High-Dose-Rate Brachytherapy Boost Effect on Local Tumor Control in Young Women With Breast Cancer

International Nuclear Information System (INIS)

Guinot, Jose-Luis; Baixauli-Perez, Cristobal; Soler, Pablo; Tortajada, Maria Isabel; Moreno, Araceli; Santos, Miguel Angel; Mut, Alejandro; Gozalbo, Francisco; Arribas, Leoncio

2015-01-01

Purpose: To evaluate the local control rate and complications of a single fraction of high-dose-rate brachytherapy (HDR BT) boost in women aged 45 yeas and younger after breast-conserving therapy. Methods and Materials: Between 1999 and 2007, 167 patients between the ages of 26 and 45 years old (72 were 40 years old or younger), with stages T1 to T2 invasive breast cancer with disease-free margin status of at least 5 mm after breast-conserving surgery received 46 to 50 Gy whole-breast irradiation plus a 7-Gy HDR-BT boost (“fast boost”). An axillary dissection was performed in 72.5% of the patients and sentinel lymph node biopsy in 27.5%. A supraclavicular area was irradiated in 19% of the patients. Chemotherapy was used in 86% of the patients and hormone treatment in 77%. Clinical nodes were present in 18% and pathological nodes in 29%. The pathological stage was pT0: 5%, pTis: 3%, pT1: 69% and pT2: 23%. Intraductal component was present in 40% and 28% were G3. Results: At a median follow-up of 92 months, 9 patients relapsed on the margin of the implant, and 1 patient in another quadrant, resulting in a 10-year local relapse rate of 4.3% and a breast relapse rate of 4.9%, with breast preservation in 93.4%; no case of mastectomy due to poor cosmesis arose. Actuarial 5- and 10-year disease-free, cause-specific, and overall survival rates were 87.9% and 85.8%, and 92.1% and 88.4%, and 92.1% and 87.3%, respectively. In a univariate analysis, triple-negative cases and negative hormone receptors did worse, but in a multivariate analysis, only the last factor was significant for local and breast control. Asymptomatic fibrosis G2 was recorded in 3 cases, and there were no other late complications. Cosmetic results were good to excellent in 97% of cases. Conclusions: A single dose of 7 Gy using the fast-boost technique is well tolerated, with a low rate of late complications and improved local tumor control in women aged 45 and younger, compared to published data

High-Dose-Rate Brachytherapy Boost Effect on Local Tumor Control in Young Women With Breast Cancer

Energy Technology Data Exchange (ETDEWEB)

Guinot, Jose-Luis, E-mail: jguinot@fivo.org [Department of Radiation Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain); Baixauli-Perez, Cristobal [Health Services Research Unit, Center for Public Health Research, Valencia (Spain); Soler, Pablo; Tortajada, Maria Isabel; Moreno, Araceli; Santos, Miguel Angel; Mut, Alejandro [Department of Radiation Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain); Gozalbo, Francisco [Department of Pathology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain); Arribas, Leoncio [Department of Radiation Oncology, Fundacion Instituto Valenciano de Oncologia, Valencia (Spain)

2015-01-01

Purpose: To evaluate the local control rate and complications of a single fraction of high-dose-rate brachytherapy (HDR BT) boost in women aged 45 yeas and younger after breast-conserving therapy. Methods and Materials: Between 1999 and 2007, 167 patients between the ages of 26 and 45 years old (72 were 40 years old or younger), with stages T1 to T2 invasive breast cancer with disease-free margin status of at least 5 mm after breast-conserving surgery received 46 to 50 Gy whole-breast irradiation plus a 7-Gy HDR-BT boost (“fast boost”). An axillary dissection was performed in 72.5% of the patients and sentinel lymph node biopsy in 27.5%. A supraclavicular area was irradiated in 19% of the patients. Chemotherapy was used in 86% of the patients and hormone treatment in 77%. Clinical nodes were present in 18% and pathological nodes in 29%. The pathological stage was pT0: 5%, pTis: 3%, pT1: 69% and pT2: 23%. Intraductal component was present in 40% and 28% were G3. Results: At a median follow-up of 92 months, 9 patients relapsed on the margin of the implant, and 1 patient in another quadrant, resulting in a 10-year local relapse rate of 4.3% and a breast relapse rate of 4.9%, with breast preservation in 93.4%; no case of mastectomy due to poor cosmesis arose. Actuarial 5- and 10-year disease-free, cause-specific, and overall survival rates were 87.9% and 85.8%, and 92.1% and 88.4%, and 92.1% and 87.3%, respectively. In a univariate analysis, triple-negative cases and negative hormone receptors did worse, but in a multivariate analysis, only the last factor was significant for local and breast control. Asymptomatic fibrosis G2 was recorded in 3 cases, and there were no other late complications. Cosmetic results were good to excellent in 97% of cases. Conclusions: A single dose of 7 Gy using the fast-boost technique is well tolerated, with a low rate of late complications and improved local tumor control in women aged 45 and younger, compared to published data

Intraoperative MRI to control the extent of brain tumor surgery

International Nuclear Information System (INIS)

Knauth, M.; Sartor, K.; Wirtz, C.R.; Tronnier, V.M.; Staubert, A.; Kunze, S.

1998-01-01

Intraoperative MRI definitely showed residual tumor in 6 of the 18 patients and resulted in ambiguous findings in 3 patients. In 7 patients surgery was continued. Early postoperative MRI showed residual tumor in 3 patients and resulted in uncertain findings in 2 patients. The rate of patients in whom complete removal of enhancing tumor could be achieved was 50% at the time of the intraoperative MR examination and 72% at the time of the early postoperative MR control. The difference in proportion of patients with 'complete tumor removal' between the groups who had been operated on using neuronavigation (NN) and intraoperative MRI (ioMRI) and those who had been operated on using only modern neurosurgical techniques except NN and ioMRI was statistically highly significant (Fisher exact test; P=0.008). Four different types of surgically induced contrast enhancement were observed. These phenomena carry different confounding potentials with residual tumor. Conclusion: Our preliminary experience with intraoperative MRI in patients with enhancing intraaxial tumors is encouraging. Combined use of neuronavigation and intraoperative MRI was able to increase the proportion of patients in whom complete removal of the enhancing parts of the tumor was achieved. Surgically induced enhancement requires careful analysis of the intraoperative MRI in order not to confuse it with residual tumor. (orig.) [de

Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

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Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

1995-01-01

Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

High-dose-rate versus low-dose-rate brachytherapy in the treatment of cervical cancer: analysis of tumor recurrence - the University of Wisconsin experience

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Petereit, Daniel G.; Sarkaria, Jann N.; Potter, David M.; Schink, Julian C.

1999-01-01

Purpose: To retrospectively compare the clinical outcome for cervical cancer patients treated with high-dose-rate (HDR) vs. low-dose-rate (LDR) brachytherapy. Methods and Materials: One hundred ninety-one LDR patients were treated from 1977 to 1988 and compared to 173 HDR patients treated from 1989 to 1996. Patients of similar stage and tumor volumes were treated with identical external beam fractionation schedules. Brachytherapy was given in either 1 or 2 LDR implants for the earlier patient cohort, and 5 HDR implants for the latter cohort. For both patient groups, Point A received a minimum total dose of 80 Gy. The linear-quadratic formula was used to calculate the LDR dose-equivalent contribution to Point A for the HDR treatments. The primary endpoints assessed were survival, pelvic control, relapse-free survival, and distant metastases. Endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards models. Results: The median follow-up was 65 months (2 to 208 months) in the LDR group and 22 months (1 to 85 months) in the HDR group. For all stages combined there was no difference in survival, pelvic control, relapse-free survival, or distant metastases between LDR and HDR patients. For Stage IB and II HDR patients, the pelvic control rates were 85% and 80% with survival rates of 86% and 65% at 3 years, respectively. In the LDR group, Stage IB and II patients had 91% and 78% pelvic control rates, with 82% and 58% survival rates at 3 years, respectively. No difference was seen in survival or pelvic control for bulky Stage I and II patients combined (> 5 cm). Pelvic control at 3 years was 44% (HDR) versus 75% (LDR) for Stage IIIB patients (p = 0.002). This difference in pelvic control was associated with a lower survival rate in the Stage IIIB HDR versus LDR population (33% versus 58%, p = 0.004). The only major difference, with regard to patient characteristics

Stereotactic radiosurgery for brainstem metastases: Survival, tumor control, and patient outcomes

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Hussain, Aamir; Brown, Paul D.; Stafford, Scott L.; Pollock, Bruce E.

2007-01-01

Purpose: Patients with brainstem metastases have limited treatment options. In this study, we reviewed outcomes after stereotactic radiosurgery (SRS) in the management of patients with brainstem metastases. Methods and Materials: Records were reviewed of 22 consecutive patients presenting with brainstem metastases who underwent SRS. The most frequent primary malignancy was the lung (n = 11), followed by breast (n = 3) and kidney (n = 2). Three patients (14%) also underwent whole-brain radiation therapy (WBRT). The median tumor volume was 0.9 mL (range, 0.1-3.3 mL); the median tumor margin dose was 16 Gy (range, 14-23 Gy). Results: Median survival time after SRS was 8.5 months. Although local tumor control was achieved in all patients with imaging follow-up (n = 19), 5 patients died from development and progression of new brain metastases. Two patients (9%) had symptom improvement after SRS, whereas 1 patient (5%) developed a new hemiparesis after SRS. Conclusions: Radiosurgery is safe and provides a high local tumor control rate for patients with small brainstem metastases. Patients with limited systemic disease and good performance status should be strongly considered for SRS

Stereotactic gamma radiosurgery of brain tumors

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Kobayashi, Tatsuya; Kida, Yoshihisa; Tanaka, Takayuki; Oyama, Hirofumi; Yoshida, Kazuo; Maesawa, Satoshi; Kai, Osamu; Nakamura, Mototoshi; Arahata, Masashige [Komaki City Hospital, Aichi (Japan)

1996-06-01

One thousand cases with various head and neck diseases have been treated by gamma radiosurgery at Komaki City Hospital since May 1991. Five hundred and sixty-eight out of 1,000 cases were neoplastic lesions which consisted of 173 cases of neurinoma, 108 of metastatic tumors, 103 of meningioma, 69 of gliomas, 27 of pituitary adenoma, 26 of craniopharyngioma, 13 of pineal tumors, 11 of chordoma, 6 of malignant lymphoma, 5 of hemangioblastoma and so on. The most effective result has been shown in metastatic brain tumors. The complete response (disappearance of the lesion) was obtained in more than 50% of the treated lesions, and the control rate of 85% was maintained for more than 12 months. Next effective results were shown in craniopharyngioma, malignant pineal tumors and malignant lymphoma. There was a group which showed moderate response but no tumor disappearance. Those were pituitary adenoma, acoustic neurinoma, meningioma and chordoma. Gliomas showed less response and even progression of tumor at relatively higher rate. It has been found that malignant gliomas showed difficult control of the tumor and progression rate of 70%, while benign gliomas showed the control rate of more than 90%. Besides intracranial lesions, malignant skull base tumors such as chordoma, naso-pharyngeal cancer, adenoid cystic cancer showed better response to gamma radiosurgery and higher control rate for longer period of time with high QOL compaired to conventional irradiation. (author)

Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

Science.gov (United States)

Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

Impact of adjuvant inhibition of vascular endothelial growth factor receptor tyrosine kinases on tumor growth delay and local tumor control after fractionated irradiation in human squamous cell carcinomas in nude mice

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Zips, Daniel; Hessel, Franziska; Krause, Mechthild; Schiefer, Yvonne; Hoinkis, Cordelia; Thames, Howard D.; Haberey, Martin; Baumann, Michael

2005-01-01

Purpose: Previous experiments have shown that adjuvant inhibition of the vascular endothelial growth factor receptor after fractionated irradiation prolonged tumor growth delay and may also improve local tumor control. To test the latter hypothesis, local tumor control experiments were performed. Methods and materials: Human FaDu and UT-SCC-14 squamous cell carcinomas were studied in nude mice. The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 (50 mg/kg body weight b.i.d.) was administered for 75 days after irradiation with 30 fractions within 6 weeks. Tumor growth time and tumor control dose 50% (TCD 50 ) were determined and compared to controls (carrier without PTK787/ZK222584). Results: Adjuvant administration of PTK787/ZK222584 significantly prolonged tumor growth time to reach 5 times the volume at start of drug treatment by an average of 11 days (95% confidence interval 0.06;22) in FaDu tumors and 29 days (0.6;58) in UT-SCC-14 tumors. In both tumor models, TCD 50 values were not statistically significantly different between the groups treated with PTK787/ZK222584 compared to controls. Conclusions: Long-term inhibition of angiogenesis after radiotherapy significantly reduced the growth rate of local recurrences but did not improve local tumor control. This indicates that recurrences after irradiation depend on vascular endothelial growth factor-driven angiogenesis, but surviving tumor cells retain their clonogenic potential during adjuvant antiangiogenic treatment with PTK787/ZK222584

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors

International Nuclear Information System (INIS)

Koizumi, Masahiko; Inoue, Takehiro; Yamazaki, Hideya; Teshima, Teruki; Tanaka, Eiichi; Yoshida, Ken; Imai, Atsushi; Shiomi, Hiroya; Kagawa, Kazufumi; Araki, Nobuto; Kuratsu, Shigeyuki; Uchida, Atsumasa; Inoue, Toshihiko

1999-01-01

Purpose: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. Methods and Materials: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/ 4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). Results: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. Conclusion: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases

Relation between the location of elements in the periodic table and tumor-uptake rate

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Ando, I; Hiraki, T; Hisada, K

1985-01-01

The bipositive ions and anions, with few exceptions, indicated a low tumor uptake rate. On the other hand, compounds of Hg, Au and Bi, which have a strong binding power to protein, showed a high tumor uptake rate. As Hg/sup 2 +/, Au/sup +/ and Bi/sup 3 +/ are soft acids according to the classification of Lewis acids, it was thought that these ions would bind strongly to soft bases (R-SH, R-S-) present in tumor tissue. For many hard acids such as /sup 85/Sr/sup 2 +/, /sup 67/Ga/sup 3 +/, /sup 181/Hf/sup 4 +/, and /sup 95/Nb/sup 5 +/, tumor uptake rates are shown as a function of ionic potentials of the metal ions. Considering the present data and previously reported results, it was presumed that hard acids of trivalence, quadrivalence and pentavalence would replace calcium in the calcium salts of hard bases. Ionic potentials of alkaline metals and Tl were small, but the tumor-uptake rate of these elements indicated various values. As Ge and Sb are bound by covalent bonds to chloride, GeCl/sub 4/ and SbCl/sub 3/ behaved differently from many metallic compounds in tumor tissue.

Relation between the location of elements in the periodic table and tumor-uptake rate.

Science.gov (United States)

Ando, A; Ando, I; Hiraki, T; Hisada, K

1985-01-01

The bipositive ions and anions, with few exceptions, indicated a low tumor uptake rate. On the other hand, compounds of Hg, Au and Bi, which have a strong binding power to protein, showed a high tumor uptake rate. As Hg2+, Au+ and Bi3+ are soft acids according to the classification of Lewis acids, it was thought that these ions would bind strongly to soft bases (R-SH, R-S-) present in tumor tissue. For many hard acids such as 85Sr2+, 67Ga3+, 181Hf4+, and 95Nb5+, tumor uptake rates are shown as a function of ionic potentials (valency/ionic radii) of the metal ions. Considering the present data and previously reported results, it was presumed that hard acids of trivalence, quadrivalence and pentavalence would replace calcium in the calcium salts of hard bases (calcium salts of acid mucopolysaccharides, etc.). Ionic potentials of alkaline metals and Tl were small, but the tumor-uptake rate of these elements indicated various values. As Ge and Sb are bound by covalent bonds to chloride, GeCl4 and SbCl3 behaved differently from many metallic compounds in tumor tissue.

Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Yeo, Seung-Gu [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan (Korea, Republic of); Kim, Dae Yong, E-mail: radiopiakim@hanmail.net [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Park, Ji Won; Oh, Jae Hwan; Kim, Sun Young; Chang, Hee Jin; Kim, Tae Hyun; Kim, Byung Chang; Sohn, Dae Kyung; Kim, Min Ju [Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of)

2012-02-01

Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints were disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.

Primary intracranial tumors among atomic bomb survivors and controls, Hiroshima and Nagasaki, 1961-75

International Nuclear Information System (INIS)

Seyama, Shinichi; Ishimaru, Toranosuke; Iijima, Soichi; Mori, Kazuo.

1980-02-01

An analysis was made of the relationship of radiation dose to the occurrence of primary intracranial tumors among atomic bomb survivors and nonexposed controls, Hiroshima and Nagasaki, in the fixed cohort of the Life Span Study (LSS) extended sample during the period 1961-75, or 16 to 30 years after the A-bombs. Based on various medical sources, 104 cases of primary intracranial tumors were identified among approximately 99,000 LSS extended sample members who were alive as of 1 January 1961. Of these 104 cases, 45 had manifested clinical signs of brain tumors, but, 59 cases were identified incidentally at postmortem examination. The distributions of morphologic type, age, and size of tumor were quite different for those primary intracranial tumors with and without a clinical sign of brain tumor. Glioma was the most frequent type of tumor with a clinical sign and meningioma was the most frequent type without. In relation to radiation dose the incidence rate of primary intracranial tumors with a clinical sign showed a significant excess risk for males in the high dose group who received 100 rad or more after adjustment for age at the time of the bomb (ATB). The standardized relative risk is around 5 in this group. The data also suggest that the crude relative risk of glioma is greater in the high dose group for younger ages ATB. However, there is no increased risk in females. Among the 5,012 autopsy subjects in the LSS extended sample during 1961-75, there is no relationship between radiation dose and the prevalence rate of primary intracranial tumors in those identified incidentally by autopsy. The relative risk of subclinical adenoma of the pituitary gland between high dose subjects and controls was also examined for a sample of 95 sex- and age-matched pairs using Hiroshima autopsy materials for 1961-74, but no relationship to dose was observed. (author)

Combination therapy with 1,3-bis(2-chloroethyl)-1-nitrosourea and low dose rate radiation in the 9L rat brain tumor and spheroid models: implications for brain tumor brachytherapy

International Nuclear Information System (INIS)

Gutin, P.H.; Bernstein, M.; Sano, Y.; Deen, D.F.

1984-01-01

The effects of combination treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and low dose rate radiation were studied in the 9L rat brain tumor in vivo model and the 9L multicellular tumor spheroid model. F-344 rats bearing intracerebral 9L gliosarcomas were implanted with removable 125 I sources. Minimal (peripheral) tumor doses of 6387 rad produced an increased life-span (ILS) of 28% over that of control rats implanted with dummy sources, BCNU alone (13.3 mg/kg) produced in an ILS of 67%, and combination treatment with BCNU and implanted 125 I sources produced an ILS of 167%. As measured by a colony-forming efficiency assay, the greatest cell kill in 9L spheroids occurred when BCNU was administered 24 hours before irradiation from a 137 Cs source at a low dose rate of 5 rad/minute. At a higher dose rate of 210 rad/minute, the time dependence of the effects of combination treatment was identical and therefore independent of dose rate

Tumor containing fragment number influences immunohistochemistry positive rate of HER2 in biopsy specimens of gastric cancer.

Science.gov (United States)

Xu, Chen; Liu, Yalan; Ge, Xiaowen; Jiang, Dongxian; Zhang, Ying; Ji, Yuan; Hou, Jun; Huang, Jie; Su, Jieakesu; Zeng, Haiying; Qin, Jing; Hou, Yingyong

2017-05-26

HER2 assessment in biopsy specimens of gastric cancer (GC) is challenging because of the intratumoral heterogeneity. False negative results may be get because of limited biopsy material. The aim of this study is to explore how tumor-containing fragment number and biopsy specimen number affect HER2 immunohistochemistry (IHC) positive rate. Eight hundred and ninety biopsy specimens and 459 paired resected specimens were collected. IHC staining of HER2 was performed. HER2 IHC positive (scored 3+) rate was compared based on tumor-containing fragment number, biopsy specimen number, average size and tumor tissue proportion of tumor-containing fragments. The positive predictability of biopsy specimens to resected specimens was analyzed based on tumor fragment number. HER2 IHC positive rates were 2.0, 3.5, 7.0, 13.2, 17.1, and 15.9% when tumor fragment numbers were 1, 2, 3, 4, 5 and 6 respectively. The rate rose with the increase of tumor fragment number (P = 0.004). ROC curve analysis showed that biopsy specimens exhibited positive predictability when tumor fragment number reached 3, but showed better performance when the number was ≥4 (P fragment number reached 4, no statistic differences were reached in either HER2 IHC positive rate or positive predictability with further increase of the number (P > 0.05). HER2 IHC positive rate was not associated with biopsy number (P = 0.127), average size of tumor fragments (P = 0.397), and tumor tissue proportion of tumor fragments (P = 0.825) directly. The number of tumor-containing fragments influences HER2 IHC positive (scored 3+) rate. Greater than or equal to 4 (≥4) tumor fragments give better results in the positive rate as well as positive predictability. We recommend the number of tumor containing fragments be described in the HER2 IHC pathology reports for clinical reference in endoscopic biopsy specimens of GC.

Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

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Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Chapman, Christopher [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of Michigan School of Medicine, Ann Arbor, MI (United States); Rao, Aarti [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Davis, School of Medicine, Davis, CA (United States); Shen, John [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Irvine, School of Medicine, Irvine, CA (United States); Quinlan-Davidson, Sean [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Filion, Edith J. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Departement de Medecine, Service de Radio-Oncologie, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Wakelee, Heather A.; Colevas, A. Dimitrios [Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); Whyte, Richard I. [Department of Cardiothoracic Surgery, Division of General Thoracic Surgery, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); and others

2012-09-01

Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume {>=}12 mL) received multifraction regimens with BED {>=}100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

Assessment of tumor control following definitive radiotherapy in carcinoma of the prostate: A continuing dilemma

International Nuclear Information System (INIS)

Pilepich, M.V.

1987-01-01

Evaluation of tumor response and tumor control after definitive radiotherapy is a relatively simple task in most malignancies arising at sites amenable to clinical examination (inspection and palpation). The rates of tumor regression following irradiation are quite variable. While some types of cancer regress completely during the radiotherapy course, some may take weeks or months to resolve. Occasionally, residual induration or a residual mass may persist for prolonged periods (many months), prompting the clinician to consider a biopsy for evaluation of the tumor status. In these circumstances histological examination may show necrotic tumor or residual fibrotic tissue. Finding viable-appearing tumor cells beyond the immediate postirradiation period (several weeks to a few months after completion of the radiotherapy course) is generally accepted as an equivalent of failure to eradicate the tumor. However, in a few types of cancer, presence of histologically identifiable and apparently viable tumor cells over protracted periods does not necessarily imply treatment failure

Tumor Hypoxia is Independent of Hemoglobin and Prognostic for Loco-regional Tumor Control after Primary Radiotherapy in Advanced Head and Neck Cancer

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Nordsmark, Marianne; Overgaard, Jens

2004-01-01

There is evidence that tumor hypoxia adversely affects loco-regional tumor control and survival in head and neck cancer. The aim of the current study was to compare pretreatment tumor oxygenation measured by Eppendorf pO2 electrodes with known prognostic factors in advanced head and neck tumors after definitive radiotherapy, and to evaluate the prognostic significance of these parameters on loco-regional tumor control. Sixty-seven patients, median age 56 years (22-82), all with primary stage III-IV squamous cell carcinoma were available for survival analysis. Tumor oxygenation was described as the fraction of pO2 values=2.5 mmHg (HP2.5) and the median tumor pO2. By regression analysis HP2.5 was independent of known prognostic factors including stage, pretreatment hemoglobin (Hb) and the largest tumor diameter at the site of pO2 measurement. By Kaplan-Meier analysis loco-regional tumor control at 5 years was in favor of less hypoxic tumors using either HP2.5 or median tumor pO2 as descriptors and stratifying by the median values. Also, Hb was prognostic of loco-regional tumor control at 5 years using the median value as cut off. HP2.5 as continuous parameter was highly significant for loco-regional tumor control in a multivariate analysis. In conclusion both HP2.5 and total Hb were prognostic for loco-regional tumor control, but HP2.5 as continuous variable was independently the strongest prognostic indicator for loco-regional tumor control after definitive primary radiotherapy in advanced head and neck tumors

Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

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Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy; Chapman, Christopher; Rao, Aarti; Shen, John; Quinlan-Davidson, Sean; Filion, Edith J.; Wakelee, Heather A.; Colevas, A. Dimitrios; Whyte, Richard I.

2012-01-01

Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18–25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50–60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

Tumor Volume Reduction Rate Measured by Magnetic Resonance Volumetry Correlated With Pathologic Tumor Response of Preoperative Chemoradiotherapy for Rectal Cancer

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Yeo, Seung-Gu; Kim, Dae Yong; Kim, Tae Hyun; Jung, Kyung Hae; Hong, Yong Sang; Chang, Hee Jin; Park, Ji Won; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong

2010-01-01

Purpose: To determine whether the tumor volume reduction rate (TVRR) measured using three-dimensional region-of-interest magnetic resonance volumetry correlates with the pathologic tumor response after preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods and Materials: The study included 405 patients with locally advanced rectal cancer (cT3-T4) who had undergone preoperative CRT and radical proctectomy. The tumor volume was measured using three-dimensional region-of-interest magnetic resonance volumetry before and after CRT but before surgery. We analyzed the correlation between the TVRR and the pathologic tumor response in terms of downstaging and tumor regression grade (TRG). Downstaging was defined as ypStage 0-I (ypT0-T2N0M0), and the TRG proposed by Dworak et al. was used. Results: The mean TVRR was 65.0% ± 22.3%. Downstaging and complete regression occurred in 167 (41.2%) and 58 (14.3%) patients, respectively. The TVRRs according to ypT classification (ypT0-T2 vs. ypT3-T4), ypN classification (ypN0 vs. ypN1-N2), downstaging (ypStage 0-I vs. ypStage II-III), good regression (TRG 3-4 vs. TRG 1-2), and complete regression (TRG 4 vs. TRG 1-3) were all significantly different (p 80%), the rates of ypT0-T2, ypN0, downstaging, and good regression were all significantly greater for patients with a TVRR of ≥60%, as was the complete regression rate for patients with a TVRR >80% (p <.05). Conclusion: The TVRR measured using three-dimensional region-of-interest magnetic resonance volumetry correlated significantly with the pathologic tumor response in terms of downstaging and TRG after preoperative CRT for locally advanced rectal cancer.

Ipsilateral Breast Tumor Relapse: Local Recurrence Versus New Primary Tumor and the Effect of Whole-Breast Radiotherapy on the Rate of New Primaries

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Gujral, Dorothy M.; Sumo, Georges; Owen, John R.; Ashton, Anita; Bliss, Judith M.; Haviland, Joanne; Yarnold, John R.

2011-01-01

Purpose: The justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses (IBTR) outside the index quadrant are mostly new primary (NP) tumors that develop despite radiotherapy. We tested the hypothesis that whole-breast radiotherapy (WBRT) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT. Methods and Materials: We retrospectively reviewed 1,410 women with breast cancer who were entered into a prospective randomized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses (IBTR) and contralateral breast cancer (CLBC). Cases of IBTR were classified into local recurrence (LR) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data. Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up. Results: At a median follow-up of 10.1 years, there were 150 documented cases of IBTR: 118 (79%) cases were definite or likely LR; 27 (18%) cases were definite or likely NP; and 5 (3%) cases could not be classified. There were 71 cases of CLBC. The crude proportion of definite-plus-likely NP was 1.9% (27/1,410) patients compared with 5% (71/1,410) CLBC patients. Cumulative incidence rates at 5, 10, and 15 years were 0.8%, 2.0%, and 3.5%, respectively, for definite-plus-likely NP and 2.4%, 5.8%, and 7.9%, respectively for CLBC, suggesting a difference in the rates of NP and CLBC. Conclusions: This analysis suggests that WBRT reduces the rate of ipsilateral NP tumors. The late presentation of NP has implications for the reporting of trials that are testing partial breast radiotherapy.

Intraoperative neuronavigation integrated high resolution 3D ultrasound for brainshift and tumor resection control

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Giovani A.

2015-06-01

Full Text Available INTRODUCTION: The link between the neurosurgeon’s knowledge and the scientific improvements made a dramatic change in the field expressed both in impressive drop in the mortality and morbidity rates that were operated in the beginning of the XXth century and in operating with high rates of success cases that were considered inoperable in the past. Neuronavigation systems have been used for many years on surgical orientation purposes especially for small, deep seated lesions where the use of neuronavigation is correlated with smaller corticotomies and with the extended use of transulcal approaches. The major problem of neuronavigation, the brainshift once the dura is opened can be solved either by integrated ultrasound or intraoperative MRI which is out of reach for many neurosurgical departments. METHOD: The procedure of neuronavigation and ultrasonic localization of the tumor is described starting with positioning the patient in the visual field of the neuronavigation integrated 3D ultrasonography system to the control of tumor resection by repeating the ultrasonographic scan in the end of the procedure. DISCUSSION: As demonstrated by many clinical trials on gliomas, the more tumor removed, the better long term control of tumor regrowth and the longer survival with a good quality of life. Of course, no matter how aggressive the surgery, no new deficits are acceptable in the modern era neurosurgery. There are many adjuvant methods for the neurosurgeon to achieve this maximal and safe tumor removal, including the 3T MRI combined with tractography and functional MRI, the intraoperative neuronavigation and neurophysiologic monitoring in both anesthetized and awake patients. The ultrasonography integrated in neuronavigaton comes as a welcomed addition to this adjuvants to help the surgeon achieve the set purpose. CONCLUSION: With the use of this real time imaging device, the common problem of brainshift encountered with the neuronavigation systems

Influence of postsurgical residual tumor volume on local control in radiotherapy for maxillary sinus cancer

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Kawashima, Mitsuhiko; Ogino, Takashi; Hayashi, Ryuichi; Ishikura, Satoshi; Nihei, Keiji; Ito, Yoshinori; Ikeda, Hiroshi; Ebihara, Satoshi [National Cancer Center, Kashiwa, Chiba (Japan). Hospital East; Itai, Yuji

2001-05-01

The aim was to study the influence of postsurgical gross residual tumor volume on local control of maxillary sinus cancer treated with radiotherapy combined with debulking surgery. Forty-three patients who underwent combined surgery and radiotherapy (50-72 Gy, median 60 Gy) for squamous cell carcinoma of the maxillary sinus were reviewed. Gross residual tumor volume (GRTV) after surgery was measured on computed tomograms obtained during the radiotherapy planning. Patients were classified according to GRTV as follows: group AA, GRTV=0 (microscopic residual, n=2); group A, GRTV <10 cm{sup 3} (n=24); group B, 10-40 cm{sup 3} (n=9); and group C, {>=}40 cm{sup 3} (n=8). The relationship between local control and GRTV was analyzed using univariate and multivariate analysis. The 2-year local control rate for all patients was 62%. The differences in local control rates between groups AA, A and B were not significant (P<0.05), but the rate was significantly lower in group C than in the other groups (69% at 2 years vs 31% at 1 year, P<0.001). Multivariate analysis showed that GRTV (P=0.002) and histological differentiation (poorly differentiated histology was favorable, P=0.035) were independent prognostic factors and that intraarterial chemotherapy and administered total dose were not. Local control in groups A and B significantly depended on the total dose of radiotherapy, with 2-year control rates of patients receiving 50 Gy (n=6) and {>=}60 Gy (n=27) of 17% vs 79%, respectively (P<0.001). Our data suggest that adequate, not complete, debulking associated with a total radiotherapy dose of {>=}60 Gy can provide satisfactory local control for patients with squamous cell carcinoma of the maxillary sinus. (author)

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

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Floyd, Scott R.; Buchholz, Thomas A.; Haffty, Bruce G.; Goldberg, Saveli; Niemierko, Andrzej; Raad, Rita Abi; Oswald, Mary J.; Sullivan, Timothy; Strom, Eric A.; Powell, Simon N.; Katz, Angela; Taghian, Alphonse G.

2006-01-01

Purpose: To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. Methods and Materials: Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. Results: With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p = 0.017) and in Cox proportional hazards analysis (p 0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. Conclusions: This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy

State-Dependent Impulsive Control Strategies for a Tumor-Immune Model

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Kwang Su Kim

2016-01-01

Full Text Available Controlling the number of tumor cells leads us to expect more efficient strategies for treatment of tumor. Towards this goal, a tumor-immune model with state-dependent impulsive treatments is established. This model may give an efficient treatment schedule to control tumor’s abnormal growth. By using the Poincaré map and analogue of Poincaré criterion, some conditions for the existence and stability of a positive order-1 periodic solution of this model are obtained. Moreover, we carry out numerical simulations to illustrate the feasibility of our main results and compare fixed-time impulsive treatment effects with state-dependent impulsive treatment effects. The results of our simulations say that, in determining optimal treatment timing, the model with state-dependent impulsive control is more efficient than that with fixed-time impulsive control.

Proton therapy for tumors of the skull base

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Munzenrider, J.E.; Liebsch, N.J. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

1999-06-01

Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

Proton therapy for tumors of the skull base

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Munzenrider, J.E.; Liebsch, N.J.

1999-01-01

Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

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Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd; Simpson, Joseph R.; Huang, Jiayi; Drzymala, Robert E.; Barani, Igor J.; Dowling, Joshua L.; Rich, Keith M.; Chicoine, Michael R.; Kim, Albert H.; Leuthardt, Eric C.; Robinson, Clifford G.

2014-01-01

Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective

Body weight considerations in the B6C3F1 mouse and the use of dietary control to standardize background tumor incidence in chronic bioassays

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Leakey, Julian E.A.; Seng, John E.; Allaben, William T.

2003-01-01

In B6C3F 1 mice, the rate of body growth influences susceptibility to liver neoplasia and large variations in body weight can complicate the interpretation of bioassay data. The relationship between body weight and liver tumor incidence was calculated for historical control populations of male and female ad libitum-fed mice (approx. 2750 and 2300 animals, respectively) and in populations of male and female mice which had been subjected to forced body weight reduction due to either dietary restriction or exposure to noncarcinogenic chemicals (approx. 1600 and 1700, respectively). Resulting tumor risk data were then used to construct idealized weight curves for male and female B6C3F 1 mice; these curves predict a terminal background liver tumor incidence of 15-20%. Use of dietary control to manipulate body growth of male B6C3F 1 mice to fit the idealized weight curve was evaluated in a 2-year bioassay of chloral hydrate. Cohorts of mice were successfully maintained at weights approximating their idealized target weights throughout the study. These mice exhibited less body weight variation than their ad libitum-fed counterparts (e.g., standard deviations of body weight were 1.4 and 3.4 g for respective control groups at 36 weeks). Historical control body weight and tumor risk data from the two male mouse populations were utilized to predict background liver tumor rates for each experimental group of the chloral hydrate study. The predicted background tumor rates closely matched the observed rates for both the dietary controlled and ad libitum-fed chloral hydrate control groups when each mouse was evaluated according to either its weekly food consumption or its weekly change in body weight

Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

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Ferrone Soldano

2007-06-01

Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

Definitive Radiotherapy for Ewing Tumors of Extremities and Pelvis: Long-Term Disease Control, Limb Function, and Treatment Toxicity

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Indelicato, Daniel J.; Keole, Sameer R.; Shahlaee, Amir H.; Shi Wenyin; Morris, Christopher G.; Marcus, Robert B.

2008-01-01

Purpose: More than 70% of Ewing tumors occur in the extremities and pelvis. This study identified factors influencing local control and functional outcomes after management with definitive radiotherapy (RT). Patients and Methods: A total of 75 patients with a localized Ewing tumor of the extremity or pelvis were treated with definitive RT at the University of Florida between 1970 and 2006 (lower extremity tumors in 30, pelvic tumors in 26, and upper extremity tumors in 19). RT was performed on a once-daily (40%) or twice-daily (60%) basis. The median dose was 55.2 Gy in 1.8-Gy daily fractions or 55.0 Gy in 1.2-Gy twice-daily fractions. The median observed follow-up was 4.7 years. Functional outcome was assessed using the Toronto Extremity Salvage Score. Results: The 10-year actuarial overall survival, cause-specific survival, freedom from relapse, and local control rate was 48%, 48%, 42%, and 71%, respectively. Of the 72 patients, 3 required salvage amputation. Inferior cause-specific survival was associated with larger tumors (81% for tumors 3 . Conclusions: Limb preservation was effectively achieved through definitive RT. Treating limited field sizes with hyperfractionated high-energy RT could minimize long-term complications and provides superior functional outcomes

Ascorbate availability affects tumor implantation-take rate and increases tumor rejection in Gulo–/– mice

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Campbell EJ

2016-04-01

Full Text Available Elizabeth J Campbell,1 Margreet CM Vissers,2 Gabi U Dachs1 1Mackenzie Cancer Research Group, 2Centre for Free Radical Research, Department of Pathology, University of Otago, Christchurch, New Zealand Abstract: In solid tumors, HIF1 upregulates the expression of hundreds of genes involved in cell survival, tumor growth, and adaptation to the hypoxic microenvironment. HIF1 stabilization and activity are suppressed by prolyl and asparagine hydroxylases, which require oxygen as a substrate and ascorbate as a cofactor. This has led us to hypothesize that intracellular ascorbate availability could modify the hypoxic HIF1 response and influence tumor growth. In this study, we investigated the effect of variable intracellular ascorbate levels on HIF1 induction in cancer cells in vitro, and on tumor-take rate and growth in the Gulo–/– mouse. These mice depend on dietary ascorbate, and were supplemented with 3,300 mg/L, 330 mg/L, or 33 mg/L ascorbate in their drinking water, resulting in saturating, medium, or low plasma and tissue ascorbate levels, respectively. In Lewis lung carcinoma cells (LL/2 in culture, optimal ascorbate supplementation reduced HIF1 accumulation under physiological but not pathological hypoxia. LL/2, B16-F10 melanoma, or CMT-93 colorectal cancer cells were implanted subcutaneously into Gulo–/– mice at a range of cell inocula. Establishment of B16-F10 tumors in mice supplemented with 3,300 mg/L ascorbate required an increased number of cancer cells to initiate tumor growth compared with the number of cells required in mice on suboptimal ascorbate intake. Elevated ascorbate intake was also associated with decreased tumor ascorbate levels and a reduction in HIF1α expression and transcriptional activity. Following initial growth, all CMT-93 tumors regressed spontaneously, but mice supplemented with 33 mg/L ascorbate had lower plasma ascorbate levels and grew larger tumors than optimally supplemented mice. The data from this

Influence of dose distribution homogeneity on the tumor control probability in heavy-ion radiotherapy

International Nuclear Information System (INIS)

Wen Xiaoqiong; Li Qiang; Zhou Guangming; Li Wenjian; Wei Zengquan

2001-01-01

In order to estimate the influence of the un-uniform dose distribution on the clinical treatment result, the Influence of dose distribution homogeneity on the tumor control probability was investigated. Basing on the formula deduced previously for survival fraction of cells irradiated by the un-uniform heavy-ion irradiation field and the theory of tumor control probability, the tumor control probability was calculated for a tumor mode exposed to different dose distribution homogeneity. The results show that the tumor control probability responding to the same total dose will decrease if the dose distribution homogeneity gets worse. In clinical treatment, the dose distribution homogeneity should be better than 95%

Regression and local control rates after radiotherapy for jugulotympanic paragangliomas: Systematic review and meta-analysis

International Nuclear Information System (INIS)

Hulsteijn, Leonie T. van; Corssmit, Eleonora P.M.; Coremans, Ida E.M.; Smit, Johannes W.A.; Jansen, Jeroen C.; Dekkers, Olaf M.

2013-01-01

The primary treatment goal of radiotherapy for paragangliomas of the head and neck region (HNPGLs) is local control of the tumor, i.e. stabilization of tumor volume. Interestingly, regression of tumor volume has also been reported. Up to the present, no meta-analysis has been performed giving an overview of regression rates after radiotherapy in HNPGLs. The main objective was to perform a systematic review and meta-analysis to assess regression of tumor volume in HNPGL-patients after radiotherapy. A second outcome was local tumor control. Design of the study is systematic review and meta-analysis. PubMed, EMBASE, Web of Science, COCHRANE and Academic Search Premier and references of key articles were searched in March 2012 to identify potentially relevant studies. Considering the indolent course of HNPGLs, only studies with ⩾12 months follow-up were eligible. Main outcomes were the pooled proportions of regression and local control after radiotherapy as initial, combined (i.e. directly post-operatively or post-embolization) or salvage treatment (i.e. after initial treatment has failed) for HNPGLs. A meta-analysis was performed with an exact likelihood approach using a logistic regression with a random effect at the study level. Pooled proportions with 95% confidence intervals (CI) were reported. Fifteen studies were included, concerning a total of 283 jugulotympanic HNPGLs in 276 patients. Pooled regression proportions for initial, combined and salvage treatment were respectively 21%, 33% and 52% in radiosurgery studies and 4%, 0% and 64% in external beam radiotherapy studies. Pooled local control proportions for radiotherapy as initial, combined and salvage treatment ranged from 79% to 100%. Radiotherapy for jugulotympanic paragangliomas results in excellent local tumor control and therefore is a valuable treatment for these types of tumors. The effects of radiotherapy on regression of tumor volume remain ambiguous, although the data suggest that regression can

Influence of radon-daughter exposure rate and uranium ore dust concentration on occurrence of lung tumors

International Nuclear Information System (INIS)

Cross, F.T.; Palmer, R.F.; Busch, R.H.

