Benign meningiomas: primary treatment selection affects survival

International Nuclear Information System (INIS)

Condra, Kellie S.; Buatti, John M.; Mendenhall, William M.; Friedman, William A.; Marcus, Robert B.; Rhoton, Albert L.

1997-01-01

Purpose: To examine the effect of primary treatment selection on outcomes for benign intracranial meningiomas at the University of Florida. Methods and Materials: For 262 patients, the impact of age, Karnofsky performance status, pathologic features, tumor size, tumor location, and treatment modality on local control and cause-specific survival was analyzed (minimum potential follow-up, 2 years; median follow-up, 8.2 years). Extent of surgery was classified by Simpson grade. Treatment groups: surgery alone (n = 229), surgery and postoperative radiotherapy (RT) (n = 21), RT alone (n = 7), radiosurgery alone (n = 5). Survival analysis: Kaplan-Meier method with univariate and multivariate analysis. Results: At 15 years, local control was 76% after total excision (TE) and 87% after subtotal excision plus RT (SE+RT), both significantly better (p = 0.0001) than after SE alone (30%). Cause-specific survival at 15 years was reduced after treatment with SE alone (51%), compared with TE (88%) or SE+RT (86%) (p = 0.0003). Recurrence after primary treatment portended decreased survival, independent of initial treatment group or salvage treatment selection (p = 0.001). Atypical pathologic features predicted reduced 15-year local control (54 vs. 71%) and cause-specific survival rates (57 vs. 86%). Multivariate analysis for cause-specific survival revealed treatment group (SE vs. others; p = 0.0001), pathologic features (atypical vs. typical; p = 0.0056), and Karnofsky performance status (≥80 vs. <80; p = 0.0153) as significant variables. Conclusion: Benign meningiomas are well managed by TE or SE+RT. SE alone is inadequate therapy and adversely affects cause-specific survival. Atypical pathologic features predict a poorer outcome, suggesting possible benefit from more aggressive treatment. Because local recurrence portends lower survival rates, primary treatment choice is important

The future and progress of proton beam radiotherapy

International Nuclear Information System (INIS)

Tsujii, Hirohiko

1994-01-01

The advantage of proton therapy is reduction of treatment volumes relative to those feasible with conventional photon therapy. The consequence is that the radiation dose to the target can be raised, with a resultant increase in tumor control probability. Proton beams, however, yield no biological gains because their biological properties are similar to conventional low LET radiations. As more sophisticated technologies are needed, there have been many advances which are applicable to photon therapy; 3-D treatment planning, DVH analysis, and systems for positioning, etc. As of January 1994, a total of about 13,000 cases were reported as having had treatments with proton beams in 16 centers world wide. The tumor sites for those include uveal melanoma (30-40%), intra-cranial small targets (40%), and others. Uveal melanomas had been most extensively treated with 70 Gy/5 fx or 60 Gy/4 fx which resulted in local control and survival rates of >96% and 80%, respectively. For chordoma and chondrosarcoma of the skull base and cervical spine, the 5 year local control rates were 65% and 91%, respectively. Promising results are also being obtained for head and neck and pelvic tumors. Deeper-seated tumors have been treated only at Tsukuba University with successful results in some anatomic sites. Among these, inoperable primary hepatocellular carcinomas were effectively treated with a total dose of 75-85 Gy (3.0-4.5 Gy/fx). The 3 year survival rates for all patients, Child A+B patient, and Child A patients were 38%, 47%, and 60%, respectively, which compare favorably to other modalities. These successful results of world wide proton therapy have led us to the conclusion that a hospital-based proton facility will provide opportunities for additional patients to be treated with protons. Thus, new plans are proposed from more than 10 institutions to build a new treatment center or upgrade the energy of currently available proton beams. (author)

The clinical case for proton beam therapy

Directory of Open Access Journals (Sweden)

Foote Robert L

2012-10-01

Full Text Available Abstract Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. Summary sentence Proton beam therapy is a technically advanced and promising form of radiation therapy.

Proton and neutron radiation in cancer treatment: clinical and economic outcomes

International Nuclear Information System (INIS)

Fleurette, F.; Charvet-Protat, S.

1996-01-01

The French National Agency for Medical Evaluation (ANDEM) was requested to assess the effectiveness of proton and neutron beam therapy in cancer treatment compared to conventional radiotherapy. This task was accomplished by a critical appraisal of the clinical and economic literature. According to the published economic literature and the capital and staffing cost analysis, it appears that the costs of proton therapy are likely to be two or three times greater than those conformal therapy. According to the published clinical literature, proton beam therapy should be proposed as a routine treatment only for uveal melanoma and skull base cancers. Neutron beam therapy should be proposed as a routine treatment for inoperable salivary gland tumors; its use may be also discussed in cases of stage C-D1 prostate cancers and soft tissue sarcomas. Based on the current scientific evidence and given the incidence rate of these tumors, the time and material requirements, the current French proton/neutron beam facilities are able to meet the current demand. FOr other cancers the medical and economic potential of proton therapy is still an open question. (author)

Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

Science.gov (United States)

Johansson, Silvia; Åström, Lennart; Sandin, Fredrik; Isacsson, Ulf; Montelius, Anders; Turesson, Ingela

2012-01-01

Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT) of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT). The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU) and gastrointestinal (GI) toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity. PMID:22848840

Hypofractionated Proton Boost Combined with External Beam Radiotherapy for Treatment of Localized Prostate Cancer

Directory of Open Access Journals (Sweden)

Silvia Johansson

2012-01-01

Full Text Available Proton boost of 20 Gy in daily 5 Gy fractions followed by external beam radiotherapy (EBRT of 50 Gy in daily 2 Gy fractions were given to 278 patients with prostate cancer with T1b to T4N0M0 disease. Fifty-three percent of the patients received neoadjuvant androgen deprivation therapy (N-ADT. The medium followup was 57 months. The 5-year PSA progression-free survival was 100%, 95%, and 74% for low-, intermediate-, and high-risk patients, respectively. The toxicity evaluation was supported by a patient-reported questionnaire before every consultant visit. Cumulative probability and actuarial prevalence of genitourinary (GU and gastrointestinal (GI toxicities are presented according to the RTOG classification. N-ADT did not influence curability. Mild pretreatment GU-symptoms were found to be a strong predictive factor for GU-toxicity attributable to treatment. The actuarial prevalence declined over 3 to 5 years for both GU and GI toxicities, indicating slow resolution of epithelial damage to the genitourinary and gastrointestinal tract. Bladder toxicities rather than gastrointestinal toxicities seem to be dose limiting. More than 5-year followup is necessary to reveal any sign of true progressive late side effects of the given treatment. Hypofractionated proton-boost combined with EBRT is associated with excellent curability of localized PC and acceptable frequencies of treatment toxicity.

Conservation treatment of the eye: Conformal proton reirradiation for recurrent uveal melanoma

International Nuclear Information System (INIS)

Marucci, Laura; Lane, Anne M.; Li Wenjun; Egan, Kathleen M.; Gragoudas, Evangelos S.; Adams, Judy; Collier, John M.; Munzenrider, John E.

2006-01-01

Purpose: To evaluate the outcomes of a second course of proton beam radiation therapy (PBRT) in patients with recurrent uveal melanoma. Methods and Materials: Thirty-one patients received a second course of PBRT. The mean interval between the first and the second PBRT course was 50.2 months (range, 8-165 months). Most patients (87%) received 70 cobalt Gray equivalent (CGE) for both courses. Visual acuity was 20/200 or better in 30 patients initially and in 22 patients at the second treatment. The mean follow-up time after the second treatment was 50 months (range, 6-164 months). Results: At the time of the last follow-up, 20 patients were classified as having no evidence of disease, defined as tumor regression or an absence of tumor progression. Nine eyes (29%) were enucleated because of local recurrence (n = 5) or intractable pain (n = 4). The 5-year eye retention rate was 55% (95% confidence interval: 25.2-77.4). Six of the 22 patients who retained the eye (27%) had useful vision (20/200 or better). Conclusions A second course of PBRT for recurrent uveal melanoma to total doses between 118 and 140 CGE was associated with a relatively good probability of local control and a low enucleation rate. Although most patients lost vision, the majority were able to retain the reirradiated eye. Further evaluation is needed to assess metastasis-free survival of additional proton irradiation vs. enucleation after local recurrence

Hypofractionated high-energy proton-beam irradiation is an alternative treatment for WHO grade I meningiomas.

Science.gov (United States)

Vlachogiannis, Pavlos; Gudjonsson, Olafur; Montelius, Anders; Grusell, Erik; Isacsson, Ulf; Nilsson, Kristina; Blomquist, Erik

2017-12-01

Radiation treatment is commonly employed in the treatment of meningiomas. The aim of this study was to evaluate the effectiveness and safety of hypofractionated high-energy proton therapy as adjuvant or primary treatment for WHO grade I meningiomas. A total of 170 patients who received irradiation with protons for grade I meningiomas between 1994 and 2007 were included in the study. The majority of the tumours were located at the skull base (n = 155). Eighty-four patients were treated post subtotal resection, 42 at tumour relapse and 44 with upfront radiotherapy after diagnosis based on the typical radiological image. Irradiation was given in a hypofractionated fashion (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy). All patients were planned for follow-up with clinical controls and magnetic resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after treatment. The median follow-up time was 84 months. Age, gender, tumour location, Simpson resection grade and target volume were assessed as possible prognostic factors for post-irradiation tumour progression and radiation related complications. The actuarial 5- and 10-year progression-free survival rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while disease-specific mortality was 1.7% (3/170 patients). Older patients and patients with tumours located in the middle cranial fossa had a lower risk for tumour progression. Radiation-related complications were seen in 16 patients (9.4%), with pituitary insufficiency being the most common. Tumour location in the anterior cranial fossa was the only factor that significantly increased the risk of complications. Hypofractionated proton-beam radiation therapy may be used particularly in the treatment of larger World Health Organisation grade I meningiomas not amenable to total surgical resection. Treatment is associated with high rates of long-term tumour growth control and acceptable risk for

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Higgins, Kristin A., E-mail: kristin.higgins@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); O' Connell, Kelli [Rollins School of Public Health, Emory University, Atlanta, Georgia (United States); Liu, Yuan [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rollins School of Public Health, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia (United States); Gillespie, Theresa W. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Surgery, Emory University, Atlanta, Georgia (United States); McDonald, Mark W. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Pillai, Rathi N. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia (United States); Patel, Kirtesh R.; Patel, Pretesh R. [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Robinson, Clifford G. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Simone, Charles B. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Owonikoko, Taofeek K. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia (United States); Belani, Chandra P. [Penn State Hershey Cancer Institute, Pennsylvania University, Hershey, Pennsylvania (United States); and others

2017-01-01

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822 patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.

SU-E-T-210: Comparison of Proton with Electron Boost in Breast Cancer Treatment

Energy Technology Data Exchange (ETDEWEB)

Zheng, Y; Chang, A [Procure Proton Therapy Center, Oklahoma City, OK (United States); Liu, Y [INTEGRIS Cancer Institute of Oklahoma, Oklahoma City, OK (United States)

2015-06-15

Purpose: Electron beams are commonly used for boost radiation following whole breast irradiation (WBI) to improve the in-breast local control. Proton beams have a finite range and a sharper distal dose falloff compared to electron beams, thus potentially sparing more heart and lung in breast treatment. The purpose of the study is to compare protons with electrons for boost breast treatment in terms of target coverage and normal tissue sparing. Methods: Six breast cancer patients were included in this study. All women received WBI to 45–50 Gy, followed by a 10–16.2 Gy boost with standard fractionation. If proton beams were used for the boost treatment, an electron plan was retrospectively generated for comparison using the same CT set and structures, and vice versa if electron beams were used for treatment. Proton plans were generated using the treatment planning system (TPS) with two to three uniform scanning proton beams. Electron plans were generated using the Pinnacle TPS with one single en face beam. Dose-volume histograms (DVH) were calculated and compared between proton and electron boost plans. Results: Proton plans show a similar boost target coverage, similar skin dose, and much better heart and lung sparing. For an example patient, V95% for PTV was 99.98% and skin (5 mm shell) received a max dose close to the prescription dose for both protons and electrons; however, V2 and V5 for the ipsilateral lung and heart were 37.5%, 17.9% and 19.9%, 4.9% respectively for electrons, but were essentially 0 for protons. Conclusions: This dosimetric comparison demonstrates that while both proton therapy and electron therapy provided similar coverage and skin dose, proton therapy could largely reduce the dose to lung and heart, thus leading to potential less side effects.

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival.

Science.gov (United States)

Eaton, Bree R; Esiashvili, Natia; Kim, Sungjin; Weyman, Elizabeth A; Thornton, Lauren T; Mazewski, Claire; MacDonald, Tobey; Ebb, David; MacDonald, Shannon M; Tarbell, Nancy J; Yock, Torunn I

2016-01-01

The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Biophysical characterization of a relativistic proton beam for image-guided radiosurgery.

Science.gov (United States)

Yu, Zhan; Vanstalle, Marie; La Tessa, Chiara; Jiang, Guo-Liang; Durante, Marco

2012-07-01

We measured the physical and radiobiological characteristics of 1 GeV protons for possible applications in stereotactic radiosurgery (image-guided plateau-proton radiosurgery). A proton beam was accelerated at 1 GeV at the Brookhaven National Laboratory (Upton, NY) and a target in polymethyl methacrylate (PMMA) was used. Clonogenic survival was measured after exposures to 1-10 Gy in three mammalian cell lines. Measurements and simulations demonstrate that the lateral scattering of the beam is very small. The lateral dose profile was measured with or without the 20-cm plastic target, showing no significant differences up to 2 cm from the axis A large number of secondary swift protons are produced in the target and this leads to an increase of approximately 40% in the measured dose on the beam axis at 20 cm depth. The relative biological effectiveness at 10% survival level ranged between 1.0 and 1.2 on the beam axis, and was slightly higher off-axis. The very low lateral scattering of relativistic protons and the possibility of using online proton radiography during the treatment make them attractive for image-guided plateau (non-Bragg peak) stereotactic radiosurgery.

Biophysical characterization of a relativistic proton beam for image-guided radiosurgery

International Nuclear Information System (INIS)

Yu, Z.; Vanstalle, M.; La Tessa, C.; Durante, M.; Jiang Guoliang

2012-01-01

We measured the physical and radiobiological characteristics of 1 GeV protons for possible applications in stereotactic radiosurgery (image-guided plateau-proton radiosurgery). A proton beam was accelerated at 1 GeV at the Brookhaven National Laboratory (Upton, NY) and a target in polymethyl methacrylate (PMMA) was used. Clonogenic survival was measured after exposures to 1-10 Gy in three mammalian cell lines. Measurements and simulations demonstrate that the lateral scattering of the beam is very small. The lateral dose profile was measured with or without the 20-cm plastic target, showing no significant differences up to 2 cm from the axis A large number of secondary swift protons are produced in the target and this leads to an increase of approximately 40% in the measured dose on the beam axis at 20 cm depth. The relative biological effectiveness at 10% survival level ranged between 1.0 and 1.2 on the beam axis, and was slightly higher off-axis. The very low lateral scattering of relativistic protons and the possibility of using online proton radiography during the treatment make them attractive for image-guided plateau (non-Bragg peak) stereotactic radiosurgery. (author)

Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes

Energy Technology Data Exchange (ETDEWEB)

Bush, David A., E-mail: dbush@llu.edu [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Do, Sharon [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Lum, Sharon; Garberoglio, Carlos [Department of Surgical Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Mirshahidi, Hamid [Department of Medical Oncology, Loma Linda University Medical Center, Loma Linda, California (United States); Patyal, Baldev; Grove, Roger; Slater, Jerry D. [Department of Radiation Oncology, Loma Linda University Medical Center, Loma Linda, California (United States)

2014-11-01

Purpose: We updated our previous report of a phase 2 trial using proton beam radiation therapy to deliver partial breast irradiation (PBI) in patients with early stage breast cancer. Methods and Materials: Eligible subjects had invasive nonlobular carcinoma with a maximal dimension of 3 cm. Patients underwent partial mastectomy with negative margins; axillary lymph nodes were negative on sampling. Subjects received postoperative proton beam radiation therapy to the surgical bed. The dose delivered was 40 Gy in 10 fractions, once daily over 2 weeks. Multiple fields were treated daily, and skin-sparing techniques were used. Following treatment, patients were evaluated with clinical assessments and annual mammograms to monitor toxicity, tumor recurrence, and cosmesis. Results: One hundred subjects were enrolled and treated. All patients completed the assigned treatment and were available for post-treatment analysis. The median follow-up was 60 months. Patients had a mean age of 63 years; 90% had ductal histology; the average tumor size was 1.3 cm. Actuarial data at 5 years included ipsilateral breast tumor recurrence-free survival of 97% (95% confidence interval: 100%-93%); disease-free survival of 94%; and overall survival of 95%. There were no cases of grade 3 or higher acute skin reactions, and late skin reactions included 7 cases of grade 1 telangiectasia. Patient- and physician-reported cosmesis was good to excellent in 90% of responses, was not changed from baseline measurements, and was well maintained throughout the entire 5-year follow-up period. Conclusions: Proton beam radiation therapy for PBI produced excellent ipsilateral breast recurrence-free survival with minimal toxicity. The treatment proved to be adaptable to all breast sizes and lumpectomy cavity configurations. Cosmetic results appear to be excellent and unchanged from baseline out to 5 years following treatment. Cosmetic results may be improved over those reported with photon

Dosimetric and clinical experience in eye proton treatment at INFN-LNS

International Nuclear Information System (INIS)

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Lojacono, P.; Mongelli, V.; Patti, I. V.; Pittera, S.; Russo, G.; Valastro, L. M.; Lo Nigro, S.; Ott, J.; Reibaldi, A.; Privitera, G.; Raffaele, L.; Salamone, V.; Spatola, C.; Sabini, M. G.

2009-01-01

After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged us in our activity in the battle against cancer

Dosimetric and clinical experience in eye proton treatment at INFN-LNS

Science.gov (United States)

Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Lojacono, P.; Mongelli, V.; Lo Nigro, S.; Ott, J.; Patti, I. V.; Pittera, S.; Privitera, G.; Raffaele, L.; Reibaldi, A.; Russo, G.; Salamone, V.; Sabini, M. G.; Spatola, C.; Valastro, L. M.

2009-05-01

After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged us in our activity in the battle against cancer

The precision of proton range calculations in proton radiotherapy treatment planning: experimental verification of the relation between CT-HU and proton stopping power

International Nuclear Information System (INIS)

Schaffner, B.; Pedroni, E.

1998-01-01

The precision in proton radiotherapy treatment planning depends on the accuracy of the information used to calculate the stopping power properties of the tissues in the patient's body. This information is obtained from computed tomography (CT) images using a calibration curve to convert CT Hounsfield units into relative proton stopping power values. The validity of a stoichiometric method to create the calibration curve has been verified by measuring pairs of Hounsfield units and stopping power values for animal tissue samples. It was found that the agreement between measurement and calibration curve is better than 1% if beam hardening effects in the acquisition of the CT images can be neglected. The influence of beam hardening effects on the quantitative reading of the CT measurements is discussed and an estimation for the overall range precision of proton beams is given. It is expected that the range of protons in the human body can be controlled to better than ±1.1% of the water equivalent range in soft tissue and ±1.8% in bone, which translates into a range precision of about 1-3 mm in typical treatment situations. (author)

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

Science.gov (United States)

Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Supuran, Claudiu T; Fais, Stefano

2017-12-23

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities compared with unicellular microorganisms. These systems are also involved in the unresponsiveness or resistance to chemotherapy, leading to the protection of cancer cells from the vast majority of drugs, that when protonated in the acidic tumor microenvironment, do not enter into cancer cells. Indeed, as usually occurs in the progression versus malignancy, resistant tumor clones emerge and proliferate, following a transient initial response to a therapy, thus giving rise to more malignant behavior and rapid tumor progression. Recent studies are supporting the use of a cocktail of proton exchanger inhibitors as a new strategy against cancer.

A Treatment Planning Comparison of Combined Photon-Proton Beams Versus Proton Beams-Only for the Treatment of Skull Base Tumors

International Nuclear Information System (INIS)

Feuvret, Loic; Noel, Georges; Weber, Damien C.; Pommier, Pascal; Ferrand, Regis; De Marzi, Ludovic; Dhermain, Frederic; Alapetite, Claire; Mammar, Hamid; Boisserie, Gilbert; Habrand, Jean-Louis; Mazeron, Jean-Jacques

2007-01-01

Purpose: To compare treatment planning between combined photon-proton planning (CP) and proton planning (PP) for skull base tumors, so as to assess the potential limitations of CP for these tumors. Methods and Materials: Plans for 10 patients were computed for both CP and PP. Prescribed dose was 67 cobalt Gray equivalent (CGE) for PP; 45 Gy (photons) and 22 CGE (protons) for CP. Dose-volume histograms (DVHs) were calculated for gross target volume (GTV), clinical target volume (CTV), normal tissues (NT), and organs at risk (OARs) for each plan. Results were analyzed using DVH parameters, inhomogeneity coefficient (IC), and conformity index (CI). Results: Mean doses delivered to the GTVs and CTVs with CP (65.0 and 61.7 CGE) and PP (65.3 and 62.2 Gy CGE) were not significantly different (p > 0.1 and p = 0.72). However, the dose inhomogeneity was drastically increased with CP, with a mean significant incremental IC value of 10.5% and CP of 6.8%, for both the GTV (p = 0.01) and CTV (p = 0.04), respectively. The CI 80% values for the GTV and CTV were significantly higher with PP compared with CP. Compared with CP, the use of protons only led to a significant reduction of NT and OAR irradiation, in the intermediate-to-low dose (≤80% isodose line) range. Conclusions: These results suggest that the use of CP results in levels of target dose conformation similar to those with PP. Use of PP significantly reduced the tumor dose inhomogeneity and the delivered intermediate-to-low dose to NT and OARs, leading us to conclude that this treatment is mainly appropriate for tumors in children

Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation

International Nuclear Information System (INIS)

Miralbell, Raymond; Lomax, Anthony; Russo, Mariateresa

1997-01-01

Purpose: Conventional postoperative photon-beam radiotherapy to the spine in children with medulloblastoma/PNET is associated with severe late effects. This morbidity (growth and developmental) is related to the exit dose of the beams and is particularly severe in young children. With the purpose of reducing this toxicity, a dosimetric study was undertaken in which proton therapy was compared to standard megavoltage photon treatment. Methods and materials: The results of a comparative dosimetric study are presented in such a way that the dose distribution achievable with a posterior modulated 100 MeV proton beam (spot scanning method) is compared with that of a standard set of posterior 6 MV x-ray fields. The potential improvements with protons are evaluated, using dose-volume histograms to examine the coverage of the target as well as the dose to the vertebral bodies (growth plates), lungs, heart, and liver. Results: The target (i.e., the spinal dural sac) received the full prescribed dose in both treatment plans. However, the proportions of the vertebral body volume receiving ≥50% of the prescribed dose were 100 and 20% for 6 MV x-rays and protons, respectively. For 6 MV x-rays >60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well. Conclusion: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET. The potential bone marrow and growth arrest sparing effects make this approach specially attractive for intensive chemotherapy protocols and for very young children. Sparing the thyroid gland, the posterior heart wall, and the gonads may be additional advantages in assuring a long-term posttreatment morbidity-free survival

MO-D-BRB-02: Pediatric Treatment Planning II: Applications of Proton Beams for Pediatric Treatment

Energy Technology Data Exchange (ETDEWEB)

Hua, C. [St. Jude Childrens Research Hospital (United States)

2015-06-15

, neuroblastoma, requiring focal abdominal irradiation to avoid kidney, liver, and vertebral body damage, retinoblastoma, requiring treatment to an eye while minimizing dose to surrounding tissues, and a variety of other tumors which occur anywhere in the body. Case studies will be presented showing the treatment technique and resulting dosimetry, highlighting the objectives for tumor coverage and organ-at-risk sparing. Practical issues that have to be faced when treating children will also be discussed such as daily sedation and immobilization. Late effects based on the current understanding of dose-volume response in normal tissues will be discussed. In the second presentation, specific focus will be on pediatric proton therapy. We will review literature publications on dosimetric comparison of proton versus photon plans, common pediatric tumors treated with protons, and available clinical outcomes. We will describe simulation technique, treatment planning, image guidance for setup verification, and proton beam delivery unique to pediatric and adolescent patients. Finally, we will discuss desired improvements, outlook, and opportunities for medical physicists in pediatric proton therapy. Learning Objectives: Improve understanding about childhood cancer and treatment with radiation Understand treatment planning and delivery issues and associated late effects specific to children Become aware of specific treatment methods for the most challenging pediatric cancers Know the current status, techniques, and desired improvements for pediatric proton therapy.

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival

International Nuclear Information System (INIS)

Eaton, Bree R.; Esiashvili, Natia; Kim, Sungjin; Weyman, Elizabeth A.; Thornton, Lauren T.; Mazewski, Claire; MacDonald, Tobey; Ebb, David; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

2016-01-01

Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.

Association Between Proton Pump Inhibitors and Metronomic Capecitabine as Salvage Treatment for Patients With Advanced Gastrointestinal Tumors: A Randomized Phase II Trial.

Science.gov (United States)

Marchetti, Paolo; Milano, Annalisa; D'Antonio, Chiara; Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Fais, Stefano

2016-12-01

The acidification of extracellular compartment represents a conceivable mechanism of drug resistance in malignant cells. In addition, it has been reported to drive proliferation and promote invasion and metastasis. Experimental evidence has shown that proton pump inhibitors can counteract tumor acidification and restore sensitivity to anticancer drugs. Moreover, early clinical data have supported the role of proton pump inhibitors in anticancer treatments. Metronomic capecitabine has demonstrated beneficial effects as salvage chemotherapy for heavily pretreated or frail patients with gastrointestinal cancer. The present study (EudraCT Number: 2013-001096-20) was aimed at investigating the activity and safety of high-dose rabeprazole in combination with metronomic capecitabine in patients with advanced gastrointestinal cancer refractory to standard treatment. A total of 66 patients will be randomized 1:1 to receive capecitabine 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg twice a day, 3 days a week until disease progression, undue toxicity, or withdrawal of informed consent. The primary endpoint is progression-free survival. The secondary endpoints are clinical benefit, which reflects the proportion of patients with complete response, partial response, and stable disease, and overall survival. Progression-free and overall survival will be evaluated using a log-rank test to determine the effect of rabeprazole independently at the 2-sided α-level of 0.05. Other assessments will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety, and the pharmacokinetics of capecitabine. The results are expected in 2016. Copyright © 2016 Elsevier Inc. All rights reserved.

Preliminary results of proton therapy in choroidal melanoma at the centre de proton therapy d'Orsay (C.P.O.): 464 initial cases

International Nuclear Information System (INIS)

Desjardins, L.; Levy, C.; D'hermies, F.; Frau, E.; Schlienger, P.; Habrand, J.L.; Mammar, H.; Schwartz, L.; Mazal, A.; Delacroix, S.; Nauraye, C.; Ferrand, R.; Asselain, B.

1997-01-01

Retrospective analysis of the treatment of choroidal melanoma with proton-therapy at the Centre de protontherapie d'Orsay, France. Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by proton-therapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. Univariate analysis showed that the actuarial local recurrence rate was 5 %, the 3-year survival rate 88 %, and the overall metastatic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. Proton-therapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor. (author)

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

Energy Technology Data Exchange (ETDEWEB)

Nichols, R. Charles, E-mail: rnichols@floridaproton.org [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Williams, Christopher R.; Costa, Joseph A. [Division of Urology, University of Florida Shands Hospital, Jacksonville, FL (United States); Mendenhall, Nancy P. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

2012-03-01

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

Proton Radiotherapy for Prostate Cancer Is Not Associated With Post-Treatment Testosterone Suppression

International Nuclear Information System (INIS)

Nichols, R. Charles; Morris, Christopher G.; Hoppe, Bradford S.; Henderson, Randal H.; Marcus, Robert B.; Mendenhall, William M.; Li Zuofeng; Williams, Christopher R.; Costa, Joseph A.; Mendenhall, Nancy P.

2012-01-01

Purpose: Three independent studies of photon (x-ray) radiotherapy (RT) for prostate cancer have demonstrated evidence of testosterone suppression after treatment. The present study was undertaken to determine whether this would also be the case with conformal protons. Methods and Materials: Between August 2006 and October 2007, 171 patients with low- and intermediate-risk prostate cancer were enrolled and underwent treatment according to University of Florida Proton Therapy Institute institutional review board-approved PR01 and PR02 protocols. Of the 171 patients, 18 were excluded because they had received androgen deprivation therapy either before (n = 17) or after (n = 1) RT. The pretreatment serum testosterone level was available for 150 of the remaining 153 patients. These 150 patients were included in the present study. The post-treatment levels were compared with the pretreatment levels. Results: The median baseline pretreatment serum testosterone level was 357.9 ng/dL. The median post-treatment testosterone value was 375.5 ng/dL at treatment completion (p = .1935) and 369.9 ng/dL (p = .1336), 348.7 ng/dL (p = .7317), 353.4 ng/dL (p = .6996), and 340.9 ng/dL (p = .1669) at 6, 12, 18, and 24 months after proton therapy, respectively. Conclusions: Conformal proton therapy to the prostate, as delivered using University of Florida Proton Therapy Institute PR01 and PR02 protocols, did not appear to significantly affect the serum testosterone levels within 24 months after RT.

Proton Stereotactic Radiosurgery for the Treatment of Benign Meningiomas

Energy Technology Data Exchange (ETDEWEB)

Halasz, Lia M., E-mail: lhalasz@partners.org [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Bussiere, Marc R.; Dennis, Elizabeth R.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chapman, Paul H. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States); Loeffler, Jay S.; Shih, Helen A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Harvard Medical School, Boston, Massachusetts (United States)

2011-12-01

Purpose: Given the excellent prognosis for patients with benign meningiomas, treatment strategies to minimize late effects are important. One strategy is proton radiation therapy (RT), which allows less integral dose to normal tissue and greater homogeneity than photon RT. Here, we report the first series of proton stereotactic radiosurgery (SRS) used for the treatment of meningiomas. Methods and Materials: We identified 50 patients with 51 histologically proven or image- defined, presumed-benign meningiomas treated at our institution between 1996 and 2007. Tumors of <4 cm in diameter and located {>=}2 mm from the optic apparatus were eligible for treatment. Indications included primary treatment (n = 32), residual tumor following surgery (n = 8), and recurrent tumor following surgery (n = 10). The median dose delivered was 13 Gray radiobiologic equivalent (Gy[RBE]) (range, 10.0-15.5 Gy[RBE]) prescribed to the 90% isodose line. Results: Median follow-up was 32 months (range, 6-133 months). Magnetic resonance imaging at the most recent follow-up or time of progression revealed 33 meningiomas with stable sizes, 13 meningiomas with decreased size, and 5 meningiomas with increased size. The 3-year actuarial tumor control rate was 94% (95% confidence interval, 77%-98%). Symptoms were improved in 47% (16/ 34) of patients, unchanged in 44% (15/34) of patients, and worse in 9% (3/34) of patients. The rate of potential permanent adverse effects after SRS was 5.9% (3/51 patients). Conclusions: Proton SRS is an effective therapy for small benign meningiomas, with a potentially lower rate of long-term treatment-related morbidity. Longer follow-up is needed to assess durability of tumor control and late effects.

Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T. [Head and Neck Surgical Oncology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts (United States); Delaney, Thomas F. [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chan, Annie W., E-mail: awchan@partners.org [Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

Long-Term Outcomes After Proton Beam Therapy for Sinonasal Squamous Cell Carcinoma

International Nuclear Information System (INIS)

Russo, Andrea L.; Adams, Judith A.; Weyman, Elizabeth A.; Busse, Paul M.; Goldberg, Saveli I.; Varvares, Mark; Deschler, Daniel D.; Lin, Derrick T.; Delaney, Thomas F.; Chan, Annie W.

2016-01-01

Purpose: Squamous cell carcinoma (SCC) is the most common sinonasal cancer and is associated with one of the poor outcomes. Proton therapy allows excellent target coverage with maximal sparing of adjacent normal tissues. We evaluated the long-term outcomes in patients with sinonasal SCC treated with proton therapy. Methods and Materials: Between 1991 and 2008, 54 patients with Stage III and IV SCC of the nasal cavity and paranasal sinus received proton beam therapy at our institution to a median dose of 72.8 Gy(RBE). Sixty-nine percent underwent prior surgical resection, and 74% received elective nodal radiation. Locoregional control and survival probabilities were estimated with the Kaplan-Meier method. Multivariate analyses were performed using the Cox proportional-hazards model. Treatment toxicity was scored using the Common Terminology Criteria for Adverse Events version 4.0. Results: With a median follow-up time of 82 months in surviving patients, there were 10 local, 7 regional, and 11 distant failures. The 2-year and 5-year actuarial local control rate was 80%. The 2-year and 5-year rates of overall survival were 67% and 47%, respectively. Only smoking status was predictive for worse locoregional control, with current smokers having a 5-year rate of 23% compared with 83% for noncurrent smokers (P=.004). Karnofsky performance status ≤80 was the most significant factor predictive for worse overall survival in multivariate analysis (adjusted hazard ratio 4.5, 95% confidence interval 1.6-12.5, P=.004). There were nine grade 3 and six grade 4 toxicities, and no grade 5 toxicity. Wound adverse events constituted the most common grade 3-4 toxicity. Conclusions: Our long-term results show that proton radiation therapy is well tolerated and yields good locoregional control for SCC of the nasal cavity and paranasal sinus. Current smokers and patients with poor performance status had inferior outcomes. Prospective study is necessary to compare IMRT with proton

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

Energy Technology Data Exchange (ETDEWEB)

Zheng, Yuanshui, E-mail: yuanshui.zheng@okc.procure.com [ProCure Proton Therapy Center, 5901 W Memorial Road, Oklahoma City, Oklahoma 73142 and Department of Physics, Oklahoma State University, Stillwater, Oklahoma 74078-3072 (United States); Johnson, Randall; Larson, Gary [ProCure Proton Therapy Center, 5901 W Memorial Road, Oklahoma City, Oklahoma 73142 (United States)

2016-06-15

Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their

Minimizing treatment planning errors in proton therapy using failure mode and effects analysis

International Nuclear Information System (INIS)

Zheng, Yuanshui; Johnson, Randall; Larson, Gary

2016-01-01

Purpose: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. Methods: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. Results: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. Conclusions: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their

Energy related germination and survival rates of water-imbibed Arabidopsis seeds irradiated with protons

International Nuclear Information System (INIS)

Qin, H.L.; Xue, J.M.; Lai, J.N.; Wang, J.Y.; Zhang, W.M.; Miao, Q.; Yan, S.; Zhao, W.J.; He, F.; Gu, H.Y.; Wang, Y.G.

2006-01-01

In order to investigate the influence of ion energy on the germination and survival rates, water-imbibed Arabidopsis seeds were irradiated with protons in atmosphere. The ion fluence used in this experiment was in the range of 4 x 10 9 -1 x 10 14 ions/cm 2 . The ion energy is from 1.1 MeV to 6.5 MeV. According to the structure of the seed and TRIM simulation, the ions with the energy of 6.5 MeV can irradiate the shoot apical meristem directly whereas the ions with the energy of 1.1 MeV cannot. The results showed that both the germination and survival rates decrease while increasing the ion fluence, and the fluence-respond curve for each energy has different character. Besides the shoot apical meristem (SAM), which is generally considered as the main radiobiological target, the existence of a secondary target around SAM is proposed in this paper

Energy related germination and survival rates of water-imbibed Arabidopsis seeds irradiated with protons

Energy Technology Data Exchange (ETDEWEB)

Qin, H.L. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Xue, J.M. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Lai, J.N. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Wang, J.Y. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Zhang, W.M. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Miao, Q. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Yan, S. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); Zhao, W.J. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China); He, F. [School of Life Science, Peking University, Beijing 100871 (China); Gu, H.Y. [School of Life Science, Peking University, Beijing 100871 (China); Wang, Y.G. [Key Laboratory of Heavy Ion Physics, MOE, Peking University, Beijing 100871 (China)]. E-mail: ygwang@pku.edu.cn

2006-04-15

In order to investigate the influence of ion energy on the germination and survival rates, water-imbibed Arabidopsis seeds were irradiated with protons in atmosphere. The ion fluence used in this experiment was in the range of 4 x 10{sup 9}-1 x 10{sup 14} ions/cm{sup 2}. The ion energy is from 1.1 MeV to 6.5 MeV. According to the structure of the seed and TRIM simulation, the ions with the energy of 6.5 MeV can irradiate the shoot apical meristem directly whereas the ions with the energy of 1.1 MeV cannot. The results showed that both the germination and survival rates decrease while increasing the ion fluence, and the fluence-respond curve for each energy has different character. Besides the shoot apical meristem (SAM), which is generally considered as the main radiobiological target, the existence of a secondary target around SAM is proposed in this paper.

Current and future applications of protons in medical imaging and treatment

Energy Technology Data Exchange (ETDEWEB)

Schulte, Reinhard W. [Loma Linda University Medical Center, CA (United States). Dept. of Radiation Medicine

2011-07-01

Protons have a more than 50-year history of applications in medical therapy and more recently also in imaging. Therapy with protons became possible after proton accelerators capable of accelerating protons to energies higher than 150 MeV had been built during the 1940s in a few places around the world. Proton radiography experiments started at the Harvard Cyclotron in the early 1960s. Physicist Allan Cormack, who shared the Nobel Prize for laying the foundation of computed tomography together with Sir Godfrey Hounsfield in 1979, suggested that protons can be used for tomographic imaging for the first time in 1963. Proton CT requires a rotating proton gantry, which did not become available until 1991, at our institution. The interest in proton CT has been renewed due to the fact that exact proton treatment planning is only possible with accurate knowledge of the relative proton stopping power distribution (with respect to water) of the patient, which is best derived by using protons for imaging. Early attempts to do proton CT were hampered by the lack of high-resolution particle trackers, fast data acquisition electronics, and sufficient computing power. Also, efficient proton CT reconstruction algorithms had to be developed that can handle reconstruction based on a large number of proton histories, taking into account the non-straight probabilistic paths of multiply scattered protons. Most of these challenges have been or are about to be solved with the help of high-energy and particle physicists, computer science engineers, and applied mathematicians. In this talk, I will give an update on the development of proton CT for applications in proton therapy. This is an update from a talk I gave at the Annual Brazilian Physics Meeting in 2001, when I first suggested that physicists should contribute to the development of modern proton CT. Brazilian physicists have provided many valuable ideas and discussions for this exciting development. (author)

Current and future applications of protons in medical imaging and treatment

International Nuclear Information System (INIS)

Schulte, Reinhard W.

2011-01-01

Protons have a more than 50-year history of applications in medical therapy and more recently also in imaging. Therapy with protons became possible after proton accelerators capable of accelerating protons to energies higher than 150 MeV had been built during the 1940s in a few places around the world. Proton radiography experiments started at the Harvard Cyclotron in the early 1960s. Physicist Allan Cormack, who shared the Nobel Prize for laying the foundation of computed tomography together with Sir Godfrey Hounsfield in 1979, suggested that protons can be used for tomographic imaging for the first time in 1963. Proton CT requires a rotating proton gantry, which did not become available until 1991, at our institution. The interest in proton CT has been renewed due to the fact that exact proton treatment planning is only possible with accurate knowledge of the relative proton stopping power distribution (with respect to water) of the patient, which is best derived by using protons for imaging. Early attempts to do proton CT were hampered by the lack of high-resolution particle trackers, fast data acquisition electronics, and sufficient computing power. Also, efficient proton CT reconstruction algorithms had to be developed that can handle reconstruction based on a large number of proton histories, taking into account the non-straight probabilistic paths of multiply scattered protons. Most of these challenges have been or are about to be solved with the help of high-energy and particle physicists, computer science engineers, and applied mathematicians. In this talk, I will give an update on the development of proton CT for applications in proton therapy. This is an update from a talk I gave at the Annual Brazilian Physics Meeting in 2001, when I first suggested that physicists should contribute to the development of modern proton CT. Brazilian physicists have provided many valuable ideas and discussions for this exciting development. (author)

The study of PDMS surface treatment and it's applications by using proton beam

International Nuclear Information System (INIS)

Baek, J. Y.; Kim, J. Y.; Kwon, K. H.; Park, J. Y.

2007-04-01

PDMS(Polydimethylsiloxane) is mainly used as a material to do lab on a chip for biochemical analysis. PDMS has many applicability at the Bio-Technology(BT) field, because it is flexible, biocompatible and has good oxygen permeability. In this study, we have investigated to physical and chemical changes of PDMS surface by proton beam radiation conditions. The used kind of ion were Ar and N, beam energy was 30keV, 60keV, 80keV, total fluence was 1E10 to 1E16 [ions/cm 2 ]. PDMS membrane was produced as 150 μm thick on the 3' silicon wafer. We inquired into physical and chemical changes up to beam radiation conditions through the investigate the change of surface roughness by AFM(Atomic Force Microscope), the change of surface morphology by SEM(Scanning Electron Microscope) and the change of chemical composition by FT-IR(Fourier Transform Infrared Raman spectroscopy) and XPS(X-ray Photoelectron Spectroscopy). From these basic data to we set up the proton beam radiation conditions to secure metal layer and PDMS adhesion. This enables to produce the electrode at the PDMS material lab on a chip. From now on, we'll investigate the cell patterning possibility after carry out of cell culture with mouse fibroblast at PDMS surface what is surface modification by using of proton beam radiation and apply this to produce lab on a chip. Physical property: Surface roughness of PDMS membrane was observed using AFM, after exposure of proton beam on it. The roughness increased as the power level of proton beam increase. This phenomena was caused by the kinetic energy of particle. Chemical property: Long term observation was conducted on the contact angles of the samples made by the proton beam exposure or oxygen plasma treatment; the hydrophilicity was found to be stronger in the samples made by the proton beam exposure. We found the reason of this was the destruction of polymer chains by proton beam. Feasibility of Through-hole: Considering that comparatively high level energy beam

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

Proton Radiography to Improve Proton Radiotherapy : Simulation Study at Different Proton Beam Energies

NARCIS (Netherlands)

Biegun, Aleksandra; Takatsu, Jun; van Goethem, Marc-Jan; van der Graaf, Emiel; van Beuzekom, Martin; Visser, Jan; Brandenburg, Sijtze

To improve the quality of cancer treatment with protons, a translation of X-ray Computed Tomography (CT) images into a map of the proton stopping powers needs to be more accurate. Proton stopping powers determined from CT images have systematic uncertainties in the calculated proton range in a

Poster - 40: Treatment Verification of a 3D-printed Eye Phantom for Proton Therapy

International Nuclear Information System (INIS)

Dunning, Chelsea; Lindsay, Clay; Unick, Nick; Sossi, Vesna; Martinez, Mark; Hoehr, Cornelia

2016-01-01

Purpose: Ocular melanoma is a form of eye cancer which is often treated using proton therapy. The benefit of the steep proton dose gradient can only be leveraged for accurate patient eye alignment. A treatment-planning program was written to plan on a 3D-printed anatomical eye-phantom, which was then irradiated to demonstrate the feasibility of verifying in vivo dosimetry for proton therapy using PET imaging. Methods: A 3D CAD eye model with critical organs was designed and voxelized into the Monte-Carlo transport code FLUKA. Proton dose and PET isotope production were simulated for a treatment plan of a test tumour, generated by a 2D treatment-planning program developed using NumPy and proton range tables. Next, a plastic eye-phantom was 3D-printed from the CAD model, irradiated at the TRIUMF Proton Therapy facility, and imaged using a PET scanner. Results: The treatment-planning program prediction of the range setting and modulator wheel was verified in FLUKA to treat the tumour with at least 90% dose coverage for both tissue and plastic. An axial isotope distribution of the PET isotopes was simulated in FLUKA and converted to PET scan counts. Meanwhile, the 3D-printed eye-phantom successfully yielded a PET signal. Conclusions: The 2D treatment-planning program can predict required parameters to sufficiently treat an eye tumour, which was experimentally verified using commercial 3D-printing hardware to manufacture eye-phantoms. Comparison between the simulated and measured PET isotope distribution could provide a more realistic test of eye alignment, and a variation of the method using radiographic film is being developed.

Poster - 40: Treatment Verification of a 3D-printed Eye Phantom for Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Dunning, Chelsea; Lindsay, Clay; Unick, Nick; Sossi, Vesna; Martinez, Mark; Hoehr, Cornelia [University of British Columbia, University of Victoria, University of British Columbia, University of British Columbia, University of British Columbia, TRIUMF (Canada)

2016-08-15

Purpose: Ocular melanoma is a form of eye cancer which is often treated using proton therapy. The benefit of the steep proton dose gradient can only be leveraged for accurate patient eye alignment. A treatment-planning program was written to plan on a 3D-printed anatomical eye-phantom, which was then irradiated to demonstrate the feasibility of verifying in vivo dosimetry for proton therapy using PET imaging. Methods: A 3D CAD eye model with critical organs was designed and voxelized into the Monte-Carlo transport code FLUKA. Proton dose and PET isotope production were simulated for a treatment plan of a test tumour, generated by a 2D treatment-planning program developed using NumPy and proton range tables. Next, a plastic eye-phantom was 3D-printed from the CAD model, irradiated at the TRIUMF Proton Therapy facility, and imaged using a PET scanner. Results: The treatment-planning program prediction of the range setting and modulator wheel was verified in FLUKA to treat the tumour with at least 90% dose coverage for both tissue and plastic. An axial isotope distribution of the PET isotopes was simulated in FLUKA and converted to PET scan counts. Meanwhile, the 3D-printed eye-phantom successfully yielded a PET signal. Conclusions: The 2D treatment-planning program can predict required parameters to sufficiently treat an eye tumour, which was experimentally verified using commercial 3D-printing hardware to manufacture eye-phantoms. Comparison between the simulated and measured PET isotope distribution could provide a more realistic test of eye alignment, and a variation of the method using radiographic film is being developed.

Review of 3D image data calibration for heterogeneity correction in proton therapy treatment planning

International Nuclear Information System (INIS)

Zhu, Jiahua; Penfold, Scott N.

2016-01-01

Correct modelling of the interaction parameters of patient tissues is of vital importance in proton therapy treatment planning because of the large dose gradients associated with the Bragg peak. Different 3D imaging techniques yield different information regarding these interaction parameters. Given the rapidly expanding interest in proton therapy, this review is written to make readers aware of the current challenges in accounting for tissue heterogeneities and the imaging systems that are proposed to tackle these challenges. A summary of the interaction parameters of interest in proton therapy and the current and developmental 3D imaging techniques used in proton therapy treatment planning is given. The different methods to translate the imaging data to the interaction parameters of interest are reviewed and a summary of the implementations in several commercial treatment planning systems is presented.

Review of 3D image data calibration for heterogeneity correction in proton therapy treatment planning.

Science.gov (United States)

Zhu, Jiahua; Penfold, Scott N

2016-06-01

Correct modelling of the interaction parameters of patient tissues is of vital importance in proton therapy treatment planning because of the large dose gradients associated with the Bragg peak. Different 3D imaging techniques yield different information regarding these interaction parameters. Given the rapidly expanding interest in proton therapy, this review is written to make readers aware of the current challenges in accounting for tissue heterogeneities and the imaging systems that are proposed to tackle these challenges. A summary of the interaction parameters of interest in proton therapy and the current and developmental 3D imaging techniques used in proton therapy treatment planning is given. The different methods to translate the imaging data to the interaction parameters of interest are reviewed and a summary of the implementations in several commercial treatment planning systems is presented.

Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: How do protons compare with other conformal techniques?

International Nuclear Information System (INIS)

Lee, Catherine T.; Bilton, Stephen D.; Famiglietti, Robin M.; Riley, Beverly A.; Mahajan, Anita; Chang, Eric L.; Maor, Moshe H.; Woo, Shiao Y.; Cox, James D.; Smith, Alfred R.

2005-01-01

Purpose: To calculate treatment plans and compare the dose distributions and dose-volume histograms (DVHs) for photon three-dimensional conformal radiation therapy (3D-CRT), electron therapy, intensity-modulated radiation therapy (IMRT), and standard (nonintensity modulated) proton therapy in three pediatric disease sites. Methods and Materials: The tumor volumes from 8 patients (3 retinoblastomas, 2 medulloblastomas, and 3 pelvic sarcomas) were studied retrospectively to compare DVHs from proton therapy with 3D-CRT, electron therapy, and IMRT. In retinoblastoma, several planning techniques were analyzed: A single electron appositional beam was compared with a single 3D-CRT lateral beam, a 3D-CRT anterior beam paired with a lateral beam, IMRT, and protons. In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons. Craniospinal irradiation (which consisted of composite plans of both the posterior fossa and craniospinal components) was also evaluated, primarily comparing spinal irradiation using 3D-CRT electrons, 3D-CRT photons, and protons. Lastly, in pelvic sarcoma, 3D-CRT, IMRT, and proton plans were assessed. Results: In retinoblastoma, protons resulted in the best target coverage combined with the most orbital bone sparing (10% was the mean orbital bone volume irradiated at ≥5 Gy for protons vs. 25% for 3D-CRT electrons, 69% for IMRT, 41% for a single 3D lateral beam, 51% for a 3D anterolateral beam with a lens block, and 65% for a 3D anterolateral beam without a lens block). A single appositional electron field was the next best technique followed by other planning approaches. In medulloblastoma, for posterior fossa and craniospinal irradiation, protons resulted in the least dose to the cochlea (for only posterior fossa irradiation at ≥20 Gy, 34% was the mean cochlear volume irradiated for protons, 87% for IMRT, 89% for 3D-CRT) and hypothalamus-pituitary axis (for only posterior fossa irradiation at ≥10 Gy

Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons.

