, a median progression-free survival (PFS) of 1.4 months, and a median overall survival (OS) of 8.3 months. The dichotomy between PFS and OS was likely associated with subsequent platinum-based chemotherapy received by 58% of the patients. Docetaxel is commonly used for second-line therapy for metastatic urothelial carcinoma (UC). However, myelosuppression is a substantial concern when the traditional 3-week docetaxel cycle is used. The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic UC. Patients with progression after previous platinum-based chemotherapy for advanced or metastatic disease were treated with docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. The primary endpoint was the response rate. The study enrolled 31 patients. Their median age was 64 years (range, 40-79 years). An Eastern Cooperative Oncology Group performance status of 1, liver metastasis, and a hemoglobin level chemotherapy had been administered for metastatic disease in 29 patients (94%). Although fatigue (13%) and anorexia (6%) were the most frequently observed grade 3 to 4 toxicities, the safety profiles were generally mild and manageable. Two patients (6%) achieved an objective response, which was maintained for 3.0 to 7.8 months. Eight patients experienced disease stabilization (disease control rate, 32%). The median progression-free survival (PFS) and overall survival (OS) were 1.4 months (95% confidence interval [CI], 1.3-1.6) and 8.3 months (95% CI, 5.9-10.6), respectively. A relatively long OS was associated with further salvage platinum-based chemotherapy (n = 18, 58%) showing an encouraging activity (response rate, 44%; median PFS, 4.0 months

Use of antibiotic beads to salvage infected breast implants.

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Sherif, Rami D; Ingargiola, Michael; Sanati-Mehrizy, Paymon; Torina, Philip J; Harmaty, Marco A

2017-10-01

When an implant becomes infected, implant salvage is often performed where the implant is removed, capsulectomy is performed, and a new implant is inserted. The patient is discharged with a PICC line and 6-8 weeks of intravenous (IV) antibiotics. This method has variable success and subjects the patient to long-term systemic antibiotics. In the 1960s, the use of antibiotic-impregnated beads for the treatment of chronic osteomyelitis was described. These beads deliver antibiotic directly to the site of the infection, thereby eliminating the complications of systemic IV antibiotics. This study aimed to present a case series illustrating the use of STIMULAN calcium sulfate beads loaded with vancomycin and tobramycin to increase the rate of salvage of the infected implant and forgo IV antibiotics. A retrospective analysis was performed of patients who were treated at Mount Sinai Hospital for implant infection with salvage and antibiotic beads. Twelve patients were identified, 10 of whom had breast cancer. Comorbidities included hypertension, smoking, and immunocompromised status. Infections were noted anywhere from 5 days to 8 years postoperatively. Salvage was successful in 9 out of the 12 infected implants using antibiotic bead therapy without home IV antibiotics. The use of antibiotic beads is promising for salvaging infected breast implants without IV antibiotics. Seventy-five percent of the implants were successfully salvaged. Of the three patients who had unsalvageable implants, one was infected with antibiotic-resistant Rhodococcus that was refractory to bead therapy and one was noncompliant with postoperative instructions. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

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Thompson, Scott M.; Callstrom, Matthew R.; McKusick, Michael A.; Woodrum, David A.

2015-01-01

PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA

Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

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Thompson, Scott M., E-mail: Thompson.scott@mayo.edu [Mayo Clinic, Mayo Graduate School, Mayo Medical School and the Mayo Clinic Medical Scientist Training Program, College of Medicine (United States); Callstrom, Matthew R., E-mail: callstrom.matthew@mayo.edu; McKusick, Michael A., E-mail: mckusick.michael@mayo.edu; Woodrum, David A., E-mail: woodrum.david@mayo.edu [Mayo Clinic, Department of Radiology, College of Medicine (United States)

2015-10-15

PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA.

Airway necrosis after salvage esophagectomy

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Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

2010-01-01

Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

Operative shortening of the sling as a second-line treatment after TVT failure

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Matuszewski, Marcin; Michajłowski, Jerzy; Krajka, Kazimierz

2011-01-01

Introduction Stress urinary incontinence (SUI) is defined as an involuntary loss of urine during physical exertion, sneezing, coughing, laughing, or other activities that put pressure on the bladder. In some cases, recurrent or persistent SUI after sling operations may be caused by too loose placement of the sling. In the current study, we describe our method of shortening of the sling as a second-line treatment of tension-free vaginal tape (TVT) failure. Materials and methods Four women, aged 46-61, after initial TVT operation were treated for persistent SUI. The severity of SUI was estimated by: physical examinations, cough tests, 24-h pad tests, and King's Health Questionnaire. The shortening procedure, based on excising the fragment of tape and suturing it back, was performed in all patients. Results All cases achieved a good result, which was defined as restoration of full continence. No complications occurred. The 12-month follow-up showed no side-effects. The postoperative control tests: the cough and 24-h pad tests were negative in all women. The general health perceptions increased after the shortening procedure by a mean value 44.25%. The incontinence impact decreased by a mean value 44.6%. In all patients, role and physical limitations significantly decreased (by 88.5% and 80.5%, respectively). The negative emotions connected with SUI significantly decreased after the second procedure. Conclusions The operative shortening of the implanted sling is a simple, cheap, and effective method of second-line treatment in cases of TVT failure and may be offered to the majority of patients with insufficient urethral support after the first procedure. PMID:24578885

External and internal hemipelvectomy for sarcomas of the pelvic girdle : consequences of limb-salvage treatment

NARCIS (Netherlands)

Ham, SJ; Veth, RPH; van Horn, [No Value; Eisma, WH; Hoekstra, HJ; Schraffordt Koops, H.

1997-01-01

The outcome of different Limb-saving treatment modalities for pelvic girdle sarcoma is controversial. The oncological and functional results after 11 external and 10 internal hemipelvectomies and the consequences of limb-salvage treatment were studied in 21 consecutive patients with primary bone (19

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

NARCIS (Netherlands)

Solin, Lawrence J.; Fourquet, Alain; Vicini, Frank A.; Taylor, Marie; Haffty, Bruce; Strom, Eric A.; Wai, Elaine; Pierce, Lori J.; Marks, Lawrence B.; Bartelink, Harry; Campana, Francois; McNeese, Marsha D.; Jhingran, Anuja; Olivotto, Ivo A.; Bijker, Nina; Hwang, Wei-Ting

2005-01-01

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of

Second-Line Treatment Options in Non-Small-Cell Lung Cancer: Report From an International Experts Panel Meeting of the Italian Association of Thoracic Oncology

NARCIS (Netherlands)

Gridelli, Cesare; Baas, Paul; Barlesi, Fabrice; Ciardiello, Fortunato; Crinò, Lucio; Felip, Enriqueta; Gadgeel, Shirish; Papadimitrakopoulou, Vali; Paz-Ares, Luis; Planchard, David; Perol, Maurice; Hanna, Nasser; Sgambato, Assunta; Casaluce, Francesca; de Marinis, Filippo

2017-01-01

Non-small-cell lung cancer (NSCLC) patients inevitably progress to first-line therapy and further active treatments are warranted. In the past few years, new second-line therapies, beyond chemotherapy agents, have become available in clinical practice. To date, several options for the second-line

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

International Nuclear Information System (INIS)

Wadasaki, Koichi; Kaneyasu, Yuko; Kenjo, Masahiro; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Ito, Katsuhide; Kiriu, Hiroshi; Ito, Atsushi

2007-01-01

The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate±seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate±seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe. (author)

Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort.

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Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

2015-06-30

Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.

Salvage Stereotactic Body Radiotherapy (SBRT) Following In-Field Failure of Initial SBRT for Spinal Metastases

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Thibault, Isabelle; Campbell, Mikki [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Chia-Lin [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Atenafu, Eshetu G. [Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Letourneau, Daniel [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Yu, Eugene [Department of Radiology, University Health Network, University of Toronto, Toronto, Ontario (Canada); Cho, B.C. John [Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada); Lee, Young K. [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Fehlings, Michael G. [Department of Radiology, University Health Network, University of Toronto, Toronto, Ontario (Canada); Sahgal, Arjun, E-mail: arjun.sahgal@sunnybrook.ca [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario (Canada)

2015-10-01

Purpose: We report our experience in salvaging spinal metastases initially irradiated with stereotactic body radiation therapy (SBRT), who subsequently progressed with imaging-confirmed local tumor progression, and were re-irradiated with a salvage second SBRT course to the same level. Methods and Materials: From a prospective database, 56 metastatic spinal segments in 40 patients were identified as having been irradiated with a salvage second SBRT course to the same level. In addition, 24 of 56 (42.9%) segments had initially been irradiated with conventional external beam radiation therapy before the first course of SBRT. Local control (LC) was defined as no progression on magnetic resonance imaging at the treated segment, and calculated according to the competing risk model. Overall survival (OS) was evaluated for each patient treated by use of the Kaplan-Meier method. Results: The median salvage second SBRT total dose and number of fractions was 30 Gy in 4 fractions (range, 20-35 Gy in 2-5 fractions), and for the first course of SBRT was 24 Gy in 2 fractions (range, 20-35 Gy in 1-5 fractions). The median follow-up time after salvage second SBRT was 6.8 months (range, 0.9-39 months), the median OS was 10.0 months, and the 1-year OS rate was 48%. A longer time interval between the first and second SBRT courses predicted for better OS (P=.02). The crude LC was 77% (43/56), the 1-year LC rate was 81%, and the median time to local failure was 3.0 months (range, 2.7-16.7 months). Of the 13 local failures, 85% (11/13) and 46% (6/13) showed progression within the epidural space and paraspinal soft tissues, respectively. Absence of baseline paraspinal disease predicted for better LC (P<.01). No radiation-induced vertebral compression fractures or cases of myelopathy were observed. Conclusion: A second course of spine SBRT, most often with 30 Gy in 4 fractions, for spinal metastases that failed initial SBRT is a feasible and efficacious salvage treatment option.

Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

DEFF Research Database (Denmark)

Desmonde, Sophie; Eboua, François T; Malateste, Karen

2015-01-01

BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric Ie...... post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....

Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.

Science.gov (United States)

Granito, Alessandro; Marinelli, Sara; Terzi, Eleonora; Piscaglia, Fabio; Renzulli, Matteo; Venerandi, Laura; Benevento, Francesca; Bolondi, Luigi

2015-06-01

No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

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Häggblom, Amanda; Santacatterina, Michele; Neogi, Ujjwal; Gisslen, Magnus; Hejdeman, Bo; Flamholc, Leo; Sönnerborg, Anders

2017-01-01

Switch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART. Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF). Most patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96) and 3.20 (95% 2.65-3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART. In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

Directory of Open Access Journals (Sweden)

Amanda Häggblom

Full Text Available Switch from first line antiretroviral therapy (ART to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART.Data from 869 patients with 14601 clinical visits between 1999-2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF.Most patients (n = 495; 57.0% switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2% or without drug resistance mutations (DRM (n = 250; 28.8% experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90-3.96 and 3.20 (95% 2.65-3.75, respectively compared with those who switched without VF (4.53 years. Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART.In the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

Science.gov (United States)

Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

2017-05-01

Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

Pharmacoeconomic analysis of the use of first- and second-line drugs in the treatment of multiple sclerosis

Directory of Open Access Journals (Sweden)

V. R. Mkrtchyan

2015-01-01

Full Text Available Objective: to make a pharmacoeconomic comparison of the administration of first- and second-line drugs in the treatment of multiple sclerosis through cost, cost-effectiveness, and budget impact analyses using the 2015 state prices.Material and methods. A pharmacoeconomic analysis was carried out on the basis of the data available in the literature on trials of the effects of the drugs on the rates of exacerbations and disability. On calculating, the authors took into account the current standards for the out- and inpatient management of patients with this nosological entity in accordance with the compulsory health insurance (CHI program; prices for state drug purchases in March 2015; prices for medical services in compliance with the CHI standards in Moscow in 2015; the average sizes of minimum wage, salary, and disability grants with consideration for a discount rate of 3%. The cost-effectiveness and budget impact analyses were performed for intramuscular interferon (INF-β1a (avonex, 30 μg, subcutaneous INF-β1a (rebif, 44 μg, subcutaneous INF-β1b (ronbetal, 8,000,000 IU, subcutaneous INF-β1b (betaferon, 9,600,000 IU, subcutaneous glatiramer acetate (copaxone, 20 mg, intravenous natalizumab (tyzabri, 300 mg, and oral fingolimod (gilenya, 0.5 mg.Results and discussion. The second-line drug tyzabri outperforms the first-line agents for cost-effectiveness. The first-line drugs betaferon and copaxone is slightly exceeded in this indicator by tyzabri; the other both first- and second-line agents compared are all the more inferior in this indicator. The budget impact analysis has shown that the cost of the second-line drugs was higher than that of the first-line ones.

Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer. A systematic review and meta-analysis of published studies.

Science.gov (United States)

Iacovelli, Roberto; Pietrantonio, Filippo; Farcomeni, Alessio; Maggi, Claudia; Palazzo, Antonella; Ricchini, Francesca; de Braud, Filippo; Di Bartolomeo, Maria

2014-01-01

Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79-0.85; posterior probability HR≥1: Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient's performance status. New trials based on a better patient stratification are awaited.

Clinical study of salvage surgery after concurrent chemoradiotherapy

International Nuclear Information System (INIS)

Shimane, Toshikazu; Nakamura, Taisuke; Shimotatara, Yuko

2013-01-01

As the use of concurrent chemoradiotherapy (CCRT) is becoming more widespread, with numerous facilities performing it to maintain function and form, the number of cases requiring salvage surgery is also increasing. We investigated the postoperative prognosis of patients who experienced complications during salvage surgery after CCRT. Subjects were 27 patients who underwent salvage surgery following CCRT at our department during the 7-year period between January 2005 and December 2011. We selected all cases of salvage surgery, comprising neck dissections, total laryngectomies, partial laryngectomies, esophageal resections, and reconstructive surgeries, for analysis. The results were favorable, with a complication rate during salvage surgery after CCRT of 14.8% and a survival rate of 77.8%. Although it is difficult to compare these complications and outcome findings with available reports on salvage surgery without CCRT, it is believed complications can arise in approximately half of the cases. Thus, surgeons should be cognizant of the potential for serious complications, which are sometimes unexpected. Different from our findings, the prognosis following salvage surgery is generally not thought to be favorable and therefore care should be taken to detect recurrence and provide treatment early in salvage surgery cases. (author)

Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study.

Science.gov (United States)

Bares, R; Khalid, N; Daniel, H; Dittmann, H; Reimold, M; Gallwitz, B; Schmotzer, C

2016-07-01

Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.

Failure pattern and salvage treatment after radical treatment of head and neck cancer

DEFF Research Database (Denmark)

Pagh, Anja; Grau, Cai; Overgaard, Jens

2016-01-01

Purpose The aim of the study was to test the hypothesis that head and neck cancer (HNC) patients benefit from specialized follow-up (FU), as this strategy ensures timely detection of relapses for successful salvage treatment. This was done by evaluation of the pattern of failure, the temporal...... recordings of recurrent disease in 567 patients with primary tumors of the larynx, pharynx, oral cavity, nasal cavity, paranasal sinuses and salivary glands. A review of medical records was performed in order to update and supplement the database. Results Failures of the 567 patients were primarily in T...

Efficacy and safety of sequential versus quadruple therapy as second-line treatment for helicobacter pylori infection-A randomized controlled trial.

Directory of Open Access Journals (Sweden)

Daniela Munteanu

Full Text Available Quadruple therapy is recommended as second-line treatment for Helicobacter pylori eradication failure. However, high cost, multiple side effects, and low adherence rates are major drawbacks to its routine use. Our aim was to compare the efficacy and safety of sequential versus quadruple regimens as second line treatment for persistent Helicobacter pylori infection.Prospective, randomized, open label trial was conducted at a large academic, tertiary care center in Israel. Patients who previously failed a standard triple treatment eradication course were randomly assigned (1:1 to receive a 10-day sequential therapy course, or a 14-day quadruple regimen. Compliance and adverse events were evaluated by telephone questionnaires. The primary endpoint for analysis was the rate of Helicobacter pylori eradication as defined by either a negative 13C-urea breath-test, or stool antigen test, 4-16 weeks after treatment assessed under the non-inferiority hypothesis. The trial was terminated prematurely due to low recruitment rates. See S1 Checklist for CONSORT checklist.One hundred and one patients were randomized. Per modified intention-to-treat analysis, eradication rate was 49% in the sequential versus 42.5% in the quadruple regimen group (p-value for non-inferiority 0.02. Forty-two (84.0% versus 33 (64.7% patients completed treatment in the sequential and quadruple groups respectively (p 0.027. Gastrointestinal side effects were more common in the quadruple regimen group.Sequential treatment when used as a second line regimen, was non-inferior to the standard of care quadruple regimen in achieving Helicobacter pylori eradication, and was associated with better compliance and fewer adverse effects. Both treatment protocols failed to show an adequate eradication rate in the population of Southern Israel.ClinicalTrials.gov NCT01481844.

Salvage treatment after r-interferon α-2a in advanced neuroendocrine tumors

International Nuclear Information System (INIS)

Zilembo, N.; Buzzoni, R.; Bajetta, E.; Di Bartolomeo, M.; De Braud, F.; Castellani, R.; Maffioli, L.; Celio, L.; Villa, E.; Lorusso, V.; Fosser, V.; Buzzi, F.

1993-01-01

The use of interferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN α-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIBG uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m 2 intravenously days 1, 2, 3 and epirubicin 75 mg/m 2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective. (orig.)

Local recurrence risk after previous salvage mastectomy.

Science.gov (United States)

Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

2016-07-01

Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

Partial medial second toe pulp free flap and dermal substitute with skin graft for salvage reconstruction of a complete skin envelope degloving of the small finger.

Science.gov (United States)

Calafat, V; Strugarek, C; Montoya-Faivre, D; Dap, F; Dautel, G

2018-04-04

Skin envelope degloving of fingers are rare injuries that require rapid care and surgical treatment. Mostly caused by ring finger injuries, these traumas include bone, tendon and neurovascular pedicle damage. The authors present an unusual case of finger degloving limited exclusively to the skin envelope, without skeletal, tendinous or vascular lesion. This rare case of skin envelope degloving rendered microsurgical revascularization impossible. The authors report the results at 12 months following salvage reconstruction combining a partial second toe pulp free flap for the volar side and a dermal substitute with a thin skin graft for the dorsum. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Malignant bone tumors and limb-salvage surgery in children

International Nuclear Information System (INIS)

Meyer, James S.; Mackenzie, William

2004-01-01

Limb-salvage surgery plays a major role in the management of children with malignant bone tumors. This article provides background on the clinical presentation and imaging evaluation of children with malignant bone tumors and describes various limb-salvage procedures used in the treatment of these children. (orig.)

Timber salvage economics

Science.gov (United States)

Jeffrey P. Prestemon; Thomas P. Holmes

2008-01-01

Timber salvage is commonly done following natural disturbances, to recover some value from damaged forests. Decision making about salvage, however, is affected by ownership objectives, the nature of the damage agent, site factors, and the strength of the local timber market. For profit-maximizing landowners, salvage decisions must balance the cost of harvesting...

Quality of Life in Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer Using Cabazitaxel or Other Therapies After Previous Docetaxel Chemotherapy: Swiss Observational Treatment Registry.

Science.gov (United States)

Stenner, Frank; Rothschild, Sacha I; Betticher, Daniel; Caspar, Clemens; Morant, Rudolf; Popescu, Razvan; Rauch, Daniel; Huber, Urs; Zenhäusern, Reinhard; Rentsch, Cyrill; Cathomas, Richard

2017-08-24

The aim was to evaluate quality of life (QoL), pain, and fatigue in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with different regimens after first-line docetaxel, as well as disease progression. Patients with mCRPC having received first-line chemotherapy with docetaxel were eligible. Second-line treatment choice was at the discretion of the local investigator. All patients had regular assessments of QoL with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, of fatigue with the Brief Fatigue Inventory, and of pain with the McGill Pain Questionnaire-Short Form. The primary end point was QoL maintenance defined as having a maximum decrease in 2 functional domains of the FACT-P. One hundred thirty-eight patients were included in 36 oncology centers across Switzerland. QoL analysis was available for all patients (59 who received cabazitaxel; 79 who received other therapy [OT] including 75 who received abiraterone). No significant differences for any of the end points were found between groups. A numerically higher number of patients had QoL maintenance with OT (25 of 79 patients, 32%) compared with cabazitaxel (8 of 59 patients, 14%). QoL improvement was found in 20% of patients (12 of 59) who received cabazitaxel and 24% (19 of 79) who received OT. Mean FACT-P score did not change in a clinically relevant manner over time in either group. Pain was present in 70% of patients (96 of 138), and a pain response to treatment was noted in 22% (13 of 59) who received cabazitaxel and 29% (23 of 79) who received OT. A similar but minor improvement of fatigue was noted in both groups. Some degree of QoL decrease was seen in most patients regardless of second-line treatment. No significant differences in QoL parameters between cabazitaxel or other second line treatments were found. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study

International Nuclear Information System (INIS)

Chen, Kuo-Hsing; Shao, Yu-Yun; Chen, Ho-Min; Lin, Yu-Lin; Lin, Zhong-Zhe; Lai, Mei-Shu; Cheng, Ann-Lii; Yeh, Kun-Huei

2016-01-01

Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004–2010) and National Health Insurance (2004–2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08–1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18–1.78, P = .0003). Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC

Survival predictors for second-line chemotherapy in Caucasian patients with metastatic gastric cancer

OpenAIRE

Bohanes, Pierre; Courvoisier, Delphine; Perneger, Thomas; Morel, Philippe; Huber, Olivier; Roth, Arnaud

2011-01-01

There are very limited data suggesting a benefit for second-line chemotherapy in advanced gastric cancer. Therefore, the number of patients who receive further treatment after failure of first-line chemotherapy varies considerably, ranging from 14% to 75%. In the absence of a demonstrated survival benefit of second-line chemotherapy, appropriate selection of patients based on survival predictors is essential. However, no clinico-pathologic parameters are currently widely adopted in clinical p...

Effect of Primary Tumor Location on Second- or Later-line Treatment Outcomes in Patients With RAS Wild-type Metastatic Colorectal Cancer and All Treatment Lines in Patients With RAS Mutations in Four Randomized Panitumumab Studies.

Science.gov (United States)

Boeckx, Nele; Koukakis, Reija; Op de Beeck, Ken; Rolfo, Christian; Van Camp, Guy; Siena, Salvatore; Tabernero, Josep; Douillard, Jean-Yves; André, Thierry; Peeters, Marc

2018-03-08

The primary tumor location has a prognostic impact in metastatic colorectal cancer (mCRC). We report the results from retrospective analyses assessing the effect of tumor location on prognosis and efficacy of second- and later-line panitumumab treatment in patients with RAS wild-type (WT) mCRC and on prognosis in all lines of treatment in patients with RAS mutant (MT) mCRC. RAS WT data (n = 483) from 2 randomized phase III panitumumab trials (ClinicalTrials.gov identifiers, NCT00339183 and NCT00113763) were analyzed for treatment outcomes stratified by tumor location. The second analysis assessed the effect of tumor location in RAS MT patients (n = 1205) from 4 panitumumab studies (ClinicalTrials.gov identifiers, NCT00364013, NCT00819780, NCT00339183, and NCT00113763). Primary tumors located in the cecum to transverse colon were coded as right-sided; those located from the splenic flexure to the rectum were coded as left-sided. Of all patients, the tumor location was ascertained for 83% to 88%; 71% to 77% of patients had left-sided tumors. RAS WT patients with right-sided tumors did worse for all efficacy parameters compared with those with left-sided tumors. The patients with left-sided tumors had better outcomes with panitumumab than with the comparator treatment. Because of the low patient numbers, no conclusions could be drawn for right-sided mCRC. The prognostic effect of tumor location on survival was unclear for RAS MT patients. These retrospective analyses have confirmed that RAS WT right-sided mCRC is associated with a poor prognosis, regardless of the treatment. RAS WT patients with left-sided tumors benefitted from the addition of panitumumab in second or later treatment lines. Further research is warranted to determine the optimum management of right-sided mCRC and RAS MT tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

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Rottenfusser Andrea

2009-10-01

Full Text Available Abstract Background In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression. Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy. Methods Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values Results Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26, and 8 months (95% CI 6.25-9.74 on first-line, respectively (n.s.. In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter. Conclusion Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.

Comparable Efficacy of Abatacept Used as First-line or Second-line Biological Agent for Severe Juvenile Idiopathic Arthritis-related Uveitis.

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Birolo, Carolina; Zannin, Maria Elisabetta; Arsenyeva, Svetlana; Cimaz, Rolando; Miserocchi, Elisabetta; Dubko, Margarita; Deslandre, Chantal Job; Falcini, Fernanda; Alessio, Maria; La Torre, Francesco; Denisova, Ekaterina; Martini, Giorgia; Nikishina, Irina; Zulian, Francesco

2016-11-01

Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)-associated uveitis refractory to anti-tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis. In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded. Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile. ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

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Rothschild SI

2014-09-01

Full Text Available Sacha I Rothschild Department of Internal Medicine, Medical Oncology, University Hospital Basel, Basel, Switzerland Abstract: The therapeutic landscape in non-small-cell lung cancer (NSCLC is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. Keywords: nintedanib, lung cancer, angiokinase inhibitor, VEGFR, PDGF, FGFR

Amputations for extremity soft tissue sarcoma in an era of limb salvage treatment : Local control and survival

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Stevenson, Marc G; Musters, Annelie H; Geertzen, Jan H B; van Leeuwen, Barbara L; Hoekstra, Harald J; Been, Lukas B

2018-01-01

BACKGROUND: Despite multimodality limb salvage treatment (LST) for locally advanced extremity soft tissue sarcoma (ESTS), some patients still need an amputation. Indications for amputation and oncological outcome for these patients are described. METHODS: Between 1996 and 2016, all patients who

Successful Treatment of Liver Aspergilloma by Caspofungin Acetate First-Line Therapy in a Non-Immunocompromised Patient

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Hong-Juan Dong

2012-09-01

Full Text Available Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

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Trojan J

2016-09-01

Full Text Available Jörg Trojan, Oliver Waidmann Medizinische Klinik 1, Universitätsklinikum Frankfurt, Germany Abstract: Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC. In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months. Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1 blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. Keywords: hepatocellular carcinoma, receptor tyrosine kinase inhibitor, sorafenib, regorafenib, lenvatinib, tivantinib, cabozantinib, ramucirumab, immunotherapy, anti-CTLA-4, anti-PD-1, oncolytic virus

First and second line drug resistance among treatment naïve pulmonary tuberculosis patients in a district under Revised National Tuberculosis Control Programme (RNTCP in New Delhi

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Vithal Prasad Myneedu

2015-12-01

Full Text Available There is limited information of level of drug resistance to first-line and second line anti-tuberculosis agents in treatment naïve pulmonary tuberculosis (PTB patients from the Indian region. Therefore, the present prospective study was conducted to determine the antimicrobial susceptibility to first-line and second line anti-TB drug resistance in such patients. Sputum samples from consecutive treatment naïve PTB cases registered in Lala Ram Sarup (LRS district, under RNTCP containing 12 Directly Observed Treatment Centre’s (DOTS, were enrolled using cluster sampling technology. A total of 453 samples were received from July 2011 to June 2012. All samples were cultured on solid medium followed by drug susceptibility to first and second line anti-tubercular drugs as per RNTCP guidelines. Primary multi-drug resistance (MDR was found to be 18/453; (4.0%. Extensively drug resistance (XDR was found in one strain (0.2%, which was found to be resistant to other antibiotics. Data of drug resistant tuberculosis among treatment naïve TB patients are lacking in India. The presence of XDR-TB and high MDR-TB in small population studied, calls for conducting systematic multi-centric surveillance across the country.

Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma

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Larson, Erik W; Peterson, Halloran E; Lamoreaux, Wayne T; MacKay, Alexander R; Fairbanks, Robert K; Call, Jason A; Carlson, Jonathan D; Ling, Benjamin C; Demakas, John J; Cooke, Barton S; Lee, Christopher M

2014-01-01

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed. PMID:24829861

Mitigating Hillslope Erosion After Post-fire Salvage Logging Operations

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Robichaud, P. R.; Bone, E. D.; Brown, R. E.

2017-12-01

In the past decades, wildfires around the world have continued to increase in size, severity, and cost. Major concerns after wildfires are the increased runoff and erosion due to loss of the protective forest floor layer, loss of water storage, and creation of water repellent soil conditions. Salvage logging is often a post-fire forest management action to recoup the economic loss of the burned timber, yet concerns arise on the impacts of this activity on water quality. Recently, several studies have been conducted to determine the effect of salvage logging on hillslope erosion. Logging skid trails have been cited as being the cause of high erosion during and after salvage operations. We investigated the impacts of adding operational logging slash to skid trails to reduce hillslope erosion after salvage operations on the 2015 North Star Fire, Washington. We implemented well-designed rapid response approach to compare slash treatment effectiveness by monitoring sediment yield and runoff response from hillslopes with a concentrated flow (rill) experiment. Various runoff amounts are incrementally added to 4 m hillslope plots with and without slash treatments. Our initial results suggest that adding logging slash increased ground cover significantly which contributed to an order of magnitude decrease in hillslope erosion. Integrating erosion mitigation strategies into salvage logging operations should be commonplace when hillslope erosion is a concern.

Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

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He YY

2016-04-01

Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

Health-related quality of life after salvage high-intensity focused ultrasound (HIFU) treatment for locally radiorecurrent prostate cancer

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Berge, V.; Baco, E.; Dahl, A.A.; Karlsen, S.J.

2011-01-01

The objective of this study was to evaluate health-related quality of life (HRQOL) after salvage high-intensity focused ultrasound (HIFU) for locally radiorecurrent prostate cancer (PCa). Since June 2006 we have treated 61 patients consecutively by salvage HIFU. All patients were offered the University of California, Los Angeles Prostate Cancer Index (UCLA-PCI) questionnaire at baseline and at follow-up. Scores ranged from 0 (worst) to 100 (best). Clinically significant changes were defined as a minimum difference of 10 points between the baseline score and the score at follow-up. Fifty-seven patients (93%) had evaluable data at baseline, compared with 46 (75%) after treatment. The mean time lapse between HIFU treatment and questionnaire response was 17.5 months (range 6-29 months). The mean score for urinary function decreased from 79.7±12.1 prior to HIFU to 67.4±17.8 after HIFU (P<0.001). The mean score for sexual function decreased from 32.1±24.1 prior to HIFU to 17.2±17.0 after HIFU (P<0.001). There were no significant effects on bowel function. There was a significant reduction in the mean score for Physical HRQOL, but the mean score for Mental HRQOL was did not change significantly. Treatment of localized radiorecurrent PCa by salvage HIFU is associated with clinically significant reductions in urinary and sexual function domains after a mean follow-up of 17.5 months. (author)

Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

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Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

2014-05-01

At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

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Abdulaziz eAl Farsi

2014-06-01

Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

Rill erosion in burned and salvage logged western montane forests: Effects of logging equipment type, traffic level, and slash treatment

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Wagenbrenner, J. W.; Robichaud, P. R.; Brown, R. E.

2016-10-01

Following wildfires, forest managers often consider salvage logging burned trees to recover monetary value of timber, reduce fuel loads, or to meet other objectives. Relatively little is known about the cumulative hydrologic effects of wildfire and subsequent timber harvest using logging equipment. We used controlled rill experiments in logged and unlogged (control) forests burned at high severity in northern Montana, eastern Washington, and southern British Columbia to quantify rill overland flow and sediment production rates (fluxes) after ground-based salvage logging. We tested different types of logging equipment-feller-bunchers, tracked and wheeled skidders, and wheeled forwarders-as well as traffic levels and the addition of slash to skid trails as a best management practice. Rill experiments were done at each location in the first year after the fire and repeated in subsequent years. Logging was completed in the first or second post-fire year. We found that ground-based logging using heavy equipment compacted soil, reduced soil water repellency, and reduced vegetation cover. Vegetation recovery rates were slower in most logged areas than the controls. Runoff rates were higher in the skidder and forwarder plots than their respective controls in the Montana and Washington sites in the year that logging occurred, and the difference in runoff between the skidder and control plots at the British Columbia site was nearly significant (p = 0.089). Most of the significant increases in runoff in the logged plots persisted for subsequent years. The type of skidder, the addition of slash, and the amount of forwarder traffic did not significantly affect the runoff rates. Across the three sites, rill sediment fluxes were 5-1900% greater in logged plots than the controls in the year of logging, and the increases were significant for all logging treatments except the low use forwarder trails. There was no difference in the first-year sediment fluxes between the feller

Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of Salvage Surgery.

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Hamaji, Masatsugu; Chen, Fengshi; Matsuo, Yukinori; Ueki, Nami; Hiraoka, Masahiro; Date, Hiroshi

2015-11-01

Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) although limited data are available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. We reviewed our institutional database in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann-Whitney U test, χ2 test, or Fisher's exact test as appropriate. Survival outcomes were estimated with Kaplan-Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and eight patients received chemotherapy, whereas 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS after LR (p = 0.014), and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.

In situ saphenous vein bypass for limb salvage.

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Sarcina, A; Carlesi, R; Bellosta, R; Agrifoglio, G

1993-02-01

A total of 130 infrapopliteal in situ saphenous vein bypasses were performed in 128 patients between January 1980 and June 1991. The indication for surgery was critical ischaemia with impending limb loss in 121 patients; seven suffered from severe claudication. The distal anastomosis was to the popliteal artery below the knee in 60 cases (46.2%) and in 70 (53.8%) to the tibioperoneal arteries. The results, in terms of secondary patency and limb salvage rates, of the first 68 procedures (1980-1985) and subsequent 62 (1986-June 1991) were compared. In the first period, a secondary patency rate of 42.6% and a limb salvage rate of 67.0% were obtained, compared with 71.3 and 80.8% respectively in the second. These differences are significant for patency (P < 0.005) and limb salvage (P < 0.01). These results show that the in situ technique can give acceptable results but a learning period with a high percentage of early failures is to be expected.

Radiotherapy salvage for Hodgkin's disease after chemotherapy failure

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Wirth, A; Corry, J; Liew, K H

1995-07-01

Purpose/Objective: The precise role of salvage radiotherapy (RT) following chemotherapy (CT) failure in patients with Hodgkin's disease (HD) remains undefined. The aims of this study are: (1) to assess the pattern of failure, failure-free and overall survival, in patients who receive salvage RT for HD after CT failure; and (2) to identify patient subsets most suitable for this treatment approach. Materials and Methods: A review of patients treated between 1978 and 1992 at the Peter MacCallum Cancer Institute identified 52 patients with relapsed/refractory HD following CT who received RT with curative intent. Eligibility for this study required either biopsy confirmation of relapse/residual disease, or else clear clinical or radiological disease progression. Patient characteristics at diagnosis: median age 26, with 32% > 40 years old; M/ F 31/21; stage I-4, II-16, III-25, IV-7. Initial CT was MOPP- 31 patients, ABVD-1, both-16. A median 6 cycles of CT was given per regimen. Prior to salvage RT, 26/52 patients had received both MOPP and ABVD, either as sequential regimens, or as alternating or hybrid protocols. The response to initial CT was: CR-30, PR/SD-18, PD-4. Duration of initial CR was < 12 months in 8/30 patients. Salvage treatment consisted of radiotherapy to all known areas of disease. Doses ranged from 3600-4000 cGy. Results: Twenty three patients (45%) achieved CR. With a median follow-up of 70 months (range 4.8-166), actuarial median failure free survival (FFS) and overall survival (OS) are 22 months and 83 months respectively. Actuarial 5 year FFS and OS are 26% and 57% respectively. Patients with CR duration > 12 months following initial CT, only one CT regimen prior to salvage RT, and anatomically limited relapse had a significantly longer FFS. These factors, and age < 40 were associated with significantly longer OS. Only 6% of patients failed solely in the irradiated volume as first site of relapse, with the total in-field relapse of 30%. Sixty

Splenectomy vs. rituximab as a second-line therapy in immune thrombocytopenic purpura: a single center experience.

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Al Askar, Ahmed S; Shaheen, Naila A; Al Zahrani, Mohsen; Al Otaibi, Mohammed G; Al Qahtani, Bader S; Ahmed, Faris; Al Zughaibi, Mohand; Kamran, Ismat; Mendoza, May Anne; Khan, Altaf

2018-01-01

Immune thrombocytopenic purpura (ITP) is a common hematological disease treated primarily by corticosteroids. The aim of the present study was to compare response rate between patients, underwent splenectomy vs. rituximab as second-line therapy. Adult patients diagnosed with ITP who did not respond to corticosteroids or relapsed during the period 1990-2014 were included in a quasi-experimental study. Categorical variables were compared using Fisher exact test. Response to treatment was compared using logistic regression. Data were analyzed using SAS V9.2. One-hundred and forty-three patients with ITP were identified through medical records. Of 62 patients treated, 30 (48.38%) required second-line therapy. 19 (63%) patients received rituximab, and 11 (37%) underwent splenectomy. Platelets at diagnosis were not different between study groups (p = 0.062). Splenectomy group patients were younger (p = 0.011). Response to second-line therapy showed no significant difference between two groups (OR 2.03, 95% CI (0.21-22.09), p = 0.549). Results did not show a statistically significant difference in platelet counts over time between treatment groups (p = 0.101). When used exclusively as a second-line therapy for steroid-refractory ITP, the response rate was not statistically different between rituximab and splenectomy. However, further large studies are needed to assess the response rates for these treatment modalities as a second-line therapy.

Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

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Taguchi, Satoru; Shiraishi, Kenshiro; Fukuhara, Hiroshi; Nakagawa, Keiichi; Morikawa, Teppei; Naito, Akihiro; Kakutani, Shigenori; Takeshima, Yuta; Miyazaki, Hideyo; Nakagawa, Tohru; Fujimura, Tetsuya; Kume, Haruki; Homma, Yukio

2016-01-01

The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL

Efficacy of S-1 plus nedaplatin compared to standard second-line chemotherapy in EGFR-negative lung adenocarcinoma after failure of first-line chemotherapy.

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Tang, Yu; Wang, Wei; Teng, Xiu-Zhi; Shi, Lin

2014-09-01

For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

International Nuclear Information System (INIS)

Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

2014-01-01

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Energy Technology Data Exchange (ETDEWEB)

Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

2014-11-04

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

DEFF Research Database (Denmark)

Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

2015-01-01

BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient...

Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

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Schuette Wolfgang

2012-01-01

Full Text Available Abstract Background Second-line treatment of advanced non-small-cell lung cancer (NSCLC improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS and health-related quality of life (HR-QoL during second-line pemetrexed treatment in routine clinical practice. Methods Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI of ≥ 10% (absolute or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response". HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D. Factors potentially associated with KI benefit response were evaluated using logistic regression models. Results Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%, 471 (90.4% completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2% achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%. Conclusions In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years, physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Trial registration Registered on ClinicalTrials.gov (NCT00540241 on October 4, 2007

Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer

DEFF Research Database (Denmark)

Joensuu, H; Holli, K; Heikkinen, M

1998-01-01

PURPOSE: We report results of a randomized prospective study that compared single agents of low toxicity given both as the first-line and second-line chemotherapy with combination chemotherapy in advanced breast cancer with distant metastases. PATIENTS AND METHODS: Patients in the single-agent arm...... (n = 153) received weekly epirubicin (E) 20 mg/m2 until progression or until the cumulative dose of 1,000 mg/m2, followed by mitomycin (M) 8 mg/m2 every 4 weeks, and those in the combination chemotherapy arm (n = 150) were first given cyclophosphamide 500 mg/m2, E 60 mg/m2, and fluorouracil 500 mg/m2...... younger than 50. RESULTS: An objective response (complete [CR] or partial [PR]) was obtained in 55%, 48%, 16%, and 7% of patients treated with CEF, E, M, and MV, respectively. A response to CEF tended to last longer than a response to E (median, 12 v 10.5 months; P = .07). Treatment-related toxicity...

Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

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Man-Hsin Hung

2013-04-01

Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

Effects of salvage logging and pile-and-burn on fuel loading, potential fire behaviour, fuel consumption and emissions

Science.gov (United States)

Morris C. Johnson; Jessica E. Halofsky; David L. Peterson

2013-01-01

We used a combination of field measurements and simulation modelling to quantify the effects of salvage logging, and a combination of salvage logging and pile-and-burn fuel surface fuel treatment (treatment combination), on fuel loadings, fire behaviour, fuel consumption and pollutant emissions at three points in time: post-windstorm (before salvage logging), post-...

Forest structure following tornado damage and salvage logging in northern Maine, USA

Science.gov (United States)

Shawn Fraver; Kevin J. Dodds; Laura S. Kenefic; Rick Morrill; Robert S. Seymour; Eben Sypitkowski

2017-01-01

Understanding forest structural changes resulting from postdisturbance management practices such as salvage logging is critical for predicting forest recovery and developing appropriate management strategies. In 2013, a tornado and subsequent salvage operations in northern Maine, USA, created three conditions (i.e., treatments) with contrasting forest structure:...

Second-line systemic therapy for metastatic colorectal cancer.

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Mocellin, Simone; Baretta, Zora; Roqué I Figuls, Marta; Solà, Ivan; Martin-Richard, Marta; Hallum, Sara; Bonfill Cosp, Xavier

2017-01-27

The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions. Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy. Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI). Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2

Second-line treatment of recurrent HNSCC: tumor debulking in combination with high-dose-rate brachytherapy and a simultaneous cetuximab-paclitaxel protocol

International Nuclear Information System (INIS)

Ritter, M.; Teudt, I. U.; Meyer, J. E.; Schröder, U.; Kovács, G.; Wollenberg, B.

2016-01-01

After the failure of first-line treatment, the clinical prognosis in head and neck cancer (HNSCC) deteriorates. Effective therapeutic strategies are limited due to the toxicity of previous treatments and the diminished tolerance of surrounding normal tissue. This study demonstrates a promising second-line regimen, with function preserving surgical tumor debulking, followed by a combination of postoperative interstitial brachytherapy and a simultaneous protocol of cetuximab and taxol. From January 2006 to May 2013, 197 patients with HNSCC were treated with brachytherapy at the University Hospital Schleswig-Holstein Campus Lübeck, including 94 patients due to recurrent cancer. Within these, 18 patients were referred to our clinic because of early progressive disease following first- or second-line treatment failure. They received the new palliative regimen. A matched-pair analysis including recurrent tumor stage, status of resection margins, tissue invasion and previous therapy was performed to evaluate this treatment retrospectively. Overall survival (OS), disease-free survival (DFS), functional outcome and treatment toxicity was analyzed on the basis of medical records and follow-up data. DFS and OS of the study group were 8.7 and 14.8 months. Whereas, DFS and OS of the control group, treated only by function preserving tumor debulking and brachytherapy, was 3.9 and 6.1 months respectively. This demonstrates a positive trend through the additional use of the cetuximab-taxane protocol. Furthermore, no increase of therapy induced toxicities was displayed. Pre-treated patients with a further relapse benefit from the ‘cetuximab-taxane recurrency scheme’. It seems to be a valuable complement to interdisciplinary and multimodal tumor therapy, which improves OS and results in acceptable toxicity. The online version of this article (doi:10.1186/s13014-016-0583-0) contains supplementary material, which is available to authorized users

Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only

International Nuclear Information System (INIS)

Rischke, Hans Christian; Schultze-Seemann, Wolfgang; Kroenig, Malte; Schlager, Daniel; Jilg, Cordula Annette; Wieser, Gesche; Drendel, Vanessa; Stegmaier, Petra; Henne, Karl; Volegova-Neher, Natalia; Grosu, Anca-Ligia; Krauss, Tobias; Kirste, Simon

2015-01-01

Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only. ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse. (orig.) [de

Ipsilateral breast tumor recurrence after breast conservation therapy: Outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation

International Nuclear Information System (INIS)

Alpert, Tracy E.; Kuerer, Henry M.; Arthur, Douglas W.; Lannin, Donald R.; Haffty, Bruce G.