1980-01-01

Groups of male SPF Wistar rats were exposed concurrently to several levels of radon daughters and uranium ore dust to study the effect of these variables on pulmonary disease states. Clinical pathology data at 1 yr postexposure indicate no significant differences among exposed animals when compared with controls. Preliminary histopathologic data suggest a trend toward increasing lung tumor risk as the exposure rate is decreased (constant total dose), but the differences are not statistically significant at the 0.05 level. A similar trend occurs with decrease in ore dust concentration (except for the 2560-WLM exposure group), but these differences are also not significant at the 0.05 level. The tumor risk is significantly (0.05 level) increased as the exposure level increases from approximately 320 and 640 WLM to 2560 WLM at the high ore dust concentration

Singlet oxygen explicit dosimetry to predict long-term local tumor control for BPD-mediated photodynamic therapy

Science.gov (United States)

Kim, Michele M.; Penjweini, Rozhin; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

Photodynamic therapy (PDT) is a well-established treatment modality for cancer and other malignant diseases; however, quantities such as light fluence, photosensitizer photobleaching rate, and PDT dose do not fully account for all of the dynamic interactions between the key components involved. In particular, fluence rate (Φ) effects are not accounted for, which has a large effect on the oxygen consumption rate. In this preclinical study, reacted singlet oxygen [1O2]rx was investigated as a dosimetric quantity for PDT outcome. The ability of [1O2]rx to predict the long-term local tumor control rate (LCR) for BPD-mediated PDT was examined. Mice bearing radioactivelyinduced fibrosarcoma (RIF) tumors were treated with different in-air fluences (250, 300, and 350 J/cm2) and in-air ϕ (75, 100, and150 mW/cm2) with a BPD dose of 1 mg/kg and a drug-light interval of 3 hours. Treatment was delivered with a collimated laser beam of 1 cm diameter at 690 nm. Explicit dosimetry of initial tissue oxygen concentration, tissue optical properties, and BPD concentration was used to calculate [1O2]rx. Φ was calculated for the treatment volume based on Monte-Carlo simulations and measured tissue optical properties. Kaplan-Meier analyses for LCR were done for an endpoint of tumor volume defined as the product of the timeintegral of photosensitizer concentration and Φ at a 3 mm tumor depth. Preliminary studies show that [1O2]rx better correlates with LCR and is an effective dosimetric quantity that can predict treatment outcome.

An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

Science.gov (United States)

El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

2015-01-01

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates

International Nuclear Information System (INIS)

Estrela-Lima, Alessandra; Araújo, Márcio SS; Costa-Neto, João M; Teixeira-Carvalho, Andréa; Barrouin-Melo, Stella M; Cardoso, Sergio V; Martins-Filho, Olindo A; Serakides, Rogéria; Cassali, Geovanni D

2010-01-01

The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas. Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry. Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4 + (≥ 66.7%) or CD8 + T-cells (<33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity ≥ 600 (P = 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (P < 0.05). The relative percentage of CD4 + T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (P < 0.05) while the proportion of CD8 + T-cells was higher in MC-BMT without

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

DEFF Research Database (Denmark)

Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

2010-01-01

as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

Diagnostic of flow rate of the tumors of the boobs at increment of the blood pressure

International Nuclear Information System (INIS)

Pohlodek, K.; Sohn, Ch.

1998-01-01

54 patients with ultrasonography evident tumors of the mammary glands were examined by angiography on flow rate of the blood in the tumor (14 patients with benign tumor and 40 patients with carcinoma at increment of the blood pressure. At evaluating of the findings 4 characteristic curves were obtained: first type was typical for malignant tumors; second type was characteristic for benign findings and third and fourth types were non-specific. (authors)

Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment.

Science.gov (United States)

Kirkpatrick, Nathaniel D; Chung, Euiheon; Cook, Daniel C; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L; Padera, Timothy P; Fukumura, Dai; Jain, Rakesh K

2012-01-01

The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion and metastasis of tumor cells, the dynamics of immune cell trafficking to and within tumors, and gene expression in tumors. However, traditional multiphoton microscopy suffers from inherently slow imaging rates-only a few frames per second, thus unable to capture more rapid events such as blood flow, lymphatic flow, and cell movement within vessels. Here, we report the development and implementation of a video-rate multiphoton microscope (VR-MPLSM) based on resonant galvanometer mirror scanning that is capable of recording at 30 frames per second and acquiring intravital multispectral images. We show that the design of the system can be readily implemented and is adaptable to various experimental models. As examples, we demonstrate the utility of the system to directly measure flow within tumors, capture metastatic cancer cells moving within the brain vasculature and cells in lymphatic vessels, and image acute responses to changes in a vascular network. VR-MPLSM thus has the potential to further advance intravital imaging and provide new insight into the biology of the tumor microenvironment.

Singlet oxygen explicit dosimetry to predict long-term local tumor control for Photofrin-mediated photodynamic therapy

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Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

Although photodynamic therapy (PDT) is an established modality for the treatment of cancer, current dosimetric quantities do not account for the variations in PDT oxygen consumption for different fluence rates (φ). In this study we examine the efficacy of reacted singlet oxygen concentration ([1O2]rx) to predict long-term local control rate (LCR) for Photofrin-mediated PDT. Radiation-induced fibrosarcoma (RIF) tumors in the right shoulders of female C3H mice are treated with different in-air fluences of 225-540 J/cm2 and in-air fluence rate (φair) of 50 and 75 mW/cm2 at 5 mg/kg Photofrin and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 630 nm wavelength. [1O2]rx is calculated by using a macroscopic model based on explicit dosimetry of Photofrin concentration, tissue optical properties, tissue oxygenation and blood flow changes during PDT. The tumor volume of each mouse is tracked for 90 days after PDT and Kaplan-Meier analyses for LCR are performed based on a tumor volume defined as a temporal integral of photosensitizer concentration and Φ at a 3 mm tumor depth. φ is calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. Our preliminary studies show that [1O2]rx is the best dosimetric quantity that can predict tumor response and correlate with LCR. Moreover, [1O2]rx calculated using the blood flow changes was in agreement with [1O2]rx calculated based on the actual tissue oxygenation.

Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

Directory of Open Access Journals (Sweden)

Jianqing Pan

Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose

International Nuclear Information System (INIS)

Teo, Peter Man Lung; Leung, Sing Fai; Lee, Wai Yee; Zee, Benny

2000-01-01

Purpose: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). Methods and Materials: All T1 and T2 (nasal infiltration) NPC treated with a curative intent from 1984 to 1996 were analyzed (n = 509). One hundred sixty-three patients were given ICT after radical external radiotherapy (ERT) (Group A). They were compared with 346 patients treated by ERT alone (Group B). The ERT delivered the tumoricidal dose (uncorrected BED-10 ≥75 Gy) to the primary tumor and did not differ between the two groups in technique or dosage. The ICT delivered a dose of 18-24 Gy in 3 fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. ICT was used to treat local persistence diagnosed at 4-6 weeks after ERT (n = 101) or as an adjuvant for the complete responders to ERT (n = 62). Results: The two groups did not differ in patients' age or sex, rate of distant metastasis, rate of regional failure, overall survival, or the follow-up duration. However, Group A had significantly more T2 lesions and Group B had significantly more advanced N-stages. Local failure was significantly less (crude rates 6.75% vs. 13.0%; 5-year actuarial rates 5.40% vs. 10.3%) and the disease-specific mortality was significantly lower (crude rates 14.1 % vs. 21.7%; 5-year actuarial rates 11.9% vs. 16.4%) in Group A compared to Group B. Multivariate analysis showed that the ICT was the only significant prognostic factor predictive for fewer local failures (Cox regression p = 0.0328, risk ratio = 0.49, 95% confidence interval (95% CI) = 0.256-0.957). However, when ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumor repopulation during the period of radiotherapy became significant in predicting ultimate local failure rate. The two groups were comparable in the incidence rates of each individual chronic radiation complication and the actuarial cumulative rate of

Therapeutic profile of single-fraction radiosurgery of vestibular schwannoma: unrelated malignancy predicts tumor control

Science.gov (United States)

Wowra, Berndt; Muacevic, Alexander; Fürweger, Christoph; Schichor, Christian; Tonn, Jörg-Christian

2012-01-01

Radiosurgery has become an accepted treatment option for vestibular schwannomas. Nevertheless, predictors of tumor control and treatment toxicity in current radiosurgery of vestibular schwannomas are not well understood. To generate new information on predictors of tumor control and cranial nerve toxicity of single-fraction radiosurgery of vestibular schwannomas, we conducted a single-institution long-term observational study of radiosurgery for sporadic vestibular schwannomas. Minimum follow-up was 3 years. Investigated as potential predictors of tumor control and cranial nerve toxicity were treatment technology; tumor resection preceding radiosurgery; tumor size; gender; patient age; history of cancer, vascular disease, or metabolic disease; tumor volume; radiosurgical prescription dose; and isodose line. Three hundred eighty-six patients met inclusion criteria. Treatment failure was observed in 27 patients. History of unrelated cancer (strongest predictor) and prescription dose significantly predicted tumor control. The cumulative incidence of treatment failure was 30% after 6.5 years in patients with unrelated malignancy and 10% after ≥15 years in patients without such cancer (P making in ambiguous cases. PMID:22561798

Mir-513a-3p contributes to the controlling of cellular migration processes in the A549 lung tumor cells by modulating integrin β-8 expression.

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da Silveira, Marina Bonfogo; Lima, Kelvin Furtado; da Silva, Andrea Renata; Dos Santos, Robson Augusto Souza; Moraes, Karen C M

2017-12-04

Lung tumors are a frequent type of cancer in humans and a leading cause of death, and the late diagnostic contributes to high mortality rates. New therapeutic strategies are needed, and the heptapeptide angiotensin-(1-7) [ang-(1-7)] demonstrated the ability to control cancer growth rates and migration in vitro and in vivo. However, the possible use of the heptapeptide in clinical trials demands deeper analyses to elucidate molecular mechanisms of its effect in the target cells. In this study, we investigated relevant elements that control pro-inflammatory environment and cellular migration, focusing in the post-transcription mechanism using lung tumor cell line. In our cellular model, the microRNA-513a-3p was identified as a novel element targeting ITG-β8, thereby controlling the protein level and its molecular function in the controlling of migration and pro-inflammatory environment. These findings provide useful information for future studies, using miR-513a-3p as an innovative molecular tool to control lung tumor cell migration, which will support more effective clinical treatment of the patients with the widely used chemotherapeutic agents, increasing survival rates.

Linear-quadratic model predictions for tumor control probability

International Nuclear Information System (INIS)

Yaes, R.J.

1987-01-01

Sigmoid dose-response curves for tumor control are calculated from the linear-quadratic model parameters α and Β, obtained from human epidermoid carcinoma cell lines, and are much steeper than the clinical dose-response curves for head and neck cancers. One possible explanation is the presence of small radiation-resistant clones arising from mutations in an initially homogeneous tumor. Using the mutation theory of Delbruck and Luria and of Goldie and Coldman, the authors discuss the implications of such radiation-resistant clones for clinical radiation therapy

Radiofrequency ablation of pulmonary tumors near the diaphragm.

Science.gov (United States)

Iguchi, T; Hiraki, T; Gobara, H; Fujiwara, H; Sakurai, J; Matsui, Y; Mitsuhashi, T; Toyooka, S; Kanazawa, S

To retrospectively evaluate the feasibility, safety, and efficacy of radiofrequency ablation (RFA) of lung tumors located near the diaphragm. A total of 26 patients (15 men, 11 women; mean age, 61.5 years±13.0 [SD]) with a total of 29 lung tumors near the diaphragm (i.e., distance<10mm) were included. Mean tumor diameter was 11.0mm±5.3 (SD) (range, 2-23mm). Efficacy of RFA, number of adverse events and number of adverse events with a grade≥3, based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, were compared between patients with lung tumors near the diaphragm and a control group of patients with more distally located lung tumors (i.e., distance≥10mm). RFA was technically feasible for all tumors near the diaphragm. Four grade 3 adverse events (1 pneumothorax requiring pleurodesis and 3 phrenic nerve injuries) were observed. No grade≥4 adverse events were reported. The median follow-up period for tumors near the diaphragm was 18.3 months. Local progression was observed 3.3 months after RFA in 1 tumor. The technique efficacy rates were 96.2% at 1 year and 96.2% at 2 years and were not different, from those observed in control subjects (186 tumors; P=0.839). Shoulder pain (P<0.001) and grade 1 pleural effusion (P<0.001) were more frequently observed in patients with lung tumor near the diaphragm. The rates of grade≥3 adverse events did not significantly differ between tumors near the diaphragm (4/26 sessions) and the controls (7/133 sessions) (P=0.083). RFA is a feasible and effective therapeutic option for lung tumors located near the diaphragm. However, it conveys a higher rate of shoulder pain and asymptomatic pleural effusion by comparison with more distant lung tumors. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Enhanced tumor imaging with pokeweed mitogen

International Nuclear Information System (INIS)

Bitner, D.M.; Mann, P.L.; D'Souza, P.; Wenk, R.; Baughman, D.G.; Quesada, S.M.; Purvis, R.; Born, J.L.; Matwiyoff, N.A.; Eshima, D.

1993-01-01

Traditional tumor imaging with biotracer techniques relies solely on the target specificity of the biomolecule. We hypothesize that specific imaging is possible by altering the rate of tissue clearance of any given radiotracer. Pokeweed mitogen (PWM) as a biomodulator, represents a class of molecules which regulate cellular differentiation and cell-cell interactions and, as part of these mechanisms alter tissue clearance rates. Utilizing the B-16/C57BL/6 model, 7 days post-transplantation, 10 animals were imaged following an i.v. injection of 1-2 mCi 99m Tc-PWM in order to visualize the tumors and determine the optimal imaging kinetics. A specific tumor image is achieved between 120 and 240 min post-injection. In addition, tumor imaging studies using a non-tumor-specific biomolecule were conducted by injecting 19 animals i.v. with 1-2 mCi of 99m Tc-human serum albumin (HSA). Twelve of these animals were given 10 μg of PWM i.p. at various intervals prior to the 99m Tc-HAS administration. Imaging and biodistribution studies were performed at various intervals up to 2 h post- 99m Tc-HSA injection. A 32-59% increase in the tumor-to-muscle ratio was observed in the PWM-treated animals relative to the non-treated controls. To further investigate the PWM-induced tissue clearance alteration hypothesis, tissue clearance studies using 99m Tc-diethylenetriaminepentaacetic acid (DTPA) were conducted in non-tumor bearing ICR mice and the B-16/C57BL/6 tumor bearing animals. 99m Tc-DTPA normal tissue clearance rates were significantly increased in the PWM treated animals relative to the non-treated controls. (author)

TU-CD-304-06: Using FFF Beams Improves Tumor Control in Radiotherapy of Lung Cancers

Energy Technology Data Exchange (ETDEWEB)

Vassiliev, O [Mary Bird Perkins Cancer Center, Baton Rouge, LA (United States); Wang, H [UT MD Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: Electron disequilibrium at the lung-tumor interface results in an under-dosage of tumor regions close to its surface. This under-dosage is known to be significant and can compromise tumor control. Previous studies have shown that in FFF beams, disequilibrium effects are less pronounced, which is manifested in an increased skin dose. In this study we investigate the improvement in tumor dose coverage that can be achieved with FFF beams. The significance of this improvement is evaluated by comparing tumor control probabilities of FFF beams and conventional flattened beams. Methods: The dosimetric coverage was investigated in a virtual phantom representing the chest wall, lung tissue and the tumor. A range of tumor sizes was investigated, and two tumor locations – central and adjacent to the chest wall. Calculations were performed with BEAMnrc Monte Carlo code. Parallel-opposed and multiple coplanar 6-MV beams were simulated. The tumor control probabilities were calculated using the logistic model with parameters derived from clinical data for non-small lung cancer patients. Results: FFF beams were not entirely immune to disequilibrium effects. They nevertheless consistently delivered more uniform dose distribution throughout the volume of the tumor, and eliminated up to ∼15% of under-dosage in the most affected by disequilibrium 1-mm thick surface region of the tumor. A voxel-by-voxel comparison of tumor control probabilities between FFF and conventional flattened beams showed an advantage of FFF beams that, depending on the set up, was from a few to ∼9 percent. Conclusion: A modest improvement in tumor control probability on the order of a few percent can be achieved by replacing conventional flattened beams with FFF beams. However, given the large number of lung cancer patients undergoing radiotherapy, these few percent can potentially prevent local tumor recurrence for a significant number of patients.

Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates.

Science.gov (United States)

Yamashita, Hideomi; Haga, Akihiro; Takahashi, Wataru; Takenaka, Ryousuke; Imae, Toshikazu; Takenaka, Shigeharu; Nakagawa, Keiichi

2014-11-11

The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. Among the 67 patients, the median age was 73 years (range, 59-95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40-1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p =0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p =0.12). Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications.

Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates

International Nuclear Information System (INIS)

Yamashita, Hideomi; Haga, Akihiro; Takahashi, Wataru; Takenaka, Ryousuke; Imae, Toshikazu; Takenaka, Shigeharu; Nakagawa, Keiichi

2014-01-01

The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. Among the 67 patients, the median age was 73 years (range, 59–95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40–1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p = 0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p = 0.12). Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications

Influence of Cell-Cell Interactions on the Population Growth Rate in a Tumor

Science.gov (United States)

Chen, Yong

2017-12-01

The understanding of the macroscopic phenomenological models of the population growth at a microscopic level is important to predict the population behaviors emerged from the interactions between the individuals. In this work, we consider the influence of the population growth rate R on the cell-cell interaction in a tumor system and show that, in most cases especially small proliferative probabilities, the regulative role of the interaction will be strengthened with the decline of the intrinsic proliferative probabilities. For the high replication rates of an individual and the cooperative interactions, the proliferative probability almost has no effect. We compute the dependences of R on the interactions between the cells under the approximation of the nearest neighbor in the rim of an avascular tumor. Our results are helpful to qualitatively understand the influence of the interactions between the individuals on the growth rate in population systems. Supported by the National Natural Science Foundation of China under Grant Nos. 11675008 and 21434001

Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer.

Science.gov (United States)

Vanderlaan, Paul A; Yamaguchi, Norihiro; Folch, Erik; Boucher, David H; Kent, Michael S; Gangadharan, Sidharta P; Majid, Adnan; Goldstein, Michael A; Huberman, Mark S; Kocher, Olivier N; Costa, Daniel B

2014-04-01

Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

International Nuclear Information System (INIS)

Helbig, Linda; Koi, Lydia; Brüchner, Kerstin; Gurtner, Kristin; Hess-Stumpp, Holger; Unterschemmann, Kerstin; Pruschy, Martin

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD 50 ) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P 50 , with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD 50 . Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of radiation response. Whether this mechanism contributes to the improved outcome of fractionated chemoradiation therapy warrants further investigation

Comparison of Survival Rates, Tumor Stages, and Localization in between Obese and Nonobese Patients with Gastric Cancer

Directory of Open Access Journals (Sweden)

Hakan Kocoglu

2016-01-01

Full Text Available Purpose. In this study we tried to determine the association between body-mass index (BMI, survival rate, and the stage of tumor at the time of diagnosis in patients with gastric cancer. Methods. A total of 270 gastric cancer patients’ hospital records were retrospectively evaluated. Patients were grouped according to their BMI at the time of tumor diagnosis. Tumor stages at admission were compared according to their BMI values. Results. There were no differences in OS among BMI subgroups (p=0.230. The percent of patients with stage III tumor was significantly higher in nonobese while the percent of stage IV tumor was surprisingly higher in obese patients (p was 0.011 and 0.004, resp.. Percent of patients who did not have any surgical intervention was significantly lower in overweight and obese patients than normal and/or underweight patients. Conclusions. At the time of diagnosis, obese patients had significantly higher percent of stage IV tumor than nonobese patients. Despite of that, there were no differences in survival rates among BMI subgroups. Our study results are consistent with “obesity paradox” in gastric cancer patients. We also did not find any relationship between BMI and localization of gastric tumor.

Tumor control and normal tissue toxicity: The two faces of radiotherapy

NARCIS (Netherlands)

van Oorschot, B.

2016-01-01

This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

Rate Control Efficacy in Permanent Atrial Fibrillation : Successful and Failed Strict Rate Control Against a Background of Lenient Rate Control

NARCIS (Netherlands)

Groenveld, Hessel F.; Tijssen, Jan G. P.; Crijns, Harry J. G. M.; Van den Berg, Maarten P.; Hillege, Hans L.; Alings, Marco; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

2013-01-01

Objectives This study sought to investigate differences in outcome between patients treated with successful strict, failed strict, and lenient rate control. Background The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation) study showed no difference in outcome between lenient and

Four-dimensional dose distributions of step-and-shoot IMRT delivered with real-time tumor tracking for patients with irregular breathing: Constant dose rate vs dose rate regulation

International Nuclear Information System (INIS)

Yang Xiaocheng; Han-Oh, Sarah; Gui Minzhi; Niu Ying; Yu, Cedric X.; Yi Byongyong

2012-01-01

Purpose: Dose-rate-regulated tracking (DRRT) is a tumor tracking strategy that programs the MLC to track the tumor under regular breathing and adapts to breathing irregularities during delivery using dose rate regulation. Constant-dose-rate tracking (CDRT) is a strategy that dynamically repositions the beam to account for intrafractional 3D target motion according to real-time information of target location obtained from an independent position monitoring system. The purpose of this study is to illustrate the differences in the effectiveness and delivery accuracy between these two tracking methods in the presence of breathing irregularities. Methods: Step-and-shoot IMRT plans optimized at a reference phase were extended to remaining phases to generate 10-phased 4D-IMRT plans using segment aperture morphing (SAM) algorithm, where both tumor displacement and deformation were considered. A SAM-based 4D plan has been demonstrated to provide better plan quality than plans not considering target deformation. However, delivering such a plan requires preprogramming of the MLC aperture sequence. Deliveries of the 4D plans using DRRT and CDRT tracking approaches were simulated assuming the breathing period is either shorter or longer than the planning day, for 4 IMRT cases: two lung and two pancreatic cases with maximum GTV centroid motion greater than 1 cm were selected. In DRRT, dose rate was regulated to speed up or slow down delivery as needed such that each planned segment is delivered at the planned breathing phase. In CDRT, MLC is separately controlled to follow the tumor motion, but dose rate was kept constant. In addition to breathing period change, effect of breathing amplitude variation on target and critical tissue dose distribution is also evaluated. Results: Delivery of preprogrammed 4D plans by the CDRT method resulted in an average of 5% increase in target dose and noticeable increase in organs at risk (OAR) dose when patient breathing is either 10% faster or

Solitary plasmacytoma treated with radiotherapy: Impact of tumor size on outcome

International Nuclear Information System (INIS)

Tsang, Richard W.; Gospodarowicz, Mary K.; Pintilie, Melania; Bezjak, Andrea; Wells, Woodrow; Hodgson, David C.; Stewart, A. Keith

2001-01-01

Purpose: Solitary plasmacytoma (SP) is a rare presentation of plasma cell neoplasms. In contrast to multiple myeloma, long-term disease-free survival and cure is possible following local radiotherapy (RT), particularly for soft tissue presentations. In this study, we attempt to identify factors that predict for local failure, progression to multiple myeloma, and disease-free survival (DFS) in patients mainly managed with local RT. Methods and Materials: We identified 46 patients referred to the Princess Margaret Hospital between 1982 and 1993. The median age was 63 years (range 35-95), with a male:female ratio of 1.9:1. All patients had biopsy-proven SP (osseous: 32, soft tissue: 14). M-protein was abnormal in 19 patients (41%). All patients were treated with local RT (median dose 35 Gy), with 5 patients (11%) also receiving chemotherapy. Maximum tumor size pre-RT ranged from 0 to 18 cm (median 2.5). Results: The 8-year overall survival, DFS, and myeloma-free rates were 65%, 44%, and 50%, respectively. The local control rate was 83%. Factors predictive of progression to myeloma (and poorer DFS) included bone presentation and older age. However, these two factors did not influence local control, which was affected by tumor size. All tumors < 5 cm in bulk (34 patients) were controlled by RT. Anatomic location did not predict outcome; however, 3 of the 5 tumors arising in paranasal sinuses did not achieve local control. Lower RT dose (≤35 Gy) was not associated with a higher risk of local failure. Conclusion: Solitary plasmacytomas are effectively treated with moderate-dose RT, although osseous tumors have a high rate of recurrence as systemic myeloma. Large tumor bulk locally (≥5 cm) predicts for local failure. Combined chemotherapy and RT should be investigated in these high-risk patients to increase the local control rate and the cure rate

Anti-tumor effect of adenovirus-mediated suicide gene therapy under control of tumor-specific and radio-inducible chimeric promoter in combination with γ-ray irradiation in vivo

International Nuclear Information System (INIS)

Sun Wenjie; Yu Haijun; Xiongjie; Xu Yu; Liao Zhengkai; Zhou Fuxiang; Xie Conghua; Zhou Yunfeng

2011-01-01

Objective: To detect the selective inhibitory effects of irradiation plus adenovirus-mediated horseradish peroxidase (HRP)/indole-3-acetic acid (IAA) suicide gene system using tumor-specific and radio-inducible chimeric promoter on human hepatocellular carcinoma subcutaneously xenografted in nude mouse. Methods: Recombinant replicated-deficient adenovirus vector containing HRP gene and chimeric human telomerase reverse transcriptase (hTERT) promoter carrying 6 radio-inducible CArG elements was constructed. A human subcutaneous transplanting hepatocellular carcinoma (MHCC97 cell line) model was treated with γ-ray irradiation plus intra-tumor injections of adenoviral vector and intra-peritoneal injections of prodrug IAA. The change of tumor volume and tumor growth inhibiting rate, the survival time of nude mice, as well as histopathology of xenograft tumor and normal tissues were evaluated. Results: Thirty one days after the treatment, the relative tumor volumes in the negative, adenovirus therapy, irradiation, and combination groups were 49.23±4.55, 27.71±7.74, 28.53±10.48 and 11.58±3.23, respectively.There was a significantly statistical difference among them (F=16.288, P<0.01).The inhibition effect in the combination group was strongest as compared with that in other groups, and its inhibition ratio was 76.5%. The survival period extended to 43 d in the combination group, which showed a significantly difference with that in the control group (χ 2 =18.307, P<0.01). The area of tumors necrosis in the combination group was larger than that in the other groups, and the normal tissues showed no treatment-related toxic effect in all groups. However, multiple hepatocellular carcinoma metastases were observed in the liver in the control group, there were a few metastases in the monotherapy groups and no metastasis in the combination group. Conclusions: Adenovirus-mediated suicide gene therapy plus radiotherapy dramatically could inhibit tumor growth and prolong

Progress in radiotherapy of diencephalohypophyseal tumor

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Takakura, Kintomo; Kubo, Osami [Tokyo Women`s Medical Coll. (Japan). Neurological Inst.

1997-12-01

The patients with hypophyseal adenoma (36 patients) were treated with peripheral irradiation (between 10 and 35 Gy) using gamma unit. The results are shown as follows: GH producing hypophyseal tumor (8 patients); tumor volume did not reduce rapidly. Growth hormone level fell, but it took more than 12 months to recover to normal level. PRL producing hypophyseal tumor (5 patients); five intractable patients were irradiated. Tumor contraction was not obvious, but the increase of tumor size was restrained. ACTH producing hypophyseal tumor (4 patients); ACTH level dropped gradually, and tumor size was reduced. However, there were 2 intractable cases. Non-functional hypophyseal tumor (19 patients); local tumor control rate was 100% in all patients and visual field was recovered. The size of craniopharyngioma was obviously reduced with peripheral irradiation of 10 Gy dimension about 10 months later. (K.H.)

Relationship among reaction rate, release rate and efficiency of nanomachine-based targeted drug delivery.

Science.gov (United States)

Zhao, Qingying; Li, Min; Luo, Jun

2017-12-04

In nanomachine applications towards targeted drug delivery, drug molecules released by nanomachines propagate and chemically react with tumor cells in aqueous environment. If the nanomachines release drug molecules faster than the tumor cells react, it will result in loss and waste of drug molecules. It is a potential issue associated with the relationship among reaction rate, release rate and efficiency. This paper aims to investigate the relationship among reaction rate, release rate and efficiency based on two drug reception models. We expect to pave a way for designing a control method of drug release. We adopted two analytical methods that one is drug reception process based on collision with tumors and another is based on Michaelis Menten enzymatic kinetics. To evaluate the analytical formulations, we used the well-known simulation framework N3Sim to establish simulations. The analytical results of the relationship among reaction rate, release rate and efficiency is obtained, which match well with the numerical simulation results in a 3-D environment. Based upon two drug reception models, the results of this paper would be beneficial for designing a control method of nanomahine-based drug release.

Analysis of 18F-FDG PET mapping in malignant tumor patients with depression by SPM

International Nuclear Information System (INIS)

Su Liang; Zuo Chuantao; Guan Yihui; Zhao Jun; Shi Shenxun

2005-01-01

Objective: To investigate brain 18 F-fluorodeoxyglucose (FDG) PET mapping in malignant tumor patients with depressive emotion. Methods: 18 F-FDG PET imaging was performed in 21 malignant tumor patients (tumor group) and 21 healthy controls (control group). All were evaluated by self-rating depression scale (SDS)and 24 questions Hamilton rating scale for depression (HAMD). Results: (1) The standard total score of SDS and HAMD of the tumor group were higher than those of the control group (P 18 F-FDG PET imagings. The abnormalities of glucose metabolism might be related to their depressive emotion. (authors)

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

International Nuclear Information System (INIS)

Huang, Peigen; Allam, Ayman; Perez, Luis A.; Taghian, Alphonse; Freeman, Jill; Suit, Herman D.

1995-01-01

Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-α) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-α with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm 3 , mice were randomly assigned to treatment: rHuTNF-α alone compared with normal saline control; or local radiation plus rHuTNF-α vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-α on this tumor. The TCD 50 (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-α with local radiation. Results: Tumor growth in mice treated with a dose of 150 μg/kg body weight rHuTNF-α, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-α also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-α starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD 50 from the control value of 60.9 Gy to 50.5 Gy (p 50 value in the treatment vs. the control groups

Cervical Gross Tumor Volume Dose Predicts Local Control Using Magnetic Resonance Imaging/Diffusion-Weighted Imaging—Guided High-Dose-Rate and Positron Emission Tomography/Computed Tomography—Guided Intensity Modulated Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Dyk, Pawel; Jiang, Naomi; Sun, Baozhou; DeWees, Todd A. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Fowler, Kathryn J.; Narra, Vamsi [Department of Diagnostic Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri (United States); Garcia-Ramirez, Jose L.; Schwarz, Julie K. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Grigsby, Perry W., E-mail: pgrigsby@wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri (United States); Division of Gynecologic Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri (United States)

2014-11-15

Purpose: Magnetic resonance imaging/diffusion weighted-imaging (MRI/DWI)-guided high-dose-rate (HDR) brachytherapy and {sup 18}F-fluorodeoxyglucose (FDG) — positron emission tomography/computed tomography (PET/CT)-guided intensity modulated radiation therapy (IMRT) for the definitive treatment of cervical cancer is a novel treatment technique. The purpose of this study was to report our analysis of dose-volume parameters predicting gross tumor volume (GTV) control. Methods and Materials: We analyzed the records of 134 patients with International Federation of Gynecology and Obstetrics stages IB1-IVB cervical cancer treated with combined MRI-guided HDR and IMRT from July 2009 to July 2011. IMRT was targeted to the metabolic tumor volume and lymph nodes by use of FDG-PET/CT simulation. The GTV for each HDR fraction was delineated by use of T2-weighted or apparent diffusion coefficient maps from diffusion-weighted sequences. The D100, D90, and Dmean delivered to the GTV from HDR and IMRT were summed to EQD2. Results: One hundred twenty-five patients received all irradiation treatment as planned, and 9 did not complete treatment. All 134 patients are included in this analysis. Treatment failure in the cervix occurred in 24 patients (18.0%). Patients with cervix failures had a lower D100, D90, and Dmean than those who did not experience failure in the cervix. The respective doses to the GTV were 41, 58, and 136 Gy for failures compared with 67, 99, and 236 Gy for those who did not experience failure (P<.001). Probit analysis estimated the minimum D100, D90, and Dmean doses required for ≥90% local control to be 69, 98, and 260 Gy (P<.001). Conclusions: Total dose delivered to the GTV from combined MRI-guided HDR and PET/CT-guided IMRT is highly correlated with local tumor control. The findings can be directly applied in the clinic for dose adaptation to maximize local control.

Megavoltage external beam irradiation of craniopharyngiomas: Analysis of tumor control and morbidity

International Nuclear Information System (INIS)

Flickinger, J.C.; Lunsford, L.D.; Singer, J.; Cano, E.R.; Deutsch, M.

1990-01-01

From 1971 to 1985, 21 patients received megavoltage external beam radiation therapy at the University of Pittsburgh for control of craniopharyngioma. Minimum tumor doses prescribed to the 95% isodose volume ranged between 51.3 to 70.0 Gy. Median total dose was 60.00 Gy and median dose per fraction was 1.83 Gy. Three deaths occurred from intercurrent disease and no deaths from tumor progression. Actuarial overall survival was 89% and 82% at 5 and 10 years. Actuarial local control was 95% at 5 and 10 years. Radiation related complications included one patient with optic neuropathy, one with brain necrosis, and one that developed optic neuropathy followed by brain necrosis. The high dose group of patients who received a NSD or Neuret equivalent of greater than 60 Gy at 1.8 Gy per fraction had a significantly greater risk of radiation complications (p = .024). The actuarial risk at 5 years for optic neuropathy was 30% and brain necrosis was 12.5% in the high dose group. Tumor control in the high dose group was not shown to be significantly better. Any possible benefit in tumor control in treating patients with craniopharyngioma with doses above 60 Gy at 1.8 Gy per fraction appears to be offset by the increased risk of radiation injury

The selection of patients for accelerated radiotherapy on the basis of tumor growth kinetics and intrinsic radiosensitivity

International Nuclear Information System (INIS)

Tucker, S.L.; Kang-Sow Chan

1990-01-01

Mathematical modelling was used to reach qualitative conclusions concerning the relative rate of local tumor control that might be achieved by using accelerated fractionation to treat only the patients with the most rapidly growing rumors, compared with the control rated that could be expected from either conventional or accelerated radiotherapy alone. The results suggest that concomitant boost therapy is equally or more effective than conventional dose fractionation for all tumors, regardless of their growth kinetics. For tumors with very short clonogen doubling times, CHART (continuous hyperfractionated accelerated radiotherapy) may be even more effective than concomitant boost treatment, but CHART is less effective than conventional or concomitant boost therapy for tumors with longer clonogen doubling times. Thus, there is a rationale for using a predictive assay of tumor clonogen doubling times to identify the patients who should be treated with CHART. However, improvements in local tumor control resulting from concomitant boost treatment or the selective use of CHART are not likely to be apparent in the population as a whole, because the overall control rated are largely determined by refractory tumors having little chance of control with any of the treatments and by higher responsive tumors that are likely to be controlled regardless of the treatment choice. Differences in control rated with different treatment strategies are most apparent in the stochastic fraction of the population, which excludes those patients for whom there is either very little change (e.g. 99%) of achieving local control with both treatments. The stochastic fraction can be approximated by excluding those patients with the most radioresistant and the most radiosensitive tumors, since intrinsic tumor radiosensitivity appears to be the single most important factor determining treatment outcome. (author). 32 refs.; 4 figs.; 5 tabs

Hyperfractionation in carcinoma of the cervix: tumor control and late bowel complications

International Nuclear Information System (INIS)

Viswanathan, Faith Rangad; Varghese, Cherian; Peedicayil, Abraham; Lakshmanan, Jeyaseelan; Narayan, Viswanathan Perungulam

1999-01-01

Purpose: Hyperfractionation has been advocated to improve local tumor control by increasing radiation dose without increasing late normal tissue complications. The aim of this study was to determine if hyperfractionation decreased late bowel complications. Methods and Materials: Thirty patients with Stage II and III cervical cancer were randomized to receive either hyperfractionation or conventional fractionation. Patients were followed for 5 years and monitored for tumor control, recurrence, and bowel complications. The relative risks of tumor control and bowel complications were computed at 1 year and 5 years of follow-up. Kaplan-Meier survival curves were plotted to determine probabilities of being tumor-free and bowel complication-free. Results: There were 15 patients in each group. At 1 year of follow-up, 2 patients in the hyperfractionation group (13%) and 7 patients in the conventional treatment group (45%) had tumor (relative risk [RR] 0.3; 95% confidence interval [CI] 0.1, 1.1; p = 0.054). Delayed bowel complications were seen in 8 patients in the hyperfractionation group and 1 patient in the conventional treatment group (RR 7.5; 95% CI 1.1, 52; p = 0.014). At 5 years, 2 patients in the hyperfractionation group and 8 patients in the conventional treatment group had tumor (RR 0.3; 95% CI 0.1, 1.1; p = 0.04). Delayed bowel complications (Grades 2 and 3) occurred in 9 women in the hyperfractionation group and 2 patients in the conventional group (RR 5.4; 95% CI 1.5, 19.5; p 0.0006). Kaplan-Meier analysis showed that the hyperfractionation group had significantly more bowel complications over the 5 years of follow-up (p 0.024). Conclusion: Hyperfractionation may result in better tumor control both at 1 year and at 5 years following treatment of cervical cancer. However, hyperfractionation could lead to increased late bowel complications and must be used judiciously in the treatment of cervical cancer

Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral Tumors and Immunologic Control.

Science.gov (United States)

Lin, Yi-Hsin; Yang, Ming-Chieh; Tseng, Ssu-Hsueh; Jiang, Rosie; Yang, Andrew; Farmer, Emily; Peng, Shiwen; Henkle, Talia; Chang, Yung-Nien; Hung, Chien-Fu; Wu, T-C

2018-01-23

Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16 + buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas G12V , luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V , luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV + tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 1-15. ©2018 AACR. ©2018 American Association for Cancer Research.

Stereotactic radiosurgery vs. fractionated radiotherapy for tumor control in vestibular schwannoma patients: a systematic review.

Science.gov (United States)

Persson, Oscar; Bartek, Jiri; Shalom, Netanel Ben; Wangerid, Theresa; Jakola, Asgeir Store; Förander, Petter

2017-06-01

Repeated controlled studies have revealed that stereotactic radiosurgery is better than microsurgery for patients with vestibular schwannoma (VS) 18 years) patients with unilateral VS, followed for a median of >5 years, were eligible for inclusion. After screening titles and abstracts of the 1094 identified articles and systematically reviewing 98 of these articles, 19 were included. Patients with unilateral VS treated with radiosurgery were compared to patients treated with fractionated stereotactic radiotherapy. No randomized controlled trial (RCT) was identified. None of the identified controlled studies comparing SRS with FSRT were eligible according to the inclusion criteria. Nineteen case series on SRS (n = 17) and FSRT (n = 2) were included in the systematic review. Loss of tumor control necessitating a new VS-targeted intervention was found in an average of 5.0% of the patients treated with SRS and in 4.8% treated with FSRT. Mean deterioration ratio for patients with serviceable hearing before treatment was 49% for SRS and 45% for FSRT, respectively. The risk for facial nerve deterioration was 3.6% for SRS and 11.2% for FSRT and for trigeminal nerve deterioration 6.0% for SRS and 8.4% for FSRT. Since these results were obtained from case series, a regular meta-analysis was not attempted. SRS and FSRT are both noninvasive treatment alternatives for patients with VS with low rates of treatment failure in need of rescue therapy. In this selection of patients, the progression-free survival rates were on the order of 92-100% for both treatment options. There is a lack of high-quality studies comparing radiation therapy alternatives for patients with VS. Finally, 19 articles reported long-term tumor control after SRS, while only 2 articles reported long-term FSRT results, making effect estimates more uncertain for FSRT.

Study on interstitial brachytherapy using 103Pd seeds on tumor-bearing rats

International Nuclear Information System (INIS)

Feng Huiru; Zhang Jingming; Tian Jiahe; Ding Weimin; Bai Hongsheng; Jin Xiaohai

2003-01-01

The effects of low-dose-rate brachytherapy are investigated in tumor-bearing rat. Walker 256 cells are transplanted subcutaneously with a trocar in the left leg of rats (Wistar). Two weeks later, rats with a tumor of 10 mm in mean diameter are divided into three groups (10 per group). Two groups are given 1 seed and 2 seeds implantation of 103 Pd, respectively, the third group is as an untreated control. Tumor size is measured twice a week until the 25th day when the rats are killed. Tumor is monitored either by palpation or further confirmed by histopathology. Kaplan-Meier statistic method is performed for survival analysis. The results show that the average weight of rats in untreated group is lower than in radiation groups (P 0.05). Tumor volumes in all treatment groups increase more obviously than in control till 16 days post-implantation. Tumor regression rate in 1 seed group is higher than in control group and in 2 seeds group. Although survival analysis show that the median survival time in 1 seed, 2 seeds and control groups are 24±0, 21±2 and 19±2 days with survival rate of 80%, 60% and 50% respectively, no significant differences are seen in all groups. So, brachytherapy with 103 Pd seed is effective on tumor-bearing rats. The implantation of seed can cause tumor edema in a self-limited way. A reasonable doses chosen for brachytherapy may play a role in treatment success

The effect of combining recombinant human tumor necrosis factor-alpha with local radiation on tumor control probability of a human glioblastoma multiforme xenograft in nude mice

Energy Technology Data Exchange (ETDEWEB)

Huang, Peigen; Allam, Ayman; Perez, Luis A; Taghian, Alphonse; Freeman, Jill; Suit, Herman D

1995-04-30

Purpose: To evaluate the antitumor activity of recombinant human tumor necrosis factor-alpha (rHuTNF-{alpha}) on a human glioblastoma multiforme (U87) xenograft in nude mice, and to study the effect of combining rHuTNF-{alpha} with local radiation on the tumor control probability of this tumor model. Methods and Materials: U87 xenograft was transplanted SC into the right hindleg of NCr/Sed nude mice (7-8 weeks old, male). When tumors reached a volume of about 110 mm{sup 3}, mice were randomly assigned to treatment: rHuTNF-{alpha} alone compared with normal saline control; or local radiation plus rHuTNF-{alpha} vs. local radiation plus normal saline. Parameters of growth delay, volume doubling time, percentage of necrosis, and cell loss factor were used to assess the antitumor effects of rHuTNF-{alpha} on this tumor. The TCD{sub 50} (tumor control dose 50%) was used as an endpoint to determine the effect of combining rHuTNF-{alpha} with local radiation. Results: Tumor growth in mice treated with a dose of 150 {mu}g/kg body weight rHuTNF-{alpha}, IP injection daily for 7 consecutive days, was delayed about 8 days compared to that in controls. Tumors in the treatment group had a significantly longer volume doubling time, and were smaller in volume and more necrotic than matched tumors in control group. rHuTNF-{alpha} also induced a 2.3 times increase of cell loss factor. The administration of the above-mentioned dose of rHuTNF-{alpha} starting 24 h after single doses of localized irradiation under hypoxic condition, resulted in a significant reduction in TCD{sub 50} from the control value of 60.9 Gy to 50.5 Gy (p < 0.01). Conclusion: rHuTNF-{alpha} exhibits an antitumor effect against U87 xenograft in nude mice, as evidenced by an increased delay in tumor growth as well as cell loss factor. Also, there was an augmentation of tumor curability when given in combination with radiotherapy, resulting in a significantly lower TCD{sub 50} value in the treatment vs. the

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

Science.gov (United States)

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A packet-based dual-rate PID control strategy for a slow-rate sensing Networked Control System.