Science.gov (United States)

Matloob, Samir A; Nasir, Haleema A; Choi, David

2016-08-01

Chordomas are rare tumours affecting the skull base. There is currently no clear consensus on the post-surgical radiation treatments that should be used after maximal tumour resection. However, high-dose proton beam therapy is an accepted option for post-operative radiotherapy to maximise local control, and in the UK, National Health Service approval for funding abroad is granted for specific patient criteria. To review the indications and efficacy of proton beam therapy in the management of skull base chordomas. The primary outcome measure for review was the efficacy of proton beam therapy in the prevention of local occurrence. A systematic review of English and non-English articles using MEDLINE (1946-present) and EMBASE (1974-present) databases was performed. Additional studies were reviewed when referenced in other studies and not available on these databases. Search terms included chordoma or chordomas. The PRISMA guidelines were followed for reporting our findings as a systematic review. A total of 76 articles met the inclusion and exclusion criteria for this review. Limitations included the lack of documentation of the extent of primary surgery, tumour size, and lack of standardised outcome measures. Level IIb/III evidence suggests proton beam therapy given post operatively for skull base chordomas results in better survival with less damage to surrounding tissue. Proton beam therapy is a grade B/C recommended treatment modality for post-operative radiation therapy to skull base chordomas. In comparison to other treatment modalities long-term local control and survival is probably improved with proton beam therapy. Further, studies are required to directly compare proton beam therapy to other treatment modalities in selected patients.

The choice of treatment after incomplete adenomectomy in acromegaly: Proton - versus highvoltage radiation

International Nuclear Information System (INIS)

Luedecke, D.K.; Lutz, B.S.; Niedworok, G.

1989-01-01

The authors report the results of a study designed to compare the effectiveness of two different types of radiation in patients with acromegaly where surgical therapy had failed to normalize growth hormone(GH). Longterm follow-up after conventional high voltage radiation in 17 patients and protons therapy in 13 patients confirmed a similar reduction of GH levels in both groups. After 4,5 years a decrease of about 80% was achieved. After 'conventional radiation' GH was normal in 8(47%) and near normal in 6(35%) while proton therapy resulted in normalization in 5 and improvement in 5(38%). The slightly better results of 'conventional radiation' must be attributed to lower pretreatment levels of GH. Side effects as additional pituitary deficits and oculomotor palsies were more often seen after proton treatment. Since the results of both radiation methods are similar and proton therapy has a tendency to more serious side effects we recommend 'conventional radiation' as secondary treatment of acromegaly. (Authors)

Secondary neutron doses received by patients of different ages during intracranial proton therapy treatments

International Nuclear Information System (INIS)

Sayah, R.

2012-01-01

Proton therapy is an advanced radiation therapy technique that allows delivering high doses to the tumor while saving the healthy surrounding tissues due to the protons' ballistic properties. However, secondary particles, especially neutrons, are created during protons' nuclear reactions in the beam-line and the treatment room components, as well as inside the patient. Those secondary neutrons lead to unwanted dose deposition to the healthy tissues located at distance from the target, which may increase the secondary cancer risks to the patients, especially the pediatric ones. The aim of this work was to calculate the neutron secondary doses received by patients of different ages treated at the Institut Curie-centre de Protontherapie d'Orsay (ICPO) for intracranial tumors, using a 178 MeV proton beam. The treatments are undertaken at the new ICPO room equipped with an IBA gantry. The treatment room and the beam-line components, as well as the proton source were modeled using the Monte Carlo code MCNPX. The obtained model was then validated by a series of comparisons between model calculations and experimental measurements. The comparisons concerned: a) depth and lateral proton dose distributions in a water phantom, b) neutron spectrometry at one position in the treatment room, c) ambient dose equivalents at different positions in the treatment room and d) secondary absorbed doses inside a physical anthropomorphic phantom. A general good agreement was found between calculations and measurements, thus our model was considered as validated. The University of Florida hybrid voxelized phantoms of different ages were introduced into the MCNPX validated model, and secondary neutron doses were calculated to many of these phantoms' organs. The calculated doses were found to decrease as the organ's distance to the treatment field increases and as the patient's age increases. The secondary doses received by a one year-old patient may be two times higher than the doses

Proton Radiotherapy for Parameningeal Rhabdomyosarcoma: Clinical Outcomes and Late Effects

Energy Technology Data Exchange (ETDEWEB)

Childs, Stephanie K. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Kozak, Kevin R. [Department of Radiation Oncology, University of Wisconsin Cancer Center Johnson Creek, Madison, WI (United States); Friedmann, Alison M. [Department of Pediatric Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Adams, Judith; MacDonald, Shannon M.; Liebsch, Norbert J.; Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States)

2012-02-01

Purpose: To report the clinical outcome and late side effect profile of proton radiotherapy in the treatment of children with parameningeal rhabdomyosarcoma (PM-RMS). Methods and Materials: Seventeen consecutive children with PM-RMS were treated with proton radiotherapy at Massachusetts General Hospital between 1996 and 2005. We reviewed the medical records of all patients and asked referring physicians to report specific side effects of interest. Results: Median patient age at diagnosis was 3.4 years (range, 0.4-17.6). Embryonal (n = 11), alveolar (n = 4), and undifferentiated (n = 2) histologies were represented. Ten patients (59%) had intracranial extension. Median prescribed dose was 50.4 cobalt gray equivalents (GyRBE) (range, 50.4-56.0 GyRBE) delivered in 1.8-2.0-GyRBE daily fractions. Median follow-up was 5.0 years for survivors. The 5-year failure-free survival estimate was 59% (95% confidence interval, 33-79%), and overall survival estimate was 64% (95% confidence interval, 37-82%). Among the 7 patients who failed, sites of first recurrence were local only (n = 2), regional only (n = 2), distant only (n = 2), and local and distant (n = 1). Late effects related to proton radiotherapy in the 10 recurrence-free patients (median follow-up, 5 years) include failure to maintain height velocity (n = 3), endocrinopathies (n = 2), mild facial hypoplasia (n = 7), failure of permanent tooth eruption (n = 3), dental caries (n = 5), and chronic nasal/sinus congestion (n = 2). Conclusions: Proton radiotherapy for patients with PM-RMS yields tumor control and survival comparable to that in historical controls with similar poor prognostic factors. Furthermore, rates of late effects from proton radiotherapy compare favorably to published reports of photon-treated cohorts.

A Prospective Outcomes Study of Proton Therapy for Chordomas and Chondrosarcomas of the Spine

Energy Technology Data Exchange (ETDEWEB)

Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Rotondo, Ronny L.; Begosh-Mayne, Dustin [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States); Scarborough, Mark T.; Gibbs, C. Parker [Department of Orthopedics and Rehabilitation, University of Florida College of Medicine, Gainesville, Florida (United States); Morris, Christopher G.; Mendenhall, William M. [Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida (United States)

2016-05-01

Purpose: To evaluate the effectiveness of definitive or adjuvant external beam proton therapy on survival in patients with chordomas and chondrosarcomas of the spine. Methods and Materials: Between March 2007 and May 2013, 51 patients with a median age of 58 years (range, 22-83 years) with chordoma (n=34) or chondrosarcomas (n=17) of the sacrum (n=21), the cervical spine (n=20), and the thoracolumbar spine (n=10) were treated with external beam proton therapy to a median dose of 70.2 Gy(RBE) [range, 64.2-75.6 Gy(RBE)] at our institution. Distant metastases, overall survival, cause-specific survival, local control, and disease-free survival were calculated. Results: The mean follow-up time was 3.7 years (range, 0.3-7.7 years). Across all time points, 25 patients experienced disease recurrence: 18 local recurrences, 6 local and distant recurrences, and 1 distant metastasis. The 4-year rates of overall survival and cause-specific survival were 72%; disease-free survival was 57%, local control was 58%, and freedom from distant metastases was 86%. The median time to local progression was 1.7 years (range, 0.2-6.0 years), and the median time to distant progression was 1.6 years (range, 0.2-6.0 years). The risk factors for local recurrence were age ≤58 years (62% vs 26%; P=.04) and recurrence after prior surgery (29% vs 81%; P=.01). Secondary cancers developed in 2 patients: B-cell lymphoma 5.5 years after treatment and bladder cancer 2 years after treatment. We observed the following toxicities: sacral soft tissue necrosis requiring surgery (n=2), T1 vertebral fracture requiring fusion surgery (n=1), chronic urinary tract infections (n=1), surgery for necrotic bone cyst (n=1), and grade 2 bilateral radiation nephritis (n=1). Conclusion: High-dose proton therapy controls more than half of spinal chordomas and chondrosarcomas and compares favorably with historic photon data. Local progression is the dominant mode of treatment failure and may be reduced by

Relative survival of hybrid x-ray-resistant, and normally sensitive mammalian cells exposed to x rays and protons under aerobic and hypoxic conditions

International Nuclear Information System (INIS)

Williams, J.R.; Gould, R.G.; Flynn, D.; Robertson, J.B.; Little, J.B.

1978-01-01

Survival of an x-ray-resistant hybrid cell line (HD 1 ) and a normally responsive cell line (H 4 ) have been compared when irradiated under induced hypoxia by both protons and X rays. The two cell lines are similarly protected when irradiated under hypoxic conditions with oxygen enhancement ratios of 2.8 and 2.7, respectively. The protection is consistent with a dose-modifying factor. No statistically significant difference is observed between cell inactivation by x rays and protons in either cell line, whether irradiated under aerobic or hypoxic conditions

Poor survival of treatment-related acute nonlymphocytic leukemia

International Nuclear Information System (INIS)

Neugut, A.I.; Nieves, J.; Murray, T.; Tsai, Weiyann; Robinson, E.

1990-01-01

Population-based data on more than 1 million patients registered in the Surveillance, Epidemiology, and End-Results Program of the National Cancer Institute, 1973-1984, were analyzed to determine the survival of patients with de novo acute nonlymphocytic leukemia (ANLL) and following a first primary tumor treated (with chemotherapy and/or radiation therapy) or untreated. Cases that occurred within 12 months of the first malignant neoplasm were excluded. Survival was estimated using Cox proportional-hazards modeling, with age, sex, and specific type of ANLL as covariates. The 6,271 patients with de novo ANLL had an estimated 12-month survival of 30%, while the 107 patients with treatment-related ANLL had an estimated 12-month survival of 10%. The authors conclude that ANLL that occurs after chemotherapy or radiation therapy is biologically more aggressive and/or resistant to therapy than spontaneous ANLL. This provides a rationale for current studies on treatment-induced cellular changes and on more aggressive therapy for these patients

The Australian National Proton Facility

International Nuclear Information System (INIS)

Jackson, M.; Rozenfeld, A.; Bishop, J.

2002-01-01

Full text: Protons have been used in the treatment of cancer since 1954 and over 30,000 patients have been treated around the world. Their precise dose distribution allows the treatment of small tumours in critical locations such as the base of skull and orbit and is an alternative to stereotactic radiotherapy in other sites. With the development of hospital-based systems in the 1990's, common tumours such as prostate, breast and lung cancer can now also be treated using simple techniques. The therapeutic ratio is improved as the dose to the tumour can be increased while sparing normal tissues. The well defined high dose region and low integral dose compared with photon treatments is a particular advantage in children and other situations where long-term survival is expected and when used in combination with chemotherapy. In January 2002, the NSW Health Department initiated a Feasibility Study for an Australian National Proton Facility. This Study will address the complex medical, scientific, engineering, commercial and legal issues required to design and build a proton facility in Australia. The Facility will be mainly designed for patient treatment but will also provide facilities for biological, physical and engineering research. The proposed facility will have a combination of fixed and rotating beams with an energy range of 70-250 MeV. Such a centre will enable the conduct of randomised clinical trials and a comparison with other radiotherapy techniques such as Intensity Modulated Radiation Therapy. Cost-utility comparisons with other medical treatments will also be made and further facilities developed if the expected benefit is confirmed. When patients are not being treated, the beam will be available for commercial and research purposes. This presentation will summarize the progress of the Study and discuss the important issues that need to be resolved before the Facility is approved and constructed

Prognostic Factors, Treatment, and Survival in Dermatofibrosarcoma Protuberans.

Science.gov (United States)

Criscito, Maressa C; Martires, Kathryn J; Stein, Jennifer A

2016-12-01

There is limited information regarding the influence of patient demographics, tumor characteristics, and treatment type on the survival of patients with dermatofibrosarcoma protuberans (DFSP). To assess prognostic factors and to evaluate the influence of treatment modality on overall survival of patients with DFSP. We examined DFSP using data for 3686 patients with histologically confirmed cases of DFSP diagnosed between 1972 and 2012 from the 18 US regional registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, with linkage to demographic data from the US Census Bureau for median household income (MHI). The analysis was performed in February 2016. The primary outcome measures were tumor characteristics, prognostic factors, and overall survival in months. There were 3686 cases of DFSP examined. Older age (hazard ratio [HR], 1.08; 95% CI, 1.06-1.10; P < .001), male sex (HR, 1.97; 95% CI, 1.09-3.55; P = .03), and tumor size (HR, 1.09; 95% CI, 1.01-1.18; P = .04) were significantly associated with poorer overall survival in a controlled analysis. Older age (odds ratio [OR], 1.01; 95% CI, 1.00-1.02; P = .01), male sex (OR, 1.95; 95% CI, 1.57-2.42; P < .001), and black race (OR, 1.78; 95% CI, 1.37-2.32; P < .001) were associated with larger (≥3.0 cm) tumors at presentation. Treatment modality did not influence overall survival; however, differences in patient characteristics affected the treatment received. Older age at presentation (OR, 1.02; 95% CI, 1.01-1.03; P =.01), black race (OR, 1.82; 95% CI, 1.13-2.92; P = .01), large tumor size (OR, 1.15; 95% CI, 1.09-1.21; P < .001), and head or neck location (OR, 4.63; 95% CI, 2.66-8.07; P <.001) increased the likelihood of a patient receiving surgery and radiation over surgery alone. In addition, white patients (OR, 0.51; 95% CI, 0.30-0.87; P=.01), women (OR, 0.53; 95% CI, 0.36-0.78; P <.001), and patients with a higher MHI (OR, 1.27; 95

Effects of fotemustine or dacarbasine on a melanoma cell line pretreated with therapeutic proton irradiation

Directory of Open Access Journals (Sweden)

Privitera Giuseppe

2009-04-01

Full Text Available Abstract Background Considering that HTB140 melanoma cells have shown a poor response to either protons or alkylating agents, the effects of a combined use of these agents have been analysed. Methods Cells were irradiated in the middle of the therapeutic 62 MeV proton spread out Bragg peak (SOBP. Irradiation doses were 12 or 16 Gy and are those frequently used in proton therapy. Four days after irradiation cells were treated with fotemustine (FM or dacarbazine (DTIC. Drug concentrations were 100 and 250 μM, values close to those that produce 50% of growth inhibition. Cell viability, proliferation, survival and cell cycle distribution were assessed 7 days after irradiation that corresponds to more than six doubling times of HTB140 cells. In this way incubation periods providing the best single effects of drugs (3 days and protons (7 days coincided at the same time. Results Single proton irradiations have reduced the number of cells to ~50%. FM caused stronger cell inactivation due to its high toxicity, while the effectiveness of DTIC, that was important at short term, almost vanished with the incubation of 7 days. Cellular mechanisms triggered by proton irradiation differently influenced the final effects of combined treatments. Combination of protons and FM did not improve cell inactivation level achieved by single treatments. A low efficiency of the single DTIC treatment was overcome when DTIC was introduced following proton irradiation, giving better inhibitory effects with respect to the single treatments. Most of the analysed cells were in G1/S phase, viable, active and able to replicate DNA. Conclusion The obtained results are the consequence of a high resistance of HTB140 melanoma cells to protons and/or drugs. The inactivation level of the HTB140 human melanoma cells after protons, FM or DTIC treatments was not enhanced by their combined application.

MO-A-BRD-10: A Fast and Accurate GPU-Based Proton Transport Monte Carlo Simulation for Validating Proton Therapy Treatment Plans

Energy Technology Data Exchange (ETDEWEB)

Wan Chan Tseung, H; Ma, J; Beltran, C [Mayo Clinic, Rochester, MN (United States)

2014-06-15

Purpose: To build a GPU-based Monte Carlo (MC) simulation of proton transport with detailed modeling of elastic and non-elastic (NE) protonnucleus interactions, for use in a very fast and cost-effective proton therapy treatment plan verification system. Methods: Using the CUDA framework, we implemented kernels for the following tasks: (1) Simulation of beam spots from our possible scanning nozzle configurations, (2) Proton propagation through CT geometry, taking into account nuclear elastic and multiple scattering, as well as energy straggling, (3) Bertini-style modeling of the intranuclear cascade stage of NE interactions, and (4) Simulation of nuclear evaporation. To validate our MC, we performed: (1) Secondary particle yield calculations in NE collisions with therapeutically-relevant nuclei, (2) Pencil-beam dose calculations in homogeneous phantoms, (3) A large number of treatment plan dose recalculations, and compared with Geant4.9.6p2/TOPAS. A workflow was devised for calculating plans from a commercially available treatment planning system, with scripts for reading DICOM files and generating inputs for our MC. Results: Yields, energy and angular distributions of secondaries from NE collisions on various nuclei are in good agreement with the Geant4.9.6p2 Bertini and Binary cascade models. The 3D-gamma pass rate at 2%–2mm for 70–230 MeV pencil-beam dose distributions in water, soft tissue, bone and Ti phantoms is 100%. The pass rate at 2%–2mm for treatment plan calculations is typically above 98%. The net computational time on a NVIDIA GTX680 card, including all CPU-GPU data transfers, is around 20s for 1×10{sup 7} proton histories. Conclusion: Our GPU-based proton transport MC is the first of its kind to include a detailed nuclear model to handle NE interactions on any nucleus. Dosimetric calculations demonstrate very good agreement with Geant4.9.6p2/TOPAS. Our MC is being integrated into a framework to perform fast routine clinical QA of pencil

Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

Energy Technology Data Exchange (ETDEWEB)

Amsbaugh, Mark J. [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Grosshans, David R., E-mail: dgrossha@mdanderson.org [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); McAleer, Mary Frances; Zhu, Ron; Wages, Cody; Crawford, Cody N.; Palmer, Matthew; De Gracia, Beth; Woo Shiao; Mahajan, Anita [Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

2012-08-01

Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas, and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.

Audit in radiation therapy: long-term survival and cost of treatment

International Nuclear Information System (INIS)

Stevens, G.; Firth, I.

1997-01-01

In order to determine the cost of radiation treatment and the survival rate of a cohort of patients treated in a 6 month period in 1988, estimates of the capital and recurrent costs of this service were made for the calendar year 1988, expressed as $A(1988). Data collected prospectively included workload statistics (including number of attendances), field treated and complexity of treatment. Patient and tumour-related data included tumour site, intent of treatment and survival. The survival rate of patients during this period was determined in June 1995. The cost per field in 1988 was estimated at $A44.32. The 1988 costs of courses of definitive, adjuvant and palliative radiation therapy were estimated at $A2545, $A2482 and $A929, respectively. The major contributor to the cost of salaries and consumables within the Radiation Oncology Department (81.6%), with capital costs accounting for 13.5%, overheads accounting for 4.5% of the costs and planned admissions accounting for 0.2%. The median survival time of 580 patients with malignant disease treated during this period in 1988 was 12.4 months. The overall 5 year survival rate was 27%. For 105 patients treated definitively with radiation therapy, the median and 5 year survival rate figures were 26.0 months and 40%. For 149 patients treated with adjuvant radiation therapy, the 5 year survival rate was 62% (median survival rate not reached). For 279 patients treated palliatively, median and 5 year survival rate figures were 5.2 months and 3%. The cost per month of survival for all patients with malignancy was $A67; the figures for definitive , adjuvant and palliative treatments being $A74, $A48 and $A105, respectively. A sensitivity analysis indicated that these figures were robust. The cost of radiation treatment per field was comparable to reports for other centres and emphasizes the utility of radiation therapy as a cost-effective cancer treatment modality. 7 refs., 6 tabs., 2 figs

Feasibility of proton pencil beam scanning treatment of free-breathing lung cancer patients

NARCIS (Netherlands)

Jakobi, Annika; Perrin, Rosalind; Knopf, Antje; Richter, Christian

BACKGROUND: The interplay effect might degrade the dose of pencil beam scanning proton therapy to a degree that free-breathing treatment might be impossible without further motion mitigation techniques, which complicate and prolong the treatment. We assessed whether treatment of free-breathing

Locally challenging osteo- and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning

Energy Technology Data Exchange (ETDEWEB)

Hug, Eugen B; Fitzek, Markus M; Liebsch, Norbert J; Munzenrider, John E

1995-02-01

Purpose: Tumors of the axial skeleton are at high risk for local failure. Total surgical resection is rarely possible. Critical normal tissues limit the efficacy of conventional photon therapy. This study reviews our experience of using combined high dose proton and photon radiation therapy following three-dimensional (3D) treatment planning. Methods and Materials: Between December 1980 and September 1992, 47 patients were treated at the Massachusetts General Hospital and Harvard Cyclotron Laboratory for primary or recurrent chordomas and chondrosarcomas (group 1, 20 patients), osteogenic sarcomas (group 2, 15 patients) and giant cell tumors, osteo- or chondroblastomas (group 3, 12 patients). Radiation treatment was given postoperatively in 23 patients, pre- and postoperatively in 17 patients, and 7 patients received radiation therapy as definitive treatment modality following biopsy only. The proton radiation component was delivered using a 160 MeV proton beam and the photon component using megavoltage photons up to 23 MV energy with 1.8-2.0 Cobalt Gray Equivalent (CGE) per fraction, once a day. Total external beam target dose ranged from 55.3 CGE to 82.0 CGE with mean target doses of 73.9 CGE (group 1), 69.8 CGE (group 2), and 61.8 CGE (group 3). Results: Group 1 (chordoma and chondrosarcoma): Five of 14 patients (36%) with chordoma recurred locally, and 2 out of 5 patients developed distant metastasis, resulting in 1 death from disease. A trend for improved local control was noted for primary vs. recurrent tumors, target doses > 77 CGE and gross total resection. All patients with chondrosarcoma achieved and maintained local control and disease-free status. Five-year actuarial local control and overall survival rates were 53% and 50% for chordomas and 100% and 100% for chondrosarcomas, respectively. Group 2 (osteogenic sarcoma): Three of 15 patients (20%) never achieved local control and died within 6 months of completion of radiation treatment. Only 1 out of 12

Status of proton treatment facility at National Cancer Center, Kashiwa

International Nuclear Information System (INIS)

Tachikawa, T.; Kohmura, I.; Kataoka, S.; Nonaka, H.; Kimura, T.; Sato, T.; Nishio, T.; Shimbo, M.; Ogino, T.; Ikeda, H.

2001-01-01

Proton treatment facility at National Cancer Center Hospital East (Kashiwa) has two rotating gantry ports and one horizontal fixed port. In order to provide the same dose distribution at different gantry angles, the beam optics from the accelerator (235 MeV cyclotron) to the entrance of nozzle is specially tuned. Recently developed automatic tuning method of beam alignment can realize a sequential treatment at three irradiation ports. (author)

Is it possible to verify directly a proton-treatment plan using positron emission tomography?

International Nuclear Information System (INIS)

Vynckier, S.; Derreumaux, S.; Richard, F.; Wambersie, A.; Bol, A.; Michel, C.

1993-01-01

A PET camera is used to visualize the positron activity induced during protonbeam therapy in order to verify directly the proton-treatment plans. The positron emitters created are predominantly the 15 O and 11 C, whose total activity amounts to 12 MBq after an irradiation with 85 MeV protons, delivering 3 Gy in a volume of approximately 300 cm 3 . Although this method is a useful verification of patient setup, care must be taken when deriving dose distributions from activity distributions. Correlation between both quantities is difficult, moreover at the last millimeters of their range, protons will no longer activate tissue. Due to the short half-lives the PET camera must be located close to the treatment facility. (author) 17 refs

Treatment Extends Survival for Women with Cervical Cancer

Science.gov (United States)

Patients with locally advanced cervical cancer who received gemcitabine (Gemzar®) both as part of initial treatment and as part of therapy following primary treatment had improved survival compared with patients whose treatment did not include gemcitabine, according to findings presented at the 2009 ASCO meeting in Orlando.

The study of PDMS surface treatment and it's applications by using proton beam

Energy Technology Data Exchange (ETDEWEB)

Baek, J. Y.; Kim, J. Y.; Kwon, K. H.; Park, J. Y. [Korea Univ., Seoul (Korea, Republic of)

2007-04-15

PDMS(Polydimethylsiloxane) is mainly used as a material to do lab on a chip for biochemical analysis. PDMS has many applicability at the Bio-Technology(BT) field, because it is flexible, biocompatible and has good oxygen permeability. In this study, we have investigated to physical and chemical changes of PDMS surface by proton beam radiation conditions. The used kind of ion were Ar and N, beam energy was 30keV, 60keV, 80keV, total fluence was 1E10 to 1E16 [ions/cm{sup 2}]. PDMS membrane was produced as 150 {mu}m thick on the 3' silicon wafer. We inquired into physical and chemical changes up to beam radiation conditions through the investigate the change of surface roughness by AFM(Atomic Force Microscope), the change of surface morphology by SEM(Scanning Electron Microscope) and the change of chemical composition by FT-IR(Fourier Transform Infrared Raman spectroscopy) and XPS(X-ray Photoelectron Spectroscopy). From these basic data to we set up the proton beam radiation conditions to secure metal layer and PDMS adhesion. This enables to produce the electrode at the PDMS material lab on a chip. From now on, we'll investigate the cell patterning possibility after carry out of cell culture with mouse fibroblast at PDMS surface what is surface modification by using of proton beam radiation and apply this to produce lab on a chip. Physical property: Surface roughness of PDMS membrane was observed using AFM, after exposure of proton beam on it. The roughness increased as the power level of proton beam increase. This phenomena was caused by the kinetic energy of particle. Chemical property: Long term observation was conducted on the contact angles of the samples made by the proton beam exposure or oxygen plasma treatment; the hydrophilicity was found to be stronger in the samples made by the proton beam exposure. We found the reason of this was the destruction of polymer chains by proton beam. Feasibility of Through-hole: Considering that comparatively high

Dosimetric Feasibility of Hypofractionated Proton Radiotherapy for Neoadjuvant Pancreatic Cancer Treatment

International Nuclear Information System (INIS)

Kozak, Kevin R.; Kachnic, Lisa A.; Adams, Judith C; Crowley, Elizabeth M.; Alexander, Brian M.; Mamon, Harvey J.; Fernandez-Del Castillo, Carlos; Ryan, David P.; DeLaney, Thomas F.; Hong, Theodore S.

2007-01-01

Purpose: To evaluate tumor and normal tissue dosimetry of a 5 cobalt gray equivalent (CGE) x 5 fraction proton radiotherapy schedule, before initiating a clinical trial of neoadjuvant, short-course proton radiotherapy for pancreatic adenocarcinoma. Methods and Materials: The first 9 pancreatic cancer patients treated with neoadjuvant intensity-modulated radiotherapy (1.8 Gy x 28) at the Massachusetts General Hospital had treatment plans generated using a 5 CGE x 5 fraction proton regimen. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing. Results: Hypofractionated proton and conventionally fractionated intensity-modulated radiotherapy plans both provided acceptable target volume coverage and dose homogeneity. Improved dose conformality provided by the hypofractionated proton regimen resulted in significant sparing of kidneys, liver, and small bowel, evidenced by significant reductions in the mean doses, expressed as percentage prescribed dose, to these structures. Kidney and liver sparing was most evident in low-dose regions (≤20% prescribed dose for both kidneys and ≤60% prescribed dose for liver). Improvements in small-bowel dosimetry were observed in high- and low-dose regions. Mean stomach and duodenum doses, expressed as percentage prescribed dose, were similar for the two techniques. Conclusions: A proton radiotherapy schedule consisting of 5 fractions of 5 CGE as part of neoadjuvant therapy for adenocarcinoma of the pancreas seems dosimetrically feasible, providing excellent target volume coverage, dose homogeneity, and normal tissue sparing. Hypofractionated proton radiotherapy in this setting merits Phase I clinical trial investigation

A Simulation Study for Radiation Treatment Planning Based on the Atomic Physics of the Proton-Boron Fusion Reaction

Energy Technology Data Exchange (ETDEWEB)

Kim, Sunmi; Yoon, Do-Kun; Shin, Han-Back; Jung, Joo-Young; Kim, Moo-Sub; Kim, Kyeong-Hyeon; Jang, Hong-Seok; Suh, Tae Suk [the Catholic University of Korea, Seoul (Korea, Republic of)

2017-03-15

The purpose of this research is to demonstrate, based on a Monte Carlo simulation code, the procedure of radiation treatment planning for proton-boron fusion therapy (PBFT). A discrete proton beam (60 - 120 MeV) relevant to the Bragg peak was simulated using a Monte Carlo particle extended (MCNPX, Ver. 2.6.0, National Laboratory, Los Alamos NM, USA) simulation code. After computed tomography (CT) scanning of a virtual water phantom including air cavities, the acquired CT images were converted using the simulation source code. We set the boron uptake regions (BURs) in the simulated water phantom to achieve the proton-boron fusion reaction. Proton sources irradiated the BUR, in the phantom. The acquired dose maps were overlapped with the original CT image of the phantom to analyze the dose volume histogram (DVH). We successfully confirmed amplifications of the proton doses (average: 130%) at the target regions. From the DVH result for each simulation, we acquired a relatively accurate dose map for the treatment. A simulation was conducted to characterize the dose distribution and verify the feasibility of proton boron fusion therapy (PBFT). We observed a variation in proton range and developed a tumor targeting technique for treatment that was more accurate and powerful than both conventional proton therapy and boron-neutron capture therapy.

Quantitative analysis of treatment process time and throughput capacity for spot scanning proton therapy

International Nuclear Information System (INIS)

Suzuki, Kazumichi; Sahoo, Narayan; Zhang, Xiaodong; Poenisch, Falk; Mackin, Dennis S.; Liu, Amy Y.; Wu, Richard; Zhu, X. Ronald; Gillin, Michael T.; Palmer, Matthew B.; Frank, Steven J.; Lee, Andrew K.

2016-01-01

Purpose: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. Methods: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. Results: The mean monthly equipment clinical availability for the spot scanning port in April 2012–March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012–August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery time increased with total target volume and accounted for

Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

International Nuclear Information System (INIS)

Newhauser, Wayne D.; Zhang, Rui; Jones, Timothy G.; Giebeler, Annelise; Taddei, Phillip J.; Stewart, Robert D.; Lee, Andrew; Vassiliev, Oleg

2015-01-01

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality

Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

Energy Technology Data Exchange (ETDEWEB)

Newhauser, Wayne D., E-mail: newhauser@lsu.edu [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Department of Physics, Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809 (United States); Zhang, Rui [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Department of Physics, Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809 (United States); Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030 (United States); Jones, Timothy G. [Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030 (United States); Department of Physics, Abilene Christian University, ACU Box 27963, Abilene, TX 79699 (United States); Giebeler, Annelise; Taddei, Phillip J. [Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030 (United States); Stewart, Robert D. [Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195 (United States); Lee, Andrew [Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); Vassiliev, Oleg [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Department of Physics, Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809 (United States)

2015-04-24

Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality.

Proton and carbon ion therapy

CERN Document Server

Lomax, Tony

2013-01-01

Proton and Carbon Ion Therapy is an up-to-date guide to using proton and carbon ion therapy in modern cancer treatment. The book covers the physics and radiobiology basics of proton and ion beams, dosimetry methods and radiation measurements, and treatment delivery systems. It gives practical guidance on patient setup, target localization, and treatment planning for clinical proton and carbon ion therapy. The text also offers detailed reports on the treatment of pediatric cancers, lymphomas, and various other cancers. After an overview, the book focuses on the fundamental aspects of proton and carbon ion therapy equipment, including accelerators, gantries, and delivery systems. It then discusses dosimetry, biology, imaging, and treatment planning basics and provides clinical guidelines on the use of proton and carbon ion therapy for the treatment of specific cancers. Suitable for anyone involved with medical physics and radiation therapy, this book offers a balanced and critical assessment of state-of-the-art...

Improved survival in HIV treatment programs in Asia

Science.gov (United States)

De La Mata, Nicole L; Kumarasamy, Nagalingeswaran; Khol, Vohith; Ng, Oon Tek; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Durier, Nicolas; Law, Matthew

2016-01-01

Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (pAsia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time. PMID:26961354

Proton dynamics in cancer.

Science.gov (United States)

Huber, Veronica; De Milito, Angelo; Harguindey, Salvador; Reshkin, Stephan J; Wahl, Miriam L; Rauch, Cyril; Chiesi, Antonio; Pouysségur, Jacques; Gatenby, Robert A; Rivoltini, Licia; Fais, Stefano

2010-06-15

Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth.Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC) in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.

Outcomes of Proton Therapy for the Treatment of Uveal Metastases

International Nuclear Information System (INIS)

Kamran, Sophia C.; Collier, John M.; Lane, Anne Marie; Kim, Ivana; Niemierko, Andrzej; Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E.; Gragoudas, Evangelos; Shih, Helen A.

2014-01-01

Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year

Outcomes of Proton Therapy for the Treatment of Uveal Metastases

Energy Technology Data Exchange (ETDEWEB)

Kamran, Sophia C. [Harvard Medical School, Boston, Massachusetts (United States); Collier, John M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lane, Anne Marie; Kim, Ivana [Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Niemierko, Andrzej [Division of Biostatistics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Chen, Yen-Lin E.; MacDonald, Shannon M.; Munzenrider, John E. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Gragoudas, Evangelos [Retina Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-12-01

Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.

Quantification of the Relative Biological Effectiveness for Ion Beam Radiotherapy: Direct Experimental Comparison of Proton and Carbon Ion Beams and a Novel Approach for Treatment Planning

International Nuclear Information System (INIS)

Elsaesser, Thilo; Weyrather, Wilma K.; Friedrich, Thomas; Durante, Marco; Iancu, Gheorghe; Kraemer, Michael; Kragl, Gabriele; Brons, Stephan; Winter, Marcus; Weber, Klaus-Josef; Scholz, Michael

2010-01-01

Purpose: To present the first direct experimental in vitro comparison of the biological effectiveness of range-equivalent protons and carbon ion beams for Chinese hamster ovary cells exposed in a three-dimensional phantom using a pencil beam scanning technique and to compare the experimental data with a novel biophysical model. Methods and Materials: Cell survival was measured in the phantom after irradiation with two opposing fields, thus mimicking the typical patient treatment scenario. The novel biophysical model represents a substantial extension of the local effect model, previously used for treatment planning in carbon ion therapy for more than 400 patients, and potentially can be used to predict effectiveness of all ion species relevant for radiotherapy. A key feature of the new approach is the more sophisticated consideration of spatially correlated damage induced by ion irradiation. Results: The experimental data obtained for Chinese hamster ovary cells clearly demonstrate that higher cell killing is achieved in the target region with carbon ions as compared with protons when the effects in the entrance channel are comparable. The model predictions demonstrate agreement with these experimental data and with data obtained with helium ions under similar conditions. Good agreement is also achieved with relative biological effectiveness values reported in the literature for other cell lines for monoenergetic proton, helium, and carbon ions. Conclusion: Both the experimental data and the new modeling approach are supportive of the advantages of carbon ions as compared with protons for treatment-like field configurations. Because the model predicts the effectiveness for several ion species with similar accuracy, it represents a powerful tool for further optimization and utilization of the potential of ion beams in tumor therapy.

Detailed Analysis of Apoptosis and Delayed Luminescence of Human Leukemia Jurkat T Cells after Proton Irradiation and Treatments with Oxidant Agents and Flavonoids

Directory of Open Access Journals (Sweden)

Irina Baran

2012-01-01

Full Text Available Following previous work, we investigated in more detail the relationship between apoptosis and delayed luminescence (DL in human leukemia Jurkat T cells under a wide variety of treatments. We used menadione and hydrogen peroxide to induce oxidative stress and two flavonoids, quercetin, and epigallocatechin gallate, applied alone or in combination with menadione or H2O2. 62 MeV proton beams were used to irradiate cells under a uniform dose of 2 or 10 Gy, respectively. We assessed apoptosis, cell cycle distributions, and DL. Menadione, H2O2 and quercetin were potent inducers of apoptosis and DL inhibitors. Quercetin decreased clonogenic survival and the NAD(PH level in a dose-dependent manner. Proton irradiation with 2 Gy but not 10 Gy increased the apoptotic rate. However, both doses induced a substantial G2/M arrest. Quercetin reduced apoptosis and prolonged the G2/M arrest induced by radiation. DL spectroscopy indicated that proton irradiation disrupted the electron flow within Complex I of the mitochondrial respiratory chain, thus explaining the massive necrosis induced by 10 Gy of protons and also suggested an equivalent action of menadione and quercetin at the level of the Fe/S center N2, which may be mediated by their binding to a common site within Complex I, probably the rotenone-binding site.

Medical Proton Accelerator Project

International Nuclear Information System (INIS)

Comsan, M.N.H.

2008-01-01

A project for a medical proton accelerator for cancer treatment is outlined. The project is motivated by the need for a precise modality for cancer curing especially in children. Proton therapy is known by its superior radiation and biological effectiveness as compared to photon or electron therapy. With 26 proton and 3 heavy-ion therapy complexes operating worldwide only one (p) exists in South Africa, and none in south Asia and the Middle East. The accelerator of choice should provide protons with energy 75 MeV for eye treatment and 250 MeV for body treatment. Four treatment rooms are suggested: two with isocentric gantries, one with fixed beams and one for development. Passive scanning is recommended. The project can serve Middle East and North Africa with ∼ 400 million populations. The annual capacity of the project is estimated as 1,100 to be compared with expected radiation cases eligible for proton cancer treatment of not less than 200,000

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

Energy Technology Data Exchange (ETDEWEB)

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin; Swisher-McClure, Samuel; Lukens, John N.; Lin, Alexander

2017-04-01

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals. Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.

Margins for treatment planning of proton therapy

International Nuclear Information System (INIS)

Thomas, Simon J

2006-01-01

For protons and other charged particles, the effect of set-up errors on the position of isodoses is considerably less in the direction of the incident beam than it is laterally. Therefore, the margins required between the clinical target volume (CTV) and planning target volume (PTV) can be less in the direction of the incident beam than laterally. Margins have been calculated for a typical head plan and a typical prostate plan, for a single field, a parallel opposed and a four-field arrangement of protons, and compared with margins calculated for photons, assuming identical geometrical uncertainties for each modality. In the head plan, where internal motion was assumed negligible, the CTV-PTV margin reduced from approximately 10 mm to 3 mm in the axial direction for the single field and parallel opposed plans. For a prostate plan, where internal motion cannot be ignored, the corresponding reduction in margin was from 11 mm to 7 mm. The planning organ at risk (PRV) margin in the axial direction reduced from 6 mm to 2 mm for the head plan, and from 7 mm to 4 mm for the prostate plan. No reduction was seen on the other axes, or for any axis of the four-field plans. Owing to the shape of proton dose distributions, there are many clinical cases in which good dose distributions can be obtained with one or two fields. When this is done, it is possible to use smaller PTV and PRV margins. This has the potential to convert untreatable cases, in which the PTV and PRV overlap, into cases with a gap between PTV and PRV of adequate size for treatment planning

Proton therapy for pediatric cranial tumors: preliminary report on treatment and disease-related morbidities

International Nuclear Information System (INIS)

McAllister, Bruce; Archambeau, John O.; Nguyen, M. Connie; Slater, Jerry D.; Loredo, Lilia; Schulte, Reinhard; Alvarez, Ofelia; Bedros, Antranik A.; Kaleita, Thomas; Moyers, Michael; Miller, Daniel; Slater, James M.

1997-01-01

Purpose: Accelerated protons were used in an attempt to limit treatment-related morbidity in children with tumors in or near the developing brain, by reducing the integral dose to adjacent normal tissues. Methods and Materials: Children treated with protons at Loma Linda University Medical Center between August 1991 and December 1994 were analyzed retrospectively. Twenty-eight children, aged 1 to 18 years, were identified as at risk for brain injury from treatment. Medical records, physical examinations, and correspondence with patients, their parents, and referring physicians were analyzed. The investigators tabulated post-treatment changes in pre-treatment signs and symptoms and made judgments as to whether improvement, no change, or worsening related to disease or treatment had supervened. Magnetic resonance images were correlated with clinical findings and radiographic impressions were tabulated. Results: Follow-up ranged from 7 to 49 months (median 25 months). Four instances of treatment-related morbidity were identified. Forty-one instances of site-specific, disease-related morbidity were identified: 15 improved or resolved and 26 remained unchanged after treatment. Four patients had radiographic evidence of local failure. Three of these patients, including two with high-grade glioma, have died. Conclusion: Early treatment-related morbidity associated with proton therapy is low. Tumor progression remains a problem when treating certain histologies such as high-grade glioma. Escalating the dose delivered to target volumes may benefit children with tumors associated with poor rates of local control. Long-term follow-up, including neurocognitive testing, is in progress to assess integral-dose effects on cognitive, behavioral and developmental outcomes in children with cranial tumors

Determination of elemental tissue composition following proton treatment using positron emission tomography

International Nuclear Information System (INIS)

Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Min, Chul Hee; Zhu, Xuping; El Fakhri, Georges; Paganetti, Harald; Mawlawi, Osama

2013-01-01

Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. A phantom consisting of sections composed of different combinations of 1 H, 12 C, 14 N, and 16 O was irradiated using a pristine Bragg peak and a 6 cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm; the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 min in list mode. Decay curves from the activated 12 C and 16 O sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of 12 C + 16 O and calculate the relative elemental composition of 12 C and 16 O. A Monte Carlo simulation was also used to determine the elemental composition of the 12 C + 16 O section. The calculated compositions of the 12 C + 16 O section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, two patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition ( 12 C and 16 O) maps that corresponded to the proton-activated regions. We compared the 12 C and 16 O compositions of seven ROIs that corresponded to the vitreous humor, adipose

First biological experiments at a vertical proton beam

Energy Technology Data Exchange (ETDEWEB)

Distel, L; Distel, B; Roessner, B; Schwotzer, G; Sauer, R [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik fuer Strahlentherapie; Eyrich, W; Fritsch, M; Teufel, A [Erlangen-Nuernberg Univ., Erlangen (Germany). Physikalisches Inst.; Besserer, J; Boer, J de; Moosburger, M; Quicken, P [Muenchen Univ. (Germany). Sektion Physik

1997-09-01

At the tandem accelerator laboratories in Munich and Erlangen vertical beamlines were installed last year. The advantage of a vertical beamline is that cells can be irradiated in a medium at 37 C and with simultaneous gassing, therefore also in physiological conditions. First experiments were carried out at the accelerator in Munich with a proton energy of 25 MeV. Chinese Hamster cells B14 were irradiated in Petri dishes where the base was of 1 mm polystyrol or 2 {mu}m hostaphan foils. The cell survival was measured by the cell survival assay and the repopulation of the colonies by the total colony volume. A solution of DNA with protein was irradiated to study DNA double strand breaks by constant field gel electrophoresis and DNA protein crosslinks by the nitrocellulose filter assay. For cell survival, total colony volume and DNA double-strand breaks X-rays and protons gave corresponding results, while with protons, higher yields of DNA-protein crosslinks were observed than with X-rays. (orig.)

First biological experiments at a vertical proton beam

International Nuclear Information System (INIS)

Distel, L.; Distel, B.; Roessner, B.; Schwotzer, G.; Sauer, R.; Eyrich, W.; Fritsch, M.; Teufel, A.; Besserer, J.; Boer, J. de; Moosburger, M.; Quicken, P.

1997-01-01

At the tandem accelerator laboratories in Munich and Erlangen vertical beamlines were installed last year. The advantage of a vertical beamline is that cells can be irradiated in a medium at 37 C and with simultaneous gassing, therefore also in physiological conditions. First experiments were carried out at the accelerator in Munich with a proton energy of 25 MeV. Chinese Hamster cells B14 were irradiated in Petri dishes where the base was of 1 mm polystyrol or 2 μm hostaphan foils. The cell survival was measured by the cell survival assay and the repopulation of the colonies by the total colony volume. A solution of DNA with protein was irradiated to study DNA double strand breaks by constant field gel electrophoresis and DNA protein crosslinks by the nitrocellulose filter assay. For cell survival, total colony volume and DNA double-strand breaks X-rays and protons gave corresponding results, while with protons, higher yields of DNA-protein crosslinks were observed than with X-rays. (orig.)

Proton dynamics in cancer

Directory of Open Access Journals (Sweden)

Pouysségur Jacques

2010-06-01

Full Text Available Abstract Cancer remains a leading cause of death in the world today. Despite decades of research to identify novel therapeutic approaches, durable regressions of metastatic disease are still scanty and survival benefits often negligible. While the current strategy is mostly converging on target-therapies aimed at selectively affecting altered molecular pathways in tumor cells, evidences are in parallel pointing to cell metabolism as a potential Achilles' heel of cancer, to be disrupted for achieving therapeutic benefit. Critical differences in the metabolism of tumor versus normal cells, which include abnormal glycolysis, high lactic acid production, protons accumulation and reversed intra-extracellular pH gradients, make tumor site a hostile microenvironment where only cancer cells can proliferate and survive. Inhibiting these pathways by blocking proton pumps and transporters may deprive cancer cells of a key mechanism of detoxification and thus represent a novel strategy for a pleiotropic and multifaceted suppression of cancer cell growth. Research groups scattered all over the world have recently started to investigate various aspects of proton dynamics in cancer cells with quite encouraging preliminary results. The intent of unifying investigators involved in this research line led to the formation of the "International Society for Proton Dynamics in Cancer" (ISPDC in January 2010. This is the manifesto of the newly formed society where both basic and clinical investigators are called to foster translational research and stimulate interdisciplinary collaboration for the development of more specific and less toxic therapeutic strategies based on proton dynamics in tumor cell biology.

Proton therapy

International Nuclear Information System (INIS)

Smith, Alfred R

2006-01-01

Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

Proton facility economics: the importance of "simple" treatments.