2005-01-01

Purpose: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. Methods and Materials: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size <3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with ≤3 positive nodes. Results: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. Conclusions: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is

Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

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Maria-Virginia Bluthgen

2015-12-01

Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

Salvage image guided radiation therapy to the prostate after cryotherapy failure

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Austin B. Hopper, BS

2018-01-01

Conclusions: High-dose IG-IMRT results in high rates of salvage and extremely low rates of serious late toxicity for patients with locally recurrent prostate cancer after cryotherapy. Although the results are encouraging, given the small number of patients in this and other series, we remain cautious with regard to this treatment and believe the use of salvage radiation therapy after cryotherapy warrants further study.

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

DEFF Research Database (Denmark)

Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

2015-01-01

BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

Singular and interactive effects of blowdown, salvage logging, and wildfire in sub-boreal pine systems

Science.gov (United States)

D'Amato, A.W.; Fraver, S.; Palik, B.J.; Bradford, J.B.; Patty, L.

2011-01-01

The role of disturbance in structuring vegetation is widely recognized; however, we are only beginning to understand the effects of multiple interacting disturbances on ecosystem recovery and development. Of particular interest is the impact of post-disturbance management interventions, particularly in light of the global controversy surrounding the effects of salvage logging on forest ecosystem recovery. Studies of salvage logging impacts have focused on the effects of post-disturbance salvage logging within the context of a single natural disturbance event. There have been no formal evaluations of how these effects may differ when followed in short sequence by a second, high severity natural disturbance. To evaluate the impact of this management practice within the context of multiple disturbances, we examined the structural and woody plant community responses of sub-boreal Pinus banksiana systems to a rapid sequence of disturbances. Specifically, we compared responses to Blowdown (B), Fire (F), Blowdown-Fire, and Blowdown-Salvage-Fire (BSF) and compared these to undisturbed control (C) stands. Comparisons between BF and BSF indicated that the primary effect of salvage logging was a decrease in the abundance of structural legacies, such as downed woody debris and snags. Both of these compound disturbance sequences (BF and BSF), resulted in similar woody plant communities, largely dominated by Populus tremuloides; however, there was greater homogeneity in community composition in salvage logged areas. Areas experiencing solely fire (F stands) were dominated by P. banksiana regeneration, and blowdown areas (B stands) were largely characterized by regeneration from shade tolerant conifer species. Our results suggest that salvage logging impacts on woody plant communities are diminished when followed by a second high severity disturbance; however, impacts on structural legacies persist. Provisions for the retention of snags, downed logs, and surviving trees as part

First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

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Johann von Felden

2016-11-01

Full Text Available Advanced hepatocellular carcinoma (HCC with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST is helpful to identify patients who do not benefit from sorafenib treatment.

25 CFR 700.99 - Salvage value.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Salvage value. 700.99 Section 700.99 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.99 Salvage value. Salvage value means the probable sale price of an...

Salvage surgery for local failure of oral squamous cell carcinoma

International Nuclear Information System (INIS)

Omura, Ken; Harada, Hiroyuki; Shimamoto, Hiroaki

2003-01-01

Local failure rates following treatment for squamous cell carcinoma of the oral cavity have been reported to be in the range of 25%-48%. This study investigated the pattern of failure for squamous cell carcinoma (SCC) of the oral cavity and evaluated salvage surgery for local recurrent disease. The tumor files of 549 patients undergoing treatment for SCC of the oral cavity between 1980 and 2000 at Chiba Cancer Center Hospital were reviewed. Of 549 patients, 289 were initially treated with radiation therapy for their primary tumor, and 260 with surgery, either with or without radiation therapy. One hundred and sixty-one patients developed failures, yielding a failure rate of 29.3%. The site of recurrent tumor was local in 72 (13.1%) patients, regional in 89 (16.2%) patients, and distant in 5 (0.9%) patients. Local failure developed in 49 (17.0%) patients with radiation therapy and in 23 (8.8%) patients with surgery. Out of these 72 patients with local failure, 41 (56.9%) patients had salvage surgery for their disease. Twenty-five (73.5%) of the 34 patients initially treated with radiation therapy were salvaged with surgery, and 4 (57.1%) of the 7 patients initially treated with surgery were cured with further surgery. For the treatment of patients with local failure, the disease should be diagnosed more carefully than untreated disease. The disease that has recurred after radiation therapy may be more likely to be salvaged by surgery, however, the disease that has developed after surgery may have a limited indication for re-surgery. (author)

Salvage HIFU after radiotherapy and salvage radiotherapy after HIFU in locally recurrent prostate cancer: Retrospective analysis of morbidity

International Nuclear Information System (INIS)

Lee, J.-W.; Hannoun-Leviac, J.-M.; Chevallier, D.; Rouscoff, Y.; Durand, M.; Amiel, J.; Gal, J.; Natale, R.; Chand, M.-E.; Raffaelli, C.; Ambrosetti, D.

2012-01-01

To evaluate the toxicity of therapeutic sequences High Intensity Focused Ultrasound (HIFU)-salvage radiotherapy (HIFU-RT) or radiotherapy-salvage HIFU (RT-HIFU) in case of locally recurrent prostate cancer. Nineteen patients had a local recurrence of prostate cancer. Among them, 10 patients were treated by HIFU-RT and 9 patients by RT- HIFU (4 by external beam radiotherapy [EBR] and 5 by brachytherapy [BRACHY]). Urinary side effects were assessed using CTCAE v4. At the time of the initial management, the median age was 66.5 years (53 72), the median PSA was 10.8 ng/mL (3.4 50) and the median initial Gleason score was 6.3 (5 8). Median follow-up after salvage treatment was 46.3 months (2 108). Thirty percent of the patients in the HIFU-RT group and 33.3 % of the patients in the RT-HIFU group, all belonging to the sub-group BRACHY-HIFU, had urinary complication greater than or equal to grade 2. Among all the patients, only 1 had grade 1 gastrointestinal toxicity. BRACHY-HIFU sequence seems to be purveyor of many significant urinary side effects. A larger database is needed to confirm this conclusion. (authors)

Exeresis and Brachytherapy as Salvage Treatment for Local Recurrence After Conservative Treatment for Breast Cancer: Results of a Ten-Year Pilot Study

International Nuclear Information System (INIS)

Guix, Benjamin; Lejarcegui, Jose Antonio; Tello, Jose Ignacio; Zanon, Gabriel; Henriquez, Ivan; Finestres, Fernando; Martinez, Antonio; Fernandez-Ibiza, Jaume; Quinzanos, Luis; Palombo, Pau; Encinas, Xavier; Guix, Ines

2010-01-01

Purpose: To analyze the long-term results of a pilot study assessing excision and brachytherapy as salvage treatment for local recurrence after conservative treatment of breast cancer. Methods and Materials: Between December 1990 and March 2001, 36 patients with breast-only recurrence less than 3 cm in diameter after conservative treatment for Stage I or II breast carcinoma were treated with local excision followed by high-dose rate brachytherapy implants (30 Gy in 12 fractions over a period of 5 days). No patient was lost to follow-up. Special attention was paid to local, regional, or distant recurrences; survival; cosmesis; and early and late side effects. Results: All patients completed treatment. During follow-up (range, 1-13 years), 8 patients presented metastases (2 regional and 6 distant) as their first site of failure, 1 had a differed local recurrence, and 1 died of the disease. Actuarial results at 10 years were as follows: local control, 89.4%; disease-free survival, 64.4%; and survival, 96.7%. Cosmetic results were satisfactory in 90.4%. No patient had Grade 3 or 4 early or late complications. Of the 11 patients followed up for at least 10 years, all but 1 still had their breast in place at the 10-year stage. Conclusions: High-dose rate brachytherapy is a safe, effective treatment for small-size, low-risk local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of high-dose rate brachytherapy (12 fractions over a period of 5 days twice daily) was well tolerated. The excellent results support the use of breast preservation as salvage treatment in selected patients with local recurrence after conservative treatment for breast cancer.

Second malignancies after treatment for Ewing's sarcoma

International Nuclear Information System (INIS)

Ahrens, Susanne; Dunst, Juergen; Ruebe, Christian; Paulussen, Michael; Hoffmann, Christine; Juergens, Herbert

1997-01-01

Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated

Second malignancies after treatment for Ewing's sarcoma

Energy Technology Data Exchange (ETDEWEB)

Ahrens, Susanne; Dunst, Juergen; Ruebe, Christian; Paulussen, Michael; Hoffmann, Christine; Juergens, Herbert

1997-07-01

Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. The median follow-up at the time of this analysis was 7 years, the maximum follow-up 16 years. Results: Eight patients developed a SM, 4 were acute myelogenic leucemias, three sarcomas and one benign neurinoma. One of the sarcomas was considered as radiation-induced because of its location in the former radiation field. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17 to 78 months for the four AMLs and 82 to 136 months for the three sarcomas. All solid second tumors occurred in irradiated patients. The cumulative risk of a SM is given in table 1. Three patients (all with AML) died of their SM, the other five were salvage by subsequent treatment and are in clinical remission with a median follow-up of 1 to 10 years. Conclusions: The risk of leukemia after treatment for Ewing's sarcoma is probably low in the range of 1-2% or less and accounts for about 1% of all deaths. There was no risk of solid tumors in surgically treated patients. Irradiated

Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

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Lam, Simon W; Wai, Maya; Lau, Jessica E; McNamara, Michael; Earl, Marc; Udeh, Belinda

2017-01-01

Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified

Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection.

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Gisbert, Javier P; Molina-Infante, Javier; Marin, Alicia C; Vinagre, Gemma; Barrio, Jesus; McNicholl, Adrian Gerald

2013-06-01

Non-bismuth quadruple "sequential" and "concomitant" regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. prospective multicenter study. in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. eradication was confirmed with (13)C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple "sequential" or "concomitant" treatment failure.

Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

International Nuclear Information System (INIS)

Pasquier, David; Ballereau, Charles

2008-01-01

Purpose: Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. Methods and Materials: A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE. Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. Results: Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). Conclusion

Long-term results of salvage radiotherapy for the treatment of recurrent cervical carcinoma after prior surgery

International Nuclear Information System (INIS)

Haasbeek, Cornelis J.A.; Uitterhoeve, Apollonia L.J.; Velden, Jacobus van der; Gonzalez, Dionisio Gonzalez; Stalpers, Lukas J.A.

2008-01-01

Abstarct: Background and purpose: Tumor recurrence after surgery for cervical carcinoma is associated with high fatality and morbidity, forming a major therapeutic challenge. This paper presents our experience with treatment of this patient group by salvage radiotherapy with curative intent. Materials and methods: Thirty-five patients with a pelvic recurrence after hysterectomy received high-dose radiotherapy. A retrospective analysis of long-term outcome and prognostic factors was performed. Results: After a median follow-up period of 12.1 years, actuarial 2-,5- and 10-year overall survival rates were 66%, 43% and 33%; disease-free survival rates were 62%, 45% and 41%, respectively. Pelvic control rates at 2-,5- and 10-years were 77%, 69% and 62%. Unfavorable prognostic factors on univariate analysis for survival were: recurrence extending to the pelvic wall versus central recurrence, early recurrence after surgery, external boost versus brachytherapy boost, low total dose and high age. Only a brachytherapy boost and a long interval between surgery and recurrence were significant on multivariate analysis. Severe complications (≥grade 3) were seen in 6 patients (17%; actuarial after 5 years, 21%). Conclusions: Salvage radiotherapy for recurrent cervical carcinoma following surgery may result in 40-50% long-term disease-free survival and an acceptable risk of severe treatment complications, even in patient with recurrences extending to the pelvic wall

Efficacy and safety of pharmacological interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a systematic review

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Sharma, Sheetal; Takyar, Shweta; Manson, Stephanie C; Powell, Sarah; Penel, Nicolas

2013-01-01

Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS. Electronic literature databases (Embase ® , MEDLINE ® , MEDLINE ® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy. The review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results. Across the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations

Post-fire salvage logging alters species composition and reduces cover, richness, and diversity in Mediterranean plant communities.

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Leverkus, Alexandro B; Lorite, Juan; Navarro, Francisco B; Sánchez-Cañete, Enrique P; Castro, Jorge

2014-01-15

An intense debate exists on the effects of post-fire salvage logging on plant community regeneration, but scant data are available derived from experimental studies. We analyzed the effects of salvage logging on plant community regeneration in terms of species richness, diversity, cover, and composition by experimentally managing a burnt forest on a Mediterranean mountain (Sierra Nevada, S Spain). In each of three plots located at different elevations, three replicates of three treatments were implemented seven months after the fire, differing in the degree of intervention: "Non-Intervention" (all trees left standing), "Partial Cut plus Lopping" (felling 90% of the trees, cutting the main branches, and leaving all the biomass in situ), and "Salvage Logging" (felling and piling the logs, and masticating the woody debris). Plant composition in each treatment was monitored two years after the fire in linear point transects. Post-fire salvage logging was associated with reduced species richness, Shannon diversity, and total plant cover. Moreover, salvaged sites hosted different species assemblages and 25% lower cover of seeder species (but equal cover of resprouters) compared to the other treatments. Cover of trees and shrubs was also lowest in Salvage Logging, which could suggest a potential slow-down of forest regeneration. Most of these results were consistent among the three plots despite plots hosting different plant communities. Concluding, our study suggests that salvage logging may reduce species richness and diversity, as well as the recruitment of woody species, which could delay the natural regeneration of the ecosystem. Copyright © 2013 Elsevier Ltd. All rights reserved.

Second acute leukemia and other malignancies following treatment for Hodgkin's disease

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Valagussa, P.; Santoro, A.; Fossati-Bellani, F.; Banfi, A.; Bonadonna, G.

1986-01-01

The records of 1329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives

Salvage brachytherapy (BT) of 85 T1 T2 oral cavity second head and neck primaries (SHNP) in previously irradiated patients

International Nuclear Information System (INIS)

Peiffert, D; Hoffstetter, S; Pernot, M.; Aletti, P.; Luporsi, E.; Kozminski, P.; Lapeyre, M.; Dartois, D.; Bey, P.

1996-01-01

The occurrence of a SNHP (20%) represents a major therapeutic dilemma for salvage treatment. BT achieves a local conservative treatment but neglects the node areas. The aim of the study is to evaluate the local control, the late complications, and the survival. Materials and Methods. From 1976 to 1994, 85 patients were treated by salvage BT for a T1 T2 SHNP (38 mobile tongues and 47 floors of mouth). All of them had been previously irradiated for a first head and neck primary by external beam irradiation (80 patients, mean dose = 55 Gy) and/or BT (31 patients, mean dose 39 Gy). A tumour resection had been performed in 33 patients. Results: They were 81 males and 4 females, their mean age was 59 (range 40-80). 78 had infiltrative squamous cell carcinomas, and 7 micro-invasive or intra-epithelial carcinomas. They were 20 T1N0, 17 T2 N0 and 1 T2 N1 mobile tongue, and 39 T1 N0, 8 T2 N0 floor of mouth tumours. The mean follow-up was 46 months (range 1-130). The BT used Ir 192 wires, at low dose rate (mean = 0.58 Gy/h, range 0.3-1.1), and delivered a mean dose of 62 Gy (range 26-70) in the 85% ref. isodose of the Paris System. For the tongue and the floor respectively, the 5 years overall survival was 41% and 26%, and the 5 years specific survival 74% and 94%. The causes of death were respectively the tumour for 32% and 5%, and another primary for 42% and 66%. The local relapse rate was respectively 18% and 8.5%, half of them occurring in the first year of follow-up, the nodal relapses were 8% and 4%. Only one patient developed a distant metastasis. 5 patients developed osteoradionecrosis (3 grade 3 with fracture and/or mandible resection) and 19 soft tissue necrosis (2 grade 3 treated by local excision, and 9 grade 2 treated by hyperbaric 02). 47 patients developed other primaries, especially in the oesophagus (18 patients) explaining the low overall survival. Conclusion: Salvage BT is a useful treatment for T1 T2 oral cavity SHNP occurring in previous irradiated

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

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Gisbert, Javier P; Pérez-Aisa, Angeles; Bermejo, Fernando; Castro-Fernández, Manuel; Almela, Pedro; Barrio, Jesús; Cosme, Angel; Modolell, Inés; Bory, Felipe; Fernández-Bermejo, Miguel; Rodrigo, Luis; Ortuño, Jesús; Sánchez-Pobre, Pilar; Khorrami, Sam; Franco, Alejandro; Tomas, Albert; Guerra, Iván; Lamas, Eloisa; Ponce, Julio; Calvet, Xavier

2013-02-01

Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Prospective multicenter study. In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

Survival outcomes following salvage surgery for oropharyngeal squamous cell carcinoma: systematic review.

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Kao, S S; Ooi, E H

2018-04-01

Recurrent oropharyngeal squamous cell carcinoma causes great morbidity and mortality. This systematic review analyses survival outcomes following salvage surgery for recurrent oropharyngeal squamous cell carcinoma. A comprehensive search of various electronic databases was conducted. Studies included patients with recurrent or residual oropharyngeal squamous cell carcinoma treated with salvage surgery. Primary outcomes were survival rates following salvage surgery. Secondary outcomes included time to recurrence, staging at time of recurrence, post-operative complications, and factors associated with mortality and recurrence. Methodological appraisal and data extraction were conducted as per Joanna Briggs Institute methodology. Eighteen articles were included. The two- and five-year survival rates of the patients were 52 per cent and 30 per cent respectively. Improvements in treatment modalities for recurrent oropharyngeal squamous cell carcinoma were associated with improvements in two-year overall survival rates, with minimal change to five-year overall survival rates. Various factors were identified as being associated with long-term overall survival, thus assisting clinicians in patient counselling and selection for salvage surgery.

Effectiveness of carboplatin and paclitaxel as first- and second-line treatment in 61 patients with metastatic melanoma.

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Annette Pflugfelder

Full Text Available BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c received CP as first-line treatment, 41 patients (90.2% M1c had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD (49 weeks compared to patients with progressive disease (18 weeks. CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.

Targeted therapies in the treatment of urothelial cancers.

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Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes

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Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B.; Sotgiu, Giovanni; Cox, Helen S.; Holtz, Timothy H.; Hollm-Delgado, Maria-Graciela; Keshavjee, Salmaan; Deriemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G.; Bauer, Melissa; Menzies, Dick; Ahuja, S. D.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M. C.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E. D.; Chiang, C. Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W. C. M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K. L.; Flood, J.; Gandhi, N.; Garcia-Garcia, M. L.; Granich, R. M.; Hollm-Delgado, M. G.; Holtz, T. H.; Hopewell, P.; Iseman, M. D.; Jarlsberg, L. G.; Keshavjee, S.; Kim, H. R.; Koh, W. J.; Lancaster, J. L.; Lange, C.; Leimane, V.; Leung, C. C.; Li, J.

2013-01-01

A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable

Experimental test of postfire management in pine forests: impact of salvage logging versus partial cutting and nonintervention on bird-species assemblages.

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Castro, Jorge; Moreno-Rueda, Gregorio; Hódar, José A

2010-06-01

There is an intense debate about the effects of postfire salvage logging versus nonintervention policies on regeneration of forest communities, but scant information from experimental studies is available. We manipulated a burned forest area on a Mediterranean mountain to experimentally analyze the effect of salvage logging on bird-species abundance, diversity, and assemblage composition. We used a randomized block design with three plots of approximately 25 ha each, established along an elevational gradient in a recently burned area in Sierra Nevada Natural and National Park (southeastern Spain). Three replicates of three treatments differing in postfire burned wood management were established per plot: salvage logging, nonintervention, and an intermediate degree of intervention (felling and lopping most of the trees but leaving all the biomass). Starting 1 year after the fire, we used point sampling to monitor bird abundance in each treatment for 2 consecutive years during the breeding and winter seasons (720 censuses total). Postfire burned-wood management altered species assemblages. Salvage logged areas had species typical of open- and early-successional habitats. Bird species that inhabit forests were still present in the unsalvaged treatments even though trees were burned, but were almost absent in salvage-logged areas. Indeed, the main dispersers of mid- and late-successional shrubs and trees, such as thrushes (Turdus spp.) and the European Jay (Garrulus glandarius) were almost restricted to unsalvaged treatments. Salvage logging might thus hamper the natural regeneration of the forest through its impact on assemblages of bird species. Moreover, salvage logging reduced species abundance by 50% and richness by 40%, approximately. The highest diversity at the landscape level (gamma diversity) resulted from a combination of all treatments. Salvage logging may be positive for bird conservation if combined in a mosaic with other, less-aggressive postfire

First-line targeted therapies in the treatment of metastatic colorectal cancer – role of cetuximab

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Giuseppe Tonini

2009-04-01

Full Text Available Giuseppe Tonini, Alice Calvieri, Bruno Vincenzi, Daniele SantiniMedical Oncology, University Campus Bio-Medico, Rome, ItalyAbstract: Worldwide, colorectal cancer (CRC is the fourth most commonly diagnosed malignant disease and the second leading cause of cancer-related death in Western nations. In 2008 there were an estimated 148,810 new cases and 49,960 deaths in the US. For several years different chemotherapeutic regimens, based on floropyrimidines, irinotecan and oxaliplatin, have been used in advanced CRC, but survival is still unsatisfactory. New targeted therapies, including drugs and monoclonal antibodies (MoABs , show great promise in the fight against CRC and have shown activity in different disease settings. Cetuximab, a chimeric IgG1 monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR, is active in metastatic colorectal cancer (mCRC. As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The combination of this drug with classical chemotherapies has shown better clinical profiles reflected in an improvement in overall and progression-free survival. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. Whereas cetuximab has a clear indication in the salvage setting, its role in first-line therapy remains investigational. It is particularly encouraging that cetuximab may enhance curative opportunities in patients with early metastatic disease, suggesting that adding cetuximab in first-line therapy may downstage disease in some patients, and, as a result, allow potentially curative resection of previously unresectable metastases. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit, and the role of cetuximab in first-line treatment of metastatic CRC

Limb salvage surgery.

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Kadam, Dinesh

2013-05-01

The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

Extended Salvage Pelvic Lymph Node Dissection in Patients with Recurrent Prostate Cancer

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Daniar K. Osmonov

2014-01-01

Full Text Available Background. Treatment of patients with a biochemical recurrence (BCR of prostate cancer (PCa is generally difficult and without valid treatment options. Since 2004 we have been developing therapeutic possibilities for these patients. Methods. We retrospectively analyzed a cohort of 41 patients with a BCR of PCa and a mean followup of 40.3±20.8 months. Group 1 (n=10: salvage radical prostatectomy (sRP with SePLND (salvage extended pelvic lymph nodes dissection (initial treatment: combined brachytherapy. Group 2 (n=22: SePLND (initial treatment: radical prostatectomy (RP. Group 3 (n=9: SePLND (initial treatment: RP and adjuvant radiation therapy (RT. We observed PSA, PSA-velocity, localization of LNs and LNs+, BCR-free period, and BR (biochemical response. Results. Group 1: 60% with BCR-freedom (mean 27.2 months. Group 2: 63.6% with BCR-freedom (mean 17.5 months. Group 3: 33.3% with BCR-freedom (mean 17.6 months. In total, BCR-freedom was observed in 23 of 41 patients (56.1% after salvage surgery. 75.6% of all patients showed a BR. 765 LNs were removed and 14.8% of these were LN+. Conclusions. The BCR-free period and BR are comparable in all three groups. Sensibility to ADT can be reestablished and prolonged as a result of SePLND. Multicenter studies are needed for a reliable output.

Helicobacter pylori second-line rescue therapy with levofloxacin- and bismuth-containing quadruple therapy, after failure of standard triple or non-bismuth quadruple treatments.

Science.gov (United States)

Gisbert, J P; Romano, M; Gravina, A G; Solís-Muñoz, P; Bermejo, F; Molina-Infante, J; Castro-Fernández, M; Ortuño, J; Lucendo, A J; Herranz, M; Modolell, I; Del Castillo, F; Gómez, J; Barrio, J; Velayos, B; Gómez, B; Domínguez, J L; Miranda, A; Martorano, M; Algaba, A; Pabón, M; Angueira, T; Fernández-Salazar, L; Federico, A; Marín, A C; McNicholl, A G

2015-04-01

The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the efficacy of rescue eradication regimens. To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment failed. This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.), levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by (13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by questionnaires. 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37). A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was serious. Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed. © 2015 John Wiley & Sons Ltd.

Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

International Nuclear Information System (INIS)

Pearce, Andrew; Choo, Richard; Danjoux, Cyril; Morton, Gerard; Loblaw, D. Andrew; Szumacher, Ewa; Cheung, Patrick; Deboer, Gerrit; Chander, Sarat

2006-01-01

Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL

Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma.

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Parikh, Neehar D; Singal, Amit G; Hutton, David W

2017-10-01

Regorafenib, a multikinase inhibitor, has demonstrated prolonged survival by 2.8 months as a second-line agent in patients with hepatocellular carcinoma (HCC) who progress on sorafenib therapy. The objective of the current study was to examine the cost effectiveness of regorafenib for the treatment of HCC. The authors constructed a Markov simulation model of patients with unresectable HCC and Child-Pugh A cirrhosis who received treatment with regorafenib versus best supportive care. Model inputs for regorafenib effectiveness and rates of adverse events in patients with HCC were based on published clinical trial data and literature review. Quality-adjusted life years (QALYs) were calculated along with the incremental cost-effectiveness ratio (ICER) of regorafenib therapy. One-way sensitivity analyses also were conducted simultaneously on all model parameters and on various Monte-Carlo simulation parameters, and the regorafenib cost threshold at which cost effectiveness would be achieved was determined. Regorafenib provided an increase of 0.18 QALYs at a cost of $47,112. The ICER for regorafenib, compared with best supportive care, was $224,362. In 1-way sensitivity analyses, there were no scenarios in which regorafenib was cost effective. In cost threshold analysis, regorafenib would have to be priced at or below $67 per pill to be cost effective at an ICER of $100,000. Regorafenib is not cost effective as a second-line agent in the treatment of HCC, with a marginal increase in QALYs at a high cost. Lowering the cost of regorafenib or improving the selection of patients who can achieve maximal survival benefit would improve its value as a second-line treatment option for patients with HCC. Cancer 2017;123:3725-3731. © 2017 American Cancer Society. © 2017 American Cancer Society.

Enhanced Morbidity of Pectoralis Major Myocutaneous Flap Used for Salvage after Previously Failed Oncological Treatment and Unsuccessful Reconstructive Head and Neck Surgery

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Christiana Maria Ribeiro Salles Vanni

2012-01-01

Full Text Available Introduction. The reconstruction of complex cervicofacial defects arising from surgical treatment for cancer is a real challenge for head and neck surgeons, especially in salvage reconstruction surgery and/or failed previous reconstruction. The pectoralis major myocutaneous flap (PMMF has been widely used in these specific situations due to its reliability and low rate of failure or complications. Objectives. Identify factors that determine complications and influence the final outcome of the reconstructions with PMMF in salvage cancer surgery or in salvage reconstruction. Methods. A cross-sectional study design was used to evaluate a sample including 17 surgical patients treated over a period of ten years that met the inclusion criteria. Results. Reconstruction was successful in 13 cases (76.5%, with two cases of partial flap loss and no case of total loss. Complications occurred in 13 cases (76.5% and were specifically related to the flap in nine instances (52.9%. An association was identified between the development of major complications and reconstruction of the hypopharynx (=0.013 as well as in patients submitted to surgery in association with radiation therapy as a previous cancer treatment (=0.002. The former condition is also associated with major reconstruction failure (=0.018. An even lower incidence of major complications was noted in patients under the age of 53 (=0.044. Conclusion. Older patients, with hypopharyngeal defects and submitted to previous surgery plus radiation therapy, presented a higher risk of complications and reconstruction failure with PMMF.

Limb salvage surgery

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Dinesh Kadam

2013-01-01

Full Text Available The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

Title of the paper goes here second line

Indian Academy of Sciences (India)

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Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

International Nuclear Information System (INIS)

King, Christopher R.; Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

2008-01-01

Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity ≤1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level ≤1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = ∼0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates

Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

International Nuclear Information System (INIS)

Holtzman, Adam L.; Hoppe, Bradford S.; Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G.; Williams, Christopher R.; Li, Zuofeng; Mendenhall, Nancy P.

2016-01-01

Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

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Holtzman, Adam L. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Williams, Christopher R. [Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida (United States); Li, Zuofeng; Mendenhall, Nancy P. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States)

2016-05-01

Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

Serum PSA Evaluations during salvage radiotherapy for post-prostatectomy biochemical failures as prognosticators for treatment outcomes

International Nuclear Information System (INIS)

Do, Tri; Dave, Giatri; Parker, Robert; Kagan, A. Robert

2001-01-01

Introduction: Serum prostate specific antigen (PSA) levels have proved to be sensitive markers for the diagnosis of prostate cancer. In addition, PSA levels are useful for detecting and monitoring prostate cancer progression after radiotherapy. Serum PSA evaluations during radiotherapy, however, have not been well documented. In this study, we investigate the prognostic value of PSA evaluations during salvage radiotherapy for prostatectomy failures. Methods: Forty-one patients with biochemical failures after prostatectomy treated with salvage radiotherapy consented to have their serum PSA levels evaluated at 30 Gy and 45 Gy of irradiation. All 41 patients had negative metastatic workup and pathologically uninvolved pelvic lymph nodes at the time of referral for salvage radiotherapy. Radiation therapy was delivered with 10-25 MV photons, with doses of 59.4-66.6 Gy. No patients received hormonal ablation therapy before irradiation. Results: The mean follow-up for all patients was 30.9 months. At last follow-up, 28/41 patients (68.3%) were free from biochemical failure, with 20 of 41 patients (48.8%) expressing undetectable PSA levels. Serum PSA evaluations at 30 Gy did not significantly predict for either biochemical (p=0.0917) or clinical (p=0.106) disease-free outcome. However, serum PSA evaluations at 45 Gy significantly predicted for both biochemical (p=0.0043) and clinical (p=0.0244) disease-free outcomes, with PSA elevations at 45 Gy significantly associated with poor outcomes. On univariate analysis of prognosticators for biochemical failures, the following were significant: an elevation in serum PSA levels at 45 Gy, detectable serum PSA immediately after prostatectomy, Gleason score 7-10, and serum PSA level >1 ng/ml before salvage radiotherapy. Conclusion: Evaluation of serum PSA level at 45 Gy of salvage radiotherapy for biochemical relapses after prostatectomy may serve as a significant prognosticator for both biochemical and clinical disease-free outcomes

Limb Salvage After Failed Initial Operative Management of Bimalleolar Ankle Fractures in Diabetic Neuropathy.

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Vaudreuil, Nicholas J; Fourman, Mitchell S; Wukich, Dane K

2017-03-01

Ankle fractures in patients with diabetes mellitus (DM) can be difficult to manage, especially in the presence of peripheral neuropathy. In patients who fail initial operative management, attempts at limb salvage can be challenging, and no clear treatment algorithm exists. This study examined outcomes of different procedures performed for limb salvage in this population. This study retrospectively reviewed 17 patients with DM complicated by peripheral neuropathy who sustained a bimalleolar ankle fracture and failed initial operative management. Patients were treated with revision open reduction internal fixation (ORIF) (3/17), closed reduction external fixation (CREF) (8/17), or primary ankle joint fusion (3/17 tibiotalocalcaneal fusion with hindfoot nail [TTCN] and 3/17 with tibiotalar arthrodesis using plates and screws [TTA]). Median follow-up was 20 months. The overall rate of limb salvage was 82.3% (14/17). All patients who went on to amputation presented with infection and were treated initially with CREF (3/3). All patients who achieved successful limb salvage ended up with a clinically fused ankle joint (14/14); 9 underwent a primary or delayed formal fusion and 5 had a clinically fused ankle joint at study conclusion after undergoing revision ORIF or CREF with adjunctive procedures. This small study suggests that in this complicated group of patients it is difficult to achieve limb salvage with an end result of a functional ankle joint. CREF can be a viable option in cases where underlying infection or poor bone quality is present. Treatment with revision ORIF frequently requires supplementary external fixator or tibiotalar Steinman pin placement for additional stability. All patients who underwent revision ORIF ended up with clinically fused ankle joints at the end of the study period. Primary fusion procedures (TTA, TTCN) were associated with a high rate of limb salvage and a decreased number of operations. Level III, retrospective case series.

Long-term follow-up of salvage radiotherapy in Hodgkin's lymphoma after chemotherapy failure

International Nuclear Information System (INIS)

Campbell, Belinda; Wirth, Andrew; Milner, Alvin; Di Iulio, Juliana; MacManus, Michael; Ryan, Gail M.

2005-01-01

Purpose: To evaluate the long-term results of salvage radiotherapy (SRT) for Hodgkin's lymphoma after chemotherapy failure. Methods and Materials: We reviewed 81 patients undergoing SRT for persistent or recurrent Hodgkin's lymphoma after chemotherapy; 19 also received conventional-dose salvage chemotherapy. Results: At SRT, the median patient age was 31 years. Of the 81 patients, 81% had Stage I-II, 25.9% had B symptoms, 14.8% had bulky disease, and 7.4% had extranodal disease. A less than a complete response (CR) to the last chemotherapy regimen occurred in 47%. SRT was generally limited to one side of the diaphragm, and the median dose was 36 Gy. After SRT, 75% of patients achieved a CR, with 82% retaining durable in-field control. In-field failure was associated with less than a CR to the last chemotherapy regimen (p = 0.0287). Most failures were at distant sites, with 60% in previously involved sites. The 10-year freedom from treatment failure and overall survival rates were 32.8% and 45.7%, respectively. The adverse prognostic factors for freedom from treatment failure were age >50 years (p 50 years (p < 0.001), B symptoms (p = 0.002), and less than a CR to the last chemotherapy regimen (p = 0.002). Favorable cohorts had a 10-year freedom from treatment failure rate of 51% and overall survival rate of 92%. Conclusions: Salvage radiotherapy is effective for selected patients with Hodgkin's lymphoma after chemotherapy failure and should be considered for incorporation into salvage programs

Systemic Chemotherapy as Salvage Treatment for Locally Advanced Rectal Cancer Patients Who Fail to Respond to Standard Neoadjuvant Chemoradiotherapy.

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Sclafani, Francesco; Brown, Gina; Cunningham, David; Rao, Sheela; Tekkis, Paris; Tait, Diana; Morano, Federica; Baratelli, Chiara; Kalaitzaki, Eleftheria; Rasheed, Shahnawaz; Watkins, David; Starling, Naureen; Wotherspoon, Andrew; Chau, Ian

2017-06-01

The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is

Salvage definitive chemo-radiotherapy for locally recurrent oesophageal carcinoma after primary surgery: retrospective review

International Nuclear Information System (INIS)

Baxi, S. H.; Burmeister, B.; Harvey, J. A.; Smithers, M.; Thomas, J.

2008-01-01

Full text: To determine the overall survival and gastrointestinal toxicity for patients treated with salvage definitive chemo-radiotherapy after primary surgery for locoregional relapse of oesophageal carcinoma. A retrospective review of 525 patients who had a resection for oesophageal or oesophagogastric carcinoma at Princess Alexandra Hospital identified 14 patients treated with salvage definitive radiotherapy or chemo-radiotherapy, following localized recurrence of their disease. We analysed the patient and treatment characteristics to determine the median overall survival as the primary end point. Gastrointestinal toxicity was examined to determine if increased toxicity occurred when the stomach was irradiated within the intrathoracic radiotherapy field. The median overall survival for patients treated with curative intent using salvage definitive chemo-radiotherapy was 16 months and the 2-year overall survival is 21%. One patient is in clinical remission more than 5 years after therapy. Age <60 years old and nodal recurrence were favourable prognostic factors. Treatment compliance was 93% with only one patient unable to complete the intended schedule. Fourteen per cent of patients experienced grade 3 or 4 gastrointestinal toxicity. Salvage definitive chemo-radiotherapy should be considered for good performance status patients with oesophageal carcinoma who have a locoregional relapse after primary surgery. The schedule is tolerable with low toxicity and an acceptable median survival

Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

Science.gov (United States)

Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

2016-06-01

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

Directory of Open Access Journals (Sweden)

Matthew Arentz

Full Text Available Use of antiretroviral therapy (ART during treatment of drug susceptible tuberculosis (TB improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR 3.4, 95% CI 1.6-7.4 and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6 during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3 and less than 50 cells/mm(3, and when correcting for drug resistance pattern.We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

Neither high-dose nor low-dose brachytherapy increases flap morbidity in salvage treatment of recurrent head and neck cancer

Directory of Open Access Journals (Sweden)

Peter W. Henderson

2016-08-01

Full Text Available Purpose: While brachytherapy is often used concurrently with flap reconstruction following surgical ablation for head and neck cancer, it remains unclear whether it increases morbidity in the particularly high risk subset of patients undergoing salvage treatment for recurrent head and neck cancer (RH&NC. Material and methods : A retrospective chart review was undertaken that evaluated patients with RH&NC who underwent flap coverage after surgical re-resection and concomitant brachytherapy. The primary endpoint was flap viability, and the secondary endpoints were flap and recipient site complications. Results : In the 23 subjects included in series, flap viability and skin graft take was 100%. Overall recipient site complication rate was 34.8%, high-dose radiation (HDR group 50%, and low-dose radiation (LDR group 29.4%. There was no statistically significant difference between these groups. Conclusions : In patients who undergo flap reconstruction and immediate postoperative radiotherapy following salvage procedures for RH&NC, flap coverage of defects in combination with brachytherapy remains a safe and effective means of providing stable soft tissue coverage.

Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy

International Nuclear Information System (INIS)

Monti, Carlos R.; Nakamura, Ricardo A.; Ferrigno, Robson; Rossi Junior, Aristides; Kawakami, Neusa S.; Trevisan, Felipe A.

2006-01-01

Objective: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. Materials and methods: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA ≥ 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81). Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. Results: The median follow-up was of 55 months (17-83). The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7% e 84.7%, respectively. The actuarial global survival rate in 5 years was 96.1%.The actuarial survival rate free of biochemical recurrence in 5 years was 83.3% with PSA pre-radiotherapy ≤ 1, 100% when > 1 and ≤ 2, and 57.1% when > 2 (p = 0.023). Dose > 70 Gy in 30% of the bladder volume implied in more acute urinary toxicity (p = 0.035). The mean time for the development of late urinary toxicity was 21 months (12-51). Dose > 55 Gy in 50% bladder volume implied in more late urinary toxicity (p = 0.018). A patient presented late rectal toxicity of second grade. Conclusions: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < 2 ng/mL have more biochemical control. (author)

Salvage Islet Auto Transplantation After Relaparatomy.

Science.gov (United States)

Balzano, Gianpaolo; Nano, Rita; Maffi, Paola; Mercalli, Alessia; Melzi, Raffaelli; Aleotti, Francesca; Gavazzi, Francesca; Berra, Cesare; De Cobelli, Francesco; Venturini, Massimo; Magistretti, Paola; Scavini, Marina; Capretti, Giovanni; Del Maschio, Alessandro; Secchi, Antonio; Zerbi, Alessandro; Falconi, Massimo; Piemonti, Lorenzo

2017-10-01

To assess feasibility, safety, and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding after pancreatic surgery. From November 2008 to October 2016, approximately 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n = 11) or bleeding (n = 11). Feasibility, efficacy, and safety of salvage IAT were compared with those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy. The percentage of candidates that received the infusion of islets was significantly lower in salvage IAT than simultaneous IAT (59.1% vs 88.9%, P = 0.008), mainly because of a higher rate of inadequate islet preparations. Even if microbial contamination of islet preparation was significantly higher in candidates to salvage IAT than in those to simultaneous IAT (78.9% vs 20%, P < 0.001), there was no evidence of a higher rate of complications related to the procedure. Median follow-up was 5.45 ± 0.52 years. Four (36%) of 11 patients reached insulin independence, 6 patients (56%) had partial graft function, and 1 patient (9%) had primary graft nonfunction. At the last follow-up visit, median fasting C-peptide was 0.43 (0.19-0.93) ng/mL; median insulin requirement was 0.38 (0.04-0.5) U/kg per day, and median HbA1c was 6.6% (5.9%-8.1%). Overall mortality, in-hospital mortality, metabolic outcome, graft survival, and insulin-free survival after salvage IAT were not different from those documented after simultaneous IAT. Our data demonstrate the feasibility, efficacy, and safety of salvage IAT after relaparotomy.

Peripheral Sympathectomy for Raynaud's Phenomenon: A Salvage Procedure

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Wen-Her Wang

2006-10-01

Full Text Available We retrospectively reviewed the effectiveness of peripheral sympathectomy for severe Raynaud's phenomenon. In this study, a total of 14 digits from six patients with chronic digital ischemic change were included. All patients had pain, ulcer, or gangrenous change in the affected digits and were unresponsive to pharmacologic or other nonsurgical therapies. In all cases, angiography showed multifocal arterial lesions, so microvascular reconstruction was unfeasible. Peripheral sympathectomy was performed as a salvage procedure to prevent digit amputation. The results were analyzed according to reduction of pain, healing of ulcers, and prevention of amputation. In 12 of the 14 digits, the ulcers healed and amputation was avoided. In the other two digits, the ulcers improved and progressive gangrene was limited. As a salvage procedure for Raynaud's phenomenon recalcitrant to conservative treatment, peripheral sympathectomy improves perfusion to ischemic digits and enables amputation to be avoided.

Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

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Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

2014-02-15

The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

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Bae, Sun Hyun [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Hee Chul, E-mail: rophc@skku.edu [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Do Hoon; Lee, Jung Ae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2012-03-15

Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

International Nuclear Information System (INIS)

Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon; Lee, Jung Ae; Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2012-01-01

Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

Perceived adherence barriers among patients failing second-line ...

African Journals Online (AJOL)

Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa. W Barnett, G Patten, B Kerschberger, K Conradie, DB Garone, G van Cutsem, CJ Colvin ...