Science.gov (United States)

Cuenca, A; Alcaina, J; Salt, J; Casanova, V; Pizá, R

2018-05-01

This paper introduces a packet-based dual-rate control strategy to face time-varying network-induced delays, packet dropouts and packet disorder in a Networked Control System. Slow-rate sensing enables to achieve energy saving and to avoid packet disorder. Fast-rate actuation makes reaching the desired control performance possible. The dual-rate PID controller is split into two parts: a slow-rate PI controller located at the remote side (with no permanent communication to the plant) and a fast-rate PD controller located at the local side. The remote side also includes a prediction stage in order to generate the packet of future, estimated slow-rate control actions. These actions are sent to the local side and converted to fast-rate ones to be used when a packet does not arrive at this side due to the network-induced delay or due to occurring dropouts. The proposed control solution is able to approximately reach the nominal (no-delay, no-dropout) performance despite the existence of time-varying delays and packet dropouts. Control system stability is ensured in terms of probabilistic Linear Matrix Inequalities (LMIs). Via real-time control for a Cartesian robot, results clearly reveal the superiority of the control solution compared to a previous proposal by authors. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180)

International Nuclear Information System (INIS)

Wirtz, F.

1987-05-01

The present experiments were designed to test the therapeutic qualification of 125 I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125 IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x10 5 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125 IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig

Treatment of nasopharyngeal tumors: literature review

International Nuclear Information System (INIS)

Noel, G.; Dessard-Diana, B.; Vignot, S.; Mazeron, J.J.; Noel, G.; Mazeron, J.J.

2002-01-01

The conventional radiotherapy and the associated treatments improved the prognostic of nasopharyngeal cancer. A better selection of the patients who must have a more aggressive treatment also probably contributed to this improvement. Even if a relation could be found between the locoregional relapse rate and the distant relapse rate, these two events remain often independent. It results from it that the improvement of local control rate necessarily does not result in a better control of the disease. The patients with a locally advanced tumor, with or not an invasion of the base of the skull and/or neurological symptoms, must have an aggressive locally treatment. This probably includes the increase in dose delivered to the tumor via a more conformational radiotherapy, a brachytherapy, radiotherapy in stereotaxic conditions or other techniques. Dose within the tumor must be at least 70 Gy and the prophylactic nodal dose, at least 50 Gy. CT scan and MRI are essential for delineating the volumes of interest. The protocols of hyperfractionated radiotherapy did not give convincing results. Association with chemotherapy allowed, on the other hand, an improvement of the prognostic locally advanced cancers. Neo-adjuvant or adjuvant chemotherapy was largely used to attempt to limit the risks of systemic dissemination, but an improvement of results was not clearly demonstrated. An improvement of the rates of survival and control of the disease, on the other hand, was observed in a certain number of studies with the chemoradiotherapy. In the event of locoregional relapse, an aggressive attitude can allow the control of the disease in the absence of systemic dissemination. Salvage treatments are, however, disappointing for when distant relapse occurs which suggests. (author)

Loci controlling lymphocyte production of interferon gamma after alloantigen stimulation in vitro and their co-localization with genes controlling lymphocyte infiltration of tumors and tumor susceptibility

Czech Academy of Sciences Publication Activity Database

Lipoldová, Marie; Havelková, Helena; Badalová, Jana; Vojtíšková, Jarmila; Quan, L.; Krulová, Magdalena; Sohrabi, Yahya; Stassen, A. P. M.; Demant, P.

2010-01-01

Roč. 59, č. 2 (2010), s. 203-213 ISSN 0340-7004 R&D Projects: GA MŠk(CZ) LC06009; GA AV ČR IAA500520606; GA ČR GD310/08/H077 Institutional research plan: CEZ:AV0Z50520514 Keywords : Tumor susceptibility * Genetic control of interferon gamma production * Lymphocyte infiltration of tumors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.293, year: 2010

Automatic Strain-Rate Controller,

Science.gov (United States)

1976-12-01

D—AO37 9~e2 ROME AIR DEVELOPMENT CENTER GRIFFISS AFB N 1’ FIG 13/ 6AUTOMATIC STRAIN—RATE CONTROLLER, (U) DEC 76 R L HUNTSINGER. J A ADAMSK I...goes to zero. CONTROLLER, Leeds and Northrup Series 80 CAT with proportional band , rate , reset, and approach controls . Input from deviation output...8) through ( 16) . (8) Move the set-point slowl y up to 3 or 4. (9) If the recorder po inter hunts , adjust the func t ion controls on tine Ser

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

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Helbig, Linda [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Koi, Lydia [OncoRay–National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Deutsches Konsortium für Translationale Krebsforschung, Site Dresden, Dresden (Germany); Brüchner, Kerstin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Institute of Radiooncology Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Gurtner, Kristin [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Hess-Stumpp, Holger; Unterschemmann, Kerstin [Global Drug Discovery, Bayer Pharma, Berlin (Germany); Pruschy, Martin [Radiation Oncology, University of Zurich, Zurich (Switzerland); and others

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluated 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of

Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

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Modh, Ankit; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Williams, Eric [Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York (United States); Foster, Amanda; Shah, Mihir [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Gelblum, Daphna Y. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Rosenzweig, Kenneth E. [Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York (United States); Yorke, Ellen D.; Jackson, Andrew [Department of Medical Physics Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

2014-12-01

Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and

Irradiation effects on the tumor and adjacent tissues of brain tumor-bearing mice

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Tsunemoto, Hiroshi; Koike, Sachiko; Furukawa, Shigeo.

1979-01-01

C 3 H mice aged 56 - 70 days, weighing 27 - 37 g were used throughout this experiment. A transplantable fibrosarcoma arising spontaneously from C 3 H mice was used. For experiment, 10 4 tumor cells suspended in 0.025 ml of saline solution were injected into the cerebral hemisphere by a 26 gauge needle with a micrometer syringe under nembutal anesthesia. Whole brain irradiation was performed at 7 days after injection of the tumor cells and the radiation doses were 2,000 and 20,000 rads, respectively. The feature of x-rays were 200 kVp, 20 mA, 0.5 mm Cu + 0.5 mm Al filtration and TSD 20 cm. The dose-rate was 340 - 360 R/min. The articles of this study were as follows: a) Determination of LD 50 values for the mice, tumor-bearing in the brain or non-tumor-bearing; and b) Observation of clinical features and gross autopsy findings of the mice following irradiation. The LD 50 values for 2,000 rad irradiation in the tumor-bearing or non-tumor-bearing mice were 10.9 and 11.4 days, respectively. LD 50 values of 3.7 days and 4.3 days were the results for the tumor-bearing and non-tumor-bearing mice irradiated by 20,000 rad, respectively. On the other hand, the LD 50 value for the control group, i.e. non-irradiated mice, was 6.7 days. At postmortem examinations, gastrointestinal bleeding was observed frequently in mice bearing tumor in the brain. Whole brain irradiation is effective to prolong the life of tumor-bearing mice. However, in some instances, deaths have occurred earlier in tumor-bearing mice compared to the control group. (author)

Clinical assessment of tumor clearance during radiotherapy as a prognostic factor of early glottic carcinoma

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, T.; Ikeda, H.; Teshima, T.; Murayama, S.

1992-01-01

From 1967 through 1985, 358 cases of early glottic carcinoma were treated with telecobalt therapy at the Department of Radiology, Osaka University Medical School. Among 278 cases treated with 2 Gy a day, the tumor response of 262 cases at 40, 50 and 60 Gy were evaluated by direct or indirect laryngoscope. The five-year local control rates of these evaluable cases of T1 and T2 glottic carcinoma were 79% and 70%, respectively. The local control rates of T1 glottic carcinoma with tumor clearance and persistence at 40 Gy were 83% (119/143) and 64% (43/67), and those of T2 cases were 86% (18/21) and 58% (18/31), respectively. The local control rates of the cases with tumor clearance and persistence at 40 Gy were same between T1 and T2 cases. The tumor clearance rates of T1 cases were significantly higher than those of T2 cases (p [de

Effects of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in tumor-bearing mice

International Nuclear Information System (INIS)

Yu Hongsheng; Lu Yanda

2001-01-01

Objective: To study the effect of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in the tumor-bearing mice. Methods: Kunming strain male mice were implanted with S 180 sarcoma cells in the right inguen subcutaneously as an experimental in situ animal model. Six hours before implantation the mice were given 75 mG whole-body X-ray irradiation and tumor-formation rate was counted 5 days late. From then, every two days the tumor volume was measured to draw a tumor growth curve. Fifteen days later, all mice were killed to measure the tumor weight, observe the necrosis area and the tumor-infiltration lymphoreticular cells (TIL) in the tumor pathologically. At the same time, erythrocyte immune function and activity of SOD were tested. Results: (1) The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without a pre-exposed (P < 0.05). (2) The tumor growth slowed down significantly in mice receiving a low does irradiation; The average tumor weight in mice receiving a low dose irradiation was lighter too (P < 0.05). (3) The tumor necrosis areas were larger and TILs were more in the irradiation group than those of the control group. (4) The erythrocyte immune function and activity of SOD in the irradiation group were all higher significantly than those of the control group ( P < 0.05). Conclusion: Low dose radiation could markedly increase anti-tumor ability of the organism and improve the erythrocyte immune function and activity of SOD in red cells, suggesting it could be useful in clinical cancer treatment

Tumor evasion from immune control: Strategies of a MISS to become a MASS

International Nuclear Information System (INIS)

D'Onofrio, Alberto

2007-01-01

We biologically describe the phenomenon of the evasion of tumors from immune surveillance where tumor cells, initially constrained to exist in a microscopic steady state (MISS) elaborate strategies to evade from the immune control and to reach a macroscopic steady state (MASS). We, then, describe 'evasion' as a long term loss of equilibrium in a framework of prey-predator-like models with adiabatic varying parameters, whose changes reflect the evolutionary adaptation of the tumor in a 'hostile' environment by means of the elaboration of new strategies of survival. Similarities and differences between the present work and the interesting seminal paper [Kuznetsov VA, Knott GD. Modeling tumor regrowth and immunotherapy. Math Comput Model 2001;33:1275-87] are discussed. We also propose and study a model of clonal resistance to the immune control with slowly varying adaptive mutation parameter

Tumor evasion from immune control: Strategies of a MISS to become a MASS

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D' Onofrio, Alberto [Department of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, I-20141 Milan (Italy)]. E-mail: alberto.d' onofrio@ieo.it

2007-01-15

We biologically describe the phenomenon of the evasion of tumors from immune surveillance where tumor cells, initially constrained to exist in a microscopic steady state (MISS) elaborate strategies to evade from the immune control and to reach a macroscopic steady state (MASS). We, then, describe 'evasion' as a long term loss of equilibrium in a framework of prey-predator-like models with adiabatic varying parameters, whose changes reflect the evolutionary adaptation of the tumor in a 'hostile' environment by means of the elaboration of new strategies of survival. Similarities and differences between the present work and the interesting seminal paper [Kuznetsov VA, Knott GD. Modeling tumor regrowth and immunotherapy. Math Comput Model 2001;33:1275-87] are discussed. We also propose and study a model of clonal resistance to the immune control with slowly varying adaptive mutation parameter.

A realistic closed-form radiobiological model of clinical tumor-control data incorporating intertumor heterogeneity

International Nuclear Information System (INIS)

Roberts, Stephen A.; Hendry, Jolyon H.

1998-01-01

Purpose: To investigate the role of intertumor heterogeneity in clinical tumor control datasets and the relationship to in vitro measurements of tumor biopsy samples. Specifically, to develop a modified linear-quadratic (LQ) model incorporating such heterogeneity that it is practical to fit to clinical tumor-control datasets. Methods and Materials: We developed a modified version of the linear-quadratic (LQ) model for tumor control, incorporating a (lagged) time factor to allow for tumor cell repopulation. We explicitly took into account the interpatient heterogeneity in clonogen number, radiosensitivity, and repopulation rate. Using this model, we could generate realistic TCP curves using parameter estimates consistent with those reported from in vitro studies, subject to the inclusion of a radiosensitivity (or dose)-modifying factor. We then demonstrated that the model was dominated by the heterogeneity in α (tumor radiosensitivity) and derived an approximate simplified model incorporating this heterogeneity. This simplified model is expressible in a compact closed form, which it is practical to fit to clinical datasets. Using two previously analysed datasets, we fit the model using direct maximum-likelihood techniques and obtained parameter estimates that were, again, consistent with the experimental data on the radiosensitivity of primary human tumor cells. This heterogeneity model includes the same number of adjustable parameters as the standard LQ model. Results: The modified model provides parameter estimates that can easily be reconciled with the in vitro measurements. The simplified (approximate) form of the heterogeneity model is a compact, closed-form probit function that can readily be fitted to clinical series by conventional maximum-likelihood methodology. This heterogeneity model provides a slightly better fit to the datasets than the conventional LQ model, with the same numbers of fitted parameters. The parameter estimates of the clinically

Novel radiosensitizers for locally advanced epithelial tumors: inhibition of the PI3K/Akt survival pathway in tumor cells and in tumor-associated endothelial cells as a novel treatment strategy?

International Nuclear Information System (INIS)

Riesterer, Oliver; Tenzer, Angela; Zingg, Daniel; Hofstetter, Barbara; Vuong, Van; Pruschy, Martin; Bodis, Stephan

2004-01-01

In locally advanced epithelial malignancies, local control can be achieved with high doses of radiotherapy (RT). Concurrent chemoradiotherapy can improve tumor control in selected solid epithelial adult tumors; however, treatment-related toxicity is of major concern and the therapeutic window often small. Therefore, novel pharmacologic radiosensitizers with a tumor-specific molecular target and a broad therapeutic window are attractive. Because of clonal heterogeneity and the high mutation rate of these tumors, combined treatment with single molecular target radiosensitizers and RT are unlikely to improve sustained local tumor control substantially. Therefore, radiosensitizers modulating entire tumor cell survival pathways in epithelial tumors are of potential clinical use. We discuss the preclinical efficacy and the mechanism of three different, potential radiosensitizers targeting the PTEN/PI3K/Akt survival pathway. These compounds were initially thought to act as single-target agents against growth factor receptors (PKI 166 and PTK 787) or protein kinase C isoforms (PKC 412). We describe an additional target for these compounds. PKI 166 (an epidermal growth factor [EGF] receptor inhibitor) and PKC 412, target the PTEN/PI3K/Akt pathway mainly in tumor cells, and PTK 787 (a vascular endothelial growth factor [VEGF] receptor inhibitor) in endothelial cells. Even for these broader range molecular radiosensitizers, the benefit could be restricted to human epithelial tumor cell clones with a distinct molecular profile. Therefore, these potential radiosensitizers have to be carefully tested in specific model systems before introduction in early clinical trials

Preoperative Chemoembolization in Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation: Influence of Emergent Versus Elective Procedures on Patient Survival and Tumor Recurrence Rate

International Nuclear Information System (INIS)

Stockland, A. H.; Walser, E. M.; Paz-Fumagalli, R.; McKinney, J. M.; May, G. R.

2007-01-01

Our purpose was to compare the recurrence rate and survival in patients with hepatocellular carcinoma (HCC) who had elective transarterial chemoembolization (TACE), immediate preoperative TACE, or no treatment prior to orthotopic liver transplantation (OLT). A total of 132 patients with HCC had TACE prior to OLT. Eighteen patients had no TACE before OLT and functioned as a control group. The urgent group included 35 patients embolized less than 24 h before OLT and the elective group included 97 patients embolized greater than 1 day before transplantation. These groups were compared with regard to tumor staging, hepatic synthetic function, and post-TACE tumor necrosis and survival and recurrence rates.Patients were followed for a mean of 780 days post OLT (1-2912 days). The tumor staging was similar between groups but the Childs-Pugh score in the urgent and untreated group was significantly higher than that of the other groups. The degree of necrosis at explant was also significantly different between the two treated groups, with an average 35% necrosis in the patients embolized less than 24 h before OLT vs 77% in the elective group (p < 0.002). Recurrence rate in the urgent group was 8 of 35 (23%) in a median of 580 days, 20 of 97 (21%) in a median of 539 days in the elective group, and 2 of 18 (11%) in a median of 331 days in the no-TACE group. Survival at 1, 3, and 5 years was 91%, 80%, and 72% in the elective group, 79%, 58%, and 39% in the urgent group, and 69%, 61%, and 41% in the no-TACE group, respectively. The urgent and no-TACE groups had significantly worse survival compared with the other groups; however, the tumor recurrence rates were statistically the same among all three groups. TACE within 24 h of OLT causes an average of 35% necrosis and elective TACE increases necrosis further to 77%. Despite this difference, the tumor recurrence rate in the three groups is equivalent and no different from that in the group that received no treatment before OLT

[Characteristics of polyamine biosynthesis regulation and tumor growth rate in hormone-dependant grafted breast tumors of mice and rats].

Science.gov (United States)

Orlovskiĭ, A A

2007-01-01

Effect of the inhibitors of polyamines biosynthesis on completely or partially hormone-dependant breast tumors (mouse Ca755 carcinoma and Walker W-256 carcinosarcoma) is essentially special: in contrary to hormone-dependant tumors, this effect may be not only breaking but stimulating as well. Change-over from one to another mode of reaction is conditioned, most probable, by hormonal status, which is determined by one or another estral cycle phase. Biochemical mechanisms of this change-over are closely connected with polyamines metabolism, namely the degree of polyamines (especially spermine) interconvertion and physiological reactivity level of the system controlling expression of ornithin-decarboxilase. At that, the first of these pathways is predominant for completely hormone-dependant Ca755 and the second one -for partially hormone-dependant W-256.

Detection and recurrence rate of transurethral resection of bladder tumors by narrow-band imaging: Prospective, randomized comparison with white light cystoscopy

Directory of Open Access Journals (Sweden)

Seung Bin Kim

2018-03-01

Full Text Available Purpose: The purpose of this study was to evaluate the efficacy of narrow-band imaging (NBI as a diagnostic tool for detecting bladder tumors during cystoscopy compared with white light cystoscopy (WLC. Materials and Methods: From December 2013 to June 2017, a randomized prospective study was conducted on 198 patients underwent transurethral resection of bladder tumor by a single surgeon. The patients were divided into two groups according to diagnostic method. In Group I, WLC only was performed. In Group II, NBI was additionally performed after WLC. We analyzed the rate of detection of bladder tumors as a primary endpoint. In addition, we evaluated rates of recurrence in each group. Results: There were no significant differences between the two groups in characteristics except hypertension. In the analysis of rates of detection, the probability of diagnosing cancer was 80.9% (114/141 in the WLC group, and the probability of diagnosing cancer using WLC in the NBI group was 85.5% (159/186. After switching from WLC to NBI for second-look cystoscopy in the NBI group, NBI was shown to detect additional tumors with a detection rate of 35.1% (13/37 from the perspective of the patients and 42.2% (27/64 from the perspective of the tumors. The 1-year recurrence-free rate was 72.2% in the WLC group and 85.2% in the NBI group (p=0.3. Conclusions: NBI had benefits for detecting tumors overlooked by WLC. Although the difference in the 1-year recurrence-free rate was not statistically significant, our results showed a trend for higher recurrence in the NBI group.

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

Science.gov (United States)

Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

2008-01-01

The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

Directory of Open Access Journals (Sweden)

Aziz Mahmoudzadeh

2016-07-01

Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

Science.gov (United States)

Mahmoudzadeh, Aziz; Mohammadpour, Hemn

2016-07-01

Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

Radiographic and metabolic response rates following image-guided stereotactic radiotherapy for lung tumors

International Nuclear Information System (INIS)

Mohammed, Nasiruddin; Grills, Inga S.; Wong, Ching-Yee Oliver; Galerani, Ana Paula; Chao, Kenneth; Welsh, Robert; Chmielewski, Gary; Yan Di; Kestin, Larry L.

2011-01-01

Purpose: To evaluate radiographic and metabolic response after stereotactic body radiotherapy (SBRT) for early lung tumors. Materials and methods: Thirty-nine tumors were treated prospectively with SBRT (dose = 48-60 Gy, 4-5 Fx). Thirty-six cases were primary NSCLC (T1N0 = 67%; T2N0 = 25%); three cases were solitary metastases. Patients were followed using CT and PET at 6, 16, and 52 weeks post-SBRT, with CT follow-up thereafter. RECIST and EORTC criteria were used to evaluate CT and PET responses. Results: At median follow-up of 9 months (0.4-26), RECIST complete response (CR), partial response (PR), and stable disease (SD) rates were 3%, 43%, 54% at 6 weeks; 15%, 38%, 46% at 16 weeks; 27%, 64%, 9% at 52 weeks. Mean baseline tumor volume was reduced by 46%, 70%, 87%, and 96%, respectively at 6, 16, 52, and 72 weeks. Mean baseline maximum standardized uptake value (SUV) was 8.3 (1.1-20.3) and reduced to 3.4, 3.0, and 3.7 at 6, 16, and 52 weeks after SBRT. EORTC metabolic CR/PR, SD, and progressive disease rates were 67%, 22%, 11% at 6 weeks; 86%, 10%, 3% at 16 weeks; 95%, 5%, 0% at 52 weeks. Conclusions: SBRT yields excellent RECIST and EORTC based response. Metabolic response is rapid however radiographic response occurs even after 1-year post treatment.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

Science.gov (United States)

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

The effect of low-dose total body irradiation on tumor control

International Nuclear Information System (INIS)

Sakamoto, Kiyohiko; Miyamoto, Miyako; Watabe, Nobuyuki.

1987-01-01

Total body irradiation (TBI) is considered to bring about an immunosuppressive effect on an organism, on the basis of data obtained from sublethal doses of TBI. However, there are no data on how low-dose TBI affects an organism. Over the last five years, we have been studying the effects of low-dose TBI on normal or tumor-bearing mice and the immunological background of these effects. In experimental studies, an increase in the TD50 value (the number of cells required for a tumor incidence of 50 %) in mice exposed to 10 rad was recognized and showed a remarkable increase at 6 hours to 15 hours after irradiation. TBI of 10 rad also showed an enhancement effect on tumor cell killing when given 12 hours before local tumor irradiation. In order to clarify the mechanism of this kind of effect, some immunological studies were performed using several immunological procedures, and the results suggested that 10 rad of TBI caused increasing tumor immunity in irradiated mice. Clinical trials in some patients with advanced tumors are now being undertaken on the basis of these experimental data, and the effect of TBI on tumor control appears promising, although it is too early to draw conclusions. (author)

Overview of Radiosensitivity of Human Tumor Cells to Low-Dose-Rate Irradiation

International Nuclear Information System (INIS)

Williams, Jerry R.; Zhang Yonggang; Zhou Haoming; Gridley, Daila S.; Koch, Cameron J.; Slater, James M.; Little, John B.

2008-01-01

Purpose: We compared clonogenic survival in 27 human tumor cell lines that vary in genotype after low-dose-rate (LDR) or high-dose rate (HDR) irradiation. We measured susceptibility to LDR-induced redistribution in the cell cycle in eight of these cell lines. Methods and Materials: We measured clonogenic survival after up to 96 hours of LDR (0.25 Gy/h) irradiation. We compared these with clonogenic survival after HDR irradiation (50 Gy/h). Using flow cytometry, we measured LDR-induced redistribution as a function of time during LDR irradiation in eight of these cell lines. Results: Coefficients that describe clonogenic survival after both LDR and HDR irradiation segregate into four radiosensitivity groups that associate with cell genotype: mutant (mut)ATM, wild-type TP53, mutTP53, and an unidentified gene in radioresistant glioma cells. The LDR and HDR radiosensitivity correlates at lower doses (∼2 Gy HDR, ∼6 Gy LDR), but not at higher doses (HDR > 4 Gy; LDR > 6 Gy). The rate of LDR-induced loss of clonogenic survival changes at approximately 24 hours; wild-type TP53 cells become more resistant and mutTP53 cells become more sensitive. Redistribution induced by LDR irradiation also changes at approximately 24 hours. Conclusions: Radiosensitivity of human tumor cells to both LDR and HDR irradiation is genotype dependent. Analysis of coefficients that describe cellular radiosensitivity segregates 27 cell lines into four statistically distinct groups, each associating with specific genotypes. Changes in cellular radiosensitivity and redistribution in the cell cycle are strongly time dependent. Our data establish a genotype-dependent time-dependent model that predicts clonogenic survival, explains the inverse dose-rate effect, and suggests possible clinical applications

Potential for tumor therapy with tritiated tetracycline. Summary evaluation

International Nuclear Information System (INIS)

Davis, R.C.; Wood, P.; Wood, L.L.; Mendelsohn, M.L.

1976-01-01

Reports of tetracycline accumulation in human and animal tumors have led a number of investigators to postulate that this drug, if radio-labeled, might have potential as a therapeutic or diagnostic agent. This paper describes attempts to investigate this potential for tritiated tetracycling. The therapeutic studies demonstrated that while a significant reduction in the growth rates of transplanted tumors could be obtained by the administration of heavy doses of TTC relative to uninjected controls, similar reductions were observed in the growth rates of tumors in animals receiving unlabeled TC. In the localization studies in rodents, the concentrations of TTC in normal tissues and tumors were compared and were correlated with the corresponding concentrations of 14 C-thymidine, a measure of proliferative activity

Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long-term tumor control in patients with craniopharyngioma.

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Ansari, Shaheryar F; Moore, Reilin J; Boaz, Joel C; Fulkerson, Daniel H

2016-04-01

OBJECT Radioactive phosphorus-32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external-beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR. For this study, the authors reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients' records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR. METHODS The authors performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors' institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR. RESULTS Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and

mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

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Guri, Yakir; Nordmann, Thierry M; Roszik, Jason

2018-01-01

Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Effects of 2-Deoxy-D-Glucose on Metabolic Status, Proliferative Capacity and Growth Rate of FSall Tumor: Observations made by In Vivo 31P-Nuclear Magnetic Resonance Spectroscopy and Flow Cytometry

International Nuclear Information System (INIS)

Chang, Hye Sook; Choi, Eun Kyung; Cho, Jeong Gill; Lim, Tae Hwan; Lee, Tae Keun; Yi, Yun; Cho, Young Joo; Kim, Gon Sup

1991-01-01

The effect of 2-deoxy-d-glucose (2-DDG) on C 3 H mouse fibrosarcoma (FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo 31 P-MRS, proliferative capacity was observed on flow cytometry (FC) and growth rate was measured after transplantation of 106 viable tumor cells in the dorsum of foot of C 3 Hf/Sed mice. One gram of 2-DDG per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantation was 250mm 3 . Growth rate of FSall tumor was measured by tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo 31 P-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and G 2 +M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy

On the influence of ultraviolet radiation on spontaneous tumors in NMRI mice

International Nuclear Information System (INIS)

Koenigsmann, G.; Kinkel, H.J.; Bocionek, P.; Wolff, F.

1981-01-01

During a period of 12 and 15 months respectively, female NMRI mice were irradiated twelve hours per day with specific parts of the ultraviolet spectrum (three groups, each comprising 100 animals: non-irradiated control group, animals irradiated with B units, animals irradiated with A/B units). No considerable influence of the chronic exposure to ultraviolet radiation could be demonstrated with regard to the development of the body weight and the hematologic condition. Group B had the same rate of spontaneous tumors of the respiratory tract as the control group; this rate was higher in group A/B. As to the development of spontaneous tumors in the lymphatic tissues, there seems to be a dependence on radiation: the animals of group B presented a slightly higher, those of group A/B a higher development than the animals of the nonirradiated control group. It cannot be definitely clarified yet to what extent this increased tumor rate was additionally induced by the higher environmental temperature or other influences involved by experiment. Harding-Passey melanomas were inoculated in NMRI mice and, 48 hours later, they were exposed to defined emission spectra within the natural ultraviolet spectrum. The exposed animals showed a slower growth of the transplanted tumors than the non-exposed animals, and especially the animals exposed to UVB radiation had a longer survival time. This chronic irradiation test was carried out in order to examine the influence of defined emission spectra on autochthonous tumors in NMRI mice and on their spontaneous tumor rate and blood count. (orig.) [de

Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

International Nuclear Information System (INIS)

Guss, Zachary D.; Batra, Sachin; Limb, Charles J.; Li, Gordon; Sughrue, Michael E.; Redmond, Kristin; Rigamonti, Daniele; Parsa, Andrew T.; Chang, Steven; Kleinberg, Lawrence; Lim, Michael

2011-01-01

Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data when Cochrane's statistic was statistically insignificant and the inconsistency among studies was 36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.

p53-Mediated Molecular Control of Autophagy in Tumor Cells

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Maria Mrakovcic

2018-03-01

Full Text Available Autophagy is an indispensable mechanism of the eukaryotic cell, facilitating the removal and renewal of cellular components and thereby balancing the cell’s energy consumption and homeostasis. Deregulation of autophagy is now regarded as one of the characteristic key features contributing to the development of tumors. In recent years, the suppression of autophagy in combination with chemotherapeutic treatment has been approached as a novel therapy in cancer treatment. However, depending on the type of cancer and context, interference with the autophagic machinery can either promote or disrupt tumorigenesis. Therefore, disclosure of the major signaling pathways that regulate autophagy and control tumorigenesis is crucial. To date, several tumor suppressor proteins and oncogenes have emerged as eminent regulators of autophagy whose depletion or mutation favor tumor formation. The mammalian cell “janitor” p53 belongs to one of these tumor suppressors that are most commonly mutated in human tumors. Experimental evidence over the last decade convincingly reports that p53 can act as either an activator or an inhibitor of autophagy depending on its subcellular localization and its mode of action. This finding gains particular significance as p53 deficiency or mutant variants of p53 that accumulate in the cytoplasm of tumor cells enable activation of autophagy. Accordingly, we recently identified p53 as a molecular hub that regulates autophagy and apoptosis in histone deacetylase inhibitor-treated uterine sarcoma cells. In light of this novel experimental evidence, in this review, we focus on p53 signaling as a mediator of the autophagic pathway in tumor cells.

Predictive value of histologic tumor necrosis after radiation.

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Chen, Y; Taghian, A G; Rosenberg, A E; O'Connell, J; Okunieff, P; Suit, H D

2001-12-20

Postsurgical evaluation of histologic changes of tumors after preoperative chemotherapy and/or radiotherapy has been a routine clinical practice of pathologists and oncologists. There appears to be secure evidence that the extent of tumor necrosis vs. viable tumor cells postchemotherapy is a clinically useful predictor of outcome. The significance of histologic tumor necrosis after radiotherapy, however, has not been clearly established and deserves further investigation. We investigated the correlation between histological extent of tumor necrosis, survival of tumor transplants, and radiation doses in an experimental model using three human tumor xenografts. Three human tumor cell lines were investigated: STS-26, SCC-21, and HGL-21. Tumors were grown subcutaneously in athymic nude mice and received external beam radiation of different doses. Tumors were excised 2 weeks postirradiation. One-half of the tumor was divided into 1-mm(3) fragments and transplanted to naive mice. The other half was examined for histologic tumor necrosis. Transplant survival was strongly correlated with radiation dose, TCD(p) (radiation dose that results in local tumor control in proportion, p, to irradiated tumors). In contrast, there was no clear association between transplant survival rate and the extent of tumor necrosis. The experimental model demonstrated a strong inverse correlation between radiation doses and tumor transplant survival. Histologic tumor necrosis did not correlate well with radiation doses or transplant survival rates. Despite common practices in histologic examination of tumors posttherapy, clinical interpretations and implications of histologic tumor necrosis after radiotherapy should be considered with caution. Copyright 2001 Wiley-Liss, Inc.

Trace metals and over-expression of metallothioneins in bladder tumoral lesions: a case-control study

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Cymbron Teresa

2009-07-01

Full Text Available Abstract Background Previous studies have provided some evidence of a possible association between cancer and metallothioneins. Whether this relates to an exposure to carcinogenic metals remains unclear. Methods In order to examine the association between the expression of metallothioneins and bladder tumors, and to compare the levels of arsenic, cadmium, chromium, lead and nickel in animals with bladder tumors and animals without bladder tumors, 37 cases of bovine bladder tumors and 17 controls were collected. The detection and quantification of metallothioneins in bladder tissue of both cases and controls was performed by immunohistochemistry. And the quantification of metals in tissue and hair was assessed by inductively coupled plasma – mass spectrometry. Results Increased expression of metallothioneins was associated with bladder tumors when compared with non-tumoral bladder tissue (OR = 9.3, 95% CI: 1.0 – 480. The concentrations of cadmium, chromium, lead and nickel in hair of cases were significantly higher than those of controls. However, as for the concentration of metals in bladder tissue, the differences were not significant. Conclusion Though the sample size was small, the present study shows an association between bladder tumors and metallothioneins. Moreover, it shows that concentrations of metals such as cadmium, chromium, lead and nickel in hair may be used as a biomarker of exposure.

Morphogenesis and Complexity of the Tumor Patterns

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Izquierdo-Kulich, E.; Nieto-Villar, J. M.

A mechanism to describe the apoptosis process at mesoscopic level through p53 is proposed in this paper. A deterministic model given by three differential equations is deduced from the mesoscopic approach, which exhibits sustained oscillations caused by a supercritical Andronov-Hopf bifurcation. Taking as hypothesis that the p53 sustained oscillation is the fundamental mechanism for apoptosis regulation; the model predicts that it is necessary a strict control of p53 to stimulated it, which is an important consideration to established new therapy strategy to fight cancer. The mathematical modeling of tumor growth allows us to describe the most important regularities of these systems. A stochastic model, based on the most important processes that take place at the level of individual cells, is proposed to predict the dynamical behavior of the expected radius of the tumor and its fractal dimension. It was found that the tumor has a characteristic fractal dimension, which contains the necessary information to predict the tumor growth until it reaches a stationary state. The mathematical modeling of tumor growth is an approach to explain the complex nature of these systems. A model that describes tumor growth was obtained by using a mesoscopic formalism and fractal dimension. This model theoretically predicts the relation between the morphology of the cell pattern and the mitosis/apoptosis quotient that helps to predict tumor growth from tumoral cells fractal dimension. The relation between the tumor macroscopic morphology and the cell pattern morphology is also determined. This could explain why the interface fractal dimension decreases with the increase of the cell pattern fractal dimension and consequently with the increase of the mitosis/apoptosis relation. Indexes to characterize tumoral cell proliferation and invasion capacities are proposed and used to predict the growth of different types of tumors. These indexes also show that the proliferation capacity is

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

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Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, pbrain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Childhood brain tumors: epidemiology, current management and future directions.

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Pollack, Ian F; Jakacki, Regina I

2011-07-26

Brain tumors are the most common solid tumors in children. With the increasingly widespread availability of MRI, the incidence of childhood brain tumors seemed to rise in the 1980s, but has subsequently remained relatively stable. However, management of brain tumors in children has evolved substantially during this time, reflecting refinements in classification of tumors, delineation of risk groups within histological subsets of tumors, and incorporation of molecular techniques to further define tumor subgroups. Although considerable progress has been made in the outcomes of certain tumors, prognosis in other childhood brain tumor types is poor. Among the tumor groups with more-favorable outcomes, attention has been focused on reducing long-term morbidity without sacrificing survival rates. Studies for high-risk groups have examined the use of intensive therapy or novel, molecularly targeted approaches to improve disease control rates. In addition to reviewing the literature and providing an overview of the complexities in diagnosing childhood brain tumors, we will discuss advances in the treatment and categorization of several tumor types in which progress has been most apparent, as well as those in which improvements have been lacking. The latest insights from molecular correlative studies that hold potential for future refinements in therapy will also be discussed.

Biology of dose rate in brachytherapy

International Nuclear Information System (INIS)

Brenner, David J.

1995-01-01

Purpose: This course is designed for practitioners and beginners in brachytherapy. The aim is to review biological principles underlying brachytherapy, to understand why current treatment regimes are the way they are, and to discuss what the future may hold in store. Brachytherapy has a long history. It was suggested as long ago as 1903 by Alexander Graham Bell, and the optimal application of this technique has been a subject of debate ever since. 'Brachy' means 'short', and the essential features of conventional brachytherapy are: positioning of the source a short distance from, or in, the tumor, allowing good dose distributions; short overall treatment times, to counter tumor repopulation; low dose rate, enabling a good therapeutic advantage between tumor control and damage to late-responding tissue. The advantages of good dose distributions speak for themselves; in some situations, as we shall see, computer-based dose optimization can be used to improve them still further. The advantages of short overall times stem from the fact that accelerated repopulation of the tumor typically begins a few weeks after the start of a radiation treatment. If all the radiation can be crammed in before that time, the risks of tumor repopulation can be considerably reduced. In fact even external-beam radiotherapy is moving in this direction, with the use of highly accelerated protocols. The advantages of low dose rate stem from the differential response to fractionation of early- and late-responding tissues. Essentially, lowering the dose rate spares late-responding tissue more than it does early-responding tissue such as tumors. We shall also discuss some recent innovations in the context of the general principles that have been outlined. For example, High dose rate brachytherapy, particularly for the uterine cervix: Does it work? If so, when and why? Use of Ir-192 sources, with a half life of 70 days: Should corrections be made for changing biological effectiveness as the dose

Stereotactic gamma radiosurgery of pineal and related tumors

International Nuclear Information System (INIS)

Kobayashi, Tatsuya; Mori, Yoshimasa; Yamada, Yasushi; Kida, Yoshihisa

2001-01-01

The role of gamma radiosurgery as an additional therapy after conventional treatments for pineal and related tumors was studied in 30 out of 33 cases with a mean follow-up of 23.3 months. Overall results showed that complete response (CR) was obtained in 8 cases (26.7%) and response rate was 73.3%. However, enlargement of the tumors was noted in 8 cases, of which 7 (23.3%) died of tumor progression (PG). Germinomas and pineocytomas showed higher response and control rates of 100%, and no tumor enlargement or death occurred after gamma knife treatment. In germinoma with STGC (syncytiotrophoblastic giant cell) which has been thought to have intermediate prognosis, two cases showed partial response (PR), but another died from progression of the disease. Malignant germ cell tumors and pineoblastomas showed unfavorable response and prognosis; the response and progression rates were 50%. However, complete response was obtained in 3 cases (25%) after gamma radiosurgery. Gamma knife was the initial treatment in three cases without pathological diagnosis in which one obtained CR and two showed partial response (PR). Stereotactic gamma radiosurgery is expected to be an effective and novel treatment for pineal and related tumors not only as an adjuvant, but also as an initial therapy. (author)

mTOR at the Transmitting and Receiving Ends in Tumor Immunity

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Yakir Guri

2018-03-01

Full Text Available Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study.

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Asante, Albert; Leonard, Phoebe H; Weaver, Amy L; Goode, Ellen L; Jensen, Jani R; Stewart, Elizabeth A; Coddington, Charles C

2013-06-01

To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Case-control study (Mayo Clinic Ovarian Cancer Study). Ongoing academic study of ovarian cancer. A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. None. Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation. Published by Elsevier Inc.

Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma

International Nuclear Information System (INIS)

Terahara, Atsuro; Niemierko, Andrzej; Goitein, Michael; Finkelstein, Dianne; Hug, Eugen; Liebsch, Norbert; O'Farrell, Desmond; Lyons, Sue; Munzenrider, John

1999-01-01

Purpose: When irradiating a tumor that abuts or displaces any normal structures, the dose constraints to those structures (if lower than the prescribed dose) may cause dose inhomogeneity in the tumor volume at the tumor-critical structure interface. The low-dose region in the tumor volume may be one of the reasons for local failure. The aim of this study is to quantitate the effect of tumor dose inhomogeneity on local control and recurrence-free survival in patients with skull base chordoma. Methods and Materials: 132 patients with skull base chordoma were treated with combined photon and proton irradiation between 1978 and 1993. This study reviews 115 patients whose dose-volume data and follow-up data are available. The prescribed doses ranged from 66.6 Cobalt-Gray-Equivalent (CGE) to 79.2 CGE (median of 68.9 CGE). The dose to the optic structures (optic nerves and chiasma), the brain stem surface, and the brain stem center was limited to 60, 64, and 53 CGE, respectively. We used the dose-volume histogram data derived with the three-dimensional treatment planning system to evaluate several dose-volume parameters including the Equivalent Uniform Dose (EUD). We also analyzed several other patient and treatment factors in relation to local control and recurrence-free survival. Results: Local failure developed in 42 of 115 patients, with the actuarial local control rates at 5 and 10 years being 59% and 44%. Gender was a significant predictor for local control with the prognosis in males being significantly better than that in females (P 0.004, hazard ratio = 2.3). In a Cox univariate analysis, with stratification by gender, the significant predictors for local control (at the probability level of 0.05) were EUD, the target volume, the minimum dose, and the D 5cc dose. The prescribed dose, histology, age, the maximum dose, the mean dose, the median dose, the D 90% dose, and the overall treatment time were not significant factors. In a Cox multivariate analysis, the

Low infection rate after tumor hip arthroplasty for metastatic bone disease in a cohort treated with extended antibiotic prophylaxis

DEFF Research Database (Denmark)

Hettwer, Werner H; Horstmann, Peter Frederik; Hovgaard, Thea Bechmann

2015-01-01

tumor resection for metastatic bone disease during a 4-year period from 2010 to 2013 (n = 105 patients). Results. Intravenous antibiotic prophylaxis was administrated for an extended duration of a mean of 7.4 days. The overall infection rate was 3.6% (4/111 implants), infection free survival was 96...... suggest that extended postoperative antibiotic prophylaxis may reduce the risk of PJI in patients undergoing tumor resection and endoprosthetic replacement for metastatic bone disease associated impending or de facto pathologic fractures of the proximal femur.......Background. Compared to conventional hip arthroplasty, endoprosthetic reconstruction after tumor resection is associated with a substantially increased risk of periprosthetic joint infection (PJI), with reported rates of around 10% in a recent systematic review. The optimal duration of antibiotic...

Laser ablation of tumors: current concepts and recent developments

International Nuclear Information System (INIS)

Stroszczynski, C.; Gaffke, G.; Gnauck, M.; Ricke, J.; Felix, R.; Puls, R.; Speck, U.; Hosten, N.; Oettle, H.; Hohenberger, P.

2004-01-01

Purpose. The purpose of this paper is to present technical innovations and clinical results of percutaneous interventional laser ablation of tumors using new techniques. Methods. Laser ablation was performed in 182 patients (liver tumors: 131, non hepatic tumors - bone, lung, others: 51) after interdisciplinary consensus was obtained. The procedure was done using a combination of imaging modalities (CT/MRI, CT/US) or only closed high field MRI (1.5 T). All patients received an MRI-scan immediately after laser ablation. Results. In 90.9% of the patients with liver tumors, a complete ablation was achieved. Major events occurred in 5.4%. The technical success rate of laser ablation in non-hepatic tumors was high, clinical results differed depending on the treated organ. Conclusions. The treatment of tumors of the liver and other organs up to 5 cm by laser ablation was a safe procedure with a low rate of complications and side effects. Image guidance by MRI is advantageous for precise tumor visualization in all dimensions, therapy monitoring, and control of laser ablation results. (orig.) [de

Rate control for electron gun evaporation

International Nuclear Information System (INIS)

Schellingerhout, A.J.G.; Janocko, M.A.; Klapwijk, T.M.; Mooij, J.E.

1989-01-01

Principles for obtaining high-quality rate control for electron gun evaporation are discussed. The design criteria for rate controllers are derived from this analysis. Results are presented which have been obtained with e-guns whose evaporation rate is controlled by a Wehnelt electrode or by sweeping of the electron beam. Further improvements of rate stability can be obtained by improved design of e-guns and power supplies

Cytologic anaplasia is a prognostic factor in osteosarcoma biopsies, but mitotic rate or extent of spontaneous tumor necrosis are not: a critique of the College of American Pathologists Bone Biopsy template.

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Cates, Justin Mm; Dupont, William D

2017-01-01

The current College of American Pathologists cancer template for reporting biopsies of bone tumors recommends including information that is of unproven prognostic significance for osteosarcoma, such as the presence of spontaneous tumor necrosis and mitotic rate. Conversely, the degree of cytologic anaplasia (degree of differentiation) is not reported in this template. This retrospective cohort study of 125 patients with high-grade osteosarcoma was performed to evaluate the prognostic impact of these factors in diagnostic biopsy specimens in predicting the clinical outcome and response to neoadjuvant chemotherapy. Multivariate Cox regression was performed to adjust survival analyses for well-established prognostic factors. Multivariate logistic regression was used to determine odds ratios for good chemotherapy response (≥90% tumor necrosis). Osteosarcomas with severe anaplasia were independently associated with increased overall and disease-free survival, but mitotic rate and spontaneous necrosis had no prognostic impact after controlling for other confounding factors. Mitotic rate showed a trend towards increased odds of a good histologic response, but this effect was diminished after controlling for other predictive factors. Neither spontaneous necrosis nor the degree of cytologic anaplasia observed in biopsy specimens was predictive of a good response to chemotherapy. Mitotic rate and spontaneous tumor necrosis observed in pretreatment biopsy specimens of high-grade osteosarcoma are not strong independent prognostic factors for clinical outcome or predictors of response to neoadjuvant chemotherapy. Therefore, reporting these parameters for osteosarcoma, as recommended in the College of American Pathologists Bone Biopsy template, does not appear to have clinical utility. In contrast, histologic grading schemes for osteosarcoma based on the degree of cytologic anaplasia may have independent prognostic value and should continue to be evaluated.

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects.

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Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E

2014-09-16

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6-70 years), among them eight children craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one's initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent.

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design.

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Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Victor; Altzibar, Jone M; Ardanaz, Eva; de Sanjosé, Sílvia; Jiménez-Moleón, José Juan; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán, Marina; Kogevinas, Manolis

2015-01-01

We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Modeling tumor growth in the presence of a therapy with an effect on rate growth and variability by means of a modified Gompertz diffusion process.

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Román-Román, Patricia; Román-Román, Sergio; Serrano-Pérez, Juan José; Torres-Ruiz, Francisco

2016-10-21

In experimental studies on tumor growth, whenever the time evolution of the relative volume of a tumor in an untreated (control) group can be fitted by a Gompertz diffusion process there is a possibility that an antiproliferative therapy, which modifies the growth rate of the process that fits the treated group, may also affect its variability. The present paper proposes several procedures for the estimation of the time function included in the infinitesimal variance of the new process, as well as the time function affecting the growth rate (which is included in the infinitesimal mean). Also, a hypothesis testing is designed to confirm or refute the need for including such a time-dependent function in the infinitesimal variance. In order to validate and compare the proposed procedures a simulation study has been carried out. In addition, a proposal is made for a strategy aimed at finding the optimal combination of procedures for each case. A real data application concerning the effects of cisplatin on a patient-derived xenograft (PDX) tumor model showcases the advantages of this model over others that have been used in the past. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Awareness rate, treatment rate and control rate of dyslipidemia in Chinese adults, 2010].

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Li, Jian-hong; Wang, Li-min; Mi, Sheng-quan; Zhang, Mei; Li, Yi-chong; Jiang, Yong; Xu, Yu; Dai, Meng; Wang, Lin-hong

2012-08-01

To explore the awareness, treatment and control rates of dyslipidemia among Chinese adults aged over 18 in 2010, and to analyze the prevalent features. 97 409 subjects aged over 18 were recruited from 162 monitoring sites around 31 provinces in China mainland in 2010, applying multi-stage stratified cluster random sampling method. Information about subjects' history of dyslipidemia, treatment and control were collected by face-to-face interview; and each subject's fasting venous blood was drawn in the morning before having food, to test total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C). In total, 51 818 cases of dyslipidemia ever or now, including 2235 subjects who once suffered from dyslipidemia but had their blood lipid controlled to normal, were screened out. And the awareness, treatment and control rates were calculated by complex weighting. The awareness rate of dyslipidemia among Chinese adults was 10.93%, while the stratified rates were 6.00%, 16.75% and 18.74% in the groups of subjects aged 18 - 44, 45 - 59 and over 60 years old, respectively (χ² = 1293.02, P China, respectively (χ² = 117.04, P China, respectively (χ² = 50.71, P control rate of dyslipidemia was 3.53% among total subjects, while whose stratified rates were 1.64%, 5.49% and 6.94% in the groups of subjects aged 18 - 44, 45 - 59 and over 60 years old, respectively (χ² = 554.12, P China, respectively (χ² = 91.45, P control rates of dyslipidemia have been comparatively low among Chinese adults, especially among the population who were young, or who were from rural area or western China.

Clinical results of radiation therapy for thymic tumors

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Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, Masaji; Fushiki, Masato

1991-12-01

From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author).

Clinical results of radiation therapy for thymic tumors

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Ono, Koji; Hiraoka, Masahiro; Kitakabu, Yoshizumi; Abe, Mitsuyuki; Takahashi, Masaji; Fushiki, Masato.

1991-01-01

From August 1968 to December 1989, 58 patients with thymoma, and 3 with thymic carcinoma were treated by radiotherapy using cobalt-60 gamma ray. Eleven cases were treated by radiotherapy alone, 1 by preoperative radiotherapy, 45 by postoperative radiotherapy, and 4 in combination with intraoperative radiotherapy. In thymoma, postoperative and intraoperative radiotherapies were effective, while concerning postoperative radiotherapy, operability was the major factor influencing survival and local control, and Stage I and II tumors resected totally or subtotally as well as Stage III tumors resected totally were good indications for such therapy. Cases of thymoma complicated by myasthenia gravis had a longer survival time and better local control rate than those without it. In the treatment of thymic carcinoma, it was suggested that the tumors can be controlled using complete resection and sufficient postoperative radiotherpay. (author)

Development of an acellular tumor extracellular matrix as a three-dimensional scaffold for tumor engineering.

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Wei-Dong Lü

Full Text Available Tumor engineering is defined as the construction of three-dimensional (3D tumors in vitro with tissue engineering approaches. The present 3D scaffolds for tumor engineering have several limitations in terms of structure and function. To get an ideal 3D scaffold for tumor culture, A549 human pulmonary adenocarcinoma cells were implanted into immunodeficient mice to establish xenotransplatation models. Tumors were retrieved at 30-day implantation and sliced into sheets. They were subsequently decellularized by four procedures. Two decellularization methods, Tris-Trypsin-Triton multi-step treatment and sodium dodecyl sulfate (SDS treatment, achieved complete cellular removal and thus were chosen for evaluation of histological and biochemical properties. Native tumor tissues were used as controls. Human breast cancer MCF-7 cells were cultured onto the two 3D scaffolds for further cell growth and growth factor secretion investigations, with the two-dimensional (2D culture and cells cultured onto the Matrigel scaffolds used as controls. Results showed that Tris-Trypsin-Triton multi-step treated tumor sheets had well-preserved extracellular matrix structures and components. Their porosity was increased but elastic modulus was decreased compared with the native tumor samples. They supported MCF-7 cell repopulation and proliferation, as well as expression of growth factors. When cultured within the Tris-Trypsin-Triton treated scaffold, A549 cells and human colorectal adenocarcinoma cells (SW-480 had similar behaviors to MCF-7 cells, but human esophageal squamous cell carcinoma cells (KYSE-510 had a relatively slow cell repopulation rate. This study provides evidence that Tris-Trypsin-Triton treated acellular tumor extracellular matrices are promising 3D scaffolds with ideal spatial arrangement, biomechanical properties and biocompatibility for improved modeling of 3D tumor microenvironments.

Investigating mechanisms of alkalinization for reducing primary breast tumor invasion.

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Robey, Ian F; Nesbit, Lance A

2013-01-01

The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P cancer where systemic alkalinization slows the rate of invasion.

Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

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Waldow, S M; Russell, G E; Wallner, P E

1992-01-01

Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

Spinal and Paraspinal Ewing Tumors

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Indelicato, Daniel J.; Keole, Sameer R.; Shahlaee, Amir H.; Morris, Christopher G.; Gibbs, C. Parker; Scarborough, Mark T.; Pincus, David W.; Marcus, Robert B.

2010-01-01

Purpose: To perform a review of the 40-year University of Florida experience treating spinal and paraspinal Ewing tumors. Patients and Methods: A total of 27 patients were treated between 1965 and 2007. For local management, 21 patients were treated with radiotherapy (RT) alone and 6 with surgery plus RT. All patients with metastatic disease were treated with RT alone. The risk profiles of each group were otherwise similar. The median age was 17 years, and the most frequent subsite was the sacral spine (n = 9). The median potential follow-up was 16 years. Results: The 5-year actuarial overall survival, cause-specific survival, and local control rate was 62%, 62%, and 90%, respectively. For the nonmetastatic subset (n = 22), the 5-year overall survival, cause-specific survival, and local control rate was 71%, 71%, and 89%, respectively. The local control rate was 84% for patients treated with RT alone vs. 100% for those treated with surgery plus RT. Patients who were >14 years old and those who were treated with intensive therapy demonstrated superior local control. Of 9 patients in our series with Frankel C or greater neurologic deficits at presentation, 7 experienced a full recovery with treatment. Of the 27 patients, 37% experienced Common Toxicity Criteria Grade 3 or greater toxicity, including 2 deaths from sepsis. Conclusion: Aggressive management of spinal and paraspinal Ewing tumors with RT with or without surgery results in high toxicity but excellent local control and neurologic outcomes. Efforts should be focused on identifying disease amenable to combined modality local therapy and improving RT techniques.

Optimal distributed control of a diffuse interface model of tumor growth

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Colli, Pierluigi; Gilardi, Gianni; Rocca, Elisabetta; Sprekels, Jürgen

2017-06-01

In this paper, a distributed optimal control problem is studied for a diffuse interface model of tumor growth which was proposed by Hawkins-Daruud et al in Hawkins-Daruud et al (2011 Int. J. Numer. Math. Biomed. Eng. 28 3-24). The model consists of a Cahn-Hilliard equation for the tumor cell fraction φ coupled to a reaction-diffusion equation for a function σ representing the nutrient-rich extracellular water volume fraction. The distributed control u monitors as a right-hand side of the equation for σ and can be interpreted as a nutrient supply or a medication, while the cost function, which is of standard tracking type, is meant to keep the tumor cell fraction under control during the evolution. We show that the control-to-state operator is Fréchet differentiable between appropriate Banach spaces and derive the first-order necessary optimality conditions in terms of a variational inequality involving the adjoint state variables. The financial support of the FP7-IDEAS-ERC-StG #256872 (EntroPhase) and of the project Fondazione Cariplo-Regione Lombardia MEGAsTAR ‘Matematica d’Eccellenza in biologia ed ingegneria come accelleratore di una nuona strateGia per l’ATtRattività dell’ateneo pavese’ is gratefully acknowledged. The paper also benefited from the support of the MIUR-PRIN Grant 2015PA5MP7 ‘Calculus of Variations’ for PC and GG, and the GNAMPA (Gruppo Nazionale per l’Analisi Matematica, la Probabilità e le loro Applicazioni) of INdAM (Istituto Nazionale di Alta Matematica) for PC, GG and ER.

Neuroendocrine Tumor: Statistics

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... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 01/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

International Nuclear Information System (INIS)

Wentworth, Stacy; Pinn, Melva; Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth; Ellis, Thomas L.; Glazier, Steven S.; McMullen, Kevin P.; Munley, Michael; Stieber, Volker W.; Tatter, Stephen B.; Shaw, Edward G.

2009-01-01

Purpose: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. Methods and Materials: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. Results: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. Conclusions: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors

Gamma Knife radiosurgery for glomus jugulare tumors: a single-center series of 75 cases.

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Ibrahim, Ramez; Ammori, Mohannad B; Yianni, John; Grainger, Alison; Rowe, Jeremy; Radatz, Matthias

2017-05-01

OBJECTIVE Glomus jugulare tumors are rare indolent tumors that frequently involve the lower cranial nerves (CNs). Complete resection can be difficult and associated with lower CN injury. Gamma Knife radiosurgery (GKRS) has established its role as a noninvasive alternative treatment option for these often formidable lesions. The authors aimed to review their experience at the National Centre for Stereotactic Radiosurgery, Sheffield, United Kingdom, specifically the long-term tumor control rate and complications of GKRS for these lesions. METHODS Clinical and radiological data were retrospectively reviewed for patients treated between March 1994 and December 2010. Data were available for 75 patients harboring 76 tumors. The tumors in 3 patients were treated in 2 stages. Familial and/or hereditary history was noted in 12 patients, 2 of whom had catecholamine-secreting and/or active tumors. Gamma Knife radiosurgery was the primary treatment modality in 47 patients (63%). The median age at the time of treatment was 55 years. The median tumor volume was 7 cm 3 , and the median radiosurgical dose to the tumor margin was 18 Gy (range 12-25 Gy). The median duration of radiological follow-up was 51.5 months (range 12-230 months), and the median clinical follow-up was 38.5 months (range 6-223 months). RESULTS The overall tumor control rate was 93.4% with low CN morbidity. Improvement of preexisting deficits was noted in 15 patients (20%). A stationary clinical course and no progression of symptoms were noted in 48 patients (64%). Twelve patients (16%) had new symptoms or progression of their preexisting symptoms. The Kaplan-Meier actuarial tumor control rate was 92.2% at 5 years and 86.3% at 10 years. CONCLUSIONS Gamma Knife radiosurgery offers a risk-versus-benefit treatment option with very low CN morbidity and stable long-term results.

Surgery of malignant pancreatic tumors

International Nuclear Information System (INIS)

Loos, M.; Friess, H.; Kleeff, J.

2009-01-01

Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite great efforts in basic and clinical pancreatic cancer research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection represents the only curative treatment option and 5-year survival rates of 20-25% can be achieved following curative resection and adjuvant chemotherapy. Although pancreatic surgery is considered one of the most technically demanding and challenging procedures, there has been constant progress in surgical techniques and advances in perioperative care with a modern interdisciplinary approach including anesthesiology, oncology, radiology and nursing. This has reduced morbidity and especially mortality rates in high-volume centers. Among extended resection procedures multivisceral and venous resections are technically feasible and should be considered if a complete tumor resection can be achieved. Multimodal regimens have shown promising results, however, only adjuvant chemotherapy is supported by solid evidence from randomized controlled trials. (orig.) [de

Long-Term Follow-up of Acoustic Schwannoma Radiosurgery With Marginal Tumor Doses of 12 to 13 Gy

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Chopra, Rahul; Kondziolka, Douglas; Niranjan, Ajay; Lunsford, L. Dade; Flickinger, John C.

2007-01-01

Purpose: To define long-term tumor control and clinical outcomes of radiosurgery with marginal tumor doses of 12 to 13 Gy for unilateral acoustic schwannoma. Methods and Materials: A total of 216 patients with previously untreated unilateral acoustic schwannoma underwent Gamma Knife radiosurgery between 1992 and 2000 with marginal tumor doses of 12 to 13 Gy (median, 13 Gy). Median follow-up was 5.7 years (maximum, 12 years; 41 patients with >8 years). Treatment volumes were 0.08-37.5 cm 3 (median, 1.3 cm 3 ). Results: The 10-year actuarial resection-free control rate was 98.3% ± 1.0%. Three patients required tumor resection: 2 for tumor growth and 1 partial resection for an enlarging adjacent subarachnoid cyst. Among 121 hearing patients with >3 years of follow-up, crude hearing preservation rates were 71% for keeping the same Gardner-Robertson hearing level, 74% for serviceable hearing, and 95% for any testable hearing. For 25 of these patients with intracanalicular tumors, the respective rates for preserving the same Gardner-Robertson level, serviceable hearing, and testable hearing were 80%, 88%, and 96%. Ten-year actuarial rates for preserving the same Gardner-Robertson hearing levels, serviceable hearing, any testable hearing, and unchanged facial and trigeminal nerve function were 44.0% ± 11.7%, 44.5% ± 10.5%, 85.3% ± 6.2%, 100%, and 94.9% ± 1.8%, respectively. Conclusions: Acoustic schwannoma radiosurgery with 12 to 13 Gy provides high rates of long-term tumor control and cranial nerve preservation after long-term follow-up

Intraoperative high-dose-rate brachytherapy for the treatment of pediatric tumors: the Ohio State University experience

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Nag, Subir; Tippin, Douglas; Ruymann, Frederick B.

2001-01-01

Purpose: To determine whether intraoperative high-dose-rate brachytherapy (IO-HDRBT) can be used to decrease the dose of external beam radiotherapy (EBRT) in the treatment of children with soft-tissue sarcomas and, thereby, reduce morbidity without compromising local control. Methods and Materials: From March 1992 through April 1999, 13 pediatric patients were treated with IO-HDRBT, low-dose EBRT, chemotherapy, and radical surgery at 21 sites that were not amenable to intraoperative electron beam therapy. The IO-HDRBT dose at 5 mm depth was 10 to 12.5 Gy for close margins/microscopic disease at 14 sites and 12.5 to 15 Gy for gross disease at 7 sites. The treatment volumes ranged from 4 to 96 cm 3 (mean 27). The EBRT dose was limited to 27-30 Gy in most cases to minimize growth retardation and preserve normal organ function. Results: After a median follow-up of 47 months (range 12-97), 11 patients were alive and without evidence of disease (overall survival rate 85%, 4-year actuarial survival rate 77%). Of the 2 who died, 1 had Stage III pulmonary blastoma with a sacral recurrence; the other had Stage IV undifferentiated synovial sarcoma with a pulmonary recurrence. One local failure occurred in a patient with gross residual disease after incomplete resection for Stage IV pulmonary blastoma. The local control rate was 95%, and morbidity was observed in 3 patients (23%). One patient developed impaired orbital growth with mild ptosis. Another patient required orthopedic pinning of her femoral subcapital epiphysis and construction of a neobladder secondary to urethral obstruction. The third patient required reimplantation of her autotransplanted kidney secondary to chronic urinary tract infection and ureteral reflux. Conclusions: IO-HDRBT allowed for reduction in EBRT without compromising local control or disease-free survival in children with soft-tissue sarcomas. Tumor beds inaccessible to electron beam methods could be satisfactorily encompassed with IO

Exploratory case-control study of brain tumors in adults

International Nuclear Information System (INIS)

Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

1987-01-01

An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies

Potential for tumor therapy with tritiated tetracycline. Summary evaluation. [Animal tests

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Davis, R.C.; Wood, P.; Wood, L.L.; Mendelsohn, M.L.

1976-10-26

Reports of tetracycline accumulation in human and animal tumors have led a number of investigators to postulate that this drug, if radio-labeled, might have potential as a therapeutic or diagnostic agent. This paper describes attempts to investigate this potential for tritiated tetracycling. The therapeutic studies demonstrated that while a significant reduction in the growth rates of transplanted tumors could be obtained by the administration of heavy doses of TTC relative to uninjected controls, similar reductions were observed in the growth rates of tumors in animals receiving unlabeled TC. In the localization studies in rodents, the concentrations of TTC in normal tissues and tumors were compared and were correlated with the corresponding concentrations of /sup 14/C-thymidine, a measure of proliferative activity.

Antigen localization controls T cell-mediated tumor immunity.

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Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

2011-08-01

Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo

International Nuclear Information System (INIS)

Perryman, L.A.; Blair, J.M.; Kingsley, E.A.; Szymanska, B.; Ow, K.T.; Wen, V.W.; MacKenzie, K.L.; Vermeulen, P.B.; Jackson, P.; Russell, P.J.

2006-01-01

This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous 'take rate' in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation

The bivariate probit model of uncomplicated control of tumor: a heuristic exposition of the methodology

International Nuclear Information System (INIS)

Herbert, Donald

1997-01-01

Purpose: To describe the concept, models, and methods for the construction of estimates of joint probability of uncomplicated control of tumors in radiation oncology. Interpolations using this model can lead to the identification of more efficient treatment regimens for an individual patient. The requirement to find the treatment regimen that will maximize the joint probability of uncomplicated control of tumors suggests a new class of evolutionary experimental designs--Response Surface Methods--for clinical trials in radiation oncology. Methods and Materials: The software developed by Lesaffre and Molenberghs is used to construct bivariate probit models of the joint probability of uncomplicated control of cancer of the oropharynx from a set of 45 patients for each of whom the presence/absence of recurrent tumor (the binary event E-bar 1 /E 1 ) and the presence/absence of necrosis (the binary event E 2 /E-bar 2 ) of the normal tissues of the target volume is recorded, together with the treatment variables dose, time, and fractionation. Results: The bivariate probit model can be used to select a treatment regime that will give a specified probability, say P(S) = 0.60, of uncomplicated control of tumor by interpolation within a set of treatment regimes with known outcomes of recurrence and necrosis. The bivariate probit model can be used to guide a sequence of clinical trials to find the maximum probability of uncomplicated control of tumor for patients in a given prognostic stratum using Response Surface methods by extrapolation from an initial set of treatment regimens. Conclusions: The design of treatments for individual patients and the design of clinical trials might be improved by use of a bivariate probit model and Response Surface Methods

Simulations of adaptive temperature control with self-focused hyperthermia system for tumor treatment.

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Hu, Jiwen; Ding, Yajun; Qian, Shengyou; Tang, Xiangde

2013-01-01

The control problem in ultrasound therapy is to destroy the tumor tissue while not harming the intervening healthy tissue with a desired temperature elevation. The objective of this research is to present a robust and feasible method to control the temperature distribution and the temperature elevation in treatment region within the prescribed time, which can improve the curative effect and decrease the treatment time for heating large tumor (≥2.0cm in diameter). An adaptive self-tuning-regulator (STR) controller has been introduced into this control method by adding a time factor with a recursive algorithm, and the speed of sound and absorption coefficient of the medium is considered as a function of temperature during heating. The presented control method is tested for a self-focused concave spherical transducer (0.5MHz, 9cm aperture, 8.0cm focal length) through numerical simulations with three control temperatures of 43°C, 50°C and 55°C. The results suggest that this control system has adaptive ability for variable parameters and has a rapid response to the temperature and acoustic power output in the prescribed time for the hyperthermia interest. There is no overshoot during temperature elevation and no oscillation after reaching the desired temperatures. It is found that the same results can be obtained for different frequencies and temperature elevations. This method can obtain an ellipsoid-shaped ablation region, which is meaningful for the treatment of large tumor. Copyright © 2012 Elsevier B.V. All rights reserved.

Radiation therapy for primary carcinoma of the eyelid. Tumor control and visual function

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Hata, M.; Koike, I.; Odagiri, K.; Kasuya, T.; Minagawa, Y.; Kaizu, H.; Mukai, Y.; Inoue, T. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Radiology; Maegawa, J. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Plastic and Reconstructive Surgery; Kaneko, A. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Ophthalmology

2012-12-15

Background and purpose: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma. Patients and methods: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions). Results: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater. Conclusion: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid. (orig.)

Leukemia and brain tumors in Norwegian railway workers, a nested case-control study.

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Tynes, T; Jynge, H; Vistnes, A I

1994-04-01

In an attempt to assess whether exposure to electromagnetic fields on Norwegian railways induces brain tumors or leukemia, the authors conducted a nested case-control study of railway workers based on incident cases from the Cancer Registry of Norway in a cohort of 13,030 male Norwegian railway workers who had worked on either electric or non-electric railways. The cohort comprised railway line, outdoor station, and electricity workers. The case series comprised 39 men with brain tumors and 52 men with leukemia (follow-up, 1958-1990). Each case was matched on age with four or five controls selected from the same cohort. The exposure of each study subject to electric and magnetic fields was evaluated from cumulative exposure measures based on present measurements and historical data. Limited information on potential confounders such as creosote, solvents, and herbicides was also collected; information on whether the subject had smoked was obtained by interviews with the subjects or work colleagues. The case-control analysis showed that men employed on electric railways, compared with non-electric ones, had an odds ratio for leukemia of 0.70 (adjusted for smoking) and an odds ratio for brain tumor of 0.87. No significant trend was shown for exposure to either magnetic or electric fields. These results do not support an association between exposure to 16 2/3-Hertz electric or magnetic fields and the risk for leukemia or brain tumors.

Increased growth rate of vestibular schwannoma after resection of contralateral tumor in neurofibromatosis type 2

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Peyre, Matthieu; Goutagny, Stephane; Imbeaud, Sandrine; Bozorg-Grayeli, Alexis; Felce, Michele; Sterkers, Olivier; Kalamarides, Michel

2011-01-01

Surgical management of bilateral vestibular schwannomas (VS) in neurofibromatosis type 2 (NF2) is often difficult, especially when both tumors threaten the brainstem. When the largest tumor has been removed, the management of the contralateral VS may become puzzling. To give new insights into the growth pattern of these tumors and to determine the best time point for treatment (surgery or medical treatment), we studied radiological growth in 11 VS (11 patients with NF2) over a long period (mean duration, 7.6 years), before and after removal of the contralateral tumor while both were threatening the brainstem. We used a quantitative approach of the radiological velocity of diametric expansion (VDE) on consecutive magnetic resonance images. Before first surgery, growth patterns of both tumors were similar in 9 of 11 cases. After the first surgery, VDE of the remaining VS was significantly elevated, compared with the preoperative period (2.5 ± 2.2 vs 4.4 ± 3.4 mm/year; P = .01, by Wilcoxon test). Decrease in hearing function was associated with increased postoperative growth in 3 cases. Growth pattern of coexisting intracranial meningiomas was not modified by VS surgery on the first side. In conclusion, removal of a large VS in a patient with NF2 might induce an increase in the growth rate of the contralateral medium or large VS. This possibility should be integrated in NF2 patient management to adequately treat the second VS. PMID:21798887

Determinants of Local Progression After Computed Tomography-Guided Percutaneous Radiofrequency Ablation for Unresectable Lung Tumors: 9-Year Experience in a Single Institution

International Nuclear Information System (INIS)

Okuma, Tomohisa; Matsuoka, Toshiyuki; Yamamoto, Akira; Oyama, Yoshimasa; Hamamoto, Shinichi; Toyoshima, Masami; Nakamura, Kenji; Miki, Yukio

2010-01-01

The purpose of this study was to retrospectively determine the local control rate and contributing factors to local progression after computed tomography (CT)-guided radiofrequency ablation (RFA) for unresectable lung tumor. This study included 138 lung tumors in 72 patients (56 men and 16 women; age 70.0 ± 11.6 years (range 31-94); mean tumor size 2.1 ± 1.2 cm [range 0.2-9]) who underwent lung RFA between June 2000 and May 2009. Mean follow-up periods for patients and tumors were 14 and 12 months, respectively. The local progression-free rate and survival rate were calculated to determine the contributing factors to local progression. During follow-up, 44 of 138 (32%) lung tumors showed local progression. The 1-, 2-, 3-, and 5-year overall local control rates were 61, 57, 57, and 38%, respectively. The risk factors for local progression were age (≥70 years), tumor size (≥2 cm), sex (male), and no achievement of roll-off during RFA (P < 0.05). Multivariate analysis identified tumor size ≥2 cm as the only independent factor for local progression (P = 0.003). For tumors <2 cm, 17 of 68 (25%) showed local progression, and the 1-, 2-, and 3-year overall local control rates were 77, 73, and 73%, respectively. Multivariate analysis identified that age ≥70 years was an independent determinant of local progression for tumors <2 cm in diameter (P = 0.011). The present study showed that 32% of lung tumors developed local progression after CT-guided RFA. The significant risk factor for local progression after RFA for lung tumors was tumor size ≥2 cm.

Mammographic density and risk of breast cancer by tumor characteristics: a case-control study.

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Krishnan, Kavitha; Baglietto, Laura; Stone, Jennifer; McLean, Catriona; Southey, Melissa C; English, Dallas R; Giles, Graham G; Hopper, John L

2017-12-16

In a previous paper, we had assumed that the risk of screen-detected breast cancer mostly reflects inherent risk, and the risk of whether a breast cancer is interval versus screen-detected mostly reflects risk of masking. We found that inherent risk was predicted by body mass index (BMI) and dense area (DA) or percent dense area (PDA), but not by non-dense area (NDA). Masking, however, was best predicted by PDA but not BMI. In this study, we aimed to investigate if these associations vary by tumor characteristics and mode of detection. We conducted a case-control study nested within the Melbourne Collaborative Cohort Study of 244 screen-detected cases matched to 700 controls and 148 interval cases matched to 446 controls. DA, NDA and PDA were measured using the Cumulus software. Tumor characteristics included size, grade, lymph node involvement, and ER, PR, and HER2 status. Conditional and unconditional logistic regression were applied as appropriate to estimate the Odds per Adjusted Standard Deviation (OPERA) adjusted for age and BMI, allowing the association with BMI to be a function of age at diagnosis. For screen-detected cancer, both DA and PDA were associated to an increased risk of tumors of large size (OPERA ~ 1.6) and positive lymph node involvement (OPERA ~ 1.8); no association was observed for BMI and NDA. For risk of interval versus screen-detected breast cancer, the association with risk for any of the three mammographic measures did not vary by tumor characteristics; an association was observed for BMI for positive lymph nodes (OPERA ~ 0.6). No associations were observed for tumor grade and ER, PR and HER2 status of tumor. Both DA and PDA were predictors of inherent risk of larger breast tumors and positive nodal status, whereas for each of the three mammographic density measures the association with risk of masking did not vary by tumor characteristics. This might raise the hypothesis that the risk of breast tumours with poorer prognosis

Mortality rate of lip, oral cavity and pharynx malignant tumors in Serbia within a period 1991-2009

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Ilić Milena

2013-01-01

Full Text Available Background/Aim. Lip, oral cavity and pharynx malignant tumors account for 3.7% of all cancer deaths worldwide, with significant geographic variations in frequency and distribution. The aim of this descriptive epidemiologic study was to analyze the mortality rate of lip, oral cavity and pharynx malignant tumors in Serbia proper within a period 1991-2009. Methods. Mortality rates standardized directly using the world population as the standard were used in data analysis. Linear trend and regression analyses were used to analyze rate trends in mortality. Results. The Serbian population demonstrated an increase in the mortality of lip, oral cavity and pharynx malignant tumors (y = 3.32 + 0.03×; p = 0.002; average annual percent change = + 0.8. The male population showed a significant increase in mortality trend (y = 5.90 + 0.03×; p = 0.020; % change = + 0.9, while the female population did not show a significant increase in mortality. The male/female cancer mortality ratio was 5.5:1. Mortality rates for lip, oral cavity and pharynx cancer increased with age in both genders, with rates being the highest in the population aged 85 and older. Increasing trends of lip, oral cavity and pharynx cancer mortality were observed in males aged 50-54; the average annual percent change was + 7.4 % (95% CI, 6.2-9.0. The population of both genders aged 55-59 demonstrated an increase in lip, oral cavity and pharynx cancer mortality, the increase being + 1.8% (95% CI, 1.4-2.2 in men and + 34.3% (95% CI, 28.4-40.2 in women. Conclusion. The increasing trend in lip, oral cavity and pharynx cancer mortality points to the necessity to investigate etiology and improve primary and secondary prevention measures.

Post-mastectomy radiation in large node-negative breast tumors: Does size really matter?

International Nuclear Information System (INIS)

Floyd, Scott R.; Taghian, Alphonse G.

2009-01-01

Treatment decisions regarding local control can be particularly challenging for T3N0 breast tumors because of difficulty in estimating rates of local failure after mastectomy. Reports in the literature detailing the rates of local failure vary widely, likely owing to the uncommon incidence of this clinical situation. The literature regarding this clinical scenario is reviewed, including recent reports that specifically address the issue of local failure rates after mastectomy in the absence of radiation for large node-negative breast tumors.

The dose-rate effect

International Nuclear Information System (INIS)

Steel, G.G.

1989-01-01

This paper presents calculations that illustrate two conclusions; for any particular cell type there will be a critical radius at which tumor control breaks down, and the radius at which this occurs is strongly dependent upon the low-dose-rate radiosensitivity of the cells

Metastasis to neck from unknown primary tumor

International Nuclear Information System (INIS)

Jose, B.; Bosch, A.; Caldwell, W.L.; Frias, Z.

1979-01-01

The records of 54 consecutive patients who were irradiated for metastatic disease in the neck from an unknown primary tumor were reviewed. The overall survival results are comparable to those of other reported series. Patients with high or posterior cervical lymph node involvement were irradiated with fields including the nasopharynx and oropharynx. Patients with high neck nodes had a better survival rate than those with low neck nodes. The size of the neck tumors and the local control after treatment also have prognostic significance. (Auth.)

Postoperative radiotherapy for malignant tumors of the submandibular gland

International Nuclear Information System (INIS)

Storey, Mark R.; Garden, Adam S.; Morrison, William H.; Eicher, Susan A.; Schechter, Naomi R.; Ang, K. Kian

2001-01-01

Purpose: This retrospective study assessed the outcome and patterns of failure for patients with malignant submandibular tumors treated with surgery and postoperative radiation. Methods and Materials: Between 1965 and 1995, 83 patients aged 11-83 years old received postoperative radiotherapy after resection of submandibular gland carcinomas. The most common radiation technique was an appositional field to the submandibular gland bed using electrons either alone or mixed with photons. Primary tumor bed doses ranged from 50 to 69 Gy (median, 60 Gy). Regional lymph nodes (ipsilateral Levels I-IV) were irradiated in 66 patients to a median dose of 50 Gy. Follow-up time ranged from 5 to 321 months (median, 82 months). Results: Actuarial locoregional control rates were 90%, 88%, and 88% at 2, 5, and 10 years, respectively. The corresponding disease-free survival rates were 76%, 60%, and 53%, because 27 of 74 patients (36%) who attained locoregional control developed distant metastases. Adenocarcinoma, high-grade histology, and treatment during the earlier years of the study were associated with worse locoregional control and disease-free survival. The median survival times for patients with and without locoregional control were 183 months and 19 months, respectively. Actuarial 2-, 5-, and 10-year survival rates were 84%, 71%, and 55%, respectively. Late complications occurred in 8 patients (osteoradionecrosis, 5 patients). Conclusions: High-risk cancers of the submandibular gland have a historic control rate of approximately 50% when treated with surgery alone. In the current series, locoregional control rates for high-risk patients with submandibular gland cancers treated with surgery and postoperative radiotherapy were excellent, with an actuarial locoregional control rate of 88% at 10 years

Long-term results of radiotherapy for pituitary adenomas. Evaluation of tumor control and hypopituitarism after radiotherapy

International Nuclear Information System (INIS)

Tsuchida, Emiko; Sakai, Kunio; Matsumoto, Yasuo; Sugita, Tadashi; Sasamoto, Ryuta

1999-01-01

To evaluate the results of conventional radiotherapy for pituitary adenomas assessed with computed tomography (CT) or magnetic resonance imaging (MRI). Endpoints include tumor control, normalization of hormone levels in functioning adenomas, and hypopituitarism after radiotherapy as an adverse effect. Forty-two patients were treated with radiotherapy from 1982 to 1995 at Niigata University Hospital. Forty patients were irradiated after surgery because of residual adenomas in 33 patients and tumor regrowth in 7 patients. One patient was treated with radiotherapy alone, and the remaining 1 patient was treated with preoperative radiotherapy. Tumor size and extension were evaluated using CT or MRI, and all tumors were macroadenomas. They consisted of 18 non-functioning and 24 functioning adenomas (growth hormone (GH)-secreting: 11, prolactinomas: 7, concomitant GH and prolactin (PRL)-secreting: 5, gonadotropin-secreting: 1). Treatment was given in 200 cGy daily fraction size and a total dose of 50 Gy was given to most patients. Sixteen patients with GH- and/or PRL-secreting adenomas received bromocriptine. Tumor progression was determined by increase in tumor size as shown by CT or MRI. Hypopituitarism after radiotherapy was evaluated using the functions of corticotropin (ACTH), thyrotropin (TSH), and gonadotropin. Median follow-up time from the end of radiotherapy was 103 months. Tumor progression occurred in 2 out of 42 patients and 10-year progression-free rate for all patients was 93.7%. Normalization of GH levels was obtained in 12 of 16 GH-secreting adenomas with a mean time of 27 months after radiotherapy, and 9 of 12 PRL-secreting adenomas achieved normalization of PRL levels with a mean time of 34 months. One gonadotropin-secreting adenoma achieved normalization of gonadotropin level at 21 months after radiotherapy. The incidence of hypopituitarism after radiotherapy increased with time, and cumulative risk of deficiencies of ACTH, TSH, and gonadotropin at 10

Pharmacologic Rhythm Control versus Rate Control in Heart Failure and Atrial Fibrillation

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Gladys Gladys

2017-01-01

Full Text Available Heart failure (HF with atrial fibrillation (AF is correlated with worse prognosis requiring special approach.Rate control has been the first line of treatment in cases of HF and HF. On the other hand, rhythm controlhas been proven to be effective in returning sinus rhythm resulting in better prognosis for patients with HFbut not HF. Its role in cocurring cases of HF and AF is not fully understood. Thus, this study aims to analysewhether pharmacologic rhythm control can be applied to cases of HF and AF to reduce mortality. A searchwas conducted via PubMed, Medline, ProQuest, and Cochrane Database on January 2016. One study wasselected after filtering process by inclusion and exclusion criteria and critical appraisal was performed. It wasfound that there was rhythm control and rate control do no have favouring effect towards mortality shown byRR 1.03 (95% CI 0.90-1.17, p=0.69. Rate control has protective effect towards hospitalizations by RR of 0.92(95% CI 0.86 – 0.98, p=0.008, NNT=19. To conclude, rhythm control is not superior to rate control in reducingmortality and rate control should be still be considered as first line treatment of HF and AF. Keywords: heart failure, pharmacologic rhythm control, rate control, atrial fibrillation   Farmakologis Rhythm Control Dibandingkan dengan Rate Control padaKasus Gagal Jantung dan Atrial Fibrilasi Abstrak Gagal jantung dengan atrial fibrilasi berhubungan dengan prognosis yang lebih buruk dan membutuhkanpenanganan khusus. Saat ini strategi rate control merupakan terapi lini pertama pada kasus gagal jantungdan atrial fibrilasi. Rhythm control memberikan prognosis yang lebih baik pada pasien gagal jantung denganmengembalikan sinus ritme. Kegunaan rhythm control pada kasus gagal jantung dan atrial fibrilasi sampaisaat ini belum sepenuhnya dimengerti. Tujuan studi ini adalah menelaah apakah terapi farmakologis rhythmcontrol dapat menurunkan mortalitas gagal jantung dan atrial fibrilasi. Pencarian data

Brain tumors : L-[1-C-11]tyrosine PET for visualization and quantification of protein synthesis rate

NARCIS (Netherlands)

Pruim, J; Willemsen, A T; Molenaar, W M; Waarde, A van; Paans, A M; Heesters, M A; Go, K G; Visser, Gerben; Franssen, E J; Vaalburg, W

1995-01-01

PURPOSE: Positron emission tomography (PET) with the amino acid tracer L-[1-C-11]-tyrosine was evaluated in 27 patients with primary and recurrent brain tumors. MATERIALS AND METHODS: Patients underwent either static (n = 14) or dynamic PET (n = 13), with quantification of protein synthesis rate

Surgical, radio and immunotherapy of syngeneic tumors in mice

International Nuclear Information System (INIS)

Engel, B.