Science.gov (United States)

Johnstone, Peter A S; Kerstiens, John; Richard, Helsper

2012-08-01

Given the cost and debt incurred to build a modern proton facility, impetus exists to minimize treatment of patients with complex setups because of their slower throughput. The aim of this study was to determine how many "simple" cases are necessary given different patient loads simply to recoup construction costs and debt service, without beginning to cover salaries, utilities, beam costs, and so on. Simple cases are ones that can be performed quickly because of an easy setup for the patient or because the patient is to receive treatment to just one or two fields. A "standard" construction cost and debt for 1, 3, and 4 gantry facilities were calculated from public documents of facilities built in the United States, with 100% of the construction funded through standard 15-year financing at 5% interest. Clinical best case (that each room was completely scheduled with patients over a 14-hour workday) was assumed, and a statistical analysis was modeled with debt, case mix, and payer mix moving independently. Treatment times and reimbursement data from the investigators' facility for varying complexities of patients were extrapolated for varying numbers treated daily. Revenue assumptions of $X per treatment were assumed both for pediatric cases (a mix of Medicaid and private payer) and state Medicare simple case rates. Private payer reimbursement averages $1.75X per treatment. The number of simple patients required daily to cover construction and debt service costs was then derived. A single gantry treating only complex or pediatric patients would need to apply 85% of its treatment slots simply to service debt. However, that same room could cover its debt treating 4 hours of simple patients, thus opening more slots for complex and pediatric patients. A 3-gantry facility treating only complex and pediatric cases would not have enough treatment slots to recoup construction and debt service costs at all. For a 4-gantry center, focusing on complex and pediatric cases alone

SU-F-T-169: A Periodic Quality Assurance Program for a Spot-Scanning Proton Treatment Facility

International Nuclear Information System (INIS)

Mundy, D; Tryggestad, E; Beltran, C; Furutani, K; Gilson, G; Ito, S; Johnson, J; Kruse, J; Remmes, N; Tasson, A; Whitaker, T; Herman, M

2016-01-01

Purpose: To develop daily and monthly quality assurance (QA) programs in support of a new spot-scanning proton treatment facility using a combination of commercial and custom equipment and software. Emphasis was placed on efficiency and evaluation of key quality parameters. Methods: The daily QA program was developed to test output, spot size and position, proton beam energy, and image guidance using the Sun Nuclear Corporation rf-DQA™3 device and Atlas QA software. The program utilizes standard Atlas linear accelerator tests repurposed for proton measurements and a custom jig for indexing the device to the treatment couch. The monthly QA program was designed to test mechanical performance, image quality, radiation quality, isocenter coincidence, and safety features. Many of these tests are similar to linear accelerator QA counterparts, but many require customized test design and equipment. Coincidence of imaging, laser marker, mechanical, and radiation isocenters, for instance, is verified using a custom film-based device devised and manufactured at our facility. Proton spot size and position as a function of energy are verified using a custom spot pattern incident on film and analysis software developed in-house. More details concerning the equipment and software developed for monthly QA are included in the supporting document. Thresholds for daily and monthly tests were established via perturbation analysis, early experience, and/or proton system specifications and associated acceptance test results. Results: The periodic QA program described here has been in effect for approximately 9 months and has proven efficient and sensitive to sub-clinical variations in treatment delivery characteristics. Conclusion: Tools and professional guidelines for periodic proton system QA are not as well developed as their photon and electron counterparts. The program described here efficiently evaluates key quality parameters and, while specific to the needs of our facility

SU-F-T-169: A Periodic Quality Assurance Program for a Spot-Scanning Proton Treatment Facility

Energy Technology Data Exchange (ETDEWEB)

Mundy, D; Tryggestad, E; Beltran, C; Furutani, K; Gilson, G; Ito, S; Johnson, J; Kruse, J; Remmes, N; Tasson, A; Whitaker, T; Herman, M [Mayo Clinic, Rochester, MN (United States)

2016-06-15

Purpose: To develop daily and monthly quality assurance (QA) programs in support of a new spot-scanning proton treatment facility using a combination of commercial and custom equipment and software. Emphasis was placed on efficiency and evaluation of key quality parameters. Methods: The daily QA program was developed to test output, spot size and position, proton beam energy, and image guidance using the Sun Nuclear Corporation rf-DQA™3 device and Atlas QA software. The program utilizes standard Atlas linear accelerator tests repurposed for proton measurements and a custom jig for indexing the device to the treatment couch. The monthly QA program was designed to test mechanical performance, image quality, radiation quality, isocenter coincidence, and safety features. Many of these tests are similar to linear accelerator QA counterparts, but many require customized test design and equipment. Coincidence of imaging, laser marker, mechanical, and radiation isocenters, for instance, is verified using a custom film-based device devised and manufactured at our facility. Proton spot size and position as a function of energy are verified using a custom spot pattern incident on film and analysis software developed in-house. More details concerning the equipment and software developed for monthly QA are included in the supporting document. Thresholds for daily and monthly tests were established via perturbation analysis, early experience, and/or proton system specifications and associated acceptance test results. Results: The periodic QA program described here has been in effect for approximately 9 months and has proven efficient and sensitive to sub-clinical variations in treatment delivery characteristics. Conclusion: Tools and professional guidelines for periodic proton system QA are not as well developed as their photon and electron counterparts. The program described here efficiently evaluates key quality parameters and, while specific to the needs of our facility

Proton Therapy Coverage for Prostate Cancer Treatment

International Nuclear Information System (INIS)

Vargas, Carlos; Wagner, Marcus; Mahajan, Chaitali; Indelicato, Daniel; Fryer, Amber; Falchook, Aaron; Horne, David C.; Chellini, Angela; McKenzie, Craig C.; Lawlor, Paula C.; Li Zuofeng; Lin Liyong; Keole, Sameer

2008-01-01

Purpose: To determine the impact of prostate motion on dose coverage in proton therapy. Methods and Materials: A total of 120 prostate positions were analyzed on 10 treatment plans for 10 prostate patients treated using our low-risk proton therapy prostate protocol (University of Florida Proton Therapy Institute 001). Computed tomography and magnetic resonance imaging T 2 -weighted turbo spin-echo scans were registered for all cases. The planning target volume included the prostate with a 5-mm axial and 8-mm superoinferior expansion. The prostate was repositioned using 5- and 10-mm one-dimensional vectors and 10-mm multidimensional vectors (Points A-D). The beam was realigned for the 5- and 10-mm displacements. The prescription dose was 78 Gy equivalent (GE). Results: The mean percentage of rectum receiving 70 Gy (V 70 ) was 7.9%, the bladder V 70 was 14.0%, and the femoral head/neck V 50 was 0.1%, and the mean pelvic dose was 4.6 GE. The percentage of prostate receiving 78 Gy (V 78 ) with the 5-mm movements changed by -0.2% (range, 0.006-0.5%, p > 0.7). However, the prostate V 78 after a 10-mm displacement changed significantly (p 78 coverage had a large and significant reduction of 17.4% (range, 13.5-17.4%, p 78 coverage of the clinical target volume. The minimal prostate dose was reduced 33% (25.8 GE), on average, for Points A-D. The prostate minimal dose improved from 69.3 GE to 78.2 GE (p < 0.001) with realignment for 10-mm movements. Conclusion: The good dose coverage and low normal doses achieved for the initial plan was maintained with movements of ≤5 mm. Beam realignment improved coverage for 10-mm displacements

Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

International Nuclear Information System (INIS)

Gomez, Daniel R.; Liao, Kai-Ping; Swisher, Stephen G.; Blumenschein, George R.; Erasmus, Jeremy J.; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

2015-01-01

Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

TU-G-BRCD-01: Will the High Cost of Proton Therapy Facilities Limit the Availability of Proton Therapy Treatment?

Science.gov (United States)

Maughan, R

2012-06-01

The potential dose distribution advantages associated with proton therapy, and particularly with pencil beam scanning (PBS) techniques, have lead to considerable interest in this modality in recent years. However, the large capital expenditure necessary for such a project requires careful financial consideration and business planning. The complexity of the beam delivery systems impacts the capital expenditure and the PBS only systems presently being advocated can reduce these costs. Also several manufacturers are considering "one-room" facilities as less expensive alternatives to multi-room facilities. This presentation includes a brief introduction to beam delivery options (passive scattering, uniform and modulated scanning) and some of the new technologies proposed for providing less expensive proton therapy systems. Based on current experience, data on proton therapy center start-up costs, running costs and the financial challenges associated with making this highly conformal therapy more widely available will be discussed. Issues associated with proton therapy implementation that are key to project success include strong project management, vendor cooperation and collaboration, staff recruitment and training. Time management during facility start up is a major concern, particularly in multi-room systems, where time must be shared between continuing vendor system validation, verification and acceptance testing, and user commissioning and patient treatments. The challenges associated with facility operation during this period and beyond are discussed, focusing on how standardization of process, downtime and smart scheduling can influence operational efficiency. 1. To understand the available choices for proton therapy facilities, the different beam delivery systems and the financial implications associated with these choices. 2. To understand the key elements necessary for successfully implementing a proton therapy program. 3. To understand the challenges

Impact of different treatment methods on survival in advanced pancreatic cancer

International Nuclear Information System (INIS)

Brasiuniene, B.; Juozaityte, E.; Barauskas, G.

2005-01-01

The aim of the study was to evaluate the impact of different treatment methods on survival of patients treated for advanced pancreatic cancer at Kaunas University of Medicine Hospital from 1987 to 2003. Data on 262 patients with advanced pancreatic cancer treated from 1987 to 2003 were analyzed retrospectively. Four groups of patients were analyzed. One hundred eighty patients underwent palliative bypass or endoscopic bile duct stenting or observation alone. Forty three patients in addition to surgery were treated by radiotherapy. Twenty five patients received gemcitabine in standard doses and schedules. Fourteen patients received concomitant chemoradiotherapy (with gemcitabine or 5-fluorouracil). All patients were grouped by treatment method and median survival was analyzed. Median survival of patients treated by palliative surgery only or observation alone was 1.9 month, and for patients treated by palliative surgery and radiotherapy was 6.1 months (p=0.00007). Median survival of patients treated with gemcitabine was 9.5 months (p<0.001), and median survival of patients treated with concomitant chemoradiotherapy was 8.5 months (p=0.00003). Patients diagnosed with advanced pancreatic cancer in addition to surgical treatment should be treated by chemotherapy, concomitant chemoradiotherapy or radiotherapy. (author)

Proteomic analysis of proton beam irradiated human melanoma cells.

Directory of Open Access Journals (Sweden)

Sylwia Kedracka-Krok

Full Text Available Proton beam irradiation is a form of advanced radiotherapy providing superior distributions of a low LET radiation dose relative to that of photon therapy for the treatment of cancer. Even though this clinical treatment has been developing for several decades, the proton radiobiology critical to the optimization of proton radiotherapy is far from being understood. Proteomic changes were analyzed in human melanoma cells treated with a sublethal dose (3 Gy of proton beam irradiation. The results were compared with untreated cells. Two-dimensional electrophoresis was performed with mass spectrometry to identify the proteins. At the dose of 3 Gy a minimal slowdown in proliferation rate was seen, as well as some DNA damage. After allowing time for damage repair, the proteomic analysis was performed. In total 17 protein levels were found to significantly (more than 1.5 times change: 4 downregulated and 13 upregulated. Functionally, they represent four categories: (i DNA repair and RNA regulation (VCP, MVP, STRAP, FAB-2, Lamine A/C, GAPDH, (ii cell survival and stress response (STRAP, MCM7, Annexin 7, MVP, Caprin-1, PDCD6, VCP, HSP70, (iii cell metabolism (TIM, GAPDH, VCP, and (iv cytoskeleton and motility (Moesin, Actinin 4, FAB-2, Vimentin, Annexin 7, Lamine A/C, Lamine B. A substantial decrease (2.3 x was seen in the level of vimentin, a marker of epithelial to mesenchymal transition and the metastatic properties of melanoma.

Relative biological effectiveness of high energy protons for a human melanoma

International Nuclear Information System (INIS)

Petrovic, I.; Ristic-Fira, A.; Todorovic, D.; Valastro, I.; Cirrone, P.; Cuttone, G.

2005-01-01

Relative biological effectiveness (RBE) for the survival of human melanoma cells induced by high linear energy transfer (LET) protons was investigated. Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons, as well as with 60 Co γ-rays, over single doses, ranging from 8-24 Gy. Clonogenic survival and cell viability were assessed up to 48 h post-irradiation, therefore considered as early inactivation effects. Dose dependent cell inactivation induced by high LET protons was observed. Surviving fractions have shown great overlapping with estimated cell viability, both with the increase of dose and with prolonged cell incubation. Evaluated RBEs were higher with the rise of dose, being in the range from 2 to 3. All analyzes performed have demonstrated a very radio-resistant nature of HTB140 melanoma cells. However, high LET protons are able to inactivate these cells in a larger extent compared to the effects of γ-rays. (author)

FoCa: a modular treatment planning system for proton radiotherapy with research and educational purposes.

Science.gov (United States)

Sánchez-Parcerisa, D; Kondrla, M; Shaindlin, A; Carabe, A

2014-12-07

FoCa is an in-house modular treatment planning system, developed entirely in MATLAB, which includes forward dose calculation of proton radiotherapy plans in both active and passive modalities as well as a generic optimization suite for inverse treatment planning. The software has a dual education and research purpose. From the educational point of view, it can be an invaluable teaching tool for educating medical physicists, showing the insights of a treatment planning system from a well-known and widely accessible software platform. From the research point of view, its current and potential uses range from the fast calculation of any physical, radiobiological or clinical quantity in a patient CT geometry, to the development of new treatment modalities not yet available in commercial treatment planning systems. The physical models in FoCa were compared with the commissioning data from our institution and show an excellent agreement in depth dose distributions and longitudinal and transversal fluence profiles for both passive scattering and active scanning modalities. 3D dose distributions in phantom and patient geometries were compared with a commercial treatment planning system, yielding a gamma-index pass rate of above 94% (using FoCa's most accurate algorithm) for all cases considered. Finally, the inverse treatment planning suite was used to produce the first prototype of intensity-modulated, passive-scattered proton therapy, using 13 passive scattering proton fields and multi-leaf modulation to produce a concave dose distribution on a cylindrical solid water phantom without any field-specific compensator.

Rare vulvar malignancies; incidence, treatment and survival in the Netherlands

NARCIS (Netherlands)

Pleunis, N.; Schuurman, M.S.; Rossum, M.M. van; Bulten, J.; Massuger, L.F.A.G.; Hullu, J.A. de; Aa, M.A. van der

2016-01-01

OBJECTIVE: To describe trends in incidence, treatment and survival of patients with basal cell carcinomas and melanomas of the vulva. Also to compare survival of vulvar and cutaneous melanoma patients. METHODS: All women with a vulvar malignancy between 1989 and 2012 were selected from the Dutch

Treatment planning study comparing proton therapy, RapidArc and intensity modulated radiation therapy for a synchronous bilateral lung cancer case

Directory of Open Access Journals (Sweden)

Suresh Rana

2014-03-01

Full Text Available Purpose: The main purpose of this study is to perform a treatment planning study on a synchronous bilateral non-small cell lung cancer case using three treatment modalities: uniform scanning proton therapy, RapidArc, and intensity modulated radiation therapy (IMRT. Methods: The maximum intensity projection (MIP images obtained from the 4 dimensional-computed tomography (4DCT scans were used for delineation of tumor volumes in the left and right lungs. The average 4D-CT was used for the treatment planning among all three modalities with identical patient contouring and treatment planning goal. A proton therapy plan was generated in XiO treatment planning system (TPS using 2 fields for each target. For a comparative purpose, IMRT and RapidArc plans were generated in Eclipse TPS. Treatment plans were generated for a total dose of 74 CGE or Gy prescribed to each planning target volume (PTV (left and right with 2 CGE or Gy per fraction. In IMRT and RapidArc plans, normalization was done based on PTV coverage values in proton plans. Results: The mean PTV dose deviation from the prescription dose was lower in proton plan (within 3.4%, but higher in IMRT (6.5% to 11.3% and RapidArc (3.8% to 11.5% plans. Proton therapy produced lower mean dose to the total lung, heart, and esophagus when compared to IMRT and RapidArc. The relative volume of the total lung receiving 20, 10, and 5 CGE or Gy (V20, V10, and V5, respectively were lower using proton therapy than using IMRT, with absolute differences of 9.71%, 22.88%, and 39.04%, respectively. The absolute differences in the V20, V10, and V5 between proton and RapidArc plans were 4.84%, 19.16%, and 36.8%, respectively, with proton therapy producing lower dosimetric values. Conclusion: Based on the results presented in this case study, uniform scanning proton therapy has a dosimetric advantage over both IMRT and RapidArc for a synchronous bi-lateral NSCLC, especially for the normal lung tissue, heart, and

Relative biological effectiveness of the therapeutic proton beams at NIRS and Tsukuba University

International Nuclear Information System (INIS)

Ando, Koichi; Koike, Sachiko; Kawachi, Kiyomitsu

1985-01-01

Relative biological effectiveness (RBE) of proton beams dedicated to radiotherapy was examined using a method of simultaneous irradiation. Mice received i.v. transplantation of syngeneic fibrosarcoma (NFSa) cells. These mice were divided into 3 groups on the following day, and thorax was simultaneously irradiated with one of the following beams: 70MeV proton beam at National Institute of Radiological Sciences (NIRS), 250 MeV Proton beam at Tsukuba University (PARMS) and 60 Co γ ray. Ten to 13 days thereafter, lungs were removed for colony counts to give dose-cell survival relationships. RBE of NIRS proton was ranging from 1.01 to 1.12 with an average of 1.06 while that of PARMS proton was ranging from 1.03 to 1.09 with an average of 1.06 at surviving fraction of 0.01. The simultaneous irradiation for RBE study was found to be reliable at large dose-low survival regions. (author)

Characterization of the microbunch time structure of proton pencil beams at a clinical treatment facility.

Science.gov (United States)

Petzoldt, J; Roemer, K E; Enghardt, W; Fiedler, F; Golnik, C; Hueso-González, F; Helmbrecht, S; Kormoll, T; Rohling, H; Smeets, J; Werner, T; Pausch, G

2016-03-21

Proton therapy is an advantageous treatment modality compared to conventional radiotherapy. In contrast to photons, charged particles have a finite range and can thus spare organs at risk. Additionally, the increased ionization density in the so-called Bragg peak close to the particle range can be utilized for maximum dose deposition in the tumour volume. Unfortunately, the accuracy of the therapy can be affected by range uncertainties, which have to be covered by additional safety margins around the treatment volume. A real-time range and dose verification is therefore highly desired and would be key to exploit the major advantages of proton therapy. Prompt gamma rays, produced in nuclear reactions between projectile and target nuclei, can be used to measure the proton's range. The prompt gamma-ray timing (PGT) method aims at obtaining this information by determining the gamma-ray emission time along the proton path using a conventional time-of-flight detector setup. First tests at a clinical accelerator have shown the feasibility to observe range shifts of about 5 mm at clinically relevant doses. However, PGT spectra are smeared out by the bunch time spread. Additionally, accelerator related proton bunch drifts against the radio frequency have been detected, preventing a potential range verification. At OncoRay, first experiments using a proton bunch monitor (PBM) at a clinical pencil beam have been conducted. Elastic proton scattering at a hydrogen-containing foil could be utilized to create a coincident proton-proton signal in two identical PBMs. The selection of coincident events helped to suppress uncorrelated background. The PBM setup was used as time reference for a PGT detector to correct for potential bunch drifts. Furthermore, the corrected PGT data were used to image an inhomogeneous phantom. In a further systematic measurement campaign, the bunch time spread and the proton transmission rate were measured for several beam energies between 69 and 225 Me

Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

Energy Technology Data Exchange (ETDEWEB)

McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

2014-11-15

Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

DoPET: an in-treatment monitoring system for proton therapy at 62 MeV

Science.gov (United States)

Rosso, V.; Belcari, N.; Bisogni, M. G.; Camarlinghi, N.; Cirrone, G. A. P.; Collini, F.; Cuttone, G.; Del Guerra, A.; Milluzzo, G.; Morrocchi, M.; Raffaele, L.; Romano, F.; Sportelli, G.; Zaccaro, E.

2016-12-01

Proton beam radiotherapy is highly effective in treating cancer thanks to its conformal dose deposition. This superior capability in dose deposition has led to a massive growth of the treated patients around the world, raising the need of treatment monitoring systems. An in-treatment PET system, DoPET, was constructed and tested at CATANA beam-line, LNS-INFN in Catania, where 62 MeV protons are used to treat ocular melanoma. The PET technique profits from the beta+ emitters generated by the proton beam in the irradiated body, mainly 15-O and 11-C. The current DoPET prototype consists of two planar 15 cm × 15 cm LYSO-based detector heads. With respect to the previous versions, the system was enlarged and the DAQ up-graded during the years so now also anthropomorphic phantoms, can be fitted within the field of view of the system. To demonstrate the capability of DoPET to detect changes in the delivered treatment plan with respect to the planned one, various treatment plans were used delivering a standard 15 Gy fraction to an anthropomorphic phantom. Data were acquired during and after the treatment delivery up to 10 minutes. When the in-treatment phase was long enough (more than 1 minute), the corresponding activated volume was visible just after the treatment delivery, even if in presence of a noisy background. The after-treatment data, acquired for about 9 minutes, were segmented finding that few minutes are enough to be able to detect changes. These experiments will be presented together with the studies performed with PMMA phantoms where the DoPET response was characterized in terms of different dose rates and in presence of range shifters: the system response is linear up to 16.9 Gy/min and has the ability to see a 1 millimeter range shifter.

DoPET: an in-treatment monitoring system for proton therapy at 62 MeV

International Nuclear Information System (INIS)

Rosso, V.; Belcari, N.; Bisogni, M.G.; Camarlinghi, N.; Guerra, A. Del; Morrocchi, M.; Sportelli, G.; Zaccaro, E.; Cirrone, G.A.P.; Cuttone, G.; Milluzzo, G.; Raffaele, L.; Romano, F.; Collini, F.

2016-01-01

Proton beam radiotherapy is highly effective in treating cancer thanks to its conformal dose deposition. This superior capability in dose deposition has led to a massive growth of the treated patients around the world, raising the need of treatment monitoring systems. An in-treatment PET system, DoPET, was constructed and tested at CATANA beam-line, LNS-INFN in Catania, where 62 MeV protons are used to treat ocular melanoma. The PET technique profits from the beta+ emitters generated by the proton beam in the irradiated body, mainly 15-O and 11-C. The current DoPET prototype consists of two planar 15 cm × 15 cm LYSO-based detector heads. With respect to the previous versions, the system was enlarged and the DAQ up-graded during the years so now also anthropomorphic phantoms, can be fitted within the field of view of the system. To demonstrate the capability of DoPET to detect changes in the delivered treatment plan with respect to the planned one, various treatment plans were used delivering a standard 15 Gy fraction to an anthropomorphic phantom. Data were acquired during and after the treatment delivery up to 10 minutes. When the in-treatment phase was long enough (more than 1 minute), the corresponding activated volume was visible just after the treatment delivery, even if in presence of a noisy background. The after-treatment data, acquired for about 9 minutes, were segmented finding that few minutes are enough to be able to detect changes. These experiments will be presented together with the studies performed with PMMA phantoms where the DoPET response was characterized in terms of different dose rates and in presence of range shifters: the system response is linear up to 16.9 Gy/min and has the ability to see a 1 millimeter range shifter.

A study of V79 cell survival after for proton and carbon ion beams as represented by the parameters of Katz' track structure model

DEFF Research Database (Denmark)

Grzanka, Leszek; Waligórski, M. P. R.; Bassler, Niels

different sets of data obtained for the same cell line and different ions, measured at different laboratories, we have fitted model parameters to a set of carbon-irradiated V79 cells, published by Furusawa et al. (2), and to a set of proton-irradiated V79 cells, published by Wouters et al. (3), separately....... We found that values of model parameters best fitted to the carbon data of Furusawa et al. yielded predictions of V79 survival after proton irradiation which did not match the V79 proton data of Wouters et al. Fitting parameters to both sets combined did not improve the accuracy of model predictions...... carbon irradiation. 1. Katz, R., Track structure in radiobiology and in radiation detection. Nuclear Track Detection 2: 1-28 (1978). 2. Furusawa Y. et al. Inactivation of aerobic and hypoxic cells from three different cell lines by accelerated 3He-, 12C- and 20Ne beams. Radiat Res. 2012 Jan; 177...

Proton energy and scattering angle radiographs to improve proton treatment planning : a Monte Carlo study

NARCIS (Netherlands)

Biegun, Aleksandra; Takatsu, Jun; Nakaji, Taku; van Goethem, Marc-Jan; van der Graaf, Emiel; Koffeman, E.; Visser, Jan; Brandenburg, Sijtze

2016-01-01

The novel proton radiography imaging technique has a large potential to be used in direct measurement of the proton energy loss (proton stopping power, PSP) in various tissues in the patient. The uncertainty of PSPs, currently obtained from translation of X-ray Computed Tomography (xCT) images,

Treatment planning with ion beams

International Nuclear Information System (INIS)

Foss, M.H.

1985-01-01

Ions have higher linear energy transfer (LET) near the end of their range and lower LET away from the end of their range. Mixing radiations of different LET complicates treatment planning because radiation kills cells in two statistically independent ways. In some cases, cells are killed by a single-particle, which causes a linear decrease in log survival at low dosage. When the linear decrease is subtracted from the log survival curve, the remaining curve has zero slope at zero dosage. This curve is the log survival curve for cells that are killed only by two or more particles. These two mechanisms are statistically independent. To calculate survival, these two kinds of doses must be accumulated separately. The effect of each accumulated dosage must be read from its survival curve, and the logarithms of the two effects added to get the log survival. Treatment plans for doses of protons, He 3 ions, and He 4 ions suggest that these ions will be useful therapeutic modalities

Implementation of pencil kernel and depth penetration algorithms for treatment planning of proton beams

International Nuclear Information System (INIS)

Russell, K.R.; Saxner, M.; Ahnesjoe, A.; Montelius, A.; Grusell, E.; Dahlgren, C.V.

2000-01-01

The implementation of two algorithms for calculating dose distributions for radiation therapy treatment planning of intermediate energy proton beams is described. A pencil kernel algorithm and a depth penetration algorithm have been incorporated into a commercial three-dimensional treatment planning system (Helax-TMS, Helax AB, Sweden) to allow conformal planning techniques using irregularly shaped fields, proton range modulation, range modification and dose calculation for non-coplanar beams. The pencil kernel algorithm is developed from the Fermi-Eyges formalism and Moliere multiple-scattering theory with range straggling corrections applied. The depth penetration algorithm is based on the energy loss in the continuous slowing down approximation with simple correction factors applied to the beam penumbra region and has been implemented for fast, interactive treatment planning. Modelling of the effects of air gaps and range modifying device thickness and position are implicit to both algorithms. Measured and calculated dose values are compared for a therapeutic proton beam in both homogeneous and heterogeneous phantoms of varying complexity. Both algorithms model the beam penumbra as a function of depth in a homogeneous phantom with acceptable accuracy. Results show that the pencil kernel algorithm is required for modelling the dose perturbation effects from scattering in heterogeneous media. (author)

WE-E-BRB-03: Implementation of PBS Proton Therapy Treatment for Free Breathing Lung Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Li, H. [UT MD Anderson Cancer Center (United States)

2016-06-15

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed. Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and

WE-E-BRB-02: Implementation of Pencil Beam Scanning (PBS) Proton Therapy Treatment for Liver Patient

Energy Technology Data Exchange (ETDEWEB)

Lin, L. [University of Pennsylvania (United States)

2016-06-15

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed. Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and

WE-E-BRB-03: Implementation of PBS Proton Therapy Treatment for Free Breathing Lung Cancer Patients

International Nuclear Information System (INIS)

Li, H.

2016-01-01

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed. Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and

WE-E-BRB-02: Implementation of Pencil Beam Scanning (PBS) Proton Therapy Treatment for Liver Patient

International Nuclear Information System (INIS)

Lin, L.

2016-01-01

Strategies for treating thoracic and liver tumors using pencil beam scanning proton therapy Thoracic and liver tumors have not been treated with pencil beam scanning (PBS) proton therapy until recently. This is because of concerns about the significant interplay effects between proton spot scanning and patient’s respiratory motion. However, not all tumors have unacceptable magnitude of motion for PBS proton therapy. Therefore it is important to analyze the motion and understand the significance of the interplay effect for each patient. The factors that affect interplay effect and its washout include magnitude of motion, spot size, spot scanning sequence and speed. Selection of beam angle, scanning direction, repainting and fractionation can all reduce the interplay effect. An overview of respiratory motion management in PBS proton therapy including assessment of tumor motion and WET evaluation will be first presented. As thoracic tumors have very different motion patterns from liver tumors, examples would be provided for both anatomic sites. As thoracic tumors are typically located within highly heterogeneous environments, dose calculation accuracy is a concern for both treatment target and surrounding organs such as spinal cord or esophagus. Strategies for mitigating the interplay effect in PBS will be presented and the pros and cons of various motion mitigation strategies will be discussed. Learning Objectives: Motion analysis for individual patients with respect to interplay effect Interplay effect and mitigation strategies for treating thoracic/liver tumors with PBS Treatment planning margins for PBS The impact of proton dose calculation engines over heterogeneous treatment target and surrounding organs I have a current research funding from Varian Medical System under the master agreement between University of Pennsylvania and Varian; L. Lin, I have a current funding from Varian Medical System under the master agreement between University of Pennsylvania and

Clinical results of proton beam therapy for skull base chordoma

International Nuclear Information System (INIS)

Igaki, Hiroshi; Tokuuye, Koichi; Okumura, Toshiyuki; Sugahara, Shinji; Kagei, Kenji; Hata, Masaharu; Ohara, Kiyoshi; Hashimoto, Takayuki; Tsuboi, Koji; Takano, Shingo; Matsumura, Akira; Akine, Yasuyuki

2004-01-01

Purpose: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. Methods and materials: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). Results: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. Conclusion: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy

Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

International Nuclear Information System (INIS)

Nikoghosyan, Anna V; Rauch, Geraldine; Münter, Marc W; Jensen, Alexandra D; Combs, Stephanie E; Kieser, Meinhard; Debus, Jürgen

2010-01-01

Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours. The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial. Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points. Up to now it was impossible to compare two different

WE-D-BRB-00: Basics of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

WE-D-BRB-00: Basics of Proton Therapy

International Nuclear Information System (INIS)

2016-01-01

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

Proton radiotherapy for chest wall and regional lymphatic radiation; dose comparisons and treatment delivery

International Nuclear Information System (INIS)

MacDonald, Shannon M; Jimenez, Rachel; Paetzold, Peter; Adams, Judith; Beatty, Jonathan; DeLaney, Thomas F; Kooy, Hanne; Taghian, Alphonse G; Lu, Hsiao-Ming

2013-01-01

The delivery of post-mastectomy radiation therapy (PMRT) can be challenging for patients with left sided breast cancer that have undergone mastectomy. This study investigates the use of protons for PMRT in selected patients with unfavorable cardiac anatomy. We also report the first clinical application of protons for these patients. Eleven patients were planned with protons, partially wide tangent photon fields (PWTF), and photon/electron (P/E) fields. Plans were generated with the goal of achieving 95% coverage of target volumes while maximally sparing cardiac and pulmonary structures. In addition, we report on two patients with unfavorable cardiac anatomy and IMN involvement that were treated with a mix of proton and standard radiation. PWTF, P/E, and proton plans were generated and compared. Reasonable target volume coverage was achieved with PWTF and P/E fields, but proton therapy achieved superior coverage with a more homogeneous plan. Substantial cardiac and pulmonary sparing was achieved with proton therapy as compared to PWTF and P/E. In the two clinical cases, the delivery of proton radiation with a 7.2 to 9 Gy photon and electron component was feasible and well tolerated. Akimbo positioning was necessary for gantry clearance for one patient; the other was treated on a breast board with standard positioning (arms above her head). LAO field arrangement was used for both patients. Erythema and fatigue were the only noted side effects. Proton RT enables delivery of radiation to the chest wall and regional lymphatics, including the IMN, without compromise of coverage and with improved sparing of surrounding normal structures. This treatment is feasible, however, optimal patient set up may vary and field size is limited without multiple fields/matching

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation. I. Initial characterization of DNA damage, micronucleus formation, apoptosis, cell survival, and cell cycle phase redistribution

Science.gov (United States)

Green, L. M.; Murray, D. K.; Bant, A. M.; Kazarians, G.; Moyers, M. F.; Nelson, G. A.; Tran, D. T.

2001-01-01

The RBE of protons has been assumed to be equivalent to that of photons. The objective of this study was to determine whether radiation-induced DNA and chromosome damage, apoptosis, cell killing and cell cycling in organized epithelial cells was influenced by radiation quality. Thyroid-stimulating hormone-dependent Fischer rat thyroid cells, established as follicles, were exposed to gamma rays or proton beams delivered acutely over a range of physical doses. Gamma-irradiated cells were able to repair DNA damage relatively rapidly so that by 1 h postirradiation they had approximately 20% fewer exposed 3' ends than their counterparts that had been irradiated with proton beams. The persistence of free ends of DNA in the samples irradiated with the proton beam implies that either more initial breaks or a quantitatively different type of damage had occurred. These results were further supported by an increased frequency of chromosomal damage as measured by the presence of micronuclei. Proton-beam irradiation induced micronuclei at a rate of 2.4% per gray, which at 12 Gy translated to 40% more micronuclei than in comparable gamma-irradiated cultures. The higher rate of micronucleus formation and the presence of larger micronuclei in proton-irradiated cells was further evidence that a qualitatively more severe class of damage had been induced than was induced by gamma rays. Differences in the type of damage produced were detected in the apoptosis assay, wherein a significant lag in the induction of apoptosis occurred after gamma irradiation that did not occur with protons. The more immediate expression of apoptotic cells in the cultures irradiated with the proton beam suggests that the damage inflicted was more severe. Alternatively, the cell cycle checkpoint mechanisms required for recovery from such damage might not have been invoked. Differences based on radiation quality were also evident in the alpha components of cell survival curves (0.05 Gy(-1) for gamma rays, 0

Proton magnetic resonance spectroscopy (1H-MRS) for the evaluation of treatment of brain tumours

International Nuclear Information System (INIS)

Houkin, K.; Kamada, K.; Sawamura, Y.; Iwasaki, Y.; Abe, H.; Kashiwaba, T.

1995-01-01

We investigated metabolic changes in brain tumours following treatment, using proton magnetic resonance spectroscopy. In meningiomas, effective therapeutic embolisation led to an acute increase in lactate. In radiosensitive tumours such as malignant lymphoma, a decrease in lactate and in increase in N-acetyl-aspartate occurred after radiotherapy, which preceded changes observed on magnetic resonance imaging. On the other hand, no significant changes in spectral patterns were observed in malignant gliomas resistant to therapy. Tissue characterisation of brain tumours by spectral patterns on proton magnetic resonance spectroscopy remains controversial. However, we have shown it to be sensitive to metabolic changes following treatment, which may reflect the efficacy of the therapy. (orig.)

Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

Energy Technology Data Exchange (ETDEWEB)

Water, Steven van de, E-mail: s.vandewater@erasmusmc.nl [Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands); Kooy, Hanne M. [F. H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Heijmen, Ben J.M.; Hoogeman, Mischa S. [Department of Radiation Oncology, Erasmus MC Cancer Institute, Rotterdam (Netherlands)

2015-06-01

Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

Clinical equipoise: protons and the child with craniopharyngioma

International Nuclear Information System (INIS)

Conroy, Ruth; Owen, Catherine; Ahern, Verity; Gomes, Lavier; Buchsbaum, Jeremy

2015-01-01

Childhood craniopharyngioma is a complex condition to manage. Survival figures are high but the potential for long-term morbidity is great. There is much debate regarding the best management for these tumours with increasing interest in the use of proton beam therapy. We have therefore reviewed our radiotherapy (RT) practice at Westmead Hospital and the literature regarding the use of protons for these children. Three children have received fractionated stereotactic RT for craniopharyngioma at Westmead Hospital since 2007. Each RT plan was reviewed and additional organs at risk were contoured to enable comparison with published proton data. Planning target volume coverage was similar with all modalities: with the conformity index ranging from 0.70 to 0.78 in our patients compared with 0.50–0.84 in the published data. RT dose to temporal lobes, hippocampi and whole brain was also similar with protons and photons. Proton beam therapy may give lower dose to the Circle of Willis than stereotactic RT. Currently there is no clear evidence that proton beam therapy will improve survival or reduce morbidity for children with craniopharyngioma. However, proton therapy has the potential to reduce RT dose to the Circle of Willis, which may reduce the risk of future cerebrovascular complications. We propose that more resources should be allocated to ensuring these patients are managed by experienced multidisciplinary teams through the continuum from diagnosis to long-term follow-up.

Clinical equipoise: Protons and the child with craniopharyngioma.

Science.gov (United States)

Conroy, Ruth; Gomes, Lavier; Owen, Catherine; Buchsbaum, Jeffrey; Ahern, Verity

2015-06-01

Childhood craniopharyngioma is a complex condition to manage. Survival figures are high but the potential for long-term morbidity is great. There is much debate regarding the best management for these tumours with increasing interest in the use of proton beam therapy. We have therefore reviewed our radiotherapy (RT) practice at Westmead Hospital and the literature regarding the use of protons for these children. Three children have received fractionated stereotactic RT for craniopharyngioma at Westmead Hospital since 2007. Each RT plan was reviewed and additional organs at risk were contoured to enable comparison with published proton data. Planning target volume coverage was similar with all modalities: with the conformity index ranging from 0.70 to 0.78 in our patients compared with 0.50-0.84 in the published data. RT dose to temporal lobes, hippocampi and whole brain was also similar with protons and photons. Proton beam therapy may give lower dose to the Circle of Willis than stereotactic RT. Currently there is no clear evidence that proton beam therapy will improve survival or reduce morbidity for children with craniopharyngioma. However, proton therapy has the potential to reduce RT dose to the Circle of Willis, which may reduce the risk of future cerebrovascular complications. We propose that more resources should be allocated to ensuring these patients are managed by experienced multidisciplinary teams through the continuum from diagnosis to long-term follow-up. © 2014 The Royal Australian and New Zealand College of Radiologists.

Proton channels and exchangers in cancer.

Science.gov (United States)

Spugnini, Enrico Pierluigi; Sonveaux, Pierre; Stock, Christian; Perez-Sayans, Mario; De Milito, Angelo; Avnet, Sofia; Garcìa, Abel Garcìa; Harguindey, Salvador; Fais, Stefano

2015-10-01

Although cancer is characterized by an intratumoral genetic heterogeneity, a totally deranged pH control is a common feature of most cancer histotypes. Major determinants of aberrant pH gradient in cancer are proton exchangers and transporters, including V-ATPase, Na+/H+ exchanger (NHE), monocarboxylate transporters (MCTs) and carbonic anhydrases (CAs). Thanks to the activity of these proton transporters and exchangers, cancer becomes isolated and/or protected not only from the body reaction against the growing tumor, but also from the vast majority of drugs that when protonated into the acidic tumor microenvironment do not enter into cancer cells. Proton transporters and exchangers represent a key feature tumor cells use to survive in the very hostile microenvironmental conditions that they create and maintain. Detoxifying mechanisms may thus represent both a key survival option and a selection outcome for cells that behave as unicellular microorganisms rather than belonging to an organ, compartment or body. It is, in fact, typical of malignant tumors that, after a clinically measurable yet transient initial response to a therapy, resistant tumor clones emerge and proliferate, thus bursting a more malignant behavior and rapid tumor progression. This review critically presents the background of a novel and efficient approach that aims to fight cancer through blocking or inhibiting well characterized proton exchangers and transporters active in human cancer cells. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

Mutation breeding of rape by using proton ion beam

International Nuclear Information System (INIS)

Eun, J. S.; Chang, Y. S.; Han, S. G.; Choi, S. R.; Kim, J. S.

2006-04-01

This experiment was carried out by irradiation the proton ion beam and gamma-ray at level 100 to 2,000 Gy on dry seeds of 3 varieties, 'Naehan', 'Hanla' and 'Tammi' to increase the cultivation area and develope for biodiesel in rape (Brassica napus) and checked the radiosensitivity test including germination rate, emergence rate and chromosome aberration and the occurrence of morphological mutant in M1 generation. The germination rate and emergence rate were 98∼100% because they had no relation with radiation source, dosage and variety. There was no significance in survival rate up to 1,000 Gy dosage after sowing of 7 days and remarkably reduced from 39.5 to 69.6% at 1,500 to 2,000 Gy dosage. The length and area of cotyledon, and hypocotyl length were highly reduced with significance by increasing dosage of proton ion and gamma-irradiation in all 3 varieties and showed the sensitive responses on 'Naehan', 'Hanla' and 'Tammi' in order. By the way, there was a radiation hormesis in 'Tammi' by increasing the length and area of cotyledon in the proton ion treatment at 100∼200 Gy dosage compared to the control (no treatment). With the same effect, it had the similar results in the fresh weight of above-aerial parts in 3∼4 weeks after sowing

Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

Science.gov (United States)

Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

2016-07-01

Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma.

Science.gov (United States)

Guttmann, David M; Frick, Melissa A; Carmona, Ruben; Deville, Curtiland; Levin, William P; Berman, Abigail T; Chinniah, Chidambaram; Hahn, Stephen M; Plastaras, John P; Simone, Charles B

2017-08-01

Proton reirradiation for sarcoma has not been previously described. We hypothesized that this strategy would provide favorable toxicity and survival outcomes. Patients with soft tissue sarcoma in a previously-irradiated field were enrolled on a prospective trial of proton reirradiation. The primary endpoint was provider-reported acute toxicity. Secondary endpoints included late toxicities, local control, and overall survival. 23 patients underwent proton reirradiation. Median time between radiation courses was 40.7months (range 10-272). No grade 4-5 toxicities were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade 2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence (13%). There were two grade 3 late wound infections (10%) and one grade 3 late wound complication (5%). Grade 2 late complications included lymphedema (10%), fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year cumulative incidence of local failure was 41% (95% CI [20-63%]). Median overall survival and progression-free survival were 44 and 29months, respectively. In extremity patients, amputation was spared in 7/10 (70%). Proton reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated. While longer follow-up is needed, early survival outcomes in this high-risk population are encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

Dosimetric comparison of stopping power calibration with dual-energy CT and single-energy CT in proton therapy treatment planning

Energy Technology Data Exchange (ETDEWEB)

Zhu, Jiahua [Department of Physics, University of Adelaide, Adelaide, SA 5005 (Australia); Penfold, Scott N., E-mail: scott.penfold@adelaide.edu.au [Department of Physics, University of Adelaide, Adelaide, SA 5005, Australia and Department of Medical Physics, Royal Adelaide Hospital, Adelaide, SA 5000 (Australia)

2016-06-15

Purpose: The accuracy of proton dose calculation is dependent on the ability to correctly characterize patient tissues with medical imaging. The most common method is to correlate computed tomography (CT) numbers obtained via single-energy CT (SECT) with proton stopping power ratio (SPR). CT numbers, however, cannot discriminate between a change in mass density and change in chemical composition of patient tissues. This limitation can have consequences on SPR calibration accuracy. Dual-energy CT (DECT) is receiving increasing interest as an alternative imaging modality for proton therapy treatment planning due to its ability to discriminate between changes in patient density and chemical composition. In the current work we use a phantom of known composition to demonstrate the dosimetric advantages of proton therapy treatment planning with DECT over SECT. Methods: A phantom of known composition was scanned with a clinical SECT radiotherapy CT-simulator. The phantom was rescanned at a lower X-ray tube potential to generate a complimentary DECT image set. A set of reference materials similar in composition to the phantom was used to perform a stoichiometric calibration of SECT CT number to proton SPRs. The same set of reference materials was used to perform a DECT stoichiometric calibration based on effective atomic number. The known composition of the phantom was used to assess the accuracy of SPR calibration with SECT and DECT. Intensity modulated proton therapy (IMPT) treatment plans were generated with the SECT and DECT image sets to assess the dosimetric effect of the imaging modality. Isodose difference maps and root mean square (RMS) error calculations were used to assess dose calculation accuracy. Results: SPR calculation accuracy was found to be superior, on average, with DECT relative to SECT. Maximum errors of 12.8% and 2.2% were found for SECT and DECT, respectively. Qualitative examination of dose difference maps clearly showed the dosimetric advantages

Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual.

Science.gov (United States)

Morisada, S; Nosaka, N; Tsukahara, K; Ugawa, T; Sato, K; Ujike, Y

2015-09-30

The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive burns (SEB) treated before and after implementation of these new guidelines at this institution. The patients included in this study had a burn index (BI) ≥30 or a prognostic burn index (PBI = BI + patient's age) ≥100. The survival rate of the patients with BI ≥30 was 65.2% with the traditional treatment and 100% with the new guidelines. Likewise, the survival rate of the patients with PBI ≥100 was 61.1% with the traditional treatment compared to 100% with the new guidelines. Together, these data demonstrate that the new treatment guidelines dramatically improved the treatment outcome and survival of SEB patients.

Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine

Energy Technology Data Exchange (ETDEWEB)

Yadav, Poonam, E-mail: yadav@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); University of Wisconsin Riverview Cancer Center, Wisconsin Rapids, WI (United States); Paliwal, Bhudatt R. [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Kozak, Kevin [Department of Human Oncology, University of Wisconsin, Madison, WI (United States)

2013-10-01

Chondrosarcomas are relatively radiotherapy resistant, and also delivering high radiation doses is not feasible owing to anatomic constraints. In this study, the feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic spine is explored and compared with other available photon and proton radiotherapy techniques in the clinical setting. A patient was treated for high-grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively, the tomotherapy plan was compared with intensity-modulated radiation therapy, dynamic arc photon therapy, and proton therapy. Two primary comparisons were made: (1) comparison of normal tissue sparing with comparable target volume coverage (plan-1), and (2) comparison of target volume coverage with a constrained maximum dose to the cord center (plan-2). With constrained target volume coverage, proton plans were found to yield lower mean doses for all organs at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning resulted in the lowest mean dose to all organs at risk amongst photon-based methods. For cord dose constrained plans, the static-field intensity-modulated radiation therapy and dynamic arc plans resulted target underdosing in 20% and 12% of planning target volume2 volumes, respectively, whereas both proton and tomotherapy plans provided clinically acceptable target volume coverage with no portion of planning target volume2 receiving less than 90% of the prescribed dose. Tomotherapy plans are comparable to proton plans and produce superior results compared with other photon modalities. This feasibility study suggests that tomotherapy is an attractive alternative to proton radiotherapy for delivering high doses to lesions in the thoracic spine.

Dosimetric comparison of photon and proton treatment techniques for chondrosarcoma of thoracic spine

International Nuclear Information System (INIS)

Yadav, Poonam; Paliwal, Bhudatt R.; Kozak, Kevin

2013-01-01

Chondrosarcomas are relatively radiotherapy resistant, and also delivering high radiation doses is not feasible owing to anatomic constraints. In this study, the feasibility of helical tomotherapy for treatment of chondrosarcoma of thoracic spine is explored and compared with other available photon and proton radiotherapy techniques in the clinical setting. A patient was treated for high-grade chondrosarcoma of the thoracic spine using tomotherapy. Retrospectively, the tomotherapy plan was compared with intensity-modulated radiation therapy, dynamic arc photon therapy, and proton therapy. Two primary comparisons were made: (1) comparison of normal tissue sparing with comparable target volume coverage (plan-1), and (2) comparison of target volume coverage with a constrained maximum dose to the cord center (plan-2). With constrained target volume coverage, proton plans were found to yield lower mean doses for all organs at risk (spinal cord, esophagus, heart, and both lungs). Tomotherapy planning resulted in the lowest mean dose to all organs at risk amongst photon-based methods. For cord dose constrained plans, the static-field intensity-modulated radiation therapy and dynamic arc plans resulted target underdosing in 20% and 12% of planning target volume2 volumes, respectively, whereas both proton and tomotherapy plans provided clinically acceptable target volume coverage with no portion of planning target volume2 receiving less than 90% of the prescribed dose. Tomotherapy plans are comparable to proton plans and produce superior results compared with other photon modalities. This feasibility study suggests that tomotherapy is an attractive alternative to proton radiotherapy for delivering high doses to lesions in the thoracic spine

Comparing photon and proton-based hypofractioned SBRT for prostate cancer accounting for robustness and realistic treatment deliverability.

Science.gov (United States)

Goddard, Lee C; Brodin, N Patrik; Bodner, William R; Garg, Madhur K; Tomé, Wolfgang A

2018-05-01

To investigate whether photon or proton-based stereotactic body radiation therapy (SBRT is the preferred modality for high dose hypofractionation prostate cancer treatment. Achievable dose distributions were compared when uncertainties in target positioning and range uncertainties were appropriately accounted for. 10 patients with prostate cancer previously treated at our institution (Montefiore Medical Center) with photon SBRT using volumetric modulated arc therapy (VMAT) were identified. MRI images fused to the treatment planning CT allowed for accurate target and organ at risk (OAR) delineation. The clinical target volume was defined as the prostate gland plus the proximal seminal vesicles. Critical OARs include the bladder wall, bowel, femoral heads, neurovascular bundle, penile bulb, rectal wall, urethra and urogenital diaphragm. Photon plan robustness was evaluated by simulating 2 mm isotropic setup variations. Comparative proton SBRT plans employing intensity modulated proton therapy (IMPT) were generated using robust optimization. Plan robustness was evaluated by simulating 2 mm setup variations and 3% or 1% Hounsfield unit (HU) calibration uncertainties. Comparable maximum OAR doses are achievable between photon and proton SBRT, however, robust optimization results in higher maximum doses for proton SBRT. Rectal maximum doses are significantly higher for Robust proton SBRT with 1% HU uncertainty compared to photon SBRT (p = 0.03), whereas maximum doses were comparable for bladder wall (p = 0.43), urethra (p = 0.82) and urogenital diaphragm (p = 0.50). Mean doses to bladder and rectal wall are lower for proton SBRT, but higher for neurovascular bundle, urethra and urogenital diaphragm due to increased lateral scatter. Similar target conformality is achieved, albeit with slightly larger treated volume ratios for proton SBRT, >1.4 compared to 1.2 for photon SBRT. Similar treatment plans can be generated with IMPT compared to VMAT in terms of

WE-D-BRB-01: Basic Physics of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Arjomandy, B. [McLaren Cancer Institute (United States)

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

WE-D-BRB-01: Basic Physics of Proton Therapy

International Nuclear Information System (INIS)

Arjomandy, B.

2016-01-01

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

Preliminary results of proton therapy in choroidal melanoma at the centre de proton therapy d`Orsay (C.P.O.): 464 initial cases; Resultats preliminaires de la protontherapie du melanome de la choroide au centre de protontherapie d`Orsay (CPO): les 464 premiers cas

Energy Technology Data Exchange (ETDEWEB)

Desjardins, L.; Levy, C.; D`hermies, F.; Frau, E.; Schlienger, P.; Habrand, J.L.; Mammar, H.; Schwartz, L.; Mazal, A.; Delacroix, S.; Nauraye, C.; Ferrand, R.; Asselain, B. [Centre de protontherapie d`Orsay, 91 - Orsay (France)

1997-06-01

Retrospective analysis of the treatment of choroidal melanoma with proton-therapy at the Centre de protontherapie d`Orsay, France. Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by proton-therapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. Univariate analysis showed that the actuarial local recurrence rate was 5 %, the 3-year survival rate 88 %, and the overall metastatic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. Proton-therapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor. (author) 16 refs.

Estimate of neutron secondary doses received by patients in proton therapy: cases of ophthalmologic treatments

International Nuclear Information System (INIS)

Martinetti, F.

2009-12-01

This research thesis aims at assessing doses due to secondary neutrons and received by the organs of a patient which are located outside of the treatment field. The study focused on ophthalmological treatments performed at the Orsay proton therapy centre. A 75 eV beam line model has first been developed with the MCNPX Monte Carlo code. Several experimental validations of this model have been performed: proton dose distribution in a water phantom, ambient equivalent dose due to secondary neutrons and neutron spectra in the treatment room, and doses deposited by secondary neutrons in an anthropomorphous phantom. Simulations and measurements are in correct agreement. Then, a numeric assessment of secondary doses received by the patient's organs has been performed by using a MIRD-type mathematical phantom. These doses have been computed for several organs: the non-treated eye, the brain, the thyroid, and other parts of the body situated either in the front part of the body (the one directly exposed to neutrons generated in the treatment line) or deeper and further from the treatment field

Proton beam characterization in the experimental room of the Trento Proton Therapy facility

Science.gov (United States)

Tommasino, F.; Rovituso, M.; Fabiano, S.; Piffer, S.; Manea, C.; Lorentini, S.; Lanzone, S.; Wang, Z.; Pasini, M.; Burger, W. J.; La Tessa, C.; Scifoni, E.; Schwarz, M.; Durante, M.