Cost-effectiveness of sunitinib as second-line treatment for gastrointestinal stromal tumor in the People’s Republic of China

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Li J

2017-01-01

Full Text Available Jian Li,1 Hong Ye Ren,2 Juanjuan Zhang,2 Peng Dong,2 Yan Wang,3 Andrea L Stevens,3 Yi Han,3 Min Huang4 1Laboratory of Carcinogenesis and Translational Research for the Ministry of National Education, Department of GI Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, 2Pfizer Inc., Beijing, People’s Republic of China; 3WG Consulting, New York, NY, USA; 4School of Pharmacy, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China Objective: To evaluate the cost-effectiveness of sunitinib as a second-line treatment in patients with advanced gastrointestinal stromal tumors that no longer respond to imatinib 400 mg/d, compared with imatinib 600 mg/d, 800 mg/d, or best supportive care (BSC in the People’s Republic of China. Methods: This study was conducted from the government payer’s perspective with a time horizon of 5 years. Three health states were considered: progression-free survival, disease progression survival, and death, with a cycle length of 6 weeks. Probabilities of disease progression and death were estimated based on survival functions using exponential distribution and progression survival data in the clinical trials. Drug costs were based on drug retail prices and the patient assistance program in the People’s Republic of China, and adverse event management costs were based on published data and/or expert opinion. Uncertainties for parameters in the study were addressed through one-way deterministic and probabilistic sensitivity analysis. Results: When sunitinib was compared with imatinib 600 mg/d and BSC, the incremental cost-effectiveness ratio was RMB75,715 with RMB121,080 per quality-adjusted life-year (QALY gained. Sunitinib demonstrated lower costs and higher QALYs than imatinib 800 mg/d. In the probabilistic sensitivity analysis, the willingness-to-pay per QALY gained was set to be three times the per capita gross domestic product of the People’s Republic of

Second malignancies after treatment for Ewing's sarcoma: a report of the CESS-studies

International Nuclear Information System (INIS)

Dunst, Juergen; Ahrens, Susanne; Paulussen, Michael; Ruebe, Christian; Winkelmann, Wilfried; Zoubek, Andreas; Harms, Dieter; Juergens, Herbert

1998-01-01

Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. Results: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but

INDONESIAN SALVAGE LAW WITHIN THE FRAMEWORK OF CONTEMPORARY MARITIME LAW

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Dhiana Puspitawati

2015-12-01

Full Text Available Located in a strategic position, that is between two great oceans and two land masses have made Indonesia a centre of international trade and shipping. In fact, 90% of international trades are carried out through the ocean. It is therefore crucial to assure that the activities in carrying goods across the ocean are incident free. However, if accident happens, assistance from professionals to preserve items of property is desirable. In such, salvage law emerged. This paper discusses comprehensively Indonesian salvage law within the framework of contemporary maritime law. While Indonesian maritime law is mostly based on its national law on the carriage of goods by the sea, in fact, the development of maritime law is highly affected by international practices which are largely based on international conventions and regulations. This research finds that while Indonesian salvage law can be found in Book II Chapter VII article 545-568k Wetboek Van Koophandel or known as Kitab Undang-undang Hukum Dagang (KUHD, which focused narrowly on the value of salved property as the primary measures of success, yet Indonesian salvage law has not been developed in accordance with current international salvage law, which adopted a broader and more balanced approached in both commercial and environmental aspects. Although it is believed that such approached is “culturally unrecognized” in Indonesia, this research argued that since Indonesian waters are part of international waters, all process by waters including salvage should confirm the relevant international practices and regulations. While Indonesia has taken out salvage law from KUHD and regulates it within Act Number 17/2008 on navigation, however, such act only provides one article for salvage stating that salvage will be regulates further by Ministry Regulation. Untill this paper was written no such government regulation produced yet by Indonesia. Since Indonesian waters is the centre of international

Modified endoscopic medial maxillectomy for zygomatic implant salvage.

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Schwartz, Joseph S; Tajudeen, Bobby A; Adappa, Nithin D; Palmer, James N

2016-01-01

Odontogenic chronic rhinosinusitis (CRS) is an epidemiologically important disease process due, in part, to the increasingly commonplace use of dental restorative procedures such as zygomatic implantation. Traditional management of this clinical entity typically entails extraction of the infected hardware via an open or endoscopic approach. We describe a novel management strategy of odontogenic CRS following bilateral zygomatic implantation for oral rehabilitation that we surgically salvaged via a modified endoscopic medial maxillectomy. We describe the presentation and management of a case of metachronous development of bilateral CRS subsequent to zygomatic implantation. The patient's postoperative course was characterized by marked endoscopic, radiologic, and symptomatic improvement as measured by the 22-item Sino-Nasal Outcome Test. We describe a novel treatment strategy for the management of odontogenic sinusitis resulting from erroneous zygomatic implant placement. Modified endoscopic medial maxillectomy in this clinical context facilitates mucosal normalization of the affected sinus, while permitting preservation of oral function through salvage of the displaced implant.

Prices of second-line antiretroviral treatment for middle-income countries inside versus outside sub-Saharan Africa.

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Simmons, Bryony; Hill, Andrew; Ford, Nathan; Ruxrungtham, Kiat; Ananworanich, Jintanat

2014-01-01

Antiretrovirals are available at low prices in sub-Saharan Africa, but these prices may not be consistently available for middle-income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub-Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub-Saharan Africa. HIV drug prices used in national programmes (2010-2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle-income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub-Saharan Africa versus those outside. Five key second-line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir. Prices of branded antiretrovirals were significantly higher outside sub-Saharan Africa (psub-Saharan Africa versus $4689 (IQR $4075-5717) in non-African middle-income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub-Saharan Africa and other regions. Pharmaceutical companies are selling antiretrovirals to non-African middle-income countries at prices 74-541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non-African middle-income countries need to be improved, to ensure sustainable treatment access.

Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy.

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Matsumoto, Kazumasa; Mochizuki, Kohei; Hirayama, Takahiro; Ikeda, Masaomi; Nishi, Morihiro; Tabata, Ken-ichi; Okazaki, Miyoko; Fujita, Tetsuo; Taoka, Yoshinori; Iwamura, Masatsugu

2015-01-01

This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine 1,000 mg/m2 on days 1, 8 and 15 and nedaplatin 70 mg/m2 on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.

In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

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Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

2016-08-02

Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

A comparison of individualized treatment guided by VeriStrat with standard of care treatment strategies in patients receiving second-line treatment for advanced non-small cell lung cancer: A cost-utility analysis.

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Nelson, Richard E; Stenehjem, David; Akerley, Wallace

2013-12-01

Two therapies are appropriate as 2nd-line treatment of non-small cell lung cancer (NSCLC) patients: chemotherapy and epidermal growth factor receptor (EGFR) inhibitor therapy. VeriStrat, a serum proteomic test, can be used to guide treatment decisions for NSCLC patients. The test classifies patients as likely to benefit from either of these two treatment options. The objective of this research was to model the anticipated survival and cost-effectiveness of four different treatment strategies: chemotherapy for all patients (C-all), EGFR inhibitor for all (E-all), a performance status guided selection strategy (PS-guided), and a strategy guided by VeriStrat test results (V-guided). We developed a Markov model with the perspective of the U.S. health care system. Model inputs were taken from published literature for the base-case analysis. One-way and probabilistic sensitivity analyses were performed. The C-all treatment strategy showed the best overall survival outcome (10.1 months), followed by V-guided (9.6 months), PS-guided (9.2 months), and E-all (8.2 months) strategies. The incremental cost-effectiveness ratio (ICER) of a V-guided treatment strategy was $91,111 (vs. E-all) and $8462 (vs. PS-guided) per quality-adjusted life year (QALY). The ICER for C-all compared to V-guided was $105,616. This cost-utility analysis indicates that a treatment strategy guided by the VeriStrat test in patients receiving second-line therapy for NSCLC may experience an overall survival benefit at an incremental cost-effectiveness ratio that is reasonable when compared with other practices, including cancer treatments, generally covered in the U.S. health care system. However, treating all patients with chemotherapy yielded the greatest expected survival. Copyright © 2013. Published by Elsevier Ireland Ltd.

Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

Science.gov (United States)

Chae, Kum Ju; Shin, Jin Yong

2016-01-01

Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, pdiabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

Outcome of salvage radiotherapy for biochemical failure after radical prostatectomy with or without hormonal therapy

International Nuclear Information System (INIS)

Cheung, Rex; Kamat, Ashish M.; Crevoisier, Renaud de; Allen, Pamela K.; Lee, Andrew K.; Tucker, Susan L.; Pisters, Louis; Babaian, Richard J.; Kuban, Deborah

2005-01-01

Background: This study analyzed the outcome of salvage radiotherapy for biochemical failure after radical prostatectomy (RP). By comparing the outcomes for patients who received RT alone and for those who received combined RT and hormonal therapy, we assessed the potential benefits of hormonal therapy. Patients and Methods: This cohort was comprised of 101 patients who received salvage RT between 1990 and 2001 for biochemical failure after RP. Fifty-nine of these patients also received hormone. Margin status (positive vs. negative), extracapsular extension (yes vs. no), seminal vesicle involvement (yes vs. no), pathologic stage, Gleason score, pre-RP PSA, post-RP PSA, pre-RT PSA, hormonal use, radiotherapy dose and technique, RP at M. D. Anderson Cancer Center, and time from RP to salvage RT were analyzed. Statistically significant variables were used to construct prognostic groups. Results: Independent prognostic factors for the RT-alone group were margin status and pre-RT PSA. RP at M. D. Anderson Cancer Center was marginally significant (p = 0.06) in multivariate analysis. Pre-RT PSA was the only significant prognostic factor for the combined-therapy group. We used a combination of margin status and pre-RT PSA to construct a prognostic model for response to the salvage treatment based on the RT group. We identified the favorable group as those patients with positive margin and pre-RT PSA ≤0.5 ng/mL vs. the unfavorable group as otherwise. This stratification separates patients into clinically meaningful groups. The 5-year PSA control probabilities for the favorable vs. the unfavorable group were 83.7% vs. 61.7% with radiotherapy alone (p = 0.03). Androgen ablation seemed to be most beneficial in the unfavorable group. Conclusion: After prostatectomy, favorable-group patients may fare well with salvage radiotherapy alone. These patients may be spared the toxicity of androgen ablation. The other patients may benefit most from a combined approach with hormonal

Perceived adherence barriers among patients failing second-line ...

African Journals Online (AJOL)

1 School of Public Health and Family Medicine, University of Cape Town, South Africa ... To examine factors affecting adherence to second-line ART from the perspective of clinic staff and .... because she did not realise her VL would go up.

Low lopinavir plasma or hair concentrations explain second-line protease inhibitor failures in a resource-limited setting

NARCIS (Netherlands)

van Zyl, Gert Uves; van Mens, Thijs E.; McIlleron, Helen; Zeier, Michele; Nachega, Jean B.; Decloedt, Eric; Malavazzi, Carolina; Smith, Peter; Huang, Yong; van der Merwe, Lize; Gandhi, Monica; Maartens, Gary

2011-01-01

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure. We conducted a cross-sectional survey to investigate the aetiology of virologic failure in 2 public

Improvement in dose escalation using off-line and on-line image feedback in the intensity modulated beam design for prostate cancer treatment

International Nuclear Information System (INIS)

Yan, D.; Birkner, M.; Nuesslin, F.; Wong, J.; Martinez, A.

2001-01-01

Purpose: To test the capability of dose escalation in the IMRT process where the organ/patient temporal geometric variation, measured using either off-line or on-line treatment CT and portal images, are adapted for the optimal design of intensity modulated beam. Materials and Methods: Retrospective study was performed on five prostate cancer patients with multiple CT scans (14∼17/patient) and daily portal images obtained during the treatment course. These images were used to determine the displacements of each subvolume in the organs of interest caused by the daily patient setup and internal organ motion/deformation. The temporal geometric information was processed in order of treatment time and fed into an inverse planning system. The inverse planning engine was specifically implemented to adapt the design of intensity modulated beam to the temporal subvolume displacement and patient internal density changes. Three image feedback strategies were applied to each patient and evaluated with respect to the capability of safe dose escalation. The first one is off-line image feedback, which designs the beam intensity based on the patient images measured within the first week of treatment. The second is an on-line 'the target of the day' strategy, which designs the beam intensity in daily bases by using 'the image of the day' alone. The last one is also the on-line based. However, it designs the instantaneous beam intensity based on also dose distribution in each organ of interest received prior to the current treatment. For each of the treatment strategies, the minimum dose delivered to the CTV was determined by applying the identical normal tissue constraints of partial dose/volumes. This minimum dose was used to represent the treatment dose for each patient. Results: The off-line strategy appears feasible after 5 days of image feedback. The average treatment dose among the patients can be 10% higher than the one in the conventional IMRT treatment where the inverse

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

Directory of Open Access Journals (Sweden)

Thumallapally N

2016-08-01

Full Text Available Nishitha Thumallapally,1 Hana Yu,1 Divya Asti,1 Adarsh Vennepureddy,1 Terenig Terjanian2 1Department of Internal Medicine, 2Division of Hematology and Oncology, Staten Island University Hospital, New York, NY, USA Abstract: The treatment landscape for multiple myeloma (MM is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development. Keywords: multiple myeloma, novel drugs, relapsed and refractory myeloma, salvage chemotherapy 

The need for second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030: a mathematical modelling study.

Science.gov (United States)

Estill, Janne; Ford, Nathan; Salazar-Vizcaya, Luisa; Haas, Andreas D; Blaser, Nello; Habiyambere, Vincent; Keiser, Olivia

2016-03-01

The number of patients in need of second-line antiretroviral drugs is increasing in sub-Saharan Africa. We aimed to project the need of second-line antiretroviral therapy in adults in sub-Saharan Africa up to 2030. We developed a simulation model for HIV and applied it to each sub-Saharan African country. We used the WHO country intelligence database to estimate the number of adult patients receiving antiretroviral therapy from 2005 to 2014. We fitted the number of adult patients receiving antiretroviral therapy to observed estimates, and predicted first-line and second-line needs between 2015 and 2030. We present results for sub-Saharan Africa, and eight selected countries. We present 18 scenarios, combining the availability of viral load monitoring, speed of antiretroviral scale-up, and rates of retention and switching to second-line. HIV transmission was not included. Depending on the scenario, 8·7-25·6 million people are expected to receive antiretroviral therapy in 2020, of whom 0·5-3·0 million will be receiving second-line antiretroviral therapy. The proportion of patients on treatment receiving second-line therapy was highest (15·6%) in the scenario with perfect retention and immediate switching, no further scale-up, and universal routine viral load monitoring. In 2030, the estimated range of patients receiving antiretroviral therapy will remain constant, but the number of patients receiving second-line antiretroviral therapy will increase to 0·8-4·6 million (6·6-19·6%). The need for second-line antiretroviral therapy was two to three times higher if routine viral load monitoring was implemented throughout the region, compared with a scenario of no further viral load monitoring scale-up. For each monitoring strategy, the future proportion of patients receiving second-line antiretroviral therapy differed only minimally between countries. Donors and countries in sub-Saharan Africa should prepare for a substantial increase in the need for second-line

[Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

Science.gov (United States)

Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

2015-06-01

This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

International Nuclear Information System (INIS)

Hsu, Charles C.; Hsu, Howard; Pickett, Barby; Crehange, Gilles; Hsu, I-Chow Joe; Dea, Ryan; Weinberg, Vivian; Gottschalk, Alexander R.; Kurhanewicz, John; Shinohara, Katsuto; Roach, Mack

2013-01-01

Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or ≥7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

Feasibility of MR Imaging/MR Spectroscopy-Planned Focal Partial Salvage Permanent Prostate Implant (PPI) for Localized Recurrence After Initial PPI for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Hsu, Charles C., E-mail: hsucc@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Hsu, Howard [Department of Radiation Oncology, New York University, New York, New York (United States); Pickett, Barby [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Crehange, Gilles [Department of Radiation Oncology, Dijon University, Dijon (France); Hsu, I-Chow Joe; Dea, Ryan [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Weinberg, Vivian [Biostatistics and Computational Biology Core, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Gottschalk, Alexander R. [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Kurhanewicz, John [Department of Radiology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Shinohara, Katsuto [Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California (United States)

2013-02-01

Purpose: To assess the feasibility of magnetic resonance imaging (MRI)-planned partial salvage permanent prostate implant (psPPI) among patients with biopsy-proven local recurrence after initial PPI without evidence of distant disease. Methods and Materials: From 2003-2009, 15 patients underwent MRI/magnetic resonance spectroscopy (MRS) planning for salvage brachytherapy (psPPI, I-125 [n=14; 144 Gy]; Pd-103 [n=1; 125 Gy]) without hormone therapy. Full dose was prescribed to areas of recurrence and underdosage, without entire prostate implantation. Limiting urethral and rectal toxicity was prioritized. Follow-up was from salvage date to prostate-specific antigen (PSA) concentration failure (Phoenix criteria = nadir + 2.0; ASTRO = 3 consecutive rises), recurrence, distant metastases, or last follow-up PSA level. Progression-free survival (PFS) was defined as no PSA failure or biopsy-proven recurrence without all-cause mortality. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Results: At salvage, median age was 68 years, and PSA concentration was 3.5 ng/mL (range, 0.9-5.6 ng/mL). Abnormal MRI/MRS findings were evident in 40% of patients. Biopsy-proven recurrences consisted of a single focus (80%) or 2 foci (20%). At recurrence, Gleason score was 6 (67%) or {>=}7 (27%). Median interval between initial and salvage implantation was 69 months (range, 28-132 months). psPPI planning characteristics limited doses to the rectum (mean V100 = 0.5% [0.07 cc]) and urethra (V100 = 12% [0.3 cc]). At median follow-up (23.3 months; range, 8-88 months), treatment failure (n=2) resulted only in localized recurrence; both patients underwent second psPPI with follow-up PSA tests at 12 and 26 months, resulting in 0.6 and 0.7 ng/mL, respectively. American Society for Radiation Oncology PFS rates at 1, 2, and 3 years were 86.7%, 78.4%, and 62.7%, respectively, with 5 patients for whom treatment failed (n=3 with negative transrectal ultrasound

Salvage central lymphatic irradiation in follicular lymphomas following failure of chemotherapy: a feasibility study

International Nuclear Information System (INIS)

Ha, Chul S.; Tucker, Susan L.; Blanco, Angel I.; Cabanillas, Fernando; Cox, James D.

1999-01-01

Purpose: Management of follicular lymphoma after chemotherapy failure has been controversial and has ranged from watchful waiting to high-dose chemotherapy. High-dose chemotherapy with bone marrow reconstitution may produce clinical and molecular complete responses at the risk of serious morbidity and mortality. It has been previously reported that central lymphatic irradiation (CLI) can achieve long-term relapse-free survival in patients with Stage I, II, or III follicular lymphoma. Therefore, we investigated the feasibility of treating patients in whom front-line chemotherapy failed with salvage CLI instead of instituting more intensive chemotherapy. Methods and Materials: Salvage CLI with curative intent for patients with follicular lymphoma was started at The University of Texas M. D. Anderson Cancer Center in 1992. Eleven patients whose disease showed poor response to or relapsed after chemotherapy were managed with this approach. The median age of the patients was 61 years. Criteria for exclusion included bone marrow involvement or other evidence of Ann Arbor Stage IV disease at any time during the course of the disease. Overall survival and relapse-free survival were calculated from the first day of CLI. Results: Ten patients were alive at a median follow-up of 25 months (range 9-73 months). The treatment was well tolerated in general. Two patients could not complete CLI: one 75-year-old patient owing to prolonged platelet count depression and deterioration in general medical condition, and a 66-year-old patient because of exacerbation of preexisting pancytopenia and worsening of heart disease. Everyone who completed CLI remains in remission at the time of this report, except for one patient who had a relapse in the right lacrimal gland at 32 months. This patient was treated with local radiation therapy and is free of disease. Eventual recovery of the blood counts was observed for the patients who completed CLI. Conclusion: These results demonstrate for the

Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

Science.gov (United States)

Brandes, Alba A; Tosoni, A; Franceschi, E; Blatt, V; Santoro, A; Faedi, M; Amistà, P; Gardiman, M; Labianca, R; Bianchini, C; Ermani, M; Reni, M

2009-09-01

Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m(2)) every 3 weeks for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

Results of salvage surgery for mammary recurrence following breast-conserving therapy

International Nuclear Information System (INIS)

Kurtz, J.M.; Amalric, R.; Brandone, H.; Ayme, Y.; Spitalier, J.M.

1988-01-01

A retrospective analysis was performed of 118 surgically treated mammary recurrences, occurring following primary conservative excision and radiation therapy for clinical Stages I and II breast cancer. Actuarial cancer-specific survival following salvage surgery was 72% at 5 years and 58% at 10 years. With a median followup of 7 years, further local-regional recurrences were observed in 20 of the 118 patients, many of whom could be treated by further surgery. Actuarial survival after recurrence was significantly influenced by initial clinical stage, as well as by the disease-free interval following primary therapy, but was similar for both premenopausal and postmenopausal patients and for patients treated by radical or breast-conserving salvage operations. For recurrences after the fifth year, actuarial survival following salvage surgery was 83% and 68% at 5 and 10 years, respectively. Survival for Stage I patients was favorable regardless of disease-free interval. It is concluded that recurrences in the breast following primary treatment with limited surgery and irradiation have a considerably more favorable prognosis than that of local failures after primary radical surgery. Suggestions for the management of these recurrences are presented

Implant breast reconstruction after salvage mastectomy in previously irradiated patients.

Science.gov (United States)

Persichetti, Paolo; Cagli, Barbara; Simone, Pierfranco; Cogliandro, Annalisa; Fortunato, Lucio; Altomare, Vittorio; Trodella, Lucio

2009-04-01

The most common surgical approach in case of local tumor recurrence after quadrantectomy and radiotherapy is salvage mastectomy. Breast reconstruction is the subsequent phase of the treatment and the plastic surgeon has to operate on previously irradiated and manipulated tissues. The medical literature highlights that breast reconstruction with tissue expanders is not a pursuable option, considering previous radiotherapy a contraindication. The purpose of this retrospective study is to evaluate the influence of previous radiotherapy on 2-stage breast reconstruction (tissue expander/implant). Only patients with analogous timing of radiation therapy and the same demolitive and reconstructive procedures were recruited. The results of this study prove that, after salvage mastectomy in previously irradiated patients, implant reconstruction is still possible. Further comparative studies are, of course, advisable to draw any conclusion on the possibility to perform implant reconstruction in previously irradiated patients.

Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

International Nuclear Information System (INIS)

Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B.

2017-01-01

Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy.

Science.gov (United States)

Narayan, Vivek; Vapiwala, Neha; Mick, Rosemarie; Subramanian, Pearl; Christodouleas, John P; Bekelman, Justin E; Deville, Curtiland; Rajendran, Ramji; Haas, Naomi B

2017-02-01

In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

Energy Technology Data Exchange (ETDEWEB)

Narayan, Vivek [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mick, Rosemarie [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Subramanian, Pearl [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Haas, Naomi B., E-mail: naomi.haas@uphs.upenn.edu [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2017-02-01

Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

Risk factors predicting the outcome of salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy

International Nuclear Information System (INIS)

Kinoshita, Hidefumi; Shimizu, Yosuke; Mizowaki, Takashi

2013-01-01

Salvage radiotherapy is the only curative treatment for patients with prostate cancer showing biochemical progression after radical prostatectomy. In this study, we evaluated the clinicopathological parameters that influence the outcome of salvage radiotherapy. Medical records of 49 patients who underwent salvage radiotherapy after radical prostatectomy from 1997 to 2008 at the Graduate School of Medicine, Kyoto University, were retrospectively reviewed. Radiotherapy was carried out with 66 Gy on the prostatic bed. Biochemical progression-free survival after salvage radiotherapy at 2, 5 and 7 years was 51.0%, 42.2% and 42.2%, respectively. Significant parameters predicting biochemical progression after salvage radiotherapy by Cox regression analysis were prostatectomy Gleason score sum ≥8 (hazard ratio 0.08; 95% confidence interval 0.03-0.22; P=0.001), prostate-specific antigen nadir after radical prostatectomy ≥0.04 ng/mL (hazard ratio 0.30; 95% confidence interval 0.13-0.69; P=0.005) and negative surgical margin (hazard ratio 0.28; 95% confidence interval 0.12-0.70; P=0.006). When the patients were subgrouped by these risk factors, the 5-year progression-free survival rates after salvage radiotherapy were 77.8%, 50.0% and 6.7% in patients with 0, 1 and ≥2 predictors, respectively. In order to discriminate favorable candidates for salvage radiotherapy, Gleason score of prostatectomy, prostate-specific antigen nadir after prostatectomy and positive surgical margin represent independent predictors. Thus, progression-free survival might be more precisely predicted according to the presence/absence of these risk factors. The significance of this risk classification should be confirmed by large prospective studies. (author)

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

International Nuclear Information System (INIS)

Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael; Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele; Geinitz, Hans; Duma, Marciana N.

2017-01-01

Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3 + T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [de

The outcome of rectal cancer after early salvage TME following TEM compared with primary TME: a case-matched study.

Science.gov (United States)

Levic, K; Bulut, O; Hesselfeldt, P; Bülow, S

2013-08-01

Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In case of unfavourable histology after TEM, or positive resection margins, salvage surgery can be performed. However, it is unclear if the results are equivalent to primary treatment with total mesorectal excision (TME). The aim of this retrospective study was to determine whether there is a difference in outcome between patients who underwent early salvage resection with TME after TEM, and those who underwent primary TME for rectal cancer. From 1997 to 2011, early salvage surgery with TME after TEM was performed in 25 patients in our institution. These patients were compared with 25 patients who underwent primary TME, matched according to gender, age (±2 years), cancer stage and operative procedure. Data were obtained from the patients' charts and reviewed retrospectively. No patients received preoperative chemotherapy. Perioperative data and oncological outcome were analysed. The Mann-Whitney U-test and Fisher's exact test were used to compare the results between the two groups. There was no significant difference between the two groups in median operating time (P = 0.39), median blood loss (P = 0.19) or intraoperative complications (P = 1.00). The 30-day mortality was 8 % (n = 2) among patients who underwent salvage TME after TEM, and no patients died in the primary TME group (P = 0.49). There was no significant difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8 %) with local recurrences among the patients with primary TME (P = 0.49). Distant metastasis occurred in one patient (4 %) after salvage TME and in 3 patients (12 %) with primary TME (P = 0.61). The median

"Salvage microbiology": detection of bacteria directly from clinical specimens following initiation of antimicrobial treatment.

Directory of Open Access Journals (Sweden)

John J Farrell

Full Text Available PCR coupled with electrospray ionization mass spectrometry (ESI-MS is a diagnostic approach that has demonstrated the capacity to detect pathogenic organisms from culture negative clinical samples after antibiotic treatment has been initiated. [1] We describe the application of PCR/ESI-MS for detection of bacteria in original patient specimens that were obtained after administration of antibiotic treatment in an open investigation analysis.We prospectively identified cases of suspected bacterial infection in which cultures were not obtained until after the initiation of antimicrobial treatment. PCR/ESI-MS was performed on 76 clinical specimens that were submitted for conventional microbiology testing from 47 patients receiving antimicrobial treatment.In our series, 72% (55/76 of cultures obtained following initiation of antimicrobial treatment were non-diagnostic (45 negative cultures; and 10 respiratory specimens with normal flora (5, yeast (4, or coagulase-negative staphylococcus (1. PCR/ESR-MS detected organisms in 83% (39/47 of cases and 76% (58/76 of the specimens. Bacterial pathogens were detected by PCR/ESI-MS in 60% (27/45 of the specimens in which cultures were negative. Notably, in two cases of relapse of prosthetic knee infections in patients on chronic suppressive antibiotics, the previous organism was not recovered in tissue cultures taken during extraction of the infected knee prostheses, but was detected by PCR/ESI-MS.Molecular methods that rely on nucleic acid amplification may offer a unique advantage in the detection of pathogens collected after initiation of antimicrobial treatment and may provide an opportunity to target antimicrobial therapy and "salvage" both individual treatment regimens as well as, in select cases, institutional antimicrobial stewardship efforts.

Experience with second line drugs in frequently relapsing and steroid dependent childhood nephrotic syndrome in a large Saudi center

Directory of Open Access Journals (Sweden)

Khalid Alsaran, M.D.

2017-06-01

Conclusion: All the second line drugs in our study were equally effective. However, we recommend that the initial treatment of FR/SD nephrotic syndrome should be chosen with the least toxic yet equally efficacious drug Levamisole.

Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Shuyang YAO

2015-06-01

Full Text Available Background and objective This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed in previously treated advanced non-small cell lung cancer (NSCLC. Methods Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS was evaluated by Kaplan-Meier method. Results Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR (28.1% vs 18.2%, P=0.341, disease control rate (DFS(43.8% vs 45.5%, P=0.890, and PFS (4.3 months vs 3.8 months, P=0.506. In the icotinib group, the ORR of epidermal growth factor receptor (EGFR mutant was significantly higher than that of EGFR unknown or wild type (P=0.017. In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001. Conclusion Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011.

Science.gov (United States)

Nguyen, Hoa Binh; Nguyen, Nhung Viet; Tran, Huong Thi Giang; Nguyen, Hai Viet; Bui, Quyen Thi Tu

2016-01-01

Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

Directory of Open Access Journals (Sweden)

S De Groot

Full Text Available Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC. Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs.Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013. The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness.In current daily practice, 54% (336/621 of all patients was treated with targeted therapies. Most patients (84%; 282/336 received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336 also received second-line therapy; the majority was treated with everolimus (40%, 40/101 or sorafenib (28%, 28/101. Current treatment practice (including patients not receiving targeted therapy led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285 was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy. This improvement is completely driven by the health

Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model.

Science.gov (United States)

Spiess, Philippe E; Levy, David A; Mouraviev, Vladimir; Pisters, Louis L; Jones, J Stephen

2013-08-01

What's known on the subject? and what does the study add?: Previous studies have identified the most important prognostic factors of the likely outcomes of salvage prostate whole-gland ablation, including initial clinical stage, biopsy Gleason score, and PSA (total and doubling time). There is potential for further optimization of candidate selection for salvage cryoablation with curative intent and nadir PSA achieved after whole-gland cryotherapy may provide additional prognostic value. The study shows that the most important prognostic factors of biochemical progression-free survival for patients who have undergone whole-gland salvage prostate cryotherapy are nadir PSA achieved after therapy and pre-therapy biopsy Gleason score. Based on these two prognostic variables, we have identified risk stratification groups (low, intermediate and high) which help predict the expected outcomes of salvage whole-gland prostate cryotherapy in a given patient. This risk stratification constitutes a useful clinical tool in defining which patients maybe best suited for this local salvage treatment method. To assess the prognostic variables predicting the risk of biochemical progression-free survival (bPFS) after salvage prostate whole-gland cryotherapy using the Phoenix definition of bPFS. A total of 132 patients underwent prostate whole-gland salvage cryotherapy with curative intent. No patient underwent neoadjuvant/adjuvant hormonal ablative therapy, and all had extended post-salvage prostate-specific antigen (PSA) follow-up data. Cox univariate and multivariate logistic regression analyses of potential predictors of bPFS were conducted. Kaplan-Meier analyses of bPFS was also performed. At a mean (range) follow-up of 4.3 (0.9-12.7) years, the median (range) post-cryotherapy nadir PSA achieved was 0.17 (0-33.9) ng/mL. On multivariate analysis, predictors of bPFS were nadir PSA post-cryotherapy and pre-salvage biopsy Gleason score (P 2.5 ng/mL or biopsy Gleason score ≥ 7, with

Cell salvage as part of a blood conservation strategy in anaesthesia.

Science.gov (United States)

Ashworth, A; Klein, A A

2010-10-01

The use of intraoperative cell salvage and autologous blood transfusion has become an important method of blood conservation. The main aim of autologous transfusion is to reduce the need for allogeneic blood transfusion and its associated complications. Allogeneic blood transfusion has been associated with increased risk of tumour recurrence, postoperative infection, acute lung injury, perioperative myocardial infarction, postoperative low-output cardiac failure, and increased mortality. We have reviewed the current evidence for cell salvage in modern surgical practice and examined the controversial issues, such as the use of cell salvage in obstetrics, and in patients with malignancy, or intra-abdominal or systemic sepsis. Cell salvage has been demonstrated to be safe and effective at reducing allogeneic blood transfusion requirements in adult elective surgery, with stronger evidence in cardiac and orthopaedic surgery. Prolonged use of cell salvage with large-volume autotransfusion may be associated with dilution of clotting factors and thrombocytopenia, and regular laboratory or near-patient monitoring is required, along with appropriate blood product use. Cell salvage should be considered in all cases where significant blood loss (>1000 ml) is expected or possible, where patients refuse allogeneic blood products or they are anaemic. The use of cell salvage in combination with a leucocyte depletion filter appears to be safe in obstetrics and cases of malignancy; however, further trials are required before definitive guidance may be provided. The only absolute contraindication to the use of cell salvage and autologous blood transfusion is patient refusal.

Short-time effect of salvage harvesting on microbial soil properties in a Mediterranean area affected by a wildfire: preliminary results

Science.gov (United States)

Moltó, Jorge; Mataix-Solera, Jorge; Arcenegui, Victoria; Morugan, Alicia; Girona, Antonio; Garcia-orenes, Fuensanta

2014-05-01

In the Mediterranean region, wildfires are considered one of the main ecological factors, which, in addition to and in relation to changes in soil use, may cause soil loss and degradation, one of the most important environmental problems that humanity must face up to. As is well known, the soil-plant system is one of the key factors determining ecological recovery after the occurrence of a wildfire. Traditionally, a variety of forestry practices have been implemented on spanish sites after the incidence of a wildfire. Among them stands out the complete extraction of the burned wood, which consist in getting rid of the branches and other wooden debris using small controlled bonfires, splintering or mechanical extraction. This set of post-fire management practices is known as salvage logging or salvage harvesting. Despite the remarkable relevance and influence that this conjunction of techniques has on land management after a wildfire, very little experimental research focused on assessing the impact of salvage logging on the vegetal community has been done. Furthermore, even less research inquiring into the mode and grade of incidence that the salvage logging produces on soil properties has taken place. The aim of this research is to assess the effects that the salvage harvesting has on different soil microbial properties and other related properties. The study area is located in the Natural Park of the "Sierra de Mariola" in the province of Alicante, southeastern Spain. This location was affected by a wildfire whose extension reached more than 500 Ha in July 2012. Different post-fire treatments were proposed by the authorities, including salvage harvesting in some areas. Two different treatments were distinguished for the study, "control" (without any kind of burned wood removal) and "harvest" (where salvage logging was carried out), in each area three 4 m2 sampling plots were set up. These two treatments were established on the same slope with the same orography

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010.

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Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; Dimeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

2014-05-01

Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to

Trauma center variation in splenic artery embolization and spleen salvage: a multicenter analysis.

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Banerjee, Aman; Duane, Therese M; Wilson, Sean P; Haney, Starre; O'Neill, Patrick J; Evans, Heather L; Como, John J; Claridge, Jeffrey A

2013-07-01

This study aimed to evaluate if variation in management of blunt splenic injury (BSI) among Level I trauma centers is associated with different outcomes related to the use of splenic artery embolization (SAE). All adult patients admitted for BSI from 2008 to 2010 at 4 Level I trauma centers were reviewed. Use of SAE was determined, and outcomes of spleen salvage and nonoperative management (NOM) failure were evaluated. A priori, a 10% SAE rate was used to group centers into high- or low-use groups. There were 1,275 BSI patients. There were intercenter differences in age, injury severity, and grade of spleen injury (Spleen Injury Scale [SIS]). Mortality was similar by center; however, BSI treatment varied significantly by center. Overall, SAE use was highest at center A compared with B, C, and D (19%, 11%, 1%, and 4%, respectively; p trauma centers. Centers with higher rates of SAE use have higher spleen salvage and less NOM failure. SAE was shown to be an independent predictor of spleen salvage. Therapeutic study, level IV.

Dabrafenib Treatment in a Patient with an Epithelioid Glioblastoma and BRAF V600E Mutation

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Garry Ceccon

2018-04-01

Full Text Available Novel therapeutic targets in malignant glioma patients are urgently needed. Point mutations of the v-Raf murine sarcoma viral oncogene homolog B (BRAF gene occur predominantly in melanoma patients, but may also occur in gliomas. Thus, this is a target of great interest for this group of patients. In a nine-year-old male patient, an anaplastic astrocytoma in the left temporoparietal region was diagnosed histologically. After first- and second-line treatment, a malignant progression to a secondary glioblastoma was observed ten years after the initial diagnosis. Within the following seven years, all other conventional treatment options were exhausted. At this time point, recurrent tumor histology revealed an epithelioid glioblastoma, without a mutation in the isocitrate dehydrogenase gene (IDH wild-type. In order to identify a potential target for an experimental salvage therapy, mutational tumor analysis showed a BRAF V600E mutation. Consecutively, dabrafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images (MRI were consistent with “Stable Disease” according to the Response Assessment in Neuro-Oncology Working Group (RANO criteria for the following ten months until tumor progression was detected. The patient died 16 months after dabrafenib treatment initiation. Particularly in younger glioma patients as well as in patients with an epithelioid glioblastoma, screening for a V600E BRAF mutation is promising since, in these cases, targeted therapy with BRAF inhibitors seems to be a useful salvage treatment option.

Helicobacter pylori first-line and rescue treatments in the presence of penicillin allergy.

Science.gov (United States)

Gisbert, Javier P; Barrio, Jesús; Modolell, Inés; Molina-Infante, Javier; Aisa, Angeles Perez; Castro-Fernández, Manuel; Rodrigo, Luis; Cosme, Angel; Gisbert, Jose Luis; Fernández-Bermejo, Miguel; Marcos, Santiago; Marín, Alicia C; McNicholl, Adrián G

2015-02-01

Helicobacter pylori eradication is a challenge in penicillin allergy. To assess the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin. Prospective multicenter study. Patients allergic to penicillin were given a first-line treatment comprising (a) 7-day omeprazole-clarithromycin-metronidazole and (b) 10-day omeprazole-bismuth-tetracycline-metronidazole. Rescue treatments were as follows: (a) bismuth quadruple therapy; (b) 10-day PPI-clarithromycin-levofloxacin; and (c) 10-day PPI-clarithromycin-rifabutin. Eradication was confirmed by (13)C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by questionnaires. In total, 267 consecutive treatments were included. (1) First-line treatment: Per-protocol and intention-to-treat eradication rates with omeprazole-clarithromycin-metronidazole were 59 % (62/105; 95 % CI 49-62 %) and 57 % (64/112; 95 % CI 47-67 %). Respective figures for PPI-bismuth-tetracycline-metronidazole were 75 % (37/49; 95 % CI 62-89 %) and 74 % (37/50; 95 % CI (61-87 %) (p failure; compliance was 88-100 %, with 23-29 % adverse effects (all mild). (3) Third-/fourth-line treatment: Intention-to-treat eradication rate with PPI-clarithromycin-rifabutin was 22 %. In allergic to penicillin patients, a first-line treatment with a bismuth-containing quadruple therapy (PPI-bismuth-tetracycline-metronidazole) seems to be a better option than the triple PPI-clarithromycin-metronidazole regimen. A levofloxacin-based regimen (together with a PPI and clarithromycin) represents a second-line rescue option in the presence of penicillin allergy.

Viable tumor in salvage neck dissections in head and neck cancer : Relation with initial treatment, change of lymph node size and human papillomavirus

NARCIS (Netherlands)

van den Bovenkamp, Karlijn; Dorgelo, Bart; Noordhuis, Maartje G; van der Laan, Bernard F A M; van der Vegt, Bert; Bijl, Hendrik P; Roodenburg, Jan L; van Dijk, Boukje A C; Oosting, Sjoukje F; Schuuring, Ed M D; Langendijk, Johannes A; Halmos, Gyorgy B; Plaat, Boudewijn E C

Objectives: To identify predictive factors for the presence of viable tumor and outcome in head and neck cancer patients who undergo therapeutic salvage neck dissections. Materials and Methods: Retrospective analysis of 76 salvage neck dissections after radiotherapy alone (n = 22), radiotherapy in

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

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Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Partner Site Munich, Munich (Germany); Geinitz, Hans [Johannes Kepler University, Department of Radiation Oncology, Ordensklinikum Linz, Krankenhaus der Barmherzigen Schwestern and Medical Faculty, Linz (Austria); Duma, Marciana N. [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany)

2017-08-15

Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3{sup +} T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [German] Die Strahlentherapie (RT) ist eine bewaehrte Behandlung beim primaeren und rezidivierten Prostatakarzinoms. In dieser Studie wurde der Einfluss einer definitiven und Salvage RT auf die Zusammensetzung der Lymphozytensubpopulationen verglichen, um potenzielle Immuneffekte einer RT zu analysieren. In die Studie wurden 33 Prostatakarzinompatienten eingeschlossen

Salvage surgery for hypopharyngeal carcinoma and cervical esophageal carcinoma with local recurrence or residual tumor after chemoradiotherapy

International Nuclear Information System (INIS)

Takemura, Hirokazu; Hayashi, Ryuichi; Yamazaki, Mitsuo

2008-01-01

In this study, we present the treatment results of salvage surgery in 34 patients with residual primary tumor or local relapse tumor in the hypopharynx and cervical esophagus after radiotherapy (15 patients) or chemoradiotherapy (19 patients) at the Division of Head and Neck Surgery, National Cancer Center Hospital East between 1997 and 2006. All patients underwent total pharyngolaryngoesophagectomy (TPLE) as salvage surgery. Among these patients, postoperative complication was observed in 11 patients (32.4%). Fisher's exact test revealed no significant difference in postoperative complication rate between the radiotherapy (RT) group and chemoradiotherapy (CRT) group. Tumors in the neck recurred in 10 patients (55.6%) after surgical resection. The tumor recurrence control rate for cervical lymph nodes was 84.7% for patients with clinically N0 disease after CRT who had not undergone neck dissection. The median survival time was 392 days. We consider that salvage surgery can he safely performed by considering the necessity and method of operation, and the outcome of patients receiving CRT would he improved by salvage surgery. (author)

Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

DEFF Research Database (Denmark)

van Imhoff, Gustaaf W; McMillan, Andrew; Matasar, Matthew J

2017-01-01

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Pat...

Title of the paper goes here second line

Indian Academy of Sciences (India)

Title of the paper goes here second line. AUTHOR11, AUTHOR21 and AUTHOR32,*. 1 Department of P, University X. 2 Department of Q, University Z. Abstract. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes here. Abstract text goes ...

Alternative Fuel Reduction Treatments in the Gunflint Corridor of the Superior National Forest: Second year results and sampling recommendations

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Daniel W. Gilmore; Douglas N. Kastendick; John C. Zasada; Paula J. Anderson

2003-01-01

Fuel loadings need to be considered in two ways: 1) the total fuel loadings of various size classes and 2) their distribution across a site. Fuel treatments in this study affected both. We conclude that 1) mechanical treatments of machine piling and salvage logging reduced fine and heavy fuel loadings and 2) prescribed fire was successful in reducing fine fuel...

Second malignancies complicating Hodgkin's disease: a Southwest Oncology Group 10-year followup

International Nuclear Information System (INIS)

Coltman, C.A. Jr.; Dixon, D.O.

1982-01-01

Thirty-two second malignancies (21 acute leukemias and 11 solid tumors) were identified among 659 patients with all stages of Hodgkin's disease treated by members of the Southwest Oncology Group. There were no leukemias and one solid tumor among 95 patients treated with radiotherapy alone. The actuarial risk of developing acute leukemia at 7 years was 6.2% for chemotherapy alone, 6.4% for combined modality, and 7.7% for salvage chemotherapy. The incidence of acute leukemia was higher (P . 0.002) among those whose treatment began at greater than or equal to 40 years of age. The actuarial risk of leukemia in that group was 20.7% at 7 years. These data are compatible with the hypothesis that chemotherapy alone, combined modality, and salvage chemotherapy have an equivalent oncogenic potential and that patients greater than or equal to 40 years of age have an enhanced susceptibility to these oncogenic stimuli

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

Science.gov (United States)

Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

DEFF Research Database (Denmark)

Felip, E; Gridelli, C; Baas, P

2011-01-01

the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study.

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Kabore, Firmin Nongodo; Eymard-Duvernay, Sabrina; Zoungrana, Jacques; Badiou, Stéphanie; Bado, Guillaume; Héma, Arsène; Diouf, Assane; Delaporte, Eric; Koulla-Shiro, Sinata; Ciaffi, Laura; Cournil, Amandine

2017-01-01

Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33-46 years) and median T-CD4 count was 199 cells/μl (IQR: 113-319 cells/μl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36-72 months) and the median baseline SI was 101 (IQR: 87-116). In multivariable analysis, factors associated with baseline SI were sex (β = -10.8 [-18.1,-3.5] for women), age (β = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (β = +0.8 [0.1,1.5] per unit of BMI), and study site (β = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.