1982-01-01

In untreated DBA/2 and (57 Black 6 mice the growth of and formation of metastases by syngeneic tumors (L 1210, EL 4, P 815 respectively Lewis Lung) was tested to obtain hints regarding the subsequent treatment modalities. In summary it can be said that each tumor type has its specific behaviour as regards the formation of metastases. Tumor-carrying mice were then operated on respectively received radiotherapy at different lengths of time after the tumor cell transplantation. The results led to the conclusion that an early therapy increased the survival rates. These findings were taken as a basis for further experiments in which tumor-carrying mice were exclusively treated 24 hours after the tumor cell transplantation. It was found that tumor-carrying animals, as compared to untreated control animals, were cured by surgical measures. Radiotherapy was successful in cases of L 1210 and EL 4 tumors. Animals carrying P 815 and Lewis Lung tumors that were irradiated 24 hours after the tumor cell transplantation died of progressive tumor growth. (orig./MG) [de

Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer

International Nuclear Information System (INIS)

Adell, Gunnar; Zhang Hong; Jansson, Agneta; Sun Xiaofeng; Staal, Olle; Nordenskjoeld, Bo

2001-01-01

Background: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival. Purpose: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy. Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen. Materials: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990. Results: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p=0.03), with a trend toward improved disease-free survival (p=0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates. Conclusion: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer

External beam irradiation of craniopharyngiomas: long-term analysis of tumor control and morbidity

International Nuclear Information System (INIS)

Varlotto, John M.; Flickinger, John C.; Kondziolka, Douglas; Lunsford, L.D.; Deutsch, Melvin

2002-01-01

Purpose: To delineate the long-term control and morbidity with external beam radiotherapy (EBRT) of craniopharyngiomas. Methods and Materials: Between 1971 and 1992, 24 craniopharyngioma patients underwent EBRT at the University of Pittsburgh. Most (19 of 24) were treated within 1-3 months after subtotal resection. The other prior surgical procedures were biopsy (n = 2) and gross total resection (n = 1); 2 patients did not undergo any surgical procedure. The median follow-up was 12.1 years. The median patient age was 29 years (range 5-69). The total radiation doses varied from 36 to 70 Gy (median 59.75). The normalized total dose (NTD, biologically equivalent dose given in 2 Gy/fraction [α/β ratio = 2]) varied from 28 to 83 Gy (median 55.35). Results: The actuarial survival rate at 10 and 20 years was 100% and 92.3%, respectively. The actuarial local control rate at 10 and 20 years was 89.1% and 54.0%, respectively. No local failures occurred with doses ≥60 Gy (n=12) or NTDs ≥55 Gy. The complication-free survival rate at 10 and 20 years was 80.1% and 72.1%, respectively. No complications were noted with an NTD of ≤55 Gy. The actuarial survival free from any adverse outcome (recurrence or complication) was 70.1% and 31.8% at 10 and 20 years, respectively. The adverse outcome-free survival appeared optimized (at 73%) with an NTD of 55-63 Gy. Multivariate analysis found that tumor control correlated significantly with the total dose (p=0.02), treatment complications with NTD (p=0.008), and adverse outcome with hypopituitarism on presentation (p=0.03). Conclusion: We recommend treating craniopharyngioma with 1.6-1.7-Gy dose fractions to 60 Gy to optimize outcome from EBRT

The role of radiation therapy in the management of desmoid tumors

International Nuclear Information System (INIS)

Schulz-Ertner, D.; Zierhut, D.; Mende, U.; Harms, W.; Branitzki, P.; Wannenmacher, M.

2002-01-01

Purpose: To investigate the role of radiation therapy (RT) in the management of desmoid tumors. Patients and Methods: Retrospective analysis was performed on 28 patients with desmoid tumors treated with radiation therapy between March 1989 and March 1999. Tumor site was intraabdominal in three, abdominal wall in three and extraabdominal in 22 patients. Median tumor dose was 48 Gy (range 36-60 Gy). Radiation therapy was delivered postoperatively in 26 of 28 patients, two patients received radiation therapy for unresectable recurrent tumors. Results: Median follow-up was 46 months (range 13-108 months). Actuarial 5-year control rate was 73%. We observed six recurrences, located within the radiation field in one patient, out of field in two and at the field margin in three patients. All patients with intraabdominal tumors have been controlled without severe side effects. Conclusions: Radiation therapy is an effective treatment after incomplete resection of desmoid tumors. We did not observe a benefit for tumor doses exceeding 50 Gy. In some patients with circumscribed intraabdominal desmoid tumors, radiation therapy might be a treatment option with low toxicity, if 3-D treatment planning is utilized. (orig.) [de

Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity.

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Yuanjie Hu

Full Text Available Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7 copy number variation (CNV in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers.

Response of melanoma tumor phospholipid metabolism to chloroethyle nitrosourea: a high resolution proton NMR spectroscopy study.

Science.gov (United States)

Morvan, Daniel; Demidem, Aïcha; Madelmont, Jean-Claude

2003-07-01

Phospholipid metabolism is tightly involved in tumor growth regulation and tumor cell survival. The response of phospholipid metabolism to chloroethyle nitrosourea treatment is investigated in a murine B16 melanoma model. Measurements of phospholipid derivatives are performed on intact tumor tissue samples using one- and two-dimensional proton NMR spectroscopy. During the tumor growth inhibition phase under treatment, tumors overexpress phosphocholine, phosphoethanolamine, glycerophosphocholine and glycerophosphoethanolamine, whereas phosphatidylcholine and phosphatidylethanolamine levels are maintained to control levels. During re-growth, which remained quantitatively much below control growth, chloroethyle nitrosourea-treated melanoma tumors overexpress phosphocholine and phosphoethanolamine only. In treated melanoma, phosphatidylcholine levels show an inverse relationship with tumor growth rates. In conclusion, chloroethyle nitrosourea-treated melanoma tumors maintain their phosphatidylcholine levels and exhibit transformed phospholipid metabolism phenotype, by mechanisms that could participate in tumor cell survival.

Metabolic Control Analysis aimed at the ribose synthesis pathways of tumor cells: a new strategy for antitumor drug development

NARCIS (Netherlands)

Boren, Joan; Montoya, Antonio Ramos; de Atauri, Pedro; Comin-Anduix, Begoña; Cortes, Antonio; Centelles, Josep J.; Frederiks, Wilma M.; van Noorden, Cornelis J. F.; Cascante, Marta

2002-01-01

Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo

Enhanced tumor responses through therapies combining CCNU, MISO and radiation

International Nuclear Information System (INIS)

Siemann, D.W.; Hill, S.A.

1984-01-01

Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

MR imaging-guided percutaneous cryotherapy for lung tumors: initial experience.

Science.gov (United States)

Liu, Shangang; Ren, Ruimei; Liu, Ming; Lv, Yubo; Li, Bin; Li, Chengli

2014-09-01

To evaluate prospectively the initial clinical experience of magnetic resonance (MR) imaging-guided percutaneous cryotherapy of lung tumors. MR imaging-guided percutaneous cryotherapy was performed in 21 patients with biopsy-proven lung tumors (12 men, 9 women; age range, 39-79 y). Follow-up consisted of contrast-enhanced chest computed tomography (CT) scan performed at 3-month intervals to assess tumor control; CT scanning was carried out for 12 months or until death. Cryotherapy procedures were successfully completed in all 21 patients. Pneumothorax occurred in 7 (33.3%) of 21 patients. Chest tube placement was required in one (4.8%) case. Hemoptysis was exhibited by 11 (52.4%) patients, and pleural effusion occurred in 6 (28.6%) patients. Other complications were observed in 14 (66.7%) patients. The mean follow-up period was 10.5 months (range, 9-12 mo) in patients who died. At month 12 of follow-up, 7 (33.3%) patients had a complete response to therapy, and 10 (47.6%) patients showed a partial response. In addition, two patients had stable disease, and two patients developed progressive disease; one patient developed a tumor in the liver, and the other developed a tumor in the brain. The 1-year local control rate was 81%, and 1-year survival rate was 90.5%. MR imaging-guided percutaneous cryotherapy appears feasible, effective, and minimally invasive for lung tumors. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Rate Control for MPEG-4 Bit Stream

Institute of Scientific and Technical Information of China (English)

王振洲; 李桂苓

2003-01-01

For a very long time video processing dealt exclusively with fixed-rate sequences of rectangular shaped images. However, interest has been recently moving toward a more flexible concept in which the subject of the processing and encoding operations is a set of visual elements organized in both time and space in a flexible and arbitrarily complex way. The moving picture experts group (MPEG-4) standard supports this concept and its verification model (VM) encoder has adopted scalable rate control (SRC) as the rate control scheme, which is based on the spatial domain and compatible with constant bit rate (CBR) and variable bit rate (VBR). In this paper,a new rate control algorithm based on the DCT domain instead of the pixel domain is presented. More-over, macroblock level rate control scheme to compute the quantization step for each macroblock has been adopted. The experimental results show that the new algorithm can achieve a much better result than the original one in both peak signal-to-noise ratio (PSNR) and the coding bits, and that the new algorithm is more flexible than test model 5 (TM5) rate control algorithm.

Rate-cost tradeoffs in control

KAUST Repository

Kostina, Victoria

2017-02-13

Consider a distributed control problem with a communication channel connecting the observer of a linear stochastic system to the controller. The goal of the controller is minimize a quadratic cost function. The most basic special case of that cost function is the mean-square deviation of the system state from the desired state. We study the fundamental tradeoff between the communication rate r bits/sec and the limsup of the expected cost b, and show a lower bound on the rate necessary to attain b. The bound applies as long as the system noise has a probability density function. If target cost b is not too large, that bound can be closely approached by a simple lattice quantization scheme that only quantizes the innovation, that is, the difference between the controller\\'s belief about the current state and the true state.

Study of CT-guided iodine-125 implantation in the treatment of rabbit VX2 tumor

International Nuclear Information System (INIS)

He Kewu; Gao Bin; Li Jiajia

2008-01-01

Objective: To evaluate the effect of CT-guided iodine-125 seed( 125 I) implantation to rabbit model VX2 tumor cell apoptosis. Methods: VX2 tumor cells were implanted into muscle of 40 rabbits legs, 3 weeks later, as the diameter of tumor reached 2 cm available for test. Randomly selected the sampling tumor on one leg of rabbit as for the test team and tumor on the contralateral leg as for control team. Under CT guidance, 125 I seeds were implanted into 20 tumor lesions of the test team, and hollow seeds were implanted into 20 tumor lesions of the control team. Instantly, 72 h, 1, 2, 3 w after operation, percutaneous tumor tissue sampling was done 0.5-1.0 cm and 1.0-1.5 cm away from seed implanted site under CT guidance; and apoptosis was investigated by FCM. Results: Instantly, 72 h, 1, 2, 3 w after treatment with iodine-125 ( 125 I) implantation, the tissue sampling away from seed 0.5-1.0 cm showed the apoptosis rates of control team and test team were respectively as follows: (5.43±0.67)% and (5.48±0.66)%, (P>0.05), (5.45±0.58)% and (11.60±0.87)%, (P O.05)of the control team and test team. Conclusions: 125 I seeds implantation can induce tumor cell apoptosis, beginning at 72 h and reached peak at 2 w and kept the high level here afterword. The apoptosis rate descended rapidly along with the increase of distance away from the 125 I seedling. (authors)

Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

Directory of Open Access Journals (Sweden)

C.M. Souza

2014-10-01

Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

The incidence rate and mortality of malignant brain tumors after 10 years of intensive cell phone use in Taiwan.

Science.gov (United States)

Hsu, Min-Huei; Syed-Abdul, Shabbir; Scholl, Jeremiah; Jian, Wen-Shan; Lee, Peisan; Iqbal, Usman; Li, Yu-Chuan

2013-11-01

The issue of whether cell phone usage can contribute toward the development of brain tumors has recently been reignited with the International Agency for Research on Cancer classifying radiofrequency electromagnetic fields as 'possibly' carcinogenic to humans in a WHO report. To our knowledge, this is the largest study reporting on the incidence and mortality of malignant brain tumors after long-term use of the cell phone by more than 23 million users. A population-based study was carried out the numbers of cell phone users were collected from the official statistics provided by the National Communication Commission. According to National Cancer Registry, there were 4 incidences and 4 deaths due to malignant neoplasms in Taiwan during the period 2000-2009. The 10 years of observational data show that the intensive user rate of cell phones has had no significant effect on the incidence rate or on the mortality of malignant brain tumors in Taiwan. In conclusion, we do not detect any correlation between the morbidity/mortality of malignant brain tumors and cell phone use in Taiwan. We thus urge international agencies to publish only confirmatory reports with more applicable conclusions in public. This will help spare the public from unnecessary worries.

Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

International Nuclear Information System (INIS)

Wasserman, Todd H.; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

2005-01-01

Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m 2 i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade ≥2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival

Effect of the pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial

International Nuclear Information System (INIS)

Xiaobin, Feng; Shuguang, Wang; Ping, Bie; Jiahong, Dong; Shuguo, Zheng; Jian, Zhou; Yudong, Qiu; Lijian, Liang; Kuansheng, Ma; Xiaowu, Li; Feng, Xia; Dong, Yi

2012-01-01

Hepatic resection is currently still the best choice of therapeutic strategies for liver cancer, but the long-term survival rate after surgery is unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The reasons for this high recurrence rate are not entirely clear. Recent studies have indicated that ischemia-reperfusion injury to the liver may be a significant factor promoting tumor recurrence and metastasis in animal models. If this is also true in humans, the effects of the Pringle maneuver, which has been widely used in hepatectomy for the past century, should be examined. To date, there are no reported data or randomized controlled studies examining the relationship between use of the Pringle maneuver and local tumor recurrence. We hypothesize that the long-term prognosis of patients with liver cancer could be worsened by use of the Pringle maneuver due to an increase in the rate of tumor recurrence in the liver remnant. We designed a multicenter, prospective, randomized surgical trial to test this hypothesis. At least 498 eligible patients from five participating centers will be enrolled and randomized into either the Pringle group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks randomization protocol. After the completion of surgical intervention, patients will be included in a 3-year follow-up program. This multicenter surgical trial will examine whether the Pringle maneuver has a negative effect on the long-term outcome of hepatocellular carcinoma patients. The trial will also provide information about prognostic differences, safety, advantages and disadvantages between Pringle and non-Pringle surgical procedures. Ultimately, the results will increase the available information about the effects of ischemia-reperfusion injury on tumor recurrence, which will be of immense benefit to general surgery.

Occurrence of mammary tumors in beagls given radium-226

International Nuclear Information System (INIS)

Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

1994-01-01

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226 Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226 Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon → polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs

Use of the Concept of Equivalent Biologically Effective Dose (BED) to Quantify the Contribution of Hyperthermia to Local Tumor Control in Radiohyperthermia Cervical Cancer Trials, and Comparison With Radiochemotherapy Results

International Nuclear Information System (INIS)

Plataniotis, George A.; Dale, Roger G.

2009-01-01

Purpose: To express the magnitude of contribution of hyperthermia to local tumor control in radiohyperthermia (RT/HT) cervical cancer trials, in terms of the radiation-equivalent biologically effective dose (BED) and to explore the potential of the combined modalities in the treatment of this neoplasm. Materials and Methods: Local control rates of both arms of each study (RT vs. RT+HT) reported from randomized controlled trials (RCT) on concurrent RT/HT for cervical cancer were reviewed. By comparing the two tumor control probabilities (TCPs) from each study, we calculated the HT-related log cell-kill and then expressed it in terms of the number of 2 Gy fraction equivalents, for a range of tumor volumes and radiosensitivities. We have compared the contribution of each modality and made some exploratory calculations on the TCPs that might be expected from a combined trimodality treatment (RT+CT+HT). Results: The HT-equivalent number of 2-Gy fractions ranges from 0.6 to 4.8 depending on radiosensitivity. Opportunities for clinically detectable improvement by the addition of HT are only available in tumors with an alpha value in the approximate range of 0.22-0.28 Gy -1 . A combined treatment (RT+CT+HT) is not expected to improve prognosis in radioresistant tumors. Conclusion: The most significant improvements in TCP, which may result from the combination of RT/CT/HT for locally advanced cervical carcinomas, are likely to be limited only to those patients with tumors of relatively low-intermediate radiosensitivity.

Origin of induced pancreatic islet tumors: a radioautographic study

International Nuclear Information System (INIS)

Michels, J.E.; Bauer, G.E.; Dixit, P.K.

1987-01-01

Endocrine tumors of the pancreas are induced in a high percentage of young rats by injections of streptozotocin and nicotinamide (SZ/NA). Benign tumors first appear 20 to 36 weeks after drug injections. To determine the possible site of their origin, the incorporation of [ 3 H]thymidine into islets, ducts, acini, microtumors, and gross tumors was examined by radioautography of histologic sections at 1 to 36 weeks after drug injection. Drug treatment led to early (1- to 6-week) increases in nuclear 3 H labeling of exocrine pancreatic structures (ductal and acinar cells), which may involve DNA repair processes. A secondary increase in labeling of duct cells during the period of tumor emergence supports the assumption that SZ/NA-induced tumors are of ductal origin. Microtumors and gross tumors also exhibited markedly elevated rates of [ 3 H]thymidine incorporation compared to control islets. Nontumorous islet tissue, which exhibited a gradual decrease in volume due to B-cell destruction by the drug injection, showed about 10-fold higher 3 H labeling than islets of controls at all time points. The results suggest that in addition to ductal precursors, islets that survive SZ/NA-induced injury may also provide sites of focal endocrine cell differentiation to tumor tissue. Once established, both microtumors and gross tumors continue to grow by accelerated cell division

Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

Science.gov (United States)

Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

2017-08-01

Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of hypofractionated radiotherapy in loco-regional tumor control in breast

International Nuclear Information System (INIS)

Riaz, O.; Mahmood, A.; Rasul, S.; Haider, N.; Gul, S.

2017-01-01

Objective: To evaluate the efficacy of hypofractionated radiotherapy (HFRT) in locoregional control (LRC) in breast cancer. Study Design: Descriptive case series. Place and Duration of Study: Oncology Department of CMH Rawalpindi, from Jan 2014 to Oct 2014. Material and Methods: Fifty three female patients with histopathologically confirmed breast cancer and Eastern Cooperative Oncology Group performance status (ECOG-PS) greater than equal to 2 were enrolled in the study. These patients required post-operative radio-therapy to intact breast/ chest wall / residual breast tissue were treated using linear accelerator. Lateral/medial tangential and ipsilateral supraclavicular fields were employed to a dose of 39 Gy in 13 fractions with 6 MV photon beam. The ipsilateral axilla was also radiated if required to same dose with postero-anterior field. Scar boost was administered using 6 MeV electron beam to a dose of 7.5 Gy in 3 fractions in patients with high risk features for local recurrence like high grade, positive axillary nodes, lymphovascular invasion and close or positive surgical resection margins. Patients were followed up weekly during radio-therapy (RT) and three monthly after completion of RT for a period of 6 months. Any suspicious lesion was subjected to biopsy. Data analysis was done with the help of the Statistical Package for the Social Sciences (SPSS) version 19 software, which included descriptive analysis. Loco-regional control (LRC) and loco-regional recurrence (LRR) rates were calculated. LRC was no recurrence of tumor/tumor control in chest wall, axilla, residual breast tissue, and/or infraclavicular/supraclavicular lymph nodes. LRR was appearance of nodules / leison at local site which was biopsied and confirmed histopathologically. Results: Fifty three female patients with histopathologically confirmed breast cancer and ECOG-PS greater than equal to 2 requiring post-operative radio-therapy to intact breast/chest wall/ residual breast tissue were

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects

International Nuclear Information System (INIS)

Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E

2014-01-01

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6–70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 – 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. During median follow up of 128 months (2 – 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one’s initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent

SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

Energy Technology Data Exchange (ETDEWEB)

Huang, Z [East Carolina University, Greenville, NC (United States); Feng, Y [East Carolina Univ, Rockville, MD (United States); Lo, S [Case Western Reserve University, Cleveland, OH (United States); Grecula, J [Ohio State University, Columbus, OH (United States); Mayr, N; Yuh, W [University of Washington, Seattle, WA (United States)

2015-06-15

Purpose: The dose–volume histogram (DVH) has been normally accepted as a tool for treatment plan evaluation. However, spatial information is lacking in DVH. As a supplement to the DVH in three-dimensional treatment planning, the differential DVH (DDVH) provides the spatial variation, the size and magnitude of the different dose regions within a region of interest, which can be incorporated into tumor control probability model. This study was to provide a method in evaluating and improving Gamma Knife treatment planning. Methods: 10 patients with brain metastases from different primary tumors including melanoma (#1,#4,#5, #10), breast cancer (#2), prostate cancer (#3) and lung cancer (#6–9) were analyzed. By using Leksell GammaPlan software, two plans were prepared for each patient. Special attention was given to the DDVHs that were different for different plans and were used for a comparison between two plans. Dose distribution inside target and tumor control probability (TCP) based on DDVH were calculated, where cell density and radiobiological parameters were adopted from literature. The plans were compared based on DVH, DDVH and TCP. Results: Using DVH, the coverage and selectivity were the same between plans for 10 patients. DDVH were different between two plans for each patient. The paired t-test showed no significant difference in TCP between the two plans. For brain metastases from melanoma (#1, #4–5), breast cancer (#2) and lung cancer (#6–8), the difference in TCP was less than 5%. But the difference in TCP was about 6.5% for patient #3 with the metastasis from prostate cancer, 10.1% and 178.7% for two patients (#9–10) with metastasis from lung cancer. Conclusion: Although DVH provides average dose–volume information, DDVH provides differential dose– volume information with respect to different regions inside the tumor. TCP provides radiobiological information and adds additional information on improving treatment planning as well as adaptive

SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

International Nuclear Information System (INIS)

Huang, Z; Feng, Y; Lo, S; Grecula, J; Mayr, N; Yuh, W

2015-01-01

Purpose: The dose–volume histogram (DVH) has been normally accepted as a tool for treatment plan evaluation. However, spatial information is lacking in DVH. As a supplement to the DVH in three-dimensional treatment planning, the differential DVH (DDVH) provides the spatial variation, the size and magnitude of the different dose regions within a region of interest, which can be incorporated into tumor control probability model. This study was to provide a method in evaluating and improving Gamma Knife treatment planning. Methods: 10 patients with brain metastases from different primary tumors including melanoma (#1,#4,#5, #10), breast cancer (#2), prostate cancer (#3) and lung cancer (#6–9) were analyzed. By using Leksell GammaPlan software, two plans were prepared for each patient. Special attention was given to the DDVHs that were different for different plans and were used for a comparison between two plans. Dose distribution inside target and tumor control probability (TCP) based on DDVH were calculated, where cell density and radiobiological parameters were adopted from literature. The plans were compared based on DVH, DDVH and TCP. Results: Using DVH, the coverage and selectivity were the same between plans for 10 patients. DDVH were different between two plans for each patient. The paired t-test showed no significant difference in TCP between the two plans. For brain metastases from melanoma (#1, #4–5), breast cancer (#2) and lung cancer (#6–8), the difference in TCP was less than 5%. But the difference in TCP was about 6.5% for patient #3 with the metastasis from prostate cancer, 10.1% and 178.7% for two patients (#9–10) with metastasis from lung cancer. Conclusion: Although DVH provides average dose–volume information, DDVH provides differential dose– volume information with respect to different regions inside the tumor. TCP provides radiobiological information and adds additional information on improving treatment planning as well as adaptive

Endoscopic third ventriculostomy and posterior fossa tumors.

Science.gov (United States)

Di Rocco, Federico; Jucá, Carlos Eduardo; Zerah, Michel; Sainte-Rose, Christian

2013-02-01

The management of hydrocephalus associated with a posterior fossa tumor is debated. Some authors emphasize the advantages of an immediate tumor removal that may normalize the cerebrospinal fluid (CSF) dynamics. However, in clinical practice, the mere excision of the lesion has been demonstrated to be accompanied by a persisting hydrocephalus in about one third of the cases. Preoperative endoscopic third ventriculostomy (ETV) offers several advantages. It may control the intracranial pressure (ICP), avoid the necessity of an emergency procedure, allow appropriate scheduling of the operation for tumor removal, and eliminate the risks related to the presence of an external drainage. The procedure also reduces the incidence of postoperative hydrocephalus. A final advantage, more difficult to weight, but obvious to the neurosurgeon, is the possibility to remove the lesion with a relaxed brain and normal ICP. In the postoperative phase, ETV can be used in case of persisting hydrocephalus, both in patients who underwent only the excision of the tumor and in those whose preoperative ETV failed as a consequence of intraventricular bleeding with secondary closure of the stoma (redoETV). The main advantage of postoperative ETV is that the procedure is carried out only in case of persisting hydrocephalus; its use is consequently more selective than preoperative ETV. The disadvantage consists in the common use of an external CSF drainage in the first few postoperative days, which is necessary to control the pressure and for ruling out those cases that reach a spontaneous cure of the hydrocephalus. The authors review the criteria for patient selection and the results of ETV performed in case of hydrocephalus secondary to a posterior fossa tumor. Preoperative ETV constitutes an effective procedure for controlling the hydrocephalus associated with posterior fossa tumors. It might lower the rate of persistent postoperative hydrocephalus and result in a short hospital stay. Low

Essential contribution of tumor-derived perlecan to epidermal tumor growth and angiogenesis

DEFF Research Database (Denmark)

Jiang, Xinnong; Multhaupt, Hinke; Chan, En

2004-01-01

As a major heparan sulfate proteoglycan (PG) in basement membranes, perlecan has been linked to tumor invasion, metastasis, and angiogenesis. Here we produced epidermal tumors in immunocompromised rats by injection of mouse RT101 tumor cells. Tumor sections stained with species-specific perlecan...... factor. In vivo, antisense perlecan-transfected cells generated no tumors, whereas untransfected and vector-transfected cells formed tumors with obvious neovascularization, suggesting that tumor perlecan rather than host perlecan controls tumor growth and angiogenesis....

Rate control is more cost-effective than rhythm control for patients with persistent atrial fibrillation - results from the RAte Control versus Electrical cardioversion (RACE) study

NARCIS (Netherlands)

Hagens, VE; Vermeulen, KM; TenVergert, EM; Van Veldhuisen, JGP; Bosker, HA; Kamp, O; Kingma, JH; Tijssen, JGP; Crijns, HJGM; Van Gelder, IC

Aims To evaluate costs between a rate and rhythm control strategy in persistent atrial. fibrillation. Methods and results In a prospective substudy of RACE (Rate control versus electrical cardioversion for persistent atrial. fibrillation) in 428 of the total 522 patients (206 rate control and 222

Relationship between the generalized equivalent uniform dose formulation and the Poisson statistics-based tumor control probability model

International Nuclear Information System (INIS)

Zhou Sumin; Das, Shiva; Wang Zhiheng; Marks, Lawrence B.

2004-01-01

The generalized equivalent uniform dose (GEUD) model uses a power-law formalism, where the outcome is related to the dose via a power law. We herein investigate the mathematical compatibility between this GEUD model and the Poisson statistics based tumor control probability (TCP) model. The GEUD and TCP formulations are combined and subjected to a compatibility constraint equation. This compatibility constraint equates tumor control probability from the original heterogeneous target dose distribution to that from the homogeneous dose from the GEUD formalism. It is shown that this constraint equation possesses a unique, analytical closed-form solution which relates radiation dose to the tumor cell survival fraction. It is further demonstrated that, when there is no positive threshold or finite critical dose in the tumor response to radiation, this relationship is not bounded within the realistic cell survival limits of 0%-100%. Thus, the GEUD and TCP formalisms are, in general, mathematically inconsistent. However, when a threshold dose or finite critical dose exists in the tumor response to radiation, there is a unique mathematical solution for the tumor cell survival fraction that allows the GEUD and TCP formalisms to coexist, provided that all portions of the tumor are confined within certain specific dose ranges

Proton radiotherapy in management of pediatric base of skull tumors

International Nuclear Information System (INIS)

Hug, Eugen B.; Sweeney, Reinhart A.; Nurre, Pamela M.; Holloway, Kitty C.; Slater, Jerry D.; Munzenrider, John E.

2002-01-01

Purpose: Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. Methods and Materials: Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma (n=10), chondrosarcoma (n=3), rhabdomyosarcoma (n=4), and other sarcomas (n=3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors (n=6), angiofibromas (n=2), and chondroblastoma (n=1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). Results: Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival

Clinical application of preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta in the resection of sacral tumors

International Nuclear Information System (INIS)

Chen Wenhua; Wang Qi; He Zhongming; Zhou Jian; Wang Yimin; Wang Jie

2012-01-01

Objective: To investigate the clinical application of preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta in performing the surgical resection of sacral tumors. Methods: Conventional surgical excision of sacral tumors was employed in 24 patients with sacral tumors (control group), while preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta was carried out in 32 patients with sacral tumors (study group). The operation time, blood loss during the surgery and the one-year recurrence rate of both groups were documented, and the results were statistically analyzed. Results: Angiography showed that in the study group the sacral tumors were supplied by several vessels, and these feeding arteries were occluded separately. The tumors were successfully removed in all patients with the help of intraoperative balloon occlusion of the abdominal aorta. During the surgery, the surgical area was clearly exposed and the blood loss wa remarkably reduced. After the surgery, no ectopic vascular embolization, renal ischemia, limb ischemia or other complications occurred. Statistically significant difference in the operation time, blood loss during the surgery and the one-year recurrence rate existed between the two groups (P<0.05). Conclusion: Preoperative embolization of tumor feeding artery combined with intraoperative balloon occlusion of the abdominal aorta can effectively shorten the operation time, reduce the blood loss during the surgery and provide a clear surgical field, and thus the surgical safety can be significantly ensured. (authors)

The Effects of Gun Ownership Rates and Gun Control Laws on Suicide Rates

OpenAIRE

Mark Gius

2011-01-01

The purpose of the present study is to determine the effects of gun control laws and gun ownership rates on state-level suicide rates. Using the most recent data on suicide rates, gun control measures, and gun ownership rates, the results of the present study suggest that states that require handgun permits have lower gun-related suicide rates, and states that have higher gun ownership rates have higher gun-related suicide rates. Regarding non-gun suicides, results suggest that stricter gun c...

Multiparametric classification links tumor microenvironments with tumor cell phenotype.

Directory of Open Access Journals (Sweden)

Bojana Gligorijevic

2014-11-01

Full Text Available While it has been established that a number of microenvironment components can affect the likelihood of metastasis, the link between microenvironment and tumor cell phenotypes is poorly understood. Here we have examined microenvironment control over two different tumor cell motility phenotypes required for metastasis. By high-resolution multiphoton microscopy of mammary carcinoma in mice, we detected two phenotypes of motile tumor cells, different in locomotion speed. Only slower tumor cells exhibited protrusions with molecular, morphological, and functional characteristics associated with invadopodia. Each region in the primary tumor exhibited either fast- or slow-locomotion. To understand how the tumor microenvironment controls invadopodium formation and tumor cell locomotion, we systematically analyzed components of the microenvironment previously associated with cell invasion and migration. No single microenvironmental property was able to predict the locations of tumor cell phenotypes in the tumor if used in isolation or combined linearly. To solve this, we utilized the support vector machine (SVM algorithm to classify phenotypes in a nonlinear fashion. This approach identified conditions that promoted either motility phenotype. We then demonstrated that varying one of the conditions may change tumor cell behavior only in a context-dependent manner. In addition, to establish the link between phenotypes and cell fates, we photoconverted and monitored the fate of tumor cells in different microenvironments, finding that only tumor cells in the invadopodium-rich microenvironments degraded extracellular matrix (ECM and disseminated. The number of invadopodia positively correlated with degradation, while the inhibiting metalloproteases eliminated degradation and lung metastasis, consistent with a direct link among invadopodia, ECM degradation, and metastasis. We have detected and characterized two phenotypes of motile tumor cells in vivo, which

Pretreatment Growth Rate Predicts Radiation Response in Vestibular Schwannomas

International Nuclear Information System (INIS)

Niu, Nina N.; Niemierko, Andrzej; Larvie, Mykol; Curtin, Hugh; Loeffler, Jay S.; McKenna, Michael J.; Shih, Helen A.

2014-01-01

Purpose: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials: Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results: In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions: Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be

Pretreatment Growth Rate Predicts Radiation Response in Vestibular Schwannomas

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Niu, Nina N. [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Medical School, Department of Medicine, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Larvie, Mykol [Harvard Medical School, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Curtin, Hugh [Harvard Medical School, Department of Radiology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Loeffler, Jay S. [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); McKenna, Michael J. [Harvard Medical School, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-05-01

Purpose: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials: Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results: In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions: Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be

Method and timing of tumor volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging

International Nuclear Information System (INIS)

Mayr, Nina A.; Taoka, Toshiaki; Yuh, William T.C.; Denning, Leah M.; Zhen, Weining K.; Paulino, Arnold C.; Gaston, Robert C.; Sorosky, Joel I.; Meeks, Sanford L.; Walker, Joan L.; Mannel, Robert S.; Buatti, John M.

2002-01-01

Purpose: Recently, imaging-based tumor volume before, during, and after radiation therapy (RT) has been shown to predict tumor response in cervical cancer. However, the effectiveness of different methods and timing of imaging-based tumor size assessment have not been investigated. The purpose of this study was to compare the predictive value for treatment outcome derived from simple diameter-based ellipsoid tumor volume measurement using orthogonal diameters (with ellipsoid computation) with that derived from more complex contour tracing/region-of-interest (ROI) analysis 3D tumor volumetry. Methods and Materials: Serial magnetic resonance imaging (MRI) examinations were prospectively performed in 60 patients with advanced cervical cancer (Stages IB 2 -IVB/recurrent) at the start of RT, during early RT (20-25 Gy), mid-RT (45-50 Gy), and at follow-up (1-2 months after RT completion). ROI-based volumetry was derived by tracing the entire tumor region in each MR slice on the computer work station. For the diameter-based surrogate ''ellipsoid volume,'' the three orthogonal diameters (d 1 , d 2 , d 3 ) were measured on film hard copies to calculate volume as an ellipsoid (d 1 x d 2 x d 3 x π/6). Serial tumor volumes and regression rates determined by each method were correlated with local control, disease-free and overall survival, and the results were compared between the two measuring methods. Median post-therapy follow-up was 4.9 years (range, 2.0-8.2 years). Results: The best method and time point of tumor size measurement for the prediction of outcome was the tumor regression rate in the mid-therapy MRI examination (at 45-50 Gy) using 3D ROI volumetry. For the pre-RT measurement both the diameter-based method and ROI volumetry provided similar predictive accuracy, particularly for patients with small ( 3 ) and large (≥100 cm 3 ) pre-RT tumor size. However, the pre-RT tumor size measured by either method had much less predictive value for the intermediate-size (40

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system.

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Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-09-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. © 2013 Anatomical Society.

Incidence of urinary bladder tumors in the control Beagle dog population at the Inhalation Toxicology Research Institute

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King, R.R.; Kusewitt, D.F.; Hahn, F.F.; Muggenburg, B.A.

1982-01-01

The report reviews the incidence and types of urinary bladder tumors in 94 dogs that have died in a population of 250 control dogs (median life span 14.0 years). Six bladder tumors, two papillomas and four transitional cell carcinomas, were found. The cumulative incidence for bladder tumors was 10.5 percent at 16 to 19 years of age; this was a 20 percent age-specific incidence

Imaging Tumor Necrosis with Ferumoxytol.

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Maryam Aghighi

Full Text Available Ultra-small superparamagnetic iron oxide nanoparticles (USPIO are promising contrast agents for magnetic resonance imaging (MRI. USPIO mediated proton relaxation rate enhancement is strongly dependent on compartmentalization of the agent and can vary depending on their intracellular or extracellular location in the tumor microenvironment. We compared the T1- and T2-enhancement pattern of intracellular and extracellular USPIO in mouse models of cancer and pilot data from patients. A better understanding of these MR signal effects will enable non-invasive characterizations of the composition of the tumor microenvironment.Six 4T1 and six MMTV-PyMT mammary tumors were grown in mice and imaged with ferumoxytol-enhanced MRI. R1 relaxation rates were calculated for different tumor types and different tumor areas and compared with histology. The transendothelial leakage rate of ferumoxytol was obtained by our measured relaxivity of ferumoxytol and compared between different tumor types, using a t-test. Additionally, 3 patients with malignant sarcomas were imaged with ferumoxytol-enhanced MRI. T1- and T2-enhancement patterns were compared with histopathology in a descriptive manner as a proof of concept for clinical translation of our observations.4T1 tumors showed central areas of high signal on T1 and low signal on T2 weighted MR images, which corresponded to extracellular nanoparticles in a necrotic core on histopathology. MMTV-PyMT tumors showed little change on T1 but decreased signal on T2 weighted images, which correlated to compartmentalized nanoparticles in tumor associated macrophages. Only 4T1 tumors demonstrated significantly increased R1 relaxation rates of the tumor core compared to the tumor periphery (p<0.001. Transendothelial USPIO leakage was significantly higher for 4T1 tumors (3.4±0.9x10-3 mL/min/100cm3 compared to MMTV-PyMT tumors (1.0±0.9x10-3 mL/min/100 cm3. Likewise, ferumoxytol imaging in patients showed similar findings with

Speed control variable rate irrigation

Science.gov (United States)

Speed control variable rate irrigation (VRI) is used to address within field variability by controlling a moving sprinkler’s travel speed to vary the application depth. Changes in speed are commonly practiced over areas that slope, pond or where soil texture is predominantly different. Dynamic presc...

Risk factors for central nervous system tumors in children: New findings from a case-control study.

Directory of Open Access Journals (Sweden)

Rebeca Ramis

Full Text Available Central nervous system tumors (CNS are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child.We carried out a population-based case-control study of CNS tumors in Spain, covering 714 incident cases collected from the Spanish Registry of Childhood Tumors (period 1996-2011 and 4284 controls, individually matched by year of birth, sex, and autonomous region of residence. We built a covariate to approximate the exposure to industrial and/or urban environment and a covariate for the exposure to crops (GCI using the coordinates of the home addresses of the children. We used the 2001 Census to obtain information about socio-economic status (SES. We fitted logistic regression models to estimate odds ratios (ORs and 95% confidence intervals (95%CIs.The results for all CNS tumors showed an excess risk (OR = 1.37; 95%CI = 1.09-1.73 for SES, i.e., children living in the least deprived areas had 37% more risk of CNS tumor than children living in the most deprived areas. For GCI, an increase of 10% in crop surface in the 1-km buffer around the residence implied an increase of 22% in the OR (OR = 1.22; 95%CI = 1.15-1.29. Children living in the intersection of industrial and urban areas could have a greater risk of CNS tumors than children who live outside these areas (OR = 1.20; 95%CI = 0.82-1.77. Living in urban areas (OR = 0.90; 95%CI = 0.65-1.24 or industrial areas (OR = 0.96; 95%CI = 0.81-1.77 did not seem to increase the risk for all CNS tumors together. By subtype, Astrocytomas, Intracranial and intraspinal embryonal tumors, and other gliomas showed similar results.Our results suggest that higher socioeconomic status and

Mature results of a randomized trial comparing two fractionation schedules of high dose rate endoluminal brachytherapy for the treatment of endobronchial tumors

International Nuclear Information System (INIS)

Niemoeller, Olivier M; Pöllinger, Barbara; Niyazi, Maximilian; Corradini, Stefanie; Manapov, Farkhad; Belka, Claus; Huber, Rudolf M

2013-01-01

To determine the efficacy of high dose rate endobronchial brachytherapy (HDR-BT) for the treatment of centrally located lung tumors, two different fractionation schedules were compared regarding local tumor response, side effects and survival. Mature retrospective results with longer follow-up and more patients were analyzed. Initial results were published by Huber et al. in 1995. 142 patients with advanced, centrally located malignant tumors with preferential endoluminal growth were randomized to receive 4 fractions of 3.8 Gy (time interval: 1 week, n = 60, group I) or 2 fractions of 7.2 Gy (time interval: 3 weeks, n = 82, group II) endobronchial HDR-BT. Age, gender, tumor stage, Karnofsky Performance Score and histology were equally distributed between both groups. Local tumor response with 2 fractions of 7.2 Gy was significantly higher as compared to 4 fractions of 3.8 Gy (median 12 vs. 6 weeks; p ≤ 0.015). Median survival was similar in both groups (19 weeks in the 4 fractions group vs. 18 weeks in the 2 fractions group). Fatal hemoptysis was less frequent following irradiation with 2 × 7.2 Gy than with 4 × 3.8 Gy, although the difference did not achieve statistical significance (12.2% vs. 18.3%, respectively. p = 0,345). Patients presenting with squamous cell carcinoma were at higher risk of bleeding compared to other histology (21.9% vs. 9%, p = 0,035). Multivariate analysis with regard to overall survival, revealed histology (p = 0.02), Karnofsky Performance Score (p < 0.0001) and response to therapy (p < 0.0001) as significant prognostic factors. For patients showing complete response the median survival was 57 weeks, while for patients with progressive disease median survival time was 8 weeks, p < 0.0001. The KPS at the start of the treatment was significantly correlated with survival. Patients presenting with a KPS ≤ 60 at the start had a significantly (p = 0,032) shorter survival time (10 weeks) than patients with a KPS > 60 (29 weeks). Moreover

[Desmoid tumors in three patients].