2017-10-01

As proton therapy is becoming an established treatment methodology for cancer patients, the number of proton centres is gradually growing worldwide. The economical effort for building these facilities is motivated by the clinical aspects, but might be also supported by the potential relevance for the research community. Experiments with high-energy protons are needed not only for medical physics applications, but represent also an essential part of activities dedicated to detector development, space research, radiation hardness tests, as well as of fundamental research in nuclear and particle physics. Here we present the characterization of the beam line installed in the experimental room of the Trento Proton Therapy Centre (Italy). Measurements of beam spot size and envelope, range verification and proton flux were performed in the energy range between 70 and 228 MeV. Methods for reducing the proton flux from typical treatments values of 106-109 particles/s down to 101-105 particles/s were also investigated. These data confirm that a proton beam produced in a clinical centre build by a commercial company can be exploited for a broad spectrum of experimental activities. The results presented here will be used as a reference for future experiments.

Proton therapy physics

CERN Document Server

2012-01-01

Proton Therapy Physics goes beyond current books on proton therapy to provide an in-depth overview of the physics aspects of this radiation therapy modality, eliminating the need to dig through information scattered in the medical physics literature. After tracing the history of proton therapy, the book summarizes the atomic and nuclear physics background necessary for understanding proton interactions with tissue. It describes the physics of proton accelerators, the parameters of clinical proton beams, and the mechanisms to generate a conformal dose distribution in a patient. The text then covers detector systems and measuring techniques for reference dosimetry, outlines basic quality assurance and commissioning guidelines, and gives examples of Monte Carlo simulations in proton therapy. The book moves on to discussions of treatment planning for single- and multiple-field uniform doses, dose calculation concepts and algorithms, and precision and uncertainties for nonmoving and moving targets. It also exami...

Impact of delay to treatment upon survival in 1067 patients with breast-cancer.

Science.gov (United States)

Rabinovich, M; Vallejo, C; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Lacava, J; Leone, B; Romero, A; Mickiewicz, E; Chacon, R; Estevez, R

1993-02-01

The medical records of 1067 patients with breast cancer were reviewed to evaluate the influence of delay between first symptom and first treatment upon survival. Three delay intervals were considered: 6 months. At a follow-up of 120 months, survival analyses identified a statistically significant difference (p=0.029) favoring patients with 3 months delay between first symptom and first treatment. Better survival rate for patients with a short delay would obey to a greater number of patients in favorable stages and a higher proportion of women aged 50 or older in this group.

Treatment for occult hepatocellular carcinoma: does it offer survival advantages over symptom-driven treatment?

Science.gov (United States)

Kim, Kwang Min; Kim, Jiyu; Sinn, Dong Hyun; Kim, Hye Seung; Kim, Kyunga; Kang, Wonseok; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

2018-04-03

In order to claim a benefit of screen-based diagnosis for asymptomatic individuals, treatment of occult disease needs to offer survival advantages compared to the treatment of symptomatic disease, yet information on this issue is scarce with regard to hepatocellular carcinoma (HCC) screening. A total of 3353 treatment-naïve, consecutive, newly diagnosed HCC patients [age: 57.9 ± 10.3, male: 2,689 (80.2%), hepatitis B virus: 2555 (76.2%)], diagnosed between 2010 and 2013 were analyzed. Data on the mode of detection was prospectively collected at the time of HCC diagnosis and was used to group patients into occult or symptomatic cases. Overall, 643 (19.2%) patients were symptomatic cases. The proportion of patients undergoing resection, radiofrequency ablation or transplantation were lower in symptomatic cases than occult cases (20.8 vs. 56.2%, p offered a survival benefit to patients over symptomatic cases. These data support screening practices for asymptomatic individuals to diagnose occult HCC.

Use of treatment log files in spot scanning proton therapy as part of patient-specific quality assurance

International Nuclear Information System (INIS)

Li Heng; Sahoo, Narayan; Poenisch, Falk; Suzuki, Kazumichi; Li Yupeng; Li Xiaoqiang; Zhang Xiaodong; Gillin, Michael T.; Zhu, X. Ronald; Lee, Andrew K.

2013-01-01

Purpose: The purpose of this work was to assess the monitor unit (MU) values and position accuracy of spot scanning proton beams as recorded by the daily treatment logs of the treatment control system, and furthermore establish the feasibility of using the delivered spot positions and MU values to calculate and evaluate delivered doses to patients. Methods: To validate the accuracy of the recorded spot positions, the authors generated and executed a test treatment plan containing nine spot positions, to which the authors delivered ten MU each. The spot positions were measured with radiographic films and Matrixx 2D ion-chambers array placed at the isocenter plane and compared for displacements from the planned and recorded positions. Treatment logs for 14 patients were then used to determine the spot MU values and position accuracy of the scanning proton beam delivery system. Univariate analysis was used to detect any systematic error or large variation between patients, treatment dates, proton energies, gantry angles, and planned spot positions. The recorded patient spot positions and MU values were then used to replace the spot positions and MU values in the plan, and the treatment planning system was used to calculate the delivered doses to patients. The results were compared with the treatment plan. Results: Within a treatment session, spot positions were reproducible within ±0.2 mm. The spot positions measured by film agreed with the planned positions within ±1 mm and with the recorded positions within ±0.5 mm. The maximum day-to-day variation for any given spot position was within ±1 mm. For all 14 patients, with ∼1 500 000 spots recorded, the total MU accuracy was within 0.1% of the planned MU values, the mean (x, y) spot displacement from the planned value was (−0.03 mm, −0.01 mm), the maximum (x, y) displacement was (1.68 mm, 2.27 mm), and the (x, y) standard deviation was (0.26 mm, 0.42 mm). The maximum dose difference between calculated dose to

Proton therapy in Australia

International Nuclear Information System (INIS)

Jackson, M.

2000-01-01

Full text: Proton therapy has been in use since 1954 and over 25,000 patients have been treated worldwide. Until recently most patients were treated at physics research facilities but with the development of more compact and reliable accelerators it is now possible to realistically plan for proton therapy in an Australian hospital. The Australian National Proton Project has been formed to look at the feasibility of a facility which would be primarily for patient treatment but would also be suitable for research and commercial applications. A detailed report will be produced by the end of the year. The initial clinical experience was mainly with small tumours and other lesions close to critical organs. Large numbers of eye tumours have also been treated. Protons have a well-defined role in these situations and are now being used in the treatment of more common cancers. With the development of hospital-based facilities, over 2,500 patients with prostate cancer have been treated using a simple technique which gives results at least as good as radical surgery, external beam radiotherapy or brachytherapy. Importantly, the incidence of severe complications is very low. There are encouraging results in many disease sites including lung, liver, soft tissue sarcomas and oesophagus. As proton therapy becomes more widely available, randomised trials comparing it with conventional radiotherapy or Intensity Modulated Radiation Therapy (IMRT) will be possible. In most situations the use of protons will enable a higher dose to be given safely but in situations where local control rates are already satisfactory, protons are expected to produce less complications than conventional treatment. The initial costs of a proton facility are high but the recurrent costs are similar to other forms of high technology radiotherapy. . Simple treatment techniques with only a few fields are usually possible and proton therapy avoids the high integral doses associated with IMRT. This reduction in

Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

International Nuclear Information System (INIS)

McGovern, Susan L.; Okcu, M. Fatih; Munsell, Mark F.; Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F.; Chintagumpala, Murali; Khatua, Soumen; Mahajan, Anita

2014-01-01

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted

Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

Energy Technology Data Exchange (ETDEWEB)

McGovern, Susan L., E-mail: slmcgove@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Okcu, M. Fatih [Texas Children' s Hematology and Oncology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, Texas (United States); Munsell, Mark F. [Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chintagumpala, Murali [Texas Children' s Hematology and Oncology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, Texas (United States); Khatua, Soumen [Department of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mahajan, Anita [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-12-01

Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

Results of treatment of Icenko-Cushing disease with proton beam irradiation of the pituitary gland

International Nuclear Information System (INIS)

Marova, E.I.; Starkova, N.T.; Kirpatovskaya, L.E.; Kolesnikova, G.S.; Bukhman, A.I.; Rozhinskaya, L.Ya.; Bel'chenko, L.V.

1987-01-01

Proton beam therapy was given to 98 patients with Icenko-Cushing disease aged 15 to 40. Mild cases were treated by proton beam irradiation only while severe cases were managed using proton beam therapy combined with unilateral adrenalectomy or ortho-para-DDD. Catamnesis duration varied from 3 to 5 years. In most cases the exposure dose was 80-90 Gy (50-110 Gy). The procedure was well tolerated by all the patients. A dynamic multipolar converting method with 15-20 entrance poles in the left temporal area was employed (with the beam energy of 200 MeV). Stabilization of the course of disease and some clinical improvement were observed in most of the patients 3-4 months after proton beam therapy. In 6-36 months after irradiation 90% of the patients showed normal biochemical indices and the absence of any clinical signs of the disease. Thus the results of proton beam therapy of 98 patients with Icenko-Cushing disease after a follow-up of 3-5 years showed a high efficacy of this type of treatment. The method can be used alone or in combination with unilateral adrenalectomy as well as with oral administration of ortho-para-DDD

A 62-MeV Proton Beam for the Treatment of Ocular Melanoma at Laboratori Nazionali del Sud-INFN

Science.gov (United States)

Cirrone, G. A. P.; Cuttone, G.; Lojacono, P. A.; Lo Nigro, S.; Mongelli, V.; Patti, I. V.; Privitera, G.; Raffaele, L.; Rifuggiato, D.; Sabini, M. G.; Salamone, V.; Spatola, C.; Valastro, L. M.

2004-06-01

At the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) in Catania, Italy, the first Italian protontherapy facility, named Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA) has been built in collaboration with the University of Catania. It is based on the use of the 62-MeV proton beam delivered by the K=800 Superconducting Cyclotron installed and working at INFN-LNS since 1995. The facility is mainly devoted to the treatment of ocular diseases like uveal melanoma. A beam treatment line in air has been assembled together with a dedicated positioning patient system. The facility has been in operation since the beginning of 2002 and 66 patients have been successfully treated up to now. The main features of CATANA together with the clinical and dosimetric features will be extensively described; particularly, the proton beam line, that has been entirely built at LNS, with all its elements, the experimental transversal and depth dose distributions of the 62-MeV proton beam obtained for a final collimator of 25-mm diameter and the experimental depth dose distributions of a modulated proton beam obtained for the same final collimator. Finally, the clinical results over 1 yr of treatments, describing the features of the treated diseases will be reported.

4D Proton treatment planning strategy for mobile lung tumors

International Nuclear Information System (INIS)

Kang Yixiu; Zhang Xiaodong; Chang, Joe Y.; Wang He; Wei Xiong; Liao Zhongxing; Komaki, Ritsuko; Cox, James D.; Balter, Peter A.; Liu, Helen; Zhu, X. Ronald; Mohan, Radhe; Dong Lei

2007-01-01

Purpose: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. Methods and Materials: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE R IGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. Results: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE R IGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. Conclusion: The AVE R IGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors

Principles and practice of proton beam therapy

CERN Document Server

Das, Indra J

2015-01-01

Commissioned by The American Association of Physicists in Medicine (AAPM) for their June 2015 Summer School, this is the first AAPM monograph printed in full color. Proton therapy has been used in radiation therapy for over 70 years, but within the last decade its use in clinics has grown exponentially. This book fills in the proton therapy gap by focusing on the physics of proton therapy, including beam production, proton interactions, biology, dosimetry, treatment planning, quality assurance, commissioning, motion management, and uncertainties. Chapters are written by the world's leading medical physicists who work at the pioneering proton treatment centers around the globe. They share their understandings after years of experience treating thousands of patients. Case studies involving specific cancer treatments show that there is some art to proton therapy as well as state-of-the-art science. Even though the focus lies on proton therapy, the content provided is also valuable to heavy charged particle th...

Perioperative blood transfusion does not decrease survival after surgical treatment of spinal metastases

DEFF Research Database (Denmark)

Clausen, Caroline; Lönn, Lars; Morgen, Søren Schmidt

2014-01-01

PURPOSE: To assess whether perioperative allogenic blood transfusions in patients undergoing surgical treatment for spinal metastases independently influence patient survival. METHODS: A retrospective study including 170 consecutive patients undergoing surgical treatment for spinal metastases in ...... 12-month survival. Future studies should assess if a liberal transfusion regime can be applied to this group of patients; thereby, prioritizing early postoperative mobilization....

Estimating the average treatment effect on survival based on observational data and using partly conditional modeling.

Science.gov (United States)

Gong, Qi; Schaubel, Douglas E

2017-03-01

Treatments are frequently evaluated in terms of their effect on patient survival. In settings where randomization of treatment is not feasible, observational data are employed, necessitating correction for covariate imbalances. Treatments are usually compared using a hazard ratio. Most existing methods which quantify the treatment effect through the survival function are applicable to treatments assigned at time 0. In the data structure of our interest, subjects typically begin follow-up untreated; time-until-treatment, and the pretreatment death hazard are both heavily influenced by longitudinal covariates; and subjects may experience periods of treatment ineligibility. We propose semiparametric methods for estimating the average difference in restricted mean survival time attributable to a time-dependent treatment, the average effect of treatment among the treated, under current treatment assignment patterns. The pre- and posttreatment models are partly conditional, in that they use the covariate history up to the time of treatment. The pre-treatment model is estimated through recently developed landmark analysis methods. For each treated patient, fitted pre- and posttreatment survival curves are projected out, then averaged in a manner which accounts for the censoring of treatment times. Asymptotic properties are derived and evaluated through simulation. The proposed methods are applied to liver transplant data in order to estimate the effect of liver transplantation on survival among transplant recipients under current practice patterns. © 2016, The International Biometric Society.

Survival of tumor cells after proton irradiation with ultra-high dose rates

International Nuclear Information System (INIS)

Auer, Susanne; Hable, Volker; Greubel, Christoph; Drexler, Guido A; Schmid, Thomas E; Belka, Claus; Dollinger, Günther; Friedl, Anna A

2011-01-01

Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >10 9 Gy s -1 may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly

Survival and behavior of silver catfish, Rhamdia quelen, submitted to antibiotics and sodium chloride treatments

Directory of Open Access Journals (Sweden)

Andrade Luciana Segura de

2006-01-01

Full Text Available In order to evaluate the use of antibiotics and NaCl on the behavior and survival of silver catfish, Rhamdia quelen, infested by Ichthyophthirius multifiliis and infected with Aeromonas hydrophila, juveniles were treated with chloramphenicol, chloramphenicol + salt, oxytetracycline, oxytetracycline + salt and water alone (control. Fish survival in the treatments with chloramphenicol + salt and oxytetracycline + salt was significantly higher than in the other treatments. The treatment with chloramphenicol presented higher survival than the treatment with oxytetracycline and both showed significantly higher survival than control. Swimming activity was higher in the fish treated with antibiotics and salt compared to control fish. A combination of the studied antibiotics plus salt is more effective to treat both A. hydrophila infection and I. multifiliis infestation in silver catfish, but since the use of chloramphenicol is not allowed in Brazil, oxytetracycline plus salt seems to be the best treatment option.

Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency.

Science.gov (United States)

Diekman, Eugene F; de Koning, Tom J; Verhoeven-Duif, Nanda M; Rovers, Maroeska M; van Hasselt, Peter M

2014-02-01

The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. MEDLINE, EMBASE, and Cochrane databases between January 1960 and December 2012. Studies that described patients with severe MTHFR deficiency who received betaine treatment. We identified 15 case reports and case series, totaling 36 patients. Data included the following: (1) families with 2 or more patients with severe MTHFR deficiency, of whom at least 1 received betaine, or (2) single patients with severe MTHFR deficiency treated with betaine. To define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as the effect of treatment (survival and/or psychomotor development). We compared the outcome in treated vs untreated patients and early- vs late-treated patients. Sensitivity analysis was performed to address definition of early treatment. To further assess the impact of treatment on mortality, we performed a subanalysis in families with at least 1 untreated deceased patient. Survival and psychomotor development. Eleven of 36 patients (31%) died. All deaths occurred in patients who did not receive treatment or in patients in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Subgroup analysis of patients with deceased siblings-their genotypically identical controls-revealed that betaine treatment prevented mortality (P = .002). In addition, psychomotor development in surviving patients treated with betaine was normal in all 5 early-treated patients but in none of the 19 surviving patients with delayed treatment (P psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

Survival analysis of patients with uveal melanoma after organ preserving and liquidation treatment

Directory of Open Access Journals (Sweden)

E. E. Grishina

2018-01-01

Full Text Available Rationale: Uveal melanoma is the most common primary malignancy of the eye.Aim: To evaluate survival in patients with uveal melanoma stratified according to the type of treatment and to identify factors significantly associated with their survival.Materials and methods: The study was performed on the data extracted from medical files and follow-up forms of patients with uveal melanoma seen in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012. Analysis of survival was used to assess the life longevity of patients with uveal melanoma. The analysis was censored at January 2013, when vital status (dead or alive of all patients was assessed. The factors included into the study analysis, were those taken from the follow-up forms. The incidence of uveal melanoma in Moscow (2012 was 0.9 per 100,000 of the population, whereas its prevalence was 11.1 per 100,000.Results: 698 patients with uveal melanoma were included into the study, among them 260 (37% men (aged from 19 to 87 years, median age 60 years and 438 (63% women (aged from 18 to 93 years, median age 63 years; therefore, the proportion of women under the follow-up monitoring was by 26% higher than that of men. The liquidation treatment (mostly enucleation was performed in 358 (51% of the patients, whereas the organ preserving treatment in 340 (49%. At 5, 7, and 10 years of the follow-up, the disease-specific survival of patients with uveal melanoma after the organ preserving treatment (median survival has not been reached and after the liquidation treatment (median, 88 months were 89 ± 2, 83 ± 3, and 75 ± 4% versus 63 ± 3, 52 ± 4, and 47 ± 5%, respectively (р = 0.001. Overall survival and disease-specific survival of the patients after the liquidation treatment were significantly lower than in the patients after the organ-preserving treatment. According to multiple regression analysis, this was associated not with the type of

Effect of different heat treatments and disinfectants on the survival of Prototheca zopfii.

Science.gov (United States)

Lassa, Henryka; Jagielski, Tomasz; Malinowski, Edward

2011-03-01

Bovine mastitis caused by the yeast-like alga Prototheca zopfii represents a serious veterinary problem and may result in heavy economic losses to particular dairy farms. The purpose of this study was to evaluate the survival of 50 isolates of P. zopfii in milk subjected to different heat treatments and the survival of further 106 P. zopfii isolates after exposure to three classes of teat disinfectants: iodine (Dipal), quaternary ammonium compounds (Teat), and dodecylbenzenesulphonic acid (Blu-gard). Of the 50 isolates tested for thermal tolerance, 29 (58%) survived heat treatment at 62 °C for 30 s and 13 (26% of all isolates) of those survived after heat treatment at 72 °C for 15 s. None of the 106 isolates were able to withstand the in-use concentrations of the three disinfectants tested. The highest disinfectant concentrations that permitted survival of at least one isolate were dilutions: 1:1,000 for Dipal (survival rate of 52.8-57.5%), 1:100 for Teat (88.7-90.6%), and 1:10 for Blu-gard (100%). No differences in the survival rates of P. zopfii were observed with respect to the duration of exposure to disinfectant. The results of this study support the previous findings that P. zopfii may resist high-temperature treatments, including that applied in the high-temperature, short-time (HTST) pasteurization process. The obtained data also demonstrate the efficacy of the three classes of teat disinfectants against P. zopfii, with the efficacy of iodine being most pronounced. The study emphasizes the necessity of using higher temperatures in the pasteurization of raw milk to kill the Prototheca algae, as well as the particular suitability of the iodine for the control procedures of protothecal mastitis.

Particle production and survival in muon acceleration

Energy Technology Data Exchange (ETDEWEB)

Noble, R.J.

1992-06-01

Because of the relative immunity of muons to synchrotron radiation, the idea of using them instead of electrons as probes in high-energy physics experiments has existed for some time, but applications were limited by the short muon lifetime. The production and survival of an adequate supply of low-emittance muons will determine the available luminosity in a high-energy physics collider. In this paper the production of pions by protons, their decay to muons and the survival of muons during acceleration are studied. Based on a combination of the various efficiencies, the number of protons needed at the pion source for every muon required in the final high-energy collider is estimated.

Evolution of dose calculation models for proton-therapy treatment planning

International Nuclear Information System (INIS)

Vidal, Marie

2011-01-01

This work was achieved in collaboration between the Institut Curie proton-therapy Center of Orsay (ICPO), the DOSIsoft company and the CREATIS laboratory, in order to develop a new dose calculation model for the new ICPO treatment room. A new accelerator and gantry room from the IBA company were installed during the up-grade project of the proton-therapy center, with the intention of enlarging the cancer localizations treated at ICPO. Developing a package of methods and new dose calculation algorithms to adapt them to the new specific characteristics of the delivered beams by the IBA system is the first goal of this PhD work. They all aim to be implemented in the DOSIsoft treatment planning software, Isogray. First, the double scattering technique is treated in taking into account major differences between the IBA system and the ICPO fixed beam lines passive system. Secondly, a model is explored for the scanned beams modality. The second objective of this work is improving the Ray-Tracing and Pencil-Beam dose calculation models already in use. For the double scattering and uniform scanning techniques, the patient personalized collimator at the end of the beam line causes indeed a patient dose distribution contamination. A reduction method of that phenomenon was set up for the passive beam system. An analytical model was developed which describes the contamination function with parameters validated through Monte-Carlo simulations on the GATE platform. It allows us to apply those methods to active scanned beams [fr

Influence of proton scattering angles on the energy radiograph in proton radiotherapy : A simulation study

NARCIS (Netherlands)

Biegun, A.K.; Takatsu, J.; van Beuzekom, M.; van der Graaf, E.R.; van Goethem, M-J.; Klaver, T.; Visser, J.; Brandenburg, S.

2015-01-01

The treatment quality of cancer patients with a proton beam critically depends on accurate predictions of proton stopping powers. Uncertainties in proton range that occur from translation of an X-ray CT patient image, of typical 3–4% or more, lead to necessary enlargements of contours around the

Survival of Bactericidal Antibiotic Treatment by a Persister Subpopulation of Listeria monocytogenes

DEFF Research Database (Denmark)

Knudsen, Gitte Maegaard; Ng, Yin; Gram, Lone

2013-01-01

Listeria monocytogenes can cause the serious infection listeriosis, which despite antibiotic treatment has a high mortality. Understanding the response of L. monocytogenes to antibiotic exposure is therefore important to ensure treatment success. Some bacteria survive antibiotic treatment...... by formation of persisters, which are a dormant antibiotic-tolerant subpopulation. The purpose of this study was to determine whether L. monocytogenes can form persisters and how bacterial physiology affects the number of persisters in the population. A stationary-phase culture of L. monocytogenes was adjusted...... that eradication of persisters is possible. Our study adds L. monocytogenes to the list of bacterial species capable of surviving bactericidal antibiotics in a dormant stage, and this persister phenomenon should be borne in mind when developing treatment regimens....

SU-E-J-72: Geant4 Simulations of Spot-Scanned Proton Beam Treatment Plans

Energy Technology Data Exchange (ETDEWEB)

Kanehira, T; Sutherland, K; Matsuura, T; Umegaki, K; Shirato, H [Hokkaido University, Sapporo, Hokkaido (Japan)

2014-06-01

Purpose: To evaluate density inhomogeneities which can effect dose distributions for real-time image gated spot-scanning proton therapy (RGPT), a dose calculation system, using treatment planning system VQA (Hitachi Ltd., Tokyo) spot position data, was developed based on Geant4. Methods: A Geant4 application was developed to simulate spot-scanned proton beams at Hokkaido University Hospital. A CT scan (0.98 × 0.98 × 1.25 mm) was performed for prostate cancer treatment with three or four inserted gold markers (diameter 1.5 mm, volume 1.77 mm3) in or near the target tumor. The CT data was read into VQA. A spot scanning plan was generated and exported to text files, specifying the beam energy and position of each spot. The text files were converted and read into our Geant4-based software. The spot position was converted into steering magnet field strength (in Tesla) for our beam nozzle. Individual protons were tracked from the vacuum chamber, through the helium chamber, steering magnets, dose monitors, etc., in a straight, horizontal line. The patient CT data was converted into materials with variable density and placed in a parametrized volume at the isocenter. Gold fiducial markers were represented in the CT data by two adjacent voxels (volume 2.38 mm3). 600,000 proton histories were tracked for each target spot. As one beam contained about 1,000 spots, approximately 600 million histories were recorded for each beam on a blade server. Two plans were considered: two beam horizontal opposed (90 and 270 degree) and three beam (0, 90 and 270 degree). Results: We are able to convert spot scanning plans from VQA and simulate them with our Geant4-based code. Our system can be used to evaluate the effect of dose reduction caused by gold markers used for RGPT. Conclusion: Our Geant4 application is able to calculate dose distributions for spot scanned proton therapy.

Reirradiation of Recurrent and Second Primary Head and Neck Cancer With Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

McDonald, Mark W., E-mail: mark.mcdonald@emory.edu [Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia (United States); Zolali-Meybodi, Omid; Lehnert, Stephen J. [Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana (United States); Estabrook, Neil C. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Liu, Yuan [Department of Biostatistics and Bioinformatics, Rollins School of Public Health of Emory University, Atlanta, Georgia (United States); Cohen-Gadol, Aaron A. [Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana (United States); Moore, Michael G. [Department of Otolaryngology–Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana (United States)

2016-11-15

Purpose: To report the clinical outcomes of head and neck reirradiation with proton therapy. Methods and Materials: From 2004 to 2014, 61 patients received curative-intent proton reirradiation, primarily for disease involving skull base structures, at a median of 23 months from the most recent previous course of radiation. Most had squamous cell (52.5%) or adenoid cystic (16.4%) carcinoma. Salvage surgery before reirradiation was undertaken in 47.5%. Gross residual disease was present in 70.5%. For patients with microscopic residual disease, the median dose of reirradiation was 66 Gy (relative biological effectiveness), and for gross disease was 70.2 Gy (relative biological effectiveness). Concurrent chemotherapy was given in 27.9%. Results: The median follow-up time was 15.2 months and was 28.7 months for patients remaining alive. The 2-year overall survival estimate was 32.7%, and the median overall survival was 16.5 months. The 2-year cumulative incidence of local failure with death as a competing risk was 19.7%; regional nodal failure, 3.3%; and distant metastases, 38.3%. On multivariable analysis, Karnofsky performance status ≤70%, the presence of a gastrostomy tube before reirradiation, and an increasing number of previous courses of radiation therapy were associated with a greater hazard ratio for death. A cutaneous primary tumor, gross residual disease, increasing gross tumor volume, and a lower radiation dose were associated with a greater hazard ratio for local failure. Grade ≥3 toxicities were seen in 14.7% acutely and 24.6% in the late setting, including 3 treatment-related deaths. Conclusions: Reirradiation with proton therapy, with or without chemotherapy, provided reasonable locoregional disease control, toxicity profiles, and survival outcomes for an advanced-stage and heavily pretreated population. Additional data are needed to identify which patients are most likely to benefit from aggressive efforts to achieve local disease control and

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.

Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

OpenAIRE

Latimer, N.R.; White, I.R.; Abrams, K.R.; Sieburt, U.

2017-01-01

Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when e...

WE-G-BRE-07: Proton Therapy Enhanced by Tumor-Targeting Gold Nanoparticles: A Pilot in Vivo Experiment at The Proton Therapy Center at MD Anderson Cancer Center

Energy Technology Data Exchange (ETDEWEB)

Wolfe, T; Grant, J; Wolfe, A; Gillin, M; Krishnan, S [MD Anderson Cancer Ctr., Houston, TX (United States)

2014-06-15

Purpose: Assess tumor-growth delay and survival in a mouse model of prostate cancer treated with tumor-targeting gold nanoparticles (AuNPs) and proton therapy. Methods: We first examined the accumulation of targeting nanoparticles within prostate tumors by imaging AuNPs with ultrasound-guided photoacoustics at 24h after the intravenous administration of goserelin-conjugated AuNPs (gAuNP) in three mice. Nanoparticles were also imaged at the cellular level with TEM in PC3 cells incubated with gAuNP for 24h. Pegylated AuNPs (pAuNP) were also imaged in vivo and in vitro for comparison. PC3 cells were then implanted subcutaneously in nude mice; 51mice with 8–10mm tumors were included. AuNPs were injected intravenously at 0.2%w/w final gold concentration 24h before irradiation. A special jig was designed to facilitate tumor irradiation perpendicular to the proton beam. Proton energy was set to 180MeV, the radiation field was 18×18cm{sup 2}, and 9cm or 13.5cm thick solid-water compensators were used to position the tumors at either the beam entrance (BE) or the SOBP. Physical doses of 5Gy were delivered to all tumors on a patient beam line at MD Anderson's Proton Therapy Center. Results: The photoacoustic experiment reveled that our nanoparticles leak from the tumor-feeding vasculature and accumulate within the tumor volume over time. Additionally, TEM images showed gAuNP are internalized in cancer cells, accumulating within the cytoplasm, whereas pAuNP are not. Tumor-growth was delayed by 11 or 32days in mice receiving gAuNP irradiated at the BE or the SOBP, relative to proton radiation alone. Survival curves (ongoing experiment) reveal that gAuNPs improved survival by 36% or 74% for tumors irradiated at the BE or SOBP. Conclusion: These important, albeit preliminary, in vivo findings reveal nanoparticles to be potent sensitizers to proton therapy. Further, conjugation of AuNPs to tumor-specific antigens that promote enhanced cellular internalization improved

Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer

DEFF Research Database (Denmark)

Bertini, Ivano; Cacciatore, Stefano; Jensen, Benny V

2012-01-01

Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist...... survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of m...

Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

2011-01-01

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

2011-11-15

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

On proton CT reconstruction using MVCT-converted virtual proton projections

Energy Technology Data Exchange (ETDEWEB)

Wang Dongxu; Mackie, T. Rockwell; Tome, Wolfgang A. [Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242 (United States); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Morgridge Institute of Research, University of Wisconsin, Madison, Wisconsin 53715 (United States); Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53705 and Oncophysics Institute, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York 10461 (United States)

2012-06-15

. If these images are used for treatment planning, the average proton range uncertainty is estimated to be less than 1.5% for an imaging dose in the milligray range. Conclusions: The proposed method can be used to convert x-ray projections into virtual proton projections. The converted proton projections can be blended with existing proton projections or can be used solely for pCT reconstruction, addressing the range limit problem of pCT using current therapeutic proton machines.

On proton CT reconstruction using MVCT-converted virtual proton projections

International Nuclear Information System (INIS)

Wang Dongxu; Mackie, T. Rockwell; Tomé, Wolfgang A.

2012-01-01

these images are used for treatment planning, the average proton range uncertainty is estimated to be less than 1.5% for an imaging dose in the milligray range. Conclusions: The proposed method can be used to convert x-ray projections into virtual proton projections. The converted proton projections can be blended with existing proton projections or can be used solely for pCT reconstruction, addressing the range limit problem of pCT using current therapeutic proton machines.

Tumor Cells Surviving Exposure to Proton or Photon Radiation Share a Common Immunogenic Modulation Signature, Rendering Them More Sensitive to T Cell–Mediated Killing

Energy Technology Data Exchange (ETDEWEB)

Gameiro, Sofia R.; Malamas, Anthony S. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bernstein, Michael B. [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Tsang, Kwong Y. [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Vassantachart, April; Sahoo, Narayan; Tailor, Ramesh; Pidikiti, Rajesh [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Guha, Chandan P. [Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York (United States); Hahn, Stephen M.; Krishnan, Sunil [Division of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas (United States); Hodge, James W., E-mail: jh241d@nih.gov [Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

2016-05-01

Purpose: To provide the foundation for combining immunotherapy to induce tumor antigen–specific T cells with proton radiation therapy to exploit the activity of those T cells. Methods and Materials: Using cell lines of tumors frequently treated with proton radiation, such as prostate, breast, lung, and chordoma, we examined the effect of proton radiation on the viability and induction of immunogenic modulation in tumor cells by flow cytometric and immunofluorescent analysis of surface phenotype and the functional immune consequences. Results: These studies show for the first time that (1) proton and photon radiation induced comparable up-regulation of surface molecules involved in immune recognition (histocompatibility leukocyte antigen, intercellular adhesion molecule 1, and the tumor-associated antigens carcinoembryonic antigen and mucin 1); (2) proton radiation mediated calreticulin cell-surface expression, increasing sensitivity to cytotoxic T-lymphocyte killing of tumor cells; and (3) cancer stem cells, which are resistant to the direct cytolytic activity of proton radiation, nonetheless up-regulated calreticulin after radiation in a manner similar to non-cancer stem cells. Conclusions: These findings offer a rationale for the use of proton radiation in combination with immunotherapy, including for patients who have failed radiation therapy alone or have limited treatment options.

Cell survival in carbon beams - comparison of amorphous track model predictions

DEFF Research Database (Denmark)

Grzanka, L.; Greilich, S.; Korcyl, M.

Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under i....... Amorphous track modelling of luminescence detector efficiency in proton and carbon beams. 4.Tsuruoka C, Suzuki M, Kanai T, et al. LET and ion species dependence for cell killing in normal human skin fibroblasts. Radiat Res. 2005;163:494-500.......Introduction: Predictions of the radiobiological effectiveness (RBE) play an essential role in treatment planning with heavy charged particles. Amorphous track models ( [1] , [2] , also referred to as track structure models) provide currently the most suitable description of cell survival under ion....... [2] . In addition, a new approach based on microdosimetric distributions is presented and investigated [3] . Material and methods: A suitable software library embrasing the mentioned amorphous track models including numerous submodels with respect to delta-electron range models, radial dose...

WE-D-BRB-04: Clinical Applications of CBCT for Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Teo, B. [University of Pennsylvania (United States)

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

WE-D-BRB-04: Clinical Applications of CBCT for Proton Therapy

International Nuclear Information System (INIS)

Teo, B.

2016-01-01

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

Cost-effectiveness of histamine receptor-2 antagonist versus proton pump inhibitor for stress ulcer prophylaxis in critically ill patients*.

Science.gov (United States)

MacLaren, Robert; Campbell, Jon

2014-04-01

To examine the cost-effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Decision analysis model examining costs and effectiveness of using histamine receptor-2 antagonist or proton pump inhibitor for stress ulcer prophylaxis. Costs were expressed in 2012 U.S. dollars from the perspective of the institution and included drug regimens and the following outcomes: clinically significant stress-related mucosal bleed, ventilator-associated pneumonia, and Clostridium difficile infection. Effectiveness was the mortality risk associated with these outcomes and represented by survival. Costs, occurrence rates, and mortality probabilities were extracted from published data. A simulation model. A mixed adult ICU population. Histamine receptor-2 antagonist or proton pump inhibitor for 9 days of stress ulcer prophylaxis therapy. Output variables were expected costs, expected survival rates, incremental cost, and incremental survival rate. Univariate sensitivity analyses were conducted to determine the drivers of incremental cost and incremental survival. Probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. For the base case analysis, the expected cost of providing stress ulcer prophylaxis was $6,707 with histamine receptor-2 antagonist and $7,802 with proton pump inhibitor, resulting in a cost saving of $1,095 with histamine receptor-2 antagonist. The associated mortality probabilities were 3.819% and 3.825%, respectively, resulting in an absolute survival benefit of 0.006% with histamine receptor-2 antagonist. The primary drivers of incremental cost and survival were the assumptions surrounding ventilator-associated pneumonia and bleed. The probabilities that histamine receptor-2 antagonist was less costly and provided favorable survival were 89.4% and 55.7%, respectively. A secondary analysis assuming equal rates of C. difficile infection showed a cost saving of $908 with histamine

Treatment strategies and survival of older breast cancer patients - an international comparison between the Netherlands and Ireland.

Science.gov (United States)

Kiderlen, Mandy; Walsh, Paul M; Bastiaannet, Esther; Kelly, Maria B; Audisio, Riccardo A; Boelens, Petra G; Brown, Chris; Dekkers, Olaf M; de Craen, Anton J M; van de Velde, Cornelis J H; Liefers, Gerrit-Jan

2015-01-01

Forty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland. From the Dutch and Irish national cancer registries, women aged ≥65 years with non-metastatic breast cancer were included (2001-2009). Proportions of patients receiving guideline-adherent locoregional treatment, endocrine therapy, and chemotherapy were calculated and compared between the countries by stage. Secondly, 5-year relative survival was calculated by stage and compared between countries. Overall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted pNetherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients. Treatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.

Proton therapy of uveal melanomas. Intercomparison of MRI-based and conventional treatment planning

Energy Technology Data Exchange (ETDEWEB)

Marnitz, S.; Hinkelbein, W. [Dept. of Radiooncology, Charite Univ. Medicine, Berlin (Germany); Cordini, D.; Heufelder, J.; Simiantonakis, I.; Kluge, H. [Eye Tumor Therapy, Hahn-Meitner Inst., Berlin (Germany); Bendl, R. [Dept. of Medical Physics, German Cancer Research Center (DKFZ), Heidelberg (Germany); Lemke, A.J. [Dept. of Diagnostic Radiology, Charite Univ. Medicine, Berlin (Germany); Bechrakis, N.E.; Foerster, M.H. [Dept. of Ophthalmology, Charite Univ. Medicine, Berlin (Germany)

2006-07-15

Background and purpose: proton therapy for uveal melanoma provides high-conformal dose application to the target volume and, thus, an optimal saving of the organs at risk nearby. Treatment planning is done with the model-based treatment-planning system eyeplan. Tumor reconstruction is based only on a fundus composite, which often leads to an overestimation of the clinical target volume (CTV). The purpose was to exploit MRI on trial in a proton therapy-planning system by using the novel image-based treatment-planning system octopus. Patients and methods: ten patients with uveal melanomas received both a high-resolution planning CT and MRI of the eye. MR examinations were made with an eye coil. Eyeplan requires eye geometry data for modeling, and tantalum marker clips for submillimeter positioning and additional information from ultrasound and 3-D imaging. By contrast, octopus provides the full integration of 3-D imaging (e.g., CT, MRI). CTVs were delineated in each slice. For all patients, CTVs (eyeplan vs. octopus) were compared intraindividually. Results: octopus planning led to a mean reduction of the target volume by a factor of 1.7 (T1-weighted [T1w]) and 2.2 (T2w) without compromising safety. The corresponding field size could be scaled down on average by a factor of 1.2 (T1w) and 1.4 (T2w), respectively. Conclusion: compared with the conventional eyeplan, MRI-based treatment planning of ocular tumors with octopus could be a powerful tool for reducing the CTV and, consequently, the treatment volume and the field size. This might be translated into a better patient compliance during treatment and a decreased late toxicity. (orig.)

Proton therapy of uveal melanomas. Intercomparison of MRI-based and conventional treatment planning

International Nuclear Information System (INIS)

Marnitz, S.; Hinkelbein, W.; Cordini, D.; Heufelder, J.; Simiantonakis, I.; Kluge, H.; Bendl, R.; Lemke, A.J.; Bechrakis, N.E.; Foerster, M.H.

2006-01-01

Background and purpose: proton therapy for uveal melanoma provides high-conformal dose application to the target volume and, thus, an optimal saving of the organs at risk nearby. Treatment planning is done with the model-based treatment-planning system eyeplan. Tumor reconstruction is based only on a fundus composite, which often leads to an overestimation of the clinical target volume (CTV). The purpose was to exploit MRI on trial in a proton therapy-planning system by using the novel image-based treatment-planning system octopus. Patients and methods: ten patients with uveal melanomas received both a high-resolution planning CT and MRI of the eye. MR examinations were made with an eye coil. Eyeplan requires eye geometry data for modeling, and tantalum marker clips for submillimeter positioning and additional information from ultrasound and 3-D imaging. By contrast, octopus provides the full integration of 3-D imaging (e.g., CT, MRI). CTVs were delineated in each slice. For all patients, CTVs (eyeplan vs. octopus) were compared intraindividually. Results: octopus planning led to a mean reduction of the target volume by a factor of 1.7 (T1-weighted [T1w]) and 2.2 (T2w) without compromising safety. The corresponding field size could be scaled down on average by a factor of 1.2 (T1w) and 1.4 (T2w), respectively. Conclusion: compared with the conventional eyeplan, MRI-based treatment planning of ocular tumors with octopus could be a powerful tool for reducing the CTV and, consequently, the treatment volume and the field size. This might be translated into a better patient compliance during treatment and a decreased late toxicity. (orig.)

Rapidity gap survival in enhanced Pomeron scheme

Energy Technology Data Exchange (ETDEWEB)

Ostapchenko, Sergey [Frankfurt Institute for Advanced Studies, Frankfurt am Main (Germany); Moscow State University, D.V. Skobeltsyn Institute of Nuclear Physics, Moscow (Russian Federation); Bleicher, Marcus [Frankfurt Institute for Advanced Studies, Frankfurt am Main (Germany); Goethe-Universitat, Institute for Theoretical Physics, Frankfurt am Main (Germany)

2018-01-15

We apply the phenomenological Reggeon field theory framework to investigate rapidity gap survival (RGS) probability for diffractive dijet production in proton-proton collisions. In particular, we study in some detail rapidity gap suppression due to elastic rescatterings of intermediate partons in the underlying parton cascades, described by enhanced (Pomeron-Pomeron interaction) diagrams. We demonstrate that such contributions play a subdominant role, compared to the usual, so-called ''eikonal'', rapidity gap suppression due to elastic rescatterings of constituent partons of the colliding protons. On the other hand, the overall RGS factor proves to be sensitive to color fluctuations in the proton. Hence, experimental data on diffractive dijet production can be used to constrain the respective model approaches. (orig.)

Socioeconomic disparities in breast cancer survival: relation to stage at diagnosis, treatment and race

Directory of Open Access Journals (Sweden)

Yu Xue

2009-10-01

Full Text Available Abstract Background Previous studies have documented lower breast cancer survival among women with lower socioeconomic status (SES in the United States. In this study, I examined the extent to which socioeconomic disparity in breast cancer survival was explained by stage at diagnosis, treatment, race and rural/urban residence using the Surveillance, Epidemiology, and End Results (SEER data. Methods Women diagnosed with breast cancer during 1998-2002 in the 13 SEER cancer registry areas were followed-up to the end of 2005. The association between an area-based measure of SES and cause-specific five-year survival was estimated using Cox regression models. Six models were used to assess the extent to which SES differences in survival were explained by clinical and demographical factors. The base model estimated the hazard ratio (HR by SES only and then additional adjustments were made sequentially for: 1 age and year of diagnosis; 2 stage at diagnosis; 3 first course treatment; 4 race; and 5 rural/urban residence. Results An inverse association was found between SES and risk of dying from breast cancer (p Conclusion Stage at diagnosis, first course treatment and race explained most of the socioeconomic disparity in breast cancer survival. Targeted interventions to increase breast cancer screening and treatment coverage in patients with lower SES could reduce much of socioeconomic disparity.

Dosimetric evaluation of proton stereotactic radiosurgery

International Nuclear Information System (INIS)

Min, Byung Jun; Shin, Dong Ho; Yoo, Seung Hoon; Jeong, Hojin; Lee, Se Byeong

2011-01-01

Surgical excision, conventional external radiotherapy, and chemotherapy could prolong survival in patients with small intracranial tumors. However, surgical excision for meningiomas located in the region of the base of skull or re-resection is often difficult. Moreover, treatment is needed for patients with recurrent tumors or postoperative residual tumors. Conventional external radiotherapy is popular and has significantly increased for treating brain tumors. Stereotactic radiosurgery is an effective alternative treatment technique to microsurgical resection such as benign brain tumor or vestibular Schwannomas. In general, the dose to OAR of 3D conformal plan is lower than that of conformal arc and dynamic conformal arc plans. However, any of OARs was not reached to tolerance dose. Although mean dose of the healthy brain tissue for 3D conformal plan was slightly higher than that of arc plans, the doses of the healthy brain tissue at V10 and V20 were significantly low for dynamic conformal arc plan. The dosimetric differences were the greatest at lower doses. In contrast, 3D conformal plan was better spare at higher doses. In this study, a dosimetric evaluation of proton stereotactic radiosurgery for brain lesion tumors was using fixed and arc beams. A brass block fitted to the PTV structure was modeled for dynamic conformal collimator. Although all treatment plans offer a very good coverage of the PTV, we found that proton arc plans had significantly better conformity to the PTV than static 3D conformal plan. The V20 dose of normal brain for dynamic conformal arc therapy is dramatically reduced compare to those for other therapy techniques.

Australian national proton facility

International Nuclear Information System (INIS)

Jackson, M.

2000-01-01

Full text: Proton therapy has been in use since 1954 and over 25,000 patients have been treated worldwide. Until recently most patients were treated at physics research facilities and apart from the Harvard Cyclotron Laboratory and some low energy machines for eye treatment, only small numbers of patients were treated in each centre and conditions were less than optimal. Limited beam time and lack of support facilities restricted the type of patient treated and conventional fractionation could not be used. The initial clinical experience was mainly with small tumours and other lesions close to critical organs. Large numbers of eye tumours have also been treated. Protons have a well-defined role in these situations and are now being used in the treatment of more common cancers. Since the development of hospital-based facilities, such as the one in Loma Linda in California, over 2,500 patients with prostate cancer have been treated using a simple technique which gives results at least as good as radical surgery, external beam radiotherapy or brachytherapy. Importantly, the incidence of severe complications is very low. There are encouraging results in many disease sites including lung, liver, soft tissue sarcomas and oesophagus. As proton therapy becomes more widely available, randomised trials comparing it with conventional radiotherapy or intensity modulated radiotherapy (IMRT) will be possible. In most situations the use of protons will enable a higher dose to be given safely but in situations where local control rates are already satisfactory, protons are expected to produce less complications than conventional treatment. The initial costs of a proton facility are high but the recurrent costs are similar to other forms of high technology radiotherapy. Simple treatment techniques with only a few fields are usually possible and proton therapy avoids the high integral doses associated with IMRT. This reduction in the low dose volume is likely to be particularly

Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer

Energy Technology Data Exchange (ETDEWEB)

Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Amini, Arya [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); UC Irvine School of Medicine, Irvine, CA (United States); Ciura, Katherine; Nguyen, Ngoc; Palmer, Matt [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Soh, Hendrick [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Department of Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Allen, Pamela K.; Paolini, Michael; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Bluett, Jaques; Mohan, Radhe [Department of Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Cox, James D.; Komaki, Ritsuko; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States)

2013-01-01

Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V{sub 20}, V{sub 30}, or V{sub 40}) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within < 2.5 cm of the CW. We found 260 cases; of these, chronic grade ≥ 2 CW pain was identified in 23 patients. We then selected 10 representative patients from this group and generated proton SBRT treatment plans, using the identical dose of 50 Gy in 4 fractions, and assessed potential differences in CW dose between the 2 plans. The proton SBRT plans reduced the CW doses at all dose levels measured. The median CW V{sub 20} was 364.0 cm{sup 3} and 160.0 cm{sup 3} (p < 0.0001), V{sub 30} was 144.6 cm{sup 3}vs 77.0 cm{sup 3} (p = 0.0012), V{sub 35} was 93.9 cm{sup 3}vs 57.9 cm{sup 3} (p = 0.005), V{sub 40} was 66.5 cm{sup 3}vs 45.4 cm{sup 3} (p = 0.0112), and mean lung dose was 5.9 Gy vs 3.8 Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures.

Hypofractionated passively scattered proton radiotherapy for low- and intermediate-risk prostate cancer is not associated with post-treatment testosterone suppression

Energy Technology Data Exchange (ETDEWEB)

Kil, Whoon Jong; Nichols, Romaine C. Jr. [Dept. of Radiation Oncology, Univ. of Florida, Gainesville (United States); Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: rnichols@floridaproton.org; And others

2013-04-15

Background: To investigate post-treatment changes in serum testosterone in low- and intermediate-risk prostate cancer patients treated with hypofractionated passively scattered proton radiotherapy. Material and methods: Between April 2008 and October 2011, 228 patients with low- and intermediate-risk prostate cancer were enrolled into an institutional review board-approved prospective protocol. Patients received doses ranging from 70 Cobalt Gray Equivalent (CGE) to 72.5 CGE at 2.5 CGE per fraction using passively scattered protons. Three patients were excluded for receiving androgen deprivation therapy (n = 2) or testosterone supplementation (n = 1) before radiation. Of the remaining 226 patients, pretreatment serum testosterone levels were available for 217. Of these patients, post-treatment serum testosterone levels were available for 207 in the final week of treatment, 165 at the six-month follow-up, and 116 at the 12-month follow-up. The post-treatment testosterone levels were compared with the pretreatment levels using Wilcoxon's signed-rank test for matched pairs. Results: The median pretreatment serum testosterone level was 367.7 ng/dl (12.8 nmol/l). The median changes in post-treatment testosterone value were as follows: +3.0 ng/dl (+0.1 nmol/l) at treatment completion; +6.0 ng/dl (+0.2 nmol/l) at six months after treatment; and +5.0 ng/dl (0.2 nmol/l) at 12 months after treatment. None of these changes were statistically significant. Conclusion: Patients with low- and intermediate-risk prostate cancer treated with hypofractionated passively scattered proton radiotherapy do not experience testosterone suppression. Our findings are consistent with physical measurements demonstrating that proton radiotherapy is associated with less scatter radiation exposure to tissues beyond the beam paths compared with intensity-modulated photon radiotherapy.

Prolonged utilization of proton pump inhibitors in patients with ischemic and valvular heart disease is associated with surgical treatments, weight loss and aggravates anemia.