Treatment paradigms for advanced stage non-small cell lung cancer in the era of multiple lines of therapy.

Science.gov (United States)

Stinchcombe, Thomas E; Socinski, Mark A

2009-02-01

The duration of first-line and the timing of second-line therapy for advanced non-small cell lung cancer has been an area of recent investigation. Five trials have been performed that have investigated shorter (3-4 cycles) versus longer duration of platinum-based therapy; four trials revealed an equivalent overall survival with the shorter duration of therapy, and one trial revealed superior survival with the longer duration of therapy. The toxicity and quality of life data has either been equivalent or favored the shorter duration of therapy. Two trials have investigated the timing of a second-line therapy after completion of four cycles of platinum-based therapy versus the standard treatment paradigm of initiating second-line therapy upon disease progression. Both of these trials have revealed a statistically significant improvement in the progression-free survival, and a trend towards improved survival for the earlier use of second-line therapy. Only 50 to 60% of patients on the standard treatment arm initiated second-line therapy, and the promising results observed are most likely related to the fact that a higher percentage of patients received second-line therapy on the experimental arm. Several trials have investigated maintenance chemotherapy, and these trials have not revealed a survival benefit probably due to the fact that many patients experience disease progression or unacceptable toxicity during the initial or maintenance therapy. The addition of a targeted agent (bevacizumab or cetuximab) to the initial chemotherapy and the continuation of the targeted agent after completion of the chemotherapy have yielded superior overall survival in comparison to chemotherapy alone. The incremental benefit of the maintenance therapy with the targeted agent is unknown.

Septic Shock following Prostate Biopsy: Aggressive Limb Salvage for Extremities after Pressor-Induced Ischemic Gangrene

Directory of Open Access Journals (Sweden)

Jocelyn Lu, BS

2017-09-01

Full Text Available Summary:. Vasopressors used to treat patients with septic shock can cause ischemic necrosis of appendages such as the ears and nose, as well as the extremities. Cases of quadruple-extremity necrosis have high morbidity and mortality, and a profound negative impact on quality of life. This case report details the successful limb salvage and return to function using free tissue transfer as a means to salvage bilateral lower extremities in a patient who suffered vasopressor-induced ischemia of upper and lower extremities after prostate biopsy–induced septic shock. Septic shock following transrectal ultrasound–guided prostate biopsy is a rare, yet life-threatening complication. Successful treatment included thorough planning and staging of therapies such as awaiting tissue demarcation and serial surgical debridement to adequately prepare the tissue bed for free tissue transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative-pressure wound therapy, and meticulous wound care played a crucial role in wound healing. This vigilant planning and coordinated care resulted in the successful lower extremity salvage, consisting of bilateral transmetatarsal amputations and free tissue transfer to both limbs. We present our long-term follow-up of a functional ambulatory patient after catastrophic, life-threatening infection and appropriate multidisciplinary care.

Salvage brachytherapy for local recurrences of prostate cancer treated previously with radiotherapy.

Science.gov (United States)

Gawkowska-Suwinska, Marzena; Fijałkowski, Marek; Białas, Brygida; Szlag, Marta; Kellas-Ślęczka, Sylwia; Nowicka, Elżbieta; Behrendt, Katarzyna; Plewicki, Grzegorz; Smolska-Ciszewska, Beata; Giglok, Monika; Zajusz, Aleksander; Owczarek, Grzegorz

2009-12-01

The aim of the study was to analyze early effects and toxicity of salvage high dose rate brachytherapy for local recurrences of adenocarcinoma of the prostate after external beam radiotherapy (EBRT). In MCS Memorial Institute of Oncology in Gliwice a research programme on salvage HDR brachytherapy for local recurrences of prostate cancer treated previously with EBRT has been ongoing since February 2008. The treatment consisted of 3 fractions of 10 Gy each given every 14 days. Maximal urethral doses were constrained to be ≤ 120% of the prescribed dose. Maximal bladder and rectum doses were constrained to be ≤ 70% of the prescribed dose. Fifteen eligible patients were treated and analyzed from February 2008. All patients completed the treatment without major complications. The most common early complications were: macroscopic haematuria, pain in lower part of the abdomen, and transient dysuria. During the first week after the procedure a transient increase in IPSS score was noticed. The Foley catheter was removed on day 2 to 5. No complications after spinal anaesthesia were observed. Acute toxicity according to EORTC/RTOG was low. For bladder EORTC/RTOG score ranged from 0 to 2. Only in two patients grade 1 toxicity for rectum was observed. The follow-up ranged from 3 to 9 months. In one patient grade 2 rectal toxicity was observed, and one had urethral stricture. Other patients did not have any other significant late toxicity of the treatment. Two patients developed bone metastases. Salvage brachytherapy for localized prostate cancer (3 × 10 Gy every 14 days) seems to be a safe and well tolerated procedure. A significant decline in prostate-specific antigen (PSA) level is seen in patients with hormone-responsive cancer. Long-term efficiency and toxicity of the procedure are yet to be established.

Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation.

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Lee, Sanghoon; Hyuck David Kwon, Choon; Man Kim, Jong; Joh, Jae-Won; Woon Paik, Seung; Kim, Bong-Wan; Wang, Hee-Jung; Lee, Kwang-Woong; Suh, Kyung-Suk; Lee, Suk-Koo

2014-09-01

Salvage liver transplantation (LT) is considered a feasible option for the treatment of recurrent hepatocellular carcinoma (HCC). We performed this multicenter study to assess the risk factors associated with the recurrence of HCC and patient survival after salvage LT. Between January 2000 and December 2011, 101 patients who had previously undergone liver resection (LR) for HCC underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at a median of 10.6 months after the initial LR, and patients underwent salvage LT. Recurrences were within the Milan criteria in 48 cases and were outside the Milan criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the 5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8 months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for poor recurrence-free survival after salvage LT. In conclusion, the timing and extent of HCC recurrence after primary LR both play significant roles in the outcome of salvage LT. © 2014 American Association for the Study of Liver Diseases.

Psychosocial reactions to upper extremity limb salvage: A cross-sectional study.

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Sposato, Lindsay; Yancosek, Kathleen; Lospinoso, Josh; Cancio, Jill

2017-08-09

Descriptive cross-sectional survey study. Limb salvage spares an extremity at risk for amputation after a major traumatic injury. Psychosocial recovery for individuals with lower extremity limb salvage has been discussed in the literature. However, to date, psychosocial reactions for individuals with upper extremity (UE) limb salvage have not been examined. To determine which factors may influence psychosocial adaptation to UE limb salvage. Participants (n = 30; 28 males) were adults (mean, 30.13; range, 18-61) who sustained an UE limb salvage from a traumatic event. Adaptation was measured using a modified version of the Reactions to Impairment and Disability Inventory. A linear mixed-effects regression found that worse psychosocial adaptation was associated with having less than a college degree, being less than 6 months post-injury, being older than 23 years, and having more pain. Dominant hand injuries were found to influence poor adaptation on the denial Reactions to Impairment and Disability Inventory subscale only. The results of this study indicate that there is potential for nonadaptive reactions and psychological distress with certain variables in UE limb salvage. Therapists may use these results to anticipate which clients may be at risk for poor psychosocial outcomes. This study indicates the need for early consideration to factors that affect psychological prognosis for the UE limb salvage population. However, future research is indicated to better understand the unique psychosocial challenges and needs of these individuals. 4. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Time interval between primary radiotherapy and salvage laryngectomy: a predictor of pharyngocutaneous fistula formation.

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Scotton, William J; Nixon, I J; Pezier, T F; Cobb, R; Joshi, A; Urbano, T Guerrero; Oakley, R; Jeannon, J P; Simo, R S

2014-08-01

Salvage laryngectomy (SL) is associated with high levels of morbidity. Rates of pharyngocutaneous fistulae (PCF) are as high as 35 % in some series. Patients at highest risk of such complications may be candidates for altered surgical management in terms of additional tissue transfer, or delayed tracheoesophageal puncture. This study investigates the relationship between the time from primary radiotherapy (RT) to salvage surgery and the development of PCF. 26 consecutive patients who underwent SL between 2000 and 2010 were identified from our institutional database. Demographic, staging, treatment and complication data were collected. Subgroup analysis was performed using the Student's t test or Mann-Whitney U test for continuous variables and either Chi-squared test or Fisher's Exact test for categorical variables. 26 patients underwent SL between October 2003 and July 2010. Of these, 15 (58 %) developed a PCF. On analysis of the time between pre-operative RT and surgery, a significant difference was seen, with a mean time of 19.5 months in those who developed a PCF versus 47.0 months in those who did not (p = 0.02). Patient characteristics, treatment, and pathology results were comparable between the two groups. There was no significant difference in distribution of the other covariates between the PCF and non-PCF groups. We reported a high rate of PCF and identified an association between PCF and a short time from primary treatment to salvage surgery. Identifying factors associated with higher rates of post-operative morbidity allows surgeons to adapt surgical planning in an attempt to minimize rates of PCF.

Multidisciplinary ''limb salvage'' treatment of soft tissue and skeletal sarcomas

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Weisenburger, T.H.; Eilber, F.R.; Grant, T.T.; Morton, D.L.; Mirra, J.J.; Steinberg, M.; Rickles, D.

1984-01-01

The goal of treating primary bone and soft tissue tumors, as with most other malignancies, is to control the disease locally and systematically while preserving as much function as possible. For soft tissue sarcomas the results following radical excision and post-operative radiation therapy with preservation of the limb have equaled the control rates of amputation. However, local recurrence rates of approximately 25-30% are reported for high-grade lesions of the proximal lower extremity. Amputations provides excellent local control for osteosarcoma but the functional results may be less than optimal. In an attempt to achieve limb salvage for these tumors, a multidisciplinary protocol was developed using intra-arterial doxorubicin, pre-operative radiation therapy and limb-sparing radical wide excision followed by post-operative chemotherapy for presumed micro-metastatic disease

The relative contribution of mannose salvage pathways to glycosylation in PMI-deficient mouse embryonic fibroblast cells.

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Fujita, Naonobu; Tamura, Ayako; Higashidani, Aya; Tonozuka, Takashi; Freeze, Hudson H; Nishikawa, Atsushi

2008-02-01

Mannose for mammalian glycan biosynthesis can be imported directly from the medium, derived from glucose or salvaged from endogenous or external glycans. All pathways must generate mannose 6-phosphate, the activated form of mannose. Imported or salvaged mannose is directly phosphorylated by hexokinase, whereas fructose 6-phosphate from glucose is converted to mannose 6-phosphate by phosphomannose isomerase (PMI). Normally, PMI provides the majority of mannose for glycan synthesis. To assess the contribution of PMI-independent pathways, we used PMI-null fibroblasts to study N-glycosylation of DNase I, a highly sensitive indicator protein. In PMI-null cells, imported mannose and salvaged mannose make a significant contribution to N-glycosylation. When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated. Adding approximately 13 microm mannose to the medium completely restored normal glycosylation. Treatment with bafilomycin A(1), an inhibitor of lysosomal acidification, also markedly reduced N-glycosylation of DNase I, but in this case only 8 microm mannose was required to restore full glycosylation, indicating that a nonlysosomal source of mannose made a significant contribution. Glycosylation levels were greatly also reduced in glycoconjugate-free medium, when endosomal membrane trafficking was blocked by expression of a mutant SKD1. From these data, we conclude that PMI-null cells can salvage mannose from both endogenous and external glycoconjugates via lysosomal and nonlysosomal degradation pathways.

Perceived adherence barriers among patients failing second-line antiretroviral therapy in Khayelitsha, South Africa

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W Barnett

2013-11-01

Full Text Available Background. The recent scale-up of antiretroviral therapy (ART coverage in resource-limited settings has greatly improved access to treatment. However, increasing numbers of patients are failing first- and second-line ART. Objective. To examine factors affecting adherence to second-line ART from the perspective of clinic staff and patients, assessing both individual and structural perceived barriers. Methods. Research was conducted at a large primary care tuberculosis (TB/HIV clinic in Khayelitsha, a peri-urban township in Cape Town, South Africa. Participants were drawn from a Médecins Sans Frontières-run programme to support patients failing second-line ART. A qualitative research approach was used, combining multiple methodologies including key informant interviews with staff (n=11, in-depth interviews with patients (n=10 and a Photovoice workshop (n=11. Responses and photographs were coded by content; data were transformed into variables and analysed accordingly. Results. Staff identified drinking, non-disclosure, not using condoms and pill fatigue as barriers to ART adherence, while patients identified side-effects, not using condoms and a lack of understanding concerning medication timing. With respect to service delivery, staff identified a need for continued counselling and educational support following ART initiation. Patients were concerned about missing medical records and poor staff attitudes in the clinic. Conclusion. These findings identify discrepancies between provider and patient perceptions of barriers to, and facilitators of adherence, as well as of service delivery solutions. This highlights the need for on-going counselling and education following ART initiation, improved quality of counselling, and improved methods to identify and address specific barriers concerning medication adherence.

Reirradiation for recurrent head and neck cancer with salvage interstitial pulsed-dose-rate brachytherapy. Long-term results

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Strnad, Vratislav; Lotter, Michael; Kreppner, Stephan; Fietkau, Rainer [University Hospital Erlangen, Dept. of Radiation Oncology, Erlangen (Germany)

2015-01-10

To assess the long-term results of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy as reirradiation combined with simultaneous chemotherapy and interstitial hyperthermia in selected patients with recurrent head and neck tumors. A total of 104 patients with biopsy-proven recurrent head and neck cancer were treated with interstitial PDR brachytherapy. Salvage surgery had also been undergone by 53/104 (51 %) patients (R1 or R2 resection in > 80 % of patients). Salvage brachytherapy alone was administered in 81 patients (78 %), with a median total dose of 56.7 Gy. Salvage brachytherapy in combination with external beam radiotherapy (EBRT) was performed in 23/104 patients (32 %), using a median total dose of D{sub REF} = 24 Gy. Simultaneously to PDR brachytherapy, concomitant chemotherapy was administered in 58/104 (55.8 %) patients. A single session of interstitial hyperthermia was also used to treat 33/104 (31.7 %) patients. The analysis was performed after a median follow-up of 60 months. Calculated according to Kaplan-Meier, local tumor control rates after 2, 5, and 10 years were 92.5, 82.4, and 58.9 %, respectively. Comparing results of salvage PDR brachytherapy with or without simultaneous chemotherapy, the 10-year local control rates were 76 vs. 39 % (p= 0014), respectively. No other patient- or treatment-related parameters had a significant influence on treatment results. Soft tissue necrosis or bone necrosis developed in 18/104 (17.3 %) and 11/104 (9.6 %) patients, respectively, but only 3 % of patients required surgical treatment. PDR interstitial brachytherapy with simultaneous chemotherapy is a very effective and, in experienced hands, also a safe treatment modality in selected patients with head and neck cancer in previously irradiated areas. (orig.) [German] Es erfolgte die Analyse der Langzeitergebnisse einer protokollbasierten interstitiellen Brachytherapie (Re-Bestrahlung) mit simultaner Chemotherapie und interstitieller Hyperthermie

Salvage felling in the Slovak forests in the period 2004–2013

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Kunca Andrej

2015-09-01

Full Text Available Salvage felling is one of the indicators of the forest health quality and stability. Most of the European Union countries monitor forest harmful agents, which account for salvage felling, in order to see trends or functionality between factors and to be able to predict their development. The systematic evidence of forest harmful agents and volume of salvage felling in Slovakia started at the Forest Research Institute in Zvolen in 1960. The paper focuses on the occurrence of the most relevant harmful agents and volume of salvage felling in the Slovak forests over the last decade. Within the 10 years period (2004–2013 salvage felling in Slovakia reached 42.31 mil. m3 of wood, which was 53.2% of the total felling. Wind and European spruce bark beetle Ips typographus damaged 78.4% of salvage wood, i.e. they were the most important pest agents. Norway spruce (Picea abies was the most frequently damaged tree species that represented the amount of 35.6 mil. m3 of wood (81.2% of total volume of salvage felling. As Norway spruce grows mostly in mountains, these regions of Central and Northern Slovakia were most affected. At the damaged localities new forests were prevailingly established with regard to suitable ecological conditions for trees, climate change scenarios and if possible, natural regeneration has been preferred. These approaches in forest stand regeneration together with silvicultural and control measures are assumed to gradually decrease the amount of salvage felling over long term perspective.

Non-Hodgkin's lymphoma - Part II: Management of primary extranodal lymphomas, generalized disease and salvage treatment

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Gospodarowicz, Mary K.; Sutcliffe, Simon B.

1996-01-01

Objective: To review the approach to the diagnosis, classification, assessment, treatment and continuing management of patients with primary extranodal non-Hodgkin's lymphoma, and the management of generalized disease with the emphasis on the current role of salvage treatment with high dose chemotherapy and stem cell/bone marrow support strategies. Non-Hodgkin's lymphoma may involve any part of the body. Many lymphomas, such as MALT, angiocentric T-cell, etc., commonly present in extranodal sites. Lymphomas presenting in the GI tract, and head and neck, are most common with the single most common site being the stomach. Gastric lymphoma is associated with Helicobacter pylorii and is most common in areas endemic for Helicobacter pylorii infection. Recent advances in the understanding of the etiology of gastric MALT, thyroid, and intestinal lymphomas present new opportunities for the application of novel therapeutic approaches e.g. antibiotic therapy for Helicobacter pylori and early stage IPSID. Lymphomas presenting in the orbit, thyroid, breast, bone, extradural and skin are of interest because of the importance of expert RT in securing local control. Primary brain lymphomas present a particular challenge to the radiation oncologist. Although localized, primary brain lymphomas are extremely difficult to control. Rare sites of extranodal lymphoma include testis, female genital tract, and lung. Extranodal lymphomas are often localized and cure with RT or CMT is possible. They represent a assorted group of diseases with diverse presentations, prognosis, sensitivity to RT and expected outcome. They are of particular importance to radiation oncologists as they require special attention to patterns of spread and treatment planning. The principles of management of primary extranodal lymphoma, however, follow those applicable to localized nodal presentations. Although primary extranodal lymphomas are highly curable, a proportion of patients will fail with disseminated

The methionine salvage pathway in Bacillus subtilis

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Danchin Antoine

2002-04-01

Full Text Available Abstract Background Polyamine synthesis produces methylthioadenosine, which has to be disposed of. The cell recycles it into methionine through methylthioribose (MTR. Very little was known about MTR recycling for methionine salvage in Bacillus subtilis. Results Using in silico genome analysis and transposon mutagenesis in B. subtilis we have experimentally uncovered the major steps of the dioxygen-dependent methionine salvage pathway, which, although similar to that found in Klebsiella pneumoniae, recruited for its implementation some entirely different proteins. The promoters of the genes have been identified by primer extension, and gene expression was analyzed by Northern blotting and lacZ reporter gene expression. Among the most remarkable discoveries in this pathway is the role of an analog of ribulose diphosphate carboxylase (Rubisco, the plant enzyme used in the Calvin cycle which recovers carbon dioxide from the atmosphere as a major step in MTR recycling. Conclusions A complete methionine salvage pathway exists in B. subtilis. This pathway is chemically similar to that in K. pneumoniae, but recruited different proteins to this purpose. In particular, a paralogue or Rubisco, MtnW, is used at one of the steps in the pathway. A major observation is that in the absence of MtnW, MTR becomes extremely toxic to the cell, opening an unexpected target for new antimicrobial drugs. In addition to methionine salvage, this pathway protects B. subtilis against dioxygen produced by its natural biotope, the surface of leaves (phylloplane.

Profile of trifluridine/tipiracil hydrochloride in the treatment of metastatic colorectal cancer: efficacy, safety, and place in therapy

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Sunakawa Y

2017-09-01

Full Text Available Yu Sunakawa, Naoki Izawa, Takuro Mizukami, Yoshiki Horie, Mami Hirakawa, Hiroyuki Arai, Takashi Ogura, Takashi Tsuda, Takako Eguchi Nakajima Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan Abstract: TAS-102, with its robust survival efficacy and feasible toxicity, is one of the standard salvage-line treatments for patients with metastatic colorectal cancer (mCRC. No definitive data are available to determine which drug should be administered first during salvage-line treatment. Therefore, it is imperative that we establish the sequence of administration by considering drug toxicity profiles based on patient characteristics, such as age, performance status, comorbidities, tolerability to previous treatments, and patient preferences. The identification of predictive biomarkers in response to TAS-102 or its toxicity is urgently needed for better patient selection. Moreover, to strengthen efficacy or relieve toxicity, combinations with other agents, which could potentially emerge as standard treatment regimens, have been investigated and compared to existing active regimens for mCRC. Keywords: TAS-102, metastatic colorectal cancer, regorafenib, biomarker

Second-line afatinib administration in an elderly patient with squamous cell carcinoma

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Hohenforst-Schmidt W

2017-03-01

Full Text Available Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2 Michael Steinheimer,1 Naim Benhassen,3 Chrysanthi Sardeli,4 Nikos Stalikas,2 Melpomeni Toitou,2 Haidong Huang5 1Sana Clinic Group Franken, Department of Cardiology/Pulmonology/Intensive Care/Nephrology, “Hof” Clinics, University of Erlangen, Hof, Germany; 2Pulmonary Department – Oncology Unit, “G Papanikolaou” General Hospital, Thessaloniki, Greece; 3Medical Clinic I, “Fuerth” Hospital, University of Erlangen, Fuerth, Germany; 4Department of Pharmacology & Clinical Pharmacology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece; 5Department of Respiratory and Critical Care Medicine, Changhai Hospital/First Affiliated Hospital of the Secondary Military Medical University, Shanghai, China Introduction: The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. Case report: This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg after disease progression with left lung atelectasis. After receiving afatinib for only 28 days, the atelectasis resolved. No adverse effects were observed from the afatinib therapy. Discussion: In this case, afatinib 40 mg proved to be an effective alternative treatment for an elderly patient. Treatment choice should be based on the performance status of the patient, cost-effectiveness, and drug treatment guidelines. Keywords: lung cancer, EGFR, afatinib

New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD+ salvage from nicotinamide

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2014-01-01

Background In an effort to reconstitute the NAD+ synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD+de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD+de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD+ metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD+ biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD+ salvage pathway from nicotinamide. Results Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Conclusions Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD+ salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD+ salvage pathway might be significant in some bacteria lacking NAD+de novo and NAD+ salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD+. However, this speculation needs to be experimentally tested. PMID:24506841

Bacterial reduction by cell salvage washing and leukocyte depletion filtration.

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Waters, Jonathan H; Tuohy, Marion J; Hobson, Donna F; Procop, Gary

2003-09-01

Blood conservation techniques are being increasingly used because of the increased cost and lack of availability of allogeneic blood. Cell salvage offers great blood savings opportunities but is thought to be contraindicated in a number of areas (e.g., blood contaminated with bacteria). Several outcome studies have suggested the safety of this technique in trauma and colorectal surgery, but many practitioners are still hesitant to apply cell salvage in the face of frank bacterial contamination. This study was undertaken to assess the efficacy of bacterial removal when cell salvage was combined with leukocyte depletion filtration. Expired packed erythrocytes were obtained and inoculated with a fixed amount of a stock bacteria (Escherichia coli American Type Culture Collections [ATCC] 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 29213, or Bacteroides fragilis ATCC 25285) in amounts ranging from 2,000 to 4,000 colony forming units/ml. The blood was processed via a cell salvage machine. The washed blood was then filtered using a leukocyte reduction filter. The results for blood taken during each step of processing were compared using a repeated-measures design. Fifteen units of blood were contaminated with each of the stock bacteria. From the prewash sample to the postfiltration sample, 99.0%, 99.6%, 100%, and 97.6% of E. coli, S. aureus, P. aeruginosa, and B. fragilis were removed, respectively. Significant but not complete removal of contaminating bacteria was seen. An increased level of patient safety may be added to cell salvage by including a leukocyte depletion filter when salvaging blood that might be grossly contaminated with bacteria.

Use of Intra-Arterial Chemotherapy and Embolization Before Limb Salvage Surgery for Osteosarcoma of the Lower Extremity

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Zhang Huojun; Yang Jijin; Lu Jianping; Lai Chaojen; Sheng Jin; Li Yuxiao; Hao Qiang; Zhang Shunmin; Gupta, Sanjay

2009-01-01

We report our experience with the use of intra-arterial chemotherapy and embolization before limb salvage surgery in patients with osteosarcoma of the lower extremity. We evaluated the effect of this procedure on the degree of tumor necrosis and on the amount of blood loss during surgery. We reviewed the medical records of all patients who received intra-arterial chemotherapy and embolization before undergoing limb salvage surgery for osteosarcoma of the lower extremity at our institution between January 2003 and April 2008. Patient demographic, tumor characteristics, treatment details, postembolization complications, and surgical and pathological findings were recorded for each patient. We evaluated the operative time, estimated blood loss (EBL), and volume of blood transfusion during surgery and in the postoperative period in all patients in the study group. The same parameters were recorded for 65 other patients with lower extremity osteosarcoma who underwent limb salvage operation at our institution without undergoing preoperative intervention. The study included 47 patients (25 males and 22 females). Angiography showed that the tumors were hypervascular. Intra-arterial chemotherapy and embolization were performed successfully, resulting in a substantial reduction or complete disappearance of tumor stain in all patients. No major complications were encountered. At the time of surgery, performed 3-7 days after embolization, a fibrous edematous band around the tumor was observed in 43 of the 47 patients, facilitating surgery. The goal of limb salvage was achieved successfully in all cases. Percentage tumor necrosis induced by treatment ranged from 70.2% to 94.2% (average, 82.9%). EBL during surgery, EBL from drains in the postoperative period, total EBL, and transfusion volumes were significantly lower in the 47 study patients compared to the 65 patients who underwent surgery without preoperative treatment with intra-arterial chemotherapy and embolization. The

Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion.

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Virgo, Katherine S; Basch, Ethan; Loblaw, D Andrew; Oliver, Thomas K; Rumble, R Bryan; Carducci, Michael A; Nordquist, Luke; Taplin, Mary-Ellen; Winquist, Eric; Singer, Eric A

2017-06-10

Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .

Hemibody irradiation. An effective second-line therapy in drug-resistance multiple myeloma

International Nuclear Information System (INIS)

Singer, C.R.; Tobias, J.S.; Giles, F.; Rudd, G.N.; Blackman, G.M.; Richards, J.D.

1989-01-01

The authors report the results of treatment of 41 patients with melphalan-resistant multiple myeloma using single half-body irradiation (HBI) or double half-body irradiation (DHBI). Patients were grouped using prognostic classification reported by the Medical Research Council. Patients in group I and II showed the best response to therapy with reduction in serum of urinary paraprotein and improvement in symptoms, most notably a marked reduction in bone pain. In these groups five patients have survived over 2 years after therapy. The therapeutic response appeared better in those patients who received DHBI as opposed to those whom treated with single HBI. Patients in group III did not achieve prolonged survival but effective relief of bone pain was a consistent finding in these patients also. Thus HBI represents an alternative to combination chemotherapy as second-line treatment of patients with melphalan-resistant multiple myeloma. A comparative study of HBI versus combination chemotherapy is now indicated to establish which therapeutic approach is most effective

National survey on the current status of salvage radiotherapy on holidays by the JASTRO committee for future scope

International Nuclear Information System (INIS)

Nagata, Yasushi; Ashino, Yasuo

2002-01-01

Recently, the impact of the overall treatment time on local tumor control has been reported by several authors. However, we in Japan have a long radiotherapy break because of the two large national holiday seasons in April-May and December-January. Therefore, a national survey on the current status of salvage radiotherapy on holidays was performed in 2001. Fifty-three % of the all institutes performed salvage radiotherapy on holidays. However, there are several problems to be solved, and a national consensus and an authorized proposal by the JASTRO are waited. (author)

Treatment Outcomes from 68Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET.

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Emmett, Louise; van Leeuwen, Pim J; Nandurkar, Rohan; Scheltema, Matthijs J; Cusick, Thomas; Hruby, George; Kneebone, Andrew; Eade, Thomas; Fogarty, Gerald; Jagavkar, Raj; Nguyen, Quoc; Ho, Bao; Joshua, Anthony M; Stricker, Phillip

2017-12-01

68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% ( n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% ( n = 71/99). Forty-five percent ( n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% ( n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% ( n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% ( n = 16/26) had treatment response after SRT. On multivariate logistic regression

Outcome analysis of salvage radiotherapy for occult cervical cancer found after simple hysterectomy

International Nuclear Information System (INIS)

Koh, Hyeon-Kang; Jeon, Wan; Kim, Hak-Jae; Wu, Hong-Gyun; Kim, Kyubo; Chie, Eui-Kyu; Ha, Sung-W.

2013-01-01

The objective was to analyze the outcomes of the patients, who received salvage radiotherapy for incidentally discovered cervical cancer following simple hysterectomy, and to identify the influence of intracavitary radiotherapy on treatment outcomes. Data from 117 patients with occult cervical cancer who underwent simple hysterectomy followed by salvage radiotherapy from September 1979 to November 2010 were collected. All the patients received external beam radiotherapy with (n=45) or without (n=72) intracavitary radiotherapy. Local control, disease-free survival, overall survival and treatment-related toxicity were investigated. The median follow-up time was 75 months. The 5- and 10-year local control/disease-free survival/overall survival rates were 93/87/87% and 90/84/83%, respectively. Among 98 patients who had no residual disease and negative resection margin on surgical specimens, 32 (33%) received intracavitary radiotherapy and 66 (67%) did not. There were no differences in patient and tumor characteristics between patients treated with and without intracavitary radiotherapy. The 5-year local control rate for the non-intracavitary radiotherapy group was 93 versus 94% for the intracavitary radiotherapy group (P=0.564); the disease-free survival rate was 88 versus 94% (P=0.894); the overall survival rate was 95 versus 85% (P=0.106), respectively. Among all patients, there were 5% of Grade 3 or higher late toxicities. Patients with occult invasive cervical cancer discovered following simple hysterectomy could be treated safely and effectively with salvage radiotherapy. For patients with no residual disease and negative resection margin, intracavitary radiotherapy could be omitted. (author)

Clinical Benefit of Second-Line Palliative Chemotherapy in Advanced Soft-Tissue Sarcoma

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Anna Minchom

2010-01-01

Full Text Available Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7% achieved disease control. Median duration of response was 11 months (95% CI: 9–13. On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1% patients who failed to respond to first-line therapy achieved disease control. Eight (2.1% patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7–10 months. On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

Implant salvage in breast reconstruction with severe peri-prosthetic infection.

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Meybodi, Farid; Sedaghat, Negin; French, James; Keighley, Caitlin; Mitchell, David; Elder, Elisabeth

2017-12-01

Although treatment of mild peri-prosthetic infection in implant-based breast reconstruction results in high rates of resolution, successful management of severe peri-prosthetic infection remains a significant challenge. In this case series, a protocol utilizing a novel dressing - negative pressure wound therapy with instillation (NPWTi) - for the management of severe peri-prosthetic infection in breast reconstruction patients is described. This is an operative technique involving: (i) explantation of the breast prosthesis and application of the NPWTi dressing to the implant pocket; (ii) change of the NPWTi dressing; (iii) intraoperative fluid/tissue cultures; and (iv) reimplantation of the breast prosthesis when cultures yield no growth. This protocol was utilized in six cases of severe peri-prosthetic infection in five patients with immediate breast reconstruction for breast cancer or risk-reducing surgery. Cultures of fluid/tissue grew typical and/or unusual organisms. Only one case did not yield an organism. The hospital length of stay upon completion of the protocol ranged from 7-16 days (mean, 12 days). Successful implant salvage was achieved in five of six cases. The protocol was aborted in one case to allow for completion of adjuvant chemotherapy. Early findings from this case series suggest that in cases of severe peri-prosthetic infection this novel operative protocol may result in successful implant salvage for breast reconstruction patients. Further studies are needed to more fully elaborate the role of NPWTi to achieve implant salvage in challenging cases of peri-prosthetic infection. © 2015 Royal Australasian College of Surgeons.

Predictors of treatment failure and time to detection and switching in HIV-infected Ethiopian children receiving first line anti-retroviral therapy

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Bacha Tigist

2012-08-01

Full Text Available Abstract Background The emergence of resistance to first line antiretroviral therapy (ART regimen leads to the need for more expensive and less tolerable second line drugs. Hence, it is essential to identify and address factors associated with an increased probability of first line ART regimen failure. The objective of this article is to report on the predictors of first line ART regimen failure, the detection rate of ART regime failure, and the delay in switching to second line ART drugs. Methods A retrospective cohort study was conducted from 2005 to 2011. All HIV infected children under the age of 15 who took first line ART for at least six months at the four major hospitals of Addis Ababa, Ethiopia were included. Data were collected, entered and analyzed using Epi info/ENA version 3.5.1 and SPSS version 16. The Cox proportional-hazard model was used to assess the predictors of first line ART failure. Results Data of 1186 children were analyzed. Five hundred seventy seven (48.8% were males with a mean age of 6.22 (SD = 3.10 years. Of the 167(14.1% children who had treatment failure, 70 (5.9% had only clinical failure, 79 (6.7% had only immunologic failure, and 18 (1.5% had both clinical and immunologic failure. Patients who had height for age in the third percentile or less at initiation of ART were found to have higher probability of ART treatment failure [Adjusted Hazard Ratio (AHR, 3.25 95% CI, 1.00-10.58]. Patients who were less than three years old [AHR, 1.85 95% CI, 1.24-2.76], chronic diarrhea after initiation of antiretroviral treatment [AHR, 3.44 95% CI, 1.37-8.62], ART drug substitution [AHR, 1.70 95% CI, 1.05-2.73] and base line CD4 count below 50 cells/mm3 [AHR, 2.30 95% CI, 1.28-4.14] were also found to be at higher risk of treatment failure. Of all the 167 first line ART failure cases, only 24 (14.4% were switched to second line ART with a mean delay of 24 (SD = 11.67 months. The remaining 143 (85.6% cases were diagnosed

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

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Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

2018-04-01

When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1

Second auto-SCT for treatment of relapsed multiple myeloma.

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Gonsalves, W I; Gertz, M A; Lacy, M Q; Dispenzieri, A; Hayman, S R; Buadi, F K; Dingli, D; Hogan, W J; Kumar, S K

2013-04-01

High-dose therapy and auto-SCT remain integral in the initial treatment of multiple myeloma (MM), and are increasingly being applied for management of relapsed disease. We examined the outcomes in 98 patients undergoing salvage auto-SCT (auto-SCT2) for relapsed MM after receiving an initial transplant (auto-SCT1) between 1994 and 2009. The median age at auto-SCT2 was 60 years (range: 35-74). The median time between auto-SCT1 and auto-SCT2 was 46 months (range: 10-130). Treatment-related mortality was seen in 4%. The median PFS from auto-SCT2 was 10.3 (95% confidence interval (CI): 7-14) months and the median OS from auto-SCT2 was 33 months (95% CI: 28-51). In a multivariable analysis, shorter time to progression (TTP) after auto-SCT1, not achieving a CR after auto-SCT2, higher number of treatment regimens before auto-SCT2 and a higher plasma cell labeling index at auto-SCT2 predicted for shorter PFS. However, only a shorter TTP after auto-SCT1 predicted for a shorter OS post auto-SCT2. Hence, auto-SCT2 is an effective and feasible therapeutic option for MM patients relapsing after other treatments, especially in patients who had a TTP of at least 12 months after their auto-SCT1.

Windthrow and salvage logging in an old-growth hemlock-northern hardwoods forest

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Lang, K.D.; Schulte, L.A.; Guntenspergen, G.R.

2009-01-01

Although the initial response to salvage (also known as, post-disturbance or sanitary) logging is known to vary among system components, little is known about longer term forest recovery. We examine forest overstory, understory, soil, and microtopographic response 25 years after a 1977 severe wind disturbance on the Flambeau River State Forest in Wisconsin, USA, a portion of which was salvage logged. Within this former old-growth hemlock-northern hardwoods forest, tree dominance has shifted from Eastern hemlock (Tsuga canadensis) to broad-leaf deciduous species (Ulmus americana, Acer saccharum, Tilia americana, Populus tremuloides, and Betula alleghaniensis) in both the salvaged and unsalvaged areas. While the biological legacies of pre-disturbance seedlings, saplings, and mature trees were initially more abundant in the unsalvaged area, regeneration through root suckers and stump sprouts was common in both areas. After 25 years, tree basal area, sapling density, shrub layer density, and seedling cover had converged between unsalvaged and salvaged areas. In contrast, understory herb communities differed between salvaged and unsalvaged forest, with salvaged forest containing significantly higher understory herb richness and cover, and greater dominance of species benefiting from disturbance, especially Solidago species. Soil bulk density, pH, organic carbon content, and organic nitrogen content were also significantly higher in the salvaged area. The structural legacy of tip-up microtopography remains more pronounced in the unsalvaged area, with significantly taller tip-up mounds and deeper pits. Mosses and some forest herbs, including Athyrium filix-femina and Hydrophyllum virginianum, showed strong positive responses to this tip-up microrelief, highlighting the importance of these structural legacies for understory biodiversity. In sum, although the pathways of recovery differed, this forest appeared to be as resilient to the compound disturbances of windthrow

Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis.

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Wang, Guodong; Pichersky, Eran

2007-03-01

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which is derived from NAD, have important roles as a redox carriers in metabolism. A combination of de novo and salvage pathways contribute to the biosynthesis of NAD in all organisms. The pathways and enzymes of the NAD salvage pathway in yeast and animals, which diverge at nicotinamide, have been extensively studied. Yeast cells convert nicotinamide to nicotinic acid, while mammals lack the enzyme nicotinamidase and instead convert nicotinamide to nicotinamide mononucleotide. Here we show that Arabidopsis thaliana gene At2g22570 encodes a nicotinamidase, which is expressed in all tissues, with the highest levels observed in roots and stems. The 244-residue protein, designated AtNIC1, converts nicotinamide to nicotinic acid and has a Km value of 118 +/- 17 microM and a Kcat value of 0.93 +/- 0.13 sec(-1). Plants homozygous for a null AtNIC1 allele, nic1-1, have lower levels of NAD and NADP under normal growth conditions, indicating that AtNIC1 participates in a yeast-type NAD salvage pathway. Mutant plants also exhibit hypersensitivity to treatments of abscisic acid and NaCl, which is correlated with their inability to increase the cellular levels of NAD(H) under these growth conditions, as occurs in wild-type plants. We also show that the growth of the roots of wild-type but not nic1-1 mutant plants is inhibited and distorted by nicotinamide.

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997–2010

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Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; DiMeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

2014-01-01

Background Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Methods Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004–2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997–2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Results Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). Conclusions We found a significant increase in overall survival, PFS, and survival after

A comparison of salvage surgery following CRT and following BRT for advanced hypopharyngeal cancer

International Nuclear Information System (INIS)

Kamijo, Tomoyuki; Onitsuka, Tetsuro; Yokota, Tomoya

2016-01-01

There are still few comparison reports regarding the safety of salvage surgery for recurrence and persistence following platinum-based chemoradiotherapy (CRT) and cetuximab-based bioradiotherapy (BRT), which are frequently used as non-surgical therapies for advanced head and neck carcinomas. This study compared the safety of salvage surgery following CRT against that following BRT for advanced hypopharyngeal cancer. The study examined 34 cases who underwent salvage surgery following CRT and 7 cases who underwent salvage surgery following BRT from September 2002 to December 2015. The number of cases that were able to undergo salvage surgery was 34 among 67 recurrence and persistence cases following CRT and 7 of 8 cases following BRT. In terms of the surgical procedure, salvage neck dissection was conducted for 22 cases in the CRT group and 5 cases in the BRT group, with no significant differences observed between both including the surgical time and amount of bleeding, and with no major complications in either group. Total hypopharynx or total laryngectomy resection for salvage was conducted for 19 cases in the CRT group and 3 cases in the BRT group, upon which we observed anastomotic leakage in 3 cases in the CRT group and 1 case in the BRT group; however, there was no significant difference in the onset frequency. There was no clear difference regarding safety between salvage surgery following CRT and following BRT for locally advanced hypopharyngeal cancer. However, regarding the adaptation of salvage surgery, the possibility of limitations in the CRT group was suggested in comparison with the BRT group. (author)

78 FR 74128 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

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2013-12-10

... Recovery Settlement; Cadie Auto Salvage Site, Belvidere, Boone County, Illinois AGENCY: Environmental... Auto Salvage Site in Belvidere, Boone County, Illinois with the following settling parties: UOP, LLC... Cadie Auto Salvage Site, Belvidere, Boone County, Illinois and EPA Docket No. and should be addressed to...

78 FR 77673 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

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2013-12-24

... Recovery Settlement; Cadie Auto Salvage Site, Belvidere, Boone County, Illinois AGENCY: Environmental... Auto Salvage Site in Belvidere, Boone County, Illinois with the following settling party: Helen E... reference the Cadie Auto Salvage Site, Belvidere, Boone County, Illinois and EPA Docket No. and should be...

Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

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Viale Giuseppe

2008-07-01

Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

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Aguiar, P N; Perry, L A; Penny-Dimri, J; Babiker, H; Tadokoro, H; de Mello, R A; Lopes, G L

2017-09-01

Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

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Christopher J. D. Wallis MD

2017-05-01

Full Text Available Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence. Methods: We constructed a health state transition (Markov model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer–specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE (58.3 months as compared with adjuvant radiotherapy (53.7 months, a difference of 4.6 months (standard deviation 8.8. Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months. Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

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Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

2012-01-01

in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment. PMID:22792406

Extracorporeal membrane oxygenation (ECMO as salvage treatment for pulmonary Echinococcus granulosus infection with acute cyst rupture

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Sören L. Becker

2017-11-01

Full Text Available Extracorporeal membrane oxygenation (ECMO has been used successfully for the treatment of patients with respiratory failure due to severe infections. Although rare, parasites can also cause severe pulmonary disease. Tapeworms of the genus Echinococcus give rise to the development of cystic structures in the liver, lungs, and other organs. Acute cyst rupture leads to potentially life-threatening infection, and affected patients may deteriorate rapidly. The case of a young woman from Bulgaria who was admitted to hospital with severe dyspnoea, progressive chest pain, and haemoptysis is described. Computed tomography of the chest was pathognomonic for cystic echinococcosis with acute cyst rupture. Following deterioration on mechanical ventilation, she was cannulated for veno-venous ECMO. The patient’s condition improved considerably, and she was weaned successfully from ECMO and mechanical ventilation. Following lobectomy of the affected left lower lobe, the patient was discharged home in good condition. This appears to be the first report of the successful use of ECMO as salvage treatment for a severe manifestation of a helminthic disease. Due to recent migration to Western Europe, the number of patients presenting with respiratory failure due to pulmonary echinococcosis with cyst rupture is likely to increase. Keywords: Extracorporeal membrane oxygenation (ECMO, Infection, Echinococcosis, Echinococcus granulosus, Hydatid disease, Infection

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

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Alessandra Romano

2014-01-01

Full Text Available During the past decade, overall results of treatment of multiple myeloma (MM have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs. However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

Salvage Therapy of Multiple Myeloma: The New Generation Drugs

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Romano, Alessandra; Conticello, Concetta; Di Raimondo, Cosimo; Schinocca, Elena; La Fauci, Alessia; Parrinello, Nunziatina Laura; Chiarenza, Annalisa

2014-01-01

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways. PMID:24967371

Coupled Responses of Sewol, Twin Barges and Slings During Salvage

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Yao, Zong; Wang, Wei-ping; Jiang, Yan; Chen, Shi-hai

2018-04-01

Korean Sewol is successfully lifted up with the strand jack system based on twin barges. During the salvage operation, two barges and Sewol encounter offshore environmental conditions of wave, current and wind. It is inevitable that the relative motions among the three bodies are coupled with the sling tensions, which may cause big dynamic loads for the lifting system. During the project engineering phase and the site operation, it is necessary to build up a simulation model that can precisely generate the coupled responses in order to define a suitable weather window and monitor risks for the salvage operation. A special method for calculating multibody coupled responses is introduced into Sewol salvage project. Each body's hydrodynamic force and moment in multibody configuration is calculated in the way that one body is treated as freely moving in space, while other bodies are set as fixed globally. The hydrodynamic force and moment are then applied into a numerical simulation model with some calibration coefficients being inserted. These coefficients are calibrated with the model test results. The simulation model built up this way can predict coupled responses with the similar accuracy as the model test and full scale measurement, and particularly generate multibody shielding effects. Site measured responses and the responses only resulted from from the simulation keep project management simultaneously to judge risks of each salvage stage, which are important for success of Sewol salvage.

[Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

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Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

2017-06-20

With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients.

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Puz, Przemysław; Lasek-Bal, Anetta

2016-11-10

BACKGROUND In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year. MATERIAL AND METHODS Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed. RESULTS The annualized relapse rate for second-line therapy was significantly lower than for first-line therapy (0.35±0.74 vs. 2.13±0.87, p=0.00005). Median of EDSS progression with first-line therapy was significantly higher than that with natalizumab or fingolimod treatment (p=0.00002). The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year second-line treatment was significantly lower in comparison to lesions in MRI performed at the end of the first-line therapy (for T2: 0.61 vs. 4.56, p=0.0004; for Gd+: 0.13 vs. 1.98, p=0.0009). No significant differences in the clinical data, MRI results, and side effects between fingolimod and natalizumab patients have been observed. CONCLUSIONS Treatment with natalizumab or fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.

Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

International Nuclear Information System (INIS)

Nijhuis, Esther R.; Zee, Ate G.J. van der; Hout, Bertha A. in 't; Boomgaard, Jantine J.; Hullu, Joanne A. de; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Nijman, Hans W.; Willemse, Pax H.B.; Mourits, Marian J.E.

2006-01-01

Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective cohort study data of all cervical cancer patients with the International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 to IVA treated with (chemo) radiation between 1994 and 2001 were analyzed. Patients underwent gynecologic examination under anesthesia 8 to 10 weeks after completion of treatment. Cervical biopsy samples were taken from patients judged to be operable. In case of residual cancer, salvage surgery was performed. Results: Between 1994 and 2001, 169 consecutive cervical cancer patients received primary (chemo) radiation, of whom 4 were lost to follow-up. Median age was 56 years (interquartile range [IQR], 44-71) and median follow-up was 3.5 years (IQR, 1.5-5.9). In each of 111 patients a biopsy sample was taken, of which 90 (81%) showed no residual tumor. Vital tumor cells were found in 21 of 111 patients (19%). Salvage surgery was performed in 13 of 21 (62%) patients; of these patients, 5 (38%) achieved long-term, complete remission after salvage surgery (median follow-up, 5.2 years; range, 3.9-8.8 years). All patients with residual disease who did not undergo operation (8/21) died of progressive disease. Locoregional control was more often obtained in patients who underwent operation (7 of 13) than in patients who were not selected for salvage surgery (0 of 8 patients) (p < 0.05). Conclusions: Gynecologic examination under anesthesia 8 to 10 weeks after (chemo) radiation with cervical biopsies allows identification of those cervical cancer patients who have residual local disease, of whom a small but significant proportion may be salvaged by surgery

First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment.

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Munier, Francis L; Mosimann, Pascal; Puccinelli, Francesco; Gaillard, Marie-Claire; Stathopoulos, Christina; Houghton, Susan; Bergin, Ciara; Beck-Popovic, Maja

2017-08-01

The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. This is a retrospective mono-centric comparative review of consecutive patients. Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2-218.6) and 41.7 months (range 19.6-89.5), respectively. Treatment duration was significantly shorter in the IAC group (pchemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

A randomized controlled trial of cell salvage in routine cardiac surgery.

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Klein, Andrew A; Nashef, Samer A M; Sharples, Linda; Bottrill, Fiona; Dyer, Matthew; Armstrong, Johanna; Vuylsteke, Alain

2008-11-01

Previous trials have indicated that cell salvage may reduce allogeneic blood transfusion during cardiac surgery, but these studies have limitations, including inconsistent use of other blood transfusion-sparing strategies. We designed a randomized controlled trial to determine whether routine cell salvage for elective uncomplicated cardiac surgery reduces blood transfusion and is cost effective in the setting of a rigorous transfusion protocol and routine administration of antifibrinolytics. Two-hundred-thirteen patients presenting for first-time coronary artery bypass grafting and/or cardiac valve surgery were prospectively randomized to control or cell salvage groups. The latter group had blood aspirate during surgery and mediastinal drainage the first 6 h after surgery processed in a cell saver device and autotransfused. All patients received tranexamic acid and were subjected to an algorithm for red blood cell and hemostatic blood factor transfusion. There was no difference between the two groups in the proportion of patients exposed to allogeneic blood (32% in both groups, relative risk 1.0 P = 0.89). At current blood products and cell saver prices, the use of cell salvage increased the costs per patient by a minimum of $103. When patients who had mediastinal re-exploration for bleeding were excluded (as planned in the protocol), significantly fewer units of allogeneic red blood cells were transfused in the cell salvage compared with the control group (65 vs 100 U, relative risk 0.71 P = 0.04). In patients undergoing routine first-time cardiac surgery in an institution with a rigorous blood conservation program, the routine use of cell salvage does not further reduce the proportion of patients exposed to allogeneic blood transfusion. However, patients who do not have excessive bleeding after surgery receive significantly fewer units of blood with cell salvage. Although the use of cell savage may reduce the demand for blood products during cardiac surgery, this

Salvage surgery for radiation failure in oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma

International Nuclear Information System (INIS)

Suzuki, Masahiro; Terada, Akihiro; Ogawa, Tetsuya; Suzuki, Hidenori; Hasegawa, Yasuhisa

2007-01-01

Few reports have covered salvage surgery after radiotherapy, especially with chemotherapy for oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. The feasibility of salvage surgery is unclear. We analyzed postoperative complications and prognosis after salvage surgery for local recurrence after definitive radiotherapy. Subjects were 37 patients with oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma treated from 1994 to 2003. Of these, 14 (37.8%) had postoperative complications. The complication rate was significantly high in the reconstructive operation group (p=0.031) and the chemotherapy group (p=0.049). The 5-year overall survival rate after salvage surgery was 70.7%. Although there was no significant improvement, the prognosis was good in early-stage groups with primary tumors. We found that salvage surgery after definitive radiotherapy was effective for recurrent oral, oropharyngeal, and hypopharyngeal squamous cell carcinoma. We stress the need to pay attention to postoperative complications in reconstructive operation and chemotherapy groups. (author)

Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

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Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

2005-10-01

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

Salvage radical prostatectomy after external radiotherapy for prostate cancer: Indications, morbidity and results. Review from CCAFU prostate section

International Nuclear Information System (INIS)

Paparel, P.; Soulie, M.; Mongiat-Artus, P.; Cornud, F.; Borgogno, C.; Les membres du sous-comite prostate du CCAFU

2010-01-01

Local recurrence after external radiotherapy for prostate cancer occurs in 30 to 50 % and is often diagnosed by a rising PSA. The absence of local control after radiotherapy is a risk factor of metastases and specific mortality. There are several therapeutic options to treat these patients: surveillance, hormonotherapy and salvage therapies (radical prostatectomy, cysto-prostatectomy, brachytherapy, high intensity focused ultrasound [HIFU] and cryotherapy). Hormonotherapy is not a curative treatment and after a couple of years, the disease will progress again. Local salvage therapies are the only treatment to have the potential to cure these patients with the condition of very strict inclusion criteria. Among these therapies, only radical prostatectomy demonstrated his efficacy with a follow-up of 10 years on specific survival and survival without biological progression respectively from 70 to 77 % and from 30 to 43 %. During last decade, morbidity of RP has strongly decreased with a percentage of rectal and ureteral injury at 3 %. Nevertheless, percentage of urinary incontinence remains high from 29 to 50 %. Salvage mini-invasive therapies (cryotherapy, HIFU and cryotherapy) are under constant evolution due to progress of technology. Functional and oncological results are better with last generation devices but need to be evaluated and compared with radical prostatectomy. (authors)

Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer

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Kim, Sang-Won [Ajou University School of Medicine, Department of Radiation Oncology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Konyang University School of Medicine, Department of Radiation Oncology, Daejeon (Korea, Republic of); Chun, Mison; Oh, Young-Taek [Ajou University School of Medicine, Department of Radiation Oncology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Ryu, Hee-Sug; Chang, Suk-Joon; Kong, Tae Wook [Ajou University School of Medicine, Department of Obstetrics and Gynecology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Lee, Eun Ju [Ajou University School of Medicine, Department of Radiology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of); Lee, Yong Hee [Ajou University School of Medicine, Department of Pathology, Yeongtong-gu, Suwon, Gyeonggi-do (Korea, Republic of)

2017-07-15

Treatment outcomes of patients with pelvic recurrence after hysterectomy alone for uterine cervical cancer who received salvage radiotherapy (RT) with or without concurrent chemotherapy were investigated. Salvage RT for recurrent cervical cancer confined to the pelvic cavity after hysterectomy alone was received by 33 patients. The median interval between initial hysterectomy and recurrence was 26 months. Whole-pelvic irradiation was delivered to median dose of 45 Gy, followed by a boost with a median dose of 16 Gy to the gross tumor volume. Cisplatin-based concurrent chemotherapy was administered to 29 patients. The median follow-up period was 53 months for surviving patients. Most patients (97.0%) completed salvage RT of ≥45 Gy. Complete response (CR) was achieved in 23 patients (69.7%). Pelvic sidewall involvement and evaluation with positron-emission tomography-computed tomography were significantly associated with CR. The 5-year progression-free survival (PFS), local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 62.7, 79.5, 72.5, and 60.1%, respectively. Initial International Federation of Gynecology and Obstetrics stage, pelvic sidewall involvement, and CR status were significant factors for PFS and OS rates in multivariate analysis. The incidence of severe acute and late toxicities (≥grade 3) was 12.1 and 3.0%, respectively. Aggressive salvage RT with or without concurrent chemotherapy for recurrent cervical cancer confined to the pelvic cavity was feasible, with promising treatment outcomes and acceptable toxicities. However, even more intensive novel treatment strategies should be investigated for patients with unfavorable prognostic factors. (orig.) [German] Untersuchung der Behandlungsergebnisse von Patientinnen mit Beckenrezidiv nach alleiniger Hysterektomie bei Zervixkarzinom, die eine Salvage-Radiotherapie (RT) mit oder ohne begleitende Chemotherapie erhalten hatten. Insgesamt 33 Patientinnen erhielten

The use of a prosthetic inlay resurfacing as a salvage procedure for a failed cartilage repair.

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Dhollander, Aad Alfons Maria; Almqvist, Karl Fredrik; Moens, Kris; Vandekerckhove, Pieter-Jan; Verdonk, René; Verdonk, Peter; Victor, Jan

2015-08-01

This study was designed to describe the clinical and radiographical outcome of the HemiCAP(®) resurfacing system as a salvage treatment for a failed index cartilage procedure. Fourteen patients were treated consecutively and clinically prospectively followed for a mean period of 26.1 ± 12.8 months. All patients were previously treated for their cartilage lesion. Radiographical data were analysed based on the Kellgren and Lawrence system. The patients involved in this study demonstrated a gradual clinical improvement in time. However, radiographically significant osteoarthritic changes were observed during the follow-up period. The position of the HemiCAP(®) resurfacing system was adequate in all cases, and no signs of loosening were observed during the follow-up period. The HemiCAP(®) resurfacing system is feasible as a salvage treatment for a failed index cartilage procedure and resulted in a gradual clinical improvement. However, the favourable clinical outcome was not confirmed by the radiographical findings. IV.

Simulation and Analysis of Passive Rolling Compensation of High Sea Salvage System

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Lin Liqun

2017-01-01

Full Text Available Method and device of a flexible interception and salvage system was introduced in this paper. In order to study the effect of wave motion on salvage operation, we proposed a passive wave compensation scheme that utilizes a combination of variable-pitch cylinders and accumulators, and established the mathematical vibration model of the rolling motion of the salvage compensation system. With the relationships between the stiffness coefficient and the accumulator parametric of passive compensated gas-liquid system, we determined the effective compensation stiffness range through Mathematica simulation analysis. The relationship between the roll displacement of the salvage arm and the initial volume Vo of the accumulator has been analysed. The results show that the accumulatorVo in a certain range has a great influence on the passive compensation. However, when the volume is greater than 20m3, the compensation effect is weakened, and tend to a certain value, irrespective of the passive system accumulator volume capacity, it does not achieve full compensation. The results have important guidance on the design and optimization of rolling passive compensation of the practical high sea salvage system.

Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

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Fernando G. Abarzua-Cabezas

2015-02-01

Full Text Available Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85% of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%. Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months. Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

LONG-TERM RESULTS OF TARGET THERAPY WITH FIRST AND * SECOND-LINE TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

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L. L. Vysotskaya

2015-01-01

Full Text Available Aim: To assess long-term efficacy of firstand second-line tyrosine kinase inhibitors in non-selected patients with chronic myeloid leukemia in a real-life clinical setting.Materials and methods: The assessment is based on long-term results of a prospective single center comparative clinical trial that was based on non-selected groups of 116 patients with various stages of chronic myeloid leukemia being treated with a first generation tyrosine kinase inhibitor imatinib, and of 44 patients being treated with a second generation tyrosine kinase inhibitor nilotinib. We analyzed all-cause mortality, progression-free survival from April 2005 to April 2013, with a median of the follow-up of 128 months.Results: In 116 patients with chronic myeloid leukemia treated with imatinib, the Kaplan-Meier survival estimate was 120 months. In 44 patients at an early chronic phase, 5-year overall survival and progression-free survival was 93.2% and 8-year overall and progression-free survival was 79.5%. In 44 patients at a late chronic stage, 5-year overall and progression-free survival was 95.5%, 8-year overall and progression-free survival, 72.7%. In 28 patients at acceleration phase, 5-years overall survival was 78.6% and 8-year overall survival, 46%. Median of overall survival in patients treated with nilotinib was not reached. During 78.6 months of combination treatment with cytotoxic agents, tyrosine kinase inhibitors of the first (imatinib and second line (nilotinib, overall survival was 100%.Conclusion: In clinical practice, inclusion of patients with chronic myeloid leukemia and imatinib resistance (disease relapse or imatinib intolerance into the treatment program with frontline therapy with general cytotoxic agents and thereafter with firstand second-line tyrosine kinase inhibitors significantly improves overall survival.

Psychosocial reactions to upper extremity limb salvage: A case series.

Science.gov (United States)

Sposato, Lindsay; Yancosek, Kathleen; Cancio, Jill

2017-11-30

Case series. A salvaged limb is one that has undergone a major traumatic injury, followed by repeated surgical attempts in order to avoid amputation. Psychological recovery for individuals with lower extremity limb salvage has been examined in a number of studies. However, psychosocial reactions for individuals with upper extremity (UE) limb salvage are understudied in the literature. The purpose of this study was to explore the process of psychosocial adaptation for 3 trauma cases after UE limb salvage. The Reactions to Impairment and Disability Inventory was used to assess psychosocial adaptation. Physical function outcomes (pain, range of motion, edema, sensation, and dexterity) are presented. The Disabilities of the Arm, Shoulder, and Hand measure was used to assess perceived disability. Medical and rehabilitation history are discussed for each case, in order to provide in-depth understanding of the impact of these injuries. Reactions to injury varied across the cases; however, outcomes suggest that psychosocial adaptation may be influenced by the experience of pain, the ability to participate in valued roles and activities, and having a supportive social network. For this population, therapists may consider emphasizing pain management, focusing on client-centered goals and interventions, and facilitating peer support. Providers should closely monitor patients for signs of poor adaptation, such as hand-hiding behaviors. This study is among the first to examine psychological outcomes for the UE limb salvage population. Future research would be beneficial to provide deeper understanding of the psychosocial challenges for these individuals. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Clinical, virological and immunological responses in Danish HIV patients receiving raltegravir as part of a salvage regimen

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Frederik N Engsig

2010-05-01

Full Text Available Frederik N Engsig1, Jan Gerstoft1, Gitte Kronborg2, Carsten S Larsen3, Gitte Pedersen4, Anne M Audelin5, Louise B Jørgensen5, Niels Obel11Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 3Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; 4Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 5Department of Virology, Statens Serum Institute, Copenhagen, DenmarkBackground: Raltegravir is the first integrase inhibitor approved for treatment of HIV-infected patients harboring multiresistant viruses.Methods: From a Danish population-based nationwide cohort of HIV patients we identified the individuals who initiated a salvage regimen including raltegravir and a matched cohort of HIV-infected patients initiating HAART for the first time. We compared these two cohorts for virological suppression, gain in CD4 count, and time to first change of initial regimen.Results: We identified 32 raltegravir patients and 64 HIV patients who initiated HAART for the first time in the period 1 January 2006 to 1 July 2009. The virological and immunological responses in the raltegravir patients were comparable to those seen in the control cohort. No patients in the two cohorts died and no patients terminated raltegravir treatment in the observation period. Time to first change of initial regimen was considerably shorter for HAART-naïve patients.Conclusion: We conclude that salvage regimens including raltegravir have high effectiveness in the everyday clinical setting. The effectiveness of the regimens is comparable to that observed for patients initiating HAART for the first time. The risk of change in the salvage regimens after initiation of raltegravir is low.Keywords: HIV, raltegravir, salvage regime, efficacy, matched cohort

Oncological outcome, complications, lower urinary tract symptoms, and health-related quality of life after low-dose-rate salvage brachytherapy for recurrent prostate cancer following primary radiotherapy: a report of 8 cases

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Makito Miyake

2017-07-01

Full Text Available Purpose: We evaluated our experience with low-dose-rate salvage brachytherapy for local recurrence after primary prostate radiotherapy, and described the changes in lower urinary tract symptoms and health-related quality of life. Material and methods: Between 2011 and 2016, eight men with local recurrence after primary prostate radiotherapy underwent iodine-125 salvage brachytherapy with a prescribed dose of 110 or 145 Gy. Recurrence-free survival was evaluated with a post-treatment prostate-specific antigen profile. The toxicity and changes in lower urinary tract symptoms and health-related quality of life during the follow-up were evaluated on the Common Terminology Criteria for Adverse Events version 4.0, International Prostate Symptom Score, Short Form-8, and Expanded Prostate Cancer Index Composite, respectively. Results: The median follow-up was 12.2 months (range, 8.3-71.9 after salvage brachytherapy. Of all eight patients, two (25% experienced treatment failure, one of whom developed left seminal vesicle recurrence 36 months after salvage brachytherapy for the right seminal vesicle recurrence, while the other developed bone metastases after 6 months. The International Prostate Symptom Scores peaked at 3 months, and returned to baseline by 6 months. The scores of all domains of health-related quality of life remained unchanged during the 12-month follow-up after salvage brachytherapy. Early grade ≤ 2 genitourinary toxicity was observed in five patients (63%, and late grade 2 gastrointestinal toxicity in one patient (13% having persistent diarrhea. No patient required intermittent catheterization and no grade 3 or greater toxicity occurred during follow-up. Conclusions: The present study is our experiment of eight patients undergoing salvage brachytherapy, suggesting that this modality is noninvasive, safe, and an effective salvage local treatment in selected patients. To our knowledge, this is the first study to evaluate lower urinary

Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure

DEFF Research Database (Denmark)

Wulff, N B; Andersen, E; Kristensen, C A

2017-01-01

with higher N classification and need for lymph node excision during salvage total laryngectomy along with use of frozen sections. The high number of patients with recurrence within 1 year after salvage total laryngectomy occurred although thorough and regular follow-up visits were performed.......OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 142...... survival, disease-specific survival and disease-free survival were 37.7%, 54.9% and 55.3%, respectively. N classification at primary diagnosis, lymph node excision and postoperative complications within 1 year after salvage total laryngectomy were prognostic factors for shorter overall survival, disease...

Cytotect®CP as salvage therapy in patients with CMV infection following allogeneic hematopoietic cell transplantation: a multicenter retrospective study.

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Alsuliman, Tamim; Kitel, Caroline; Dulery, Rémy; Guillaume, Thierry; Larosa, Fabrice; Cornillon, Jérôme; Labussière-Wallet, Helene; Médiavilla, Clémence; Belaiche, Stéphanie; Delage, Jeremy; Alain, Sophie; Yakoub-Agha, Ibrahim

2018-04-13

Cytomegalovirus is one of the main contributing factors to high mortality rates in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The main factors of treatment failure are both drug resistance and intolerance. In some cases, Cytotect®CP CMV-hyperimmune globulin is used as salvage therapy. This study aims to investigate the safety and efficacy of Cytotect®CP as a salvage therapy in patients with CMV infection after allo-HCT. Twenty-three consecutive patients received Cytotect®CP for CMV infection after prior CMV therapy. At the time of Cytotect®CP introduction, 17 patients (74%) had developed acute GVHD and 15 patients (64%) were receiving steroid treatment; Cytotect®CP was used as monotherapy (n = 7) and in combination (n = 16). Overall, response was observed in 18 patients (78%) with a median time of 15 days (range: 3-51). Of the 18 responders, 4 experienced CMV reactivation, while 5 responders died within 100 days of beginning treatment. Of these 5 deaths, 4 were due to causes unrelated to CMV. Estimated 100-day OS from the introduction of Cytotect®CP was 69.6%. No statistically significant difference was observed in 100-day OS between responders and non-responders (73.7% vs 50.0%, p = 0.258). Cytotect®CP as salvage therapy is effective and well-tolerated. Given its safety profile, early treatment use should be considered.

Socioeconomic and psychological impact of treatment for unilateral intraocular retinoblastoma.

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Soliman, S E; Dimaras, H; Souka, A A; Ashry, M H; Gallie, B L

2015-06-01

To identify the socioeconomic and psychosocial impacts of clinical treatment decisions for advanced unilateral intraocular retinoblastoma. Retrospective observational case series. institutional study at Alexandria Main University Hospital. records of 66 unilateral retinoblastoma cases treated from May 2005 to May 2013 were retrospectively reviewed. Sixty cases were eligible (International Intraocular Retinoblastoma Classification [IIRC] group C, D or E). two treatment groups were compared: enucleation vs. salvage treatment. Salvage treatment eyes were further subdivided based on IIRC group. Six socioeconomic parameters (financial burden, financial impact, psychological, social, medical and tumor impacts) were scored. Parameter scores ranged from 0 to 3, for overall score range 0 (no adverse impact) to 18 (severe adverse impact). derived Socioeconomic scores were correlated with treatment and outcomes. The enucleation group (28 eyes) had a median overall Socioeconomic score of 4/18, significantly lower than the salvage treatment group (32 eyes), median score 11/18 (PSocioeconomic score varied with IIRC group. Attempted eye salvage failed in 25 children, due to uncontrolled tumor (44%) and socioeconomic impact of cumulative therapies (56%). Treatment duration and Socioeconomic score were higher for the 5 children in the salvage treatment group who developed metastatic disease compared to those without metastasis (Psocioeconomic and psychosocial impacts of attempted ocular salvage for unilateral intraocular retinoblastoma are severe, in comparison to primary enucleation. Primary enucleation is a good treatment for unilateral retinoblastoma. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients.

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Domínguez-Hermosillo, Juan Carlos; Mata-Marin, José Antonio; Herrera-González, Norma Estela; Chávez-García, Marcelino; Huerta-García, Gloria; Nuñez-Rodríguez, Nohemí; García-Gámez, José Gerardo; Jiménez-Romero, Anai; Gaytán-Martínez, Jesús Enrique

2016-09-30

Although both tipranavir (TPV) and darunavir (DRV) represent important options for the management of patients with multi-protease inhibitor (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies comparing the effectiveness and safety of these two drugs in the Mexican population. The aim of this study was to compare the effectiveness of TPV versus DRV as a salvage therapy in HIV-1 treatment-experienced patients. This was a comparative, prospective, cohort study. Patients with HIV and triple-class drug resistance evaluated at the Hospital de Infectología "La Raza", National Medical Center, were included. All patients had the protease and retrotranscriptase genotype; resistance mutation interpretation was done using the Stanford database. A total of 35 HIV-1 triple-class drug-resistant patients were analyzed. All of them received tenofovir and raltegravir, 22 received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177-320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR, 252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load HIV-1 patients who were highly experienced in antiretroviral therapy.

Salvage logging effect on soil properties in a fire-affected Mediterranean forest: a two years monitoring research

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Mataix-Solera, Jorge; Moltó, Jorge; Arcenegui, Vicky; García-Orenes, Fuensanta; Chrenkovà, Katerina; Torres, Pilar; Jara-Navarro, Ana B.; Díaz, Gisela; Izquierdo, Ezequiel

2015-04-01

In the Mediterranean countries, forest fires are common and must be considered as an ecological factor, but changes in land use, especially in the last five decades have provoked a modification in their natural regime. Moreover, post-fire management can have an additional impact on the ecosystem; in some cases, even more severe than the fire. Salvage logging is a traditional management in most fire-affected areas. In some cases, the way of doing it, using heavy machinery, and the vulnerability of soils to erosion and degradation make this management potentially very agresive to soil, and therefore to the ecosystem. Very little research has been done to study how this treatment could affect soil health. In this research we show 2 years of monitoring of some soil properties in an area affected by a forest fire, where some months later this treatment was applied. The study area is located in 'Sierra de Mariola Natural Park' in Alcoi, Alicante (E Spain). A big forest fire (>500 has) occurred in July 2012. The forest is composed mainly of Pinus halepensis trees with an understory of typical Mediterranean shrubs species such as Quercus coccifera, Rosmarinus officinalis, Thymus vulgaris, Brachypodium retusum, etc. Soil is classified as a Typic Xerorthent (Soil Survey Staff, 2014) developed over marls. In February 2013, salvage logging (SL) treatment consisting in a complete extraction of the burned wood using heavy machinery was applied in a part of the affected forest. Plots for monitoring this effect were installed in this area and in a similar nearby area where no treatment was done, and then used as control (C) for comparison. Soil samplings were done immediately after treatment and every 6 months. Some soil properties were analysed, including soil organic matter (SOM) content, basal soil respiration (BSR), microbial biomass carbon (MBC), bulk density (BD), soil water repellency (SWR), aggregate stability (AS), field capacity, nitrogen, etc. After two years of

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

Science.gov (United States)

Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

2014-06-01

To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

Post-fire salvage logging reduces carbon sequestration in Mediterranean coniferous forest

OpenAIRE

Serrano-Ortiz, P.; Marañón-Jiménez, S.; Reverter, B.R.; Sánchez-Cañete, E.P.; Castro, J.; Zamora, R.; Kowalski, A.S.

2011-01-01

Post-fire salvage logging is a common silvicultural practice around the world, with the potential to alter the regenerative capacity of an ecosystem and thus its role as a source or a sink of carbon. However, there is no information on the effect of burnt wood management on the net ecosystem carbon balance. Here, we examine for the first time the effect of post-fire burnt wood management on the net ecosystem carbon balance by comparing the carbon exchange of two treatments in a burnt Mediterr...

A phase I/II trial to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor Temsirolimus added to standard therapy of Rituximab and DHAP for the treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma – the STORM trial

International Nuclear Information System (INIS)

Witzens-Harig, Mathias; Memmer, Marie Luise; Dreyling, Martin; Hess, Georg

2013-01-01

The current standard treatment of patients with relapsed or refractory diffuse large cell B-Cell lymphoma (DLBCL) primarily consists of intensified salvage therapy and, if the disease is chemo-sensitive, high dose therapy followed with autologous stem cell transplantation. In the rituximab era however, this treatment approach has shown only limited benefit. In particular, patients relapsing after rituximab-containing primary treatment have an adverse prognosis, especially if this occurs within the first year after therapy or if the disease is primarily refractory. Therefore there is an ultimate need for improved salvage treatment approaches. The STORM study is a prospective, multicentre phase I/II study to evaluate the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to the standard therapy rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. The primary objective of the phase I of the trial is to establish the maximum tolerated dose (MTD) of temsirolimus in combination with rituximab and DHAP. The secondary objective is to demonstrate that stem cells can be mobilized during this regimen in patients scheduled to proceed to high dose therapy. In phase II, the previously established maximum tolerated dose of temsirolimus will be used. The primary objective is to evaluate the overall response rate (ORR) in patients with relapsed DLBCL. The secondary objective is to evaluate progression free survival (PFS), overall survival (OS) and toxicity. The study will be accompanied by an analysis of lymphoma subtypes determined by gene expression analysis (GEP). The STORM trial evaluates the safety, feasibility and activity of salvage therapy consisting of the mTOR inhibitor temsirolimus added to standard therapy of rituximab and DHAP for the treatment of patients with relapsed or refractory DLBCL. It also might identify predictive markers for this treatment modality. ClinicalTrials.gov http

HEK293T cell lines defective for O-linked glycosylation.

Directory of Open Access Journals (Sweden)

James M Termini

Full Text Available Here we describe derivatives of the HEK293T cell line that are defective in their ability to generate mucin-type O-linked glycosylation. Using CRISPR/Cas9 and a single-cell GFP-sorting procedure, the UDP-galactose-4-epimerase (GALE, galactokinase 1 (GALK1, and galactokinase 2 (GALK2 genes were knocked out individually and in combinations with greater than 90% of recovered clones having the desired mutations. Although HEK293T cells are tetraploid, we found this approach to be an efficient method to target and disrupt all 4 copies of the target gene. Deficient glycosylation in the GALE knockout cell line could be rescued by the addition of galactose and N-acetylgalactosamine (GalNAc to the cell culture media. However, when key enzymes of the galactose/GalNAc salvage pathways were disrupted in tandem (GALE+GALK1 or GALE+GALK2, O-glycosylation was eliminated and could not be rescued by the addition of either galactose plus GalNAc or UDP-galactose plus UDP-GalNAc. GALK1 and GALK2 are key enzymes of the galactose/GalNAc salvage pathways. Mass spectrometry was performed on whole cell lysate of the knockout cell lines to verify the glycosylation phenotype. As expected, the GALE knockout was almost completely devoid of all O-glycosylation, with minimal glycosylation as a result of functional salvage pathways. However, the GALE+GALK1 and GALE+GALK2 knockout lines were devoid of all O-glycans. Mass spectrometry analysis revealed that the disruption of GALE, GALK1, and GALE+GALK2 had little effect on the N-glycome. But when GALE was knocked out in tandem with GALK1, N-glycans were exclusively of the high mannose type. Due to the well-characterized nature of these five knockout cell lines, they will likely prove useful for a wide variety of applications.

Accuracy of post-radiotherapy biopsy before salvage radical prostatectomy.

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Meeks, Joshua J; Walker, Marc; Bernstein, Melanie; Kent, Matthew; Eastham, James A

2013-08-01

To determine whether post-radiotherapy (RT) biopsy (PRB) adequately predicts the presence, location, and histological features of cancer in the salvage radical prostatectomy (SRP) specimen. Before salvage treatment, a PRB is required to confirm the presence of locally recurrent or persistent cancer and to determine the extent and location of the prostate cancer. SRP was performed between 1998 and 2011 on 198 patients. All patients underwent a PRB. PRB and SRP specimens were evaluated by a genitourinary pathologist. Patients had external-beam RT alone (EBRT; 71%) or brachytherapy with or without EBRT (29%). Of the men undergoing SRP, 26 (14%) were clinical stage ≥T3, with 13% of PRBs with Gleason score ≥8. Cancer was unilateral in 120 (61%) biopsies, with contralateral or bilateral prostate cancer at SRP in 49%. In the SRP specimen, cancer was multifocal in 57%. Cancer was upgraded at SRP in 58% of men, with 20% having an increase in primary Gleason grade. The accuracy of PRB varied by region from 62% to 76%, with undetected cancers ranging from 12% to 26% and most likely to occur at the mid-gland. Radiation-recurrent prostate cancers were often multifocal, and biopsy missed up to 20% of tumours. More than half of the cancers were upgraded at SRP, and many that were unilateral on PRB were bilateral at SRP. © 2013 BJU International.

Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer

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Morris, M M; Dallow, K C; Zietman, A L; Althausen, A F; Heney, N M; McGovern, F J; Shipley, W U

1995-07-01

Purpose: To assess the ability of adjuvant irradiation to prevent PSA failure in cases of pT3N0 disease, and of salvage irradiation to durably suppress a rising PSA following radical prostatectomy. Methods and Materials: 62 patients treated by post-operative radiation therapy (60-64Gy in 1.8Gy fractions to the tumor bed) between 1988 and 1993 were evaluated. All had complete pre- and post-radiation PSA data. Median follow up was 3.2 years from time of surgery and 2.2 years from irradiation. 20 patients had Gleason grade 3 disease (moderately differentiated) and 41 Gleason 4-5 (poorly differentiated). 46 had positive inked surgical margins, 18 involved seminal vesicles and 5 had palpable recurrent disease. None had known nodal or metastatic disease. 32 patients underwent adjuvant treatment (undetectable PSA at time of irradiation) and 30 salvage (detectable PSA at time of irradiation). Kaplan-Meier life table analysis was employed. The endpoint studied was freedom from biochemical failure. This was defined as a rise in the PSA of greater than 10% (intra laboratory error <8%) or a previously undetectable PSA becoming detectable. Results: The overall actuarial freedom from biochemical failure at 4 years from radiotherapy was 59%. A significant difference was seen between those receiving adjuvant and those receiving salvage irradiation (71% vs 51%, p=0.03). Amongst those in the salvage group neither the PSA prior to surgery, the PSA at the time of irradiation, the seminal vesicle status, nor the Gleason score (3 vs 4-5) correlated significantly with outcome. The time interval between surgery and irradiation was, however, significant. Those being treated within 6 months fared better than those treated later (60% vs 36%, p=0.04). Further, those treated early were more likely to achieve an undetectable nadir PSA level (94% vs 71%). Conclusion: The addition of adjuvant irradiation appears to improve the 4 year biochemical disease-free survival of patients with poor

Salvage surgery following radiation failure in squamous cell carcinoma of the supraglottic larynx

International Nuclear Information System (INIS)

Parsons, James T.; Mendenhall, William M.; Stringer, Scott P.; Cassisi, Nicholas J.; Million, Rodney R.

1995-01-01

Purpose: We analyzed the clinical course of patients who developed local (primary) recurrence following high-dose irradiation of squamous cell carcinoma of the supraglottic larynx. Methods and Materials: Between October 1964 and July 1991, 206 patients with previously untreated squamous cell carcinoma of the supraglottic larynx underwent radiotherapy with curative intent. Local failure occurred in 46 (22%) patients. Successful surgical salvage was defined as no evidence of recurrent cancer for at least 2 years after salvage surgery and continuously thereafter. Results: Sixteen patients did not undergo salvage surgery because of refusal (7 patients), severe medical illness (2 patients), concurrent distant metastasis (5 patients), or unresectable neck disease (2 patients). Twenty-six patients underwent total laryngectomy, and 4 patients had a voice-sparing procedure. Successful salvage was achieved in 50% of patients who underwent surgery. The rate of successful salvage did not correlate with preirradiation T-stage or time to failure after irradiation. Most of the failures after surgery were because of failure to control the primary cancer. The overall rate of postsurgical complications was 37%. No operative or perioperative deaths occurred. The 5-year survival rate for all 46 patients, calculated from the date of irradiation failure, was 20%, while the 5-year survival rate after salvage surgery for the 30 patients who underwent the procedure was 29%. Conclusion: There are few data in the literature regarding the clinical outcome in patients whose tumors are not controlled by initial radiotherapy. In the current and previous series, one-half to two-thirds of patients who developed primary failure underwent salvage surgery, which was successful in approximately half of the operated patients, leading to a 25-30% rate of long-term disease-free survival among the entire group of patients who developed failure

An experience of second-trimester anhydramnios salvaged by single amnioinfusion.

Science.gov (United States)

Io, Shingo; Kondoh, Eiji; Chigusa, Yoshitsugu; Tani, Hirohiko; Hamanishi, Junzo; Konishi, Ikuo

2017-11-20

Second-trimester anhydramnios, which is primarily caused by ruptured membranes, placental dysfunction, or congenital renal malformations, is associated with high perinatal morbidity and mortality. Although amnioinfusion temporarily increases amniotic fluid volume, it does not generally provide a fundamental solution. We describe a case of second-trimester anhydramnios with an umbilical cord factor, wherein single amnioinfusion may have successfully broken a vicious circle involving non-reassuring fetal status. A 34-year-old primigravid woman was referred to our hospital because of anhydramnios at 22 weeks' gestation. Single amnioinfusion improved the fetal circulatory failure, and the patient delivered a healthy full-term newborn. Single amnioinfusion may be a therapeutic approach to improve the prognosis of pregnancy when second-trimester anhydramnios results from umbilical cord factors.

Immediate free jejunum transfer for salvage surgery of gastric tube necrosis.

Science.gov (United States)

Umezawa, Hiroki; Matsutani, Takeshi; Ogawa, Rei; Hyakusoku, Hiko

2014-01-01

Gastric tube necrosis after esophagus cancer surgery is a rare but critical situation. Salvage reconstruction of the esophagus remains a challenging procedure for head and neck surgeons. Historically, surgeons have employed a two-stage salvage surgery consisting of debridement followed by reconstruction. While this procedure generates good results, the time to restart oral alimentation is long. The present report describes the case of a 62-year-old male who developed gastric tube necrosis 3 days after undergoing surgery for thoracic-cervical esophageal cancer and immediate reconstruction with the retrosternal gastric pullup technique. He was treated with debridement and simultaneous free jejunum transfer 4 days after the primary surgery. He was able to restart oral alimentation 10 days after the salvage surgery. This rapid return to oral alimentation is a major advantage of the one-stage immediate esophagus salvage reconstruction. Another advantage is the ease of the reconstructive procedure: the absence of scarring and prolonged inflammation, which are disadvantages of the two-stage procedure, meant that recipient vessel selection and anastomosis were uncomplicated. The one-step procedure may be particularly useful in cases where the inflammation is discovered early.

Immunotherapy “Shock” a case series of PD-L1 100% and pembrolizumab first-line treatment

Directory of Open Access Journals (Sweden)

Paul Zarogoulidis

2017-01-01

Full Text Available In this decade a “bloom” of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

Impact of salvage therapy for biochemical recurrence on health-related quality of life following radical prostatectomy

International Nuclear Information System (INIS)

Namiki, Shunichi; Saito, Seiichi; Arai, Yoichi; Tochigi, Tatsuo; Ioritani, Naomasa; Terai, Akito

2007-01-01

The objective of this study was to determine the impact of salvage therapy for prostate-specific antigen (PSA) recurrence on the health-related quality of life (HRQOL) of patients after radical retropubic prostatectomy (RP). Between January 2000 and December 2003, a total of 249 patients who underwent RP were available for 2-year follow up. Of the respondents, 203 men did not show evidence of recurrence (group A), and 46 men received salvage hormonal therapy and/or radiotherapy after RP because of a rise in PSA (group B). The general and prostate-target HRQOL was assessed with the Medical Outcomes Study 36-Item Short Form and University of California, Los Angeles Prostate Cancer Index, respectively. Patients completed the HRQOL instruments by mail at baseline and at 24 months after RP. All of the patients completed both questionnaires. At baseline no significant differences were found between the two groups in any of the HRQOL domains. There were significant improvements in mental health and social function for the patients without biochemical recurrence postoperatively. Repeated measure analysis of variance (ANOVA) revealed significantly different patterns of alteration in several general HRQOL domains among the treatment groups. The urinary and bowel domains were equivalent between the two treatment groups at baseline and 24 months after RP. The patients treated with salvage hormonal therapy tended to show delayed recovery of sexual function. Using a self-administered questionnaire, biochemical recurrence following RP was found to impose a substantial burden in patients with localized prostate cancer. (author)

Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

Science.gov (United States)

Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

2017-06-28

Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

"To look at death another way": Black teenage males' perspectives on second-lines and regular funerals in New Orleans.

Science.gov (United States)

Bordere, Tashel C

The purpose of this study was to describe how Black adolescent males understand "second-line" (musical processions) and "regular"/traditional funeral rituals in New Orleans following the violent deaths of significant persons in their lives. In-depth interviews were conducted with 10 Black males between the ages of 12 and 15 using descriptive phenomenology methodology. Findings revealed that these participants understood death as a cause for celebration, remembrance, and unity related to their experiences with the second-line ritual. Three elements of the life world of Black teenage males were descriptive of second lines, including: a) observed locations of second lines; b) dancing to good music; and c) observed messages conveyed through t-shirts. Participants provided gender-based descriptions of perceived spoken and unspoken rights in grieving at the two distinct rituals. Related to their second-line experience, the teens reflect on ways in which they wish to have their deaths ritualized.

Second Line of Defense Spares Program Assessment

Energy Technology Data Exchange (ETDEWEB)

Henderson, Dale L.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.

2012-11-20

The Office of the Second Line of Defense (SLD) is part of the Department of Energy‘s (DOE) National Nuclear Security Administration (NNSA). The SLD Program accomplishes its critical global security mission by forming cooperative relationships with partner countries to install passive radiation detection systems that augment traditional inspection and law enforcement measures by alerting border officials to the presence of special nuclear or other radiological materials in cross-border traffic. An important tenet of the program is to work collaboratively with these countries to establish the necessary processes, procedures, infrastructure and conditions that will enable them to fully assume the financial and technical responsibilities for operating the equipment. As the number of operational deployments grows, the SLD Program faces an increasingly complex logistics process to promote the timely and efficient supply of spare parts.