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Mohos, E; Kovács, T; Brittig, F; Nagy, A

2001-12-01

Desmoids are rare tumors of the connective tissue. It develops about 1:1000 times more in patients with familial adenomatous polyposis (FAP, Gardner syndrome) compared to normal population. It has been shown in molecular genetic examinations, that different mutations of the APC gene are responsible for desmoid tumors in FAP. It means, that this disease is one of the extraintestinal manifestations of Gardner syndrome. This tumor has high recurrence rate and is growing rapidly, and as a result it is the second most common cause of death in FAP patients. That is why genetic examination for FAP patients is advised to decide if the patient has higher risk for desmoid formation. If the result of the genetic test is positive, it is advisable to try to slow the progression of polyposis with medical treatment, and so to delay the date of the colectomy because the surgical intervention--and connective tissue damage--can induce desmoid formation in these patients. At the same time it is reasonable to examine and regularly control patients with sporadic desmoid tumors searching for other manifestations of Gardner syndrome (colon, stomach and duodenum polyposis, tumor of papilla Vateri, retinopathy, etc.). Palliative surgery is not indicated in patients with inoperable intraabdominal desmoid tumors, because partial resections (R1, R2, debulking) result in further tumor progression. In these patients medical treatment (sulindac, tamoxifen), chemotherapy (doxorubicin, dacarbazin) and radiotherapy or combination of them can result tumor remission. We describe our three patients (an abdominal wall desmoid four years following Cesarean section; a desmoid tumor in the retroperitoneum and in the pelvis diagnosed three years after total colectomy; and a retroperitoneal and abdominal wall desmoid one year after total colectomy) and etiology, diagnosis and therapy of desmoid tumors are discussed.

Dose prescription complexity versus tumor control probability in biologically conformal radiotherapy

International Nuclear Information System (INIS)

South, C. P.; Evans, P. M.; Partridge, M.

2009-01-01

The technical feasibility and potential benefits of voxel-based nonuniform dose prescriptions for biologically heterogeneous tumors have been widely demonstrated. In some cases, an ''ideal'' dose prescription has been generated by individualizing the dose to every voxel within the target, but often this voxel-based prescription has been discretized into a small number of compartments. The number of dose levels utilized and the methods used for prescribing doses and assigning tumor voxels to different dose compartments have varied significantly. The authors present an investigation into the relationship between the complexity of the dose prescription and the tumor control probability (TCP) for a number of these methods. The linear quadratic model of cell killing was used in conjunction with a number of modeled tumors heterogeneous in clonogen density, oxygenation, or proliferation. Models based on simple mathematical functions, published biological data, and biological image data were investigated. Target voxels were assigned to dose compartments using (i) simple rules based on the initial biological distribution, (ii) iterative methods designed to maximize the achievable TCP, or (iii) methods based on an ideal dose prescription. The relative performance of the simple rules was found to depend on the form of heterogeneity of the tumor, while the iterative and ideal dose methods performed comparably for all models investigated. In all cases the maximum achievable TCP was approached within the first few (typically two to five) compartments. Results suggest that irrespective of the pattern of heterogeneity, the optimal dose prescription can be well approximated using only a few dose levels but only if both the compartment boundaries and prescribed dose levels are well chosen.

Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

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Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp

2012-04-01

Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effect of hyperthermia, radiation and adriamycin combinations on tumor vascular function

International Nuclear Information System (INIS)

Eddy, H.A.; Chmielewski, G.

1982-01-01

Pathophysiologic studies of tumor vascular responses to hyperthermia, radiation or adriamycin given alone or in specific combinations have been made in the cervical carcinoma grown in the transparent cheek pouch chamber of the Syrian hamster. A specially designed chamber containing a compartment for flowing water enabled controlled heating of the tumor and pouch to within 0.2 0 C; the desired temperatures were achieved within one minute. Heating at 42 0 C for 30 minutes was followed, at 1, 5 or 24 hours, by a second heating for 30 minutes at 42 0 C. In addition, the same period of heating was preceded or followed, at 1, 5 or 24 hour intervals, by a single exposure to 2000R or a single intravenous injectionof adriamycin given at a rate of 0.45 mg/100 gm body weight. Of the three modalities, heat appeared to have the greatest acute effect on the tumor vascular system. A single dose of heat produced a rapid but transient constriction followed by a prominent dilation of vessels. Two heating periods given at a 1 hour interval caused persistent stasis in the tumor which progressed to coagulation necrosis. Although heating prior to irradiation or adriamycin, in general, increased the vascular responses to these agents, this sequence gave no tumor control. Radiation or adriamycin given prior to heating had relatively little effect on the vascular response to heating and produced no tumor control except when heat was applied shortly after irradiation. These studies indicate that changes in the microvasculature and perfusion in tumors, in response to hyperthermia alone or combined in specific sequences with radiation, can alter the internal environment of the tumor to produce a greater degree of tumor control than can be attributed to direct cell killing by these agents

Localization of indium-111 in human malignant tumor xenografts and control by chelators

International Nuclear Information System (INIS)

Watanabe, Naoyuki; Oriuchi, Noboru; Endo, Keigo; Inoue, Tomio; Tanada, Shuji; Murata, Hajime; Kim, E. Edmund; Sasaki, Yasuhito

1999-01-01

The kinetics of soluble indium-111 ( 111 In) in human malignant tumor xenografts and cells was investigated in combination with chelators. Firstly, without chelator, the kinetics of 111 In-chloride was investigated in vitro and in vivo using four human malignant neuroblastoma SK-N-MC, pulmonary papillary adenocarcinoma NCI-H441, pulmonary squamous cell carcinoma PC 9, and colon adenocarcinoma LS 180 cells and xenografts. 111 In was incorporated into tumor cells in vitro to a maximum level during a 60-min incubation. A maximum level of radioactivity was demonstrated in vivo in four human malignant tumors xenografted into nude mice at 24 h postinjection of 111 In-chloride. Secondly, the effect of edetate calcium disodium (CaNa 2 EDTA) on radioactivity in 111 In-labeled tumors xenografts and cells was studied in vitro and in vivo. CaNa 2 EDTA significantly reduced 111 In-activity from the labeled tumor xenografts, whereas it had no affect on the radioactivity in the labeled cells. Thirdly, the effect of CaNa 2 EDTA on radioactivity in human malignant tumors xenografted into nude mice injected with 111 In-chloride was investigated. In one group of mice CaNa 2 EDTA administered intraperitoneally at 1, 22, 34, 46, 58, and 70 h after injection of 111 In-chloride (postadministration), the localization of 111 In at the tumors was significantly decreased at 72 h compared with the control in all four tumor types. In the other group of mice, CaNa 2 EDTA administered intraperitoneally at 12 and 1 h before injection of 111 In-chloride and 1, 22, 34, 46, 58, and 70 h postinjection (pre- and postadministration), the radioactivity of tumors was also significantly decreased at 72 h, and the reduction was greater than that with use of postadministration. In a comparative study, CaNa 3 DTPA had a more powerful effect than CaNa 2 EDTA. In conclusion, 111 In-activity in tumors consists of intracellular and extracellular components, and the extracellular 111 In may be cleared by

Role of tumor necrosis factor in flavone acetic acid-induced tumor vasculature shutdown

International Nuclear Information System (INIS)

Mahadevan, V.; Malik, S.T.; Meager, A.; Fiers, W.; Lewis, G.P.; Hart, I.R.

1990-01-01

Flavone acetic acid (FAA), a novel investigational antitumor agent, has been shown to cause early vascular shutdown in several experimental murine tumors, and this phenomenon is believed to be crucial to FAA's antitumor effects. However, the basis of this FAA-induced tumor vascular shutdown is unknown. In this study a radioactive tracer-clearance technique has been used as an objective indication of tumor blood flow to show that i.p. administered FAA induces a progressive and sustained reduction in blood flow in a colon 26 tumor growing s.c. in syngeneic mice. As early as 1 h after administration, there was a significant increase in the t1/2 clearance value for intratumorally injected 133Xe, reaching a peak at 3 h (117.3 +/- 36.4 versus 7.8 +/- 0.85 min for controls). Significant inhibition of blood flow was still apparent 48 h after a single injection of drug. This FAA-induced vascular shutdown was virtually abolished in tumor-bearing mice pretreated with an antiserum against tumor necrosis factor, while no such effect was observed in controls pretreated with nonimmune serum (t1/2 of 10.8 +/- 1.2 versus 65.6 +/- 8.0 min for controls). Furthermore, in vitro FAA was seen to induce tumor necrosis factor secretion from murine peritoneal cells and splenocytes. These studies suggest that FAA-induced tumor vascular shutdown in the colon 26 tumor is mediated by tumor necrosis factor

Radiolabeled anti-EGFR-antibody improves local tumor control after external beam radiotherapy and offers theragnostic potential

International Nuclear Information System (INIS)

Koi, Lydia; Bergmann, Ralf; Brüchner, Kerstin; Pietzsch, Jens; Pietzsch, Hans-Jürgen; Krause, Mechthild

2014-01-01

Purpose: The effect of radioimmunotherapy (RIT) using the therapeutic radionuclide Y-90 bound to the anti-EGFR antibody cetuximab combined with external beam irradiation (EBRT) (EBRIT) on permanent local tumor control in vivo was examined. Methods: Growth delay was evaluated in three human squamous cell carcinoma models after RIT with [ 90 Y]Y-(CHX-A′′-DTPA) 4 -cetuximab (Y-90-cetuximab). The EBRT dose required to cure 50% of the tumors (TCD 50 ) for EBRT alone or EBRIT was evaluated in one RIT-responder (FaDu) and one RIT-non-responder (UT-SCC-5). EGFR expression and microenvironmental parameters were evaluated in untreated tumors, bioavailability was visualized by PET using ([ 86 Y]Y-(CHX-A′′-DTPA) 4 -cetuximab (Y-86-cetuximab) and biodistribution using Y-90-cetuximab. Results: In UT-SCC-8 and FaDu but not in UT-SCC-5 radiolabeled cetuximab led to significant tumor growth delay. TCD 50 after EBRT was significantly decreased by EGFR-targeted RIT in FaDu but not in UT-SCC-5. In contrast to EGFR expression, parameters of the tumor micromilieu and in particular the Y-90-cetuximab biodistribution or Y-86-cetuximab visualization in PET correlated with the responsiveness to RIT or EBRIT. Conclusion: EGFR-targeted EBRIT can improve permanent local tumor control compared to EBRT alone. PET imaging of bioavailability of labeled cetuximab appears to be a suitable predictor for response to EBRIT. This theragnostic approach should be further explored for clinical translation

Visual outcome, endocrine function and tumor control after fractionated stereotactic radiation therapy of craniopharyngiomas in adults

DEFF Research Database (Denmark)

Astradsson, Arnar; Munck Af Rosenschöld, Per; Feldt-Rasmussen, Ulla

2017-01-01

BACKGROUND: The purpose of this study was to examine visual outcome, endocrine function and tumor control in a prospective cohort of craniopharyngioma patients, treated with fractionated stereotactic radiation therapy (FSRT). MATERIAL AND METHODS: Sixteen adult patients with craniopharyngiomas were...... eligible for analysis. They were treated with linear accelerator-based FSRT during 1999-2015. In all cases, diagnosis was confirmed by histological analysis. The prescription dose to the tumor was 54 Gy (median, range 48-54) in 1.8 or 2.0 Gy per fraction, and the maximum radiation dose to the optic nerves.......7-13.1) for visual outcome, endocrine function, and tumor control, respectively. RESULTS: Visual acuity impairment was present in 10 patients (62.5%) and visual field defects were present in 12 patients (75%) before FSRT. One patient developed radiation-induced optic neuropathy at seven years after FSRT. Thirteen...

Rescue treatment with interstitial brachytherapy irradiation re very low dose rate iridium-192 (UBT) in inoperable tumors of the oral cavity, oropharynx and nodal: experience of 28 cases in the Gustave-Roussy Institute in Paris

International Nuclear Information System (INIS)

Quarneti, A.; Cordova, A.; Barrios, E.; Bonomi, M.; Haie-Meder, C.; Gerbaulet, A.; Eschwege, F.

2004-01-01

Purpose: A retrospective analysis of the evolution of 28 patients was performed local recurrences, second tumors and advanced disease in neck nodes in territory previously irradiated, which were re-irradiated using interstitial brachytherapy Ir-192 at very low dose rate (UBT) in the Gustave-Roussy Institute in Paris. Material and Methods: A series of 28 who had received radiation therapy is reported as part of heir initial treatment. 17 patients were treated for local recurrences or second tumors while 11 patients had presented nodal disease. All of them were inoperable. So were treated with interstitial brachytherapy with Ir-192 wires at very low rate dose (UBT), plastic tube technique, re-irradiation regime between 1978 and 1988 Gustave Roussy Institute. Two groups were considered. Group 1 included 17 patients with local recurrences, lesion progression and second tumors. Group 2 included 11 patients with metastatic nodal disease. The mean treatment volume was 45.25 cc, the average dose was 65 Gy, and the average treatment time between the first treatment and re irradiation was 56 months. The average duration of treatment was 14.6 days with a average dose rate of 0.18 Gy / h. After loading technique was used in plastic tubes. They were previously performed to load the simulation with orthogonal plates, false sources and provisional dosimetry. Late toxicity was assessed according to the RTOG score. Local control rates were studied complications and survive on some factors of possible prognostic significance. The statistical analysis of significance was performed by the method and log rank test were prepared survival curves and disease-free survival by Kaplan-Meier. Results: 2 groups were analyzed separately. In group 1, procedures were performed 17 UBTD and method of low dose rate (LDR). 10 of 17 patients achieved complete responses. The patient that the procedure was performed at low dose rate also achieved a complete response. In 3 cases, no response is not

Actual and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET and intracranial germ cell tumors in childhood

International Nuclear Information System (INIS)

Kortmann, R.D.; Timmermann, B.; Bamberg, M.; Kuehl, J.; Calaminus, G.; Goebel, U.; Dieckmann, K.; Wurm, R.; Soerensen, N.; Urban, C.

2001-01-01

Methods: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. Results: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing chemotherapies in conjunction with radiotherapy achieve a long-term survival rate of 80% today. Especially in high risk medulloblastoma and secreting germ cell tumors chemotherapies are playing an increasingly important role in the interdisciplinary management. It can be expected that future developments of chemotherapeutic protocols and the introduction of new cytostatic substances will further improve the therapeutic outcome. (orig.) [de

Significance of changes of serum NSE and CEA levels in patients with pneumonia and malignant tumors

International Nuclear Information System (INIS)

Liu Hengguo; Luo Nanping; Wang Ruishan; Bai Lu

2005-01-01

Objective: To investigate the significance of changes of serum NSE and CEA levels in patients with pneumonia and malignant tumors. Methods: Serum NSE (with RIA) and CEA (with ECLIA) levels in patients with pneumonia or various kinds of malignant tumors (altogether 140 patients) and 32 controls. Results: Serum NSE and CEA levels were significantly higher in patients with lung cancer, gastric cancer, renal cancer, brain tumor and pneumonia than those in the controls (P<0.05,P <0. 05 ,P <0. 01, P<0.01, P<0.01). Positive rate of serum NSE highest in patients with pneumonia, followed successively by renal cancer, brain tumor and lung cancer. NSE levels were positively correlated with CEA levels (r=0.29, P<0.05). Conclusion: As a tumor marker, NSE has important clinical significance in the diagnoses of malignant tumor and pneumonia. (authors)

Absence of regulation of tumor cholesterogenesis in cell-free synthesizing systems

International Nuclear Information System (INIS)

Azrolan, N.; Coleman, P.S.

1986-01-01

In tumors, cholesterol synthesis de novo is deregulated relative to normal tissues. But no previous study has demonstrated the decontrol of tumor cholesterogenesis with cell-free cytosolic systems. They have utilized a lipid synthesizing, post-mitochondrial supernatant system (PMS), with 14 C-citrate as substrate, to characterize the cholesterogenic pathway in Morris Hepatoma 3924A and normal rat liver. The rate of cholesterogenesis in the hepatoma PMS was 6-fold higher than that in the liver system on a per cell basis. The ratio of sterol-to-fatty acid synthesis was also significantly greater in the tumor versus the liver PMS. The authors determined the steady-state carbon flux through the early intermediates of the lipogenic pathways. Whereas the liver system displayed a metabolic crossover point at the HMG-CoA reductase reaction, the hepatoma system showed no evidence of control at this rate-limiting site of sterol synthesis. Furthermore, acetyl-CoA formation from added citrate (via ATP-citrate lyase) exhibited rates of 42% and 88% in excess of that required for lipidogenesis by liver and tumor PMS systems, respectively. Clearly, a cell-free PMS system from tumor tissue displays the property of deregulated lipidogenesis, especially cholesterol biosynthesis. The authors suggest that deregulated and continuously operating cholesterogenesis would provide for an increased level of a mevalonate-derived sterol pathway intermediate proposed as a trigger for DNA synthesis and cell proliferation in tumors

Biologic behavior and prognostic factors for mast cell tumors of the canine muzzle: 24 cases (1990-2001).

Science.gov (United States)

Gieger, Tracy L; Théon, Alain P; Werner, Jonathan A; McEntee, Margaret C; Rassnick, Kenneth M; DeCock, Hilde E V

2003-01-01

The medical records of 24 dogs with histologically confirmed mast cell tumors (MCT) of the muzzle were retrospectively evaluated to determine their biologic behavior and prognostic factors. Information on signalment, tumor grade and stage, treatment methods, and pattern of and time to failure and death was obtained from the medical record. Twenty-three dogs were treated with combinations of radiotherapy, surgery, and chemotherapy; 1 dog received no treatment. There were 2 Grade 1, 15 Grade 11, and 7 Grade III tumors. Tumors were stage 0 (n = 8), stage 1 (5), stage 2 (6), stage 3 (4), and stage 4 (1). Mean and median survival times of treated dogs were 36 and 30 months, respectively. Prognostic factors affecting survival time included tumor grade and presence of metastasis at diagnosis. Dogs with Grade I and II tumors survived longer than dogs with Grade III tumors. Variables, including sex, age, gross versus microscopic disease, and treatment type were not found to affect survival. Local control rate was 75% at 1 year and 50% at 3 years. Tumor grade was the only variable found to affect local control. Dogs with Grade I tumors had longer disease-free intervals than those with Grade II tumors, and dogs with Grade II tumors had longer disease-free intervals than dogs with Grade III tumors. Eight of 9 dogs dying of MCT had local or regional disease progression. Muzzle MCT a rebiologically aggressive tumors with higher regional metastatic rates than previously reported for MCT in other sites.

uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.

Science.gov (United States)

Sobrevals, Luciano; Mato-Berciano, Ana; Urtasun, Nerea; Mazo, Adela; Fillat, Cristina

2014-01-01

Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells. © 2013.

The effect of endostatin gene in combination with radiotherapy on rats with implanted tumor

International Nuclear Information System (INIS)

Li Yong; Jin Ning; Yang Haishan; Piao Chunji; Lv Zhe

2005-01-01

Objective: To study the combination therapy effect of the radiotherapy with endostatin gene therapy on the rats with implanted tumor. Methods: Immediate Walker-256 cancerous ascetic injection method was used to make a rat tumor-bearing model, then the tumor was treated with saline, endostatin gene, irradiation or endostatin gene plus irradiation. The tumor growth rate and weight were observed, Western blot and RT-PCR were adopted to check the expressions of endostatin mRNA and protein. Results: The expressions of endostatin mRNA and protein were significant in the gene therapy group and the gene plus radiotherapy group, but there was a significant difference between these two groups. As compared with the control group, the tumor growth rate and weight decreased significantly in all the therapy groups (P 0.05). Conclusion: After the pCMV-Endostatin was induced, the expressions of endostatin mRNA and protein was significant in Walker-256 tumor and the tumor growth was inhibited. However, the effect of the endostatin gene plus radiotherapy was obviously better than that of the endostatin gene therapy group or the radiotherapy group for inhibiting tumor growth. (authors)

Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

Directory of Open Access Journals (Sweden)

Shweta Joshi

Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

Aging and insulin signaling differentially control normal and tumorous germline stem cells.

Science.gov (United States)

Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

2015-02-01

Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Incorporation of diffusion-weighted magnetic resonance imaging data into a simple mathematical model of tumor growth

International Nuclear Information System (INIS)

Atuegwu, N C; Colvin, D C; Loveless, M E; Gore, J C; Yankeelov, T E; Xu, L

2012-01-01

We build on previous work to show how serial diffusion-weighted MRI (DW-MRI) data can be used to estimate proliferation rates in a rat model of brain cancer. Thirteen rats were inoculated intracranially with 9L tumor cells; eight rats were treated with the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea and five rats were untreated controls. All animals underwent DW-MRI immediately before, one day and three days after treatment. Values of the apparent diffusion coefficient (ADC) were calculated from the DW-MRI data and then used to estimate the number of cells in each voxel and also for whole tumor regions of interest. The data from the first two imaging time points were then used to estimate the proliferation rate of each tumor. The proliferation rates were used to predict the number of tumor cells at day three, and this was correlated with the corresponding experimental data. The voxel-by-voxel analysis yielded Pearson's correlation coefficients ranging from −0.06 to 0.65, whereas the region of interest analysis provided Pearson's and concordance correlation coefficients of 0.88 and 0.80, respectively. Additionally, the ratio of positive to negative proliferation values was used to separate the treated and control animals (p <0.05) at an earlier point than the mean ADC values. These results further illustrate how quantitative measurements of tumor state obtained non-invasively by imaging can be incorporated into mathematical models that predict tumor growth. (paper)

A nonlinear competitive model of the prostate tumor growth under intermittent androgen suppression.

Science.gov (United States)

Yang, Jing; Zhao, Tong-Jun; Yuan, Chang-Qing; Xie, Jing-Hui; Hao, Fang-Fang

2016-09-07

Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Immune system and tumors].

Science.gov (United States)

Terme, Magali; Tanchot, Corinne

2017-02-01

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

Stereotactic radiosurgery vs. fractionated radiotherapy for tumor control in vestibular schwannoma patients

DEFF Research Database (Denmark)

Persson, Oscar; Bartek, Jiri; Shalom, Netanel Ben

2017-01-01

OBJECTIVE: Repeated controlled studies have revealed that stereotactic radiosurgery is better than microsurgery for patients with vestibular schwannoma (VS) ... to patients treated with fractionated stereotactic radiotherapy. RESULTS: No randomized controlled trial (RCT) was identified. None of the identified controlled studies comparing SRS with FSRT were eligible according to the inclusion criteria. Nineteen case series on SRS (n = 17) and FSRT (n = 2) were...... included in the systematic review. Loss of tumor control necessitating a new VS-targeted intervention was found in an average of 5.0% of the patients treated with SRS and in 4.8% treated with FSRT. Mean deterioration ratio for patients with serviceable hearing before treatment was 49% for SRS and 45...

Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

DEFF Research Database (Denmark)

Tietze, Anna; Mouridsen, Kim; Lassen-Ramshad, Yasmin

2015-01-01

Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome...... than does the established PWI angiogenesis marker, cerebral blood volume (CBV). Material and Methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and COV, its ratio to blood mean transit time, provide indices...... of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival...

Central nervous system tumors

International Nuclear Information System (INIS)

Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

1995-01-01

Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

Local recurrence after microwave thermosphere ablation of malignant liver tumors: results of a surgical series.

Science.gov (United States)

Takahashi, Hideo; Kahramangil, Bora; Berber, Eren

2018-04-01

Microwave thermosphere ablation is a new treatment modality that creates spherical ablation zones using a single antenna. This study aims to analyze local recurrence associated with this new treatment modality in patients with malignant liver tumors. This is a prospective clinical study of patients who underwent microwave thermosphere ablation of malignant liver tumors between September 2014 and March 2017. Clinical, operative, and oncologic parameters were analyzed using Kaplan-Meier survival and Cox proportional hazards model. One hundred patients underwent 301 ablations. Ablations were performed laparoscopically in 87 and open in 13 patients. Pathology included neuroendocrine liver metastasis (n = 115), colorectal liver metastasis (n = 100), hepatocellular cancer (n = 21), and other tumor types (n = 65). Ninety-day morbidity was 7% with one not procedure-related mortality. Median follow-up was 16 months with 65% of patients completing at least 12 months of follow-up. The rate of local tumor recurrence rate per lesion was 6.6% (20/301). Local tumor, new hepatic, and extrahepatic recurrences were detected in 15%, 40%, and 40% of patients, respectively. Local recurrence rate per pathology was 12% for both colorectal liver metastasis (12/100) and other metastatic tumors (8/65). No local recurrence was observed to date in the neuroendocrine liver metastasis and in the limited number of patients with hepatocellular cancers. Tumor size >3 cm and tumor type were independent predictors of local recurrence. This is the first study to analyze local recurrence after microwave thermosphere ablation of malignant liver tumors. Short-term local tumor control rate compares favorably with that reported for radiofrequency and other microwave technologies in the literature. Copyright © 2017 Elsevier Inc. All rights reserved.

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

International Nuclear Information System (INIS)

Duprez, Fréderic; Madani, Indira; Morbée, Lieve; Bonte, Katrien; Deron, Philippe; Domján, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

2012-01-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60–66 Gy (n = 13) at 2 Gy per fraction over 6–7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1–2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15–121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment (≥6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1–2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

Energy Technology Data Exchange (ETDEWEB)

Duprez, Frederic, E-mail: frederic.duprez@ugent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Madani, Indira; Morbee, Lieve [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Bonte, Katrien; Deron, Philippe; Domjan, Vilmos [Department of Head and Neck Surgery, Ghent University Hospital, Ghent (Belgium); Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

2012-05-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

The impact of microscopic disease on the tumor control probability in non-small-cell lung cancer

International Nuclear Information System (INIS)

Siedschlag, Christian; Boersma, Liesbeth; Loon, Judith van; Rossi, Maddalena; Baardwijk, Angela van; Gilhuijs, Kenneth; Stroom, Joep

2011-01-01

Purpose: To indicate which clinical target volume (CTV) margin (if any) is needed for an adequate treatment of non-small-cell lung cancer (NSCLC) using either 3D conformal or stereotactic radiotherapy, taking the distribution of the microscopic disease extension (MDE) into account. Methods and materials: On the basis of the linear-quadratic biological model, a Monte-Carlo simulation was used to study the impact of MDE and setup deviations on the tumor control probability (TCP) after typical 3D conformal and stereotactic irradiation techniques. Setup deviations were properly accounted for in the planning target volume (PTV) margin. Previously measured distributions of MDE outside the macroscopic tumor in NSCLC patients were used. The dependence of the TCP on the CTV margins was quantified. Results: The presence of MDE had a demonstratable influence on the TCP in both the 3D conformal and the stereotactic technique when no CTV margins were employed. The impact of MDE on the TCP values was greater in the 3D conformal scenario (67% TCP with MDE; 84% TCP without MDE) than for stereotactic radiotherapy (91% TCP with MDE; 100% TCP without MDE). Accordingly, an increase of the CTV margin had the greatest impact for the 3D conformal technique. Larger setup errors, with appropriate PTV margins, lead to an increase in TCP for both techniques, showing the interdependence of CTV and PTV margins. Conclusions: MDE may not always be eradicated by the beam penumbra or existing PTV margins using either 3D conformal or stereotactic radiotherapy. Nonetheless, TCP modeling indicates an overall local control rate above 90% for the stereotactic technique, while a non-zero CTV margin is recommended for better local control of MDE when using the 3D conformal technique.

Radiotherapy in desmoid tumors. Treatment response, local control, and analysis of local failures

Energy Technology Data Exchange (ETDEWEB)

Santti, Kirsi; Beule, Annette; Tuomikoski, Laura; Jaeaeskelaeinen, Anna-Stina; Saarilahti, Kauko; Tarkkanen, Maija; Blomqvist, Carl [Helsinki University Hospital and University of Helsinki, Comprehensive Cancer Center, Helsinki (Finland); Roenty, Mikko [HUSLAB and University of Helsinki, Department of Pathology, Helsinki (Finland); Ihalainen, Hanna [Helsinki University Hospital and University of Helsinki, Department of Plastic Surgery, Helsinki (Finland)

2017-04-15

Desmoid tumors (aggressive fibromatosis) are rare soft tissue tumors which frequently recur after surgery. Desmoid tumors arise from musculoaponeurotic tissue in the extremities, head and neck, abdominal wall, or intra-abdominally. Our aim was to examine the outcome of radiotherapy of desmoid tumors in a single institution series. We evaluated 41 patients with desmoid tumors treated with 49 radiotherapies between 1987 and 2012. Radiologic images for response evaluation were reassessed and responses to treatment registered according to RECIST criteria 1.1. For patients with local failures radiation dose distribution was determined in each local failure volume using image co-registration. Recurrences were classified as in-target, marginal, or out-of-target. Prognostic factors for radiotherapy treatment failure were evaluated. Radiotherapy doses varied from 20-63 Gy (median 50 Gy) with a median fraction size of 2 Gy. The objective response rate to definitive radiotherapy was 55% (12/22 patients). Median time to response was 14 months. A statistically significant dose-response relation for definitive and postoperative radiotherapy was observed both in univariate (p-value 0.002) and in multivariate analysis (p-value 0.02) adjusted for potential confounding factors. Surgery before radiotherapy or surgical margin had no significant effect on time to progression. Nine of 11 (82%) local failures were classified as marginal and two of 11 (18%) in-target. None of the recurrences occurred totally out-of-target. Radiotherapy is a valuable option for treating desmoid tumors. Radiotherapy dose appears to be significantly associated to local control. (orig.) [German] Desmoide (aggressive Fibromatosen) sind seltene Weichteiltumore der muskulaeren Membranen von Kopf, Hals, Extremitaeten und Bauchwand. Ziel war es, die Wirksamkeit der Strahlentherapie bei aggressiver Fibromatose an einer einzelnen Klinik zu untersuchen. Ausgewertet wurden 41 Patienten mit aggressiver Fibromatose, die

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko; Yamazaki, Hideya; Koizumi, Masahiko; Kagawa, Kazufumi; Yoshida, Ken; Shiomi, Hiroya; Imai, Atsushi; Shimizutani, Kimishige; Tanaka, Eichii; Nose, Takayuki; Teshima, Teruki; Furukawa, Souhei; Fuchihata, Hajime

1998-01-01

Purpose: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. Methods and Materials: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198 Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. Results: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198 Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff

The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Allibhai, Zishan [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Taremi, Mojgan [Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket (Canada); Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada); Cho, B.C. John, E-mail: john.cho@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto (Canada)

2013-12-01

Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

Gamma knife radiosurgery for metastatic brain tumors from lung cancer

Energy Technology Data Exchange (ETDEWEB)

Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

2003-01-01

The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

Effects of continued psychological care toward brain tumor patients and their family members' negative emotions.

Science.gov (United States)

Xiao, Ning; Zhu, Dan; Xiao, Shuiyuan

2018-01-01

Numerous studies have confirmed that brain tumor patients and their family members frequently exhibit negative emotional reactions, such as anxiety and depression, during diagnosis and treatment of the disease. Family members experience increasing pressure as the year of survival of patient progress. The aim of this study was to investigate the effects of the continued psychological care (CPC) toward the brain tumor patients and their family members' emotions. The asynchronous clinical control trial was performed, and 162 brain tumor patients and their family members were divided into the control group and the intervention group. The control group was only performed the telephone follow-up toward the patients. Beside this way, the intervention group was performed the CPC toward the patients and their family member. The self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were used to measure the negative emotions of the patients and their family members, and the patients' treatment compliance and the incidence of seizures were compared. The SAS and SDS scores of the intervention group on the 14 days, 28 days and 3 months of the CPC were significantly lower than the control group (P family members.

Hemithorax irradiation for Ewing tumors of the chest wall

International Nuclear Information System (INIS)

Schuck, Andreas; Ahrens, Susanne; Konarzewska, Agnieszka; Paulussen, Michael; Froehlich, Birgit; Koenemann, Stefan; Ruebe, Christian; Ruebe, Claudia E.; Dunst, Juergen; Willich, Normann; Juergens, Heribert

2002-01-01

Purpose: In the Cooperative Ewing's Sarcoma Study 86 and the European Intergroup Cooperative Ewing's Sarcoma Study 92, hemithorax irradiation (RT) was performed in patients with Ewing tumors of the chest wall involving the pleura or contaminating the pleural cavity. In a retrospective analysis, the outcomes of these patients were evaluated and compared with those of patients with chest wall tumors who did not receive hemithorax RT. Methods and Materials: Between 1985 and 1996, 138 patients presented with nonmetastatic Ewing tumors of the chest wall. They were treated in a multimodal treatment regimen that included polychemotherapy and local therapy depending on the tumor characteristics. Hemithorax RT was performed at a dose of 15 Gy for patients <14 years old and 20 Gy for patients ≥14 years old. Forty-two patients received hemithorax RT (Group 1) and 86 patients did not (Group 2). The data were insufficient for the other 10 patients. Results: Comparing both groups, the initial pleural effusion, pleural infiltration, and intraoperative contamination of the pleural space were significantly more frequent in Group 1. The event-free survival rate after 7 years was 63% for patients in Group 1 and 46% for patients in Group 2 (not statistically significant). The 7-year local relapse rate (including combined local-systemic relapses) was 12% in Group 1 and 10% in Group 2; the corresponding systemic relapse rates were 22% and 39%. Conclusion: Patients with chest wall tumors who received hemithorax RT were negatively selected; yet the rate of event-free survival was better for patients who received hemithorax RT than for those who did not (although the difference was not statistically significant). This result was due to a reduction of metastases, mainly lung metastases. Local control was equivalent between the two groups. These favorable results have caused us to continue using hemithorax RT to treat high-risk patients with Ewing tumors of the chest wall

Dose-response relationship between probability of pathologic tumor control and glucose metabolic rate measured with FDG PET after preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer

International Nuclear Information System (INIS)

Choi, Noah C.; Fischman, Alan J.; Niemierko, Andrzej; Ryu, Jin-Sook; Lynch, Thomas; Wain, John; Wright, Cameron; Fidias, Panos; Mathisen, Douglas

2002-01-01

Purpose: To determine the dose-response relationship between the probability of tumor control on the basis of pathologic tumor response (pTCP) and the residual metabolic rate of glucose (MRglc) in response to preoperative chemoradiotherapy in locally advanced non-small-cell lung cancer and to define the level of residual MRglc that corresponds to pTCP 50% and pTCP ≥95%. Methods and Materials: Quantitative dynamic 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography was performed to measure regional MRglc at the primary lesion before and 2 weeks after preoperative chemoradiotherapy in an initial group of 13 patients with locally advanced NSCLC. A simplified kinetic method was developed subsequently from the initial dynamic study and used in the subsequent 16 patients. The preoperative radiotherapy programs consisted of (1) a split course of 42 Gy in 28 fractions within a period of 28 days using a twice-daily treatment schedule for Stage IIIA(N2) NSCLC (n=18) and (2) standard once-daily radiation schedule of 45-63 Gy in 25-35 fractions during a 5-7-week period (n=11). The preoperative chemotherapy regimens included two cycles of cisplatin, vinblastine, and 5-fluorouracil (n=24), cisplatin and etoposide (n=2), and cisplatin, Taxol, and 5-fluorouracil (n=3). Patients free of tumor progression after preoperative chemoradiotherapy underwent surgery. The degree of residual MRglc measured 2 weeks after preoperative chemoradiotherapy and 2 weeks before surgery was correlated with the pathologic tumor response. The relationship between MRglc and pTCP was modeled using logistic regression. Results: Of 32 patients entered into the study, 29 (16 men and 13 women; 30 lesions) were evaluated for the correlation between residual MRglc and pathologic tumor response. Three patients did not participate in the second study because of a steady decline in general condition. The median age was 60 years (range 42-78). One of the 29 patients had two separate lesions, and

Five-chlorodeoxycytidine, a tumor-selective enzyme-driven radiosensitizer, effectively controls five advanced human tumors in nude mice

International Nuclear Information System (INIS)

Greer, Sheldon; Alvarez, Marcy; Mas, Marisol; Wozniak, Chandra; Arnold, David; Knapinska, Anna; Norris, Christina; Burk, Ronald; Aller, Alex; Dauphinee, Michael

2001-01-01

Purpose: The study's goals were as follows: (1) to extend our past findings with rodent tumors to human tumors in nude mice, (2) to determine if the drug protocol could be simplified so that only CldC and one modulator, tetrahydrouridine (H 4 U), would be sufficient to obtain efficacy, (3) to determine the levels of deoxycytidine kinase and dCMP deaminase in human tumors, compared to adjacent normal tissue, and (4) to determine the effect of CldC on normal tissue radiation damage to the cervical spinal cord of nude mice. Methods and Materials: The five human tumors used were as follows: prostate tumors, PC-3 and H-1579; glioblastoma, SF-295; breast tumor, GI-101; and lung tumor, H-165. The duration of treatment was 3-5 weeks, with drugs administered on Days 1-4 and radiation on Days 3-5 of each week. The biomodulators of CldC were N-(Phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartyl transcarbamoylase, 5-fluorodeoxycytidine (FdC), resulting in tumor-directed inhibition of thymidylate synthetase, and H 4 U, an inhibitor of cytidine deaminase. The total dose of focused irradiation of the tumors was usually 45 Gy in 12 fractions. Results: Marked radiosensitization was obtained with CldC and the three modulators. The average days in tumor regrowth delay for X-ray compared to drugs plus X-ray, respectively, were: PC-3 prostate, 42-97; H-1579 prostate, 29-115; glioblastoma, 5-51; breast, 50-80; lung, 32-123. Comparative studies with PC-3 and H-1579 using CldC coadministered with H 4 U, showed that both PALA and FdC are dispensable, and the protocol can be simplified with equal and possibly heightened efficacy. For example, PC-3 with X-ray and (1) no drugs, (2) CldC plus the three modulators, (3) a high dose of CldC, and (4) escalating doses of CldC resulted in 0/10, 3/9, 5/10, and 6/9 cures, respectively. The tumor regrowth delay data followed a similar pattern. After treating mice only 1((1)/(2)) weeks with CldC + H 4 U, 92% of the PC-3 tumor cells were found

Epilepsy and Brain Tumors

Institute of Scientific and Technical Information of China (English)

Zhi-yi Sha

2009-01-01

@@ Epidemiology It is estimated 61,414 new cases of primary brain tumors are expected to be diagnosed in 2009 in the U.S. The incidence statistic of 61,414 persons diagnosed per year includes both malignant (22,738) and non-malignant (38,677) brain tumors. (Data from American Brain Tumor Association). During the years 2004-2005, approximately 359,000 people in the United States were living with the diagnosis of a primary brain or central nervous system tumor. Specifically, more than 81,000 persons were living with a malignant tumor, more than 267,000 persons with a benign tumor. For every 100,000 people in the United States, approximately 131 are living following the diagnosis of a brain tumor. This represents a prevalence rate of 130.8 per 100,000 person years[1].

Initial treatment results using cyberknife for head and neck tumor

International Nuclear Information System (INIS)

Himei, Kengo; Katsui, Kuniaki; Yoshida, Atsushi; Takemoto, Mitsuhiro; Kobayashi, Mitsuru; Kuroda, Masahiro; Hiraki, Yoshio

2002-01-01

The CyberKnife, a medical device for stereotactic radiotherapy, is composed of a combination of a robot manipulator and LINAC. For the treatment of head and neck tumors, this system has been applied. Between June 2000 and January 2001, 18 patients with head and neck tumor were treated with this system because of tumor recurrence, difficulty in surgery or additional increase after external radiotherapy. The median age was 64 years. Primary lesions were skull base (4), nasopharynx (3), paranasal sinus (3), nasal cavity (2), lacrimal gland (1), oropharynx (1), oral floor (1), and buccul mucosa (1), metastatic lymph nodes were found in three. The prescribed dose was 12-38 Gy as for marginal dose. The response rate (CR+PR) was 44.4% and local control rate (CR+PR+NC) was 77.8%. The adverse effects were assessed by the NCI-CTC Version 2.0 and observed grade 3 in two cases. Our early experience indicates that this system could to be feasible for the treatment of locally advanced or recurrent head and neck tumor, and for the reduction of adverse effect and maintenance of useful QOL of patients. (author)

Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

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Thomas Gress

2012-02-01

Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

Combining polyamine depletion with radiation therapy for rapidly dividing head and neck tumors: Strategies for improved locoregional control

International Nuclear Information System (INIS)

Petereit, D.G.; Harari, P.M.; Contreras, L.; Pickart, M.A.; Verma, A.K.; Kinsella, T.J.; Gerner, E.W.