Science.gov (United States)

Boban, Marko; Zulj, Marinko; Persic, Viktor; Medved, Igor; Zekanovic, Drazen; Vcev, Aleksandar

2016-09-15

Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. The study included consecutive patients scheduled for cardiovascular rehabilitation 2-6months after index cardiovascular treatment. Two hundred ninety-four patients (n=294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05-8.22; pvalvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A Monte Carlo pencil beam scanning model for proton treatment plan simulation using GATE/GEANT4

Energy Technology Data Exchange (ETDEWEB)

Grevillot, L; Freud, N; Sarrut, D [Universite de Lyon, CREATIS, CNRS UMR5220, Inserm U1044, INSA-Lyon, Universite Lyon 1, Centre Leon Berard, Lyon (France); Bertrand, D; Dessy, F, E-mail: loic.grevillot@creatis.insa-lyon.fr [IBA, B-1348, Louvain-la Neuve (Belgium)

2011-08-21

This work proposes a generic method for modeling scanned ion beam delivery systems, without simulation of the treatment nozzle and based exclusively on beam data library (BDL) measurements required for treatment planning systems (TPS). To this aim, new tools dedicated to treatment plan simulation were implemented in the Gate Monte Carlo platform. The method was applied to a dedicated nozzle from IBA for proton pencil beam scanning delivery. Optical and energy parameters of the system were modeled using a set of proton depth-dose profiles and spot sizes measured at 27 therapeutic energies. For further validation of the beam model, specific 2D and 3D plans were produced and then measured with appropriate dosimetric tools. Dose contributions from secondary particles produced by nuclear interactions were also investigated using field size factor experiments. Pristine Bragg peaks were reproduced with 0.7 mm range and 0.2 mm spot size accuracy. A 32 cm range spread-out Bragg peak with 10 cm modulation was reproduced with 0.8 mm range accuracy and a maximum point-to-point dose difference of less than 2%. A 2D test pattern consisting of a combination of homogeneous and high-gradient dose regions passed a 2%/2 mm gamma index comparison for 97% of the points. In conclusion, the generic modeling method proposed for scanned ion beam delivery systems was applicable to an IBA proton therapy system. The key advantage of the method is that it only requires BDL measurements of the system. The validation tests performed so far demonstrated that the beam model achieves clinical performance, paving the way for further studies toward TPS benchmarking. The method involves new sources that are available in the new Gate release V6.1 and could be further applied to other particle therapy systems delivering protons or other types of ions like carbon.

SU-E-T-755: Timing Characteristics of Proton and Carbon Ion Treatments Using a Synchrotron and Modulated Scanning

International Nuclear Information System (INIS)

Zhao, J; Li, Y; Huang, Z; Deng, Y; Sun, L; Moyers, M; Hsi, W; Wu, X

2015-01-01

Purpose: The time required to deliver a treatment impacts not only the number of patients that can be treated each day but also the accuracy of delivery due to potential movements of patient tissues. Both macroscopic and microscopic timing characteristics of a beam delivery system were studied to examine their impacts on patient treatments. Methods: 35 patients were treated during a clinical trial to demonstrate safety and efficacy of a Siemens Iontris system prior to receiving approval from the Chinese Food and Drug Administration. The system has a variable cycle time and can provide proton beams from 48 to 221 MeV/n and carbon ions from 86 to 430 MeV/n. A modulated scanning beam delivery technique is used where the beam remains stationary at each spot aiming location and is not turned off while the spot quickly moves from one aiming location to the next. The treatment log files for 28 of the trial patients were analyzed to determine several timing characteristics. Results: The average portal time per target dose was 172.5 s/Gy for protons and 150.7 s/Gy for carbon ions. The maximum delivery time for any portal was less than 300 s. The average dwell time per spot was 12 ms for protons and 3.0 ms for carbon ions. The number of aiming positions per energy layer varied from 1 to 258 for protons and 1 to 621 for carbon ions. The average spill time and cycle time per energy layer were 1.20 and 2.68 s for protons and 0.95 and 4.73 s for carbon ions respectively. For 3 of the patients, the beam was gated on and off to reduce the effects of respiration. Conclusion: For a typical target volume of 153 cc as used in this clinical trial, the portal delivery times were acceptable

Proton therapy project at PSI

International Nuclear Information System (INIS)

Nakagawa, K.; Akanuma, A.; Karasawa, K.

1990-01-01

Particle radiation which might present steeper dose distribution has received much attention as the third particle facility at the Paul Scherrer Institute (PSI), Switzerland. Proton conformation with sharp fall-off is considered to be the radiation beam suitable for confining high doses to a target volume without complications and for verifying which factor out of high RBE or physical dose distribution is more essential for local control in malignant tumors. This paper discusses the current status of the spot scanning method, which allows three dimensional conformation radiotherapy, and preliminary results. Preliminary dose distribution with proton conformation technique was acquired by modifying a computer program for treatment planning in pion treatment. In a patient with prostate carcinoma receiving both proton and pion radiation therapy, proton conformation was found to confine high doses to the target area and spare both the bladder and rectum well; and pion therapy was found to deliver non-homogeneous radiation to these organs. Although there are some obstacles in the proton project at PSI, experimental investigations are encouraging. The dynamic spot scanning method with combination of the kicker magnet, wobbler magnet, range shifter, patient transporter, and position sensitive monitor provides highly confined dose distribution, making it possible to increase total doses and thus to improve local control rate. Proton confirmation is considered to be useful for verifying possible biological effectiveness of negative pion treatment of PSI as well. (N.K.)

Proton: the particle.

Science.gov (United States)

Suit, Herman

2013-11-01

The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10(80). Protons were created at 10(-6) -1 second after the Big Bang at ≈1.37 × 10(10) years beforethe present. Proton life span has been experimentally determined to be ≥10(34) years; that is, the age of the universe is 10(-24)th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W(+), W(-), Z(0), and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter. Copyright © 2013 Elsevier Inc. All

Proton: The Particle

Energy Technology Data Exchange (ETDEWEB)

Suit, Herman

2013-11-01

The purpose of this article is to review briefly the nature of protons: creation at the Big Bang, abundance, physical characteristics, internal components, and life span. Several particle discoveries by proton as the experimental tool are considered. Protons play important roles in science, medicine, and industry. This article was prompted by my experience in the curative treatment of cancer patients by protons and my interest in the nature of protons as particles. The latter has been stimulated by many discussions with particle physicists and reading related books and journals. Protons in our universe number ≈10{sup 80}. Protons were created at 10{sup −6} –1 second after the Big Bang at ≈1.37 × 10{sup 10} years beforethe present. Proton life span has been experimentally determined to be ≥10{sup 34} years; that is, the age of the universe is 10{sup −24}th of the minimum life span of a proton. The abundance of the elements is hydrogen, ≈74%; helium, ≈24%; and heavier atoms, ≈2%. Accordingly, protons are the dominant baryonic subatomic particle in the universe because ≈87% are protons. They are in each atom in our universe and thus involved in virtually every activity of matter in the visible universe, including life on our planet. Protons were discovered in 1919. In 1968, they were determined to be composed of even smaller particles, principally quarks and gluons. Protons have been the experimental tool in the discoveries of quarks (charm, bottom, and top), bosons (W{sup +}, W{sup −}, Z{sup 0}, and Higgs), antiprotons, and antineutrons. Industrial applications of protons are numerous and important. Additionally, protons are well appreciated in medicine for their role in radiation oncology and in magnetic resonance imaging. Protons are the dominant baryonic subatomic particle in the visible universe, comprising ≈87% of the particle mass. They are present in each atom of our universe and thus a participant in every activity involving matter.

Expected proton signal sizes in the PRaVDA Range Telescope for proton Computed Tomography

International Nuclear Information System (INIS)

Price, T.; Parker, D.J.; Green, S.; Esposito, M.; Waltham, C.; Allinson, N.M.; Poludniowski, G.; Evans, P.; Taylor, J.; Manolopoulos, S.; Anaxagoras, T.; Nieto-Camero, J.

2015-01-01

Proton radiotherapy has demonstrated benefits in the treatment of certain cancers. Accurate measurements of the proton stopping powers in body tissues are required in order to fully optimise the delivery of such treaments. The PRaVDA Consortium is developing a novel, fully solid state device to measure these stopping powers. The PRaVDA Range Telescope (RT), uses a stack of 24 CMOS Active Pixel Sensors (APS) to measure the residual proton energy after the patient. We present here the ability of the CMOS sensors to detect changes in the signal sizes as the proton traverses the RT, compare the results with theory, and discuss the implications of these results on the reconstruction of proton tracks

The first private-hospital based proton therapy center in Korea; Status of the proton therapy center at Samsung Medical Center

International Nuclear Information System (INIS)

Chung, Kwang Zoo; Han, Young Yih; Kim, Jin Sung

2015-01-01

The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015

The first private-hospital based proton therapy center in Korea; status of the Proton Therapy Center at Samsung Medical Center.

Science.gov (United States)

Chung, Kwangzoo; Han, Youngyih; Kim, Jinsung; Ahn, Sung Hwan; Ju, Sang Gyu; Jung, Sang Hoon; Chung, Yoonsun; Cho, Sungkoo; Jo, Kwanghyun; Shin, Eun Hyuk; Hong, Chae-Seon; Shin, Jung Suk; Park, Seyjoon; Kim, Dae-Hyun; Kim, Hye Young; Lee, Boram; Shibagaki, Gantaro; Nonaka, Hideki; Sasai, Kenzo; Koyabu, Yukio; Choi, Changhoon; Huh, Seung Jae; Ahn, Yong Chan; Pyo, Hong Ryull; Lim, Do Hoon; Park, Hee Chul; Park, Won; Oh, Dong Ryul; Noh, Jae Myung; Yu, Jeong Il; Song, Sanghyuk; Lee, Ji Eun; Lee, Bomi; Choi, Doo Ho

2015-12-01

The purpose of this report is to describe the proton therapy system at Samsung Medical Center (SMC-PTS) including the proton beam generator, irradiation system, patient positioning system, patient position verification system, respiratory gating system, and operating and safety control system, and review the current status of the SMC-PTS. The SMC-PTS has a cyclotron (230 MeV) and two treatment rooms: one treatment room is equipped with a multi-purpose nozzle and the other treatment room is equipped with a dedicated pencil beam scanning nozzle. The proton beam generator including the cyclotron and the energy selection system can lower the energy of protons down to 70 MeV from the maximum 230 MeV. The multi-purpose nozzle can deliver both wobbling proton beam and active scanning proton beam, and a multi-leaf collimator has been installed in the downstream of the nozzle. The dedicated scanning nozzle can deliver active scanning proton beam with a helium gas filled pipe minimizing unnecessary interactions with the air in the beam path. The equipment was provided by Sumitomo Heavy Industries Ltd., RayStation from RaySearch Laboratories AB is the selected treatment planning system, and data management will be handled by the MOSAIQ system from Elekta AB. The SMC-PTS located in Seoul, Korea, is scheduled to begin treating cancer patients in 2015.

Combined treatment with atorvastatin and imipenem improves survival and vascular functions in mouse model of sepsis.

Science.gov (United States)

Choudhury, Soumen; Kannan, Kandasamy; Pule Addison, M; Darzi, Sazad A; Singh, Vishakha; Singh, Thakur Uttam; Thangamalai, Ramasamy; Dash, Jeevan Ranjan; Parida, Subhashree; Debroy, Biplab; Paul, Avishek; Mishra, Santosh Kumar

2015-08-01

We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00±4.62h from 20.00±1.66h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50±1.89h and 27.00±4.09h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α1D AR mRNA/protein expression and reversal of α1D AR desensitization mediated by GRK2/Gβγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO availability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice. Copyright © 2015 Elsevier Inc. All rights reserved.

TH-A-19A-01: An Open Source Software for Proton Treatment Planning in Heterogeneous Medium

International Nuclear Information System (INIS)

Desplanques, M; Baroni, G; Wang, K; Phillips, J; Gueorguiev, G; Sharp, G

2014-01-01

Purpose: Due to its success in Radiation Oncology during the last decade, interest in proton therapy is on the rise. Unfortunately, despite the global enthusiasm in the field, there is presently no free, multiplatform and customizable Treatment Planning System (TPS) providing proton dose distributions in heterogenous medium. This restricts substantially the progress of clinical research for groups without access to a commercial Proton TPS. The latest implementation of our pencil beam dose calculation algorithm for proton beams within the 3D Slicer open-source environment fulfills all the conditions described above. Methods: The core dose calculation algorithm is based on the Hong algorithm (1), which was upgraded with the Kanematsu theory describing the evolution of the lateral scattering of proton beamlets in heterogeneous medium. This algorithm deals with both mono-energetic beams and Spread Out Bragg Peak (SOBP). In order to be user-friendly, we provide a graphical user interface implemented with the Qt libraries, and visualization with the 3D Slicer medical image analysis software. Two different pencil beam algorithms were developed, and the clinical proton beam line at our facility was modeled. Results: The dose distributions provided by our algorithms were compared to dose distributions coming from both commercialized XiO TPS and literature (dose measurements, GEANT4 and MCNPx) and turned out to be in a good agreement, with maximum dose discrepancies of 5% in homogeneous phantoms and 10% in heterogeneous phantoms. The algorithm of SOBP creation from an optimized weigthing of mono-energetic beams results in flat SOBP. Conclusion: We hope that our efforts in implementing this new, open-source proton TPS will help the research groups to have a free access to a useful, reliable proton dose calculation software.(1) L. Hong et al., A pencil beam algorithm for proton dose calculations, Phys. Med. Biol. 41 (1996) 1305–1330. This project is paid for by NCI

Repeated proton beam therapy for hepatocellular carcinoma

International Nuclear Information System (INIS)

Hashimoto, Takayuki; Tokuuye, Koichi; Fukumitsu, Nobuyoshi; Igaki, Hiroshi; Hata, Masaharu; Kagei, Kenji; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki

2006-01-01

Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A

Absolute measurements methods for proton beam dosimetry

International Nuclear Information System (INIS)

Laitano, R.F.

1998-01-01

A widespread interest in improving proton beam characteristics and related dosimetry became apparent in the recent years, even if the advantages of protons in radiotherapy were pointed out since 1946. The early treatments by proton beams were made for a long time on a small number of patients in very few accelerators sharing their use with nuclear-physics experiments. The first proton accelerator totally dedicated to radiotherapy was established just in 1990 at the Loma Linda Medical Center in the USA. A further reason of the slowly growing use of protons for therapy in the early years, was the lack of adequate means for accurate localization of the treatment volume. The potentialities of protons in imparting a largest part of their energy to very small volumes became exploitable only after the established clinical use of accurate imaging techniques such as based on CT, NMR, PET, etc

Paediatric Photon and Proton Radiotherapy Treatment Planning Based on Advanced Imaging

DEFF Research Database (Denmark)

Kornerup, Josefine S.

The overall cure-rates for young cancer patients are continuously increasing and about 80% of the children diagnosed with cancer today will survive for more than five years. However, the cancer treatment, usually a combination of surgery, radiotherapy and chemotherapy, is aggressive. Apart from a...

Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis.

Science.gov (United States)

Kang, Young Ae; Kim, Song Yee; Jo, Kyung-Wook; Kim, Hee Jin; Park, Seung-Kyu; Kim, Tae-Hyung; Kim, Eun Kyung; Lee, Ki Man; Lee, Sung Soon; Park, Jae Seuk; Koh, Won-Jung; Kim, Dae Yun; Shim, Tae Sun

2013-01-01

Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death. Copyright © 2013 S. Karger AG, Basel.

Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

Science.gov (United States)

Glaser, Scott M; Dohopolski, Michael J; Balasubramani, Goundappa K; Flickinger, John C; Beriwal, Sushil

2017-08-01

The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

Corticosteroid Treatment Influences TA-Proteinuria and Renal Survival in IgA Nephropathy.

Directory of Open Access Journals (Sweden)

Cristina Sarcina

Full Text Available The clinical course of IgA nephropathy (IgAN and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6% and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6% and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP and diastolic (DBP blood pressure during follow-up and treatment with either steroid (CS or steroid plus azathioprine (CS+A were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.

Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation

Energy Technology Data Exchange (ETDEWEB)

Liu, Qi [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Underwood, Tracy S.A.; Kung, Jong [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Meng [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lu, Hsiao-Ming; Paganetti, Harald [Division of Radiation Physics, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Held, Kathryn D.; Hong, Theodore S.; Efstathiou, Jason A. [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Willers, Henning, E-mail: hwillers@mgh.harvard.edu [Laboratory of Cellular and Molecular Radiation Oncology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2016-05-01

Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of ∼1.1. However, emerging data have suggested that Fanconi anemia (FA) and homologous recombination pathway defects can lead to a variable RBE, at least in vitro. We investigated the role of SLX4 (FANCP), which acts as a docking platform for the assembly of multiple structure-specific endonucleases, in the response to proton irradiation. Methods and Materials: Isogenic cell pairs for the study of SLX4, XPF/ERCC1, MUS81, and SLX1 were irradiated at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer 2.5 keV/μm) or with 250 kVp x-rays, and the clonogenic survival fractions were determined. To estimate the RBE of the protons relative to cobalt-60 photons (Co60Eq), we assigned a RBE(Co60Eq) of 1.1 to x-rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor the damage responses, and the cell cycle distributions were assessed by flow cytometry. The poly(ADP-ribose) polymerase inhibitor olaparib was used for comparison. Results: Loss of SLX4 function resulted in an enhanced proton RBE(Co60Eq) of 1.42 compared with 1.11 for wild-type cells (at a survival fraction of 0.1; P<.05), which correlated with increased persistent DNA double-strand breaks in cells in the S/G{sub 2} phase. Genetic analysis identified the SLX4-binding partner MUS81 as a mediator of resistance to proton radiation. Both proton irradiation and olaparib treatment resulted in a similar prolonged accumulation of RAD51 foci in SLX4/MUS81-deficient cells, suggesting a common defect in the repair of DNA replication fork-associated damage. Conclusions: A defect in the FA pathway at the level of SLX4 results in hypersensitivity to proton radiation, which is, at least in part, due to impaired MUS81-mediated processing of replication forks that stall at clustered DNA damage. In vivo and clinical studies are needed to

Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells.

Science.gov (United States)

Iwata, Hiromitsu; Ogino, Hiroyuki; Hashimoto, Shingo; Yamada, Maho; Shibata, Hiroki; Yasui, Keisuke; Toshito, Toshiyuki; Omachi, Chihiro; Tatekawa, Kotoha; Manabe, Yoshihiko; Mizoe, Jun-etsu; Shibamoto, Yuta

2016-05-01

To determine the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and contribution of the indirect effect of spot scanning proton beams, passive scattering proton beams, or both in cultured cells in comparison with clinically used photons. The RBE of passive scattering proton beams at the center of the spread-out Bragg peak (SOBP) was determined from dose-survival curves in 4 cell lines using 6-MV X rays as controls. Survival of 2 cell lines after spot scanning and passive scattering proton irradiation was then compared. Biological effects at the distal end region of the SOBP were also investigated. The OER of passive scattering proton beams and 6 MX X rays were investigated in 2 cell lines. The RBE and OER values were estimated at a 10% cell survival level. The maximum degree of protection of radiation effects by dimethyl sulfoxide was determined to estimate the contribution of the indirect effect against DNA damage. All experiments comparing protons and X rays were made under the same biological conditions. The RBE values of passive scattering proton beams in the 4 cell lines examined were 1.01 to 1.22 (average, 1.14) and were almost identical to those of spot scanning beams. Biological effects increased at the distal end of the SOBP. In the 2 cell lines examined, the OER was 2.74 (95% confidence interval, 2.56-2.80) and 3.08 (2.84-3.11), respectively, for X rays, and 2.39 (2.38-2.43) and 2.72 (2.69-2.75), respectively, for protons (Pcells between X rays and protons). The maximum degree of protection was significantly higher for X rays than for proton beams (P<.05). The RBE values of spot scanning and passive scattering proton beams were almost identical. The OER was lower for protons than for X rays. The lower contribution of the indirect effect may partly account for the lower OER of protons. Copyright © 2016 Elsevier Inc. All rights reserved.

High-dose proton beam therapy for sinonasal mucosal malignant melanoma

International Nuclear Information System (INIS)

Fuji, Hiroshi; Yoshikawa, Shusuke; Kasami, Masako; Murayama, Shigeyuki; Onitsuka, Tetsuro; Kashiwagi, Hiroya; Kiyohara, Yoshio

2014-01-01

The significance of definitive radiotherapy for sinonasal mucosal melanoma (SMM) is sill controvertial. This study was to evaluate the role of high-dose proton beam therapy (PBT) in patients with SMM. The cases of 20 patients with SMM localized to the primary site who were treated by PBT between 2006 and 2012 were retrospectively analyzed. The patterns of overall survival and morbidity were assessed. The median follow-up time was 35 months (range, 6–77 months). The 5-year overall and disease-free survival rates were 51% and 38%, respectively. Four patients showed local failure, 2 showed regrowth of the primary tumor, and 2 showed new sinonasal tumors beyond the primary site. The 5-year local control rate after PBT was 62%. Nodal and distant failure was seen in 7 patients. Three grade 4 late toxicities were observed in tumor-involved optic nerve. Our findings suggested that high-dose PBT is an effective local treatment that is less invasive than surgery but with comparable outcomes

Fan-beam intensity modulated proton therapy.

Science.gov (United States)

Hill, Patrick; Westerly, David; Mackie, Thomas

2013-11-01

This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0-255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage. Overall, the sharp distal

Radiomodifying effect of caffeine on mammalian cellular system using gamma radiation and proton beam radiation

International Nuclear Information System (INIS)

Samanth, Sneha P.; Yadav, Usha; Shirsath, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Bhat, Nagesh N.; Anjaria, K.B.; Sapra, B.K.

2016-01-01

Caffeine is a commonly consumed neurostimulant in the world. Reports suggest the radiomodifying effects of caffeine against low Linear Energy Transfer (LET) radiation when administered pre and post irradiation by releasing checkpoint arrest. In the present report, the radioprotective and radiosensitizing ability of caffeine (10μM - 2mM) were studied on Chinese Hamster Ovary (CRO) cell line against low as well as high LET radiation when administered pre, post and continuously during radiation. Effect of caffeine treatment on the genotoxicity induced by gamma and proton beam radiation was assessed by micronucleus assay. Effect of caffeine treatment on clonogenic survival of irradiated cells was also assessed

Evidence-based support for the use of proton pump inhibitors in cancer therapy.

Science.gov (United States)

Fais, Stefano

2015-11-24

'We can only cure what we can understand first', said Otto H. Warburg, the 1931 Nobel laureate for his discovery on tumor metabolism. Unfortunately, we still don't know too much the mechanisms underlying of cancer development and progression. One of the unsolved mystery includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery, that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. One of the most mechanism to survive to the acidic tumor microenvironment are proton exchangers not allowing intracellular acidification through a continuous elimination of H(+) either outside the cells or within the internal vacuoles. This article wants to comment a translational process through which from the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed chemosensitizers as well, we have got to the clinical proof of concept that PPI may well be included in new anti-cancer strategies, and with a solid background and rationale.

Conformal proton radiation therapy for pediatric low-grade astrocytomas

International Nuclear Information System (INIS)

Hug, E.B.; Loma Linda Univ. Medical Center, Loma Linda, CA; Darthmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Muenter, M.W.; Archambeau, J.O.; DeVries, A.; Loredo, L.N.; Grove, R.I.; Slater, J.D.; Liwnicz, B.

2002-01-01

Background: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). Patients and Method: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephatic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (cobalt gray equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. Results: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. Conclusions: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment

Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy

DEFF Research Database (Denmark)

Murphy, P. S.; Viviers, L; Abson, C

2004-01-01

Assessment of low-grade glioma treatment response remains as much of a challenge as the treatment itself. Proton magnetic resonance spectroscopy ((1)H-MRS) and imaging were incorporated into a study of patients receiving temozolomide therapy for low-grade glioma in order to evaluate and monitor...... tumour metabolite and volume changes during treatment. Patients (n=12) received oral temozolomide (200 mg m(-2) day(-1)) over 5 days on a 28-day cycle for 12 cycles. Response assessment included baseline and three-monthly magnetic resonance imaging studies (pretreatment, 3, 6, 9 and 12 months) assessing...... months, a significant reduction in the mean choline signal was observed compared with the pretreatment (P=0.035) and 3-month scan (P=0.021). The reduction in the tumour choline/water signal paralleled tumour volume change and may reflect the therapeutic effect of temozolomide...

FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

Energy Technology Data Exchange (ETDEWEB)

Gerbaudo, Victor H.; Mamede, Marcelo [Brigham and Women' s Hospital, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston, MA (United States); Trotman-Dickenson, Beatrice; Hatabu, Hiroto [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Radiology, Boston, MA (United States); Sugarbaker, David J. [Brigham and Women' s Hospital, Harvard Medical School, Division of Thoracic Surgery, Boston, MA (United States)

2011-05-15

This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 {+-} 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

International Nuclear Information System (INIS)

Gerbaudo, Victor H.; Mamede, Marcelo; Trotman-Dickenson, Beatrice; Hatabu, Hiroto; Sugarbaker, David J.

2011-01-01

This study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm. Fifty patients with MPM underwent FDG PET/CT for restaging 11 ± 6 months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date. Treatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously

Reirradiation of Head and Neck Cancers With Proton Therapy: Outcomes and Analyses

Energy Technology Data Exchange (ETDEWEB)

Phan, Jack [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Sio, Terence T. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Oncology, Mayo Clinic, Scottsdale, Arizona (United States); Nguyen, Theresa P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Takiar, Vinita [Department of Radiation Oncology, University of Cincinnati, Cincinnati, Ohio (United States); Gunn, G. Brandon; Garden, Adam S.; Rosenthal, David I.; Fuller, Clifton D.; Morrison, William H.; Beadle, Beth; Ma, Dominic [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zafereo, Mark E. [Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hutcheson, Kate A. [Department of Speech Pathology University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kupferman, Michael E. [Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); William, William N. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-09-01

Purpose: Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. Methods and Materials: We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events Version 4.0. Results: The conditions of 60 patients were evaluated, with a median follow-up time of 13.6 months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure–free survival, overall survival, progression-free survival, and distant metastasis–free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). Conclusions: Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.

Reirradiation of Head and Neck Cancers With Proton Therapy: Outcomes and Analyses

International Nuclear Information System (INIS)

Phan, Jack; Sio, Terence T.; Nguyen, Theresa P.; Takiar, Vinita; Gunn, G. Brandon; Garden, Adam S.; Rosenthal, David I.; Fuller, Clifton D.; Morrison, William H.; Beadle, Beth; Ma, Dominic; Zafereo, Mark E.; Hutcheson, Kate A.; Kupferman, Michael E.; William, William N.; Frank, Steven J.

2016-01-01

Purpose: Reirradiation of head and neck (H&N) cancer is a clinical challenge. Proton radiation therapy (PRT) offers dosimetric advantages for normal tissue sparing and may benefit previously irradiated patients. Here, we report our initial experience with the use of PRT for H&N reirradiation, with focus on clinical outcomes and toxicity. Methods and Materials: We retrospectively reviewed the records of patients who received H&N reirradiation with PRT from April 2011 through June 2015. Patients reirradiated with palliative intent or without prior documentation of H&N radiation therapy were excluded. Radiation-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events Version 4.0. Results: The conditions of 60 patients were evaluated, with a median follow-up time of 13.6 months. Fifteen patients (25%) received passive scatter proton therapy (PSPT), and 45 (75%) received intensity modulated proton therapy (IMPT). Thirty-five patients (58%) received upfront surgery, and 44 (73%) received concurrent chemotherapy. The 1-year rates of locoregional failure–free survival, overall survival, progression-free survival, and distant metastasis–free survival were 68.4%, 83.8%, 60.1%, and 74.9%, respectively. Eighteen patients (30%) experienced acute grade 3 (G3) toxicity, and 13 (22%) required a feeding tube at the end of PRT. The 1-year rates of late G3 toxicity and feeding tube independence were 16.7% and 2.0%, respectively. Three patients may have died of reirradiation-related effects (1 acute and 2 late). Conclusions: Proton beam therapy can be a safe and effective curative reirradiation strategy, with acceptable rates of toxicity and durable disease control.

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Hua, C. [St. Jude Children’s Research Hospital (United States)

2016-06-15

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

WE-D-BRB-03: Current State of Volumetric Image Guidance for Proton Therapy

International Nuclear Information System (INIS)

Hua, C.

2016-01-01

The goal of this session is to review the physics of proton therapy, treatment planning techniques, and the use of volumetric imaging in proton therapy. The course material covers the physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for double scattering (DS), uniform scanning (US), and pencil beam scanning (PBS). The session covers the treatment planning strategies used in DS, US, and PBS for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. It introduces the audience to the current status of image guided proton therapy and clinical applications of CBCT for proton therapy. It outlines the importance of volumetric imaging in proton therapy. Learning Objectives: Gain knowledge in proton therapy physics, and treatment planning for proton therapy including intensity modulated proton therapy. The current state of volumetric image guidance equipment in proton therapy. Clinical applications of CBCT and its advantage over orthogonal imaging for proton therapy. B. Teo, B.K Teo had received travel funds from IBA in 2015.

Effects of proton beam irradiation on seed germination and growth of soybean ( Glycine max L. Merr.)

Science.gov (United States)

Im, Juhyun; Kim, Woon Ji; Kim, Sang Hun; Ha, Bo-Keun

2017-12-01

The present study aimed to evaluate the morphological effects of proton beam irradiation on the seed germination, seedling survival, and plant growth of soybean. Seeds of three Korean elite cultivars (Kwangankong, Daepungkong, and Pungsannamulkong) were irradiated with a 57-MeV proton beam in the range of 50 - 400 Gy. The germination rates of all the varieties increased to > 95%; however, the survival rates were significantly reduced. At doses of > 300 Gy irradiation, the Daepungkong, Kwangankong, and Pungsannamulkong cultivars exhibited 39, 75, and 71% survival rates, respectively. In addition, plant height and the fresh weight of shoots and roots were significantly decreased by doses of > 100 Gy irradiation, as were the dry weights of the shoots and roots. However, SPAD values increased with increasing doses of irradiation. Abnormal plants with atypically branched stems, modified leaves, and chlorophyll mutations were observed. Based on the survival rate, plant growth inhibition, and mutation frequency, it appears that the optimum dosage of proton beam irradiation for soybean mutation breeding is between 250 and 300 Gy.

Optimization of a general-purpose, actively scanned proton beamline for ocular treatments: Geant4 simulations.

Science.gov (United States)

Piersimoni, Pierluigi; Rimoldi, Adele; Riccardi, Cristina; Pirola, Michele; Molinelli, Silvia; Ciocca, Mario

2015-03-08

The Italian National Center for Hadrontherapy (CNAO, Centro Nazionale di Adroterapia Oncologica), a synchrotron-based hospital facility, started the treatment of patients within selected clinical trials in late 2011 and 2012 with actively scanned proton and carbon ion beams, respectively. The activation of a new clinical protocol for the irradiation of uveal melanoma using the existing general-purpose proton beamline is foreseen for late 2014. Beam characteristics and patient treatment setup need to be tuned to meet the specific requirements for such a type of treatment technique. The aim of this study is to optimize the CNAO transport beamline by adding passive components and minimizing air gap to achieve the optimal conditions for ocular tumor irradiation. The CNAO setup with the active and passive components along the transport beamline, as well as a human eye-modeled detector also including a realistic target volume, were simulated using the Monte Carlo Geant4 toolkit. The strong reduction of the air gap between the nozzle and patient skin, as well as the insertion of a range shifter plus a patient-specific brass collimator at a short distance from the eye, were found to be effective tools to be implemented. In perspective, this simulation toolkit could also be used as a benchmark for future developments and testing purposes on commercial treatment planning systems.

SU-E-T-161: Characterization and Validation of CT Simulator Hounsfield Units to Relative Stopping Power Values for Proton Treatment Planning

International Nuclear Information System (INIS)

Schnell, E; Ahmad, S; De La Fuente Herman, T

2015-01-01

Purpose: To develop a calibration curve that includes and minimizes the variations of Hounsfield Unit (HU) from a CT scanner to Relative Stopping Power (RSP) of tissues along the proton beam path. The variations are due to scanner and proton energy, technique, phantom size and placement, and tissue arrangement. Methods: A CIRS 062 M phantom with 10 plugs of known relative electron density (RED) was scanned through a 16 slice GE Discovery CT Simulator scanner. Three setup combinations of plug distributions and techniques clinically implemented for five treatment regions were scanned with energies of 100, 120, and 140 kV. Volumetric HU values were measured for each plug and scan. The RSP values derived through the Bethe-Bloch formula are currently being verified with parallel-plate ionization chamber measurements in water using 80, 150, and 225 MeV proton beam. Typical treatment plans for treatment regions of brain, head-&-neck, chest, abdomen, and pelvis are being planned and dose delivered will be compared with film and Optically Stimulated Luminescence (OSL) measurements. Results: Percentage variations were determined for each variable. For tissues close to water, variations were <1% from any given parameter. Tissues far from water equivalence (lung and bone) showed the greatest sensitivity to change (7.4% maximum) with scanner energy and up to 5.3% with positioning of the phantom. No major variations were observed for proton energies within the treatment range. Conclusion: When deriving a calibration curve, attention should be placed to low and high HU values. A thorough verification process of calculated vs. water-phantom measured RSP values at different proton energies, followed by dose validation of planned vs. measured doses in phantom with film and OSL detectors are currently being undertaken

[Neoplastic transformation of mouse fibroblasts under the influence of high-energy protons and gamma-rays].

Science.gov (United States)

Voskanian, K Sh

2004-01-01

Oncoginic transformations of mouse fibroblasts C3H10T1/2 after exposure to proton energies 150 and 584 MeV were compared with fibroblast effects of gamma-radiation. Prior to exposure, cell populations (2.7 x 10(3) cells/cm2) were inoculated in plastic vials with the surface area of 75 cm2 and cultivated 11 days. Survivability was determined by comparing the number of cell colonies in irradiated and non-irradiated (control) vials. Transformation rate was calculated by dividing the total transformation focus number by the number of survived cells in a vial. Rate of oncogenic transformations after gamma- and proton (584 MeV) irradiation was essentially identical, i.e. the parameter grew rapidly at the doses 1 Gy. In the dose interval between 1 and 5 Gy, transformation rate for proton energy 150 MeV was found low compared with gamma-radiation and proton energy 584 MeV. It is hypothesized that the different transformation rate after exposure to proton energy 150 MeV is linked with the high linear energy transfer as compared with the proton energy of 584 MeV and gamma-radiation.

Survival after treatment with phenylacetate and benzoate for urea-cycle disorders.

Science.gov (United States)

Enns, Gregory M; Berry, Susan A; Berry, Gerard T; Rhead, William J; Brusilow, Saul W; Hamosh, Ada

2007-05-31

The combination of intravenous sodium phenylacetate and sodium benzoate has been shown to lower plasma ammonium levels and improve survival in small cohorts of patients with historically lethal urea-cycle enzyme defects. We report the results of a 25-year, open-label, uncontrolled study of sodium phenylacetate and sodium benzoate therapy (Ammonul, Ucyclyd Pharma) in 299 patients with urea-cycle disorders in whom there were 1181 episodes of acute hyperammonemia. Overall survival was 84% (250 of 299 patients). Ninety-six percent of the patients survived episodes of hyperammonemia (1132 of 1181 episodes). Patients over 30 days of age were more likely than neonates to survive an episode (98% vs. 73%, Purea-cycle disorder and treatment with both sodium phenylacetate and sodium benzoate, in conjunction with other therapies, such as intravenous arginine hydrochloride and the provision of adequate calories to prevent catabolism, effectively lower plasma ammonium levels and result in survival in the majority of patients. Hemodialysis may also be needed to control hyperammonemia, especially in neonates and older patients who do not have a response to intravenous sodium phenylacetate and sodium benzoate. Copyright 2007 Massachusetts Medical Society.

Advances in compact proton spectrometers for inertial-confinement fusion and plasma nuclear science.

Science.gov (United States)

Seguin, F H; Sinenian, N; Rosenberg, M; Zylstra, A; Manuel, M J-E; Sio, H; Waugh, C; Rinderknecht, H G; Johnson, M Gatu; Frenje, J; Li, C K; Petrasso, R; Sangster, T C; Roberts, S

2012-10-01

Compact wedge-range-filter proton spectrometers cover proton energies ∼3-20 MeV. They have been used at the OMEGA laser facility for more than a decade for measuring spectra of primary D(3)He protons in D(3)He implosions, secondary D(3)He protons in DD implosions, and ablator protons in DT implosions; they are now being used also at the National Ignition Facility. The spectra are used to determine proton yields, shell areal density at shock-bang time and compression-bang time, fuel areal density, and implosion symmetry. There have been changes in fabrication and in analysis algorithms, resulting in a wider energy range, better accuracy and precision, and better robustness for survivability with indirect-drive inertial-confinement-fusion experiments.

Preparation of pediatric patients for treatment with proton beam therapy

International Nuclear Information System (INIS)

Mizumoto, Masashi; Oshiro, Yoshiko; Ayuzawa, Kaoru; Miyamoto, Toshio; Okumura, Toshiyuki; Fukushima, Takashi; Fukushima, Hiroko; Ishikawa, Hitoshi; Tsuboi, Koji; Sakurai, Hideyuki

2015-01-01

Purpose: Anesthesia is often used in proton beam therapy (PBT) for pediatric patients and this may prolong the treatment time. The aim of the study was to examine preparation of pediatric patients to allow smooth performance of PBT. Material and methods: Preparation was initiated 1–2 days before treatment planning CT and continued for 10 days. The patient first visited the facility to become familiar with the treatment room and staff. As the second step, the patient stayed in the treatment bed for a certain time with their mother, and then stayed on the treatment bed alone. Special fixtures painted with characters, music, and gifts were also prepared. Results: From 2010 to 2014, 111 pediatric patients underwent PBT. These patients were divided into 3 groups: 40 who could follow instructions well (group A, median age: 13.6 years old), 60 who could communicate, but found it difficult to stay alone for a long time (group B, median age: 4.6 years old), and 11 who could not follow instructions (group C, median age: 1.6 years old). Preparation was used for patients in group B. The mean treatment times in groups A, B and C were 13.6, 17.1, and 15.6 min, respectively, on PBT treatment days 2–6, and 11.8, 13.0, and 16.9 min, respectively, for the last 5 days of PBT treatment. The time reduction was significant in group B (p = 0.003). Conclusion: Preparation is useful for pediatric patients who can communicate. This approach allows PBT to be conducted more smoothly over a shorter treatment time

Reassessment of the Necessity of the Proton Gantry: Analysis of Beam Orientations From 4332 Treatments at the Massachusetts General Hospital Proton Center Over the Past 10 Years

Energy Technology Data Exchange (ETDEWEB)

Yan, Susu, E-mail: syan5@mgh.harvard.edu; Lu, Hsiao-Ming; Flanz, Jay; Adams, Judith; Trofimov, Alexei; Bortfeld, Thomas

2016-05-01

Purpose: To retrospectively analyze the beam approaches used in gantry-based proton treatments, and to reassess the practical advantages of the gantry, compared with beam approaches that are achievable without a gantry, in the context of present-day technology. Methods and Materials: We reviewed the proton therapy plans of 4332 patients treated on gantries at our hospital, delivered by the double scattering technique (n=4228) and, more recently, pencil beam scanning (PBS) (n=104). Beam approaches, relative to the patient frame, were analyzed individually to identify cases that could be treated without a gantry. Three treatment configurations were considered, with the patient in lying position, sitting position, or both. The FIXED geometry includes a fixed horizontal portal. The BEND geometry enables a limited vertical inflection of the beam by up to 20°. The MOVE geometry allows for flexibility of the patient head and body setup. Results: The percentage of patients with head and neck tumors that could be treated without a gantry using double scattering was 44% in FIXED, 70% in 20° BEND, and 100% in 90° MOVE. For torso regions, 99% of patients could be treated in 20° BEND. Of 104 PBS treatments, all but 1 could be reproduced with FIXED geometry. The only exception would require a 10° BEND capability. Note here that the PBS treatments were applied to select anatomic sites, including only 2 patients with skull-base tumors. Conclusions: The majority of practical beam approaches can be realized with gantry-less delivery, aided by limited beam bending and patient movements. Practical limitations of the MOVE geometry, and treatments requiring a combination of lying and sitting positions, may lower the percentage of head and neck patients who could be treated without a gantry. Further investigation into planning, immobilization, and imaging is needed to remove the practical limitations and to facilitate proton treatment without a gantry.

Cell-based neurotrophin treatment supports long-term auditory neuron survival in the deaf guinea pig.

Science.gov (United States)

Gillespie, Lisa N; Zanin, Mark P; Shepherd, Robert K

2015-01-28

The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the primary auditory neurons (ANs) of the cochlea. However, ANs degenerate in deafness; the preservation of a robust AN target population, in combination with advances in cochlear implant technology, may provide improved hearing outcomes for cochlear implant patients. The exogenous delivery of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 is well known to support AN survival in deafness, and cell-based therapies provide a potential clinically viable option for delivering neurotrophins into the deaf cochlea. This study utilized cells that were genetically modified to express BDNF and encapsulated in alginate microspheres, and investigated AN survival in the deaf guinea pig following (a) cell-based neurotrophin treatment in conjunction with chronic electrical stimulation from a cochlear implant, and (b) long-term cell-based neurotrophin delivery. In comparison to deafened controls, there was significantly greater AN survival following the cell-based neurotrophin treatment, and there were ongoing survival effects for at least six months. In addition, functional benefits were observed following cell-based neurotrophin treatment and chronic electrical stimulation, with a statistically significant decrease in electrically evoked auditory brainstem response thresholds observed during the experimental period. This study demonstrates that cell-based therapies, in conjunction with a cochlear implant, shows potential as a clinically transferable means of providing neurotrophin treatment to support AN survival in deafness. This technology also has the potential to deliver other therapeutic agents, and to be used in conjunction with other biomedical devices for the treatment of a variety of neurodegenerative conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program

Science.gov (United States)

Zacharia, Brad E.; Bruce, Samuel S.; Goldstein, Hannah; Malone, Hani R.; Neugut, Alfred I.; Bruce, Jeffrey N.

2012-01-01

Craniopharyngioma is a rare primary central nervous system neoplasm. Our objective was to determine factors associated with incidence, treatment, and survival of craniopharyngiomas in the United States. We used the surveillance, epidemiology and end results program (SEER) database to identify patients who received a diagnosis of craniopharyngioma during 2004–2008. We analyzed clinical and demographic information, including age, race, sex, tumor histology, and treatment. Age-adjusted incidence rates and age, sex, and race-adjusted expected survival rates were calculated. We used Cox proportional hazards models to determine the association between covariates and overall survival. We identified 644 patients with a diagnosis of craniopharyngioma. Black race was associated with an age-adjusted relative risk for craniopharyngioma of 1.26 (95% confidence interval [CI], 0.98–1.59), compared with white race. One- and 3-year survival rates of 91.5% (95% CI, 88.9%–93.5%), and 86.2% (95% CI, 82.7%–89.0%) were observed for the cohort; relative survival rates were 92.1% (95% CI, 89.5%–94.0%) and 87.6% (95% CI, 84.1%–90.4%) for 1- and 3-years, respectively. In the multivariable model, factors associated with prolonged survival included younger age, smaller tumor size, subtotal resection, and radiation therapy. Black race, on the other hand, was associated with worse overall survival in the final model. We demonstrated that >85% of patients survived 3 years after diagnosis and that subtotal resection and radiation therapy were associated with prolonged survival. We also noted a higher incidence rate and worse 1- and 3-year survival rates in the black population. Future investigations should examine these racial disparities and focus on evaluating the efficacy of emerging treatment paradigms. PMID:22735773

Corticosterone, but not Glucose, Treatment Enables Fasted Adrenalectomized Rats to Survive Moderate Hemorrhage

Science.gov (United States)

Darlington, Daniel N.; Chew, Gordon; Ha, Taryn; Keil, Lanny C.; Dallman, Mary F.

1990-01-01

Fed adrenalectomized rats survive the stress of hemorrhage and hypovolemia, whereas fasted adrenalectomized rats become hypotensive and hypoglycemic after the first 90 min and die within 4 hours (h). We have studied the effects of glucose and corticosterone (B) infusions after hemorrhage as well as treatment with B at the time of adrenalectomy on the capacity of chronically prepared, conscious, fasted, adrenalectomized rats to survive hemorrhage. We have also measured the magnitudes of vasoactive hormone responses to hemorrhage. Maintenance of plasma glucose concentrations did not sustain life; however, treatment of rats at the time of adrenalectomy with B allowed 100 percent survival, and acute treatment of adrenalectomized rats at the time of hemorrhage allowed about 50 percent survival during the 5-h posthemorrhage observation period. Rats in the acute B infusion group that died exhibited significantly increased plasma B and significantly decreased plasma glucose concentrations by 2 h compared to the rats that lived. Plasma vasopressin, renin, and norepinephrine responses to hemorrhage were markedly augmented in the adrenalectomized rats not treated with B, and plasma vasopressin concentrations were significantly elevated at 1 and 2 h in all of the rats that subsequently died compared to values in those that lived. We conclude that: 1) death after hemorrhage in fasted adrenalectomized rats is not a result of lack of glucose; 2) chronic and, to an extent, acute treatment of fasted adrenalectomized rats with B enables survival; 3) fasted adrenalectomized rats exhibit strong evidence of hepatic insufficiency which is not apparent in either fed adrenalectomized rats or B-treated fasted adrenalectomized rats; 4) death after hemorrhage in fasted adrenalectomized rats may result from hepatic failure as a consequence of marked splanchnic vasoconstriction mediated bv the actions of extraordinarily high levels of vasoactive hormones after hemorrhage; and 5) B appears to

IBA's state of art Proton Therapy System

International Nuclear Information System (INIS)

Ternier, Sonja

2001-01-01

Full text: In recent years, IBA has developed a state-of-the-art Proton Therapy System that is currently being implemented at the Northeast Proton Therapy Center in Boston. First patient treatment is predicted for the fourth quarter of 2001. The IBA Proton Therapy System consists of a 230 MeV accelerator (a fixed energy isochronous cyclotron), an Energy Selection System that can decrease the energy down to 70 MeV and up to five treatment rooms. There are two types of treatment rooms. A gantry treatment room in which a patient can be treated from virtually any angle or a fixed horizontal beam line aimed at treatments of the of the head and neck. The system is equipped with a Therapy Control System and a Global Safety Management System. The Integrated Therapy Control System is an integrated system ensuring the control of the treatment sessions through independent but networked therapy control units and, therefore, the control of each equipment subsystem. The integrated safety management system, independent of the Therapy Control System, includes a set of hard-wired safety devices, ensuring the safety of the patient and personnel. The system will be capable of delivering proton treatments in four-treatment modes: Double Scattering, Single Scattering, Wobbling and Pencil Beam Scanning. The presentation will show the most important subsystems and treatment modes capabilities as well as the most recent advances in the technology. (author)

Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

International Nuclear Information System (INIS)

Greenberger, Benjamin A.; Pulsifer, Margaret B.; Ebb, David H.; MacDonald, Shannon M.; Jones, Robin M.; Butler, William E.; Huang, Mary S.; Marcus, Karen J.; Oberg, Jennifer A.; Tarbell, Nancy J.; Yock, Torunn I.

2014-01-01

Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy RBE (48.6-54 Gy RBE ). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 Gy RBE to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis

Clinical Outcomes and Late Endocrine, Neurocognitive, and Visual Profiles of Proton Radiation for Pediatric Low-Grade Gliomas

Energy Technology Data Exchange (ETDEWEB)

Greenberger, Benjamin A. [Harvard Medical School, Boston, Massachusetts (United States); Pulsifer, Margaret B. [Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (United States); Ebb, David H. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Jones, Robin M. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts (United States); Butler, William E. [Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Huang, Mary S. [Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts (United States); Marcus, Karen J. [Department of Radiation Oncology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Oberg, Jennifer A. [Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York (United States); Tarbell, Nancy J. [Harvard Medical School, Boston, Massachusetts (United States); Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-08-01

Purpose/Objective(s): Primary low-grade gliomas are common brain tumors of childhood, many of which require radiation therapy (RT) as definitive treatment. Increased conformality of RT could decrease the incidence and severity of late effects. We report our experience with 32 pediatric patients treated with proton RT. Methods and Materials: Thirty-two pediatric patients with low-grade gliomas of the brain or spinal cord were treated with proton RT from 1995 to 2007. Sixteen patients received at least 1 regimen of chemotherapy before definitive RT. The median radiation dose was 52.2 Gy{sub RBE} (48.6-54 Gy{sub RBE}). Results: The median age at treatment was 11.0 years (range, 2.7-21.5 years), with a median follow-up time of 7.6 years (range, 3.2-18.2 years). The 6-year and 8-year rates of progression-free survival were 89.7% and 82.8%, respectively, with an 8-year overall survival of 100%. For the subset of patients who received serial neurocognitive testing, there were no significant declines in Full-Scale Intelligence Quotient (P=.80), with a median neurocognitive testing interval of 4.5 years (range, 1.2-8.1 years) from baseline to follow-up, but subgroup analysis indicated some significant decline in neurocognitive outcomes for young children (<7 years) and those with significant dose to the left temporal lobe/hippocampus. The incidence of endocrinopathy correlated with a mean dose of ≥40 Gy{sub RBE} to the hypothalamus, pituitary, or optic chiasm. Stabilization or improvement of visual acuity was achieved in 83.3% of patients at risk for radiation-induced injury to the optic pathways. Conclusions: This report of late effects in children with low-grade gliomas after proton RT is encouraging. Proton RT appears to be associated with good clinical outcome, especially when the tumor location allows for increased sparing of the left temporal lobe, hippocampus, and hypothalamic-pituitary axis.