Protocol-based image-guided salvage brachytherapy. Early results in patients with local failure of prostate cancer after radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Lahmer, G.; Lotter, M.; Kreppner, S.; Fietkau, R.; Strnad, V. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

2013-08-15

Purpose: To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects. Patients and methods: Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005-2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V{sub 100} > 95 %) simultaneously respecting the protocol-based dose volume constraints for the urethra (D{sub 0.1} {sub cc} < 130 %) and the rectum (D{sub 2} {sub cc} < 50-60 %) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities - particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival. Results: We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1 % (2/18) and 16.7 % (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17 % (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1 %. The overall survival at 3 years was 88.9 %; 22 % (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8-77 months). Conclusion: Salvage PDR

Clinical results for salvage surgery in head and neck carcinoma after chemoradiation or radiation

International Nuclear Information System (INIS)

Ishida, Katsuhiro; Makino, Yohjiroh; Nagaoka, Masato; Seino, Youichi; Hama, Takanori; Aoki, Kensuke; Uchida, Mitsuru; Kato, Takakuni

2013-01-01

The objective of this study was to examine the post-operative complications of surgical procedures in oral or pharyngeal carcinoma by analyzing and comparing between patients who underwent salvage surgery after chemoradiation and radiation. A retrospective review was performed of 18 patients who underwent salvage surgery and reconstruction after concurrent chemoradiotherapy (CCRT group), and another 41 patients who underwent salvage surgery and reconstruction after radiation therapy (RT group). No perioperative deaths or life threatening systemic complications occurred, and all flaps survived completely in both groups. Surgical site infection (SSI) occurred in five patients (12.2%) in the RT group and seven patients (38%) in the CCRT group. SSI other than donor site infection occurred in four patients (9%) in the RT group and four patients (22%) in the CCRT group. The rate of SSI excluding donor site infection did not differ significantly between patients who underwent salvage surgery after CCRT and RT. The rate of donor site infection was higher in the CCRT group than in the RT group (p=0.04). This study showed that salvage surgery after CCRT or RT can be performed safely, without significant morbidity or mortality. However, patients who received CCRT are at risk for major complications caused by minor troubles, and thus reconstruction after salvage surgery should be performed with sufficient care. (author)

Surgical complications of salvage surgery following concurrent chemoradiotherapy for laryngeal cancer

International Nuclear Information System (INIS)

Furuta, Yasushi; Homma, Akihiro; Oridate, Nobuhiko

2007-01-01

Surgical complication rates of salvage laryngectomy after chemoradiotherapy (CRT) have been reported to be high. Wound complications after salvage laryngectomy following concurrent chemoradiotherapy (CCRT) were analyzed. Eighty-six patients who had undergone total laryngectomy for laryngeal cancer at Hokkaido University Hospital between 1990 and 2006 were divided into three groups according to preoperative treatments received: total laryngectomy (TL) group (n=35) without radiotherapy (RT) or CCRT, RT-TL group (n=17) with RT alone, CRT-TL group (n=34) with low-dose CCRT. Major wound complications were defined as major pharyngocutaneous fistulas which caused inpatient care for more than eight weeks or which were closed by surgery, bleeding that required surgical reintervention, and wound infection or skin necrosis that caused inpatient care for more than eight weeks. Minor complications were self-limited, managed with local wound care, and did not prolong inpatient care for more than eight weeks. We also analyzed wound complications of larynx preservation surgery after CCRT. Overall wound complications, both major and minor, were observed in 26% of the TL group, 35% of the RT-TL group, and 47% of the CRT-TL group. Major wound complications were observed in 11%, 18%, and 29%, respectively. A considerable but not statistically significant increase in the incidence of overall and major wound complications was observed between the TL and CRT-TL groups (p=0.082 and 0.078, respectively). Pharyngocutaneous fistulas were the most common complication, occurring in 14/86 (16%) of patients. Patients who developed pharyngocutaneous fistulas after CCRT tended to require surgical reintervention and longer periods before the initiation of oral intake. Wound complications were observed in 2/3 (67%) of patients who had undergone larynx preservation surgery. High incidences of wound complications and poor wound recovery in patients undergoing salvage laryngectomy following CCRT should

Saphenous vein grafts for perforator flap salvage in autologous breast reconstruction.

Science.gov (United States)

Flores, Jaime I; Rad, Ariel N; Shridharani, Sachin M; Stapleton, Sahael M; Rosson, Gedge D

2009-01-01

Although the use of saphenous vein grafts in free-flap salvage and extremity replantation is relatively common, their use in breast reconstruction is rare. These two case reports represent extreme alternatives for breast reconstruction flap salvage. In our normal daily practice, the overwhelming majority of elective breast reconstructions proceed smoothly. However, the occasional patient may require saphenous vein graft flap rescue for completion of the reconstruction. (c) 2008 Wiley-Liss, Inc.

The impact of joint line restoration on functional results after hinged knee prosthesis

Directory of Open Access Journals (Sweden)

Serdar Yilmaz

2016-01-01

Conclusion: RHKA is an effective salvage procedure for serious instability and large bone defects. Restoration of the joint line improves the patellar score although it had no effect on the clinical outcome.

Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

Science.gov (United States)

Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

2013-12-01

Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer.

Science.gov (United States)

Ju, Huai-Qiang; Zhuang, Zhuo-Nan; Li, Hao; Tian, Tian; Lu, Yun-Xin; Fan, Xiao-Qiang; Zhou, Hai-Jun; Mo, Hai-Yu; Sheng, Hui; Chiao, Paul J; Xu, Rui-Hua

2016-08-28

Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor for the redox reactions in the metabolic pathways of cancer cells that have elevated aerobic glycolysis (Warburg effect). Cancer cells are reported to rely on NAD recycling and inhibition of the NAD salvage pathway causes metabolic collapse and cell death. However, the underlying regulatory mechanisms and clinical implications for the NAD salvage pathway in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study showed that the expression of Nampt, the rate-limiting enzyme of the NAD salvage pathway, was significantly increased in PDAC cells and PDAC tissues. Additionally, inhibition of Nampt impaired tumor growth in vitro and tumorigenesis in vivo, which was accompanied by a decreased cellular NAD level and glycolytic activity. Mechanistically, the Nampt expression was independent of Kras and p16 status, but it was directly regulated by miR-206, which was inversely correlated with the expression of Nampt in PDAC tissues. Importantly, pharmacological inhibition of Nampt by its inhibitor, FK866, significantly enhanced the antitumor activity of gemcitabine in PDAC cells and in orthotopic xenograft mouse models. In conclusion, the present study revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

19 CFR 4.97 - Salvage vessels.

Science.gov (United States)

2010-04-01

... United States and Great Britain ‘concerning reciprocal rights for United States and Canada in the... meaning of this statute. (e) A Mexican vessel may engage in a salvage operation on a Mexican vessel in any territorial waters of the United States in which Mexican vessels are permitted to conduct such operations by...

Salvage Stereotactic Body Radiation Therapy (SBRT) for Local Failure After Primary Lung SBRT

Energy Technology Data Exchange (ETDEWEB)

Hearn, Jason W.D., E-mail: hearnj@ccf.org; Videtic, Gregory M.M.; Djemil, Toufik; Stephans, Kevin L.

2014-10-01

Purpose: Local failure after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is uncommon. We report the safety and efficacy of SBRT for salvage of local failure after previous SBRT with a biologically effective dose (BED) of ≥100 Gy{sub 10}. Methods and Materials: Using an institutional review board–approved lung SBRT registry, we identified all patients initially treated for early-stage NSCLC between August 2004 and January 2012 who received salvage SBRT for isolated local failure. Failure was defined radiographically and confirmed histologically unless contraindicated. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance, and received a BED of ≥100 Gy{sub 10} for each SBRT course. Tumor motion control involved a Bodyfix vacuum system for immobilization along with abdominal compression. Results: Of 436 patients treated from August 2004 through January 2012, we identified 22 patients with isolated local failure, 10 of whom received SBRT for salvage. The median length of follow-up was 13.8 months from salvage SBRT (range 5.3-43.5 months). Median tumor size was 3.4 cm (range 1.7-4.8 cm). Two of the 10 lesions were “central” by proximity to the mediastinum, but were outside the zone of the proximal bronchial tree. Since completing salvage, 3 patients are alive and without evidence of disease. A fourth patient died of medical comorbidities without recurrence 13.0 months after salvage SBRT. Two patients developed distant disease only. Four patients had local failure. Toxicity included grade 1-2 fatigue (3 patients) and grade 1-2 chest wall pain (5 patients). There was no grade 3-5 toxicity. Conclusions: Repeat SBRT with a BED of ≥100 Gy{sub 10} after local failure in patients with early-stage medically inoperable NSCLC was well tolerated in this series and may represent a viable salvage strategy in select patients with peripheral tumors ≤5 cm.

Postoperative internal iliac artery embolisation as salvage therapy ...

African Journals Online (AJOL)

Postoperative internal iliac artery embolisation as salvage therapy for ... of blood products. Damage control surgery was performed, and bleeding was ultimately only ... abdomen was packed with adrenalin-soaked swabs. Coagulation.

Re-irradiation of the chest wall for local breast cancer recurrence. Results of salvage brachytherapy with hyperthermia

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Auoragh, A. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Fuerth, Department of Radiation Oncology, Fuerth (Germany); Strnad, V.; Ott, O.J.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Beckmann, M.W. [University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen (Germany)

2016-09-15

Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects. (orig.) [German] Nach einer Mastektomie und adjuvanter Strahlentherapie bei Patientinnen mit Mammakarzinom kommt es bei 9 % (2-20 %) zum lokalen bzw. lokoregionaeren Rezidiv. Neben den oft limitierten operativen Behandlungsmoeglichkeiten ist die Strahlentherapie mit Oberflaechenhyperthermie die

Salvage cryotherapy for local recurrence after radiotherapy for prostate cancer.

Science.gov (United States)

Kvorning Ternov, Klara; Krag Jakobsen, Ane; Bratt, Ola; Ahlgren, Göran

2015-04-01

The aim of this study was to present the outcome of patients treated with salvage cryotherapy after radiotherapy for prostate cancer at one institution. Consecutive patients treated between 2007 and 2013 with transperineal cryotherapy for biopsy-verified local recurrence after radiotherapy were investigated. An external reviewer retrieved outcome data retrospectively from medical records. Complications were graded according to the Clavien classification. One patient with less than 1 year of follow-up was excluded from the analysis of side-effects. Thirty patients were included, 29 of whom had a follow-up of at least 1 year. The median follow-up was 2.7 years (range 1-6.5 years). Eleven of the 23 patients without hormonal treatment at the time of cryotherapy reached a prostate-specific antigen (PSA) nadir of less than 0.5 ng/ml. At the end of follow-up five of these 23 patients still had a PSA below 0.5 ng/ml and 10 were free from recurrence according to the Phoenix definition. Clinical recurrence (verified with imaging or biopsies) was detected in 13 patients, six of which were local. One patient died from prostate cancer. Eleven patients had urinary incontinence grade 1-2 and three had grade 3-4, seven had pelvic pain, three had severe but transitory tissue sloughing, three developed a urethral stricture or had prolonged urinary retention, and one developed a urinary fistula 4.5 years after cryotherapy. Salvage cryotherapy should be considered as an alternative to hormonal treatment and surgery for local recurrence after radiotherapy for prostate cancer. The results compare well to those reported from centres with longer experience.

Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer

International Nuclear Information System (INIS)

Yamashita, Hideomi; Haga, Akihiro; Takenaka, Ryousuke; Kiritoshi, Tomoki; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

2016-01-01

Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m 2 was given on days 1 and 29, and S-1 80 mg/m 2 on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. Between August 2011 and June 2015, 89 patients (age range, 44–86 years; K-PS 90–100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT

Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer.

Science.gov (United States)

Yamashita, Hideomi; Haga, Akihiro; Takenaka, Ryousuke; Kiritoshi, Tomoki; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

2016-01-19

Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m(2) was given on days 1 and 29, and S-1 80 mg/m(2) on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. Between August 2011 and June 2015, 89 patients (age range, 44-86 years; K-PS 90-100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT.

Second Line of Defense Spares Program

Energy Technology Data Exchange (ETDEWEB)

Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.

2012-11-20

During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.

Combined stent placement and high dose PGE1 drip infusion for chronic occlusion of the superficial femoral artery as a modality to salvage chronic critical limb ischemia

Energy Technology Data Exchange (ETDEWEB)

Ikushima, Ichiro [Department of Radiology, Miyakonojo Medical Association Hospital, 5822-3 Oiwadacho, Miyakonojo 885-0062 (Japan)], E-mail: iku-i@fk.enjoy.ne.jp; Hirai, Toshinori [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University (Japan); Ishii, Akihiko [Department of Radiology, Miyakonojo Medical Association Hospital, 5822-3 Oiwadacho, Miyakonojo 885-0062 (Japan); Yamashita, Yasuyuki [Department of Diagnostic Radiology, Graduate School of Medical Sciences, Kumamoto University (Japan)

2008-04-15

Purpose: To assess the initial effect, short-term patency, and limb salvage rates of combined stent placement and high-dose prostaglandin E-1 (PGE1) drip infusion for chronic occlusion of the superficial femoral artery (SFA). Materials and methods: A total of 15 arteriosclerotic occlusive lesions of the SFA were treated in 11 consecutive patients (mean age: 78.4 years old). All cases were of category 4 or 5, based on the criteria of the Society of Vascular Surgery and Intermittent Society for Cardiovascular Surgery (SVC/ISCVS). In all cases a self-expandable stainless steel stent was implanted. PGE1 treatment was started 3-5 days before stent placement and continued for 7-10 days after the intervention. The technical success, limb salvage outcomes, patency rates, and complications were examined. Results: In all cases, the technical success rate of the procedure was 100%. After stent implantation, the clinical status of all cases was improved by at least +2, and major amputation was not required in any cases. The 12-month primary, secondary patency rates, and limb salvage rate were 57%, 100%, and 100%, respectively. Conclusion: Combined stent placement and high-dose PGE1 drip infusion is a treatment of choice for salvaging the lower limb of a patient with chronic critical ischemia.

A telephone questionnaire in order to assess functional outcome after post-traumatic limb salvage surgery: Development and preliminary validation.

Science.gov (United States)

Wulterkens, Leonie; Aurégan, Jean-Charles; Letellier, Thomas; Mebtouche, Nasser; Levante, Stéphane; Cottin, Philippe; Bégué, Thierry

2015-12-01

Post-traumatic limb salvage surgery is challenging and evaluation of the results remains arduous. No questionnaire specifically assessing functional outcome after post-traumatic limb salvage surgery of the lower extremity exists. Due to regionalization of specialized care, the patients' travel time to the hospital increases. To overcome a higher patients' travel burden, patients' follow up by telephone is an option. We aimed to develop a telephone questionnaire in order to assess functional outcome after post-traumatic limb salvage surgery of the lower extremity. From a review of scores of functional assessment of the lower limb surgery, we have developed a telephone questionnaire. A prospective study was performed to validate this telephone questionnaire. Twenty patients were included. The participants were called to complete the telephone questionnaire twice with an interval of a week. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was completed during the second telephone call. The internal consistency was analyzed by the Cronbach's alpha (α). With the outcome scores of both completions, the test-retest reliability was analyzed by the interclass correlation coefficient (ICC) 2,k with a 95% confidence interval (95% CI). The outcome scores of the second telephone questionnaire and the WOMAC questionnaire were used for the construct validity analysis by the Spearman's rank correlation coefficient (r(s)) with a 95% CI. The internal consistency analysis revealed a α=0.62 which improved to α=0.92 after removing one question from the telephone questionnaire. The final version of the telephone questionnaire comprises 32 questions, divided in 3 subscales: function, daily life and psychology. The total score varies between 0 and 86 points. The test-retest reliability was ICC 2,k=0.93 (95% CI: 0.82-0.97) and the construct validity was r(s)=0.92 (95% CI: 0.81-0.97). We present a specific telephone questionnaire in order to assess functional

Deep Brain Stimulation Salvages a Flourishing Dental Practice: A Dentist with Essential Tremor Recounts his Experience.

Science.gov (United States)

Giacopuzzi, Guy; Lising, Melanie; Halpern, Casey H

2016-10-22

In recounting his experience with deep brain stimulation (DBS), a practicing dentist challenged with long-standing bilateral essential tremor of the hands shares insights into his diagnosis, treatments, and ultimately successful DBS surgery at Stanford University Medical Center, CA, USA. Now nearly one year after his surgery, his practice continues to flourish and he encourages others in his profession to consider the possibility of DBS as a definitive treatment for tremors of the hand, which may salvage their practice.

Salvage High-intensity Focused Ultrasound for the Recurrent Prostate Cancer after Radiotherapy

International Nuclear Information System (INIS)

Shoji, S.; Nakano, M.; Omata, T.; Harano, Y.; Nagata, Y.; Uchida, T.; Usui, Y.; Terachi, T.

2010-01-01

To investigate the use of minimally invasive high-intensity focused ultrasound (HIFU) as a salvage therapy in men with localized prostate cancer recurrence following external beam radiotherapy (EBRT), brachytherapy or proton therapy. A review of 20 cases treated using the Sonablate registered 500 HIFU device, between August 28, 2002 and September 1, 2009, was carried out. All men had presumed organ-confined, histologically confirmed recurrent prostate adenocarcinoma following radiation therapy. All men with presumed, organ-confined, recurrent disease following EBRT in 8 patients, brachytherapy in 7 patients or proton therapy in 5 patients treated with salvage HIFU were included. The patients were followed for a mean (range) of 16.0 (3-80) months. Biochemical disease-free survival (bDFS) rates in patients with low-intermediate and high risk groups were 86% and 50%, respectively. Side-effects included urethral stricture in 2 of the 16 patients (13%), urinary tract infection or dysuria syndrome in eight (26%), and urinary incontinence in one (6%). Recto-urethral fistula occurred in one patient (6%). Transrectal HIFU is an effective treatment for recurrence after radiotherapy especially in patients with low- and intermediate risk groups.

Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

Directory of Open Access Journals (Sweden)

Zhang Jian

2012-06-01

Full Text Available Abstract Purpose To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. Methods 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy combined with chemotherapy consisting of either 5-fluorouracil (5-FU plus cisplatin (DDP (R-FP group or paclitaxel plus DDP (R-TP group. Results The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS and overall survival (OS time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months in the R-TP group was superior to that in the R-FP group (median: 9.8 months (p = 0.012. Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months and OS (16.3 months were significantly superior to the PFS (8.7 months and OS (11.3 months among those patients did not (all p  Conclusions For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome.

Salvage conformal radiotherapy for biochemical recurrent prostate cancer after radical prostatectomy

Directory of Open Access Journals (Sweden)

Carlos R. Monti

2006-08-01

Full Text Available OBJECTIVE: Assess the results of salvage conformal radiotherapy in patients with biochemical failure after radical prostatectomy and identify prognostic factors for biochemical recurrence and toxicity of the treatment. MATERIALS AND METHODS: From June 1998 to November 2001, 35 patients were submitted to conformal radiotherapy for PSA > 0.2 ng/mL in progression after radical prostatectomy and were retrospectively analyzed. The mean dose of radiation in prostatic bed was of 77.4 Gy (68-81. Variables related to the treatment and to tumor were assessed to identify prognostic factors for biochemical recurrence after salvage radiotherapy. RESULTS: The median follow-up was of 55 months (17-83. The actuarial survival rates free of biochemical recurrence and free of metastasis at a distance of 5 years were 79.7% e 84.7%, respectively. The actuarial global survival rate in 5 years was 96.1%.The actuarial survival rate free of biochemical recurrence in 5 years was 83.3% with PSA pre-radiotherapy 1 and 2 (p = 0.023. Dose > 70 Gy in 30% of the bladder volume implied in more acute urinary toxicity (p = 0.035. The mean time for the development of late urinary toxicity was 21 months (12-51. Dose > 55 Gy in 50% bladder volume implied in more late urinary toxicity (p = 0.018. A patient presented late rectal toxicity of 2nd grade. CONCLUSIONS: Conformal radiotherapy showed to be effective for the control of biochemical recurrence after radical prostatectomy. Patients with pre-therapy PSA < 2 ng/mL have more biochemical control.

Long term outcomes after salvage radiotherapy for postoperative locoregionally recurrent non-small-cell lung cancer

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Kim, Eun Ji; Song, Chang Hoon; Kim, Jae Sung [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Mi Young [Dept. of Radiation Oncology, Kyungpook National University Medical Center, Daegu (Korea, Republic of)

2017-03-15

The outcomes and toxicities of locoregionally recurrent non-small-cell lung cancer (NSCLC) patients treated with curative radiotherapy were evaluated in the modern era. Fifty-seven patients receiving radical radiotherapy for locoregionally recurrent NSCLC without distant metastasis after surgery from 2004 to 2014 were reviewed. Forty-two patients were treated with concurrent chemoradiotherapy (CCRT), and 15 patients with radiotherapy alone. The median radiation dose was 66 Gy (range, 45 to 70 Gy). Lung function change after radiotherapy was evaluated by comparing pulmonary function tests before and at 1, 6, and 12 months after radiotherapy. Median follow-up was 53.6 months (range, 12.0 to 107.5 months) among the survivors. The median overall survival (OS) and progression-free survival (PFS) were 54.8 months (range, 3.0 to 116.9 months) and 12.2 months (range, 0.8 to 100.2 months), respectively. Multivariate analyses revealed that single locoregional recurrence focus and use of concurrent chemotherapy were significant prognostic factors for OS (p = 0.048 and p = 0.001, respectively) and PFS (p = 0.002 and p = 0.026, respectively). There was no significant change in predicted forced expiratory volume in one second after radiotherapy. Although diffusing lung capacity for carbon monoxide decreased significantly at 1 month after radiotherapy (p < 0.001), it recovered to pretreatment levels within 12 months. Acute grade 3 radiation pneumonitis and esophagitis were observed in 3 and 2 patients, respectively. There was no chronic complication observed in all patients. Salvage radiotherapy showed good survival outcomes without severe complications in postoperative locoregionally recurrent NSCLC patients. A single locoregional recurrent focus and the use of CCRT chemotherapy were associated with improved survival. CCRT should be considered as a salvage treatment in patients with good prognostic factors.

Retrograde nail for tibiotalocalcaneal arthrodesis as a limb salvage procedure for open distal tibia and talus fractures with severe bone loss.

Science.gov (United States)

Ochman, Sabine; Evers, Julia; Raschke, Michael J; Vordemvenne, Thomas

2012-01-01

The treatment of complex fractures of the distal tibia, ankle, and talus with soft tissue damage, bone loss, and nonreconstructable joints for which the optimal timing for reduction and fixation has been missed is challenging. In such cases primary arthrodesis might be a treatment option. We report a series of multi-injured patients with severe soft tissue damage and bone loss, who were treated with a retrograde tibiotalocalcaneal arthrodesis nail as a minimally invasive treatment option for limb salvage. After a median follow-up of 5.4 years, all patients returned to their former profession. The ankle and bone fusion was complete, with moderate functional results and quality of life. Calcaneotibial arthrodesis using a retrograde nail is a good treatment option for nonreconstructable fractures of the ankle joint with severe bone loss and poor soft tissue quality in selected patients with multiple injuries, in particular, those involving both lower extremities, as a salvage procedure. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

NAD+ salvage pathway in cancer metabolism and therapy.

Science.gov (United States)

Kennedy, Barry E; Sharif, Tanveer; Martell, Emma; Dai, Cathleen; Kim, Youra; Lee, Patrick W K; Gujar, Shashi A

2016-12-01

Nicotinamide adenine dinucleotide (NAD + ) is an essential coenzyme for various physiological processes including energy metabolism, DNA repair, cell growth, and cell death. Many of these pathways are typically dysregulated in cancer cells, making NAD + an intriguing target for cancer therapeutics. NAD + is mainly synthesized by the NAD + salvage pathway in cancer cells, and not surprisingly, the pharmacological targeting of the NAD + salvage pathway causes cancer cell cytotoxicity in vitro and in vivo. Several studies have described the precise consequences of NAD + depletion on cancer biology, and have demonstrated that NAD+ depletion results in depletion of energy levels through lowered rates of glycolysis, reduced citric acid cycle activity, and decreased oxidative phosphorylation. Additionally, depletion of NAD + causes sensitization of cancer cells to oxidative damage by disruption of the anti-oxidant defense system, decreased cell proliferation, and initiation of cell death through manipulation of cell signaling pathways (e.g., SIRT1 and p53). Recently, studies have explored the effect of well-known cancer therapeutics in combination with pharmacological depletion of NAD + levels, and found in many cases a synergistic effect on cancer cell cytotoxicity. In this context, we will discuss the effects of NAD + salvage pathway inhibition on cancer cell biology and provide insight on this pathway as a novel anti-cancer therapeutic target. Copyright © 2016 Elsevier Ltd. All rights reserved.

Washed cell salvage in surgical patients: A review and meta-analysis of prospective randomized trials under PRISMA.

Science.gov (United States)

Meybohm, Patrick; Choorapoikayil, Suma; Wessels, Anke; Herrmann, Eva; Zacharowski, Kai; Spahn, Donat R

2016-08-01

Cell salvage is commonly used as part of a blood conservation strategy. However concerns among clinicians exist about the efficacy of transfusion of washed cell salvage. We performed a meta-analysis of randomized controlled trials in which patients, scheduled for all types of surgery, were randomized to washed cell salvage or to a control group with no cell salvage. Data were independently extracted, risk ratio (RR), and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random effects model. The primary endpoint was the number of patients exposed to allogeneic red blood cell (RBC) transfusion. Out of 1140 search results, a total of 47 trials were included. Overall, the use of washed cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 39% (RR = 0.61; 95% CI 0.57 to 0.65; P platelets, or rate of myocardial infarction and stroke. Washed cell salvage is efficacious in reducing the need for allogeneic RBC transfusion and risk of infection in surgery.

Potential for water salvage by removal of non-native woody vegetation from dryland river systems

Science.gov (United States)

Doody, T.M.; Nagler, P.L.; Glenn, E.P.; Moore, G.W.; Morino, K.; Hultine, K.R.; Benyon, R.G.

2011-01-01

Globally, expansion of non-native woody vegetation across floodplains has raised concern of increased evapotranspiration (ET) water loss with consequent reduced river flows and groundwater supplies. Water salvage programs, established to meet water supply demands by removing introduced species, show little documented evidence of program effectiveness. We use two case studies in the USA and Australia to illustrate factors that contribute to water salvage feasibility for a given ecological setting. In the USA, saltcedar (Tamarix spp.) has become widespread on western rivers, with water salvage programs attempted over a 50-year period. Some studies document riparian transpiration or ET reduction after saltcedar removal, but detectable increases in river base flow are not conclusively shown. Furthermore, measurements of riparian vegetation ET in natural settings show saltcedar ET overlaps the range measured for native riparian species, thereby constraining the possibility of water salvage by replacing saltcedar with native vegetation. In Australia, introduced willows (Salix spp.) have become widespread in riparian systems in the Murray-Darling Basin. Although large-scale removal projects have been undertaken, no attempts have been made to quantify increases in base flows. Recent studies of ET indicate that willows growing in permanently inundated stream beds have high transpiration rates, indicating water savings could be achieved from removal. In contrast, native Eucalyptus trees and willows growing on stream banks show similar ET rates with no net water salvage from replacing willows with native trees. We conclude that water salvage feasibility is highly dependent on the ecohydrological setting in which the non-native trees occur. We provide an overview of conditions favorable to water salvage. Copyright ?? 2011 John Wiley & Sons, Ltd.

Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans.

Science.gov (United States)

Vrablik, Tracy L; Wang, Wenqing; Upadhyay, Awani; Hanna-Rose, Wendy

2011-01-15

Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) from nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD(+) after it is hydrolyzed. This pathway is emerging as a regulator of multiple biological processes. Here we probe the contribution of the NAM-NAD(+) salvage pathway to muscle development and function using Caenorhabditis elegans. C. elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the first step of this NAD(+) salvage pathway, cannot mate due to a spicule muscle defect. Multiple muscle types are impaired in the hermaphrodites, including body wall muscles, pharyngeal muscles and vulval muscles. An active NAD(+) salvage pathway is required for optimal function of each muscle cell type. However, we found surprising muscle-cell-type specificity in terms of both the timing and relative sensitivity to perturbation of NAD(+) production or NAM levels. Active NAD(+) biosynthesis during development is critical for function of the male spicule protractor muscles during adulthood, but these muscles can surprisingly do without salvage biosynthesis in adulthood under the conditions examined. The body wall muscles require ongoing NAD(+) salvage biosynthesis both during development and adulthood for maximum function. The vulval muscles do not function in the presence of elevated NAM concentrations, but NAM supplementation is only slightly deleterious to body wall muscles during development or upon acute application in adults. Thus, the pathway plays distinct roles in different tissues. As NAM-NAD(+) biosynthesis also impacts muscle differentiation in vertebrates, we propose that similar complexities may be found among vertebrate muscle cell types. Copyright © 2010 Elsevier Inc. All rights reserved.

De novo and salvage pathway precursor incorporation during DNA replication at the nuclear matrix

International Nuclear Information System (INIS)

Panzeter, P.L.

1988-01-01

Total nuclear DNA can be empirically subdivided into low salt-soluble (LS) DNA (75-80%), high salt-soluble (HS) DNA (18-23%), and nuclear matrix-associated (NM) DNA which remains tightly bound to the nuclear matrix (∼2%). The most-newly replicated DNA is that associated with the nuclear matrix in regenerating rat liver. Analyses of the DNA fractions after various pulse times revealed that the salvage and de novo pathway DNA precursors investigated were incorporated preferentially into NM-DNA at early pulse times, after which the radioactivity became progressively incorporated into HS- and LS-DNA, respectively. These results support two models of nuclear matrix-associated DNA replication, proposed previously, and a third model presented in this dissertation. In addition, the incorporation of de novo pathway precursors lagged significantly (> 10 minutes) behind the incorporation of precursors entering through the salvage pathway. Channeling of salvage pathway precursors to DNA replication sites would explain the more rapid uptake of salvage precursors into NM-DNA than de novo precursors. To investigate the possibility of this heretofore in vitro phenomenon, the incorporation of the salvage precursor, ( 3 H)deoxythymidine, and the de novo precursor, ( 14 C)orotic acid, into NM-DNA and dTTP was examined in regenerating rat liver. There was no significant difference between the incorporation pattern of ( 14 C)orotic acid into NM-DNA thymine and that of ( 14 C)orotic acid into soluble dTTP. Contrastingly, the salvage pathway precursor, ( 3 H)deoxythymidine, labeled NM-DNA before labeling the dTTP pool

PREDICTORS OF OVERALL SURVIVAL IN PATIENTS WITH RECURRENT NON-SEMINOMATOUS GERMINAL TESTICULAR TUMORS ON CURRENT SECOND-LINE CHEMOTHERAPY

Directory of Open Access Journals (Sweden)

M. Yu. Fedyanin

2010-01-01

Full Text Available Objective: to define predictors that influence longevity in patients with recurrent non-seminomatous germinal testicular tumors (NGTT on standard second-line chemotherapy (CT including cisplatin and iphosphamide. Statistical analysis was performed using the statistical packages Graph Pad Prism 4.00 for Windows and SPSS 15.0 for Windows. Subjects and methods. Case history data were analyzed in 693 patients with disseminated NGTT who had received current CT and followed up at the Department of Clinical Pharmacology and CT, N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences. The median follow-up was 32 (range 3-215 months. The disease progressed in 181 (26% patients. Detailed information was available on the nature of second-line CT in only 138 patients. Half (71 (51.7% of the 138 patients had second-line CT including iphosphamide. Uni- and multivariate analyses were made to identify predictors that influence longevity in patients with recurrent NGTT on standard secondline CT including cisplatin and iphosphamide. Results. Five-year overall survival (OS was 32% (95% confidence interval 25-41%. The multivariate analysis showed the morphological pattern of a primary tumor (a yolk sac tumor component, a pre-induction CT lactate dehydrogenase (LDH level of ?d1.5 units of the upper normal range, progression during induction CT, and a pre-second-line CT LDH level of ?d 1000 U/l to be negative predictors. According to the number of negative factors, the patients were classified into 3 groups: 1 good prognosis [n = 10 (14% of the 71 patients], 100% 3-year OS; 2 intermediate prognosis (one negative factor [n = 33 (46.5% of the 71 patients], 50.2% 3-year OS; 3 poor prognosis (?d 2 negative factors, 6.7% 3-year OS. Conclusion. Standard iphosphamide-containing therapy enables all patients to be treated in the good prognosis group of those with recurrent NGTT. That fails to achieve such striking results in the intermediate and

Association of Preoperative Nutritional Status with Prognosis in Patients with Esophageal Cancer Undergoing Salvage Esophagectomy.

Science.gov (United States)

Sakai, Makoto; Sohda, Makoto; Miyazaki, Tatsuya; Yoshida, Tomonori; Kumakura, Yuji; Honjo, Hiroaki; Hara, Keigo; Ozawa, Daigo; Suzuki, Shigemasa; Tanaka, Naritaka; Yokobori, Takehiko; Kuwano, Hiroyuki

2018-02-01

To investigate whether malnutrition is associated with poor prognosis of patients who undergo salvage esophagectomy. We examined the association between the preoperative prognostic nutritional index (PNI) and prognosis of patients who undergo salvage esophagectomy. We conducted a single-center retrospective study and reviewed hospital patient records for tumor characteristics and patient outcomes. Univariate and multivariate survival analyses were carried out using the Cox proportional hazards regression model. Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who underwent salvage esophagectomy between 1998 and 2015 at our Institute were included in this study. Univariate analysis revealed that clinical response (p=0.045), preoperative PNI (pnutritional status is associated with the prognosis of patients undergoing salvage esophagectomy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Bipolar hip arthroplasty as salvage treatment for loosening of the acetabular cup with significant bone defects

Directory of Open Access Journals (Sweden)

Ghanem, Mohamed

2016-04-01

Full Text Available Introduction: Revision arthroplasty of the hip is becoming increasingly important in recent years. Early primary arthroplasty and longer life expectancy of the patients increases the number of revision surgery. Revision surgery of hip arthroplasty is major surgery for the patients, especially the elderly, with significant risks concerning the general condition of the patient. The aim of this work is to evaluate the outcome of bipolar hip arthroplasty as a salvage procedure for treatment of loosening of the acetabular cup with significant acetabular bone defects after total hip replacement (THR in multi-morbid patients.Patients and methods: During the period from January 1 2007 to December 31 2011 19 revision hip surgeries were performed in , in which the loosened acetabular cup was replaced by a bipolar head. The examined patient group consisted exclusively of female patients with an average of 75 years. The predominant diagnosis was “aseptic loosening” (84.2%. All patients in our study were multi-morbid. We decided to resort to bipolar hip arthroplasty due to the compromised general condition of patients and the major acetabular bone defects, which were confirmed intraoperatively. The postoperative follow-up ranged from 0.5 to 67 months (average 19.1 months. Results: Evaluation of the modified Harris Hip Score showed an overall improvement of the function of the hip joint after surgery of approximately 45%.Surgery was less time consuming and thus adequate for patients with significantly poor general health condition. We noticed different complications in a significant amount of patients (68.4%. The most common complication encountered was the proximal migration of the bipolar head.The rate of revision following the use of bipolar hip arthroplasty in revision surgery of the hip in our patients was high (21%. Despite the high number of complications reported in our study, we have noticed significant improvement of hip joint function as well

Postoperative blood salvage versus allogeneic blood transfusion in total knee and hip arthroplasty: a literature review.

Science.gov (United States)

Leigheb, Massimiliano; Pogliacomi, Francesco; Bosetti, Michela; Boccafoschi, Francesca; Sabbatini, Maurizio; Cannas, Mario; Grassi, Federico

2016-04-15

We aimed to compare Postoperative Blood Salvage (PBS) with Allogeneic Blood Transfusion (ABT) in patients undergoing Total Hip and Knee Arthroplasty (THA, TKA).  A bibliographic research was carried out in order to review the literature dedicated to postoperative blood salvage in major orthopaedic surgery, excluding papers dealing exclusively with preoperative autologous donation, intraoperative blood salvage and ABT. PBS and ABT were compared according to complications, costs and duration of hospitalization. PBS effectiveness in reducing ABT was also assessed. PBS system is useful for reducing the complication rate and the length of hospital stay if compared to ABT. Costs for the reinfusion of unwashed shed blood, washed blood, and allogeneic transfusion are controversial among the different authors. Several papers demonstrate that PBS significantly reduces the need of postoperative ABT in both THA and TKA, while there is low evidence that PBS does not affect the risk of surgical wound complications. To reduce potential risks related to PBS, including non-hemolytic febrile reaction, the reinfusion of saved blood should begin within 4-6 hours after the start of collection through the wound drainage. According to literature, PBS appears to be a valid alternative to ABT, which is the standard treatment for postoperative anemia in THA and TKA. Contraindications to PBS must be ruled out before recommending it to patients undergoing major orthopaedic procedures.

The evolutionary portrait of metazoan NAD salvage.

Science.gov (United States)

Carneiro, João; Duarte-Pereira, Sara; Azevedo, Luísa; Castro, L Filipe C; Aguiar, Paulo; Moreira, Irina S; Amorim, António; Silva, Raquel M

2013-01-01

Nicotinamide Adenine Dinucleotide (NAD) levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs) and Nicotinamidases (PNCs) have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

Cetuximab in first line treatment of metastatic colorectal cancer

Directory of Open Access Journals (Sweden)

Carlo Barone

2012-07-01

Full Text Available The present health technology assessment report evaluates the clinical and economic profile of cetuximab in first-line metastatic colorectal cancer (mCRC in Italy. The first part of the report addresses the epidemiological, clinical, social and economic impact of mCRC. In the second part, evidence of efficacy, safety and cost-effectiveness of cetuximab and its available alternatives is shown. Finally, a model-based economic evaluation aimed at comparing cetuximab-based re­gimens vs. alternative therapeutic strategies indicated in mCRC in Italy is presented. The model estimates the incremental cost-effectiveness of adding cetuximab to FOLFOX-4 or FOLFIRI based on KRAS status, vs. adding bevacizumab to FOLFOX-4 or vs. FOLFOX-4 or FOLFIRI alone. A theoretical analysis vs. panitumumab has also been performed, despite panitumumab is not yet reimbursed in Italy in first-line mCRC. Survival outcomes, quality of life and costs of patient ma­nagement are estimated through a Markov model, using the Italian National Healthcare Service (NHS perspective, over a 10 year period, taking into account KRAS status of patients. The results of the pharmaco-economic analysis show that cetuximab + FOLFOX-4 and cetuximab + FOLFIRI are associated with increased survival, increased cost and increased quality adjusted survival, compared to all other treatments currently indicated and reimbursed in Italy. Adding cetuximab to FOLFOX-4 or FOLFIRI, based on KRAS status shows favorable incremental cost-effectiveness ratio (ICER vs. adding bevacizumab to FOLFIRI or vs. FOLFOX-4 or FOLFIRI alone. ICER of cetuximab (in combination with FOLFOX-4 or FOLFIRI, compared to currently reimbursed alternatives, is estimated between 6 and 13 thousand Euros per QALY gai­ned, depending on alternative treatment. These estimates are robust in extensive sensitivity analyses. As a final result, both clinical and economic evidence analyzed in this health technology assessment leads to

Salvage versus amputation: Utility of mangled extremity severity score in severely injured lower limbs

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Kumar M

2007-01-01

Full Text Available Background: The purpose of the present study was to evaluate the clinical utility of Mangled extremity severity score (MESS in severely injured lower limbs. Materials and Methods: Retrospectively 25 and prospectively 36 lower limbs in 58 patients with high-energy injuries were evaluated with the use of MESS, to assist in the decision-making process for the care of patients with such injuries. Difference between the mean MESS scores for amputated and salvaged limbs was analyzed. Results: In the retrospective study 4.65 (4.65 ± 1.32 was the mean score for the salvaged limbs and 8.80 (8.8 ± 1.4 for the amputated limbs. In the prospective study 4.53 (4.53 ± 2.44 was the mean score for the salvaged limbs and 8.83 (8.83 ± 2.34 for the amputated limbs. There was a significant difference in the mean scores for salvaged and amputated limbs. Retrospective 21 (84% and prospective 29 (80.5% limbs remained in the salvage pathway six months after the injury. Conclusion: MESS could predict amputation of severely injured lower limbs, having score of equal or more than 7 with 91% sensitivity and 98% specificity. There was a significant difference in the mean MESS scores in the prospective study (n=36, 4.53 (4.53 ± 2.44 in thirty salvaged limbs (83.33% and 8.83 (8.83 ± 2.34 in six amputated limbs (16.66% with a P -value 0.002 ( P -value < 0.01. Similarly there was a significant difference in the mean MESS score in the retrospective study (n=25, 4.65 (4.65 ± 1.32 in twenty salvaged limbs (80% and 8.80 (8.8 ± 1.4 in five amputated limbs (20% with a P -value 0.00005 ( P -value < 0.01. MESS is a simple and relatively easy and readily available scoring system which can help the surgeon to decide the fate of the lower extremity with a high-energy injury.

Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125)

DEFF Research Database (Denmark)

Grønlund, B; Høgdall, E V S; Christensen, Ib Jarle

2006-01-01

for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses...... (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value...... for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). CONCLUSION: Low serum levels of tetranectin, or high serum levels...

Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

International Nuclear Information System (INIS)

Bianco, Fernando J.; Scardino, Peter T.; Stephenson, Andrew J.; DiBlasio, Christopher J.; Fearn, Paul A.; Eastham, James A.

2005-01-01

Purpose: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. Methods and Materials: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of ≥0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). Results: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of 10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. Conclusions: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent

Nonoperative active management of critical limb ischemia: initial experience using a sequential compression biomechanical device for limb salvage.

LENUS (Irish Health Repository)

Sultan, Sherif

2008-01-01

Critical limb ischemia (CLI) patients are at high risk of primary amputation. Using a sequential compression biomechanical device (SCBD) represents a nonoperative option in threatened limbs. We aimed to determine the outcome of using SCBD in amputation-bound nonreconstructable CLI patients regarding limb salvage and 90-day mortality. Thirty-five patients with 39 critically ischemic limbs (rest pain = 12, tissue loss = 27) presented over 24 months. Thirty patients had nonreconstructable arterial outflow vessels, and five were inoperable owing to severe comorbidity scores. All were Rutherford classification 4 or 5 with multilevel disease. All underwent a 12-week treatment protocol and received the best medical treatment. The mean follow-up was 10 months (SD +\\/- 6 months). There were four amputations, with an 18-month cumulative limb salvage rate of 88% (standard error [SE] +\\/- 7.62%). Ninety-day mortality was zero. Mean toe pressures increased from 38.2 to 67 mm Hg (SD +\\/- 33.7, 95% confidence interval [CI] 55-79). Popliteal artery flow velocity increased from 45 to 47.9 cm\\/s (95% CI 35.9-59.7). Cumulative survival at 12 months was 81.2% (SE +\\/- 11.1) for SCBD, compared with 69.2% in the control group (SE +\\/- 12.8%) (p = .4, hazards ratio = 0.58, 95% CI 0.15-2.32). The mean total cost of primary amputation per patient is euro29,815 ($44,000) in comparison with euro13,900 ($20,515) for SCBD patients. SCBD enhances limb salvage and reduces length of hospital stay, nonoperatively, in patients with nonreconstructable vessels.

Risk factors for local failure requiring salvage neurosurgery after radiosurgery for brain metastases

International Nuclear Information System (INIS)

Weltman, Eduardo; Hanriot, Rodrigo de Morais; Prisco, Flavio Eduardo; Nadalin, Wladimir; Brandt, Reynaldo Andre; Moreira, Frederico Rafael

2004-01-01

Objective: the aim of this study is to select the risk factors for local failure requiring salvage neurosurgery in patients with brain metastases treated with stereotactic radiosurgery in a single institution. Methods: the follow-up of 123 patients, with 255 brain metastases treated with radiosurgery at the Radiation Oncology Department of the Hospital Israelita Albert Einstein from July 1993 to August 2001, was retrospectively analyzed. The criteria for salvage neurosurgery were tumor volume enlargement, or tumor persistence leading to severe neurological symptoms, life threatening situation or critical steroid dependence. We considered the case as local failure when the histopathologic evaluation showed morphologically preserved cancer cells (tumor recurrence, persistence or progression). We applied the Fisher's exact test to evaluate the statistical correlation between local failure and primary tumor histology, volume of the brain metastases, prescribed radiosurgery dose, and whole brain radiotherapy. Results: fourteen of 123 patients (11%) underwent salvage neurosurgery. Histology showed preserved cancer cells with necrosis and/or bleeding in 11 cases (9% of the total accrual), and only necrosis with or without bleeding (without preserved cancer cells) in three cases. The primary tumor histology among the 11 patients considered with active neoplasia was malignant melanoma in five cases (21% of the patients with melanoma), breast adenocarcinoma in three (16% of the patients with breast cancer), and other histology in the remaining three. Breast cancer diagnosis, non-elective whole brain irradiation, volume of the brain metastases, and the prescribed radiosurgery dose did not correlate with the risk of local failure. Patients treated with elective whole brain radiotherapy showed fewer local failures, when compared to all patients receiving whole brain radiotherapy, and to the patients not receiving this treatment, with incidence of failure in 4%,7% and 14

Robot-assisted Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer.