1994-01-01

Locoregional control is adversely affected as clonogens from rapidly proliferating tumors repopulate during a course of radiation therapy. The cytostatic agent α-difluoromethylornithine (DFMO) was investigated for its capacity to slow proliferation kinetics in human squamous cell carcinomas (SSC) of the head and neck (H ampersand N), with the ultimate objective of improving locoregional control in rapidly dividing tumors treated with radiation therapy. Three human SSC cell lines established from primary H ampersand N tumors were evaluated in vitro (cell culture) and in vivo (SSC tumor xenografts in athymic mice) for the capacity of DFMO to induce growth inhibition. Flow cytometry analysis of SCC tumor growth kinetics and quantitative assessment of polyamine biosynthesis inhibition was performed to verify DFMO activity. DFMO effects on in vitro SSC radiosensitivity using clonogenic survival were also studied. A noncytotoxic exposure to DFMO (5mM x 72 hours) induced pronounced growth inhibition in all three SSC cell lines (70-90% at 7 days), and induced a 2-3 fold delay in volume doubling time for SCC tumor xenografts when administered orally in the drinking water (1.5%) to athymic mice. Kinetic analysis via flow cytometry confirmed that DFMO produced a lengthening of SCC cell cycle times, but did not alter in vitro radiosensitivity. Inhibition of ornithine decarboxylase (ODC) activity and depletion of endogenous polyamines (putrescine and spermidine), were confirmed in normal tissue (mouse skin) and in human SSC tumor xenografts of athymic mice receiving continuous oral DFMO. These data indicate that antiproliferative agents, such as DFMO, are capable of altering human SSC growth kinetics without altering intrinsic radiosensitivity. Such kinetic modulation may therefore provide a strategy to reduce the adverse impact of tumor cell proliferation during a radiotherapy treatment course for rapidly dividing tumors such as those in the H ampersand N. 33 refs., 5 figs

Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas

International Nuclear Information System (INIS)

Rush, Stephen; Cooper, Paul R.

1997-01-01

This study reports the outcome of 70 patients who were treated by a consistent treatment plan of surgery and postoperative radiotherapy (RT) for pituitary macroadenomas in the modern era [computed tomographic scan or magnetic resonance imaging (MRI), dopamine agonist therapy (DA) added as indicated, and immunohistochemical staining]. Sixty-two patients underwent transsphenoidal surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions postoperatively (vs. other dose fractionation schemes). Twenty-four patients received DA for prolactin-secreting tumors. With a median follow-up of 8 years (range 2-15), 68 patients have experienced continuous control of their tumors. Most symptoms related to mass effect abated, while physiologic symptoms such as amenorrhea from markedly elevated prolactin levels tended to persist. Treatment-induced hypopituitarism occurred in 42% of the patients at risk. No patients in this series have died as a result of their pituitary tumor. No gross neuropsychologic dysfunction after treatment has been noted. While it is possible at this time with serial MRI to withhold postoperative RT and observe some patients who have had a 'gross total' resection of a macroadenoma, the therapeutic ratio for surgery and adjuvant radiotherapy for patients with nonfunctional tumors as well as select patients with secretory macroadenomas is favorable

Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

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Maciej H Swat

Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation

International Nuclear Information System (INIS)

Kocher, M.; Treuer, H.

1995-01-01

A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm 3 which were displaced by the growing tumor was simulated. Tumors contained 10 4 cells when irradiation started, intrinsic radiosensitivity was set to either low (α=0.3 Gy -1 , β=0.03 Gy -2 ) or high (α=0.4 Gy -1 , β=0.04 Gy -2 ) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time T pot =1, 2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (T pot =2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (T pot =1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. (orig./MG) [de

Tumor response to ionizing radiation and combined 2-deoxy-D-glucose application in EATC tumor bearing mice: monitoring of tumor size and microscopic observations

International Nuclear Information System (INIS)

Latz, D.; Thonke, A.; Jueling-Pohlit, L.; Pohlit, W.

1993-01-01

The present study deals with the changes induced by two fractionation schedules (5x9 Gy and 10x4.5 Gy; 30 MeV-electrons) of ionizing radiations and 2-Deoxy-D-Glucose (2-DG) application on EATC tumor bearing swiss albino mice. The monitoring of tumor response was carried out by means of calliper measurement on the macroscopic level and by histopathological examination of tumor preparations stained with hematoxiline and eosine on the microscopic level. The tumor material was assessed at suitable intervals after treatment by killing the animals. The tumor response was analysed in the histological preparations and the thickness of the tumor band was determined quantitatively by an ocularmicrometric technique. Tumor damage was most extensive in the combined treated animals (5x9 Gy + 2-DG). Only in this group local tumor control was achievable. The histological analysis of tumor preparations revealed additional data about treatment-induced changes in the tumor compared to the measurement of the tumor volume with mechanical callipers. We also found that the treatment outcome could be predicted from the histopathological analysis. It is concluded that studies involving histopathological examinations may give some insight into the way cancer is controlled by radiotherapy and may be of value in prognosis and selection of treatment in patients. (orig.) [de

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network.

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Caroline J Voskens

Full Text Available Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4 blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.Patient files (n = 752 were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS, granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.

Diltiazem enhances tumor blood flow: MRI study in a murine tumor

International Nuclear Information System (INIS)

Muruganandham, M.; Kasiviswanathan, A.; Jagannathan, N.R.; Raghunathan, P.; Jain, P.C.; Jain, V.

1999-01-01

Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1 H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in congruent with 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor

Analysis of locally controlled esophageal carcinomas treated with radiotherapy

International Nuclear Information System (INIS)

Gotoh, Yasuo; Yamada, Shogo; Takai, Yoshihiro; Nemoto, Kenji; Ogawa, Yoshihiro; Hoshi, Akihiko; Ariga, Hisanori; Sakamoto, Kiyohiko

1996-01-01

Of 227 esophageal carcinomas treated with a radiation dose of 60 Gy or more, 100 patients had no tumor or ulceration (with or without stenosis) of the esophagus after irradiation. We analyzed local control factors of these 100 patients to determine the need for further treatment. The cumulative local control rate at five years was 40% in all cases, 37% in 21 cases without any stenosis of the esophagus and 40% in 79 cases with stenosis. The presence of stenosis of the esophagus after irradiation was not a critical factor in predicting final local control. Local recurrence of tumors with findings of Borrmann III or Borrmann IV by the pretreatment esophageal barium study, tumors controlled after a total dose of more than 80 Gy, tumors without low dose rate telecobalt therapy (LDRT: 1 Gy/hour, 5 to 7 Gy/day, a total dose of 12 to 15 Gy) as boost therapy, and apparently controlled tumors with a stenotic ratio of 60% or more or with 5 cm or more length of stenosis of the esophagus after irradiation was significantly higher than that of the others (p<0.05). Multivariate analysis revealed that findings of pretreatment barium study, total dose, with or without LDRT, and length of stenosis of the esophagus after irradiation were significantly important factors in local control. Members of the high risk group of apparently controlled tumors should undertake surgical treatment or further intensive chemotherapy. (author)

Influence of random daughter exposure rate, unattachment fraction, and disequilibrium on occurrence of lung tumors

International Nuclear Information System (INIS)

Cross, F.T.; Palmer, R.F.; Dagle, G.E.; Busch, R.H.; Buschbom, R.L.

1983-10-01

Groups of male, specific-pathogen-free (SPF), Wistar rats were exposed to several concentrations of radon daughters and uranium ore dust to clarify the roles of exposure rate, unattached RaA daughters, and the degree of radon daughter disequilibrium, in the development of respiratory system disease. Modeled, human-dosimetric data indicate that the dose to sensitive tissues of the respiratory tract increases with increasing radon-daughter unattachment fraction and degree of disequilibrium. Experimental verification of these dose-effect relationships is needed to protect the health of workers and of the public exposed to radon-daughter environments. Data bearing on these relationships as well as updated results of experiments designed to test the role of radon-daughter exposure rate on lung-tumor incidence are reported. 13 references, 3 tables

Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

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Ian F. Robey

2013-01-01

Full Text Available The extracellular pH (pHe of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs. We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (. Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs. To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (. Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX. The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion.

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.

Science.gov (United States)

Arvola, René M; Weidmann, Chase A; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2017-11-02

Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.

Automatic dose-rate controlling equipment

International Nuclear Information System (INIS)

Szasz, T.; Nagy Czirok, Cs.; Batki, L.; Antal, S.

1977-01-01

The patent of a dose-rate controlling equipment that can be attached to X-ray image-amplifiers is presented. In the new equipment the current of the photocatode of the image-amplifier is led into the regulating unit, which controls the X-ray generator automatically. The advantages of the equipment are the following: it can be simply attached to any type of X-ray image-amplifier, it accomplishes fast and sensitive regulation, it makes possible the control of both the mA and the kV values, it is attached to the most reliable point of the image-transmission chain. (L.E.)

PHYLLODES TUMOR OF THE BREAST : A CLINICOPATHOLOGICAL ANALYSIS FROM A SINGLE INSTITUTION

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Naoual Benhmidou

2017-07-01

Full Text Available The aim of our study is to examine the clinical and pathological features of patients with breast phyllodes tumors and to determine features that are correlated to outcome. Forty four phyllodes tumors were assessed. There were 11 benign, 11 borderline and 22 malignant tumors. 10 of 44 patients (22.72 % relapsed at any site. Seven patients (15.9 % had a local recurrence and 3 patients experienced local and metastatic relapse. The 5-year and 10-year survival rates are 97% and 95 % respectively. The 5 years and 10 years DFS are 81% and 77% respectively. Grade, histological size, margin involvement impacted disease free survival. Adjuvant radiation therapy improved local control in high grade tumors although it didn’t reach significance.

Determination of the Optimal Exchange Rate Via Control of the Domestic Interest Rate in Nigeria

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Virtue U. Ekhosuehi

2014-01-01

Full Text Available An economic scenario has been considered where the government seeks to achieve a favourable balance-of-payments over a fixed planning horizon through exchange rate policy and control of the domestic interest rate. The dynamics of such an economy was considered in terms of a bounded optimal control problem where the exchange rate is the state variable and the domestic interest rate is the control variable. The idea of balance-of-payments was used as a theoretical underpinning to specify the objective function. By assuming that, changes in exchange rates were induced by two effects: the impact of the domestic interest rate on the exchange rate and the exchange rate system adopted by the government. Instances for both fixed and flexible optimal exchange rate regimes have been determined. The use of the approach has been illustrated employing data obtained from the Central Bank of Nigeria (CBN statistical bulletin. (original abstract

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

2015-01-01

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

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Lindsay, WD [University of Pennsylvania, Philadelphia, PA (United States); Oncora Medical, LLC, Philadelphia, PA (United States); Berlind, CG [Georgia Institute of Technology, Atlanta, GA (Georgia); Oncora Medical, LLC, Philadelphia, PA (United States); Gee, JC; Simone, CB [University of Pennsylvania, Philadelphia, PA (United States)

2015-06-15

Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

Tracking Control of Hysteretic Piezoelectric Actuator using Adaptive Rate-Dependent Controller.

Science.gov (United States)

Tan, U-Xuan; Latt, Win Tun; Widjaja, Ferdinan; Shee, Cheng Yap; Riviere, Cameron N; Ang, Wei Tech

2009-03-16

With the increasing popularity of actuators involving smart materials like piezoelectric, control of such materials becomes important. The existence of the inherent hysteretic behavior hinders the tracking accuracy of the actuators. To make matters worse, the hysteretic behavior changes with rate. One of the suggested ways is to have a feedforward controller to linearize the relationship between the input and output. Thus, the hysteretic behavior of the actuator must first be modeled by sensing the relationship between the input voltage and output displacement. Unfortunately, the hysteretic behavior is dependent on individual actuator and also environmental conditions like temperature. It is troublesome and costly to model the hysteresis regularly. In addition, the hysteretic behavior of the actuators also changes with age. Most literature model the actuator using a cascade of rate-independent hysteresis operators and a dynamical system. However, the inertial dynamics of the structure is not the only contributing factor. A complete model will be complex. Thus, based on the studies done on the phenomenological hysteretic behavior with rate, this paper proposes an adaptive rate-dependent feedforward controller with Prandtl-Ishlinskii (PI) hysteresis operators for piezoelectric actuators. This adaptive controller is achieved by adapting the coefficients to manipulate the weights of the play operators. Actual experiments are conducted to demonstrate the effectiveness of the adaptive controller. The main contribution of this paper is its ability to perform tracking control of non-periodic motion and is illustrated with the tracking control ability of a couple of different non-periodic waveforms which were created by passing random numbers through a low pass filter with a cutoff frequency of 20Hz.

CT-guided high-dose-rate brachytherapy of unresectable hepatocellular carcinoma

International Nuclear Information System (INIS)

Collettini, Federico; Schreiber, Nadja; Schnapauff, Dirk; Denecke, Timm; Hamm, Bernd; Gebauer, Bernhard; Wust, Peter; Schott, Eckart

2015-01-01

The purpose of the present study was to evaluate the clinical outcome of CT-guided high-dose-rate brachytherapy (CT-HDRBT) in patients with unresectable hepatocellular carcinoma (HCC). Over a 6-year period, 98 patients with 212 unresectable HCC underwent CT-HDRBT applying a 192 Ir source at our institution. Magnetic resonance imaging (MRI) follow-up was performed 6 weeks after the intervention and then every 3 months. The primary endpoint was local tumor control (LTC); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Patients were available for MRI evaluation for a mean follow-up of 23.1 months (range 4-64 months; median 20 months). Mean tumor diameter was 5 cm (range 1.8-12 cm). Eighteen of 212 (8.5 %) tumors showed local progression after a mean LTC of 21.1 months. In all, 67 patients (68.4 %) experienced distant tumor progression. The mean PFS was 15.2 months. Forty-six patients died during the follow-up period. Median OS was 29.2 months. Actuarial 1-, 2-, and 3-year OS rates were 80, 62, and 46 %, respectively. CT-HDRBT is an effective therapy to attain local tumor control in patients with unresectable HCC. Prospective randomized studies comparing CT-HDRBT with the standard treatments like Radiofrequency ablation (RFA) and chemoembolization (TACE) are mandatory. (orig.) [de

Endocrine and visual function after fractionated stereotactic radiotherapy of perioptic tumors

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Kocher, M.; Semrau, R.; Mueller, R.P. [Universitaetsklinikum Koeln (Germany). Klinik und Poliklinik fuer Strahlentherapie; Treuer, H.; Hoevels, M.; Sturm, V. [Koeln Univ. (Germany). Dept. of Stereotaxy and Functional Neurosurgery

2013-02-15

Purpose: To find out whether the use of stereotactic techniques for fractionated radiotherapy reduces toxicity to the endocrine and visual system in patients with benign perioptic tumors. Patients and methods: From 1993 to 2009, 29 patients were treated with fractionated stereotactic radiotherapy. The most frequent tumor types were grade I meningioma (n = 11) and pituitary adenoma (n = 10, 7 nonfunctioning, 3 growth hormone-producing). Patients were immobilized with the GTC frame (Radionics, USA) and the planning target volume (PTV; median 24.7, 4.6-58.6 ml) was irradiated with a total dose of 52.2 Gy (range, 45.0-55.8 Gy) in 1.8-Gy fractions using a linear accelerator (6 MeV photons) equipped with a micro-multileaf collimator. Maximum doses to the optic system and pituitary gland were 53.4 Gy (range, 11.5-57.6 Gy) and 53.6 Gy (range, 12.0-57.9 Gy). Results: Median follow-up was 45 months (range, 10-105 months). Local control was achieved in all but 1 patient (actuarial rate 92% at 5 years and 10 years). In 9 of 29 patients (31%), partial remission was observed (actuarial response rate 40% at 5 years and 10 years). In 4 of 26 patients (15%) with at least partial pituitary function, new hormonal deficits developed (actuarial rate 21% at 5 years and 10 years). This rate was significantly higher in patients treated for a larger PTV ( 25 ml: 0% vs. 42% at 5 years and 10 years, p = 0.028). Visual function improved in 4 of 15 patients (27%) who had prior impairment. None of the patients developed treatment-related optic neuropathy, but 2 patients experienced new disease-related visual deficits. Conclusion: Fractionated stereotactic radiotherapy for benign tumors of the perioptic and sellar region results in satisfactory response and local control rates and does not affect the visual system. The assumption that patients can be spared hypophyseal insufficiency only holds for small tumors. (orig.)

Endocrine and visual function after fractionated stereotactic radiotherapy of perioptic tumors

International Nuclear Information System (INIS)

Kocher, M.; Semrau, R.; Mueller, R.P.; Treuer, H.; Hoevels, M.; Sturm, V.

2013-01-01

Purpose: To find out whether the use of stereotactic techniques for fractionated radiotherapy reduces toxicity to the endocrine and visual system in patients with benign perioptic tumors. Patients and methods: From 1993 to 2009, 29 patients were treated with fractionated stereotactic radiotherapy. The most frequent tumor types were grade I meningioma (n = 11) and pituitary adenoma (n = 10, 7 nonfunctioning, 3 growth hormone-producing). Patients were immobilized with the GTC frame (Radionics, USA) and the planning target volume (PTV; median 24.7, 4.6-58.6 ml) was irradiated with a total dose of 52.2 Gy (range, 45.0-55.8 Gy) in 1.8-Gy fractions using a linear accelerator (6 MeV photons) equipped with a micro-multileaf collimator. Maximum doses to the optic system and pituitary gland were 53.4 Gy (range, 11.5-57.6 Gy) and 53.6 Gy (range, 12.0-57.9 Gy). Results: Median follow-up was 45 months (range, 10-105 months). Local control was achieved in all but 1 patient (actuarial rate 92% at 5 years and 10 years). In 9 of 29 patients (31%), partial remission was observed (actuarial response rate 40% at 5 years and 10 years). In 4 of 26 patients (15%) with at least partial pituitary function, new hormonal deficits developed (actuarial rate 21% at 5 years and 10 years). This rate was significantly higher in patients treated for a larger PTV ( 25 ml: 0% vs. 42% at 5 years and 10 years, p = 0.028). Visual function improved in 4 of 15 patients (27%) who had prior impairment. None of the patients developed treatment-related optic neuropathy, but 2 patients experienced new disease-related visual deficits. Conclusion: Fractionated stereotactic radiotherapy for benign tumors of the perioptic and sellar region results in satisfactory response and local control rates and does not affect the visual system. The assumption that patients can be spared hypophyseal insufficiency only holds for small tumors. (orig.)

Urinary bladder tumors among atomic bomb survivors Hiroshima and Nagasaki, 1961-1972

International Nuclear Information System (INIS)

Sanefuji, Hayato; Ishimaru, Toranosuke.

1980-03-01

A study was made of the relationship of radiation dose to the incidence of urinary bladder tumors among atomic bomb survivors and controls in the RERF Life Span Study extended sample. A total of 112 cases of urinary bladder tumors was identified among approximately 99,000 subjects in this fixed cohort during 1961-72. Morphologic diagnoses were available for 86 cases (76.8%), cystoscopy alone for 21 cases (18.7%), and only the cause of death recorded on death certificates for 5 cases (4.5%). Urothelial carcinoma (transitional cell carcinoma) is the most common type of urinary bladder tumor for which morphologic diagnoses are available. The 1961-72 incidence rate was calculated using 106 cases identified as urinary bladder tumors. Although the crude annual incidence rate in the high dose group (100 rad or more) is elevated in both cities and both sexes, all nine cases with this dose were aged 40 years or more at the time of the bomb (ATB). The standardized relative risk adjusted for city and sex for those of age 40 or more ATB in the high dose group is 1.8 in comparison with the control group and this is a suggestive statistical difference. A statistically significant elevation of risk occurs in the high dose group for urothelial carcinoma and adenocarcinoma of the urinary bladder among those aged 40 or more ATB. (author)

The application of 3D printed surgical guides in resection and reconstruction of malignant bone tumor.

Science.gov (United States)

Wang, Fengping; Zhu, Jun; Peng, Xuejun; Su, Jing

2017-10-01

The clinical value of 3D printed surgical guides in resection and reconstruction of malignant bone tumor around the knee joint were studied. For this purpose, a sample of 66 patients from October 2013 to October 2015 were randomly selected and further divided into control group and observation group, each group consisted of 33 cases. The control group was treated by conventional tumor resection whereas, in the observation group, the tumor was resected with 3D printed surgical guide. However, reconstruction of tumor-type hinge prosthesis was performed in both groups and then the clinical effect was compared. Results show that there was no significant difference in the operation time between the two groups (p>0.05). However, the blood loss, resection length and complication rate were found significantly lower in the observation group than in the control group (p0.05) between two groups were statistically the same (p>0.05), whereas the Musculoskeletal Tumor Society (MSTS) score of the knee joint in the observation group was significantly better than that of the control group (p3D printed surgical guides can significantly improve the postoperative joint function after resection and reconstruction of malignant bone tumor around the knee joint and can reduce the incidence of complications.

The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

International Nuclear Information System (INIS)

Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

2007-01-01

Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

International Nuclear Information System (INIS)

Ciria, HC; Quevedo, MS; Cabrales, LB; Bruzón, RP; Salas, MF; Pena, OG; González, TR; López, DS; Flores, JM

2004-01-01

In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 10 6 and 1 × 10 5 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm 3 , four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm 3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm 3 (27.0 C in 0.35 cm 3 ) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm 3 , two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm 3 , respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory

Cross-immunity among allogeneic tumors of rats immunized with solid tumors

International Nuclear Information System (INIS)

Ogasawara, Masamichi

1979-01-01

Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis

International Nuclear Information System (INIS)

Addison, Christina L; Belperio, John A; Burdick, Marie D; Strieter, Robert M

2004-01-01

The Duffy antigen receptor for chemokines (DARC) is known to be a promiscuous chemokine receptor that binds a variety of CXC and CC chemokines in the absence of any detectable signal transduction events. Within the CXC group of chemokines, DARC binds the angiogenic CXC chemokines including IL-8 (CXCL8), GROα (CXCL1) and ENA-78 (CXCL5), all of which have previously been shown to be important in non-small cell lung carcinoma (NSCLC) tumor growth. We hypothesized that overexpression of DARC by a NSCLC tumor cell line would result in the binding of the angiogenic ELR+ CXC chemokines by the tumor cells themselves, and thus interfere with the stimulation of endothelial cells and induction of angiogenesis by the tumor cell-derived angiogenic chemokines. NSCLC tumor cells that constitutively expressed DARC were generated and their growth characteristics were compared to control transfected cells in vitro and in vivo in SCID animals. We found that tumors derived from DARC-expressing cells were significantly larger in size than tumors derived from control-transfected cells. However, upon histological examination we found that DARC-expressing tumors had significantly more necrosis and decreased tumor cellularity, as compared to control tumors. Expression of DARC by NSCLC cells was also associated with a decrease in tumor-associated vasculature and a reduction in metastatic potential. The expression of DARC in the context of NSCLC tumors may act as a chemokine decoy receptor and interferes with normal tumor growth and chemokine-induced tumor neovascularization

Radiotherapy using bleomycin, ACNU, and vincristine for malignant brain tumors

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Ryuichi; Murakami, Naoto; Suzuki, Yasuo; Takeda, Norio; Arai, Hiroyuki; Konno, Kimikazu; Tanimura, Ken-ichi

1984-08-01

Radiotherapy combined with bleomycin, ACNU, and vincristine was performed on 106 patients with malignant brain tumors. The treatment protocol was based on the concept of combination chemotherapy or chemoradiotherapy and synchronized chemoradiotherapy. For the purpose of synchronized chemoradiotherapy, bleomycin, ACNU, and vincristine were used as G/sub 2/M cell cycle phase accumulator, and radiation and bleomycin were used as agents to which G/sub 2/M or G/sub 2/ phase cells are sensitive. The short-term results of the chemoradiotherapy were evaluated by measuring tumor regression by computerized tomography (CT) in 80 patients with evaluable CT lesions. The response rate was 67% (6/9) for astrocytoma, 29% (7/24) for anaplastic glioma, 67% (4/6) for pontine glioma, 100%(5/5) for malignant lymphoma, 100% (8/8) for germ cell tumors and 65% (15/23) for metastatic tumors. A control study was performed using radiation alone on another 18 patients with metastatic tumors, and the response rate was 50% (9/18). Among the 106 patients treated with chemoradiotherapy, the major side effects observed were as follows: leukopenia in 33 patients (31%), thrombocytopenia in 14 (13%), paralytic ileus in 2 (2%), peripheral neuropathy in 2 (2%), and lung fibrosis in 1 (1%). Contrary to expectation, low-grade astrocytomas responded much better to the chemoradiotherapy than high-grade astrocytomas.

Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

Science.gov (United States)

Matsui, Yusuke; Horikawa, Masahiro; Jahangiri Noudeh, Younes; Kaufman, John A; Kolbeck, Kenneth J; Farsad, Khashayar

2017-12-01

The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence ( P = 0.001 and Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

Oxygen tension measurements of tumors growing in mice

International Nuclear Information System (INIS)

Adam, Markus F.; Dorie, Mary Jo; Brown, J. Martin

1999-01-01

Purpose: Clinical studies using the Eppendorf histograph have shown that patients whose tumors have a low pO 2 have worse local control after radiotherapy, and have higher metastatic rates. Because preclinical studies of methods of overcoming, or exploiting, hypoxia generally use transplanted tumors in mice, we have compared the oxygenation of mouse tumors with human tumors to determine the appropriateness of the transplanted mouse model for such preclinical studies. Methods and Materials: We evaluated the oxygenation status of subcutaneous (s.c.) tissue and of 12 intradermally (i.d.)- and 7 s.c.-growing mouse or human transplanted tumors in mice using the Eppendorf histograph, and compared the values obtained with measurements of human head and neck nodes. Results: The normal tissue pO 2 profile of air-breathing mice showed a nearly Gaussian distribution (38.2 ± 14.9 mmHg). Breathing 10% O 2 or carbogen resulted in dramatic changes in normal tissue oxygenation. Tumors growing intradermally in the back of air-breathing mice were extremely hypoxic and resistant to expected changes in oxygenation (carbogen breathing, size, and use of anesthetics). Tumors growing s.c. in the foot showed higher oxygen profiles with marked changes in oxygenation when exposing the animals to different levels of oxygen. However, the oxygenation of the mouse tumors transplanted in either site was only a fraction of that of the majority of human tumors. Conclusion: Experimental mouse tumors are markedly hypoxic, with median values of 10-20% of those of human tumors. Hence, mouse tumors are probably good models for the most hypoxic human tumors that respond poorly to radiotherapy; however, caution has to be exercised in extrapolating data from mouse to man

Animal tumors

International Nuclear Information System (INIS)

Gillette, E.L.

1983-01-01

There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

Science.gov (United States)

Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

2010-04-01

Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

Formation and utilization of acetoin, an unusual product of pyruvate metabolism by Ehrlich and AS30-D tumor mitochondria.

Science.gov (United States)

Baggetto, L G; Lehninger, A L

1987-07-15

[14C]Pyruvate was rapidly non-oxidatively decarboxylated by Ehrlich tumor mitochondria at a rate of 40 nmol/min/mg of protein in the presence or absence of ADP. A search for decarboxylation products led to significant amounts of acetoin formed when Ehrlich tumor mitochondria were incubated with 1 mM [14C] pyruvate in the presence of ATP. Added acetoin to aerobic tumor mitochondria was rapidly utilized in the presence of ATP at a rate of 65 nmol/min/mg of protein. Citrate has been found as a product of acetoin utilization and was exported from the tumor mitochondria. Acetoin has been found in the ascitic liquid of Ehrlich and AS30-D tumor-bearing animals. These unusual reactions were not observed in control rat liver mitochondria.

Epilepsy and brain tumors

Science.gov (United States)

ENGLOT, DARIO J.; CHANG, EDWARD F.; VECHT, CHARLES J.

2016-01-01

Seizures are common in patients with brain tumors, and epilepsy can significantly impact patient quality of life. Therefore, a thorough understanding of rates and predictors of seizures, and the likelihood of seizure freedom after resection, is critical in the treatment of brain tumors. Among all tumor types, seizures are most common with glioneuronal tumors (70–80%), particularly in patients with frontotemporal or insular lesions. Seizures are also common in individuals with glioma, with the highest rates of epilepsy (60–75%) observed in patients with low-grade gliomas located in superficial cortical or insular regions. Approximately 20–50% of patients with meningioma and 20–35% of those with brain metastases also suffer from seizures. After tumor resection, approximately 60–90% are rendered seizure-free, with most favorable seizure outcomes seen in individuals with glioneuronal tumors. Gross total resection, earlier surgical therapy, and a lack of generalized seizures are common predictors of a favorable seizure outcome. With regard to anticonvulsant medication selection, evidence-based guidelines for the treatment of focal epilepsy should be followed, and individual patient factors should also be considered, including patient age, sex, organ dysfunction, comorbidity, or cotherapy. As concomitant chemotherapy commonly forms an essential part of glioma treatment, enzyme-inducing anticonvulsants should be avoided when possible. Seizure freedom is the ultimate goal in the treatment of brain tumor patients with epilepsy, given the adverse effects of seizures on quality of life. PMID:26948360

Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

Science.gov (United States)

Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

2017-12-01

Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

Tumor response parameters for head and neck cancer derived from tumor-volume variation during radiation therapy

International Nuclear Information System (INIS)

Chvetsov, Alexei V.

2013-01-01

Purpose: The main goal of this paper is to reconstruct a distribution of cell survival fractions from tumor-volume variation for a heterogeneous group of head and neck cancer patients and compare this distribution to the data from predictive assays. Methods: To characterize the tumor-volume variation during radiation therapy treatment, the authors use a two-level tumor-volume model of cell population that separates the entire tumor cell population into two subpopulations of viable cells and lethally damaged cells. This parameterized radiobiological model is integrated with a least squares objective function and a simulated annealing optimization algorithm to describe time-dependent tumor-volume variation rates in individual patients. Several constraints have been used in the optimization problem because tumor-volume variation during radiotherapy is described by a sum of exponentials; therefore, the problem of accurately fitting a model to measured data is ill-posed. The model was applied to measured tumor-volume variation curves from a clinical study on tumor-volume variation during radiotherapy for 14 head and neck cancer patients in which an integrated CT/linear particle accelerator (LINAC) system was used for tumor-volume measurements. Results: The two-level cell population tumor-volume modeling is capable of describing tumor-volume variation throughout the entire treatment for 11 of the 14 patients. For three patients, the tumor-volume variation was described only during the initial part of treatment, a fact that may be related to the neglected hypoxia in the two-level approximation. The predicted probability density distribution for the survival fractions agrees with the data obtained using in vitro studies with predictive assays. The mean value 0.35 of survival fraction obtained in this study is larger than the value 0.32 from in vitro studies, which could be expected because of greater repair in vivo. The mean half-life obtained in this study for the head

Evaluation bias in objective response rate and disease control rate between blinded independent central review and local assessment: a study-level pooled analysis of phase III randomized control trials in the past seven years.

Science.gov (United States)

Zhang, Jianrong; Zhang, Yiyin; Tang, Shiyan; Liang, Hengrui; Chen, Difei; Jiang, Long; He, Qihua; Huang, Yu; Wang, Xinyu; Deng, Kexin; Jiang, Shuhan; Zhou, Jiaqing; Xu, Jiaxuan; Chen, Xuanzuo; Liang, Wenhua; He, Jianxing

2017-12-01

In previous studies, complete-case implementation of blind independent central review has been considered unnecessary based on no sign of systematic bias between central and local assessments. In order to further evaluate its value, this study investigated evaluation status between both assessments in phase III trials of anti-cancer drugs for non-hematologic solid tumors. Eligible trials were searched in PubMed with the date of Jan 1, 2010 to Jun 30, 2017. We compared objective response rate (ORR) and disease control rate (DCR) between central and local assessments by study-level pooled analysis and correlation analysis. In pooled analysis, direct comparison was measured by the odds ratio (OR) of central-assessed response status to local-assessed response status; to investigate evaluation bias between central and local assessments, the above calculated OR between experimental (exp-) and control (con-) arms were compared, measured by the ratio of OR. A total of 28 included trials involving 17,466 patients were included (28 with ORR, 16 with DCR). Pooled analysis showed central assessment reported lower ORR and DCR than local assessment, especially in trials with open-label design, central-assessed primary endpoint, and positive primary endpoint outcome, respectively. However, this finding could be found in both experimental [exp-ORR: OR=0.81 (95% CI: 0.76-0.87), Pevaluation bias between two assessments was indicated through further analysis [ORR: ratio of OR=1.02 (0.97-1.07), P=0.42, I 2 =0%; DCR: ratio of OR=0.98 (0.93-1.03), P=0.37, I 2 =0%], regardless of mask (open/blind), sample size, tumor type, primary endpoint (central-assessed/local-assessed), and primary endpoint outcome (positive/negative). Correlation analysis demonstrated a high-degree concordance between central and local assessments (exp-ORR, con-ORR, exp-DCR, con-DCR: r>0.90, P<0.01). Blind independent central review remained irreplaceable to monitor local assessment, but its complete

[Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

Science.gov (United States)

Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

2007-01-30

To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

Gene expression and hormone autonomy in radiation-induced tumors of Arabidopsis thaliana

International Nuclear Information System (INIS)

Persinger, S.M.; Town, C.D.

1989-01-01

In order to study the molecular genetics of factor controlling plant cell growth, we have isolated a group of radiation-induced tumors from Arabidopsis thaliana. Tumors appeared on plants derived from 60 Co gamma-irradiated seed or seedlings, and are capable of hormone-autonomous growth in culture. We have used vertebrate oncogene probes to explore the hypothesis that the tumors arose by the radiation-induced activation of growth-regulating plant oncogenes. One probe, int-2, was used to isolate cDNA clones representing an mRNA differentially expressed between tumors and hormone-dependent callus tissue. The genomic organization and function of this and other differentially expressed Arabidopsis sequences are being further characterized. A second area of study concerns the hormonal status of individual tumors. Tumor tissue varies in color, texture, and degree of differentiation: while some tumors appear undifferentiated, one consistently produces roots, and others occasionally develop shoots or leaflets. The tumors have characteristic growth rates on hormone-free medium, and growth in response to exogenous hormones differs among the tumors themselves and from wild-type. Characterization of the relationships between hormonal status, morphogenesis, and gene expression should yield valuable insights into the mechanisms regulating plant growth and development

Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors

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Cha, Yu Jin; Kim, Mi Sook; Jang, Won Il; Seo, Young Seok; Cho, Chul Koo; Yoo, Hyung Jun; Paik, Eun Kyung [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2017-06-15

To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3–4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1–2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

Stereotactic Body Radiation Therapy for Patients with Heavily Pretreated Liver Metastases and Liver Tumors

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Lanciano, Rachelle; Lamond, John; Yang, Jun; Feng, Jing; Arrigo, Steve; Good, Michael; Brady, Luther, E-mail: rlancmd@gmail.com [Philadelphia CyberKnife, Drexel University, Havertown, PA (United States)

2012-03-09

We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1–4 tumors per patient) who received an ablative radiation dose (BED ≥ 79.2 Gy10 = 66 Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4 months or more follow-up. At a median follow-up of 22 months (range, 10–40 months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55% of tumors receiving a BED ≤ 100 Gy10 (10/18) had local failure compared with 19% receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients treated with BED ≤ 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20 months from treatment and 57 months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED > 100 Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients.

Stage, tumor growth rate and optimal dose fractionation schedules in the treatment of squamous cell carcinoma of the head and neck

International Nuclear Information System (INIS)

Sugawara, Tadashi; Morita, Mamoru; Aihara, Toshinori; Tanaka, Osamu

1983-01-01

In 77 patients with cancer of the head and neck, 45 patients received radiotherapy alone, while 32 patients with T 1 or T 2 glottic cancer received combined therapy with laryngomicrosurgery performed prior to or during the course of irradiation. These T 1 and T 2 groups were separately analyzed from other T 1 and T 2 groups as T sub(LMS). Local recurrence rates were compared concerning overall time and fraction size in following three subgroups, i.e., T sub(LMS), Tsub(1+2), and Tsub(3+4). No significant correlation was detected between total dose converted to partial tolerance (PT) and local control in all subgroups except for Tsub(3+4), in which local recurrence rate was rather higher in high PT range. Local control was significantly dependent on overall treatment time and fraction size, differently by tumor stage. Favorable fractionation schedules considered as optimal for T sub(LMS) were those in which treatment was given 5 times weekly with a daily dose rate more than 196 rad in a shorter overall time of less than 42 days. In contrast to T sub(LMS), effective schedules for Tsub(3+4) consisted of longer overall time of more than 60 days and a lower daily dose rate of less than 153 rad. In Tsub(1+2), the optimal schedule was needed to be altered according to rapidness of progression of disease characterised by duration of the complaints, which was statistically proved to be significantly shorter in Tsub(1+2) than Tsub(3+4). Rapidity-adjusted schedule consisted of a shorter over-all time of less than 49 days with a daily dose rate of more than 175 rad 5 fractions a week for a case having a duration of complaints of less than 2.9 months, and a longer overall time of more than 50 days with a daily dose rate of less than 174 rad for a case having a duration of more than 3 months. (J.P.N.)

Speed and amplitude of lung tumor motion precisely detected in four-dimensional setup and in real-time tumor-tracking radiotherapy

International Nuclear Information System (INIS)

Shirato, Hiroki; Suzuki, Keishiro; Sharp, Gregory C.; Fujita, Katsuhisa R.T.; Onimaru, Rikiya; Fujino, Masaharu; Kato, Norio; Osaka, Yasuhiro; Kinoshita, Rumiko; Taguchi, Hiroshi; Onodera, Shunsuke; Miyasaka, Kazuo

2006-01-01

Background: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. Methods and Materials: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. Results: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. Conclusion: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology

Maximizing Tumor Immunity With Fractionated Radiation

International Nuclear Information System (INIS)

Schaue, Dörthe; Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H.

2012-01-01

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-γ enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4 + CD25 hi Foxp3 + T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

Radiation Treatment for Ewing Family of Tumors in Adults: University of Florida Experience

International Nuclear Information System (INIS)

Shi Wenyin; Indelicato, Daniel J.; Keole, Sameer R.; Morris, Christopher G.; Scarborough, Mark T.; Gibbs, Parker C.; Zlotecki, Robert A.

2008-01-01

Purpose: To review the clinical characteristics and outcomes of adult patients with Ewing family of tumors treated with radiation at University of Florida. Methods and Materials: Clinical features, treatment, and outcomes of 47 patients older than 18 years with Ewing family of tumors treated with combined radiation therapy and chemotherapy from 1970 to 2005 were retrospectively reviewed. Analysis was stratified by age older or younger than 30 years. Patients with metastatic disease at the time of diagnosis were excluded from the study. Results: The 29 men and 18 women had a median age of 24 years. Thirty-three patients were 18-30 years old and 14 patients were older than 30 years. Median follow-up of living patients was 8.2 years. The 5-year overall survival rate for all patients was 43% (p = 0.8523). The 5-year local control rate for all patients was 75% (p = 0.9326). The 5-year rate of freedom from distant metastasis for all patients was 45% (p = 0.5471). There were no significant differences in 5-year overall survival, local control, and freedom from distant metastasis rates; patterns of distant failure; or toxicity profiles between older adult patients and younger adult patients. Conclusions: We found that the natural history and treatment outcomes of the Ewing family of tumors were consistently similar in adults (young and old) and children. Thus, aggressive combined modality approaches should be considered for adult patients

The study on linac stereotactic radiosurgery for acoustic tumors

International Nuclear Information System (INIS)

Ohishi, Hitoshi

1995-01-01

We have designed and manufactured a new type of device for stereotactic radiosurgery characterized by the combined use of a rotatory chair and a linear accelerator. In this study, 20 acoustic tumors treated by our modality were evaluated by serial neuroimaging, neurofunctional outcome and, in a few cases, pathological findings of surgical specimens. Because tumor size usually changed very slowly after radiosurgery, 12 cases that had a minimum of 12 months of follow-up were employed in the analysis of tumor size. Serial neuroimaging studies revealed the reduction of tumor size in 3 cases and prevention of tumor growth in 7 cases, therefore, the rate of tumor control was evaluated as 83%. Growth of tumor size occurred in 3 cases, two were cases harbouring a large cyst in the tumor and another was a case of neurofibromatosis type 2. In 13 cases (68%), loss of the gadolinium enhancement effect inside the tumor was observed. This is a characteristic change after radiosurgery for acoustic tumors, and attributable to a necrotic change. Cranial nerve neuropathies as a complication also occurred (facial nerve palsy in 2 and trigeminal nerve dysfunction in 1). Adjacent parenchymal change appeared in 1 case. This patient had two prior operations and the tumor had an irregular shape, therefore, planning for radiosurgery encountered some difficulty. Hydrocephalus occurred in 1 case. Surgical specimens in 2 cases in which microsurgery was undertaken for growing tumors, revealed a necrotic tumor tissue and proliferation of fibrous tissue. In conclusion, our new device for stereotactic radiosurgery is particularly useful for the treatment of acoustic tumors. Similar therapeutic results of the gamma knife have been achieved. Radiosurgery is a recommendable treatment for acoustic tumors. However, the superiority of radiosurgery over microsurgery is still controversial and needs a longer term follow-up and multivariate analysis for a final conclusion. (author)

Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer

DEFF Research Database (Denmark)

Tanderup, Kari; Fokdal, Lars Ulrik; Sturdza, Alina

2016-01-01

-center patient series (retroEMBRACE). Materials and methods This study analyzed 488 locally advanced cervical cancer patients treated with external beam radiotherapy ± chemotherapy combined with IGABT. Brachytherapy contouring and reporting was according to ICRU/GEC-ESTRO recommendations. The Cox Proportional...... Hazards model was applied to analyze the effect on local control of dose-volume metrics as well as overall treatment time (OTT), dose rate, chemotherapy, and tumor histology. Results With a median follow up of 46 months, 43 local failures were observed. Dose (D90) to the High Risk Clinical Target Volume...