Recircular accelerator to proton ocular therapy

International Nuclear Information System (INIS)

Rabelo, Luisa A.; Campos, Tarcisio P.R.

2013-01-01

Proton therapy has been used for the treatment of Ocular Tumors, showing control in most cases as well as conservation of the eyeball, avoiding the enucleation. The protons provide higher energetic deposition in depth with reduced lateral spread, compared to the beam of photons and electrons, with characteristic dose deposition peak (Bragg peak). This technique requires large particle accelerators hampering the deployment a Proton Therapy Center in some countries due to the need for an investment of millions of dollars. This study is related to a new project of an electromagnetic unit of proton circular accelerator to be coupled to the national radiopharmaceutical production cyclotrons, to attend ocular therapy. This project evaluated physical parameters of proton beam circulating through classical and relativistic mechanical formulations and simulations based on an ion transport code in electromagnetic fields namely CST (Computer Simulation Technology). The structure is differentiated from other circular accelerations (patent CTIT/UFMG NRI research group/UFMG). The results show the feasibility of developing compact proton therapy equipment that works like pre-accelerator or post-accelerator to cyclotrons, satisfying the interval energy of 15 MeV to 64 MeV. Methods of reducing costs of manufacture, installation and operation of this equipment will facilitate the dissemination of the proton treatment in Brazil and consequently advances in fighting cancer. (author)

Recircular accelerator to proton ocular therapy

Energy Technology Data Exchange (ETDEWEB)

Rabelo, Luisa A.; Campos, Tarcisio P.R., E-mail: luisarabelo88@gmail.com, E-mail: tprcampos@pq.cnpq.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear

2013-07-01

Proton therapy has been used for the treatment of Ocular Tumors, showing control in most cases as well as conservation of the eyeball, avoiding the enucleation. The protons provide higher energetic deposition in depth with reduced lateral spread, compared to the beam of photons and electrons, with characteristic dose deposition peak (Bragg peak). This technique requires large particle accelerators hampering the deployment a Proton Therapy Center in some countries due to the need for an investment of millions of dollars. This study is related to a new project of an electromagnetic unit of proton circular accelerator to be coupled to the national radiopharmaceutical production cyclotrons, to attend ocular therapy. This project evaluated physical parameters of proton beam circulating through classical and relativistic mechanical formulations and simulations based on an ion transport code in electromagnetic fields namely CST (Computer Simulation Technology). The structure is differentiated from other circular accelerations (patent CTIT/UFMG NRI research group/UFMG). The results show the feasibility of developing compact proton therapy equipment that works like pre-accelerator or post-accelerator to cyclotrons, satisfying the interval energy of 15 MeV to 64 MeV. Methods of reducing costs of manufacture, installation and operation of this equipment will facilitate the dissemination of the proton treatment in Brazil and consequently advances in fighting cancer. (author)

The influence of cultural treatments of the long-term survival and growth of planted Quercus rubra

Science.gov (United States)

James J. Zaczek; Kim C. Steiner

2011-01-01

A northern red oak (Quercus rubra L.) plantation testing 20 nursery stock and planting methods was used to evaluate treatments 3, 6, 10, and 17 years after planting. Survival over all treatments was 92 percent at age 3 and declined to 74 percent, 56 percent, and 39 percent at ages 6, 10, and 17, respectively. At age 17, survival was highest for...

WE-E-BRF-01: The ESTRO-AAPM Joint Symposium On Imaging for Proton Treatment Planning and Guidance

Energy Technology Data Exchange (ETDEWEB)

Parodi, K [Ludwig-Maximilians-University Munich, Garching, Bavaria (Germany); Dauvergne, D [Institut de Physique Nucleaire de Lyon, Lyon (France); Kruse, J [Mayo Clinic, Rochester, MN (United States)

2014-06-15

beam scale for active proton beam delivery in homogenous targets. The development of gamma cameras, that has been studied by several groups worldwide over the last years, now reaches - for some of them - the stage of being applicable in clinical conditions, with real size prototypes and count rate capability matching the therapeutic beam intensities. We will review the different concepts of gamma cameras, the advantages and limitations of this method, and the main challenges that should still be overcome before the widespread of prompt gamma quality assurance for proton and hadrontherapy. Jon Kruse (Mayo Clinic, Rochester, MN, USA) Treatment simulation images for proton therapy are used to determine proton stopping power and range in the patient. This talk will discuss the careful control of CT numbers and conversion of CT number to stopping power required in proton therapy. Imaging for treatment guidance of proton therapy also presents unique challenges which will be addressed. Among them are the enhanced relationship between internal anatomy changes and dosimetry, the need for imaging to support adaptive planning protocols, and high operational efficiency. Learning Objectives: To learn about the possibilities of using activation products to determine the range of particle beams in a patient treatment setting To be informed on an alternative methodology using prompt gamma detectors To understand the impact of the accuracy of the knowledge of the patient information with respect to the delivered treatment.

Clinical commissioning of an in vivo range verification system for prostate cancer treatment with anterior and anterior oblique proton beams

Science.gov (United States)

Hoesl, M.; Deepak, S.; Moteabbed, M.; Jassens, G.; Orban, J.; Park, Y. K.; Parodi, K.; Bentefour, E. H.; Lu, H. M.

2016-04-01

The purpose of this work is the clinical commissioning of a recently developed in vivo range verification system (IRVS) for treatment of prostate cancer by anterior and anterior oblique proton beams. The IRVS is designed to perform a complete workflow for pre-treatment range verification and adjustment. It contains specifically designed dosimetry and electronic hardware and a specific software for workflow control with database connection to the treatment and imaging systems. An essential part of the IRVS system is an array of Si-diode detectors, designed to be mounted to the endorectal water balloon routinely used for prostate immobilization. The diodes can measure dose rate as function of time from which the water equivalent path length (WEPL) and the dose received are extracted. The former is used for pre-treatment beam range verification and correction, if necessary, while the latter is to monitor the dose delivered to patient rectum during the treatment and serves as an additional verification. The entire IRVS workflow was tested for anterior and 30 degree inclined proton beam in both solid water and anthropomorphic pelvic phantoms, with the measured WEPL and rectal doses compared to the treatment plan. Gafchromic films were also used for measurement of the rectal dose and compared to IRVS results. The WEPL measurement accuracy was in the order of 1 mm and after beam range correction, the dose received by the rectal wall were 1.6% and 0.4% from treatment planning, respectively, for the anterior and anterior oblique field. We believe the implementation of IRVS would make the treatment of prostate with anterior proton beams more accurate and reliable.

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protontherapie D'Orsay experience

International Nuclear Information System (INIS)

Noeel, Georges; Habrand, Jean-Louis; Mammar, Hamid; Pontvert, Dominique; Haie-Meder, Christine; Hasboun, Dominique; Moisson, Patricia; Ferrand, Regis; Beaudre, Anne; Boisserie, Gilbert; Gaboriaud, Genevieve; Mazal, Alexandre; Kerody, Katia; Schlienger, Michel; Mazeron, Jean-Jacques

2001-01-01

Purpose: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. Methods and Materials : Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protontherapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). Results: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. Conclusion: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up

SU-F-T-216: Evaluating Dosimetry Accuracy of a Treatment Planning System On Small Proton Fields

Energy Technology Data Exchange (ETDEWEB)

Zhang, M; Xiao, Z; Zou, J; Chen, T; Yue, N [Rutgers University, New Brunswick, NJ (United States)

2016-06-15

Purpose: This study is aiming to identify the smallest field size for which a treatment planning system (TPS) can accurately calculate the relative dose distribution. The finding would be used as a guideline to choose the smallest proton field for clinical treatment. Methods: Mevion S250™ double scattering proton delivery system and Eclipse™ TPS (Varian) with pencil beam convolution (PBC) dose algorithm were used in this study. Square sized fields of 1 cm, 2 cm, 3 cm, 4 cm, 5 cm, and 10 cm were planned on a cubical water phantom with iso-center placed at 10 cm depth. All beams used the same proton beam option: range 15 cm and modulation 10 cm. Dose in water was calculated without any compensator. Gafchromic™ EBT3 film and diode detectors were used to measure the central axis dose distribution and lateral dose profiles at 5 cm, 10 cm, and 14 cm depth. Results: The preliminary film measurement shows good agreement between Eclipse calculated lateral dose profiles for all tested field sizes. The differences on full width half maximum were ≤ 1 mm while the differences on the penumbras were between 1 mm and 2 mm between Eclipse and film. For the depth dose, Eclipse results matched well with film measurements for field sizes down to 2 cm{sup 2}. With smaller field size of 1 cm{sup 2}, Eclipse was able to predict the decreasing of SOBP due to the lack of lateral charged particle equilibrium in depth. However, it did not match the film measurement. Diode measurement results will be available at the time of presentation. Conclusion: The PBC dose algorithm in Eclipse can accurately calculate relative dose distribution in double scattered proton system for field size down to 2 cm{sup 2}.

In vivo verification of proton beam path by using post-treatment PET/CT imaging

Energy Technology Data Exchange (ETDEWEB)

Hsi, Wen C.; Indelicato, Daniel J.; Vargas, Carlos; Duvvuri, Srividya; Li Zuofeng; Palta, Jatinder [Proton Therapy Institute, University of Florida, Jacksonville, Florida 32206 (United States); Boca Radiation Oncology Associates, Boca Raton, Florida 33431 (United States); Proton Therapy Institute, University of Florida, Jacksonville, Florida 32206 (United States); Department of Radiation Oncology, University of Florida, Gainesville, Florida 32610 (United States)

2009-09-15

Purpose: The purpose of this study is to establish the in vivo verification of proton beam path by using proton-activated positron emission distributions. Methods: A total of 50 PET/CT imaging studies were performed on ten prostate cancer patients immediately after daily proton therapy treatment through a single lateral portal. The PET/CT and planning CT were registered by matching the pelvic bones, and the beam path of delivered protons was defined in vivo by the positron emission distribution seen only within the pelvic bones, referred to as the PET-defined beam path. Because of the patient position correction at each fraction, the marker-defined beam path, determined by the centroid of implanted markers seen in the post-treatment (post-Tx) CT, is used for the planned beam path. The angular variation and discordance between the PET- and marker-defined paths were derived to investigate the intrafraction prostate motion. For studies with large discordance, the relative location between the centroid and pelvic bones seen in the post-Tx CT was examined. The PET/CT studies are categorized for distinguishing the prostate motion that occurred before or after beam delivery. The post-PET CT was acquired after PET imaging to investigate prostate motion due to physiological changes during the extended PET acquisition. Results: The less than 2 deg. of angular variation indicates that the patient roll was minimal within the immobilization device. Thirty of the 50 studies with small discordance, referred as good cases, show a consistent alignment between the field edges and the positron emission distributions from the entrance to the distal edge. For those good cases, average displacements are 0.6 and 1.3 mm along the anterior-posterior (D{sub AP}) and superior-inferior (D{sub SI}) directions, respectively, with 1.6 mm standard deviations in both directions. For the remaining 20 studies demonstrating a large discordance (more than 6 mm in either D{sub AP} or D{sub SI}), 13

Neurocognitive functioning in pediatric craniopharyngioma: performance before treatment with proton therapy.

Science.gov (United States)

Fournier-Goodnight, Ashley S; Ashford, Jason M; Merchant, Thomas E; Boop, Frederick A; Indelicato, Daniel J; Wang, Lei; Zhang, Hui; Conklin, Heather M

2017-08-01

The goal of this study was to investigate the impact of patient-, disease-, and treatment-related variables upon neurocognitive outcomes in pediatric patients with craniopharyngioma prior to treatment with proton therapy or observation after radical resection. For all participants (N = 104), relevant clinical and demographic variables were attained and neurocognitive evaluations completed prior to irradiation or planned observation. One-sample t-tests were conducted to compare performance to published normative data. Linear models were used to investigate predictors of performance on measures where performance was below normative expectations. Participants showed poorer performance in comparison to the normative group across neurocognitive domains including executive functions (e.g., working memory; Wechsler Digit Span Backward p = 0.03), learning and memory (e.g., California Verbal Learning Test [CVLT] Total T p = 0.00), and fine-motor coordination (e.g., Grooved Pegboard Dominant Hand p = 0.00). Poor performance across areas was predicted by presurgical hypothalamic involvement (e.g., Behavior Rating Inventory of Executive Function Working Memory Index Grade 2 β = -7.68, p = 0.03; CVLT Total T Grade 2 β = 7.94, p = 0.04; Grade 3 β = -9.80, p = 0.00), extent of surgery (e.g., CVLT Total T Resection β = -7.77, p = 0.04; Grooved Pegboard Dominant Hand β = -1.58, p = 0.04), and vision status (e.g., CVLT Total T Reduced vision without impairment β = -10.01, p = 0.02; Grooved Pegboard Dominant Hand Bilateral field defect β = -1.45, p = 0.01; Reduced vision without impairment β = -2.30, p = 0.00). This study demonstrated that patients with craniopharyngioma show weaker neurocognitive performance in comparison to the normative population resulting from tumor, events leading to diagnosis, and early surgical intervention. Systematic investigation of neurocognitive performance before

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Colaco, Rovel J.; Huh, Soon; Nichols, Romaine; Morris, Christopher G.; Flampouri, Stella; Li, Zuofeng; Hoppe, Bradford S. [Univ. of Florida Proton Therapy Inst., Jacksonville (United States)], e-mail: bhoppe@floridaproton.org; D' Agostino, Harry [Dept. of Thoracic Surgery, Univ. of Florida Coll. of Medicine, Gainesville (United States); Pham, Dat C. [Dept. of Hematology and Medical Oncology, Univ. of Florida Coll. of Medicine, Gainesville (United States); Bajwa, Abubakr A. [Dept. of Medicine, Univ. of Florida Coll. of Medicine, Gainesville (United States)

2013-04-15

Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods: Six patients were treated; five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died; two of progressive disease and one after a fall. The latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer

International Nuclear Information System (INIS)

Colaco, Rovel J.; Huh, Soon; Nichols, Romaine; Morris, Christopher G.; Flampouri, Stella; Li, Zuofeng; Hoppe, Bradford S.; D'Agostino, Harry; Pham, Dat C.; Bajwa, Abubakr A.

2013-01-01

Background: Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Material and methods: Six patients were treated; five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. Results: The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died; two of progressive disease and one after a fall. The latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. Conclusion. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further

Proton-air and proton-proton cross sections

Directory of Open Access Journals (Sweden)

Ulrich Ralf

2013-06-01

Full Text Available Different attempts to measure hadronic cross sections with cosmic ray data are reviewed. The major results are compared to each other and the differences in the corresponding analyses are discussed. Besides some important differences, it is crucial to see that all analyses are based on the same fundamental relation of longitudinal air shower development to the observed fluctuation of experimental observables. Furthermore, the relation of the measured proton-air to the more fundamental proton-proton cross section is discussed. The current global picture combines hadronic proton-proton cross section data from accelerator and cosmic ray measurements and indicates a good consistency with predictions of models up to the highest energies.

Physical and biological factors determining the effective proton range

International Nuclear Information System (INIS)

Grün, Rebecca; Friedrich, Thomas; Krämer, Michael; Scholz, Michael; Zink, Klemens; Durante, Marco; Engenhart-Cabillic, Rita

2013-01-01

Purpose: Proton radiotherapy is rapidly becoming a standard treatment option for cancer. However, even though experimental data show an increase of the relative biological effectiveness (RBE) with depth, particularly at the distal end of the treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy. This discrepancy might affect the effective penetration depth of the proton beam and thus the dose to the surrounding tissue and organs at risk. The purpose of this study was thus to analyze the impact of a tissue and dose dependent RBE of protons on the effective range of the proton beam in comparison to the range based on a generic RBE of 1.1.Methods: Factors influencing the biologically effective proton range were systematically analyzed by means of treatment planning studies using the Local Effect Model (LEM IV) and the treatment planning software TRiP98. Special emphasis was put on the comparison of passive and active range modulation techniques.Results: Beam energy, tissue type, and dose level significantly affected the biological extension of the treatment field at the distal edge. Up to 4 mm increased penetration depth as compared to the depth based on a constant RBE of 1.1. The extension of the biologically effective range strongly depends on the initial proton energy used for the most distal layer of the field and correlates with the width of the distal penumbra. Thus, the range extension, in general, was more pronounced for passive as compared to active range modulation systems, whereas the maximum RBE was higher for active systems.Conclusions: The analysis showed that the physical characteristics of the proton beam in terms of the width of the distal penumbra have a great impact on the RBE gradient and thus also the biologically effective penetration depth of the beam

SU-E-T-130: Are Proton Gantries Needed? An Analysis of 4332 Patient Proton Gantry Treatment Plans From the Past 10 Years

International Nuclear Information System (INIS)

Yan, S; Lu, H; Flanz, J; Depauw, N; Adams, J; Gorissen, BL; Wang, Y; Daartz, J; Bortfeld, T

2015-01-01

Purpose: To ascertain the necessity of a proton gantry, as compared to the feasibility of using a horizontal fixed proton beam-line for treatment with advanced technology. Methods: To calculate the percentage of patients that can be treated with a horizontal fixed beam-line instead of a gantry, we analyze the distributions of beam orientations of our proton gantry patients treated over the past 10 years. We identify three horizontal fixed beam geometries (FIXED, BEND and MOVE) with the patient in lying and/or sitting positions. The FIXED geometry includes only table/chair rotations and translations. In BEND, the beam can be bent up/down for up to 20 degrees. MOVE allows for patient head/body angle adjustment. Based on the analysis, we select eight patients whose plan involves beams which are still challenging to achieve with a horizontal fixed beam. These beams are removed in the pencil beam scanning (PBS) plan optimized for the fixed beam-line (PBS-fix). We generate non-coplanar PBS-gantry plans for comparison, and perform a robustness analysis. Results: The percentage of patients with head-and-neck/brain tumors that can be treated with horizontal fixed beam is 44% in FIXED, 70% in 20-degrees BEND, and 100% in 90-degrees MOVE. For torso regions, 99% of the patients can be treated in 20-degree BEND. The target coverage is more homogeneous with PBS-fix plans compared to the clinical scattering treatment plans. The PBS-fix plans reduce the mean dose to organs-at-risk by a factor of 1.1–28.5. PBS-gantry plans are as good as PBS-fix plans, sometimes marginally better. Conclusion: The majority of the beam orientations can be realized with a horizontal fixed beam-line. Challenging non-coplanar beams can be eliminated with PBS delivery. Clinical implementation of the proposed fixed beam-line requires use of robotic patient positioning, further developments in immobilization, and image guidance. However, our results suggest that fixed beam-lines can be as effective as

SU-E-T-130: Are Proton Gantries Needed? An Analysis of 4332 Patient Proton Gantry Treatment Plans From the Past 10 Years

Energy Technology Data Exchange (ETDEWEB)

Yan, S; Lu, H; Flanz, J; Depauw, N; Adams, J; Gorissen, BL; Wang, Y; Daartz, J; Bortfeld, T [Massachusetts General Hospital, Boston, MA (United States)

2015-06-15

Purpose: To ascertain the necessity of a proton gantry, as compared to the feasibility of using a horizontal fixed proton beam-line for treatment with advanced technology. Methods: To calculate the percentage of patients that can be treated with a horizontal fixed beam-line instead of a gantry, we analyze the distributions of beam orientations of our proton gantry patients treated over the past 10 years. We identify three horizontal fixed beam geometries (FIXED, BEND and MOVE) with the patient in lying and/or sitting positions. The FIXED geometry includes only table/chair rotations and translations. In BEND, the beam can be bent up/down for up to 20 degrees. MOVE allows for patient head/body angle adjustment. Based on the analysis, we select eight patients whose plan involves beams which are still challenging to achieve with a horizontal fixed beam. These beams are removed in the pencil beam scanning (PBS) plan optimized for the fixed beam-line (PBS-fix). We generate non-coplanar PBS-gantry plans for comparison, and perform a robustness analysis. Results: The percentage of patients with head-and-neck/brain tumors that can be treated with horizontal fixed beam is 44% in FIXED, 70% in 20-degrees BEND, and 100% in 90-degrees MOVE. For torso regions, 99% of the patients can be treated in 20-degree BEND. The target coverage is more homogeneous with PBS-fix plans compared to the clinical scattering treatment plans. The PBS-fix plans reduce the mean dose to organs-at-risk by a factor of 1.1–28.5. PBS-gantry plans are as good as PBS-fix plans, sometimes marginally better. Conclusion: The majority of the beam orientations can be realized with a horizontal fixed beam-line. Challenging non-coplanar beams can be eliminated with PBS delivery. Clinical implementation of the proposed fixed beam-line requires use of robotic patient positioning, further developments in immobilization, and image guidance. However, our results suggest that fixed beam-lines can be as effective as

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients

DEFF Research Database (Denmark)

Møller, Henrik; Coupland, Victoria H; Tataru, Daniela

2018-01-01

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment...... and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following...... diagnosis. RESULTS: Survival improved over the period studied. The use of active treatment varied between geographical areas, with inter-quintile ranges of 9%-17% for surgical resection, 4%-13% for radical radiotherapy, and 22%-35% for chemotherapy. At 2 years, there were 188 potentially avoidable deaths...

Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

Directory of Open Access Journals (Sweden)

Kristoffer Watten Brudvik

2013-01-01

Full Text Available Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months. Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

Affluence and Private Health Insurance Influence Treatment and Survival in Non-Hodgkin's Lymphoma.

Directory of Open Access Journals (Sweden)

Harry Comber

Full Text Available The aim of this study was to investigate inequalities in survival for non-Hodgkin's lymphoma (NHL, distinguishing between direct and indirect effects of patient, social and process-of-care factors.All cases of NHL diagnosed in Ireland in 2004-2008 were included. Variables describing patient, cancer, stage and process of care were included in a discrete-time model of survival using Structural Equation Modelling software.Emergency admissions were more common in patients with co-morbid conditions or with more aggressive cancers, and less frequent for patients from more affluent areas. Aggressive morphology, female sex, emergency admission, increasing age, comorbidity, treatment in a high caseload hospital and late stage were associated with increased hazard of mortality. Private patients had a reduced hazard of mortality, mediated by systemic therapy, admission to high caseload hospitals and fewer emergency admissions.The higher rate of emergency presentation, and consequent poorer survival, of uninsured patients, suggests they face barriers to early presentation. Social, educational and cultural factors may also discourage disadvantaged patients from consulting with early symptoms of NHL. Non-insured patients, who present later and have more emergency admissions would benefit from better access to diagnostic services. Older patients remain disadvantaged by sub-optimal treatment, treatment in non-specialist centres and emergency admission.

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: A treatment planning comparison

International Nuclear Information System (INIS)

Kandula, Shravan; Zhu, Xiaorong; Garden, Adam S.; Gillin, Michael; Rosenthal, David I.; Ang, Kie-Kian; Mohan, Radhe; Amin, Mayankkumar V.; Garcia, John A.; Wu, Richard; Sahoo, Narayan; Frank, Steven J.

2013-01-01

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V 10 , V 30 , and V 50 values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life

Proton therapy with spot scanning: the Rinecker Proton Therapy Center in Munich. Part 2: Technical and physical aspects

International Nuclear Information System (INIS)

Borchert, H. J.; Mayr, M.; Schneider, R. A.; Arnold, M. R.; Geismar, D. E.; Wilms, M.; Wisser, L.; Herbst, M.

2008-01-01

The Rinecker Proton Therapy Center (RPTC) in Munich is about to introduce into clinical radiation therapy, a 2D scanning technique (spot scanning) of a single proton pencil beam. It will be available at four gantries and a fifth treatment room allocates a fixed beam unit for a scattering technique. A superconducting cyclotron extracts protons with a constant energy of 250 MeV. Far upstream of the patient follows modulation of the energy with a degrader according to the prescription of the patients treatment planning. A 10 mm pencil beam at full width of half maximum (FWHM) will enable scanning of individual tumour volumes at any depth i.e. 1 minute for a target volume of 1 litre and a dose of 2 Gy. Innovative solutions will be established for other important issues such as dosimetric monitoring, safety concepts and positioning of the patient. The physical characteristics of proton beam spot scanning offer exceptional possibilities in conformal radiation therapy. Together with intensity modulated proton therapy (IMPT) it significantly improves the sparing of organs at risk and of healthy tissues. (author)

Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

International Nuclear Information System (INIS)

Griffiths, Robert; Gleeson, Michelle; Knopf, Kevin; Danese, Mark

2010-01-01

Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL. Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality. Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1

Commissioning of output factors for uniform scanning proton beams

International Nuclear Information System (INIS)

Zheng Yuanshui; Ramirez, Eric; Mascia, Anthony; Ding Xiaoning; Okoth, Benny; Zeidan, Omar; Hsi Wen; Harris, Ben; Schreuder, Andries N.; Keole, Sameer

2011-01-01

Purpose: Current commercial treatment planning systems are not able to accurately predict output factors and calculate monitor units for proton fields. Patient-specific field output factors are thus determined by either measurements or empirical modeling based on commissioning data. The objective of this study is to commission output factors for uniform scanning beams utilized at the ProCure proton therapy centers. Methods: Using water phantoms and a plane parallel ionization chamber, the authors first measured output factors with a fixed 10 cm diameter aperture as a function of proton range and modulation width for clinically available proton beams with ranges between 4 and 31.5 cm and modulation widths between 2 and 15 cm. The authors then measured the output factor as a function of collimated field size at various calibration depths for proton beams of various ranges and modulation widths. The authors further examined the dependence of the output factor on the scanning area (i.e., uncollimated proton field), snout position, and phantom material. An empirical model was developed to calculate the output factor for patient-specific fields and the model-predicted output factors were compared to measurements. Results: The output factor increased with proton range and field size, and decreased with modulation width. The scanning area and snout position have a small but non-negligible effect on the output factors. The predicted output factors based on the empirical modeling agreed within 2% of measurements for all prostate treatment fields and within 3% for 98.5% of all treatment fields. Conclusions: Comprehensive measurements at a large subset of available beam conditions are needed to commission output factors for proton therapy beams. The empirical modeling agrees well with the measured output factor data. This investigation indicates that it is possible to accurately predict output factors and thus eliminate or reduce time-consuming patient-specific output

Survival and metamorphosis of low-density populations of larval sea lampreys (Petromyzon marinus) in streams following lampricide treatment

Science.gov (United States)

Johnson, Nicholas S.; Swink, William D.; Brenden, Travis O.; Slade, Jeffrey W.; Steeves, Todd B.; Fodale, Michael F.; Jones, Michael L.

2014-01-01

Sea lamprey Petromyzon marinus control in the Great Lakes primarily involves application of lampricides to streams where larval production occurs to kill larvae prior to their metamorphosing and entering the lakes as parasites (juveniles). Because lampricides are not 100% effective, larvae that survive treatment maymetamorphose before streams are again treated. Larvae that survive treatment have not beenwidely studied, so their dynamics are notwell understood.Wetagged and released larvae in six Great Lake tributaries following lampricide treatment and estimated vital demographic rates using multistate tag-recovery models. Model-averaged larval survivals ranged from 56.8 to 57.6%. Model-averaged adult recovery rates, which were the product of juvenile survivals and adult capture probabilities, ranged from 6.8 to 9.3%. Using stochastic simulations, we estimated production of juvenile sea lampreys from a hypothetical population of treatment survivors under different growth conditions based on parameter estimates from this research. For fast-growing populations, juvenile production peaked 2 years after treatment. For slow-growing populations, juvenile production was approximately one-third that of fast-growing populations,with production not peaking until 4 years after treatment. Our results suggest that dynamics (i.e., survival, metamorphosis) of residual larval populations are very similar to those of untreated larval populations. Consequently, residual populations do not necessarily warrant special consideration for the purpose of sea lamprey control and can be ranked for treatment along with other populations. Consecutive lampricide treatments, which are under evaluation by the sea lamprey control program, would bemost effective for reducing juvenile production in large, fast-growing populations.

Power of protons in the fight against cancer

International Nuclear Information System (INIS)

Hansen, W.

2011-01-01

a large percentage of patients with cancer are receiving radiotherapy as part of their treatment. At present it is possible to plan with precision these treatments, reducing the risk of side effects and increasing therapeutic efficiency. Proton therapy (also known as particle therapy) is a form external radiotherapy that uses beams of energized protons to treat cancer. The main advantage of proton therapy is its ability to accurately manage an optimal dose of radiation to the tumor, without damaging surrounding healthy tissues and significantly reducing the likelihood and/or severity of side effects. (Author)

Biological Considerations When Comparing Proton Therapy. With Photon Therapy

NARCIS (Netherlands)

Paganetti, Harald; van Luijk, Peter

Owing to the limited availability of data on the outcome of proton therapy, treatments are generally optimized based on broadly available data on photon-based treatments. However, the microscopic pattern of energy deposition of protons differs from that of photons, leading to a different biological

WE-H-BRA-01: BEST IN PHYSICS (THERAPY): Nano-Dosimetric Kinetic Model for Variable Relative Biological Effectiveness of Proton and Ion Beams

Energy Technology Data Exchange (ETDEWEB)

Abolfath, R; Bronk, L; Titt, U.; Grosshans, D; Mohan, R [The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Helo, Y [University College London, London (United Kingdom); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States)

2016-06-15

Purpose: Recent clonogenic cell survival and γH2AX studies suggest proton relative biological effectiveness (RBE) may be a non-linear function of linear energy transfer (LET) in the distal edge of the Bragg peak and beyond. We sought to develop a multiscale model to account for non-linear response phenomena to aid in the optimization of intensity-modulated proton therapy. Methods: The model is based on first-principle simulations of proton track structures, including secondary ions, and an analytical derivation of the dependence on particle LET of the linear-quadratic (LQ) model parameters α and β. The derived formulas are an extension of the microdosimetric kinetic (MK) model that captures dissipative track structures and non-Poissonian distribution of DNA damage at the distal edge of the Bragg peak and beyond. Monte Carlo simulations were performed to confirm the non-linear dose-response characteristics arising from the non-Poisson distribution of initial DNA damage. Results: In contrast to low LET segments of the proton depth dose, from the beam entrance to the Bragg peak, strong deviations from non-dissipative track structures and Poisson distribution in the ionization events in the Bragg peak distal edge govern the non-linear cell response and result in the transformation α=(1+c-1 L) α-x+2(c-0 L+c-2 L^2 )(1+c-1 L) β-x and β=(1+c-1 L)^2 β-x. Here L is the charged particle LET, and c-0,c-1, and c-2 are functions of microscopic parameters and can be served as fitting parameters to the cell-survival data. In the low LET limit c-1, and c-2 are negligible hence the linear model proposed and used by Wilkins-Oelfke for the proton treatment planning system can be retrieved. The present model fits well the recent clonogenic survival data measured recently in our group in MDACC. Conclusion: The present hybrid method provides higher accuracy in calculating the RBE-weighted dose in the target and normal tissues.

WE-H-BRA-01: BEST IN PHYSICS (THERAPY): Nano-Dosimetric Kinetic Model for Variable Relative Biological Effectiveness of Proton and Ion Beams

International Nuclear Information System (INIS)

Abolfath, R; Bronk, L; Titt, U.; Grosshans, D; Mohan, R; Helo, Y; Schuemann, J

2016-01-01

Purpose: Recent clonogenic cell survival and γH2AX studies suggest proton relative biological effectiveness (RBE) may be a non-linear function of linear energy transfer (LET) in the distal edge of the Bragg peak and beyond. We sought to develop a multiscale model to account for non-linear response phenomena to aid in the optimization of intensity-modulated proton therapy. Methods: The model is based on first-principle simulations of proton track structures, including secondary ions, and an analytical derivation of the dependence on particle LET of the linear-quadratic (LQ) model parameters α and β. The derived formulas are an extension of the microdosimetric kinetic (MK) model that captures dissipative track structures and non-Poissonian distribution of DNA damage at the distal edge of the Bragg peak and beyond. Monte Carlo simulations were performed to confirm the non-linear dose-response characteristics arising from the non-Poisson distribution of initial DNA damage. Results: In contrast to low LET segments of the proton depth dose, from the beam entrance to the Bragg peak, strong deviations from non-dissipative track structures and Poisson distribution in the ionization events in the Bragg peak distal edge govern the non-linear cell response and result in the transformation α=(1+c_1 L) α_x+2(c_0 L+c_2 L^2 )(1+c_1 L) β_x and β=(1+c_1 L)^2 β_x. Here L is the charged particle LET, and c_0,c_1, and c_2 are functions of microscopic parameters and can be served as fitting parameters to the cell-survival data. In the low LET limit c_1, and c_2 are negligible hence the linear model proposed and used by Wilkins-Oelfke for the proton treatment planning system can be retrieved. The present model fits well the recent clonogenic survival data measured recently in our group in MDACC. Conclusion: The present hybrid method provides higher accuracy in calculating the RBE-weighted dose in the target and normal tissues.

Gluon saturation: Survival probability for leading neutrons in DIS

International Nuclear Information System (INIS)

Levin, Eugene; Tapia, Sebastian

2012-01-01

In this paper we discuss the example of one rapidity gap process: the inclusive cross sections of the leading neutrons in deep inelastic scattering with protons (DIS). The equations for this process are proposed and solved, giving the example of theoretical calculation of the survival probability for one rapidity gap processes. It turns out that the value of the survival probability is small and it decreases with energy.

Effect of proton-pump inhibitor treatment on symptoms and quality of life in GERD patients depends on the symptom-reflux association

NARCIS (Netherlands)

Aanen, Marissa C.; Weusten, Bas L. A. M.; Numans, Mattijs E.; de Wit, Niek J.; Samsom, Melvin; Smout, Andre J. P. M.

2008-01-01

Backgound: Gastroesophageal reflux disease patients demonstrate various pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump inhibitor (PPI) treatment can be expected. We investigated the effect of short-term PPI treatment on symptoms and quality of life (QOL) in primary

Brain tumors in children: long-term survival after radiation treatment

Energy Technology Data Exchange (ETDEWEB)

Jenkin, Derek; Greenberg, Mark; Hoffman, Harold; Hendrick, Bruce; Humphreys, Robin; Vatter, Annette

1995-02-01

Purpose: To determine the cause of death in children who survive more than 5 years after radiation treatment of a brain tumor. Methods and Material: Nine hundred and twelve consecutive children with a primary brain tumor irradiated at the Princess Margaret Hospital or Toronto-Bayview Regional Cancer Center from 1958 to 1991, were evaluated for long-term outcome. Results: Overall 10- and 20-year survival rates were 44% and 37%. Subsequent survival of 377 5-year survivors was, at an additional 10 and 20 years, 78% and 67%. Most (83%) deaths that occurred more than 5 years from diagnosis were a result of relapse of the original tumor. The 10-year survival rate subsequent to relapse was 9% when the first relapse occurred less than one year from diagnosis, 17% for 1-2 years, and 31% when the time to relapse was 3 years or greater. The cumulative actuarial incidence of, and death from, second malignant tumors at 30 years from diagnosis was 18% and 13%, respectively. Conclusions: Death later than 5 years from diagnosis of a brain tumor in children is common and is usually due to progressive disease in slowly evolving low grade tumors. Death from a second malignant tumor becomes more frequent than death from the original tumor after 15 years from diagnosis.

Spot Scanning Proton Therapy for Malignancies of the Base of Skull: Treatment Planning, Acute Toxicities, and Preliminary Clinical Outcomes

Energy Technology Data Exchange (ETDEWEB)

Grosshans, David R., E-mail: dgrossha@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, X. Ronald; Melancon, Adam [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Poenisch, Falk; Palmer, Matthew [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); McAleer, Mary Frances; McGovern, Susan L. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); DeMonte, Franco [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chang, Eric L. [Department of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California (United States); Brown, Paul D.; Mahajan, Anita [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-11-01

Purpose: To describe treatment planning techniques and early clinical outcomes in patients treated with spot scanning proton therapy for chordoma or chondrosarcoma of the skull base. Methods and Materials: From June 2010 through August 2011, 15 patients were treated with spot scanning proton therapy for chordoma (n=10) or chondrosarcoma (n=5) at a single institution. Toxicity was prospectively evaluated and scored weekly and at all follow-up visits according to Common Terminology Criteria for Adverse Events, version 3.0. Treatment planning techniques and dosimetric data were recorded and compared with those of passive scattering plans created with clinically applicable dose constraints. Results: Ten patients were treated with single-field-optimized scanning beam plans and 5 with multifield-optimized intensity modulated proton therapy. All but 2 patients received a simultaneous integrated boost as well. The mean prescribed radiation doses were 69.8 Gy (relative biological effectiveness [RBE]; range, 68-70 Gy [RBE]) for chordoma and 68.4 Gy (RBE) (range, 66-70) for chondrosarcoma. In comparison with passive scattering plans, spot scanning plans demonstrated improved high-dose conformality and sparing of temporal lobes and brainstem. Clinically, the most common acute toxicities included fatigue (grade 2 for 2 patients, grade 1 for 8 patients) and nausea (grade 2 for 2 patients, grade 1 for 6 patients). No toxicities of grades 3 to 5 were recorded. At a median follow-up time of 27 months (range, 13-42 months), 1 patient had experienced local recurrence and a second developed distant metastatic disease. Two patients had magnetic resonance imaging-documented temporal lobe changes, and a third patient developed facial numbness. No other subacute or late effects were recorded. Conclusions: In comparison to passive scattering, treatment plans for spot scanning proton therapy displayed improved high-dose conformality. Clinically, the treatment was well tolerated, and

SU-F-T-163: Improve Proton Therapy Efficiency: Report of a Workshop

Energy Technology Data Exchange (ETDEWEB)

Zheng, Y [Procure Proton Therapy Center, Oklahoma City, OK (United States); Flanz, J [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Mah, D [Procure Treatment Center, Somerset, NJ (United States); Pankuch, M; Kreydick, B [Northwestern Medicine Proton Center, Warrenville, IL (United States); Beltran, C [Mayo Clinic, Rochester, MN (United States); Robison, B; Schreuder, A [Provision Healthcare Partners, Knoxville, TN (United States)

2016-06-15

Purpose: The technology of proton therapy, especially the pencil beam scanning technique, is evolving very quickly. However, the efficiency of proton therapy seems to lag behind conventional photon therapy. The purpose of the abstract is to report on the findings of a workshop on improvement of QA, planning and treatment efficiency in proton therapy. Methods: A panel of physicists, clinicians, and vendor representatives from over 18 institutions in the United States and internationally were convened in Knoxville, Tennessee in November, 2015. The panel discussed several topics on how to improve proton therapy efficiency, including 1) lean principle and failure mode and effects analysis, 2) commissioning and machine QA, 3) treatment planning, optimization and evaluation, 4) patient positioning and IGRT, 5) vendor liaison and machine availability, and 6) staffing, education and training. Results: The relative time needed for machine QA, treatment planning & check in proton therapy was found to range from 1 to 2.5 times of that in photon therapy. Current status in proton QA, planning and treatment was assessed. Key areas for efficiency improvement, such as elimination of unnecessary QA items or steps and development of efficient software or hardware tools, were identified. A white paper to summarize our findings is being written. Conclusion: It is critical to improve efficiency by developing reliable proton beam lines, efficient software tools on treatment planning, optimization and evaluation, and dedicated proton QA device. Conscious efforts and collaborations from both industry leaders and proton therapy centers are needed to achieve this goal and further advance the technology of proton therapy.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

International Nuclear Information System (INIS)

Zenda, Sadamoto; Kawashima, Mitsuhiko; Nishio, Teiji; Kohno, Ryosuke; Nihei, Keiji; Onozawa, Masakatsu; Arahira, Satoko; Ogino, Takashi

2011-01-01

Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

Energy Technology Data Exchange (ETDEWEB)

Zenda, Sadamoto [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan); Kawashima, Mitsuhiko; Nishio, Teiji; Kohno, Ryosuke; Nihei, Keiji; Onozawa, Masakatsu; Arahira, Satoko; Ogino, Takashi [Division of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Chiba (Japan)

2011-09-01

Purpose: The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. Methods and Materials: Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. Results: Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. Conclusions: Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

Monte-Carlo simulation of proton radiotherapy for human eye

International Nuclear Information System (INIS)

Liu Yunpeng; Tang Xiaobin; Xie Qin; Chen Feida; Geng Changran; Chen Da

2010-01-01

The 62 MeV proton beam was selected to develop a MCNPX model of the human eye to approximate dose delivered from proton therapy by. In the course of proton therapy, two treatment simulations were considered. The first simulation was an ideal treatment scenario. In this case, the dose of tumor was 50.03 Gy, which was at the level of effective treatment, while other organizations were in the range of acceptable dose. The second case was a worst case scenario to simulate a patient gazing directly into the treatment beam during therapy. The bulk of dose deposited in the cornea, lens, and anterior chamber region. However, the dose of tumor area was zero. The calculated results show an agreement accordance with the relative reference, which confirmed that the MCNPX code can simulate proton radiotherapy perfectly, and is a capable platform for patient planning. The data from the worst case can be used for dose reconstruction of the clinical accident. (authors)

Proton-proton bremsstrahlung

International Nuclear Information System (INIS)

Fearing, H.W.

1990-01-01

We summarize some of the information about the nucleon-nucleon force which has been obtained by comparing recent calculations of proton-proton bremsstrahlung with cross section and analyzing power data from the new TRIUMF bremsstrahlung experiment. Some comments are made as to how these results can be extended to neutron-proton bremsstrahlung. (Author) 17 refs., 6 figs

MO-FG-CAMPUS-TeP3-02: Benchmarks of a Proton Relative Biological Effectiveness (RBE) Model for DNA Double Strand Break (DSB) Induction in the FLUKA, MCNP, TOPAS, and RayStation™ Treatment Planning System

Energy Technology Data Exchange (ETDEWEB)

Stewart, R [University of Washington, Seattle, WA (United States); Streitmatter, S [University of Utah Hospitals, Salt Lake City, UT (United States); Traneus, E [RAYSEARCH LABORATORIES AB, Stockholm (Sweden); Moskvin, V [St. Jude Children’s Hospital, Memphis, TN (United States); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States)

2016-06-15

Purpose: Validate implementation of a published RBE model for DSB induction (RBEDSB) in several general purpose Monte Carlo (MC) code systems and the RayStation™ treatment planning system (TPS). For protons and other light ions, DSB induction is a critical initiating molecular event that correlates well with the RBE for cell survival. Methods: An efficient algorithm to incorporate information on proton and light ion RBEDSB from the independently tested Monte Carlo Damage Simulation (MCDS) has now been integrated into MCNP (Stewart et al. PMB 60, 8249–8274, 2015), FLUKA, TOPAS and a research build of the RayStation™ TPS. To cross-validate the RBEDSB model implementation LET distributions, depth-dose and lateral (dose and RBEDSB) profiles for monodirectional monoenergetic (100 to 200 MeV) protons incident on a water phantom are compared. The effects of recoil and secondary ion production ({sub 2}H{sub +}, {sub 3}H{sub +}, {sub 3}He{sub 2+}, {sub 4}He{sub 2+}), spot size (3 and 10 mm), and transport physics on beam profiles and RBEDSB are examined. Results: Depth-dose and RBEDSB profiles among all of the MC models are in excellent agreement using a 1 mm distance criterion (width of a voxel). For a 100 MeV proton beam (10 mm spot), RBEDSB = 1.2 ± 0.03 (− 2–3%) at the tip of the Bragg peak and increases to 1.59 ± 0.3 two mm distal to the Bragg peak. RBEDSB tends to decrease as the kinetic energy of the incident proton increases. Conclusion: The model for proton RBEDSB has been accurately implemented into FLUKA, MCNP, TOPAS and the RayStation™TPS. The transport of secondary light ions (Z > 1) has a significant impact on RBEDSB, especially distal to the Bragg peak, although light ions have a small effect on (dosexRBEDSB) profiles. The ability to incorporate spatial variations in proton RBE within a TPS creates new opportunities to individualize treatment plans and increase the therapeutic ratio. Dr. Erik Traneus is employed full-time as a Research Scientist

Do patient characteristics, disease, or treatment explain social inequality in survival from colorectal cancer?

DEFF Research Database (Denmark)

Frederiksen, Birgitte Lidegaard; Osler, Merete; Harling, Henrik

2009-01-01

This paper investigates the association between individually measured socioeconomic status (SES) and all-cause survival in colorectal cancer patients, and explores whether factors related to the patient, the disease, or the surgical treatment mediate the observed social gradient. The data were...... on comorbidity from previous hospitalizations and use of medication. Only patients with colorectal cancer as their first primary tumour and those born after 1920 were included. A total of 8763 patients were included in the study. Cox proportional hazard regression models revealed a positive social gradient......, while no evidence of a mediating effect was found for disease or surgical treatment factors. This indicates that the difference in survival among colorectal cancer patients from different social groups was probably not caused by unintentional differences in treatment factors related to surgery...

Acute skin reactions observed in fractionated proton irradiation

International Nuclear Information System (INIS)

Arimoto, Takuro; Maruhashi, Noboru; Takada, Yoshihisa; Hayakawa, Yoshinori; Inada, Tetsuo; Kitagawa, Toshio

1989-01-01

Between May 1985 and July 1987, 49 skin reactions of 43 patients treated by proton irradiation were observed at the Particle Radiation Medical Science Center (PARMS), the University of Tsukuba. Taking the peak skin score as an endpoint, the radiobiological effects [relative biological effectiveness (RBE) and time-dose relationship] of the proton beam in multi-fractionated treatments were estimated. Factors influencing the skin dose, such as the prescribed tumor dose, tumor site, and number of applied fields, were also analyzed. The following conclusions regarding acute skin reactions to the clinical use of proton irradiation were obtained: 1) the physical skin-sparing effect of proton irradiation in single-field irradiation, especially in superficial regions, is not large compared with that of high-energy photon irradiation; 2) multidirectional proton irradiation significantly reduced the skin dose and severity of acute reasons; 3) the radiobiological effects of the proton beam, RBE and the time factor, estimated in human skin in multi-fractional treatment were slightly smaller than those of X-rays, i.e., 0.92 and -0.25±0.09, respectively. (author)

Effect of integrated surgery + radiotherapy + chemotherapy treatment on survival status and serum indexes in patients with gallbladder carcinoma

Directory of Open Access Journals (Sweden)

Zhi-Li Wei

2016-12-01

Full Text Available Objective: To study the effect of integrated surgery + radiotherapy + chemotherapy treatment on the survival status and serum indexes in patients with gallbladder carcinoma. Methods: A total of 68 patients with gallbladder carcinoma were divided into observation group (received integrated surgery + radiotherapy + chemotherapy treatment and control group (received surgery + radiotherapy according to different treatments. Differences in the content of tumor markers, growth factors and adhesion molecules in serum as well as the median survival time and survival rate in 5 years of follow-up were compared between the two groups 1 month after treatment. Results: Tumor markers β2-MG, CA19-9, CA242, CA125, CA724, CEA and AFP content in serum of observation group after treatment were significantly lower than those of control group; growth factors VEGF, FGF, EGFR and HER2 content in serum were significantly lower than those of control group while IGFBP-2 and IGFBP-3 content were significantly higher than those of control group; adhesion molecules E-selectin, ICAM-1, VCAM-1 and sE-Cd content in serum were significantly lower than those of control group; the median survival time of 5-year follow-up as well as 1-, 3- and 5-year survival rate were significantly greater than those of control group. Conclusions: Integrated treatment of surgery + radiotherapy + chemotherapy can optimize the short-term and long-term curative effect in patients with gallbladder carcinoma.

HTB140 melanoma cells under proton irradiation and/or alkylating agents

Science.gov (United States)

Korićanac, L.; Petrović, I.; Privitera, G.; Cuttone, G.; Ristić-Fira, A.

2007-09-01

Chemoresistance is a major problem in the treatment of malignant melanoma. The mainstay of treatment for melanoma is the DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), a member of the chloroethylnitrosourea group of alkylating agents, has also demonstrated significant antitumor effects in malignant melanoma. However, the intrinsic and acquired resistance of melanoma limits the clinical application of these drugs. Melanomas are also extremely radioresistant. With the objective of enhancing growth inhibition of melanoma cells, combined treatments of FM or DTIC with proton irradiation have been investigated. These effects were studied on HTB140 melanoma cell viability and proliferation. Cells exposed to treatment with FM and protons have shown inhibition of cell growth and significant reduction of proliferation capacity compared to single irradiation or drug treatment. Treatment with DTIC and protons has shown improved growth inhibition compared to appropriate single drug treatment, while the effects of single proton irradiation have been the most pronounced.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

International Nuclear Information System (INIS)

McMillan, Matthew T.; Ojerholm, Eric; Roses, Robert E.; Plastaras, John P.; Metz, James M.; Mamtani, Ronac; Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A.; Stripp, Diana; Ben-Josef, Edgar; Datta, Jashodeep

2015-01-01

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

Energy Technology Data Exchange (ETDEWEB)

McMillan, Matthew T. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Ojerholm, Eric [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Roses, Robert E., E-mail: Robert.Roses@uphs.upenn.edu [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Plastaras, John P.; Metz, James M. [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Mamtani, Ronac [Department of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Karakousis, Giorgos C.; Fraker, Douglas L.; Drebin, Jeffrey A. [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Stripp, Diana; Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States); Datta, Jashodeep [Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania (United States)

2015-10-01

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiation therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.

Review of medical radiography and tomography with proton beams

Science.gov (United States)

Johnson, Robert P.