Science.gov (United States)

Montorsi, Francesco; Gandaglia, Giorgio; Fossati, Nicola; Suardi, Nazareno; Pultrone, Cristian; De Groote, Ruben; Dovey, Zach; Umari, Paolo; Gallina, Andrea; Briganti, Alberto; Mottrie, Alexandre

2017-09-01

Salvage lymph node dissection has been described as a feasible treatment for the management of prostate cancer patients with nodal recurrence after primary treatment. To report perioperative, pathologic, and oncologic outcomes of robot-assisted salvage nodal dissection (RASND) in patients with nodal recurrence after radical prostatectomy (RP). We retrospectively evaluated 16 patients affected by nodal recurrence following RP documented by positive positron emission tomography/computed tomography scan. Surgery was performed using DaVinci Si and Xi systems. A pelvic nodal dissection that included lymphatic stations overlying the external, internal, and common iliac vessels, the obturator fossa, and the presacral nodes was performed. In 13 (81.3%) patients a retroperitoneal lymph node dissection that included all nodal tissue located between the aortic bifurcation and the renal vessels was performed. Perioperative outcomes consisted of operative time, blood loss, length of hospital stay, and complications occurred within 30 d after surgery. Biochemical response (BR) was defined as a prostate-specific antigen level <0.2 ng/ml at 40 d after RASND. Median operative time, blood loss, and length of hospital stay were 210min, 250ml, and 3.5 d. The median number of nodes removed was 16.5. Positive lymph nodes were detected in 11 (68.8%) patients. Overall, four (25.0%) and five (31.2%) patients experienced intraoperative and postoperative complications, respectively. Overall, one (6.3%) and four (25.0%) patients had Clavien I and II complications within 30 d after RASND, respectively. Overall, five (33.3%) patients experienced BR after surgery. Our study is limited by the small cohort of patients evaluated and by the follow-up duration. RASND represents a feasible procedure in patients with nodal recurrence after RP and provides acceptable short-term oncologic outcomes, where one out of three patients experience BR immediately after surgery. Long-term data are needed to

Modified Pectoralis Major Tendon Transfer for Reanimation of Elbow Flexion as a Salvage Procedure in Complete Brachial Plexus Injury: A Case Report

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S Taran

2013-03-01

Full Text Available Traumatic brachial plexus injuries rarely recover spontaneously and if the window period for neurotisation has elapsed, the only option for restoration of function lies in a salvage procedure. Many such salvage procedures have been described in the literature with variable functional results. We report the case of a 16-year-old boy who presented after unsuccessful treatment for a complete brachial plexus injury; we performed a pectoralis major tendon transfer to attain elbow flexion. Postoperatively, the elbow was splinted with flexion at 100°. After 4 weeks of immobilization the splint was removed and the patient could actively flex his elbow from 30° to 100°.

Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report

Directory of Open Access Journals (Sweden)

María Espinosa Bosch

2016-07-01

Full Text Available Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5–12.6] vs. 7.9 months [6.7–9.1]; HR 0.75 [95% CI 0.60–0.92], p=0.0073. The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER per year of life with PFS in the overall population of 134,274.47 € (notified price. In the adenocarcinoma population per each life of year gained (LYG, the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and

TEXTILE SALVAGE

CERN Multimedia

Relations with the Host States Service

2002-01-01

Readers are reminded that Geneva's agency for salvaging used clothing, other textiles and old shoes (Coordination d'oeuvres d'entraide pour la récupération de vêtements, textiles et chaussures usagés dans le canton de Genève) has a container in the car park outside CERN's Meyrin site. In 2001, 1000 tonnes of such items were collected in the Canton of Geneva (as compared with 840 tonnes in 2000), of which 4460 kg came from the container outside the Meyrin site. The operation's organisers (Caritas, Centre Social Protestant, the Geneva Section of the Swiss Red Cross, Terre des Hommes, the Geneva branch of Terre des Hommes Suisse and Emmaüs, Geneva) would like to thank all those who have donated clothing or otherwise supported their campaign. Relations with the Host States Service Tel. 72848 http://www.cern.ch/relations/

A retrospective review of visual outcome and complications in the treatment of retinoblastoma.

LENUS (Irish Health Repository)

O'Doherty, M

2005-01-01

The aim of this study was to look at the visual outcome and treatment complications of children diagnosed with Retinoblastoma during the years 1985-2003 inclusive. A retrospective review of all patients records was performed. Patient characteristics, treatment methods and complications were recorded. Twenty eight children presented to Temple street Hospital between 1985-2003. Six of these infants had bilateral tumours. The mean age at presentation was 23.7 months. Sixty-nine percent presented with Leucocoria, of these 33% also had a squint. The mean duration of symptoms was only known in 58% and this figure was approximately 19.8 months. Enucleation was performed in 24 eyes of 24 patients. Three patients required adjuvant chemotherapy post enucleation. Two eyes was treated with external beam radiation and one eye with plaque radiotherapy. One eye (second eye) was treated with systemic chemotherapy and radiation. Five eyes of three patients were treated with systemic chemotherapy followed by adjuvant Argon laser, cryotherapy and diode laser to each eye.The complications of each treatment group was recorded. The visual outcome in the salvaged eyes was favourable. There were no deaths recorded. Though chemotherapy with adjuvant local treatments provide adequate treatment for early tumours, enucleation still plays a major role in the treatment of Retinoblastoma. The total eye salvage rate in this study was 29% with an enucleation rate of 90% in unilateral cases and 33% in bilateral cases. Sixty-six percent of bilateral eyes affected were salvaged. Seventy-one percent of tumours were diagnosed after a parent noticed a gross abnormality of the eye. This highlights the possible need for screening for retinoblastoma in the infant population.

Salvage concurrent radio-chemotherapy for post-operative local recurrence of squamous-cell esophageal cancer

International Nuclear Information System (INIS)

Zhang, Jian; Gong, Youling; Peng, Feng; Li, Na; Liu, Yongmei; Xu, Yong; Zhou, Lin; Wang, Jin; Zhu, Jiang; Huang, Meijuan

2012-01-01

To evaluate the treatment outcome of salvage concurrent radio-chemotherapy for patients with loco-recurrent esophageal cancer after surgery. 50 patients with loco-recurrent squamous-cell cancer after curative esophagectomy were retrospectively analyzed. Patients were treated with radiotherapy (median 60 Gy) combined with chemotherapy consisting of either 5-fluorouracil (5-FU) plus cisplatin (DDP) (R-FP group) or paclitaxel plus DDP (R-TP group). The median follow-up period was 16.0 months. The 1-year and 3-year survival rates were 56% and 14%, respectively. The median progression-free survival (PFS) and overall survival (OS) time was 9.8 and 13.3 months respectively. There was no statistical significance of the PFS of the two groups. The OS (median 16.3 months) in the R-TP group was superior to that in the R-FP group (median: 9.8 months) (p = 0.012). Among the patients who had received ≥60 Gy irradiation dose, the median PFS (10.6 months) and OS (16.3 months) were significantly superior to the PFS (8.7 months) and OS (11.3 months) among those patients did not (all p < 0.05). Grade 3 treatment-related gastritis were observed in 6 (27.3%) and 7 (25%) patients in the R-FP and R-TP group respectively. By univariate survival analysis, the age (<60 years), TP regimen and higher irradiation dose might improve the OS of such patients in present study. For those patients with post-operative loco-recurrent squamous-cell esophageal carcinoma, radiotherapy combined with either FP or TP regimen chemotherapy was an effective salvage treatment. Younger age, treatment with the TP regimen and an irradiation dose ≥60 Gy might improve the patients’ treatment outcome

Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

Energy Technology Data Exchange (ETDEWEB)

Jang, Joanne W. [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Guzzo, Thomas J.; Wein, Alan J. [Department of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Haas, Naomi B. [Department of Medical Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Both, Stefan [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Vapiwala, Neha, E-mail: vapiwala@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States)

2012-08-01

Purpose: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Methods and Materials: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. Results: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores {<=}7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). Conclusions: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in

28 CFR 25.56 - Responsibilities of junk yards and salvage yards and auto recyclers.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Responsibilities of junk yards and salvage yards and auto recyclers. 25.56 Section 25.56 Judicial Administration DEPARTMENT OF JUSTICE... Responsibilities of junk yards and salvage yards and auto recyclers. (a) By no later than March 31, 2009, and...

Focal salvage iodine-125 brachytherapy for prostate cancer recurrences after primary radiotherapy: A retrospective study regarding toxicity, biochemical outcome and quality of life

International Nuclear Information System (INIS)

Peters, Max; Maenhout, Metha; Voort van Zyp, Jochem R.N. van der; Moerland, Marinus A.; Moman, Maaike R.; Steuten, Lotte M.G.; Deursen, Marijke J.H. van; Vulpen, Marco van

2014-01-01

Purpose: Whole-gland salvage for recurrent prostate cancer (PCa) shows high failure and toxicity rates. Early and adequate localization of recurrences enables focal salvage, thereby potentially improving functional outcomes, while maintaining cancer control. Materials and methods: Retrospective analysis yielded 20 focal salvage I125 brachytherapy patients for locally recurrent PCa after primary radiotherapy. Tumor was defined by multiparametric MRI and correspondence with transrectal biopsies. Dose data were obtained intra-operatively. The tumor was prescribed ⩾144 Gy. Toxicity was scored by the Common Terminology Criteria for Adverse Events version 4 (CTCAE-4). Biochemical failure (BF) was defined using the Phoenix criteria (PSA-nadir + 2.0 ng/ml). Quality of life (QoL) was measured by SF-36 Health Survey and European Organization of Research and Treatment of Cancer (EORTC) C30+3 and PR25 questionnaires. Results: With a median follow-up of 36 months (range 10–45), six patients experienced BF, of which three had no initial response. Grade 3 genitourinary (GU) toxicity occurred in one patient (a urethral stricture). The five previously potent patients retained erectile function. QoL remained decreased with regard to urinary symptoms. Conclusion: Focal salvage I125 brachytherapy showed one grade 3 GU toxicity in the 20 treated patients. Biochemical response and QoL were acceptable

Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction

International Nuclear Information System (INIS)

Breault, Stéphane; Glauser, Frédéric; Babaker, Malik; Doenz, Francesco; Qanadli, Salah Dine

2015-01-01

PurposeImplanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques.Methods and MaterialsThrough a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new “mechanical adhesiolysis” maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication.ResultsEighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted.ConclusionThese IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement

Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction

Energy Technology Data Exchange (ETDEWEB)

Breault, Stéphane, E-mail: stephane.breault@chuv.ch [Lausanne University Hospital, Diagnostic and Interventional Radiology Department (Switzerland); Glauser, Frédéric, E-mail: frederic.glauser@chuv.ch [Lausanne University Hospital, Angiology and Diagnostic and Interventional Radiology Departments (Switzerland); Babaker, Malik, E-mail: malik.babaker@chuv.ch; Doenz, Francesco, E-mail: francesco.doenz@chuv.ch; Qanadli, Salah Dine, E-mail: salah.qanadli@chuv.ch [Lausanne University Hospital, Diagnostic and Interventional Radiology Department (Switzerland)

2015-06-15

PurposeImplanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques.Methods and MaterialsThrough a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new “mechanical adhesiolysis” maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication.ResultsEighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted.ConclusionThese IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement.

First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta)

International Nuclear Information System (INIS)

Sanita di Toppi, L.; Pawlik-Skowronska, B.; Vurro, E.; Vattuone, Z.; Kalinowska, R.; Restivo, F.M.; Musetti, R.; Skowronski, T.

2008-01-01

'First line' defence mechanisms, such as phytochelatin biosynthesis, and 'second line' mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 μM Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 μM) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a 'second line' mechanism to counteract Cd stress, activated when there is a decline in the 'first line' mechanism of Cd detoxification given by phytochelatins. - Trebouxia impressa photobionts protect themselves against cadmium stress by means of phytochelatins and stress proteins

First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta)

Energy Technology Data Exchange (ETDEWEB)

Sanita di Toppi, L. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy)], E-mail: luigi.sanitaditoppi@unipr.it; Pawlik-Skowronska, B. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Vurro, E. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Vattuone, Z. [Dipartimento di Biologia Evolutiva e Funzionale, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Kalinowska, R. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland); Restivo, F.M. [Dipartimento di Genetica, Biologia dei Microrganismi, Antropologia, Evoluzione, viale G.P. Usberti 11/A, Universita di Parma, 43100 Parma (Italy); Musetti, R. [Dipartimento di Biologia Applicata alla Difesa delle Piante, via delle Scienze 208, Universita di Udine, 33100 Udine (Italy); Skowronski, T. [Centre for Ecological Research, Polish Academy of Sciences, Experimental Station, Niecala 18/3, 20080 Lublin (Poland)

2008-01-15

'First line' defence mechanisms, such as phytochelatin biosynthesis, and 'second line' mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 {mu}M Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 {mu}M) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a 'second line' mechanism to counteract Cd stress, activated when there is a decline in the 'first line' mechanism of Cd detoxification given by phytochelatins. - Trebouxia impressa photobionts protect themselves against cadmium stress by means of phytochelatins and stress proteins.

Process for gasification of heavy hydrocarbons or salvaged oil. [German patent

Energy Technology Data Exchange (ETDEWEB)

Koch, C

1978-09-14

The invention refers to the separation of solids which are carried over during evaporation of salvaged oil (oil recovered from used oil or fat). They are removed by exposing the oil vapour to an acceleration of 500 g to 20,000g in a hot gas cyclone. Subsequently the cleaned gas is converted to fission gas in a fission gas generator using an air-water gas mixture and is taken to the combustion equipment. By this process salvaged oil and heavy hydrocarbons can be used for burning in Diesel engines without previous refining.

Second primary cancer following Hodgkin's disease: Updated results of an Italian multicentric study

International Nuclear Information System (INIS)

Cimino, G.; Papa, G.; Tura, S.; Mazza, P.; Rossi Ferrini, P.L.; Bosi, A.; Amadori, S.; Lo Coco, F.; D'Arcangelo, E.; Giannarelli, D.

1991-01-01

The risk of second primary cancer (SPC) was evaluated in 947 patients treated for Hodgkin's disease (HD) during the period January 1969 to December 1979. The median follow-up of this series was 10.5 years (range, 9 to 19). Treatment categories included radiotherapy (RT) alone (115 patients, 12%), chemotherapy (CHT) alone (161 patients, 17%), combined RT plus CHT (381 patients, 40%), and salvage treatment for resistant or relapsing HD (290 patients, 30.6%). Fifty-six SPCs were observed, occurring between 1 and 17 years from initial treatment. Among these, secondary acute nonlymphoid leukemia (s-ANLL) was the most frequent SPC (23 cases). Secondary non-Hodgkin's lymphoma (s-NHL) occurred in 5 patients, whereas a secondary solid tumor (s-ST) was observed in 28 patients. The calculated actuarial risk (+/- SE) of developing SPC was 5.0% (+/- 0.9%) and 23.1% (+/- 5.8%) at 10 and 19 years, respectively. Concerning treatment modalities and s-ANLL risk, no cases were observed in the radiotherapy group, whereas CHT plus RT and salvage groups showed the highest actuarial risk. This was, in fact, at 10 and 19 years, 3.1% (+/- 0.9%) and 8.1% (+/- 4.0%) in the former group, and 1.8% (+/- 1.0%) and 16% (+/- 9.0%) in the latter. A statistically significant difference was observed when the CHT plus RT group was compared with CHT and RT groups (P = .04). Concerning the relationships with chemotherapeutic regimens, 12 s-ANLL cases occurred in the mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) plus RT group, and only one case in the group receiving doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) plus RT. A statistically significant difference of s-ANLL actuarial risk was found comparing patients receiving MOPP plus RT to all other treatment groups (P = .04)

Cost-Effectiveness Analysis of Bendamustine Plus Rituximab as a First-Line Treatment for Patients with Follicular Lymphoma in Spain.

Science.gov (United States)

Sabater, Eliazar; López-Guillermo, Armando; Rueda, Antonio; Salar, Antonio; Oyagüez, Itziar; Collar, Juan Manuel

2016-08-01

Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe. The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain. A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness. Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations. First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost

Rill erosion in burned and salvage logged western montane forests: Effects of logging equipment type, traffic level, and slash treatment

Science.gov (United States)

J. W. Wagenbrenner; P. R. Robichaud; R. E. Brown

2016-01-01

Following wildfires, forest managers often consider salvage logging burned trees to recover monetary value of timber, reduce fuel loads, or to meet other objectives. Relatively little is known about the cumulative hydrologic effects of wildfire and subsequent timber harvest using logging equipment. We used controlled rill experiments in logged and unlogged (control)...

Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy

NARCIS (Netherlands)

Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to

Estimation of second primary cancers risk based on the treatment planning system

International Nuclear Information System (INIS)

Jin Chufeng; Sun Guangyao; Liu Hui; Zheng Huaqing; Cheng Mengyun; Li Gui; Wu Yican; FDS Team

2011-01-01

Estimates of second primary cancers risk after radiotherapy has become increasingly important for comparative treatment planning. A new method based on the treatment planning system to estimate the risk of second primary cancers was introduced in this paper. Using the Advanced/Accurate Radiotherapy Treatment System(ARTS), a treatment planning system developed by the FDS team,the risk of second primary cancer was estimated over two treatment plans for a patient with pancreatic cancer. Based on the second primary cancer risk, the two plans were compared. It was found that,kidney and gall-bladder had higher risk to develop second primary cancer. A better plan was chosen by the analysis of second primary cancer risk. The results showed that this risk estimation method we developed could be used to evaluate treatment plans. (authors)

Posterior transpedicular approach with circumferential debridement and anterior reconstruction as a salvage procedure for symptomatic failed vertebroplasty

OpenAIRE

Chiu, Yen-Chun; Yang, Shih-Chieh; Chen, Hung-Shu; Kao, Yu-Hsien; Tu, Yuan-Kun

2015-01-01

Background Complications and failure of vertebroplasty, such as cement dislodgement, cement leakage, or spinal infection, usually result in spinal instability and neural element compression. Combined anterior and posterior approaches are the most common salvage procedure for symptomatic failed vertebroplasty. The purpose of this study is to evaluate the feasibility and efficacy of a single posterior approach technique for the treatment of patients with symptomatic failed vertebroplasty. Metho...

Grande-Baie tugboat sinking and salvage operations

International Nuclear Information System (INIS)

Dussault, M.; Gauthier, F.

2009-01-01

This paper described the operations that took place during an oil spill that occurred in December 2007 when the Grande-Baie tugboat sank at the wharf in Port Alfred, in the Ha-Ha Bay on the Saguenay River, Quebec. Approximately 100 tonnes of diesel fuel was onboard the tug. Although the exact amount of diesel spilled during this event is not known, it is assumed that half of the ship's load in diesel was spilled into the ice-infested waters. Poor weather, the presence of pack ice and tides of 2.5 meters were present at the time. Two Canadian Coast Guard officers, one emergency officer from Environment Quebec and one from Environment Canada were called for response purposes, particularly to avoid spreading of the diesel fuel and to ensure that the oily water was recovered from inside the vessel during salvage operations. One of the key objectives was to prevent diesel spills by capping vessel vents, which proved to be very challenging. Oily water was pumped from inside the boat directly in the bay of the Saguenay River to facilitate salvage of the ship. This was the first time that this method was used in Canada, and was successful because of proper risk assessment. Many conditions were followed for the purpose of environmental protection, such as confinement, good observations by divers, agreed upon criteria to stop pumping, and adequate monitoring the the Regional Environmental Emergency Team (REET). The salvage operation lasted 19 days. The challenges associated with the migration and recovery of oil in icy waters were discussed along with the environmental issues associated with the spill, particularly with the imminent opening of the ice fishing season. 2 refs., 2 tabs.,5 figs.

Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

Science.gov (United States)

Luealon, Phanida; Khempech, Nipon; Vasuratna, Apichai; Hanvoravongchai, Piya; Havanond, Piyalamporn

2016-01-01

There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All

Freshwater mussel salvage and relocation at the Pond Eddy Bridge, Delaware River, New York and Pennsylvania

Science.gov (United States)

Galbraith, Heather S.; Blakeslee, Carrie J.; Cole, Jeffrey C.

2018-03-01

In a study conducted by the U.S. Geological Survey, in cooperation with the Pennsylvania Department of Transportation, freshwater mussels were salvaged and relocated from the anticipated zone of impact for the Pond Eddy Bridge construction project in New York and Pennsylvania. Five 25-meter (m) by 25-m cells along the Pennsylvania bank of the Delaware River were sampled in three generally straight-line passes by four surveyors wearing snorkel gear for a total of 180 survey minutes per cell. All mussels encountered were collected and identified to species. A subset of individuals was marked with shellfish tags, weighed, and measured prior to relocation upstream from the zone of impact. A total of 3,434 mussels, including 3,393 Elliptio complanata (eastern elliptio mussels), 39 Anodonta implicata (alewife floaters), 1 Strophitus undulatus (creeper), and 1 Pyganodon cataracta (eastern floater), were salvaged and relocated. All non-eastern elliptio species were georeferenced using a high-resolution global positioning system unit; a subset of tagged eastern elliptio was placed in transects between georeferenced points. These mussels will be monitored to assess the effects of translocation on mortality and body condition at 1 month, 1 year, and 2 years.

The evolutionary portrait of metazoan NAD salvage.

Directory of Open Access Journals (Sweden)

João Carneiro

Full Text Available Nicotinamide Adenine Dinucleotide (NAD levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs and Nicotinamidases (PNCs have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

Energy Technology Data Exchange (ETDEWEB)

Rimner, Andreas; Lovie, Shona [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Hsu, Meier [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chelius, Monica [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Chau, Karen [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Moskowitz, Alison J.; Matasar, Matthew; Moskowitz, Craig H. [Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

2017-04-01

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.

Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

International Nuclear Information System (INIS)

Rimner, Andreas; Lovie, Shona; Hsu, Meier; Chelius, Monica; Zhang, Zhigang; Chau, Karen; Moskowitz, Alison J.; Matasar, Matthew; Moskowitz, Craig H.; Yahalom, Joachim

2017-01-01

Purpose: We report the long-term results of integrated accelerated involved field radiation therapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation or autologous stem cell transplantation in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials: From November 1985 to July 2008, 186 previously unirradiated patients with relapsed or refractory HL underwent salvage therapy on 4 consecutive institutional review board–approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18-20 Gy) was given to relapsed or refractory sites, followed by TLI (15-18 Gy) and high-dose chemotherapy. Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing-risk regression. Results: With a median follow-up period of 57 months among survivors, 5- and 10-year OS rates were 68% and 56%, respectively; 5- and 10-year EFS rates were 62% and 56%, respectively; and 5- and 10-year cumulative incidences of HL-related deaths were 21% and 29%, respectively. On multivariate analysis, complete response to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade 3 or higher cardiac toxicity, with 3 deaths. Second malignancies developed in 10 patients, 5 of whom died. Conclusions: Accelerated IFRT followed by TLI and high-dose chemotherapy is an effective, feasible, and safe salvage strategy for patients with relapsed or refractory HL with excellent long-term OS, EFS, and DSS. Complete response to SC is the most important prognostic factor.

Efficacy of Salvage Interferential Electrical Stimulation Therapy in Patients With Medication-Refractory Enuresis: A Pilot Study

Directory of Open Access Journals (Sweden)

Hahn-Ey Lee

2013-09-01

Full Text Available Purpose In pediatric patients with enuresis, the protocol for salvage therapy in patients in whom first-line therapy was not successful has not yet been established. Interferential electrical stimulation (IF-ES therapy is advantageous because it is noninvasive and shows high compliance. We aimed to investigate the efficacy and safety of IF-ES therapy on pediatric enuresis in a pilot study. Methods We investigated 10 patients who underwent IF-ES therapy between August 2012 and March 2013 at our clinic. Patients with a history of previous treatment with desmopressin and anticholinergic agents for at least 3 months and those in whom alarm treatment previously failed or was refused by parents were eligible. Electrical current was given starting at approximately 20 mA and was increased until the patient complained of discomfort. Treatment was performed once a week, 20 minutes per treatment, 6 times per cycle. After each cycle, an interview was performed and voiding diaries were filled. The physician in charge evaluated improvement according to the International Children's Continence Society criteria. Results A final analysis was performed in 10 patients (5 male and 5 female patients in whom therapy for nocturnal enuresis had failed. Eight patients had nonmonosymptomatic enuresis and 2 had monosymptomatic enuresis. The mean age of the patients was 8.5±2.4 years, and the mean number of treatments was 10.6±3.6 times. A full response was observed in 1 patient (10%; a good response, in 1 patient (10%; a partial response, in 7 patients (70%; and no response, in 1 patient (10%. Conclusions Our study demonstrated that IF-ES therapy can be a promising treatment for the future, is safe, and can benefit from appropriate clinical trials in carefully selected groups. IF-ES therapy is expected to be a safe and effective treatment modality for children with enuresis.

Effect of a hydrophilic and a hydrophobic statin on cardiac salvage after ST-elevated acute myocardial infarction - a pilot study.

Science.gov (United States)

Chitose, Tadasuke; Sugiyama, Seigo; Sakamoto, Kenji; Shimomura, Hideki; Yamashita, Takuro; Hokamaki, Jun; Tsunoda, Ryusuke; Shiraishi, Shinya; Yamashita, Yasuyuki; Ogawa, Hisao

2014-11-01

Early statin therapy after acute coronary syndrome reduces atherothrombotic vascular events. This study aimed to compare the effects of hydrophilic and hydrophobic statins on myocardial salvage and left ventricular (LV) function in patients with ST-elevated myocardial infarction (STEMI). Seventy-five STEMI patients who had received emergency reperfusion therapy were enrolled and randomized into the hydrophilic statin group (rosuvastatin; 5 mg/day, n = 38) and hydrophobic statin group (atorvastatin; 10 mg/day, n = 37) for 6 months. LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) and co-enzyme Q10 (CoQ10) levels were measured at baseline and the end of treatment. The myocardial salvage index was assessed by single photon emission computed tomography with (123-)I-β-methyl-iodophenylpentadecanoic acid (ischemic area-at-risk at onset of STEMI: AAR) and (201-)thallium scintigraphy (area-at-infarction at 6 months: AAI) [myocardial salvage index = (AAR-AAI) × 100/AAR (%)]. Onset-to-balloon time and maximum creatine phosphokinase levels were comparable between the groups. After 6 months, rosuvastatin (-37.6% ± 17.2%) and atorvastatin (-32.4% ± 22.4%) equally reduced low-density lipoprotein-cholesterol (LDL-C) levels (p = 0.28). However, rosuvastatin (+3.1% ± 5.9%, p < 0.05), but not atorvastatin (+1.6% ± 5.7%, p = 0.15), improved LVEF. Rosuvastatin reduced BNP levels compared with atorvastatin (-53.3% ± 48.8% versus -13.8% ± 82.9%, p < 0.05). The myocardial salvage index was significantly higher in the rosuvastatin group than the atorvastatin group (78.6% ± 29.1% versus 52.5% ± 38.0%, p < 0.05). CoQ10/LDL-C levels at 6 months were increased in the rosuvastatin group (+23.5%, p < 0.01) and percent changes in CoQ10/LDL-C were correlated with the myocardial salvage index (r = 0.56, p < 0.01). Rosuvastatin shows better beneficial effects on myocardial salvage than atorvastatin in STEMI patients, including long-term cardiac function, associated with

Development of Composite Case Salvage Procedures

Science.gov (United States)

1982-04-01

impacted by the high pressure water. Figure 25 shows damage to EPDM rubber from an MX case. Figure 26 shows the effect of the water on the V-45 ( NBR ... Rubber plus Polyester plus Degradation Elastomer Polyether Cleavage Recycling Reclamation Solvolysis Also: Salvage Rubber Reclamation Elastomers... rubber . 2. Analysis of the material extracted from the insu- lation showed that plasticizer (phthalates) was removed by the solvents. 3. After

Busulfan is effective second-line therapy for older patients with Philadelphia-negative myeloproliferative neoplasms intolerant of or unresponsive to hydroxyurea.

Science.gov (United States)

Douglas, Genevieve; Harrison, Claire; Forsyth, Cecily; Bennett, Michael; Stevenson, William; Hounsell, John; Ratnasingam, Sumita; Ritchie, David; Ross, David M; Grigg, Andrew

2017-01-01

Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

Science.gov (United States)

Bøtker, Hans Erik; Kharbanda, Rajesh; Schmidt, Michael R; Bøttcher, Morten; Kaltoft, Anne K; Terkelsen, Christian J; Munk, Kim; Andersen, Niels H; Hansen, Troels M; Trautner, Sven; Lassen, Jens Flensted; Christiansen, Evald Høj; Krusell, Lars R; Kristensen, Steen D; Thuesen, Leif; Nielsen, Søren S; Rehling, Michael; Sørensen, Henrik Toft; Redington, Andrew N; Nielsen, Torsten T

2010-02-27

Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote

On the use of dental ceramics as a possible second-line approach to accident irradiation dosimetry

International Nuclear Information System (INIS)

Davies, J.E.

1979-01-01

Recent development in dental ceramic production has resulted in natural or depleted uranium, used for over half a century to mimic the fluorescence of natural teeth, being substituted in such ceramics by non-radioactive fluorescent materials. This creates the possibility of using dental ceramics incorporating the latter as second-line dosimeters in cases of accidental irradiation. This pilot study shows the feasbility of such an approach using both thermally stimulated exoelectron and thermoluminescent techniques. In conclusion, it is considered that it would be of interest to continue this investigation of dental ceramic materials as second-line accident dosimeters

Our Experiences with Erlotinib in Second and Third Line Treatment Patients with Advanced Stage Iiib/ Iv Non-Small Cell Lung Cancer

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Bakir Mehić

2008-11-01

Full Text Available HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV openlabel, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H were selected from two Clinical centres (Sarajevo and Banja Luka. The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19. This population is defined as the Intent to Treat (ITT population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III. Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI disorders.

Biomodulation with sequential intravenous IFN-alpha2b and 5-fluorouracil as second-line treatment in patients with advanced colorectal cancer.

Science.gov (United States)

Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Marrone, N; Ortiz, E H; Leone, B A; Vallejo, C T; Machiavelli, M R; Romero, A O

1998-08-01

A phase II trial was carried out by the Grupo Oncologico Cooperativo del Sur (G.O.C.S.) to assess the efficacy and toxicity of a biochemical modulation of 5-fluorouracil (5-FU) by i.v. pretreatment with interferon (IFN)-alpha2b in patients with advanced colorectal carcinoma refractory to previous therapy with 5-FU modulated by methotrexate (MTX) or leucovorin (LV) or both. Between January 1993 and October 1995, 34 patients were entered on the study. The treatment was IFN-alpha2b 5 x 10(6)/m2 IU in a 1-h i.v. infusion, followed immediately by 5-FU 600 mg/m2 i.v. bolus injection. Courses were repeated weekly until observation of progressive disease or severe toxicity. One patient could not be assessed for response. Objective regression was observed in 2 of 33 patients (6%, 95% confidence interval, 0%-14%). No patient achieved a complete response. Two patients had partial responses (6%). No change was recorded in 14 patients (41%), and progressive disease occurred in 17 (52%). The median time to treatment failure was 3 months, and the median survival was 5 months. Toxicity was within acceptable limits. The main side effects were mucositis and diarrhea. Four episodes of grade 2 stomatitis were observed, causing dosage modifications. The most frequent toxic effects attributable to IFN-alpha2b were mild fatigue and fever. In conclusion, second-line therapy with i.v. IFN-alpha2b preceding 5-FU has shown an interesting profile of activity in a patient population with clearly unfavorable characteristics. From this perspective, further appropriately designed studies are needed to identify the greatest potential of IFN-alpha2b as a modulator of 5-FU.

Endoscopic Transsphenoidal Salvage Surgery for Symptomatic Residual Cystic Craniopharyngioma after Radiotherapy.

Science.gov (United States)

Emanuelli, Enzo; Frasson, Giuliana; Cazzador, Diego; Borsetto, Daniele; Denaro, Luca

2018-04-01

Objectives  Ideal treatment of craniopharyngiomas is still controversial. Radiotherapy (RT) is considered effective for recurrences or after subtotal tumor removal (STR). About 40 to 50% of patients may experience tumor cyst expansion soon after RT; in these cases, the role of salvage surgery is debated. Design  Operative video. Setting  Tertiary care center. Participants  An 11-year-old boy diagnosed with persistent craniopharyngioma. In 2015, the patient underwent right frontotemporal craniotomy for STR at another center, complicated by panhypopituitarism. Two years later, fractionated 54-Gy RT was performed on growing residual tumor. After 3 months, he was admitted to our hospital due to persistent malaise, vomiting, pulsating headache, and epistaxis. Ophthalmologic evaluation evidenced left homonymous hemianopsia. Results  A contrast-enhanced magnetic resonance imaging (MRI) showed a 27-mm cystic component enlarging from the cranial end of the persistent craniopharyngioma lesion, extending into the third ventricle. Biventricular hydrocephalus and brain midline shift to the right were present. Compared with the early post-RT MRI, the cystic component of the tumor demonstrated growth. The patient underwent external ventricular drainage placement for emergent treatment of hydrocephalus and endoscopic transsphenoidal surgery. After cystic content drainage, the lesion was completely removed with its capsule. A "gasket seal" technique was performed for skull base reconstruction, with autologous fascia lata, septal bone, and mucoperiosteum from inferior turbinate. Histologic examination confirmed the craniopharyngioma diagnosis. Postoperative MRI showed resolution of the hydrocephalus and complete tumor removal. Conclusion  Although shrinkage of cystic components of craniopharyngioma residuals may occur within 5 to 6 months after RT, salvage surgery is indicated in symptomatic patients. The link to the video can be found at https://youtu.be/4x6Qe76bf60 .

Benign aggressive lesions of femoral head and neck: Is salvage possible?

Directory of Open Access Journals (Sweden)

Yogesh Panchwagh

2018-01-01

Full Text Available Background: Benign aggressive bone lesions of the femoral head and neck are mostly seen in young adults and warrant treatment for pain, impending fracture or established fracture, and disease clearance. It becomes challenging to treat them effectively while attempting salvage of the femoral head and yet achieving long term disease control with minimum complications. We describe our technique and experience in dealing with these lesions which can achieve the above-mentioned goals and can be easily replicated. Materials and Methods: We analyzed 15 cases of surgically treated, biopsy-proven benign, locally aggressive lesions affecting the femoral head and neck in skeletally mature individuals. All cases were treated with extended curettage through anterolateral modified Smith–Petersen approach along with tricortical iliac crest bone graft (combined with fibular graft in some cases reconstruction with or without suitable internal fixation. Results: All, except one, patients were available for follow up. The age ranged from 18 to 43 years and the follow up ranged between 24 and 124 months (average 78 months. These included aneurysmal bone cysts (9, giant cell tumors (4, and fibrous dysplasia (2. The indication was pain (8, with impending (2 or established pathological neck femur fracture (5. In all cases, there was satisfactory healing of lesion and timely rehabilitation. Nonunion, avascular necrosis or local recurrences were not seen. The MSTS functional score was good or excellent in all (range 26–29, average 28. Conclusion: Benign aggressive lesions affecting femoral head and neck in young and middle-aged adults pose a treatment challenge. A sturdy, lasting reconstruct with acceptable functional outcome and minimal recurrence rate can be achieved by salvaging the femoral head and neck using curettage and reconstruction, obviating the need for replacement at such an early age.

Second conservative radiosurgical treatment for ipsilateral breast cancer recurrence

International Nuclear Information System (INIS)

Castelli, J.; Courdi, A.; Hannoun-Levi, J.M.; Figl, A.; Raoust, I.; Lallement, M.; Flipo, B.; Ettore, F.; Chapelier, C.; Ferrero, J.M.

2011-01-01

Purpose. - Currently, radical mastectomy represents the gold standard for ipsilateral breast cancer recurrence. However, we already showed that a second conservative treatment was feasible combining lumpectomy plus low-dose rate interstitial brachytherapy. In this study, we reported the preliminary results of a second conservative treatment using a high-dose rate brachytherapy. Patients and methods. - From June 2005 to July 2009, 42 patients presenting with an ipsilateral breast cancer recurrence underwent a second conservative treatment. Plastic tubes were implanted intraoperatively at the time of the lumpectomy. After a post-implant CT scan, a total dose of 34 Gy in 10 fractions over 5 consecutive days was delivered through an ambulatory procedure. The toxicity evaluation used the Common Terminology Criteria for Adverse Events v3.0. Results. - The median follow-up was 21 months (6-50 months), median age at the time of the local recurrence was 65 years (30-85 years). The median delay between the primary and the recurrence was 11 years (1-35 years). The location of the recurrence was in the tumor bed for 22 patients (52.4%), in the same quadrant for 14 patients (33.3%) and unknown for six patients (14.3%). The median tumor size of the recurrence was 12 mm (2-30 mm). The median number of plastic tubes and plans were nine (5-12) and two (1-3) respectively. The median CTV was 68 cm 3 (31.2-146 cm 3 ). The rate of second local control was 97%. Twenty-two patients (60%) experienced complications. The most frequent side effect consisted in cutaneous and sub-cutaneous fibrosis (72% of all the observed complications). Conclusion. - A second conservative treatment for ipsilateral breast cancer recurrence using high-dose rate brachytherapy appears feasible leading to encouraging results in terms of second local control with an acceptable toxicity. Considering that a non-inferiority randomized trial comparing mastectomy versus second conservative treatment could be difficult

Salvage radiotherapy for carcinoma of the ovary following chemotherapy

International Nuclear Information System (INIS)

Cheung, A.Y.

1988-01-01

Following single-agent or combination chemotherapy, 9 patients with epithelial carcinoma of the ovary had elective second-look laparotomy. Macroscopic intraperitoneal disease was resected in 4 patients. Therefore, after the laparotomy, all 9 patients had only biopsy-proven, microscopic residual disease, and they received whole abdominopelvic irradiation. Hematological tolerance was satisfactory, with only 2 patients developing asymptomatic thrombocytopenia. Mild gastrointestinal reactions, while frequent during radiotherapy, did not interrupt treatment in any patient. After follow-up ranging from 6 to 28 months (median 12 months), 2 patients died of cancer, 2 were alive with cancer, 3 were alive without clinical recurrence, and 2 were alive without biopsy-proven recurrence. Bowel complication occurred in 4 patients: 2 developed intestinal obstruction due to recurrent tumor, 1 developed subacute bowel obstruction which spontaneously resolved, and 1 patient required bowel resection because of a radiation complication. This study indicated that after single- or multiple-drug chemotherapy, most patients could complete the course of whole abdominopelvic irradiation. Gastrointestinal complications could be secondary to radiation damage or to recurrent tumor. While whole abdominopelvic irradiation was not an effective second-line treatment, some long-term survivors could still be expected

Natural recovery and leaf water potential after fire influenced by salvage logging and induced drought stress

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D. Moya

2013-01-01

Full Text Available Salvage logging is one of the most common emergency actions in the short-term management after a fire. Several studies have been carried out and some obtained positive results which incite to carry it out but other, found negative effects on seedling establishment and regeneration. In addition, climatic changes will have large impacts on vegetation productivity and resilience since the regional models for south-eastern Spain predicts a rainfall decrease of about 20% and temperature increase of 4.5 ºC. Our aim was to determine how short-term forest management and induced drought affect the ecosystem recovery in Aleppo pine stands naturally recovered after a fire.In summer 2009, a mid-high severity fire burned 968 ha of Aleppo pine (Pinus halepensis Mill. forest in south-eastern Spain. Six months later, a salvage logging was carried out. The Aleppo pine recruitment was negligible. During summer 2010, twelve square plots (2m x 2m were set in the three scenarios: control, salvaged and drought induced. The surface cover and soil water availability for three dominant understory species were recorded in four field campaigns: Spring-2010, Fall-2010, Spring-2011 and Fall-2011.The season, management and the target species showed significant differences in growing and water stress. In general, Esparto grass showed lower water stress, mainly in Fall, a higher increase of total coverage. Both effects were showing their highest values in non-salvaged areas and no drought. Changes in leaf water potential and soil water content after the drought season influence the survival and development of individuals.Our results indicate that soil water content and ecosystem response can be modified by short-term silvicultural treatments. Therefore, management after fire could cause opposite effects to those initially foreseen, since they depend on fire severity, and type of ecosystem management response. So, their application must be evaluated and assessed before

12 CFR 714.6 - Are you required to retain salvage powers over the leased property?

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Are you required to retain salvage powers over the leased property? 714.6 Section 714.6 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS LEASING § 714.6 Are you required to retain salvage powers over the leased...

Meta-analysis of published efficacy and safety data for docetaxel in second-line treatment of patients with advanced non-small-cell lung cancer.

Science.gov (United States)

Stroh, Mark; Green, Michelle; Cha, Edward; Zhang, Nancy; Wada, Russ; Jin, Jin

2016-03-01

To gain a better understanding of the impact of dose and other prognostic factors on safety and efficacy of docetaxel in second-line non-small-cell lung cancer patients. A model-based meta-analysis (MBMA) of a published docetaxel monotherapy data in 6085 second-line non-small-cell lung cancer patients from 46 trials was conducted. The logit of grade 3/4 neutropenia incidence was a linear function of dose, with a 5% increase in the odds of neutropenia per mg/m(2) increase in dose [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.04-1.06], and a Japanese study effect (OR 17.1, 95% CI 6.05-48.4). The logit of overall response rate (ORR) was a linear function of cumulative dose (0.4% increase in the odds of response per mg/m(2) increase; OR 1.004, 95% CI 1.001-1.008) and median population age (OR 1.08 per year, 95% CI 1.02-1.15). A Japanese study effect was identified for overall survival (OS) in addition to prognostic factors identified by a previous meta-analysis. This current MBMA identified docetaxel dose-response relationships for both neutropenia and ORR, an effect of age on ORR, and Japanese study effects on both neutropenia and OS.

What is the benefit of treatment with multiple lines of chemotherapy for patients with metastatic breast cancer? A retrospective cohort study.