SU-E-T-34: An in Vivo Study On Pulsed Low Dose-Rate Radiotherapy for Prostate Cancer

International Nuclear Information System (INIS)

Wang, B; Cvetkovic, D; Chen, L; Ma, C; Chen, X; Zhang, P; Zhang, C

2014-01-01

Purpose: Re-irradiation with conventional radiotherapy techniques (CRT) may pose significant risks due to high accumulative radiation doses. Pulsed low dose-rate radiotherapy (PLDR) has been used in clinical trials for recurrent cancer treatment. In our previous studies, PLDR irradiation showed significantly lower toxicity than CRT, resulting in much longer survival of mice after PLDR total body irradiation (TBI) than conventional TBI. The purpose of this study was to investigate tumor control efficacy of PLDR treatment for prostate cancer with an animal model of prostate cancer LNCaP. Methods: We used an orthotopic murine model of LNCaP cell line for this study. LNCaP cells were implanted into immune-suppressed male nude mice via surgery. We monitored the tumor growth with MRI. The tumor-bearing mice were allocated into a PLDR(n=9), CRT(n=7), and control group(n=7) randomly. The mice in the PLDR and CRT groups were irradiated with 2Gy dose for one time. For the CRT treatment, the mice received 2Gy at a dose-rate of 300 MU/minute. For the PLDR treatment, the 2Gy dose was further divided into ten pulses of 0.2Gy at the same dose-rate with an interval of 3 minutes between the pulses. Results: Sizable tumor growth delays were observed for the PLDR and CRT groups through weekly MRI scans. The mean values of the normalized tumor volumes (± standard deviation of the mean) were 1.53±0.07, 1.53±0.14, and 1.81±0.09 at one week after treatment, 2.28±0.13, 2.19±0.16, and 3.04±0.25 at two weeks after treatment, and 3.31±0.23, 3.14±0.24 and 4.62±0.49 at three weeks after treatment, for the PLDR, CRT, and control groups, respectively. Conclusion: The PLDR and CRT treatments showed comparable tumor control rates in this study. Our in vivo results indicate that PLDR may be a viable option for treating recurrent prostate cancer due to its equivalent tumor control but low normal tissue toxocities

Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report

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Norio Yokoigawa

2009-04-01

Full Text Available We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

Effects of nursing intervention models on social adaption capability development in preschool children with malignant tumors: a randomized control trial.

Science.gov (United States)

Yu, Lu; Mo, Lin; Tang, Yan; Huang, Xiaoyan; Tan, Juan

2014-06-01

The objectives of this study are to compare the effects of two nursing intervention models on the ability of preschool children with malignant tumors to socialize and to determine if these interventions improved their social adaption capability (SAC) and quality of life. Inpatient preschool children with malignant tumors admitted to the hospital between December 2009 and March 2012 were recruited and randomized into either the experimental or control groups. The control group received routine nursing care, and the experimental group received family-centered nursing care, including physical, psychological, and social interventions. The Infants-Junior Middle School Student's Social-Life Abilities Scale was used to evaluate SAC development of participants. Participants (n = 240) were recruited and randomized into two groups. After the intervention, the excellent and normal SAC rates were 27.5% and 55% in the experimental group, respectively, compared with 2.5% and 32.5% in the control group (p intervention, SAC in experimental group was improved compared with before intervention (54.68 ± 10.85 vs 79.9 ± 22.3, p intervention in the control group (54.70 ± 11.47 vs. 52 ± 15.8, p = 0.38). The family-centered nursing care model that included physical, psychological, and social interventions improved the SAC of children with malignancies compared with children receiving routine nursing care. Establishing a standardized family-school-community-hospital hierarchical multi-management intervention model for children is important to the efficacy of long-term interventions and to the improvement of SAC of children with malignancies. Copyright © 2014 John Wiley & Sons, Ltd.

A Phase II Trial of Brachytherapy Alone After Lumpectomy for Select Breast Cancer: Tumor Control and Survival Outcomes of RTOG 95-17

International Nuclear Information System (INIS)

Arthur, Douglas W.; Winter, Kathryn; Kuske, Robert R.; Bolton, John; Rabinovitch, Rachel; White, Julia; Hanson, William F.; Wilenzick, Raymond M.; McCormick, Beryl

2008-01-01

Purpose: Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported. Methods and Materials: Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison. Results: Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively. Conclusion: Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up

Early experience with percutaneous cryoablation of extra-abdominal desmoid tumors

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Kujak, Jennifer L.; Liu, Patrick T. [Mayo Clinic Arizona, Department of Radiology, Phoenix, AZ (United States); Johnson, Geoffrey B.; Callstrom, Matthew R. [Mayo Clinic Rochester, Department of Radiology, Rochester, MN (United States)

2010-02-15

Surgical resection, radiation therapy and chemotherapy are all accepted as standard treatments for extra-abdominal desmoid (EAD) tumors, but their effectiveness has been limited by frequent local recurrence. The purpose of this article is to describe our early experiences with using percutaneous cryoablation for local control of extra-abdominal desmoid tumors in five patients whose tumors had failed to respond to standard therapy. In a retrospective search of our institution's radiology database for patients who had undergone percutaneous cryoablation for treatment of EAD tumors between June 2004 and July 2007, we identified five patients (three female and two male). No patients were excluded from this review. Three of these patients had been referred for cryoablation for local tumor control, and two had been referred for palliation of inoperable tumors. The age range of the patients at the time of cryoablation was 9-41 years. The treated EAD tumors were located in the neck, shoulders and trunk and ranged in size from 3.0 cm to 10.0 cm. Medical records were reviewed for short-term and long-term follow-up, and patients were contacted for additional follow-up. Patients were asked to rate their pain as absent, mild, moderate or severe, and to compare it with their levels before cryoablation, describing it as improved, unchanged or worsened. Radiology records were reviewed to follow the size of the EAD tumors before and after cryotherapy. For the three patients referred for local control of EAD tumors, complete tumor coverage with the ablation zones was achieved. Two of these patients, with masses 3.0 cm and 4.9 cm in diameter, reported complete absence of pain at both short-term and long-term follow-up at 13 months and 49 months. Their tumors had completely resolved on long-term imaging follow-up at 19 months and 43 months. The third patient, with a 6.1 cm mass, reported improved mild pain at 6 months, and imaging showed a moderate decrease of tumor size. For the

Curettage of benign bone tumors and tumor like lesions: A retrospective analysis

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Zile Singh Kundu

2013-01-01

Full Text Available Background: Curettage is one of the most common treatment options for benign lytic bone tumors and tumor like lesions. The resultant defect is usually filled. We report our outcome curettage of benign bone tumors and tumor like lesions without filling the cavity. Materials and Methods: We retrospectively studied 42 patients (28 males and 14 females with benign bone tumors who had undergone curettage without grafting or filling of the defect by any other bone graft substitute. The age of the patients ranged from 14 to 66 years. The most common histological diagnosis was that of giant cell tumor followed by simple bone cyst, aneurysamal bone cyst, enchondroma, fibrous dysplasia, chondromyxoid fibroma, and chondroblastoma and giant cell reparative granuloma. Of the 15 giant cell tumors, 4 were radiographic grade 1 lesions, 8 were grade 2 and 3 grade 3. The mean maximum diameter of the cysts was 5.1 (range 1.1-9 cm cm and the mean volume of the lesions was 34.89 cm 3 (range 0.94-194.52 cm 3 . The plain radiographs of the part before and after curettage were reviewed to establish the size of the initial defect and the rate of reconstitution, filling and remodeling of the bone defect. Patients were reviewed every 3 monthly for a minimum period of 2 years. Results: Most of the bone defects completely reconstituted to a normal appearance while the rest filled partially. Two patients had preoperative and three had postoperative fractures. All the fractures healed uneventfully. Local recurrence occurred in three patients with giant cell tumor who were then reoperated. All other patients had unrestricted activities of daily living after surgery. The rate of bone reconstitution, risk of subsequent fracture or the incidence of complications was related to the size of the cyst/tumor at diagnosis. The benign cystic bone lesions with volume greater than approximately 70 cm 3 were found to have higher incidence of complications. Conclusion: This study

Tenosynovial Giant Cell Tumor: Better molecular understanding revolutionizes treatment outcome

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Emad Shash

2016-01-01

Full Text Available Tenosynovial giant cell tumors (TGCTs are rare tumors, which are primarily treated via surgery with a low likelihood of metastasis. Although wide excision is an excellent choice for local control, tumors located within or close to major joints, along with the benign nature of the disease, make such resection impractical. An increase in local recurrences and the need for multiple surgical procedures promoted the interest in targeted-therapies for this disease. TGCTs contain a mixture of giant cells, mononuclear cells and inflammatory cells, with clonal cytogenetic abnormalities through rearrangements involving 1p11–13. Colony stimulating factor (CSF1 gene encodes for the ligand of CSF1 receptor (CSF1R. The CSF1 gene is located at the chromosome 1p13 breakpoint and is found to be translocated in 63%–77% of patients with TGCTs. Selective CSF1R inhibitors yield high response rate and disease control, demonstrating the integration of a new drug development technology that could revolutionize treatment outcomes.

Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma

International Nuclear Information System (INIS)

Yang, C.M.; Olsen, K.R.; Schwade, J.G.; Houdek, P.V.; Markoe, A.M.; Pisciotta, V.; Xiaodong Wu

1993-01-01

The dose rate effect of radiation by 125 I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plagues (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10 000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr -1 while that in ten eyes with low activity plaques was 239.9 cGy hr -1 . For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumours more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. In the second part of the experiment, 125 I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. (Author)

Tumor scintigram, 2

International Nuclear Information System (INIS)

Nakano, Shunichi; Hasegawa, Yoshihisa; Shimura, Kazuo; Ifuka, Keijiro

1975-01-01

In various cases of malignant tumors, especially those of lung cancer and liver cancer, scans were made with 57 Co-bleomycin(BLM), and its diagnostic significance was evaluated. Tumors were visualized with 57 Co-BLM in 22 of the 26 cases of lung cancer (84.6%). Concentrations of the RI were noted in all of the cases of squamous epithelium cancer, adenoid cancer and cellule-type undifferentiated cancer. The smallest tumor that could be detected was a 2 x 2 cm adenoid cancer. Tumors were imaged in 19 of the 27 cases of liver cancer (70.4%). This detection rate was increased by a combination of 57 Co-BLM and 198 Au-colloid scanning. The authors believe that 57 Co-BLM will help to establish the diagnosis of lung cancer or liver cancer. Tumors were also imaged in 6 of the 15 cases of breast cancer, but no distinct concentration was noted in the 7 cases of thyroid cancer. (Ueda, J.)

Use of Semiflexible Applicators for Radiofrequency Ablation of Liver Tumors

International Nuclear Information System (INIS)

Gaffke, G.; Gebauer, B.; Knollmann, F.D.; Helmberger, T.; Ricke, J.; Oettle, H.; Felix, R.; Stroszczynski, C.

2006-01-01

Purpose. To evaluate the feasibility and potential advantages of the radiofrequency ablation of liver tumors using new MRI-compatible semiflexible applicators in a closed-bore high-field MRI scanner. Methods. We treated 8 patients with 12 malignant liver tumors of different origin (5 colorectal carcinoma, 2 cholangiocellular carcinoma, 1 breast cancer) under MRI guidance. Radiofrequency ablation (RFA) was performed using 5 cm Rita Starburst Semi-Flex applicators (Rita Medical Systems, Milwaukee, WI, USA) which are suitable for MR- and CT-guided interventions and a 150 W RF generator. All interventions were performed in a closed-bore 1.5 T high-field MRI scanner for MRI-guided RFA using fast T1-weighted gradient echo sequences and T2-weighted ultra-turbo spin echo sequences. Control and follow-up MRI examinations were performed on the next day, at 6 weeks, and every 3 months after RFA. Control MRI were performed as double-contrast MRI examinations (enhancement with iron oxide and gadopentetate dimeglumine). All interventions were performed with the patient under local anesthesia and analgo-sedation. Results. The mean diameter of the treated hepatic tumors was 2.4 cm (±0.6 cm, range 1.0-3.2 cm). The mean diameter of induced necrosis was 3.1 cm (±0.4 cm). We achieved complete ablation in all patients. Follow-up examinations over a duration of 7 months (±1.3 months, range 4-9 month) showed a local control rate of 100% in this group of patients. All interventions were performed without major complications; only 2 subcapsular hematomas were documented. Conclusion. RFA of liver tumors using semiflexible applicators in closed-bore 1.5 T scanner systems is feasible. These applicators might simplify the RFA of liver tumors under MRI control. The stiff distal part of the applicator facilitates its repositioning

The prognostic role of controlling nutritional status scores in patients with solid tumors.

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Liang, Ruo-Fei; Li, Jun-Hong; Li, Mao; Yang, Yuan; Liu, Yan-Hui

2017-11-01

We conducted a meta-analysis to investigate the association between preoperative controlling nutritional status (CONUT) scores in various solid tumors and clinical outcomes. Relevant studies published up to August 12, 2017 were identified using electronic databases, including PubMed, Embase, and Web of Science. The pooled hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for overall survival (OS) and event-free survival (EFS) were calculated to explore the relationship between preoperative CONUT score and prognosis. In total, 674 patients with solid tumors from four published studies were included in this meta-analysis. The pooled HR for OS was 1.98 (95% CI, 1.34-2.91, p=0.001), indicating that patients with high CONUT scores had worse OS. The pooled HR for EFS was 1.98 (95% CI, 1.34-2.93, p=0.001), revealing that high CONUT scores were significantly associated with short EFS. Our data suggest that high preoperative CONUT scores indicate poor prognosis for patients with solid tumors. Further studies are needed to verify the significance of CONUT scores in clinical practice. Copyright © 2017. Published by Elsevier B.V.

Pituitary tumor risk in relation to mobile phone use: A case-control study.

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Shrestha, Mithila; Raitanen, Jani; Salminen, Tiina; Lahkola, Anna; Auvinen, Anssi

2015-01-01

The number of mobile phone users has grown rapidly, which has generated mounting public concern regarding possible health hazards. This study aims to assess pituitary tumor risk, as it has rarely been investigated. A case-control study was conducted with 80 eligible cases identified from all five university hospitals in Finland and frequency-matched 240 controls from the national population register. Controls were matched to cases by age, sex, region of residence and date of interview. A detailed history of mobile phone use was obtained using a structured interview. Several indicators of mobile phone use were assessed using conditional logistic regression. A reduced odds ratio was seen among regular mobile phone users [OR 0.39, 95% confidence interval (CI) 0.21, 0.72] relative to never/non-regular users, possibly reflecting methodological limitations. Pituitary tumor risk was not increased after 10 or more years since first use (OR 0.69, 95% CI 0.25, 1.89). The risk was not increased in relation to duration, cumulative hours of use, or cumulative number of calls. The results were similar for analog and digital phones. We found no excess risk associated with self-reported short- or medium-term use of mobile phones. This is consistent with most of the published studies. However, uncertainties remained for longer duration of use, as a very small proportion of study participants reported use beyond 10 years.

Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

International Nuclear Information System (INIS)

Chen Yidong; Feng Qinfu; Lu Haizhen; Mao Yousheng; Zhou Zongmei; Ou Guangfei; Wang Mei; Zhao Jun; Zhang Hongxing; Xiao Zefen; Chen Dongfu; Liang Jun; Zhai Yirui; Wang Luhua; He Jie

2010-01-01

Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

Rate of Clinical Complete Response for 1 Year or More in Bone-Metastatic Breast Cancer after Comprehensive Treatments including Autologous Formalin-Fixed Tumor Vaccine.

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Kuranishi, Fumito; Imaoka, Yuki; Sumi, Yuusuke; Uemae, Yoji; Yasuda-Kurihara, Hiroko; Ishihara, Takeshi; Miyazaki, Tsubasa; Ohno, Tadao

2018-01-01

No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Three patients maintained cCR status of the bone metastasis for 17 months or more. Rate of cCR for 1 year or more appeared to be 15% (3/20) after comprehensive treatments including AFTV. The median overall survival time (60.0 months) and the 3- to 8-year survival rates after diagnosis of bone metastasis were greater than those of historical control cohorts in Japan (1988-2002) and in the nationwide population-based cohort study of Denmark (1999-2007). Bone-metastatic breast cancer may be curable after comprehensive treatments including AFTV, although larger scale clinical trial is required.

Anti-Tumor Activity of a Polysaccharide from Blueberry

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Xiyun Sun

2015-02-01

Full Text Available Blueberries (Vaccinium spp. are rich in bioactive compounds. However, the biological activity of polysaccharides from blueberry has not been reported so far. This study evaluated the anti-tumor and immunological activities of a polysaccharide (BBP3-1 from blueberry in S180-bearing mice. The experimental results indicated that BBP3-1 (100 mg·kg−1·d−1 inhibited the tumor growth rate by 73.4%. Moreover, this group, compared with the model control, had shown an effect of increasing both the spleen and thymus indices (p < 0.05, increasing phagocytosis by macrophages (p < 0.05, boosting the proliferation and transformation of lymphocytes (p < 0.01, promoting the secretion of TNF-α, IFN-γ, and IL-2 (p < 0.05 and improving NK cell activity (p < 0.01. From this study, we could easily conclude that BBP3-1 has the ability to inhibit tumor progression and could act as a good immunomodulator.

Radiotherapy in the treament of gastrointestinal stromal tumors

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Rebecca C. Heintzelman

2011-10-01

Full Text Available Gastrointestinal stromal tumors (GIST are uncommon mesenchymal tumors of the gastrointestinal tract. Up to one-third of GISTs are malignant with a high rate of metastasis. Surgical resection is the mainstay of care for patients with resectable disease. Imatinib mesylate, a selective tyrosine kinase inhibitor, is the current standard of care for GISTs that cannot be completely resected or in cases of metastatic GIST. Although often overlooked, radiation therapy is a viable option for select patients with GIST. We report the case of a patient with unresectable GIST who was treated with local radiotherapy and achieved longterm response. We also present a review of the literature regarding the use of radiotherapy in the treatment of GIST. GIST has been shown to be a radiosensitive tumor. Radiotherapy can offer long-term local control and should be considered in the adjuvant or palliative setting. The role of radiotherapy delivered concurrently with imatinib in the treatment of GIST may warrant further investigation.

Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

International Nuclear Information System (INIS)

Zheng Chuansheng; Xia Xiangwen; Feng Gansheng; Li Xin; Liang Huimin; Liang Bin

2010-01-01

Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CI I L- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CI I L-12) to liver cancer cell HepG 2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX 2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-Cl I L-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

International Nuclear Information System (INIS)

Wu Congmei; Li Xiuyi; Liu Shuzheng

2001-01-01

Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study.

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Schüz, Joachim; Schmidt, Lisbeth Samsø; Kogner, Per; Lähteenmäki, Päivi M; Pal, Niklas; Stokland, Tore; Schmiegelow, Kjeld

2011-05-01

Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor. Copyright © 2010 UICC.

Adjuvant radiotherapy for phyllodes tumor of the breast

International Nuclear Information System (INIS)

Chaney, Arthur W.; Pollack, Alan; Zagars, Gunar K.

1997-01-01

. The choice of procedure was related to tumor size. Median size was 13.5 cm in patients undergoing mastectomy, and 4.3 cm in those undergoing lumpectomy. Final margin status was positive in one patient, and negative in seven patients. Seven patients received adjuvant radiation to the breast to a dose of 6000 cGy. One patient received 5000 cGy to the breast, followed by an interstitial boost of 2000 cGy for a total of 7000 cGy. No attempt was made to treat the lymphatics. There were no local or distant failures, with a median length of follow-up of 36.5 months. Conclusion: Phyllodes tumors of the breast are relatively uncommon and are unpredictable in behavior. Both benign and malignant histotypes can recur locally, and can metastasize. Current recommendations, in regards to definitive surgery, call for breast conservation with adequate margins when possible. Mastectomy is recommended for high tumor to breast ratios or an inability to obtain adequate margins with conservative surgery. Recurrence rates with surgery alone range from 10 to 40%. Higher rates are observed with malignant tumors and with conservative surgery. Although the numbers are small, this is the largest reported study evaluating the role of adjuvant radiotherapy. All eight patients achieved local control despite adverse features including malignant histology, large size, positive margins, and recurrent disease. In summary, adjuvant radiotherapy for phyllodes tumors that are at high risk of local failure is underutilized. Diffuse breast involvement, malignant histology, positive margins, or local excision are all indications for adjuvant radiotherapy. Our results indicate that treatment of the breast only (not the lymphatics) to 6000 cGy is effective, although a dose-response has not been established

Maximizing Tumor Immunity With Fractionated Radiation

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Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Ratikan, Josephine A.; Iwamoto, Keisuke S.; McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

2012-07-15

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma} enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.

On the Inclusion of Short-distance Bystander Effects into a Logistic Tumor Control Probability Model.

Science.gov (United States)

Tempel, David G; Brodin, N Patrik; Tomé, Wolfgang A

2018-01-01

Currently, interactions between voxels are neglected in the tumor control probability (TCP) models used in biologically-driven intensity-modulated radiotherapy treatment planning. However, experimental data suggests that this may not always be justified when bystander effects are important. We propose a model inspired by the Ising model, a short-range interaction model, to investigate if and when it is important to include voxel to voxel interactions in biologically-driven treatment planning. This Ising-like model for TCP is derived by first showing that the logistic model of tumor control is mathematically equivalent to a non-interacting Ising model. Using this correspondence, the parameters of the logistic model are mapped to the parameters of an Ising-like model and bystander interactions are introduced as a short-range interaction as is the case for the Ising model. As an example, we apply the model to study the effect of bystander interactions in the case of radiation therapy for prostate cancer. The model shows that it is adequate to neglect bystander interactions for dose distributions that completely cover the treatment target and yield TCP estimates that lie in the shoulder of the dose response curve. However, for dose distributions that yield TCP estimates that lie on the steep part of the dose response curve or for inhomogeneous dose distributions having significant hot and/or cold regions, bystander effects may be important. Furthermore, the proposed model highlights a previously unexplored and potentially fruitful connection between the fields of statistical mechanics and tumor control probability/normal tissue complication probability modeling.

Adrenocortical tumors in children

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R.C. Ribeiro

2000-10-01

Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

Postoperative HDR afterloading brachytherapy: Vaginal tumor recurrence rates in patients with endometrial carcinoma dependent on treatment volumes

International Nuclear Information System (INIS)

Kloetzer, K.H.; Guenther, R.; Wendt, T.

1997-01-01

Patients and Method: At Jena University, Department of Radiotherapy, from 1981 to 1990 108 patients with endometrical carcinoma were postoperatively treated with high dose radiation brachytherapy of the vagina without additional percutaneous radiotherapy. Histology showed more or less differenciated adenocarcinoma in 90% of all patients, all patients were postoperatively stage I or II without proven lymphatic metastases. Dependent on individual figures patients were distributed to 3 different gorups: group A: 4 x 10 Gy, tissue-thickness of 1 cm (vaginal apex) respectively 0.5 cm (lower vaginal walls); group B: 4 x 10 Gy, tissue thickness of 1 cm (upper vaginal wall); group C: 4 x 10 Gy, tissue-thickness of 0.5 cm (both excluding the lower vaginal walls). Results: Both 3-year survival rates (group A: 96.6%, group B: 96.9%, group C: 97.7%) and tumor relapse rates of the vaginal apex (group A: 0, group B: 3.1%, group C: 2.2%) don't show significant differences. No case of local tumor recurrence was seen in the upper 2/3 of the vagina and the pelvic walls. Late side effects concerning bladder and rectum (grade III to IV, EORTC/RTOG) could be minimized by reducing the treatment volume (group A: 6.8%/12.6%, group B: 6,2%/3.1%, group C: 2.2%/0). (orig./AJ) [de

Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma.

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Sekar, Divya; Govene, Luisa; Del Río, María-Luisa; Sirait-Fischer, Evelyn; Fink, Annika F; Brüne, Bernhard; Rodriguez-Barbosa, José I; Weigert, Andreas

2018-03-07

Natural Killer T cells (NKT cells) are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.

Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma

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Divya Sekar

2018-03-01

Full Text Available Natural Killer T cells (NKT cells are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA on type I NKT cells in polyoma middle T oncogene-driven (PyMT murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1 were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.

Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors

International Nuclear Information System (INIS)

Sato, Tatsusuke; Suga, Michio; Kudo, Hajime; Waga, Takashi; Ogasawara, Masamichi

1980-01-01

Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (Tetraploid type, 10 5 cells) after repeated immunization with gamma-irradiated (13,000 rads 60 Co) allogeneic non-viral tumors of ascites type (Tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation. (author)

Visual Perception Based Rate Control Algorithm for HEVC

Science.gov (United States)

Feng, Zeqi; Liu, PengYu; Jia, Kebin

2018-01-01

For HEVC, rate control is an indispensably important video coding technology to alleviate the contradiction between video quality and the limited encoding resources during video communication. However, the rate control benchmark algorithm of HEVC ignores subjective visual perception. For key focus regions, bit allocation of LCU is not ideal and subjective quality is unsatisfied. In this paper, a visual perception based rate control algorithm for HEVC is proposed. First bit allocation weight of LCU level is optimized based on the visual perception of luminance and motion to ameliorate video subjective quality. Then λ and QP are adjusted in combination with the bit allocation weight to improve rate distortion performance. Experimental results show that the proposed algorithm reduces average 0.5% BD-BR and maximum 1.09% BD-BR at no cost in bitrate accuracy compared with HEVC (HM15.0). The proposed algorithm devotes to improving video subjective quality under various video applications.

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

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Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Head and neck tumors and impaired mental function following scalp irradiation

International Nuclear Information System (INIS)

Modan, B.; Ron, E.; Werner, A.; Yaar, I.

1977-01-01

This is a second report of a comprehensive case-control study of 11,000 individuals subjected to scalp x-irradiation in childhood between 1949 and 1960. Follow up was conducted through the following national records: Tumor, Registry, Central Population Registry, Mental Health Registry, Nationwide High School Aptitude Test, Police, Ministry of Welfare and the Army. In addition, a sample of the cases and of the controls was brought in for clinical examinations, psychological testing and computerized EEG. The mean dose delivered to the brain, as determined by dosimetric studies, was 140r and to the thyroid 6-9r. Specific topics to be presented and discussed are as follows: an increased risk of head and neck tumors and the presence of a dose response relationship. The implication of the marked increase in risk for thyroid tumors, in view of the low dose delivered to this organ. Radiation effect on brain function as evidenced by a lower educational achievement, a lower basic intelligence level, somewhat impaired mental ability, and an increased rate of admissions to mental hospitals among cases, as compared to each of the two control groups, as well as the presence of a hyperactivity pattern on EEG

Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data

DEFF Research Database (Denmark)

Lühr, Armin; Löck, Steffen; Jakobi, Annika

2017-01-01

PURPOSE: Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. METHODS AND ...

Repeat Brachytherapy for Patients With Residual or Recurrent Tumors of Oral Cavity

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Yoshimura, Ryo-ichi, E-mail: ysmrmrad@tmd.ac.jp [Department of Diagnostic Radiology and Oncology, Tokyo Medical and Dental University, Tokyo (Japan); Shibuya, Hitoshi; Hayashi, Keiji; Nakagawa, Keiko; Toda, Kazuma [Department of Diagnostic Radiology and Oncology, Tokyo Medical and Dental University, Tokyo (Japan); Watanabe, Hiroshi [Department of Oral and Maxillofacial Radiology, Tokyo Medical and Dental University, Tokyo (Japan); Kaida, Atushi; Miura, Masahiko [Department of Oral Radiation Oncology, Tokyo Medical and Dental University, Tokyo (Japan)

2012-07-15

Purpose: To analyze data from patients receiving repeat brachytherapy (re-BT) for the treatment of residual or recurrent tumor in the oral cavity. Methods and Materials: Between January 2003 and December 2007, 62 patients who had undergone definitive BT as an initial treatment of oral cancer subsequently underwent re-BT for the treatment of residual or recurrent tumors at the diagnostic radiology and oncology department (Tokyo Medical and Dental University Hospital). Re-BT was performed 0.9-73 months (median, 5.7) after the initial BT. Au-198 grains were used as the re-BT source in all 62 patients, and an area of 0.8-6.3 cm{sup 2} (median, 3.1) was permanently irradiated with 60-110 Gy (median, 83) according to the system of Paterson-Parker. Results: The 2-year local control and overall survival rate was 53% and 66%, respectively, and local control significantly affected overall survival. Both local control and overall survival were affected by the initial tumor characteristics and the macroscopic appearance of the residual or recurrent tumor. Grade 3 or 4 complications were seen in 5 patients. The incidence of mandibular and mucosal complications was significantly related to a biologic effective dose of {alpha}/{beta} of 3 Gy to the surface of the gingiva and mucosa, respectively. Conclusion: Re-BT using Au-198 grains for the treatment of residual or recurrent tumor after definitive BT in the oral cavity is effective and well tolerated.

Evaluation of the effect of prostate volume change on tumor control probability in LDR brachytherapy.

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Knaup, Courtney; Mavroidis, Panayiotis; Stathakis, Sotirios; Smith, Mark; Swanson, Gregory; Papanikolaou, Niko

2011-09-01

This study evaluates low dose-rate brachytherapy (LDR) prostate plans to determine the biological effect of dose degradation due to prostate volume changes. In this study, 39 patients were evaluated. Pre-implant prostate volume was determined using ultrasound. These images were used with the treatment planning system (Nucletron Spot Pro 3.1(®)) to create treatment plans using (103)Pd seeds. Following the implant, patients were imaged using CT for post-implant dosimetry. From the pre and post-implant DVHs, the biologically equivalent dose and the tumor control probability (TCP) were determined using the biologically effective uniform dose. The model used RBE = 1.75 and α/β = 2 Gy. The prostate volume changed between pre and post implant image sets ranged from -8% to 110%. TCP and the mean dose were reduced up to 21% and 56%, respectively. TCP is observed to decrease as the mean dose decreases to the prostate. The post-implant tumor dose was generally observed to decrease, compared to the planned dose. A critical uniform dose of 130 Gy was established. Below this dose, TCP begins to fall-off. It was also determined that patients with a small prostates were more likely to suffer TCP decrease. The biological effect of post operative prostate growth due to operative trauma in LDR was evaluated using the concept. The post-implant dose was lower than the planned dose due to an increase of prostate volume post-implant. A critical uniform dose of 130 Gy was determined, below which TCP begun to decline.

Evaluation of the effect of prostate volume change on tumor control probability in LDR brachytherapy

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Courtney Knaup

2011-09-01

Full Text Available Purpose: This study evaluates low dose-rate brachytherapy (LDR prostate plans to determine the biological effectof dose degradation due to prostate volume changes. Material and methods: In this study, 39 patients were evaluated. Pre-implant prostate volume was determinedusing ultrasound. These images were used with the treatment planning system (Nucletron Spot Pro 3.1® to create treatmentplans using 103Pd seeds. Following the implant, patients were imaged using CT for post-implant dosimetry. Fromthe pre and post-implant DVHs, the biologically equivalent dose and the tumor control probability (TCP were determinedusing the biologically effective uniform dose. The model used RBE = 1.75 and α/β = 2 Gy. Results: The prostate volume changed between pre and post implant image sets ranged from –8% to 110%. TCP andthe mean dose were reduced up to 21% and 56%, respectively. TCP is observed to decrease as the mean dose decreasesto the prostate. The post-implant tumor dose was generally observed to decrease, compared to the planned dose.A critical uniform dose of 130 Gy was established. Below this dose, TCP begins to fall-off. It was also determined thatpatients with a small prostates were more likely to suffer TCP decrease. Conclusions: The biological effect of post operative prostate growth due to operative trauma in LDR was evaluatedusing the concept. The post-implant dose was lower than the planned dose due to an increase of prostate volumepost-implant. A critical uniform dose of 130 Gy was determined, below which TCP begun to decline.

Monotonicity of fitness landscapes and mutation rate control.

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Belavkin, Roman V; Channon, Alastair; Aston, Elizabeth; Aston, John; Krašovec, Rok; Knight, Christopher G

2016-12-01

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms.

Postoperative Stereotactic Radiosurgery Without Whole-Brain Radiation Therapy for Brain Metastases: Potential Role of Preoperative Tumor Size

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Hartford, Alan C.; Paravati, Anthony J.; Spire, William J.; Li, Zhongze; Jarvis, Lesley A.; Fadul, Camilo E.; Rhodes, C. Harker; Erkmen, Kadir; Friedman, Jonathan; Gladstone, David J.; Hug, Eugen B.; Roberts, David W.; Simmons, Nathan E.

2013-01-01

Purpose: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). Methods and Materials: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or “distant” recurrence (DR) in the brain, for time to WBRT, and for OS. Results: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. Conclusions: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to

IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

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Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

2016-10-27

Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

Differential diagnostic value of combined detection of serum CA153, CEA and TPA levels in patients with breast tumor

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Ding Wei

2007-01-01

Objective: To assess the differential diagnostic value of combined detection of serum CA153, CEA and TPA levels in patients with breast tumor. Methods: Serum levels of CA153, CEA and TPA were measured with RIA in 269 patients with breast tumor and 150 controls. Results: The serum levels of CA153, CEA and TPA in patients with breast cancer were significantly higher than those in the patients with benign breast tumor and controls. The positive rate of CA153 was 63.8% in the patients with breast cancer and that of CEA and TPA was 22.4% and 62.1% respectively, with combined detection of CA153 and CEA, the positive rate was 69.8%, with CA153 and TPA combined, the positive rate was 87.1%, with the three marker combined, the positive rate was 90.5%. The specificity was 77.9% with CA153, 77.9% with CA153 and CEA, 71.9% with CA153 and TPA, and 73.4% with all the three markers combined. Conclusion: The positive rate was increased remarkably with combined detection of CA153, CEA and TPA, however the specificity was not much changed, so the combined detection was valuable for differential diagnosis. (authors)

Post-operative high dose rate brachytherapy in patients with low to intermediate risk endometrial cancer

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Pearcey, R.G.; Petereit, D.G.

2000-01-01

This paper investigates the outcome using different dose/fractionation schedules in high dose rate (HDR) post-operative vaginal vault radiotherapy in patients with low to intermediate risk endometrial cancer. The world literature was reviewed and thirteen series were analyzed representing 1800 cases. A total of 12 vaginal vault recurrences were identified representing an overall vaginal control rate of 99.3%. A wide range of dose fractionation schedules and techniques have been reported. In order to analyze a dose response relationship for tumor control and complications, the biologically effective doses to the tumor and late responding tissues were calculated using the linear quadratic model. A threshold was identified for complications, but not vaginal control. While dose fractionation schedules that delivered a biologically effective dose to the late responding tissues in excess of 100 Gy 3 (LQED = 60 Gy) predicted for late complications, dose fractionation schedules that delivered a modest dose to the vaginal surface (50 Gy 10 or LQED = 30 Gy) appeared tumoricidal with vaginal control rates of at least 98%. By using convenient, modest dose fractionation schedules, HDR vaginal vault - brachytherapy yields very high local control and extremely low morbidity rates. (author)

Qualitative and Computational Analysis of a Mathematical Model for Tumor-Immune Interactions

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F. A. Rihan

2012-01-01

Full Text Available We provide a family of ordinary and delay differential equations to model the dynamics of tumor-growth and immunotherapy interactions. We explore the effects of adoptive cellular immunotherapy on the model and describe under what circumstances the tumor can be eliminated. The possibility of clearing the tumor, with a strategy, is based on two parameters in the model: the rate of influx of the effector cells and the rate of influx of IL-2. The critical tumor-growth rate, below which endemic tumor does not exist, has been found. One can use the model to make predictions about tumor dormancy.

Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo

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Zwicker, F.; Roeder, F.; Debus, J.; Huber, P.E. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology; Kirsner, A.; Weber, K.J. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Peschke, P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology

2013-08-15

Background: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. Materials and methods: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. Results: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. Conclusion: DCA induced tumor-specific radiosensitization in vitro but not in vivo

Fractionated stereotactic radiotherapy of glomus jugulare tumors. Local control, toxicity, symptomatology, and quality of life

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Henzel, M.; Gross, M.W.; Failing, T.; Strassmann, G.; Engenhart-Cabillic, R.; Hamm, K.; Surber, G.; Kleinert, G.; Sitter, H.

2007-01-01

Background and Purpose: For glomus jugulare tumors, the goal of treatment is microsurgical excision. To minimize postoperative neurologic deficits, stereotactic radiosurgery (SRS) was performed as an alternative treatment option. Stereotactic fractionated radiotherapy (SRT) could be a further alternative. This study aims at the assessment of local control, side effects, and quality of life (QoL). Patients and Methods: Between 1999-2005, 17 patients were treated with SRT. 11/17 underwent previous operations. 6/17 received primary SRT. Treatment was delivered by a linear accelerator with 6-MV photons. Median cumulative dose was 57.0 Gy. Local control, radiologic regression, toxicity, and symptomatology were evaluated half-yearly by clinical examination and MRI scans. QoL was assessed by Short Form-36 (SF-36). Results: Median follow-up was 40 months. Freedom from progression and overall survival for 5 years were 100% and 93.8%. Radiologic regression was seen in 5/16 cases, 11/16 patients were stable. Median tumor shrinkage was 17.9% (p = 0.14). Severe acute toxicity (grade 3-4) or any late toxicity was never seen. Main symptoms improved in 9/16 patients, 7/16 were stable. QoL was not affected in patients receiving primary SRT. Conclusion: SRT offers an additional treatment option of high efficacy with less side effects, especially in cases of large tumors, morbidity, or recurrences after incomplete resections. (orig.)

Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment

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Kirkpatrick, Nathaniel D.; Chung, Euiheon; Cook, Daniel C.; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L.; Padera, Timothy P.; Fukumura, Dai; Jain, Rakesh K.

2012-01-01

The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion...

Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control.

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Kratochwil, Clemens; Bruchertseifer, Frank; Rathke, Hendrik; Hohenfellner, Markus; Giesel, Frederik L; Haberkorn, Uwe; Morgenstern, Alfred

2018-05-01

The aim of this evaluation was to identify the first indicators of efficacy for 225 Ac-labeled prostate-specific membrane antigen (PSMA)-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with three 100 kBq/kg cycles of 225 Ac-PSMA-617 at 2-mo intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 wk. PSMA PET/CT or PSMA SPECT/CT were used for baseline staging and imaging follow-up at month 6. Follow-up included the duration of PSA response and radiologic progression-free survival at month 6. Patient histories were reviewed for the duration of previous treatment lines, and a swimmer plot was used to intraindividually compare the duration of tumor control by PSMA therapy versus prior treatment modalities. Results: Thirty-one of 40 patients were treated per protocol. Five patients discontinued treatment because of nonresponse, and 4 because of xerostomia. Of the 38 patients surviving at least 8 wk, 24 (63%) had a PSA decline of more than 50%, and 33 (87%) had a PSA response of any degree. The median duration of tumor control under 225 Ac-PSMA-617 last-line therapy was 9.0 mo; 5 patients had an enduring response of more than 2 y. Because all patients had advanced disease, this result compares favorably with the tumor control rates associated with earlier-phase disease; the most common preceding first-, second-, third-, and fourth-line therapies were abiraterone (median duration 10.0 mo), docetaxel (6.5 mo), enzalutamide (6.5 mo), and cabazitaxel (6.0 mo), respectively. Conclusion: A positive response for surrogate parameters demonstrates remarkable antitumor activity for 225 Ac-PSMA-617. Swimmer-plot analysis indicates a promising duration of tumor control, especially considering the unfavorable prognostic profile of the selected advanced-stage patients. Xerostomia was the main reason patients discontinued therapy or refused

A comparison study on of tumor cell-killing effects between low-dose-rate β-irradiation of 32P and γ-irradiation of 60Co

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Feng Huiru; Tian Jiahe; Ding Weimin; Zhang Jinming; Chen Yingmao

2004-01-01

The paper is to elucidate radiobiological characteristics and radiobiological mechanism in killing tumor cells with low dose rate β-rays and high dose rate γ-rays. HeLa cells were exposed to low-rate β-irradiation of 32 P or high-dose-rate γ-irradiation of 60 Co. Cell response-patterns were compared between two the types of radiations in terms of their inhibition of cell proliferation and cell cycle blockage, evaluated by trypanblue excluded method and flow cytometry, respectively. Results show that there is a different way in growth inhibition effect on HeLa cells between low-dose-rate irradiation of 32 P and high-dose-rate irradiation of 60 Co γ. In exposure to 32 P, the inhibition of cell proliferation in HeLa cell was a prolong course, whereas and the effect was in a more serious and quick way in 60 Co irradiation. Cell cycle arrest in G 2 phase induced by 32 P was lower and more prolong than that induced by 60 Co. The inhibition effect on tumor cells between the two types of radiations is different. Impaired DNA repair system by continuous low-dose-rate radiation might contribute to the final radiation effect of 32 P

Mobile phones, cordless phones and rates of brain tumors in different age groups in the Swedish National Inpatient Register and the Swedish Cancer Register during 1998-2015.

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Lennart Hardell

Full Text Available We used the Swedish Inpatient Register (IPR to analyze rates of brain tumors of unknown type (D43 during 1998-2015. Average Annual Percentage Change (AAPC per 100,000 increased with +2.06%, 95% confidence interval (CI +1.27, +2.86% in both genders combined. A joinpoint was found in 2007 with Annual Percentage Change (APC 1998-2007 of +0.16%, 95% CI -0.94, +1.28%, and 2007-2015 of +4.24%, 95% CI +2.87, +5.63%. Highest AAPC was found in the age group 20-39 years. In the Swedish Cancer Register the age-standardized incidence rate per 100,000 increased for brain tumors, ICD-code 193.0, during 1998-2015 with AAPC in men +0.49%, 95% CI +0.05, +0.94%, and in women +0.33%, 95% CI -0.29, +0.45%. The cases with brain tumor of unknown type lack morphological examination. Brain tumor diagnosis was based on cytology/histopathology in 83% for men and in 87% for women in 1980. This frequency increased to 90% in men and 88% in women in 2015. During the same time period CT and MRI imaging techniques were introduced and morphology is not always necessary for diagnosis. If all brain tumors based on clinical diagnosis with CT or MRI had been reported to the Cancer Register the frequency of diagnoses based on cytology/histology would have decreased in the register. The results indicate underreporting of brain tumor cases to the Cancer Register. The real incidence would be higher. Thus, incidence trends based on the Cancer Register should be used with caution. Use of wireless phones should be considered in relation to the change of incidence rates.