2018-01-01

The use of hadron beams, especially proton beams, in cancer radiotherapy has expanded rapidly in the past two decades. To fully realize the advantages of hadron therapy over traditional x-ray and gamma-ray therapy requires accurate positioning of the Bragg peak throughout the tumor being treated. A half century ago, suggestions had already been made to use protons themselves to develop images of tumors and surrounding tissue, to be used for treatment planning. The recent global expansion of hadron therapy, coupled with modern advances in computation and particle detection, has led several collaborations around the world to develop prototype detector systems and associated reconstruction codes for proton computed tomography (pCT), as well as more simple proton radiography, with the ultimate intent to use such systems in clinical treatment planning and verification. Recent imaging results of phantoms in hospital proton beams are encouraging, but many technical and programmatic challenges remain to be overcome before pCT scanners will be introduced into clinics. This review introduces hadron therapy and the perceived advantages of pCT and proton radiography for treatment planning, reviews its historical development, and discusses the physics related to proton imaging, the associated experimental and computation issues, the technologies used to attack the problem, contemporary efforts in detector and computational development, and the current status and outlook.

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

International Nuclear Information System (INIS)

Kruse, J.

2016-01-01

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

International Nuclear Information System (INIS)

2016-01-01

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

MO-A-201-00: A Cliff’s Notes Version of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2016-06-15

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

MO-A-201-01: A Cliff’s Notes Version of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Kruse, J. [Mayo Clinic (United States)

2016-06-15

Proton therapy is a rapidly growing modality in the fight against cancer. From a high-level perspective the process of proton therapy is identical to x-ray based external beam radiotherapy. However, this course is meant to illustrate for x-ray physicists the many differences between x-ray and proton based practices. Unlike in x-ray therapy, proton dose calculations use CT Hounsfield Units (HU) to determine proton stopping power and calculate the range of a beam in a patient. Errors in stopping power dominate the dosimetric uncertainty in the beam direction, while variations in patient position determine uncertainties orthogonal to the beam path. Mismatches between geometric and range errors lead to asymmetric uncertainties, and so while geometric uncertainties in x-ray therapy are mitigated through the use of a Planning Target Volume (PTV), this approach is not suitable for proton therapy. Robust treatment planning and evaluation are critical in proton therapy, and will be discussed in this course. Predicting the biological effect of a proton dose distribution within a patient is also a complex undertaking. The proton therapy community has generally regarded the Radiobiological Effectiveness (RBE) of a proton beam to be 1.1 everywhere in the patient, but there are increasing data to suggest that the RBE probably climbs higher than 1.1 near the end of a proton beam when the energy deposition density increases. This lecture will discuss the evidence for variable RBE in proton therapy and describe how this is incorporated into current proton treatment planning strategies. Finally, there are unique challenges presented by the delivery process of proton therapy. Many modern systems use a spot scanning technique which has several advantages over earlier scattered beam designs. However, the time dependence of the dose deposition leads to greater concern with organ motion than with scattered protons or x-rays. Image guidance techniques in proton therapy may also differ

Proton Radiotherapy for Pediatric Ewing’s Sarcoma: Initial Clinical Outcomes

International Nuclear Information System (INIS)

Rombi, Barbara; DeLaney, Thomas F.; MacDonald, Shannon M.; Huang, Mary S.; Ebb, David H.; Liebsch, Norbert J.; Raskin, Kevin A.; Yeap, Beow Y.; Marcus, Karen J.; Tarbell, Nancy J.; Yock, Torunn I.

2012-01-01

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing’s sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing’s sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.

Arginine promotes Proteus mirabilis motility and fitness by contributing to conservation of the proton gradient and proton motive force.

Science.gov (United States)

Armbruster, Chelsie E; Hodges, Steven A; Smith, Sara N; Alteri, Christopher J; Mobley, Harry L T

2014-10-01

Swarming contributes to Proteus mirabilis pathogenicity by facilitating access to the catheterized urinary tract. We previously demonstrated that 0.1-20 mmol/L arginine promotes swarming on normally nonpermissive media and that putrescine biosynthesis is required for arginine-induced swarming. We also previously determined that arginine-induced swarming is pH dependent, indicating that the external proton concentration is critical for arginine-dependent effects on swarming. In this study, we utilized survival at pH 5 and motility as surrogates for measuring changes in the proton gradient (ΔpH) and proton motive force (μH(+) ) in response to arginine. We determined that arginine primarily contributes to ΔpH (and therefore μH(+) ) through the action of arginine decarboxylase (speA), independent of the role of this enzyme in putrescine biosynthesis. In addition to being required for motility, speA also contributed to fitness during infection. In conclusion, consumption of intracellular protons via arginine decarboxylase is one mechanism used by P. mirabilis to conserve ΔpH and μH(+) for motility. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Trends in incidence, treatment and survival of aggressive B-cell lymphoma in the Netherlands 1989–2010

Science.gov (United States)

Issa, Djamila E.; van de Schans, Saskia A.M.; Chamuleau, Martine E.D.; Karim-Kos, Henrike E.; Wondergem, Marielle; Huijgens, Peter C.; Coebergh, Jan Willem W.; Zweegman, Sonja; Visser, Otto

2015-01-01

Only a small number of patients with aggressive B-cell lymphoma take part in clinical trials, and elderly patients in particular are under-represented. Therefore, we studied data of the population-based nationwide Netherlands Cancer Registry to determine trends in incidence, treatment and survival in an unselected patient population. We included all patients aged 15 years and older with newly diagnosed diffuse large B-cell lymphoma or Burkitt lymphoma in the period 1989–2010 and mantle cell lymphoma in the period 2001–2010, with follow up until February 2013. We examined incidence, first-line treatment and survival. We calculated annual percentage of change in incidence and carried out relative survival analyses. Incidence remained stable for diffuse large B-cell lymphoma (n=23,527), while for mantle cell lymphoma (n=1,634) and Burkitt lymphoma (n=724) incidence increased for men and remained stable for women. No increase in survival for patients with aggressive B-cell lymphoma was observed during the period 1989–1993 and the period 1994–1998 [5-year relative survival 42% (95%CI: 39%–45%) and 41% (38%–44%), respectively], but increased to 46% (43%–48%) in the period 1999–2004 and to 58% (56%–61%) in the period 2005–2010. The increase in survival was most prominent in patients under 65 years of age, while there was a smaller increase in patients over 75 years of age. However, when untreated patients were excluded, patients over 75 years of age had a similar increase in survival to younger patients. In the Netherlands, survival for patients with aggressive B-cell lymphoma increased over time, particularly in younger patients, but also in elderly patients when treatment had been initiated. The improvement in survival coincided with the introduction of rituximab therapy and stem cell transplantation into clinical practice. PMID:25512643

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

Energy Technology Data Exchange (ETDEWEB)

Pham, R; Sun, B; Zhao, T; Li, H; Yang, D; Grantham, K; Goddu, S; Santanam, L; Bradley, J; Mutic, S; Kandlakunta, P; Zhang, T [Washington University School of Medicine, Saint Louis, MO (United States)

2016-06-15

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculated on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.

Biologically-equivalent dose and long-term survival time in radiation treatments

International Nuclear Information System (INIS)

Zaider, Marco; Hanin, Leonid

2007-01-01

Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

Dosimetric properties of a proton beamline dedicated to the treatment of ocular disease

International Nuclear Information System (INIS)

Slopsema, R. L.; Mamalui, M.; Yeung, D.; Malyapa, R.; Li, Z.; Zhao, T.

2014-01-01

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systems and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm 2 ; the modulation width can be varied in steps of 0.3 g/cm 2 or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm 2 , larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up

Dosimetric properties of a proton beamline dedicated to the treatment of ocular disease

Energy Technology Data Exchange (ETDEWEB)

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.; Malyapa, R.; Li, Z. [University of Florida Proton Therapy Institute, 2015 North Jefferson Street, Jacksonville, Florida 32205 (United States); Zhao, T. [Department of Radiation Oncology, Washington University School of Medicine, 4921 Parkview Place, St. Louis, Missouri 63110 (United States)

2014-01-15

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systems and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence

Assessing the quality of proton PBS treatment delivery using machine log files: comprehensive analysis of clinical treatments delivered at PSI Gantry 2

International Nuclear Information System (INIS)

Scandurra, D; Albertini, F; Van der Meer, R; Meier, G; Weber, D C; Bolsi, A; Lomax, A

2016-01-01

Pencil beam scanning (PBS) proton therapy requires the delivery of many thousand proton beams, each modulated for position, energy and monitor units, to provide a highly conformal patient treatment. The quality of the treatment is dependent on the delivery accuracy of each beam and at each fraction. In this work we describe the use of treatment log files, which are a record of the machine parameters for a given field delivery on a given fraction, to investigate the integrity of treatment delivery compared to the nominal planned dose. The dosimetry-relevant log file parameters are used to reconstruct the 3D dose distribution on the patient anatomy, using a TPS-independent dose calculation system. The analysis was performed for patients treated at Paul Scherrer Institute on Gantry 2, both for individual fields and per series (or plan), and delivery quality was assessed by determining the percentage of voxels in the log file dose distribution within  +/−  1% of the nominal dose. It was seen that, for all series delivered, the mean pass rate is 96.4%. Furthermore, this work establishes a correlation between the delivery quality of a field and the beam position accuracy. This correlation is evident for all delivered fields regardless of individual patient or plan characteristics. We have also detailed further usefulness of log file analysis within our clinical workflow. In summary, we have highlighted that the integrity of PBS treatment delivery is dependent on daily machine performance and is specifically highly correlated with the accuracy of beam position. We believe this information will be useful for driving machine performance improvements in the PBS field. (paper)

A Gene Expression Signature Associated With Overall Survival in Patients With Hepatocellular Carcinoma Suggests a New Treatment Strategy

DEFF Research Database (Denmark)

Gillet, Jean-Pierre; Andersen, Jesper B; Madigan, James P

2015-01-01

Despite improvements in the management of liver cancer, the survival rate for individuals with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure...... are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance-associated genes in two independent cohorts of patients with advanced hepatocellular carcinoma, with the aim of finding ways to improve survival in this poor-prognosis cancer...

SU-F-T-598: Robotic Radiosurgery System Versus Pencil Beam Scanning Proton Therapy for Definitive Intracranial Treatments

International Nuclear Information System (INIS)

Lin, M; Pompos, A; Gu, X; Yan, Y; Abdulrahman, R; Timmerman, R; Jiang, S

2016-01-01

image guidance would improve the efficacy of proton therapy for intracranial treatments.

SU-F-T-598: Robotic Radiosurgery System Versus Pencil Beam Scanning Proton Therapy for Definitive Intracranial Treatments

Energy Technology Data Exchange (ETDEWEB)

Lin, M; Pompos, A; Gu, X; Yan, Y; Abdulrahman, R; Timmerman, R; Jiang, S [UT Southwestern Medical Center, Dallas, TX (United States)

2016-06-15

image guidance would improve the efficacy of proton therapy for intracranial treatments.

Disparities in breast cancer tumor characteristics, treatment, time to treatment, and survival probability among African American and white women.

Science.gov (United States)

Foy, Kevin Chu; Fisher, James L; Lustberg, Maryam B; Gray, Darrell M; DeGraffinreid, Cecilia R; Paskett, Electra D

2018-01-01

African American (AA) women have a 42% higher breast cancer death rate compared to white women despite recent advancements in management of the disease. We examined racial differences in clinical and tumor characteristics, treatment and survival in patients diagnosed with breast cancer between 2005 and 2014 at a single institution, the James Cancer Hospital, and who were included in the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Cancer Registry in Columbus OH. Statistical analyses included likelihood ratio chi-square tests for differences in proportions, as well as univariate and multivariate Cox proportional hazards regressions to examine associations between race and overall and progression-free survival probabilities. AA women made up 10.2% (469 of 4593) the sample. Average time to onset of treatment after diagnosis was almost two times longer in AA women compared to white women (62.0 days vs 35.5 days, p  triple negative and late stage breast cancer, and were less likely to receive surgery, especially mastectomy and reconstruction following mastectomy. After adjustment for confounding factors (age, grade, and surgery), overall survival probability was significantly associated with race (HR = 1.33; 95% CI 1.03-1.72). These findings highlight the need for efforts focused on screening and receipt of prompt treatment among AA women diagnosed with breast cancer.

Protein proton-proton dynamics from amide proton spin flip rates

International Nuclear Information System (INIS)

Weaver, Daniel S.; Zuiderweg, Erik R. P.

2009-01-01

Residue-specific amide proton spin-flip rates K were measured for peptide-free and peptide-bound calmodulin. K approximates the sum of NOE build-up rates between the amide proton and all other protons. This work outlines the theory of multi-proton relaxation, cross relaxation and cross correlation, and how to approximate it with a simple model based on a variable number of equidistant protons. This model is used to extract the sums of K-rates from the experimental data. Error in K is estimated using bootstrap methodology. We define a parameter Q as the ratio of experimental K-rates to theoretical K-rates, where the theoretical K-rates are computed from atomic coordinates. Q is 1 in the case of no local motion, but decreases to values as low as 0.5 with increasing domination of sidechain protons of the same residue to the amide proton flips. This establishes Q as a monotonous measure of local dynamics of the proton network surrounding the amide protons. The method is applied to the study of proton dynamics in Ca 2+ -saturated calmodulin, both free in solution and bound to smMLCK peptide. The mean Q is 0.81 ± 0.02 for free calmodulin and 0.88 ± 0.02 for peptide-bound calmodulin. This novel methodology thus reveals the presence of significant interproton disorder in this protein, while the increase in Q indicates rigidification of the proton network upon peptide binding, confirming the known high entropic cost of this process

Identification of markers that functionally define a quiescent multiple myeloma cell sub-population surviving bortezomib treatment

International Nuclear Information System (INIS)

Adomako, Alfred; Calvo, Veronica; Biran, Noa; Osman, Keren; Chari, Ajai; Paton, James C; Paton, Adrienne W; Moore, Kateri; Schewe, Denis M; Aguirre-Ghiso, Julio A

2015-01-01

The mechanisms allowing residual multiple myeloma (MM) cells to persist after bortezomib (Bz) treatment remain unclear. We hypothesized that studying the biology of bortezomib-surviving cells may reveal markers to identify these cells and survival signals to target and kill residual MM cells. We used H2B-GFP label retention, biochemical tools and in vitro and in vivo experiments to characterize growth arrest and the unfolded protein responses in quiescent Bz-surviving cells. We also tested the effect of a demethylating agent, 5-Azacytidine, on Bz-induced quiescence and whether inhibiting the chaperone GRP78/BiP (henceforth GRP78) with a specific toxin induced apoptosis in Bz-surviving cells. Finally, we used MM patient samples to test whether GRP78 levels might associate with disease progression. Statistical analysis employed t-test and Mann-Whitney tests at a 95% confidence. We report that Bz-surviving MM cells in vitro and in vivo enter quiescence characterized by p21 CIP1 upregulation. Bz-surviving MM cells also downregulated CDK6, Ki67 and P-Rb. H2B-GFP label retention showed that Bz-surviving MM cells are either slow-cycling or deeply quiescent. The Bz-induced quiescence was stabilized by low dose (500nM) of 5-azacytidine (Aza) pre-treatment, which also potentiated the initial Bz-induced apoptosis. We also found that expression of GRP78, an unfolded protein response (UPR) survival factor, persisted in MM quiescent cells. Importantly, GRP78 downregulation using a specific SubAB bacterial toxin killed Bz-surviving MM cells. Finally, quantification of Grp78 high /CD138+ MM cells from patients suggested that high levels correlated with progressive disease. We conclude that Bz-surviving MM cells display a GRP78 HIGH /p21 HIGH /CDK6 LOW /P-Rb LOW profile, and these markers may identify quiescent MM cells capable of fueling recurrences. We further conclude that Aza + Bz treatment of MM may represent a novel strategy to delay recurrences by enhancing Bz

Control of Pre-treatment for Carbon Nanotube Synthesis Using Proton Ion Beam Irradiation

International Nuclear Information System (INIS)

Kim, Y. H.; Kim, D. W.; Lee, S. M.; Kim, W. J.

2008-04-01

The carbon nanotubes are the next generation material in fuel storage system, the gas sensor, the life science sensor or the nano-size transistor, the stiffener and the heat dissipation field. For use at appropriate position in various field, it must be developed that control technique makes carbon nanotubes with high performance synthesized at appropriate location. The density of the carbon nanotube is 1 - 2g/cm3 with aluminum (2 - 3g/cm3) to be light, the elastic modulus is the level where as many of as 30 - 50 times of iron's elastic modulus and thermal conductivity is similar to the diamond, electric conductivity is high as well above the metal. Generally, many researchers have tried to synthesize the carbon nanotubes of mm length unit using the hydrogen and porous substrate, which play a role of more activating the catalyst. The proton beam which consist of H+ was able to directly inject the hydrogen into target materials such as Ni, Co, Fe as well as transfer high activation energy to them. so we were able to carry out feasibility of controlling the porosity of thin film and substrate to synthesize carbon nanotubes. The pre-treatment method of existing which is used generally heat treatment and the ammonia controls has generated island of catalyst which has increased the surface to react the hydrocarbon. However, pre-treatment method of existing caused the random nuclear creation so it was hard to control the island size of catalyst. It was not enough to understand the porous effect against synthesis of carbon nanotubes deduced from altering various substrates. In this report, it is possible investigate how hydrogen and the porous effect influence on growth of carbon nanotubes through controlling the nuclear creation of catalysts directly and the porosity of them using proton beam

The proton therapy system for Massachusetts General Hospital's Northeast Proton Therapy Center

International Nuclear Information System (INIS)

Jongen, Y.

1996-01-01

In 1989, two companies, Ion Beam Applications in Belgium (IBA) and Sumitomo Heavy Industries in Japan (SHI) started to design proton therapy equipments based on cyclotrons. In 1991, SHI and IBA decided to join their development efforts in this field. In 1993, the Massachusetts General Hospital (MGH), pioneer in the field of proton therapy, launched an international request for proposals for the procurement of an in-hospital proton therapy facility. The 18 may 1994, the contract was signed with a team of industries led by IBA, including also SHI and General Atomics (GA) of California. The proposed system is based on a fixed energy, isochronous cyclotron, followed by an energy degrader and an energy selection system. The variable energy beam can be rapidly switched in any one of three treatment rooms. Two rooms are equipped with large isocentric gantries and robotic patient positioners allowing to direct the proton beam within the patient from any direction. The third room is equipped with fixed horizontal beam. The complete system is computer controlled by a distributed network of computers, programmable logic controllers and workstations. This computer control allows to change the energy in one treatment room is less than two second, a performance matching or exceeding the flexibility offered by synchrotrons. The system is now built and undergoing factory tests. The beam has been accelerated to full energy in the cyclotron, and beam extraction tests are underway. Installation in the hospital building will take place in 1997. (author)

The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

Energy Technology Data Exchange (ETDEWEB)

Liebl, Jakob, E-mail: jakob.liebl@medaustron.at [EBG MedAustron GmbH, 2700 Wiener Neustadt (Austria); Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Department of Therapeutic Radiology and Oncology, Medical University of Graz, 8036 Graz (Austria); Paganetti, Harald; Zhu, Mingyao; Winey, Brian A. [Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2014-09-15

Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions

Late effects of craniospinal irradiation for standard risk medulloblastoma in paediatric patients: A comparison of treatment techniques

International Nuclear Information System (INIS)

Leman, J.

2016-01-01

Background: Survival rates for standard risk medulloblastoma are favourable, but craniospinal irradiation (CSI) necessary to eradicate microscopic spread causes life limiting late effects. Aims: The aim of this paper is to compare CSI techniques in terms of toxicity and quality of life for survivors. Methods and materials: A literature search was conducted using synonyms of ‘medulloblastoma’, ’craniospinal’, ‘radiotherapy’ and ‘side effects’ to highlight 29 papers that would facilitate this discussion. Results and discussion: Intensity modulated radiotherapy (IMRT), tomotherapy and protons all provide CSI which can reduce dose to normal tissue, however photon methods cannot eliminate exit dose as well as protons can. Research for each technique requires longer term follow up in order to prove that survival rates remain high whilst reducing late effects. Findings/conclusion: Proton therapy is the superior method of CSI in term of late effects, but more research is needed to evidence this. Until proton therapy is available in the UK IMRT should be utilised. - Highlights: • Craniospinal irradiation is vital in the treatment of medulloblastoma. • Survivors often suffer long term side effects which reduce quality of life. • Tomotherapy, IMRT and proton therapy reduce late effects by sparing normal tissue. • Proton therapy offers superior dose distribution but further research is necessary. • IMRT should be employed for photon radiotherapy.

Ten-Year Effect of Six Site-Preparation Treatments on Piedmont Loblolly Pine Survival and Growth

Science.gov (United States)

M. Boyd Edwards

1994-01-01

Limited information is available on growth responses to different levels of intensity for site preparation in the Piedmont. In the present study, six intensities of site preparation were compared for their effect on survival, height and diameter growth, total volume produced, and basal area per acre for the first 10 years after treatment. Rates of survival and growth...

Practical Radiobiology for Proton Therapy Planning

Science.gov (United States)

Jones, Bleddyn

2017-12-01

Practical Radiobiology for Proton Therapy Planning covers the principles, advantages and potential pitfalls that occur in proton therapy, especially its radiobiological modelling applications. This book is intended to educate, inform and to stimulate further research questions. Additionally, it will help proton therapy centres when designing new treatments or when unintended errors or delays occur. The clear descriptions of useful equations for high LET particle beam applications, worked examples of many important clinical situations, and discussion of how proton therapy may be optimized are all important features of the text. This important book blends the relevant physics, biology and medical aspects of this multidisciplinary subject. Part of Series in Physics and Engineering in Medicine and Biology.

Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer

International Nuclear Information System (INIS)

Welsh, James; Amini, Arya; Ciura, Katherine; Nguyen, Ngoc; Palmer, Matt; Soh, Hendrick; Allen, Pamela K.; Paolini, Michael; Liao, Zhongxing; Bluett, Jaques; Mohan, Radhe; Gomez, Daniel; Cox, James D.; Komaki, Ritsuko; Chang, Joe Y.

2013-01-01

Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V 20 , V 30 , or V 40 ) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within 20 was 364.0 cm 3 and 160.0 cm 3 (p 30 was 144.6 cm 3 vs 77.0 cm 3 (p = 0.0012), V 35 was 93.9 cm 3 vs 57.9 cm 3 (p = 0.005), V 40 was 66.5 cm 3 vs 45.4 cm 3 (p = 0.0112), and mean lung dose was 5.9 Gy vs 3.8 Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures

A Phase 2 Trial of Concurrent Chemotherapy and Proton Therapy for Stage III Non-Small Cell Lung Cancer: Results and Reflections Following Early Closure of a Single-Institution Study

Energy Technology Data Exchange (ETDEWEB)

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); Henderson, Randal [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); Pham, Dat; Cury, James D.; Bajwa, Abubakr [Department of Medicine, University of Florida College of Medicine, Jacksonville, Florida (United States); Morris, Christopher G. [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); D' Agostino, Harry [Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida (United States); Flampouri, Stella; Huh, Soon; Li, Zuofeng [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); McCook, Barry [Department of Radiology, University of Florida College of Medicine, Jacksonville, Florida (United States); Nichols, Romaine C. [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States)

2016-05-01

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after just 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.

Properties of the proton therapy. A high precision radiotherapy

International Nuclear Information System (INIS)

Anon.

2005-01-01

The proton therapy is a radiotherapy using protons beams. The protons present interesting characteristics but they need heavy technologies to be used, such particles accelerators, radiation protection wall and sophisticated technologies to reach the high precision allowed by their ballistic qualities (planning of treatment, beam conformation and patient positioning). (N.C.)

Survival and Psychomotor Development With Early Betaine Treatment in Patients With Severe Methylenetetrahydrofolate Reductase Deficiency

NARCIS (Netherlands)

Diekman, Eugene F.; de Koning, Tom J.; Verhoeven-Duif, Nanda M.; Rovers, Maroeska M.; van Hasselt, Peter M.

IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency

NARCIS (Netherlands)

Diekman, E.F.; Koning, T.J. de; Verhoeven-Duif, N.M.; Rovers, M.M.; Hasselt, P.M. van

2014-01-01

IMPORTANCE The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. OBJECTIVE To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. DATA SOURCES

Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

International Nuclear Information System (INIS)

Gerber, Naamit Kurshan; Wexler, Leonard H.; Singer, Samuel; Alektiar, Kaled M.; Keohan, Mary Louise; Shi, Weiji; Zhang, Zhigang; Wolden, Suzanne

2013-01-01

Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults

Adult Rhabdomyosarcoma Survival Improved With Treatment on Multimodality Protocols

Energy Technology Data Exchange (ETDEWEB)

Gerber, Naamit Kurshan [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wexler, Leonard H. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Singer, Samuel [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Keohan, Mary Louise [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne, E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2013-05-01

Purpose: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. Methods and Materials: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. Results: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. Conclusions: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients

DEFF Research Database (Denmark)

Møller, Henrik; Coupland, Victoria H; Tataru, Daniela

2018-01-01

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment...... and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following...... to statistical adjustments for age, sex, socio-economic status, performance status and co-morbidity. CONCLUSION: The extent of use of different treatment modalities varies between geographical areas in England. These variations are not attributable to measurable patient and tumour characteristics, and more...

Phase I/II study of proton beam irradiation for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: treatment techniques and preliminary results

International Nuclear Information System (INIS)

Yonemoto, Leslie T.; Slater, Jerry D.; Friedrichsen, Eric J.; Loredo, Lilia N.; Ing, Jeffrey; Archambeau, John O.; Teichman, Sandra; Moyers, Michael F.; Blacharski, Paul A.; Slater, James M.

1996-01-01

Purpose: Age-related macular degeneration is the prevalent etiology of subfoveal choroidal neovascularization (CNV). The only effective treatment is laser photocoagulation, which is associated with decreased visual acuity following treatment in most patients. This study assessed both the response of subfoveal CNV to proton beam irradiation and treatment-related morbidity. We evaluated preliminary results in patients treated with an initial dose of 8 Cobalt Gray Equivalents (CGE) using a relative biological effectiveness (RBE) of 1.1. Methods and Materials: Twenty-one patients with subfoveal CNV received proton irradiation to the central macula with a single fraction of 8 CGE; 19 were eligible for evaluation. Treatment-related morbidity was based on Radiation Therapy Oncology Group (RTOG) criteria; response was evaluated by Macular Photocoagulation Study (MPS) guidelines. Fluorescein angiography was performed; visual acuity, contrast sensitivity, and reading speed were measured at study entry and at 3-month intervals after treatment. Follow-up ranged from 6 to 15 months. Results: No measurable treatment-related morbidity was seen during or after treatment. Of 19 patients evaluated at 6 months, fluorescein angiography demonstrated treatment response in 10 (53%); 14 (74%) patients had improved or stable visual acuity. With a mean follow-up of 11.6 months, 11 (58%) patients have demonstrated improved or stable visual acuity. Conclusion: A macular dose of 8 CGE yielded no measurable treatment morbidity in patients studied. Fluorescein nagiography demonstrated that regressed or stabilized lesions were associated with improved visual acuity as compared with MPS results. In the next phase, a dose of 14 CGE in a single fraction will be used to further define the optimal dose fractionation schedule

Relative biological effectiveness (RBE) of proton beams in radiotherapy

International Nuclear Information System (INIS)

Calugaru, V.

2011-01-01

Treatment planning in proton therapy uses a generic value for the Relative Biological Efficiency (RBE) of 1.1 relative to 60 Co gamma-rays throughout the Spread Out Bragg Peak (SOBP). We have studied the variation of the RBE at three positions in the SOBP of the 76 and 201 MeV proton beams used for cancer treatment at the Institut Curie Proton Therapy in Orsay (ICPO) in two human tumor cell lines using clonogenic cell death and the incidence of DNA double-strand breaks (DSB) as measured by pulse-field gel electrophoresis without and with endonuclease treatment to reveal clustered lesions as endpoints.The RBE for induced cell killing by the 76 MeV beam increased with depth in the SOBP. However for the 201 MeV protons it was close to that for 137 Cs gamma-rays and did not vary significantly. The incidence of DSBs and clustered lesions was higher for protons than for 137 Cs g-rays, but did not depend on the proton energy or the position in the SOBP. In the second part of our work, we have shown using cell clones made deficient for known repair genes by stable or transient shRNA transfection, that the D-NHEJ pathway determine the response to protons. The response of DNA damages created in the distal part of the 76 MeV SOBP suggests that those damages belong to the class of DNA 'complex lesions' (LMDS). It also appears that the particle fluence is a major determinant of the outcome of treatment in the distal part of the SOBP. (author)

WE-FG-202-09: Voxel-Level Analysis of Adverse Treatment Response in Pediatric Patients Treated for Ependymoma with Passive Scattering Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Peeler, C [The University of Texas MD Anderson Cancer Center, Houston, TX (United States); The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX (United States); Mirkovic, D; Titt, U; Grosshans, D; Mohan, R [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: We identified patients treated for ependymoma with passive scattering proton therapy who subsequently developed treatment-related imaging changes on MRI. We sought to determine if there is any spatial correlation between imaged response, dose, and LET. Methods: A group of 14 patients treated for ependymoma were identified as having post-treatment MR imaging changes observable as T2-FLAIR hyperintensity with or without enhancement on T1 post-contrast sequences. MR images were registered with treatment planning CT images and regions of treatment-related change contoured by a practicing radiation oncologist. The contoured regions were identified as response with voxels represented as 1 while voxels within the brain outside of the response region were represented as 0. An in-house Monte Carlo system was used to recalculate treatment plans to obtain dose and LET information. Voxels were binned according to LET values in 0.3 keV µm{sup −1} bins. Dose and corresponding response value (0 or 1) for each voxel for a given LET bin were then plotted and fit with the Lyman-Kutcher-Burman dose response model to determine TD{sub 50} and m parameters for each LET value. Response parameters from all patients were then collated, and linear fits of the data were performed. Results: The response parameters TD50 and m both show trends with LET. Outliers were observed due to low numbers of response voxels in some cases. TD{sub 50} values decreased with LET while m increased with LET. The former result would indicate that for higher LET values, the dose is more effective, which is consistent with relative biological effectiveness (RBE) models for proton therapy. Conclusion: A novel method of voxel-level analysis of image biomarker-based adverse patient treatment response in proton therapy according to dose and LET has been presented. Fitted TD{sub 50} values show a decreasing trend with LET supporting the typical models of proton RBE. Funding provided by NIH Program Project

Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

International Nuclear Information System (INIS)

Hata, Masaharu; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

2007-01-01

Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade ≥3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC

PROTON RADIATION THERAPY: CLINICAL APPLICATION OPPORTUNITIES AND RESEARCH PROSPECTS

Directory of Open Access Journals (Sweden)

M. V. Zabelin

2018-01-01

Full Text Available This article is the review of literature concerning use of proton beam therapy in treatment of oncology. The staticized data on comparison of effi ciency of this method at an eye melanoma are lit. Advantages of proton therapy on the level of local control and depression of frequency of development of the radio induced cataract are refl ected in the provided data. In evident material the technology of preparation and carrying out radiation of an eye is shortly covered with a fascicle of protons. The experience of use of proton therapy of tumors of a skull base got for the last several decades, showed good results. Physical properties of a fascicle of protons allow to achieve the maximum dose conformality, having lowered, thereby, a radial load on the next crucial anatomical structures. The presented material on an oncopediatrics shows insuffi cient knowledge of scientists concerning advantage of a fascicle of protons over modern methods of photon radiation. There are only preliminary clinical results concerning generally of treatment of cranyopharyngiomas. At cancer therapy of a mammary gland, proton therapy showed the best local control of postoperative recurrent tumors, and also depression of a dose load on the contralateral party. The available results of the retrospective analysis of clinical data in the University medical center of Lome Linda, testify to advantages of proton therapy of the localized prostate cancer. The lack of a biochemical recurrence and a local tumoral progression within 5 years after radiation was shown. The data obtained from experience of use of proton radiation therapy with passively scattered fascicle for cancer therapy of a prostate at an early stage showed the admixed results in comparison with modern methods of radiation therapy with the modulated intensity. In treatment of non-small cell cancer of mild advantage of proton therapy aren’t absolutely proved yet. There are data on extreme toxicity of a combination

TU-H-CAMPUS-JeP3-04: Factors Predicting a Need for Treatment Replanning with Proton Radiotherapy for Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Teng, C; Janssens, G; Ainsley, C; Teo, B; Valdes, G; Burgdorf, B; Berman, A; Levin, W; Xiao, Y; Lin, L; Gabriel, P; Simone, C; Solberg, T [University of Pennsylvania, Philadelphia, PA (United States)

2016-06-15

Purpose: Proton dose distribution is sensitive to tumor regression and tissue and normal anatomy changes. Replanning is sometimes necessary during treatment to ensure continue tumor coverage or avoid overtreatment of organs at risk (OARs). We investigated action thresholds for replanning and identified both dosimetric and non-dosimetric metrics that would predict a need for replan. Methods: All consecutive lung cancer patients (n = 188) who received definitive proton radiotherapy and had more than two evaluation CT scans at the Roberts Proton Therapy Center (Philadelphia, USA) from 2011 to 2015 were included in this study. The cohort included a variety of tumor sizes, locations, histology, beam angles, as well as radiation-induced tumor and lung change. Dosimetric changes during therapy were characterized by changes in the dose volume distribution of PTV, ITV, and OARs (heart, cord, esophagus, brachial plexus and lungs). Tumor and lung change were characterized by changes in sizes, and in the distribution of Hounsfield numbers and water equivalent thickness (WET) along the beam path. We applied machine learning tools to identify both dosimetric and non-dosimetric metrics that predicted a replan. Results: Preliminary data showed that clinical indicators (n = 54) were highly correlated; thus, a simple indicator may be derived to guide the action threshold for replanning. Additionally, tumor regression alone could not predict dosimetric changes in OARs; it required further information about beam angles and tumor locations. Conclusion: Both dosimetric and non-dosimetric factors are predictive of the need for replanning during proton treatment.

Method and apparatus for laser-controlled proton beam radiology

Science.gov (United States)

Johnstone, Carol J.

1998-01-01

A proton beam radiology system provides cancer treatment and proton radiography. The system includes an accelerator for producing an H.sup.- beam and a laser source for generating a laser beam. A photodetachment module is located proximate the periphery of the accelerator. The photodetachment module combines the H.sup.- beam and laser beam to produce a neutral beam therefrom within a subsection of the H.sup.- beam. The photodetachment module emits the neutral beam along a trajectory defined by the laser beam. The photodetachment module includes a stripping foil which forms a proton beam from the neutral beam. The proton beam is delivered to a conveyance segment which transports the proton beam to a patient treatment station. The photodetachment module further includes a laser scanner which moves the laser beam along a path transverse to the cross-section of the H.sup.- beam in order to form the neutral beam in subsections of the H.sup.- beam. As the scanning laser moves across the H.sup.- beam, it similarly varies the trajectory of the proton beam emitted from the photodetachment module and in turn varies the target location of the proton beam upon the patient. Intensity modulation of the proton beam can also be achieved by controlling the output of the laser.

First experiences in treatment of low-grade glioma grade I and II with proton therapy

International Nuclear Information System (INIS)

Hauswald, Henrik; Rieken, Stefan; Ecker, Swantje; Kessel, Kerstin A; Herfarth, Klaus; Debus, Jürgen; Combs, Stephanie E

2012-01-01

To retrospectively assess feasibility and toxicity of proton therapy in patients with low-grade glioma (WHO °I/II). Proton beam therapy only administered in 19 patients (median age 29 years; 9 female, 10 male) for low-grade glioma between 2010 and 2011 was reviewed. In 6 cases proton therapy was performed due to tumor progression after biopsy, in 8 cases each due to tumor progression after (partial-) resection, and in 5 cases due to tumor progression after chemotherapy. Median total dose applied was 54 GyE (range, 48,6-54 GyE) in single fractions of median 1.8 GyE. Median clinical target volume was 99 cc (range, 6–463 cc) and treated using median 2 beams (range, 1–2). Proton therapy was finished as planned in all cases. At end of proton therapy, 13 patients showed focal alopecia, 6 patients reported mild fatigue, one patient with temporal tumor localization concentration deficits and speech errors and one more patient deficits in short-term memory. Four patients did not report any side effects. During follow-up, one patient presented with pseudo-progression showing worsening of general condition and brain edema 1–2 months after last irradiation and restitution after 6 months. In the present MR imaging (median follow-up 5 months; range 0–22 months) 12 patients had stable disease, 2 (1) patients partial (complete) remission, one more patient pseudo-progression (differential diagnosis: tumor progression) 4 weeks after irradiation without having had further follow-up imaging so far, and one patient tumor progression approximately 9 months after irradiation. Regarding early side effects, mild alopecia was the predominant finding. The rate of alopecia seems to be due to large treatment volumes as well as the anatomical locations of the target volumes and might be avoided by using multiple beams and the gantry in the future. Further evaluations including neuropsychological testing are in preparation

Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

Science.gov (United States)

Islam, M. R.; Collums, T. L.; Zheng, Y.; Monson, J.; Benton, E. R.

2013-11-01

The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy-1 for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy-1 for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body.

Off-axis dose equivalent due to secondary neutrons from uniform scanning proton beams during proton radiotherapy

International Nuclear Information System (INIS)

Islam, M R; Collums, T L; Monson, J; Benton, E R; Zheng, Y

2013-01-01

The production of secondary neutrons is an undesirable byproduct of proton therapy and it is important to quantify the contribution from secondary neutrons to patient dose received outside the treatment volume. The purpose of this study is to investigate the off-axis dose equivalent from secondary neutrons experimentally using CR-39 plastic nuclear track detectors (PNTD) at ProCure Proton Therapy Center, Oklahoma City, OK. In this experiment, we placed several layers of CR-39 PNTD laterally outside the treatment volume inside a phantom and in air at various depths and angles with respect to the primary beam axis. Three different proton beams with max energies of 78, 162 and 226 MeV and 4 cm modulation width, a 5 cm diameter brass aperture, and a small snout located 38 cm from isocenter were used for the entire experiment. Monte Carlo simulations were also performed based on the experimental setup using a simplified snout configuration and the FLUKA Monte Carlo radiation transport code. The measured ratio of secondary neutron dose equivalent to therapeutic primary proton dose (H/D) ranged from 0.3 ± 0.08 mSv Gy −1  for 78 MeV proton beam to 37.4 ± 2.42 mSv Gy −1  for 226 MeV proton beam. Both experiment and simulation showed a similar decreasing trend in dose equivalent with distance to the central axis and the magnitude varied by a factor of about 2 in most locations. H/D was found to increase as the energy of the primary proton beam increased and higher H/D was observed at 135° compared to 45° and 90°. The overall higher H/D in air indicates the predominance of external neutrons produced in the nozzle rather than inside the body. (paper)

Evaluation of the breath-hold approach in proton therapy of lung tumors

DEFF Research Database (Denmark)

Gorgisyan, Jenny

Proton therapy has the potential to improve the treatment effect as compared to conventional radiation therapy for lung cancer patients. However, the proton therapy delivery is prone to uncertainties caused by anatomical changes and motion during the treatment and between the treatment fractions ...

Malariotherapy at Mont Park: the earliest surviving movie of psychiatric treatment in Australia.

Science.gov (United States)

Kaplan, Robert M

2013-02-01

A movie on malariotherapy for neurosyphilis made at Mont Park and filmed by Reg Ellery in 1926 is believed to be the oldest surviving movie of psychiatric treatment in Australia. The objective is to review the movie and discuss the background and context of the film, which shows the conditions of patients in a psychiatric hospital in the 1920s. Movie film is a guide to a psychiatric past that is rapidly being forgotten. The Ellery movie is an incentive to collect surviving footage before it is too late.

Combined proton and photon irradiation for craniopharyngioma: Long-term results of the early cohort of patients treated at Harvard Cyclotron Laboratory and Massachusetts General Hospital

International Nuclear Information System (INIS)

Fitzek, Markus M.; Linggood, Rita M.; Adams, Judy; Munzenrider, John E.

2006-01-01

Purpose: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory. Methods and Materials: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractionated 160 MeV proton beam therapy. The group consisted of 5 children (median age, 15.9 years) and 10 adults (median age, 36.2 years). Median dose prescribed to the tumor was 56.9 cobalt Gray equivalent (CGE; 1 proton Gray = 1.1 CGE). The median proton component was 26.9 CGE. Patients were treated after documented recurrence after initial surgery (n = 6) or after subtotal resection or biopsy (n = 9). None had had prior radiation therapy. Results: Median observation period of surviving patients (n = 11) was 13.1 years from radiotherapy. One patient was lost to follow-up with tumor control after 5.2 years. Actuarial 10-year survival rate was 72%. Four patients have died 5-9.1 years after treatment, two from local failure. Actuarial 5- and 10-year local control rates were 93% and 85%, respectively. The functional status of the living adult patients is unaltered from their preradiotherapy status; all of them continued leading normal or near normal working lives. None of the patients treated as a child had experienced recurrence of tumor. One child shows learning difficulties and slight retardation, comparable to his preradiotherapy status. The others have professional achievements within the normal range. Conclusion: Results in terms of survival and local control are comparable with other contemporary series. Although no formal neuropsychological testing was performed, the surrogate measures of lifestyle and professional accomplishments appear to be satisfactory

Evaluation and comparison of New 4DCT based strategies for proton treatment planning for lung tumors

International Nuclear Information System (INIS)

Wang, Ning; Patyal, Baldev; Ghebremedhin, Abiel; Bush, David

2013-01-01

To evaluate different strategies for proton lung treatment planning based on four-dimensional CT (4DCT) scans. Twelve cases, involving only gross tumor volumes (GTV), were evaluated. Single image sets of (1) maximum intensity projection (MIP3) of end inhale (EI), middle exhale (ME) and end exhale (EE) images; (2) average intensity projection (AVG) of all phase images; and (3) EE images from 4DCT scans were selected as primary images for proton treatment planning. Internal target volumes (ITVs) outlined by a clinician were imported into MIP3, AVG, and EE images as planning targets. Initially, treatment uncertainties were not included in planning. Each plan was imported into phase images of 4DCT scans. Relative volumes of GTVs covered by 95% of prescribed dose and mean ipsilateral lung dose of a phase image obtained by averaging the dose in inspiration and expiration phases were used to evaluate the quality of a plan for a particular case. For comparing different planning strategies, the mean of the averaged relative volumes of GTVs covered by 95% of prescribed dose and its standard deviation for each planning strategy for all cases were used. Then, treatment uncertainties were included in planning. Each plan was recalculated in phase images of 4DCT scans. Same strategies were used for plan evaluation except dose-volume histograms of the planning target volumes (PTVs) instead of GTVs were used and the mean and standard deviation of the relative volumes of PTVs covered by 95% of prescribed dose and the ipsilateral lung dose were used to compare different planning strategies. MIP3 plans without treatment uncertainties yielded 96.7% of the mean relative GTV covered by 95% of prescribed dose (standard deviations of 5.7% for all cases). With treatment uncertainties, MIP3 plans yielded 99.5% of mean relative PTV covered by 95% of prescribed dose (standard deviations of 0.7%). Inclusion of treatment uncertainties improved PTV dose coverage but also increased the ipsilateral

RENAL SAFETY OF PROTON PUMP INHIBITORS

Directory of Open Access Journals (Sweden)

A. I. Dyadyk

2017-01-01

Full Text Available Proton pump inhibitors are a widely used in clinical practice, and are taken by millions of patients around the world for a long time. While proton pump inhibitors are well-tolerated class of drugs, the number of publications has been raised about adverse renal effects, specially their association with acute tubulointerstitial nephritis. It is one of the leading causes of acute renal injury and have catastrophic long-term consequences called chronic kidney disease. In this review, we consider epidemiology, pathogenesis, diagnostic criteria (including biopsy and morphological pattern, clinical manifestations and treatment of proton pump inhibitors-induced acute tubulointerstitial nephritis. A subclinical course without classical manifestations of a cell-mediated hypersensitivity reaction (fever, skin rash, eosinophilia, arthralgia is characteristic of acute tubulointerstitial nephritis. Increased serum creatinine, decreased glomerular filtration rate, electrolyte disorders, pathological changes in urine tests are not highly specific indicators, but allow to suspect the development of acute tubulointerstitial nephritis. The “gold” standard of diagnosis is the intravital morphological examination of the kidney tissue. Timely diagnosis and immediate discontinuation of the potentially causative drug is the mainstay of therapy and the first necessary step in the early management of suspected or biopsy-proven drug-induced acute tubulointerstitial nephritis. The usage of proton pump inhibitors should be performed only on strict indications with optimal duration of treatment and careful monitoring of kidney function. Multiple comorbidities (older age, heart failure, diabetes, cirrhosis, chronic kidney disease, hypovolemia increase potential nephrotoxicity. Awareness of this iatrogenic complication will improve diagnosis of proton pump inhibitors-induced acute tubulointerstitial nephritis by multidisciplinary specialists and increase the possibility

Proton Radiotherapy for Pediatric Ewing's Sarcoma: Initial Clinical Outcomes

Energy Technology Data Exchange (ETDEWEB)

Rombi, Barbara [ATreP (Provincial Agency for Proton Therapy), Trento (Italy); DeLaney, Thomas F.; MacDonald, Shannon M. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Huang, Mary S.; Ebb, David H. [Department of Pediatric Hematology and Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Liebsch, Norbert J. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Raskin, Kevin A. [Department of Orthopaedic Surgery, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Yeap, Beow Y. [Department of Medicine, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Marcus, Karen J. [Division of Radiation Oncology, Children' s Hospital Boston, MA (United States); Tarbell, Nancy J. [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States); Yock, Torunn I., E-mail: tyock@partners.org [Department of Radiation Oncology, Massachusetts General Hospital-Harvard Medical School, Boston, MA (United States)

2012-03-01

Purpose: Proton radiotherapy (PT) has been prescribed similarly to photon radiotherapy to achieve comparable disease control rates at comparable doses. The chief advantage of protons in this setting is to reduce acute and late toxicities by decreasing the amount of normal tissue irradiated. We report the preliminary clinical outcomes including late effects on our pediatric Ewing's sarcoma patients treated with PT at the Francis H. Burr Proton Therapy Center at Massachusetts General Hospital (Boston, MA). Methods and Materials: This was a retrospective review of the medical records of 30 children with Ewing's sarcoma who were treated with PT between April 2003 and April 2009. Results: A total of 14 male and 16 female patients with tumors in several anatomic sites were treated with PT at a median age of 10 years. The median dose was 54 Gy (relative biological effectiveness) with a median follow-up of 38.4 months. The 3-year actuarial rates of event-free survival, local control, and overall survival were 60%, 86%, and 89%, respectively. PT was acutely well tolerated, with mostly mild-to-moderate skin reactions. At the time of writing, the only serious late effects have been four hematologic malignancies, which are known risks of topoisomerase and anthracyline exposure. Conclusions: Proton radiotherapy was well tolerated, with few adverse events. Longer follow-up is needed to more fully assess tumor control and late effects, but the preliminary results are encouraging.

Computational details of the Monte Carlo simulation of proton and electron tracks

International Nuclear Information System (INIS)

Zaider, M.; Brenner, D.J.

1983-01-01

The code PROTON simulates the elastic and nonelastic interactions of protons and electrons in water vapor. In this paper, the treatment of elastic angular scattering of electrons as utilized in PROTON is described and compared with alternate formalisms. The sensitivity of the calculation to different treatments of this process is examined in terms of proximity functions of energy deposition. 5 figures

Sensitivity of HTB140 cell exposed to protons and alkylating agents

International Nuclear Information System (INIS)

Koricanac, L.; Petrovic, I.; Privitera, G.; Cuttone, G.; Ristic-Fira, A.

2006-01-01

Malignant melanoma is a highly aggressive cancer with a poor prognosis due to resistance to radiotherapy and chemotherapy regimens. The mainstay of treatment remains DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), chloroethylnitrosourea agent, also has demonstrated significant antitumoral effects in malignant melanoma. However, the resistance of melanoma cells limits their clinical application. In order to enhance the inhibition of melanoma cell growth, in this study, combined treatment of FM and DTIC with proton irradiation, was investigated. We analyzed the effects of combined treatment on HTB140 melanoma cell viability and proliferation. Significant inhibition of cell growth, especially cell proliferation, was obtained after treatment with protons and FM compare to single irradiation or drug treatment. Treatment with protons and DTIC has shown improved growth inhibition compare to appropriate single drug treatment, but not compare to irradiation as a single treatment. (author)

Proton Beam Radiotherapy for Uveal Melanomas at Nice Teaching Hospital: 16 Years' Experience

International Nuclear Information System (INIS)

Caujolle, Jean-Pierre; Mammar, Hamid; Chamorey, Emmanuel Phar; Pinon, Fabien; Herault, Joel; Gastaud, Pierre

2010-01-01

Purpose: To present the results of uveal melanomas treated at Nice Teaching Hospital. Methods and Materials: This retrospective study included 886 consecutive patients referred to our clinic for the treatment of uveal melanomas by proton beam radiotherapy from June 1991 to December 2007. Survival rates were determined by using Kaplan-Meier estimates, and prognostic factors were evaluated using the log-rank test or Cox model. Results: The number (percent total) of subjects staged according to the TNM classification system (6th edition) of malignant tumors included 39 stage T1 (4.4%), 420 stage T2 (47.40%), 409 stage T3 (46.16%), and 18 stage T4 (2.03%) patients. The median follow-up was 63.7 months. The Kaplan-Meier overall survival rate at 5 years according to the sixth edition TNM classification was 92% for T1, 89% for T2, 67% for T3, and 62% for T4; and at 10 years, 86% for T1, 78% for T2, 43% for T3, and 41% for T4. Five factors were found to be associated with an increased death rate: advanced age, tumor thickness, largest tumor basal diameter, tumor volume, and tumor volume-to-eyeball volume ratio. The metastasis-free survival rates were 88.3 % at 5 years and 76.4 % at 10 years. The local control rates were 93.9% at 5 years and 92.1% at 10 years. The ocular conservation rates were 91.1% at 5 years and 87.3% at 10 years. Conclusions: We report the results of a large series of patients treated for uveal melanomas with a very long follow-up. Despite the large tumor volume treated, our results were similar to previously published findings relating to proton beam therapy.