Science.gov (United States)

Bakker, J L; Wever, K; van Waesberghe, J H; Beeker, A; Meijers-Heijboer, H; Konings, I R; Verheul, H M W

2015-12-01

Despite the extensive clinical experience, it is still under debate to what extent patients with metastatic breast cancer (MBC) benefit from multiple lines of chemotherapy beyond standard first or second line treatment. Selection of patients with MBC who will benefit from treatment is crucial to improve outcome and reduce unnecessary toxicity. In this retrospective study, systemic treatment outcome for patients with metastatic MBC is being evaluated. We evaluated to what extent the clinical benefit of prior chemotherapy can predict the success of a subsequent treatment line. Ninety-one patients treated with chemotherapy for MBC between January 2005 and January 2009 were included in this study. Clinical characteristics of patients, choices of chemotherapy and response at first evaluation of every treatment line was evaluated based on radiologic and clinical data. Patients received multiple systemic cytotoxic and biological (combination) therapies. 30% of these patients received more than five consecutive systemic (combination) treatments. First line chemotherapy was mostly anthracycline-based, followed by taxanes, capecitabine and vinorelbine. The response rate (RR, complete response plus partial response according to RECIST 1.1) decreased from 20% (95% CI 11-28%) upon first line of treatment to 0% upon the fourth line. The clinical benefit rate (combining RR and stable disease) decreased from 85% (95% CI 78-93%) in the first to 54% (95% CI 26-67) upon the fourth line. 24% of the patients with clinical benefit at first evaluation did not receive a subsequent line of treatment when progressive disease occurred, while sixty-one percent of the patients with progressive disease at first evaluation of a treatment did not receive a subsequent line of chemotherapy. When applied, the efficacy of a subsequent line of treatment was similar for patients independent of previous treatment benefit. The clinical benefit at first evaluation from systemic treatment in MBC does not

Autologous Latissimus Dorsi Breast Reconstruction Flap Salvage: Microvascular Anastomosis with Serratus Branch

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Victoria Kuta, BScH

2017-07-01

Full Text Available Summary:. Autologous breast reconstruction has become a standard option during the recovery of breast cancer survivors. Although pedicle damage is a rare complication of this procedure, extensive torsion or tension can lead to partial or total flap failure. We report a case of partial flap salvage after accidental transection of the pedicled blood supply within the intramuscular course of a latissimus dorsi musculocutaneous flap. This salvage technique involved microvascular anastomosis between the remaining vasculature of the latissimus dorsi pedicle and the serratus branch of the thoracodorsal artery and vein.

Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection

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Guang-Hong Jheng

2015-01-01

Full Text Available The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or “concomitant therapy” is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%. The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, P=0.02, but only seven patients (11.5% experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries.

Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma

Science.gov (United States)

Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L.

2018-01-01

Importance Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti–programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). Objective To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. Design, Setting, and Participants JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Interventions Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Main Outcomes and Measures Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. Results As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing

TA-60 Warehouse and Salvage SWPPP Rev 2 Jan 2017-Final

Energy Technology Data Exchange (ETDEWEB)

Burgin, Jillian Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-02-07

The Stormwater Pollution Prevention Team (PPT) for the TA-60-0002 Salvage and Warehouse Area consists of operations and management personnel from the facility, Multi-Sector General Permitting (MSGP) stormwater personnel from Environmental Compliance Programs (EPC-CP) organization, and Deployed Environmental Professionals. The EPC-CP representative is responsible for Laboratory compliance under the National Pollutant Discharge Elimination System (NPDES) permit regulations. The team members are selected on the basis of their familiarity with the activities at the facility and the potential impacts of those activities on stormwater runoff. The Warehouse and Salvage Yard are a single shift operation; therefore, a member of the PPT is always present during operations.

Long-Term Outcome and Toxicity of Salvage Brachytherapy for Local Failure After Initial Radiotherapy for Prostate Cancer

International Nuclear Information System (INIS)

Burri, Ryan J.; Stone, Nelson N.; Unger, Pam; Stock, Richard G.

2010-01-01

Purpose: To describe long-term outcomes and toxicity after salvage brachytherapy (BT) for local failure after initial radiotherapy for prostate cancer. Methods and Materials: Between 1994 and 2008, 37 men with local failure after initial prostate radiotherapy (32 external-beam radiation therapy [EBRT] and 5 BT) underwent salvage BT with 103 Pd or 125 I. Estimates of freedom from biochemical failure (FFbF, Phoenix definition) and cause-specific survival (CSS) were calculated using the Kaplan-Meier method. Toxicities were graded using CTCv3.0. Results: Median follow-up was 86 months (range, 2-156). The median dose to 90% of the prostate volume was 122 Gy (range, 67-166). The 10-year FFbF and CSS were 54% and 96%, respectively. On univariate analysis, prostate-specific antigen (PSA) >10 ng/mL at initial diagnosis was significantly associated with FFbF (p = 0.01), and there were trends for both age <70 years (p = 0.08) and PSA <6 ng/mL (p = 0.08) at the time of salvage BT. On multivariate analysis, only presalvage PSA <6 ng/mL (p = 0.046) was significantly associated with improved FFbF. There were three Grade 3 toxicities and one Grade 4 toxicity. Pelvic lymph node dissection before salvage BT was the only variable significantly associated with Grade ≥2 toxicity (p = 0.03). Conclusion: With a median follow-up of 86 months, salvage prostate BT was associated with a 10-year FFbF of 54% and CSS of 96%. Improved FFbF was associated with a presalvage PSA <6 ng/mL. Toxicity was worse in patients who had undergone pelvic lymph node dissection before salvage BT. Careful patient selection for salvage BT may result in improved outcomes and reduced toxicity.

Second Line of Defense Virtual Private Network Guidance for Deployed and New CAS Systems

Energy Technology Data Exchange (ETDEWEB)

Singh, Surya V.; Thronas, Aaron I.

2010-01-01

This paper discusses the importance of remote access via virtual private network (VPN) for the Second Line of Defense (SLD) Central Alarm System (CAS) sites, the requirements for maintaining secure channels while using VPN and implementation requirements for current and future sites.

Distinction of salvaged and infarcted myocardium within the ischaemic area-at-risk with T2 mapping

DEFF Research Database (Denmark)

Hammer-Hansen, Sophia; Ugander, Martin; Hsu, Li-Yueh

2014-01-01

values from T2 maps and signal intensities on T2-weighted images were measured in the corresponding areas. RESULTS: At both imaging time points, the T2 of the salvaged myocardium was longer than of remote (66.0 ± 6.9 vs. 51.4 ± 3.5 ms, P ...AIM: Area-at-risk (AAR) measurements often rely on T2-weighted images, but subtle differences in T2 may be overlooked with this method. To determine the differences in oedema between salvaged and infarcted myocardium, we performed quantitative T2 mapping of the AAR. We also aimed to determine...... (14.7 ± 5.6 vs. 8.7 ± 5.1 ms, P = 0.02). CONCLUSIONS: T2 relaxation parameters are different in the infarcted and salvaged myocardium, and both are significantly longer than remote. Furthermore, the magnitude of increase in T2 was less in the salvaged myocardium after longer reperfusion, indicating...

Salvage lymphadenectomy of the right recurrent nerve node with tracheal involvement after definitive chemoradiation therapy for esophageal squamous cell carcinoma. Report of two cases

International Nuclear Information System (INIS)

Doki, Yuichiro; Yasuda, Takushi; Miyata, Hiroshi

2007-01-01

Thoracic esophageal cancers frequently metastasize to the right recurrent nerve nodes (RRNNs). In fact, huge RRNNs invading the trachea sometimes remain after definitive chemoradiation therapy (CRT), despite complete remission of the primary lesion. We performed salvage lymphadenectomy of a large RRNN combined with partial resection of the trachea in two patients. Using an anterior approach, we removed part of the sternum, clavicle, and the first and second costal cartilage; then, we removed the RRNNs with combined resection of the lateral quarter circumference of the trachea, the esophageal wall, and the recurrent nerve. Reconstruction was done with a musculocutaneous patch of major pectoral muscle to cover the tracheal defect. The only minor complication was venous thrombosis in one patient. Thus, combined removal of the RRNN and trachea was performed safely as a salvage operation after definitive CRT for esophageal squamous cell carcinoma. (author)

Outcome of Surgical Treatment of Pelvic Osteosarcoma: Hospital Universiti Sains Malaysia Experience

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MS Ariff

2013-03-01

Full Text Available We reviewed the surgical treatment and outcomes of 13 patients with pelvic osteosarcoma treated in our centre in the past decade. The study sample included 9 males and 4 females with a mean age of 28.1 years. Four patients had ileal lesions, five had acetabulum lesions, one had a ischiopubis lesion, and three had involvement of the whole hemipelvis. Seven patients presented with distant metastases at diagnosis. Limb salvage was performed in 6 patients and amputation in 7. In 60% of cases in the limb salvage surgery group, we attempted wide resection with positive microscopic margin compared to only 16.7% in the amputation group. Local recurrence was higher in the limb salvage group. Overall survival was 18 months for mean follow up of 14.8 months. Median survival was 19 months in the limb salvage group compared to 9 months in amputation group. The outcome of surgical treatment of pelvic osteosarcoma remains poor despite advancements in musculoskeletal oncology treatment.

Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

Energy Technology Data Exchange (ETDEWEB)

Valicenti, Richard K., E-mail: Richard.valicenti@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California, Davis School of Medicine, Davis, California (United States); Thompson, Ian [Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Albertsen, Peter [Division of Urology, University of Connecticut Health Center, Farmington, Connecticut (United States); Davis, Brian J. [Department of Radiation Oncology, Mayo Medical School, Rochester, Minnesota (United States); Goldenberg, S. Larry [Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia (Canada); Wolf, J. Stuart [Department of Urology, University of Michigan, Ann Arbor, Michigan (United States); Sartor, Oliver [Department of Medicine and Urology, Tulane Medical School, New Orleans, Louisiana (United States); Klein, Eric [Glickman Urological Kidney Institute, Cleveland Clinic, Cleveland, Ohio (United States); Hahn, Carol [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Michalski, Jeff [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Roach, Mack [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Faraday, Martha M. [Four Oaks, Inc (United States)

2013-08-01

Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review.

Adjuvant and Salvage Radiation Therapy After Prostatectomy: American Society for Radiation Oncology/American Urological Association Guidelines

International Nuclear Information System (INIS)

Valicenti, Richard K.; Thompson, Ian; Albertsen, Peter; Davis, Brian J.; Goldenberg, S. Larry; Wolf, J. Stuart; Sartor, Oliver; Klein, Eric; Hahn, Carol; Michalski, Jeff; Roach, Mack; Faraday, Martha M.

2013-01-01

Purpose: The purpose of this guideline was to provide a clinical framework for the use of radiation therapy after radical prostatectomy as adjuvant or salvage therapy. Methods and Materials: A systematic literature review using PubMed, Embase, and Cochrane database was conducted to identify peer-reviewed publications relevant to the use of radiation therapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Results: Guideline statements are provided for patient counseling, use of radiation therapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a restaging evaluation. Conclusions: Physicians should offer adjuvant radiation therapy to patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invastion, positive surgical margins, extraprostatic extension) and salvage radiation therapy to patients with prostate-specific antigen (PSA) or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiation therapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiation therapy as well as the potential benefits of preventing recurrence. The decision to administer radiation therapy should be made by the patient and the multidisciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. The American Society for Radiation Oncology and American Urological Association websites show this guideline in its entirety, including the full literature review

Evaluation of MGIT 960 System for the Second-Line Drugs Susceptibility Testing of Mycobacterium tuberculosis

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Hyejin Kim

2013-01-01

Full Text Available Many laboratories validate DST of the second-line drugs by BACTEC MGIT 960 system. The objective of this study is to evaluate the critical concentration and perform DST for the 2nd line drugs. We evaluated 193 clinical strains of M. tuberculosis isolated from patients in South Korea. Testing the critical concentration of six second-line drugs was performed by MGIT 960 and compared with L-J proportion method. The critical concentration was determined to establish the most one that gave the difference between drug resistance and susceptibility in MGIT960 system. Good agreement of the following concentrations was found: Concordance was 95% for 0.5 μg/mL of moxifloxacin; 93.6%, 1.0 μg/mL of levofloxacin; 97.5%, 2.5 μg/mL of kanamycin; 90.6%, 2.5 μg/mL of capreomycin; 86.2%, 5.0 μg/mL of ethionamide; and 90.8%, 2.0 μg/mL of ρ-aminosalicylic acid. The critical concentrations of the four drugs, moxifloxacin, levofloxacin, kanamycin, and capreomycin, were concordant and reliable for testing 2nd line drug resistance. Further study of ethionamide and ρ-aminosalicylic acid is required.

Effectiveness and Morbidity Associated With Reirradiation in Conservative Salvage Management of Recurrent Soft-Tissue Sarcoma

International Nuclear Information System (INIS)

Indelicato, Daniel J.; Meadows, Kenyon; Gibbs, Charles P.; Morris, Christopher G.; Scarborough, Mark T.; Zlotecki, Robert A.

2009-01-01

Purpose: The management of isolated local recurrence of soft-tissue sarcoma is therapeutically complex, and functional conservative management is preferable to radical or amputative salvage surgery. This study reviews University of Florida experience using conservative resection and reirradiation to manage isolated local recurrences of soft-tissue sarcoma. Methods and Materials: Between 1976 and 2005, a total of 14 patients who underwent primary conservative resection and irradiation developed isolated local recurrence and were managed with salvage conservative resection and reirradiation. Of the patients treated, 3 had tumors of the distal extremity, 8 had tumors of the proximal extremity, and 3 had tumors of the trunk. At the time of recurrence, 64% of tumors were greater than 5 cm and 79% were high grade. In combination with gross total resection, 13 of 14 patients received external beam radiotherapy with or without brachytherapy, and 1 patient was treated with brachytherapy alone. Two patients received chemotherapy. Results: The median follow-up was 30 months, and no living patients were lost during follow-up. From retreatment, the 5-year actuarial overall survival, cause-specific survival, and local control rates were 40%, 40%, and 18% respectively. There was a 50% incidence of serious complication requiring either reoperation or leading to permanent functional impairment. Of the 14 patients, only 1 has remained disease free and without significant complications. No treatment factors, including achieving wide surgical margins or delivering higher radiation dosages, seemed to confer an advantage in local control. Conclusions: Salvage therapy for management of locally recurrent soft-tissue sarcoma is challenging, and the effects of reoperation and reirradiation can be severe

33 CFR 155.4035 - Required pre-incident information and arrangements for the salvage and marine firefighting...

Science.gov (United States)

2010-07-01

... and arrangements for the salvage and marine firefighting resource providers listed in response plans... marine firefighting resource providers listed in response plans. (a) You must provide the information listed in §§ 155.1035(c) and 155.1040(c) to your salvage and marine firefighting resource providers. (b...

33 CFR 155.4045 - Required agreements or contracts with the salvage and marine firefighting resource providers.

Science.gov (United States)

2010-07-01

... with the salvage and marine firefighting resource providers. 155.4045 Section 155.4045 Navigation and... agreements or contracts with the salvage and marine firefighting resource providers. (a) You may only list resource providers in your plan that have been arranged by contract or other approved means. (b) You must...

18F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

International Nuclear Information System (INIS)

D'Angelillo, Rolando M.; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A.; Trodella, Luca E.; Fiore, Michele; Gallucci, Michele; Maini, Carlo L.; Trodella, Lucio

2014-01-01

Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic 18 F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, 18 F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity

Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer

NARCIS (Netherlands)

N. Verstegen (Naomi); A.W.P.M. Maat (Alex); F.J. Lagerwaard (Frank); M.A. Paul (Marinus); M. Versteegh (Michel); J.J. Joosten (Joris); W. Lastdrager (Willem); E.F. Smit (Egbert); B.J. Slotman (Ben); J.J.M.E. Nuyttens (Joost); S. Senan (Suresh)

2016-01-01

markdownabstract__Introduction:__ The literature on surgical salvage, i.e. lung resections in patients who develop a local recurrence following stereotactic ablative radiotherapy (SABR), is limited. We describe our experience with salvage surgery in nine patients who developed a local recurrence

Second malignancy in relation to treatment modality of primary malignancy

International Nuclear Information System (INIS)

Singh, Harpreet; Kaur, Parveen; Vashistha, Rajesh; Singh, Jaskaran; Passi, Kamlesh; Jain, Satish

2001-01-01

Second malignant tumors among long-term survivors are a sensitive indicator of successful oncologic treatment, particularly in this area of multimodal therapy. 11 patients of abdominopelvic primary malignancy were detected to have a second malignancy of different pathology, and at a different site. These patients were assessed regarding treatment modality of initial cancer and time gap between the first and second malignancy. Lack of proper cancer registries, illiteracy, and lack of resources lead to poor patient follow-up; therefore population based studies is not possible

Surgical and cryosurgical salvage of oral and oropharyngeal cancer recurring after radical radiotherapy

International Nuclear Information System (INIS)

Meyza, J.W.; Towpik, E.

1991-01-01

The results of salvage surgery or cryosurgery performed in 62 cases or oral or oropharyngeal cancer, recurring or persisting after radical radiotherapy, were analysed retrospectively. Salvage surgery was performed in 33 cases. The relatively high frequency of postoperative complications observed in years 1973-1984 has declined since 1985, concomitant with the introduction of myocutaneous flaps for reconstruction. Twenty-nine patients who were disqualified from major surgery, were treated by cryosurgery. Using both methods, 3-year overall survival was obtained in 24.1% of cases. (author)

Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

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V. A. Solodkiy

2016-01-01

Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

Radiation therapy alone is not successful as salvage treatment for locally recurrent prostate cancer after radical prostatectomy

Energy Technology Data Exchange (ETDEWEB)

Oas, Lute G; Zagars, Gunar K; Pollack, Alan

1995-07-01

Purpose/Objectives: To evaluate radiotherapy (XRT) as potential salvage treatment for patients with locally recurrent prostate cancer after redical prostatectomy (RP). Materials and Methods: Twenty-four consecutive patients with adenocarcinoma of the prostate who received definitive XRT between 1987 and 1993 for biopsy-proven (n=18) or for prostate-specific antigen (PSA) - producing (n=6) recurrent disease following RP were evaluated. No patient had clinically or radiographically evident distant disease. Biopsies of suspicious nodules or ultrasound findings in the prostatic fossa were positive in 18 and negative in 3. Three patients had no focal abnormalities and had no biopsy. The time between RP and XRT varied from 6 to 277 months (mean 52 months). XRT doses to the prostatic fossa ranged from 60 to 70 Gy (median, 66 Gy). Outcome was analyzed relative to local control, metastatic disease and PSA status. Persistently undetectable PSA was required to define freedom from disease. Results: Pre-XRT PSA levels ranged from 0.7 to 26.8 ng/ml (mean 7.3 ng/ml, median 2.5 ng/ml). Although PSA fell post-XRT in all but 3 patients and 10 (52%) achieved undetectable levels, the outcome at a median follow-up of 42 months (range 13-90 months) was poor, with 15 patients (63%) developing persistent/progressive disease. The patterns of progression in these 15 were: local 3, metastatic 3, persistent PSA 9. All patients whose PSA was persistently detectable developed a rising PSA profile. The actuarial incidence of freedom from disease at 1, 2, 3 and 4 years was 75%, 43%, 36% and 27% respectively. The only factor correlating to outcome was the pre-XRT PSA level. The 9 patients who remain free of disease had a mean PSA level of 3.6 ng/ml compared to a mean level of 9.6 ng/ml among the 15 who failed (p<0.01). All patients with a pre-XRT level >2.5 ng/ml developed disease relapse, whereas the 4-year freedom from disease in those with levels {<=}2.5 ng/ml was 52%. Eleven of the 15 patients

Responses of cavity-nesting birds to stand-replacement fire and salvage logging in ponderosa pine/Douglas-fir forests of southwestern Idaho

Science.gov (United States)

Victoria A. Saab; Jonathan G. Dudley

1998-01-01

From 1994 to 1996, researchers monitored 695 nests of nine cavity-nesting bird species and measured vegetation at nest sites and at 90 randomly located sites in burned ponderosa pine forests of southwestern Idaho. Site treatments included two types of salvage logging, and unlogged controls. All bird species selected nest sites with higher tree densities, larger...

Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

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Hung-Bo Wu

2013-01-01

Full Text Available Up to 40% of patients with advanced Hodgkin lymphoma (HL become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

New insights into the consequences of post-windthrow salvage logging revealed by functional structure of saproxylic beetles assemblages.

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Simon Thorn

Full Text Available Windstorms, bark beetle outbreaks and fires are important natural disturbances in coniferous forests worldwide. Wind-thrown trees promote biodiversity and restoration within production forests, but also cause large economic losses due to bark beetle infestation and accelerated fungal decomposition. Such damaged trees are often removed by salvage logging, which leads to decreased biodiversity and thus increasingly evokes discussions between economists and ecologists about appropriate strategies. To reveal the reasons behind species loss after salvage logging, we used a functional approach based on four habitat-related ecological traits and focused on saproxylic beetles. We predicted that salvage logging would decrease functional diversity (measured as effect sizes of mean pairwise distances using null models as well as mean values of beetle body size, wood diameter niche and canopy cover niche, but would increase decay stage niche. As expected, salvage logging caused a decrease in species richness, but led to an increase in functional diversity by altering the species composition from habitat-filtered assemblages toward random assemblages. Even though salvage logging removes tree trunks, the most negative effects were found for small and heliophilous species and for species specialized on wood of small diameter. Our results suggested that salvage logging disrupts the natural assembly process on windthrown trees and that negative ecological impacts are caused more by microclimate alteration of the dead-wood objects than by loss of resource amount. These insights underline the power of functional approaches to detect ecosystem responses to anthropogenic disturbance and form a basis for management decisions in conservation. To mitigate negative effects on saproxylic beetle diversity after windthrows, we recommend preserving single windthrown trees or at least their tops with exposed branches during salvage logging. Such an extension of the green

New insights into the consequences of post-windthrow salvage logging revealed by functional structure of saproxylic beetles assemblages.

Science.gov (United States)

Thorn, Simon; Bässler, Claus; Gottschalk, Thomas; Hothorn, Torsten; Bussler, Heinz; Raffa, Kenneth; Müller, Jörg

2014-01-01

Windstorms, bark beetle outbreaks and fires are important natural disturbances in coniferous forests worldwide. Wind-thrown trees promote biodiversity and restoration within production forests, but also cause large economic losses due to bark beetle infestation and accelerated fungal decomposition. Such damaged trees are often removed by salvage logging, which leads to decreased biodiversity and thus increasingly evokes discussions between economists and ecologists about appropriate strategies. To reveal the reasons behind species loss after salvage logging, we used a functional approach based on four habitat-related ecological traits and focused on saproxylic beetles. We predicted that salvage logging would decrease functional diversity (measured as effect sizes of mean pairwise distances using null models) as well as mean values of beetle body size, wood diameter niche and canopy cover niche, but would increase decay stage niche. As expected, salvage logging caused a decrease in species richness, but led to an increase in functional diversity by altering the species composition from habitat-filtered assemblages toward random assemblages. Even though salvage logging removes tree trunks, the most negative effects were found for small and heliophilous species and for species specialized on wood of small diameter. Our results suggested that salvage logging disrupts the natural assembly process on windthrown trees and that negative ecological impacts are caused more by microclimate alteration of the dead-wood objects than by loss of resource amount. These insights underline the power of functional approaches to detect ecosystem responses to anthropogenic disturbance and form a basis for management decisions in conservation. To mitigate negative effects on saproxylic beetle diversity after windthrows, we recommend preserving single windthrown trees or at least their tops with exposed branches during salvage logging. Such an extension of the green-tree retention

Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis.

Science.gov (United States)

Basken, Robyn; Bazzell, Charles M; Smith, Richard; Janardhanan, Rajesh; Khalpey, Zain

2017-07-01

Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention. © 2017 Wiley Periodicals, Inc.

Paclitaxel with Cisplatin as Salvage Treatment for Patients with Previously Treated Advanced Transitional Cell Carcinoma of the Urothelial Tract

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Ji Eun Uhm

2007-01-01

Full Text Available BACKGROUND: This study was performed to evaluate the safety and efficacy of paclitaxel with cisplatin as salvage therapy in patients previously treated with gemcitabine and cisplatin (G/C for advanced transitional cell carcinoma (TCC of the urothelial tract. METHODS: Twenty-eight patients with metastatic or locally advanced TCC who had received prior G/C chemotherapy were enrolled. All patients received paclitaxel (175 mg/m2 and cisplatin (60 mg/m2 every 3 weeks for eight cycles or until disease progression. RESULTS: The median age was 61 years (range, 43–83 years, and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2. The overall response rate was 36% [95% confidence interval (95% CI = 18–54], with three complete responses and seven partial responses. The median time to progression was 6.2 months (95% CI = 3.9–8.5, and the median overall survival was 10.3 months (95% CI = 6.1–14.1. The most common Grade 3/4 nonhematologic and hematologic toxicities were emesis (10 of 28 patients; 36% and neutropenia (5 of 110 cycles; 5%. CONCLUSIONS: Salvage chemotherapy with paclitaxel and cisplatin displayed promising results with tolerable toxicity profiles in patients with metastatic or locally advanced TCC who had been pretreated with G/C.

Tuberculosis drug issues: prices, fixed-dose combination products and second-line drugs.

Science.gov (United States)

Laing, R O; McGoldrick, K M

2000-12-01

Access to tuberculosis drugs depends on multiple factors. Selection of a standard list of TB drugs to procure is the first step. This paper reviews the advantages and disadvantages of procuring and using fixed-dose combination (FDC) products for both the intensive and continuation phases of treatment. The major advantages are to prevent the emergence of resistance, to simplify logistic management and to reduce costs. The major disadvantage is the need for the manufacturers to assure the quality of these FDCs by bioavailability testing. The paper reports on the inclusion of second-line TB drugs in the 1999 WHO Essential Drug List (EDL). The need to ensure that these drugs are used within established DOTS-Plus programs is stressed. The price of TB drugs is determined by many factors, including producer prices, local taxes and duties as well as mark-ups and fees. TB drug prices for both the public and private sectors from industrialized and developing countries are reported. Price trends over time are also reported. The key findings of this study are that TB drug prices have generally declined in developing countries while they have increased in developed countries, both for the public and private sectors. Prices vary between countries, with the US paying as much as 95 times the price paid in a specific developing country. The prices of public sector first-line TB drugs vary little between countries, although differences do exist due to the procurement methods used. The price of tuberculin, a diagnostic agent, has increased dramatically in the US, with substantial inter-country variations in price. The paper suggests that further research is necessary to identify the reasons for the price disparities and changes over time, and suggests methods which can be used by National Tuberculosis Programme managers to ensure availability of quality assured TB drugs at low prices.

Pancreas Transplant Venous Thrombosis: Role of Endovascular Interventions for Graft Salvage

International Nuclear Information System (INIS)

Stockland, Andrew H.; Willingham, Darrin L.; Paz-Fumagalli, Ricardo; Grewal, Hani P.; McKinney, J. Mark; Hughes, Christopher B.; Walser, Eric M.

2009-01-01

Venous thrombosis of pancreas transplant allografts often leads to graft loss. We evaluated the efficacy of emergent endovascular techniques to salvage thrombosed pancreatic allografts in a series of six patients. Of the 76 pancreas transplants performed between 2002 and 2006, six patients were diagnosed with venous thrombosis on MRI between 2 and 28 days posttransplant (mean, 9 days). Five patients were systemic-enteric (donor portal vein anastomosis to recipient iliac vein) and one patient was portal-enteric (donor portal vein anastomosis to recipient superior mesenteric vein). Conventional venography confirmed the diagnosis of venous thrombosis in all patients. One patient was treated with catheter-directed venous thrombolysis and balloon thrombectomy. Another patient was treated with rheolytic thrombectomy alone. The remaining four patients were treated with a combination of these mechanical and thrombolytic techniques. Completion venography revealed >50% clot reduction and resumption of venous drainage in all patients. One patient required additional intervention 16 days later for recurrent thrombosis. Two patients required metal stent placement for anastomotic stenoses or kinks. One patient required pancreatectomy 36 h after attempted salvage secondary to a major hemorrhage and graft necrosis. Two patients recovered pancreatic function initially but lost graft function at 8 and 14 months, respectively, from severe chronic rejection. Patient survival was 100%, long-term graft survival was 50%, rethrombosis rate was 16.6%, and graft loss from rejection was 33%. In conclusion, early recognition and treatment of venous thrombosis after pancreas transplantation has acceptable morbidity and no mortality using short-term endovascular pharmacomechanical therapy.

[Fast-track treatment--second revolution of colorectal surgery].

Science.gov (United States)

Kellokumpu, Ilmo

2012-01-01

The fast-track treatment model can be regarded as the second revolution of colorectal surgery after the introduction of laparoscopic surgery. In the gastro-surgical unit of the Central Hospital of Central Finland, results equivalent to international studies in colorectal surgery have been achieved by using fast-track model. In a study setting, this treatment model has resulted in significant decrease of total treatment costs and speeded up discharge of the patients from the hospital. The fast-track treatment model requires both a motivated, trained medical team and a motivated patient.

Outcome and renal function following salvage surgery for bilateral ...

African Journals Online (AJOL)

Objective: The aim of this study was to determine the surgical outcomes and renal function following salvage surgery for bilateral Wilms tumor (BWT). Summary background data The challenge for the surgeon treating BWT lies in striking a fine balance between renal preservation and oncological clearance. Methods: This is ...

Fourteen-day high-dose esomeprazole, amoxicillin and metronidazole as third-line treatment for Helicobacter pylori infection.

Science.gov (United States)

Puig, Ignasi; González-Santiago, Jesús M; Molina-Infante, Javier; Barrio, Jesús; Herranz, Maria Teresa; Algaba, Alicia; Castro, Manuel; Gisbert, Javier P; Calvet, Xavier

2017-09-01

The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole. Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or 13 C-UBT both before and after treatment. A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred. Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens. © 2017 John Wiley & Sons Ltd.

Second-Line Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian, Tubal and Peritoneal Cancer: A Propensity Score-Matching Study.

Science.gov (United States)

Lu, Chien-Hsing; Chang, Yen-Hou; Lee, Wai-Hou; Chang, Yi; Peng, Chia-Wen; Chuang, Chi-Mu

2016-01-01

The superiority of frontline intraperitoneal (IP) over intravenous (IV) chemotherapy is well established in the treatment of epithelial ovarian cancer. However, the role of IP chemotherapy in the second-line setting has rarely been investigated. Consecutive patients diagnosed with recurrent epithelial, tubal and peritoneal cancers between January 2000 and December 2012 were recruited using a propensity score-matching technique to adjust relevant risk factors. In total, 310 patients were included in the final analysis (94 for platinum-refractory/resistant disease and 216 for platinum-sensitive disease). IP chemotherapy demonstrated significantly longer median progression-free survival than IV chemotherapy (4.9 vs. 2.4 months, p chemotherapy confers longer progression-free survival than IV chemotherapy. Large-scale clinical trials should be conducted to validate the true efficacy. © 2016 S. Karger AG, Basel.

Synthesizing and salvaging NAD: lessons learned from Chlamydomonas reinhardtii.

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Huawen Lin

2010-09-01

Full Text Available The essential coenzyme nicotinamide adenine dinucleotide (NAD+ plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis, as in plants, or nicotinamide, as in mammals (salvage synthesis. The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO, quinolinate synthetase (QS, quinolate phosphoribosyltransferase (QPT, nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT, and NAD+ synthetase (NS. Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1 or plasmids with cloned genes (nic1-1 and nic15-1 into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1 has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial

DEFF Research Database (Denmark)

Gimsing, P; Hjertner, Ø; Abildgaard, N

2015-01-01

, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared......Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib...... included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT...

Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

Science.gov (United States)

Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

2016-01-01

Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

Directory of Open Access Journals (Sweden)

Chunxiang Zhang

Full Text Available Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC from the perspective of the Chinese healthcare system.Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs and incremental cost-utility ratios (ICURs were calculated. One-way and probabilistic sensitivity analyses (PSA were performed.Our model suggested that the median progression-free survival (PFS was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

The impact of post-fire salvage logging on microbial nitrogen cyclers in Mediterranean forest soil.

Science.gov (United States)

Pereg, Lily; Mataix-Solera, Jorge; McMillan, Mary; García-Orenes, Fuensanta

2018-04-01

Forest fires are a regular occurrence in the Mediterranean basin. High severity fires and post-fire management can affect biological, chemical and physical properties of soil, including the composition and abundance of soil microbial communities. Salvage logging is a post-fire management strategy, which involves the removal of burnt wood from land after a fire. The main objective of this work was to evaluate the impact of post-fire salvage logging and microaggregation on soil microbial communities, specifically on the abundance of nitrogen cyclers and, thus, the potential of the soil for microbial nitrogen cycling. The abundance of nitrogen cyclers was assessed by quantification of microbial nitrogen cycling genes in soil DNA, including nifH (involved in nitrogen fixation), nirS/K and nosZ (involved in denitrification), amoA-B and amoA-Arch (involved in bacterial and archaeal nitrification, respectively). It was demonstrated that salvage logging reduced bacterial load post-fire when compared to tree retention control and resulted in significant changes to the abundance of functional bacteria involved in nitrogen cycling. Microbial gene pools involved in various stages of the nitrogen cycle were larger in control soil than in soil subjected to post-fire salvage logging and were significantly correlated with organic matter, available phosphorous, nitrogen and aggregate stability. The microaggregate fraction of the soil, which has been associated with greater organic carbon, was shown to be a hotspot for nitrogen cyclers particularly under salvage logging. The impact of post-fire management strategies on soil microbial communities needs to be considered in relation to maintaining ecosystem productivity, resilience and potential impact on climate change. Copyright © 2017 Elsevier B.V. All rights reserved.

Salvage Stereotactic Reirradiation With or Without Cetuximab for Locally Recurrent Head-and-Neck Cancer: A Feasibility Study

Energy Technology Data Exchange (ETDEWEB)

Comet, Benedicte [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France); Kramar, Andrew [Department of Statistical Analysis, Centre Oscar Lambret and University Lille II, Lille (France); Faivre-Pierret, Mathieu [Department of Radiology, Centre Oscar Lambret and University Lille II, Lille (France); Dewas, Sylvain; Coche-Dequeant, Bernard [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France); Degardin, Marian; Lefebvre, Jean-Louis [Department of Head and Neck Surgery, Centre Oscar Lambret and University Lille II, Lille (France); Lacornerie, Thomas [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France); Lartigau, Eric F., E-mail: e-lartigau@o-lambret.fr [Department of Academic Radiotherapy, Centre Oscar Lambret and University Lille II, Lille (France)

2012-09-01

Purpose: Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC. Methods and Materials: Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab. Results: Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients. Conclusion: These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.

Salvage Stereotactic Reirradiation With or Without Cetuximab for Locally Recurrent Head-and-Neck Cancer: A Feasibility Study

International Nuclear Information System (INIS)

Comet, Bénédicte; Kramar, Andrew; Faivre-Pierret, Mathieu; Dewas, Sylvain; Coche-Dequeant, Bernard; Degardin, Marian; Lefebvre, Jean-Louis; Lacornerie, Thomas; Lartigau, Eric F.

2012-01-01

Purpose: Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC. Methods and Materials: Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab. Results: Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients. Conclusion: These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.

The Prestige oil spill response in the French coastal waters : setting up a second-line response system

International Nuclear Information System (INIS)

Kerambrun, L.; Lavenant, M.; Cariou, G.; Poisson, H.; Goasguen, H.; Peltier, M.

2005-01-01

A heavy fuel oil spill from the Prestige oil tanker in early 2003 threatened the coastline of France, particularly the sensitive sandy dunes of the Aquitaine coast. The spill posed a long-term threat to two affected tourist islands that host a rich marine life, including the Marennes-Oleron oysters and juvenile eel fisheries. An oil spill response system was established by the French Maritime Affairs Department. The two-tiered response system was constructed with dynamic and static components and was adapted for strong tidal currents and muddy waters where fuel patches from the spill might not be visible. Local fishermen with knowledge of the waters used their trawlers and eel-fishing boats that were equipped with oil recovery trawls. A local netting device was also tested. The second response line for shallow waters consisted of small boats with net bags. The storage, transfer and treatment of the oily waste were controlled and available oil waste treatment procedures were assessed at local, regional and national levels for each type of oil waste fuel. 2 refs

The second therapeutic trial for children with hematological malignancies who relapsed after their first allogeneic SCT: long-term outcomes.

Science.gov (United States)

Nishikawa, Takuro; Inagaki, Jiro; Nagatoshi, Yoshihisa; Fukano, Reiji; Nakashima, Kentaro; Ito, Nobuhiro; Sawa, Daisuke; Kawano, Yoshifumi; Okamura, Jun

2012-11-01

The impact of a second all-SCT on the long-term outcomes of children who relapse after allo-SCT has been unclear. We retrospectively analyzed the long-term outcomes of different salvage treatments for such children. Sixty-six children with hematological malignancies (40 ALL, 22 AML, three MDS, and one CML) who relapsed after a first allo-SCT received either a second allo-SCT (n = 16) or CTx and/or DLI (n = 50). The median follow-up for all children was 9.1 yr. The five-yr OS after relapse was significantly better in patients who underwent a second allo-SCT (42.9%) than in patients treated with CTx and/or DLI (11.8%) (p SCT, two died more than five yr after the second allo-SCT. A second allo-SCT can therefore lead to a prolonged OS in patients who relapse after allo-SCT. However, a second allo-SCT should be selected carefully. This is because the mortality rate is still high, even when there is an extensive duration of time following the second allo-SCT. © 2012 John Wiley & Sons A/S.

A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

Science.gov (United States)

Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

2017-07-01

It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

Science.gov (United States)

Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

2014-07-01

In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

26 CFR 1.167(f)-1 - Reduction of salvage value taken into account for certain personal property.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Reduction of salvage value taken into account for certain personal property. 1.167(f)-1 Section 1.167(f)-1 Internal Revenue INTERNAL REVENUE SERVICE... for Individuals and Corporations § 1.167(f)-1 Reduction of salvage value taken into account for...

Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma.

Science.gov (United States)

Batschinski, K; Dervisis, N G; Kitchell, B E

2014-12-01

A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m(-2) (median dose 375 mg m(-2)), with a median of two doses administered per dog (range 1-7 doses). The overall response to ifosfamide was 11.8% [complete response (CR) = 1/17, partial response (PR) = 1/17, stable disease (SD) = 2/17, progressive disease (PD) = 13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed. © 2012 Blackwell Publishing Ltd.

Medical treatment of second-trimester fetal miscarriage; A retrospective analysis

OpenAIRE

Niinimaki, Maarit; Mentula, Maarit; Jahangiri, Reetta; Mannisto, Jaana; Haverinen, Annina; Heikinheimo, Oskari

2017-01-01

Abstract Objectives: Research on the treatment of second-trimester miscarriages is scarce. We studied the outcomes, and the factors associated with adverse events and need for hospital resources in the medical treatment of second-trimester miscarriage. Materials and methods: In these retrospective analyses we studied women treated for spontaneous fetal miscarriage with misoprostol-only (n = 24) or mifepristone and misoprostol (n = 177) in duration of gestation 12+1–21+6. Primary outcome...

Bacterial variations on the methionine salvage pathway

Directory of Open Access Journals (Sweden)

Haas Dieter

2004-03-01

Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

Expert System Development on On-line Measurement of Sewage Treatment Based Process

Directory of Open Access Journals (Sweden)

Jianjun QIN

2014-02-01

Full Text Available This article puts forward a solution in which an instrument on-line automatic measurement and expert system process are optimized according to the complexity and great process dynamics of sewage treatment process. Firstly modeling has been set up with configuration sewage treatment process in which the process has been integrated into the computer software environment. Secondly certain number of water quality automatic monitoring instruments and sensor probes are set in the reaction tanks according to the needs of process changes and management. The data information acquired can be displayed and recorded at the real time. A human-machine integration expert system featuring computer automation management is developed for the base by one-off method thus to realize the intelligent and unmanned management. The advantages brought about from it can fill up the inexperience of the on-site management personnel and solve the contradiction between the water quality dynamics and difficulty in the process adjustment.

Salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy for prostate cancer. A single-center experience

International Nuclear Information System (INIS)

Yoshida, Takahiro; Nakayama, Masashi; Suzuki, Osamu

2011-01-01

The aim of this study was to investigate the efficacy and prognostic factors of salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy for prostate cancer at a single center in Japan. A retrospective review of the medical records of 51 patients who underwent salvage radiotherapy for prostate-specific antigen relapse after radical prostatectomy was carried out. Salvage radiotherapy was undergone for the single indication of at least two consecutive prostate-specific antigen elevations >0.1 ng/ml. Salvage radiotherapy was delivered to the prostatic bed at a total dose of 60 or 64 Gy. Late toxicity was scored according to the Common Terminology Criteria for Adverse Events 3.0. A total dose of 60 and 64 Gy were administered to 26 and 25 patients, respectively. The median prostate-specific antigen level at the initiation of radiotherapy was 0.29 ng/ml (range, 0.11-1.10 ng/ml). With a median follow-up of 57.3 months (range, 9.9-134.0 months), the prostate-specific antigen relapse-free rate at 5 years was 50.7%. Multivariate analysis using Cox's proportional hazards regression model revealed that the Gleason score at radical prostatectomy ≥8 significantly predicted prostate-specific antigen relapse after salvage radiotherapy (hazard ratio 4.531; 95% confidence interval 1.413-14.535; P=0.011). The prostate-specific antigen relapse-free rate at 5 years in the Gleason score at radical prostatectomy ≤7 and at radical prostatectomy ≥8 was 62.7 and 15.4%, respectively. Salvage radiotherapy was effective for prostate-specific antigen relapse after radical prostatectomy with tolerable toxicities in Japanese patients. A high Gleason score seemed to be a poor prognostic factor. (author)

Salvage radiation therapy following radical prostatectomy. A national Danish study

DEFF Research Database (Denmark)

Ervandian, Maria; Høyer, Morten; Petersen, Stine Elleberg

2015-01-01

BACKGROUND: The purpose of this observational cohort study was to evaluate the outcome and prognostic factors following salvage radiotherapy (SRT) in a consecutive national cohort. MATERIAL AND METHODS: Between 2006 and 2010, 259 patients received SRT in Denmark. Patient- and cancer-related chara...

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

Science.gov (United States)

Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

2014-08-01

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

Percutaneous Creation of Bare Intervascular Tunnels for Salvage of Thrombosed Hemodialysis Fistulas Without Recanalizable Outflow

International Nuclear Information System (INIS)

Chen, Matt Chiung-Yu; Wang, Yen-Chi; Weng, Mei-Jui

2015-01-01

PurposeThis study aimed to retrospectively assess the efficacy of a bare intervascular tunnel for salvage of a thrombosed hemodialysis fistula. We examined the clinical outcomes and provided follow-up images of the bare intervascular tunnel.Materials and MethodsEight thrombosed fistulas lacked available recanalizable outflow veins were included in this study. These fistulas were salvaged by re-directing access site flow to a new outflow vein through a percutaneously created intervascular tunnel without stent graft placement. The post-intervention primary and secondary access patency rates were calculated using the Kaplan–Meier method.ResultsThe procedural and clinical success rates were 100 %. Post-intervention primary and secondary access patency at 300 days were 18.7 ± 15.8 and 87.5 ± 11.7 %, respectively. The mean follow-up period was 218.7 days (range 10–368 days). One patient died of acute myocardial infarction 10 days after the procedure. No other major complications were observed. Minor complications, such as swelling, ecchymosis, and pain around the tunnel, occurred in all of the patients.ConclusionsPercutaneous creation of a bare intervascular tunnel is a treatment option for thrombosed hemodialysis fistulas without recanalizable outflow in selected patients

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

Science.gov (United States)

Young, M; Plosker, G L

2001-01-01

Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life

49 CFR 599.402 - Requirements and limitations for salvage auctions that are consigned trade-in vehicles under the...

Science.gov (United States)

2010-10-01

... that are consigned trade-in vehicles under the CARS program. 599.402 Section 599.402 Transportation... SAVE ACT PROGRAM Disposal of Trade-in Vehicle § 599.402 Requirements and limitations for salvage auctions that are consigned trade-in vehicles under the CARS program. (a) The salvage auction must: (1...

Dismal salvage of testicular torsion: A call to action! | Maranya ...

African Journals Online (AJOL)

... were not subjected to orchidopexy. There was no occurrence of torsion after orchidopexy. Conclusion: Testicular torsions were associated with low salvage rates. Increased public awareness coupled with clinician, parental, teacher, teenage and adult male education with respect to the consequences of acute scrotal pain ...