In vivo verification of proton beam path by using post-treatment PET/CT imaging.

Science.gov (United States)

Hsi, Wen C; Indelicato, Daniel J; Vargas, Carlos; Duvvuri, Srividya; Li, Zuofeng; Palta, Jatinder

2009-09-01

The purpose of this study is to establish the in vivo verification of proton beam path by using proton-activated positron emission distributions. A total of 50 PET/CT imaging studies were performed on ten prostate cancer patients immediately after daily proton therapy treatment through a single lateral portal. The PET/CT and planning CT were registered by matching the pelvic bones, and the beam path of delivered protons was defined in vivo by the positron emission distribution seen only within the pelvic bones, referred to as the PET-defined beam path. Because of the patient position correction at each fraction, the marker-defined beam path, determined by the centroid of implanted markers seen in the posttreatment (post-Tx) CT, is used for the planned beam path. The angular variation and discordance between the PET- and marker-defined paths were derived to investigate the intrafraction prostate motion. For studies with large discordance, the relative location between the centroid and pelvic bones seen in the post-Tx CT was examined. The PET/CT studies are categorized for distinguishing the prostate motion that occurred before or after beam delivery. The post-PET CT was acquired after PET imaging to investigate prostate motion due to physiological changes during the extended PET acquisition. The less than 2 degrees of angular variation indicates that the patient roll was minimal within the immobilization device. Thirty of the 50 studies with small discordance, referred as good cases, show a consistent alignment between the field edges and the positron emission distributions from the entrance to the distal edge. For those good cases, average displacements are 0.6 and 1.3 mm along the anterior-posterior (D(AP)) and superior-inferior (D(SI)) directions, respectively, with 1.6 mm standard deviations in both directions. For the remaining 20 studies demonstrating a large discordance (more than 6 mm in either D(AP) or D(SI)), 13 studies, referred as motion-after-Tx cases

Quantum treatment of protons with the reduced explicitly correlated Hartree-Fock approach

Energy Technology Data Exchange (ETDEWEB)

Sirjoosingh, Andrew; Pak, Michael V.; Brorsen, Kurt R.; Hammes-Schiffer, Sharon, E-mail: shs3@illinois.edu [Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Ave., Urbana, Illinois 61801 (United States)

2015-06-07

The nuclear-electronic orbital (NEO) approach treats select nuclei quantum mechanically on the same level as the electrons and includes nonadiabatic effects between the electrons and the quantum nuclei. The practical implementation of this approach is challenging due to the significance of electron-nucleus dynamical correlation. Herein, we present a general extension of the previously developed reduced NEO explicitly correlated Hartree-Fock (RXCHF) approach, in which only select electronic orbitals are explicitly correlated to each quantum nuclear orbital via Gaussian-type geminal functions. Approximations of the electronic exchange between the geminal-coupled electronic orbitals and the other electronic orbitals are also explored. This general approach enables computationally tractable yet accurate calculations on molecular systems with quantum protons. The RXCHF method is applied to the hydrogen cyanide (HCN) and FHF{sup −} systems, where the proton and all electrons are treated quantum mechanically. For the HCN system, only the two electronic orbitals associated with the CH covalent bond are geminal-coupled to the proton orbital. For the FHF{sup −} system, only the four electronic orbitals associated with the two FH covalent bonds are geminal-coupled to the proton orbital. For both systems, the RXCHF method produces qualitatively accurate nuclear densities, in contrast to mean field-based NEO approaches. The development and implementation of the RXCHF method provide the framework to perform calculations on systems such as proton-coupled electron transfer reactions, where electron-proton nonadiabatic effects are important.

Is there an overprescription of proton pump inhibitors in oncohematologic patients undergoing ambulatory oncospecific treatment?

Directory of Open Access Journals (Sweden)

Meritxell Pujal Herranz

2016-09-01

Full Text Available Objective: The aim of this study is to evaluate the prevalence of proton pump inhibitors (PPIs prescription, and the level of adequacy of the indication of these drugs in oncohematologic patients under ambulatory oncoespecific treatment. Method: An observational descriptive study in oncohematologic patients under ambulatory oncoespecific treatment. A protocol for the rational use of PPI targeted to oncohematologic patients based on the PPI protocol of our hospital was designed. Patients under active treatment with PPIs were quantified and the appropriateness of their indications evaluated. Results: 111 patients (71 oncologic and 40 hematologic were included. 56% of all oncologic patients and 63% of all hematologic patients were under active treatment with PPIs. After reviewing the indications for PPI in all patients, 72% of oncologic and 12% of hematologic patients did not present evidence justifying treatment with these drugs. Conclusion: It is important the pharmacist to detect unappropriated prescriptions of PPIs, especially among oncologic patients, and to promote a deprescription of these drugs

Proton radiation therapy for clivus chordoma

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Tsunoda, Takashi; Hyodo, Akio; Nose, Tadao; Tsujii, Hirohiko; Tsuji, Hiroshi; Inada, Tetsuo; Maruhashi, Akira; Hayakawa, Yoshinori.

1993-01-01

A 57-year-old male with clival chordoma developed severe hoarseness, dysphagia, and dysphonia 1 month after a second removal of the tumor. Magnetic resonance imaging demonstrated a mass 10 cm in diameter in the region of the middle clivus enhanced inhomogeneously by gadolinium-diethylenetriaminepenta-acetic acid, and a defect in the skull base. There was evidence of compression of the anterior surface of the pons. He received proton irradiation employing a pair of parallel opposed lateral proton beams. The dose aimed at the tumor mass was 75.5 Gy, to the pharyngeal wall less than 38 Gy, and to the anterior portion of the pons less than 30 Gy. Time dose and fractionation factor was calculated at 148. Thirty-one months following treatment, he was free of clinical neurological sequelae. Proton therapy should be considered in treatment planning following initial surgical removal or for inoperable clivus chordoma. (author)

Conception of a New Recoil Proton Telescope for Real-Time Neutron Spectrometry in Proton-Therapy

Science.gov (United States)

Combe, Rodolphe; Arbor, Nicolas; el Bitar, Ziad; Higueret, Stéphane; Husson, Daniel

2018-01-01

Neutrons are the main type of secondary particles emitted in proton-therapy. Because of the risk of secondary cancer and other late occurring effects, the neutron dose should be included in the out-of-field dose calculations. A neutron spectrometer has to be used to take into account the energy dependence of the neutron radiological weighting factor. Due to its high dependence on various parameters of the irradiation (beam, accelerator, patient), the neutron spectrum should be measured independently for each treatment. The current reference method for the measurement of the neutron energy, the Bonner Sphere System, consists of several homogeneous polyethylene spheres with increasing diameters equipped with a proportional counter. It provides a highresolution reconstruction of the neutron spectrum but requires a time-consuming work of signal deconvolution. New neutron spectrometers are being developed, but the main experimental limitation remains the high neutron flux in proton therapy treatment rooms. A new model of a real-time neutron spectrometer, based on a Recoil Proton Telescope technology, has been developed at the IPHC. It enables a real-time high-rate reconstruction of the neutron spectrum from the measurement of the recoil proton trajectory and energy. A new fast-readout microelectronic integrated sensor, called FastPixN, has been developed for this specific purpose. A first prototype, able to detect neutrons between 5 and 20 MeV, has already been validated for metrology with the AMANDE facility at Cadarache. The geometry of the new Recoil Proton Telescope has been optimized via extensive Geant4 Monte Carlo simulations. Uncertainty sources have been carefully studied in order to improve simultaneously efficiency and energy resolution, and solutions have been found to suppress the various expected backgrounds. We are currently upgrading the prototype for secondary neutron detection in proton therapy applications.

Estimation dose of secondary neutrons in proton therapy

International Nuclear Information System (INIS)

Urban, T.

2014-01-01

Most of proton therapy centers for cancer treatment are still based on the passive scattering, in some of them there is system of the active scanning installed as well. The aim of this study is to compare secondary neutron doses in and around target volumes in proton therapy for both treatment techniques and for different energies and profile of incident proton beam. The proton induced neutrons have been simulated in the very simple geometry of tissue equivalent phantom (imitate the patient) and scattering and scanning nozzle, respectively. In simulations of the scattering nozzle, different types of scattering filters and brass collimators have been used as well. 3D map of neutron doses in and around the chosen/potential target volume in the phantom/patient have been evaluated and compared in the context of the dose deposited in the target volume. Finally, the simulation results have been compared with published data. (author)

Sparse-view proton computed tomography using modulated proton beams

Energy Technology Data Exchange (ETDEWEB)

Lee, Jiseoc; Kim, Changhwan; Cho, Seungryong, E-mail: scho@kaist.ac.kr [Department of Nuclear and Quantum Engineering, Korea Advanced Institute of Science and Technology, Daejon 305-701 (Korea, Republic of); Min, Byungjun [Department of Radiation Oncology, Kangbuk Samsung Hospital, 110–746 (Korea, Republic of); Kwak, Jungwon [Department of Radiation Oncology, Asan Medical Center, 138–736 (Korea, Republic of); Park, Seyjoon; Lee, Se Byeong [Proton Therapy Center, National Cancer Center, 410–769 (Korea, Republic of); Park, Sungyong [Proton Therapy Center, McLaren Cancer Institute, Flint, Michigan 48532 (United States)

2015-02-15

within 1% error. EM-based algorithms produced an increased image noise and RMSE as the iteration reaches about 20, while the POCS-based algorithms showed a monotonic convergence with iterations. The ASD-POCS algorithm outperformed the others in terms of CNR, RMSE, and the accuracy of the reconstructed relative stopping power in the region of lung and soft tissues. Conclusions: The four iterative algorithms, i.e., ASD-POCS, SM-POCS, SM-EM, and EM-TV, have been developed and applied for proton CT image reconstruction. Although it still seems that the images need to be improved for practical applications to the treatment planning, proton CT imaging by use of the modulated beams in sparse-view sampling has demonstrated its feasibility.

Evaluation of medical treatments to increase survival of ebullism in guinea pigs

Science.gov (United States)

Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.

1993-01-01

Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

Proton Beam Writing

International Nuclear Information System (INIS)

Rajta, I.; Szilasi, S.Z.; Csige, I.; Baradacs, E.

2005-01-01

flow channel, which were also implanted at the same irradiation. During the porous Si formation we developed the sample 6-8 μm deeper than the implanting ion range damaged the crystal. Due to the isotropic nature of the porous Si etching, the thick sidewall blocks are still connected to the crystal while the thin membranes detached from the bottom, and they are only connected to one of the sidewalls. The other construction utilized the goniometer facility mounted on the microbeam chamber, we implanted the samples at 40 degrees tilt, and developed the samples not as deep as the ion range. This way both the sidewalls and the membranes are attached to the bottom of the sample. The SEM images of the samples showed that both of these types of valves can be actively working, however, the thickness of the moving membrane requires extremely large force according to the fluidic tests. In order to achieve a successful demonstration of the functionality, the membrane rigidity should be reduced by decreasing the wall thickness. Reduction of optimal fluence by CO 2 treatment after exposure and vacuum effects in proton beam micromachining of CR-39 CR-39 has been shown to be a suitable material as a thick resist for Proton Beam Writing [5]. These samples are normally used to detect single alpha particles in normal air conditions. However, to use this material as proton or alpha micromachinable resists, we need to irradiate the samples in vacuum. In this work, we investigated the effects of vacuum on the micromachinable properties of CR-39. Our investigations proved that there were no drawbacks of the vacuum storage of the samples, so we concluded that CR-39 is a suitable material as a PBM resist in this respect, too. Another part of the current work concentrated on the effect of post-irradiaton CO 2 treatment of the samples. Such a treatment increased the radiation sensitivity of CR-39, i.e. decreased the necessary optimal ion fluence. We have found that approximately 60% of fluence

Treatment of primary liver tumors with Yttrium-90 microspheres (TheraSphere) in high risk patients: analysis of survival and toxicities.

Science.gov (United States)

Reardon, Kelli A; McIntosh, Alyson F; Shilling, A Tanner; Hagspiel, Klaus D; Al-Osaimi, Abdullah; Berg, Carl; Caldwell, Stephen H; Northup, Patrick G; Angle, Fritz; Mulder, Robert; Rich, Tyvin A

2009-02-01

This retrospective study was undertaken to obtain information regarding the survival and toxicities after Yttrium-90 microspheres treatment in patients with primary liver malignancies. Baseline, treatment, and follow-up data were collected and analyzed for 21 patients treated with Yttrium-90 microspheres. Survival analysis was then performed. The results of this study showed that median survival for all the patients was 120 days. Twenty of 21 patients were categorized as high-risk with a median survival of 114 days. It was also found that one high-risk patient has survived 858 days with no recurrence of disease. Acute grade 3-5 toxicities were recorded for nine patients and consisted of elevations in AST and bilirubin, thrombocytopenia, abdominal pain, ascites, nausea, fatigue, and death. This study concluded that Yttrium-90 is a low-toxicity, outpatient alternative for individuals with liver cancer and without many options. The maximal value, however, may lie in the treatment of low-risk patients.

The growth of Propionibacterium cyclohexanicum in fruit juices and its survival following elevated temperature treatments.

Science.gov (United States)

Walker, Michelle; Phillips, Carol A

2007-06-01

This study investigated the growth of Propionibacterium cyclohexanicum in orange juice over a temperature range from 4 to 40 degrees C and its ability to multiply in tomato, grapefruit, apple, pineapple and cranberry juices at 30 and 35 degrees C. Survival after 10 min exposure to 50, 60, 70, 80, 85, 90 and 95 degrees C in culture medium and in orange juice was also assessed. In orange juice the organism was able to multiply by 2 logs at temperatures from 4 to 35 degrees C and survived for up to 52 days. However, at 40 degrees C viable counts were reduced after 6 days and no viable cells isolated after 17 days. The optimum growth temperature in orange juice over 6 days was 25 degrees C but over 4 days it was 35 degrees C. The growth of P. cyclohexanicum was monitored in tomato, grapefruit, cranberry, pineapple and apple juices at 30 and 35 degrees C over 29 days. Cranberry, grapefruit and apple juice did not support the growth of P. cyclohexanicum. At 30 degrees C no viable cells were detected after 8 days in cranberry juice or after 22 days in grapefruit juice while at 35 degrees C no viable cells were detected after 5 and 15 days, respectively. However, in apple juice, although a 5 log reduction occurred, viable cells could be detected after 29 days. P. cyclohexanicum was able to multiply in both tomato and pineapple juices. In tomato juice, there was a 2 log increase in viable counts after 8 days at 30 degrees C but no increase at 35 degrees C, while in pineapple juice there was a 1 log increase in numbers over 29 days with no significant difference between numbers of viable cells present at 30 and 35 degrees C. The organism survived at 50 degrees C for 10 min in culture medium without a significant loss of viability while similar treatment at 60, 70 and 80 degrees C resulted in approximately a 3-4 log reduction, with no viable cells detected after treatment at 85 or 90 or 95 degrees C but, when pre-treated at intermediate temperatures before exposure to higher

GEANT4 simulations for Proton computed tomography applications

International Nuclear Information System (INIS)

Yevseyeva, Olga; Assis, Joaquim T. de; Evseev, Ivan; Schelin, Hugo R.; Shtejer Diaz, Katherin; Lopes, Ricardo T.

2011-01-01

Proton radiation therapy is a highly precise form of cancer treatment. In existing proton treatment centers, dose calculations are performed based on X-ray computed tomography (CT). Alternatively, one could image the tumor directly with proton CT (pCT). Proton beams in medical applications deal with relatively thick targets like the human head or trunk. Thus, the fidelity of proton computed tomography (pCT) simulations as a tool for proton therapy planning depends in the general case on the accuracy of results obtained for the proton interaction with thick absorbers. GEANT4 simulations of proton energy spectra after passing thick absorbers do not agree well with existing experimental data, as showed previously. The spectra simulated for the Bethe-Bloch domain showed an unexpected sensitivity to the choice of low-energy electromagnetic models during the code execution. These observations were done with the GEANT4 version 8.2 during our simulations for pCT. This work describes in more details the simulations of the proton passage through gold absorbers with varied thickness. The simulations were done by modifying only the geometry in the Hadron therapy Example, and for all available choices of the Electromagnetic Physics Models. As the most probable reasons for these effects is some specific feature in the code or some specific implicit parameters in the GEANT4 manual, we continued our study with version 9.2 of the code. Some improvements in comparison with our previous results were obtained. The simulations were performed considering further applications for pCT development. The authors want to thank CNPq, CAPES and 'Fundacao Araucaria' for financial support of this work. (Author)

Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

Energy Technology Data Exchange (ETDEWEB)

Feuvret, Loïc, E-mail: loic.feuvret@psl.aphp.fr [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bracci, Stefano [Institute of Radiation Oncology, Sapienza University, Sant' Andrea Hospital, Rome (Italy); Calugaru, Valentin [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bolle, Stéphanie [Department of Radiation Oncology, Gustave Roussy, Villejuif (France); Mammar, Hamid; De Marzi, Ludovic [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bresson, Damien [Department of Neurosurgery, Hôpital Lariboisière (Assistance Publique–Hôpitaux de Paris), Paris (France); Habrand, Jean-Louis [Department of Radiation Oncology, Centre François Baclesse, Caen (France); Mazeron, Jean-Jacques [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Dendale, Rémi [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); and others

2016-05-01

Purpose: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). Methods and Materials: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. Results: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Conclusions: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

SU-E-T-337: Treatment Planning Study of Craniospinal Irradiation with Spot Scanning Proton Therapy

International Nuclear Information System (INIS)

Tasson, A; Beltran, C; Laack, N; Childs, S; Tryggestad, E; Whitaker, T

2014-01-01

Purpose: To develop a treatment planning technique that achieves optimal robustness against systematic position and range uncertainties, and interfield position errors for craniospinal irradiation (CSI) using spot scanning proton radiotherapy. Methods: Eighteen CSI patients who had previously been treated using photon radiation were used for this study. Eight patients were less than 10 years old. The prescription dose was 23.4Gy in 1.8Gy fractions. Two different field arrangement types were investigated: 1 posterior field per isocenter and 2 posterior oblique fields per isocenter. For each field type, two delivery configurations were used: 5cm bolus attached to the treatment table and a 4.5cm range shifter located inside the nozzle. The target for each plan was the whole brain and thecal sac. For children under the age of 10, all plan types were repeated with an additional dose of 21Gy prescribed to the vertebral bodies. Treatment fields were matched by stepping down the dose in 10% increments over 9cm. Robustness against 3% and 3mm uncertainties, as well as a 3mm inter-field error was analyzed. Dose coverage of the target and critical structure sparing for each plan type will be considered. Ease of planning and treatment delivery was also considered for each plan type. Results: The mean dose volume histograms show that the bolus plan with posterior beams gave the best overall plan, and all proton plans were comparable to or better than the photon plans. The plan type that was the most robust against the imposed uncertainties was also the bolus plan with posterior beams. This is also the plan configuration that is the easiest to deliver and plan. Conclusion: The bolus plan with posterior beams achieved optimal robustness against systematic position and range uncertainties, as well as inter-field position errors

Improved Beam Angle Arrangement in Intensity Modulated Proton Therapy Treatment Planning for Localized Prostate Cancer

International Nuclear Information System (INIS)

Cao, Wenhua; Lim, Gino J.; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

2015-01-01

Purpose: This study investigates potential gains of an improved beam angle arrangement compared to a conventional fixed gantry setup in intensity modulated proton therapy (IMPT) treatment for localized prostate cancer patients based on a proof of principle study. Materials and Methods: Three patients with localized prostate cancer retrospectively selected from our institution were studied. For each patient, IMPT plans were designed using two, three and four beam angles, respectively, obtained from a beam angle optimization algorithm. Those plans were then compared with ones using two lateral parallel-opposed beams according to the conventional planning protocol for localized prostate cancer adopted at our institution. Results: IMPT plans with two optimized angles achieved significant improvements in rectum sparing and moderate improvements in bladder sparing against those with two lateral angles. Plans with three optimized angles further improved rectum sparing significantly over those two-angle plans, whereas four-angle plans found no advantage over three-angle plans. A possible three-beam class solution for localized prostate patients was suggested and demonstrated with preserved dosimetric benefits because individually optimized three-angle solutions were found sharing a very similar pattern. Conclusions: This study has demonstrated the potential of using an improved beam angle arrangement to better exploit the theoretical dosimetric benefits of proton therapy and provided insights of selecting quality beam angles for localized prostate cancer treatment

MSPT: Motion Simulator for Proton Therapy

International Nuclear Information System (INIS)

Morel, Paul

2014-01-01

In proton therapy, the delivery method named spot scanning, can provide a particularly efficient treatment in terms of tumor coverage and healthy tissues protection. The dosimetric benefits of proton therapy may be greatly degraded due to intra-fraction motions. Hence, the study of mitigation or adaptive methods is necessary. For this purpose, we developed an open-source 4D dose computation and evaluation software, MSPT (Motion Simulator for Proton Therapy), for the spot-scanning delivery technique. It aims at highlighting the impact of intra-fraction motions during a treatment delivery by computing the dose distribution in the moving patient. In addition, the use of MSPT allowed us to develop and propose a new motion mitigation strategy based on the adjustment of the beam's weight when the proton beam is scanning across the tumor. In photon therapy, a main concern for deliveries using a multi-leaf collimator (MLC) relies on finding a series of MLC configurations to deliver properly the treatment. The efficiency of such series is measured by the total beam-on time and the total setup time. In our work, we study the minimization of these efficiency criteria from an algorithmic point of view, for new variants of MLCs: the rotating MLC and the dual-layer MLC. In addition, we propose an approximation algorithm to find a series of configurations that minimizes the total beam-on time for the rotating MLC. (author) [fr

Survival of localized NSCLC patients without active treatment or treated with SBRT

DEFF Research Database (Denmark)

Jeppesen, S S; Hansen, N C G; Schytte, T

2018-01-01

BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for pati......BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment...... for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival. MATERIAL AND METHODS: From 2007 to 2013, 136 patients treated...... with SBRT at Odense University Hospital were prospectively recorded. The thoracic SBRT consisted of three fractions of 15-22 Gy delivered in 9 days. For comparison, a national group of 73 untreated patients in the same time period was extracted from the Danish Lung Cancer Registry. All patients had...

Proton pump inhibitors for the treatment of patients with erosive esophagitis and gastroesophageal reflux disease: current evidence and safety of dexlansoprazole

Directory of Open Access Journals (Sweden)

Mermelstein J

2016-07-01

Full Text Available Joseph Mermelstein,1 Alanna Chait Mermelstein,2 Maxwell M Chait,3 1Department of Medicine, Mount Sinai Beth Israel/Icahn School of Medicine, 2Department of Psychiatry, New York Presbyterian Hospital/Weill Cornell Medicine, 3Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA Abstract: Gastroesophageal reflux disease is the most common upper gastroenterology disorder in the US. It is associated with a variety of complications and significantly impacts quality of life. Proton pump inhibitors are the most effective treatment. Dexlansoprazole modified release (MR is a proton pump inhibitor that employs a novel release formulation that prolongs its absorption and allows for more flexibility in dosing. Dexlansoprazole MR can be dosed without regard to food intake or time of day, and once-daily dosing may replace twice-daily dosing of other agents. Dexlansoprazole MR is effective for healing and maintenance of erosive esophagitis, and for the treatment of nonerosive disease, including nocturnal gastroesophageal reflux disease. Dexlansoprazole MR is safe and well tolerated, and can improve quality of life. Keywords: dexlansoprazole, proton pump inhibitors, gastroesophageal reflux disease, erosive esophagitis

Advanced proton imaging in computed tomography

CERN Document Server

Mattiazzo, S; Giubilato, P; Pantano, D; Pozzobon, N; Snoeys, W; Wyss, J

2015-01-01

In recent years the use of hadrons for cancer radiation treatment has grown in importance, and many facilities are currently operational or under construction worldwide. To fully exploit the therapeutic advantages offered by hadron therapy, precise body imaging for accurate beam delivery is decisive. Proton computed tomography (pCT) scanners, currently in their R&D phase, provide the ultimate 3D imaging for hadrons treatment guidance. A key component of a pCT scanner is the detector used to track the protons, which has great impact on the scanner performances and ultimately limits its maximum speed. In this article, a novel proton-tracking detector was presented that would have higher scanning speed, better spatial resolution and lower material budget with respect to present state-of-the-art detectors, leading to enhanced performances. This advancement in performances is achieved by employing the very latest development in monolithic active pixel detectors (to build high granularity, low material budget, ...

Rationale and early outcomes for the management of thymoma with proton therapy.

Science.gov (United States)

Zhu, He J; Hoppe, Bradford S; Flampouri, Stella; Louis, Debbie; Pirris, John; Nichols, R Charles; Henderson, Randal H; Mercado, Catherine E

2018-04-01

Radiotherapy for thymic malignancies is technically challenging due to their close proximity to the heart, lungs, esophagus, and breasts, raising concerns about significant acute and late toxicities from conventional photon radiotherapy. Proton therapy (PT) may reduce the radiation dose to these vital organs, leading to less toxicity. We reviewed the dosimetry and outcomes among patients treated with PT for thymic malignancies at our institution. From January 2008 to March 2017, six patients with de novo Masaoka stages II-III thymic malignancies were treated with PT on an IRB-approved outcomes tracking protocol. Patients were evaluated weekly during treatment, then every 3 months for 2 years, then every 6 months for 3 more years, and then annually for CTCAE vs. four toxicities and disease recurrence. Comparison intensity-modulated radiotherapy (IMRT) plans were developed for each patient. Mean doses to the heart, esophagus, bilateral breasts, lungs, and V20 of bilateral lungs were evaluated for the two treatment plans. At last follow-up (median follow-up, 2.6 years), there were two patients with recurrences, including metastatic disease in the patient treated definitively with chemotherapy and PT without surgery and a local-regional recurrence in the lung outside the proton field in one of the post-operative cases. No patients with de novo disease experienced grade ≥3 toxicities after PT. The mean dose to the heart, lung, and esophagus was reduced on average by 36.5%, 33.5%, and 60%, respectively, using PT compared with IMRT (P<0.05 for each dose parameter). PT achieved superior dose sparing to the heart, lung, and esophagus compared to IMRT for thymic malignancies. Patients treated with PT had few radiation-induced toxicities and similar survival compared to historic proton data.

Radiosensitizing effect of nitric oxide in tumor cells and experimental tumors irradiated with gamma rays and proton beams; Efecto radiosensibilizador del oxido nitrico en celulas tumorales y en tumores experimentales irradiados con radiacion gamma y con haces de protones

Energy Technology Data Exchange (ETDEWEB)

Policastro, Lucia L; Duran, Hebe; Molinari, Beatriz L [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Radiobiologia; Schuff, Juan A; Kreiner, Andres J; Burlon, Alejandro A; Debray, Mario E; Kesque, Jose M; Ozafran, Mabel J; Vazquez, Monica E [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Fisica; Davidson, Jorge; Davidson, Miguel [Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Buenos Aires (Argentina); Somacal, Hector R; Valda, Alejandro A [Universidad Nacional de General San Martin , Villa Ballester (Argentina). Escuela de Ciencia y Tecnologia

2003-07-01

Nitric oxide (NO) has been reported to be a radiosensitizer of mammalian cells under hypoxic conditions. In a previous study, we demonstrated an enhancement in radiation response induced by NO in mouse tumor cells under aerobic conditions, with an increasing effect as a function of malignancy. The aim of the present study was to evaluate the effect of NO in tumor cells and in experimental tumors irradiated with {gamma} rays and proton beams. Irradiations were performed with a {sup 137}Cs {gamma} source and with proton beams generated by the TANDAR accelerator. Tumor cells were treated with the NO donor DETA-NO and the sensitizer enhancement ratio (SER) was calculated using the {alpha} parameter of the survival curve fitted to the linear-quadratic model. Tumor cells irradiated with protons were radio sensitized by DETA-NO only in the more malignant cells irradiated with low LET protons (2.69{+-}0.08 keV/{mu}m). For higher LET protons there were no radiosensitizing effect. For human tumor cells pre-treated with DETA-NO and irradiated with {gamma} rays, a significantly greater effect was demonstrated in the malignant cells (MCF-7) as compared with the near normal cells (HBL-100). Moreover, a significant decrease in tumor growth was demonstrated in mice pre-treated with the NO donor spermine and irradiated with {gamma} rays and low LET protons as compared with mice irradiated without pre-treatment with the NO donor. In conclusion, we demonstrated a differential effect of NO as a radiosensitizer of malignant cells, both with {gamma} rays and low LET protons. This selectivity, coupled to the in vivo inhibition of tumor growth, is of great interest for the potential use of NO releasing agents in radiotherapy. (author)

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma.

Science.gov (United States)

Ho, Evangeline S Q; Barrett, Sarah A; Mullaney, Laura M

2017-08-01

Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI) delivers significant dose to surrounding normal tissue (NT). Research into pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of exploiting the potential to reduce NT dose and associated post-treatment complications. This review aims to compare treatment outcomes of pediatric medulloblastoma patients between Proton- and Photon-CSI treatments. A search and review of studies published between 1990 and 2016 comparing pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects - normal organ sparing and target coverage; normal organ dysfunction and second malignancy risks - was completed. Fifteen studies were selected for review and the results were directly compared. Proton-CSI reported improved out-of-field organ sparing while target coverage improvements were inconsistent. Normal organ dysfunction risks were predicted to be lower following Proton-CSI. Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on several different risk models. Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Marital status, treatment, and survival in patients with glioblastoma multiforme: a population based study.

Science.gov (United States)

Chang, Susan M; Barker, Fred G

2005-11-01

Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). On multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.79-0.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% CI, 0.62-0.77; P Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared with married patients, even after adjustment for treatment and other prognostic factors. (c) 2005 American Cancer Society.

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor

International Nuclear Information System (INIS)

Park, Lily; De Laney, Thomas F.; Liebsch, Norbert J.; Hornicek, Francis J.; Goldberg, Saveli; Mankin, Henry; Rosenberg, Andrew E.; Rosenthal, Daniel I.; Suit, Herman D.

2006-01-01

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received ≥73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by ≥73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option

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

Science.gov (United States)

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

2017-01-01

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

Proton radioactivity from proton-rich nuclei

International Nuclear Information System (INIS)

Guzman, F.; Goncalves, M.; Tavares, O.A.P.; Duarte, S.B.; Garcia, F.; Rodriguez, O.

1999-03-01

Half-lives for proton emission from proton-rich nuclei have been calculated by using the effective liquid drop model of heavy-particle decay of nuclei. It is shown that this model is able to offer results or spontaneous proton-emission half-life-values in excellent agreement with the existing experimental data. Predictions of half-life-values for other possible proton-emission cases are present for null orbital angular momentum. (author)

Bragg peak proton beam treatment of arteriovenous malformations of the brain

International Nuclear Information System (INIS)

Kjellberg, R.N.; Poletti, C.E.; Roberson, G.H.; Adams, R.D.

1978-01-01

This report describes 27 patients treated for arteriovenous malformations of the brain by the Bragg Peak proton beam method during the past 12 years. The authors are led to a measure of confidence that Bragg Peak proton therapy can be provided without lethal risk attributed to the procedure. In 21 patients no neurological change has occurred, two patients experienced neurological improvement and four have developed new neurological abnormalities considered complications of the therapy. (Auth.)

Obesity does not affect treatment outcomes with proton pump inhibitors.

Science.gov (United States)

Sharma, Prateek; Vakil, Nimish; Monyak, John T; Silberg, Debra G

2013-09-01

Obesity is associated with increased risk of gastroesophageal reflux disease (GERD). To evaluate the effect of obesity on symptom resolution in patients with nonerosive reflux disease (NERD) and healing rates in patients with erosive esophagitis (EE). Two post hoc analyses were performed. Analyses included pooled data from randomized, double-blind, multicenter studies of proton pump inhibitors (PPIs) in GERD patients. Analysis 1 included 704 patients with NERD receiving esomeprazole 20 mg, esomeprazole 40 mg, or placebo. Analysis 2 included 11,027 patients with EE receiving esomeprazole 40 mg, omeprazole 20 mg, or lansoprazole 30 mg. For NERD patients, no significant association between baseline heartburn severity and body mass index (BMI) was observed. In EE patients, overweight (BMI 25 to <35 kg/m) and obese (BMI ≥35 kg/m) patients had significantly higher rates of Los Angeles (LA) grade C or D EE than patients with BMI <25 kg/m (P<0.0001). Percentages of PPI-treated patients who achieved heartburn resolution or EE healing within a given LA grade were similar across BMI categories. Heartburn resolution was significantly associated with treatment (esomeprazole vs. placebo), increasing age, and for men versus women (all P≤0.0284). EE healing was significantly associated with PPI treatment (esomeprazole and lansoprazole vs. omeprazole), increasing age, race, presence of a hiatal hernia, and lower LA grade at baseline (all P≤0.0183). In patients with GERD, high BMI was associated with more severe EE at baseline. However, during PPI treatment, BMI is not a significant independent predictor of heartburn resolution or EE healing.

Multicomponent Time-Dependent Density Functional Theory: Proton and Electron Excitation Energies.

Science.gov (United States)

Yang, Yang; Culpitt, Tanner; Hammes-Schiffer, Sharon

2018-04-05

The quantum mechanical treatment of both electrons and protons in the calculation of excited state properties is critical for describing nonadiabatic processes such as photoinduced proton-coupled electron transfer. Multicomponent density functional theory enables the consistent quantum mechanical treatment of more than one type of particle and has been implemented previously for studying ground state molecular properties within the nuclear-electronic orbital (NEO) framework, where all electrons and specified protons are treated quantum mechanically. To enable the study of excited state molecular properties, herein the linear response multicomponent time-dependent density functional theory (TDDFT) is derived and implemented within the NEO framework. Initial applications to FHF - and HCN illustrate that NEO-TDDFT provides accurate proton and electron excitation energies within a single calculation. As its computational cost is similar to that of conventional electronic TDDFT, the NEO-TDDFT approach is promising for diverse applications, particularly nonadiabatic proton transfer reactions, which may exhibit mixed electron-proton vibronic excitations.

Adaptation of proton total dose with respect to dosimetric parameters within the frame of treatment of skull base or upper cervical spine chordomas; Adaptation de la dose totale de protons en fonction des parametres dosimetriques dans le cadre du traitement des chordomes de la base du crane et du rachis cervical haut

Energy Technology Data Exchange (ETDEWEB)

Hemery, C.G.; Mazeron, J.J.; Feuvret, L. [Groupe hospitalier Pitie-Salpetriere (AP-HP), 75 - Paris (France); Calugaru, V.; Bolle, S.; Habrand, J.L.; Datcharty, J.; Alapetite, C.; Dendale, R.; Feuvret, L. [Institut Curie-Centre de protontherapie d' Orsay, 91 (France); Habrand, J.L.; Datcharty, J. [Institut Gustave-Roussy, 94 - Villejuif (France); Noel, G. [Centre Paul-Strauss, 67 - Strasbourg (France)

2010-10-15

The authors report the study of the feasibility of a photon-proton irradiation protocol with a dose adaptation with respect to dosimetric factors for patients suffering form a skull base and upper cervical spine chordoma. Sixty patients have been treated between May 2006 and June 2008 with a combination of high energy photons and protons. As five tumours have locally relapsed and one at distance, the authors comment the local control rates, the number of attained cranial nerves, the value of the macroscopic tumour volume, the survival rate without relapse in terms of multifactorial of uni-factorial analysis. Short communication

SU-F-T-666: Molecular-Targeted Gold Nanorods Enhances the RBE of Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Khoo, A; Sahoo, N; Krishnan, S; Diagaradjane, P [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: In recent years, proton beam radiation therapy (PBRT) has gained significant attention in the treatment of tumors in anatomically complex locations. However, the therapeutic benefit of PBRT is limited by a relative biological effectiveness (RBE) of just 1.1. The purpose of this study is to evaluate whether this limitation can be overcome by artificially enhancing the RBE using molecular-targeted gold nanorods (GNRs). Methods: Molecular-targeting of GNRs was accomplished using Cetuximab (antibody specific to epidermal growth factor receptor that is over-expressed in tumors) conjugated GNRs (cGNRs) and their binding affinity to Head and Neck cancer cells was confirmed using dark field microscopy and Transmission Electron Microscopy (TEM). The radiosensitization potential of cGNRs when irradiated with photon (6MV) and proton (100 and 160 MeV) beams was determined using clonogenic assays. The RBE at 10% surviving fraction (RBE{sub 10}) for proton therapies at central and distal locations of SOBP was calculated with respect to 6 MV photons. IgGconjugated GNRs (iGNRs) were used as controls in all experiments. Results: cGNRs demonstrated significant radiosensitization when compared to iGNRs for 6MV photons (1.14 vs 1.04), 100 MeV protons (1.19 vs 1.04), and 160 MeV protons (1.17 vs 1.04). While RBE10 for proton beams at the center of SOBP revealed similar effects for both 100 and 160 MeV (RBE{sup 10}=1.39 vs 1.38; p>0.05), enhanced radiosensitization was observed at the distal SOBP with 100 MeV beams demonstrating greater effect than 160 MeV beams (RBE{sup 10}=1.79 vs 1.6; p<0.05). Conclusion: EGFR-targeting GNRs significantly enhance the RBE of protons well above the accepted 1.1 value. The enhanced RBE observed for lower energy protons (100 MeV) and at the distal SOBP suggests that low energy components may play a role in the observed radiosensitization effect. This strategy holds promise for clinical translation and could evolve as a paradigm-changing approach

Data acquisition system for a proton imaging apparatus

CERN Document Server

Sipala, V; Bruzzi, M; Bucciolini, M; Candiano, G; Capineri, L; Cirrone, G A P; Civinini, C; Cuttone, G; Lo Presti, D; Marrazzo, L; Mazzaglia, E; Menichelli, D; Randazzo, N; Talamonti, C; Tesi, M; Valentini, S

2009-01-01

New developments in the proton-therapy field for cancer treatments, leaded Italian physics researchers to realize a proton imaging apparatus consisting of a silicon microstrip tracker to reconstruct the proton trajectories and a calorimeter to measure their residual energy. For clinical requirements, the detectors used and the data acquisition system should be able to sustain about 1 MHz proton rate. The tracker read-out, using an ASICs developed by the collaboration, acquires the signals detector and sends data in parallel to an FPGA. The YAG:Ce calorimeter generates also the global trigger. The data acquisition system and the results obtained in the calibration phase are presented and discussed.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

Science.gov (United States)

Wacker, Katrin; Denker, Sophy; Hildebrand, Antonia; Eberwein, Philipp; Reinhard, Thomas; Schwartzkopff, Johannes

2013-01-01

Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM) following experimental keratoplasty in rats. Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+), CD4(+), CD8(+), CD25(+), CD161(+) and CD163(+) cells were quantified via immunohistochemistry. AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls. Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Short-term azithromycin treatment promotes cornea allograft survival in the rat.

Directory of Open Access Journals (Sweden)

Katrin Wacker

Full Text Available Any inflammatory response following corneal transplantation may induce rejection and irreversible graft failure. The purpose of this study is to analyze the anti-inflammatory effect of azithromycin (AZM following experimental keratoplasty in rats.Corneal transplants were performed between Fisher-donor and Lewis-recipient rats. Recipients were postoperatively treated three times daily with AZM, miglyol, ofloxacin or dexamethasone eye drops. As an additional control, AZM was applied following syngeneic keratoplasty. Furthermore, short-term treatments with AZM for seven days perioperatively or with AZM only three days prior to the transplantation were compared to appropriate controls. All transplants were monitored clinically for opacity, edema, and vascularization. Infiltrating CD45(+, CD4(+, CD8(+, CD25(+, CD161(+ and CD163(+ cells were quantified via immunohistochemistry.AZM significantly promoted corneal graft survival compared with miglyol or ofloxacin treatment. This effect was comparable to topical dexamethasone. No adverse AZM effect was observed. Histology confirmed a significant reduction of infiltrating leukocytes. The short-term application of AZM for three days prior to transplantation or for seven days perioperatively reduced corneal graft rejection significantly compared with the controls.Along with antibiotic properties, topical AZM has a strong anti-inflammatory effect. Following keratoplasty, this effect is comparable to topical dexamethasone without the risk of steroid-induced adverse effects. Short-term treatment with AZM three days prior to the transplantation was sufficient to promote graft survival in the rat keratoplasty model. We therefore suggest further assessing the anti-inflammatory function of topical AZM following keratoplasty in humans.

Geant4 simulation of clinical proton and carbon ion beams for the treatment of ocular melanomas with the full 3-D pencil beam scanning system

Energy Technology Data Exchange (ETDEWEB)

Farina, Edoardo; Riccardi, Cristina; Rimoldi, Adele; Tamborini, Aurora [University of Pavia and the INFN section of Pavia, via Bassi 6, 27100 Pavia (Italy); Piersimoni, Pierluigi [Division of Radiation Research, Loma Linda University, Loma Linda, CA 92354 (United States); Ciocca, Mario [Medical Physics Unit, CNAO Foundation, Strada Campeggi 53, 27100 Pavia (Italy)

2015-07-01

This work investigates the possibility to use carbon ion beams delivered with active scanning modality, for the treatment of ocular melanomas at the Centro Nazionale di Adroterapia Oncologica (CNAO) in Pavia. The radiotherapy with carbon ions offers many advantages with respect to the radiotherapy with protons or photons, such as a higher relative radio-biological effectiveness (RBE) and a dose release better localized to the tumor. The Monte Carlo (MC) Geant4 10.00 patch-03 toolkit is used to reproduce the complete CNAO extraction beam line, including all the active and passive components characterizing it. The simulation of proton and carbon ion beams and radiation scanned field is validated against CNAO experimental data. For the irradiation study of the ocular melanoma an eye-detector, representing a model of a human eye, is implemented in the simulation. Each element of the eye is reproduced with its chemical and physical properties. Inside the eye-detector a realistic tumor volume is placed and used as the irradiation target. A comparison between protons and carbon ions eye irradiations allows to study possible treatment benefits if carbon ions are used instead of protons. (authors)

Radiobiology of Proton Therapy - Results of an international expert workshop

DEFF Research Database (Denmark)

Lühr, Armin; von Neubeck, Cläre; Pawelke, Jörg

2018-01-01

The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full...... in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness...... of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data...

MO-F-CAMPUS-T-01: IROC Houston QA Center’s Anthropomorphic Proton Phantom Program

International Nuclear Information System (INIS)

Lujano, C; Hernandez, N; Keith, T; Nguyen, T; Taylor, P; Molineu, A; Followill, D

2015-01-01

Purpose: To describe the proton phantoms that IROC Houston uses to approve and credential proton institutions to participate in NCI-sponsored clinical trials. Methods: Photon phantoms cannot necessarily be used for proton measurements because protons react differently than photons in some plastics. As such plastics that are tissue equivalent for protons were identified. Another required alteration is to ensure that the film dosimeters are housed in the phantom with no air gap to avoid proton streaming. Proton-equivalent plastics/materials used include RMI Solid Water, Techron HPV, blue water, RANDO soft tissue material, balsa wood, compressed cork and polyethylene. Institutions wishing to be approved or credentialed request a phantom and are prioritized for delivery. At the institution, the phantom is imaged, a treatment plan is developed, positioned on the treatment couch and the treatment is delivered. The phantom is returned and the measured dose distributions are compared to the institution’s electronically submitted treatment plan dosimetry data. Results: IROC Houston has developed an extensive proton phantom approval/credentialing program consisting of five different phantoms designs: head, prostate, lung, liver and spine. The phantoms are made with proton equivalent plastics that have HU and relative stopping powers similar (within 5%) of human tissues. They also have imageable targets, avoidance structures, and heterogeneities. TLD and radiochromic film are contained in the target structures. There have been 13 head, 33 prostate, 18 lung, 2 liver and 16 spine irradiations with either passive scatter, or scanned proton beams. The pass rates have been: 100%, 69.7%, 72.2%, 50%, and 81.3%, respectively. Conclusion: IROC Houston has responded to the recent surge in proton facilities by developing a family of anthropomorphic phantoms that are able to be used for remote audits of proton beams. Work supported by PHS grant CA10953 and CA081647

MO-F-CAMPUS-T-01: IROC Houston QA Center’s Anthropomorphic Proton Phantom Program

Energy Technology Data Exchange (ETDEWEB)

Lujano, C; Hernandez, N; Keith, T; Nguyen, T; Taylor, P; Molineu, A; Followill, D [UT MD Anderson Cancer Center, Houston, TX (United States)

2015-06-15

Purpose: To describe the proton phantoms that IROC Houston uses to approve and credential proton institutions to participate in NCI-sponsored clinical trials. Methods: Photon phantoms cannot necessarily be used for proton measurements because protons react differently than photons in some plastics. As such plastics that are tissue equivalent for protons were identified. Another required alteration is to ensure that the film dosimeters are housed in the phantom with no air gap to avoid proton streaming. Proton-equivalent plastics/materials used include RMI Solid Water, Techron HPV, blue water, RANDO soft tissue material, balsa wood, compressed cork and polyethylene. Institutions wishing to be approved or credentialed request a phantom and are prioritized for delivery. At the institution, the phantom is imaged, a treatment plan is developed, positioned on the treatment couch and the treatment is delivered. The phantom is returned and the measured dose distributions are compared to the institution’s electronically submitted treatment plan dosimetry data. Results: IROC Houston has developed an extensive proton phantom approval/credentialing program consisting of five different phantoms designs: head, prostate, lung, liver and spine. The phantoms are made with proton equivalent plastics that have HU and relative stopping powers similar (within 5%) of human tissues. They also have imageable targets, avoidance structures, and heterogeneities. TLD and radiochromic film are contained in the target structures. There have been 13 head, 33 prostate, 18 lung, 2 liver and 16 spine irradiations with either passive scatter, or scanned proton beams. The pass rates have been: 100%, 69.7%, 72.2%, 50%, and 81.3%, respectively. Conclusion: IROC Houston has responded to the recent surge in proton facilities by developing a family of anthropomorphic phantoms that are able to be used for remote audits of proton beams. Work supported by PHS grant CA10953 and CA081647.

Artificially regenerating longleaf pine on wet sites: preliminary analysis of effects of site preparation treatments on early survival and growth

Science.gov (United States)

Benjamin O. Knapp; G. Geoff Wang; Joan L. Walker

2010-01-01

Our study, conducted over two years on poorly drained, sandy sites in Onslow County, NC, compared the effects of eight common site preparation treatments on early survival and growth of planted longleaf pine seedlings. Through two growing seasons, we found survival to be similar across all treatments (p = 0.8806), but root collar diameter was greatest with combinations...

Proton solvation and proton transfer in chemical and electrochemical processes

International Nuclear Information System (INIS)

Lengyel, S.; Conway, B.E.

1983-01-01

This chapter examines the proton solvation and characterization of the H 3 O + ion, proton transfer in chemical ionization processes in solution, continuous proton transfer in conductance processes, and proton transfer in electrode processes. Topics considered include the condition of the proton in solution, the molecular structure of the H 3 O + ion, thermodynamics of proton solvation, overall hydration energy of the proton, hydration of H 3 O + , deuteron solvation, partial molal entropy and volume and the entropy of proton hydration, proton solvation in alcoholic solutions, analogies to electrons in semiconductors, continuous proton transfer in conductance, definition and phenomenology of the unusual mobility of the proton in solution, solvent structure changes in relation to anomalous proton mobility, the kinetics of the proton-transfer event, theories of abnormal proton conductance, and the general theory of the contribution of transfer reactions to overall transport processes

Radiosensitizing effect of nitric oxide in tumor cells and experimental tumors irradiated with gamma rays and proton beams

International Nuclear Information System (INIS)

Policastro, Lucia L.; Duran, Hebe; Molinari, Beatriz L.; Somacal, Hector R.; Valda, Alejandro A.

2003-01-01

Nitric oxide (NO) has been reported to be a radiosensitizer of mammalian cells under hypoxic conditions. In a previous study, we demonstrated an enhancement in radiation response induced by NO in mouse tumor cells under aerobic conditions, with an increasing effect as a function of malignancy. The aim of the present study was to evaluate the effect of NO in tumor cells and in experimental tumors irradiated with γ rays and proton beams. Irradiations were performed with a 137 Cs γ source and with proton beams generated by the TANDAR accelerator. Tumor cells were treated with the NO donor DETA-NO and the sensitizer enhancement ratio (SER) was calculated using the α parameter of the survival curve fitted to the linear-quadratic model. Tumor cells irradiated with protons were radio sensitized by DETA-NO only in the more malignant cells irradiated with low LET protons (2.69±0.08 keV/μm). For higher LET protons there were no radiosensitizing effect. For human tumor cells pre-treated with DETA-NO and irradiated with γ rays, a significantly greater effect was demonstrated in the malignant cells (MCF-7) as compared with the near normal cells (HBL-100). Moreover, a significant decrease in tumor growth was demonstrated in mice pre-treated with the NO donor spermine and irradiated with γ rays and low LET protons as compared with mice irradiated without pre-treatment with the NO donor. In conclusion, we demonstrated a differential effect of NO as a radiosensitizer of malignant cells, both with γ rays and low LET protons. This selectivity, coupled to the in vivo inhibition of tumor growth, is of great interest for the potential use of NO releasing agents in radiotherapy. (author)

Protons and how they are transported by proton pumps