W.F. Hartsell

Proton beam radiotherapy as part of comprehensive regional nodal irradiation for locally advanced breast cancer

PURPOSEnThis study evaluates acute toxicity outcomes in breast cancer patients treated with adjuvant proton beam therapy (PBT).nnnMETHODSnFrom 2011 to 2016, 91 patients (93 cancers) were treated with adjuvant PBT targeting the intact breast/chest wall and comprehensive regional nodes including the axilla, supraclavicular fossa, and internal mammary lymph nodes. Toxicity was recorded weekly during treatment, one month following treatment, and then every 6months according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Charts were retrospectively reviewed to verify toxicities, patient parameters, disease and treatment characteristics, and disease-related outcomes.nnnRESULTSnMedian follow-up was 15.5months. Median PBT dose was 50.4 Gray relative biological effectiveness (GyRBE), with subsequent boost as clinically indicated (N=61, median 10 GyRBE). Chemotherapy, when administered, was given adjuvantly (N=42) or neoadjuvantly (N=46). Grades 1, 2, and 3 dermatitis occurred in 23%, 72%, and 5%, respectively. Eight percent required treatment breaks owing to dermatitis. Median time to resolution of dermatitis was 32days. Grades 1, 2, and 3 esophagitis developed in 31%, 33%, and 0%, respectively.nnnCONCLUSIONSnPBT displays acceptable toxicity in the setting of comprehensive regional nodal irradiation.

Multi-Institutional Prospective Study of Reirradiation with Proton Beam Radiotherapy for Locoregionally Recurrent Non–Small Cell Lung Cancer

Objectives: The management of recurrent NSCLC in the setting of prior radiation therapy is challenging. Proton radiotherapy (PRT) is ideally suited to minimize toxicity to previously irradiated organs. We report the safety/feasibility of PRT for NSCLC reirradiation in a prospective multi‐institutional study. Materials and Methods: Between October 2010 and December 2015, 57 patients with recurrent NSCLC in or near their prior radiation field were treated at three proton centers. Patients were classified by tumor volume, location, and clinical characteristics. Toxicities were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Survival outcomes were estimated by using Kaplan‐Meier analysis. Results: Fifty‐two patients (93%) completed the reirradiation course. Their median age was 65 years (41–86). Patients with high tumor volume (clinical target volume–to–internal target volume ratio ≥250 cm3) were closed to enrollment owing to infeasibility in August 2012. Concurrent systemic therapy was delivered to 67% of patients. Fourteen patients (25%) had evidence of local (n = 9) or regional (n = 5) recurrence. Distant metastases after reirradiation developed in six patients (11%). The 1‐year rates of overall and progression‐free survival were 59% and 58%, respectively. In total, grade 3 or higher acute and/or late toxicity developed in 24 patients (42%), acute toxicity developed in 22 (39%), and late toxicity developed in seven (12%). Six grade 5 toxicities were observed. Increased overlap with the central airway region, mean esophagus and heart doses, and concurrent chemotherapy were associated with significantly higher rates of grade 3 or higher toxicity. Decreased overall survival was seen with increased mean esophagus dose (p = 0.007). Conclusions: In this prospective study, PRT for recurrent NSCLC is feasible but can be associated with significant toxicity. Providers should remain cautious in reirradiating NSCLC, paying close consideration to tumor volume, location, and relevant dosimetric parameters. Further research is needed for optimal patient selection to improve overall outcomes.

Anterior-oriented proton beams for prostate cancer: A multi-institutional experience.

Abstract Background. Proton beam therapy (PBT) for prostate cancer generally involves the use of two lateral beams that transverse the hips. In patients with hip replacements or a previously irradiated hip, this arrangement is contraindicated. The use of non-lateral beams is possible, but not well described. Here we report a multi-institutional experience for patients treated with at least one non-lateral proton beam for prostate cancer. Material and methods. Between 2010 and 2014, 20 patients with organ-confined prostate cancer and a history of hip prosthesis underwent proton therapy utilizing at least one anterior oblique beam (defined as between 10° and 85° from vertical) at one of three proton centers. Results. The median follow-up was 6.4 months. No patients have developed PSA failure or distant metastases. The median planning target volume (PTV) D95 was 79.2 Gy (RBE) (range 69.7–79.9). The median rectal V70 was 9.2% (2.5–15.4). The median bladder V50, V80, and mean dose were 12.4% (3.7–27.1), 3.5 cm3 (0–7.1), and 14.9 Gy (RBE) (4.6–37.8), respectively. The median contralateral femur head V45 and max dose were 0.01 cm3 (0–16.6) and 43.7 Gy (RBE) (15.6–52.5), respectively. The incidence of acute Grade 2 urinary toxicity was 40%. There were no Grade ≥ 3 urinary toxicities. There was one patient who developed late Grade 2 rectal proctitis, with no other cases of acute or late ≥ Grade 2 gastrointestinal toxicity. Grade 2 erectile dysfunction occurred in two patients (11.1%). Mild hip pain was experienced by five patients (25%). There were no cases of hip fracture. Conclusion. PBT for prostate cancer utilizing anterior oblique beam trajectories is feasible with favorable dosimetry and acceptable toxicity. Further follow-up is needed to assess for long-term outcomes and toxicities.

Proton therapy patterns-of-care and early outcomes for Hodgkin lymphoma: results from the Proton Collaborative Group Registry.

Bradford S. Hoppe, Henry Tsai, Gary Larson, George E. Laramore, Carlos Vargas, Yolanda D. Tseng, Megan Dunn, Lisa McGee, Oren Cahlon and William Hartsell University of Florida Health Proton Therapy Institute, Jacksonville, Florida, USA; Procure Proton Therapy Center, Somerset, New Jersey, USA; Procure Proton Therapy Center, Oklahoma City, Oklahoma, USA; Seattle Cancer Care Alliance Proton Therapy Center, Seattle, Washington, USA; Mayo Clinic, Scottsdale, Arizona, USA; Chicago Proton Center, Warrenville, Illinois, USA; Memorial Sloan-Kettering Cancer Center, New York City, New York, USA

Severe Radiation Necrosis Successfully Treated With Bevacizumab in an Infant with Low‐Grade Glioma and Tumor‐Associated Intractable Trigeminal Neuralgia

We present a unique case of radiation necrosis in a child with brain stem low‐grade glioma (LGG) presenting with trigeminal neuralgia. Despite extensive therapies, severe pain persisted. She received proton beam radiation with significant improvement. However, she developed radiation necrosis and hydrocephalus. Despite surgical correction of hydrocephalus, the patient remained critically ill. She was treated with dexamethasone and bevacizumab with rapid clinical improvement. Subsequent MRIs revealed almost complete resolution of the necrosis. This case illustrates the successful treatment of trigeminal neuralgia with radiation and a rare case of radiation necrosis in an LGG successfully treated with bevacizumab and dexamethasone.

Proton therapy and helical tomotherapy result in reduced dose deposition to the pancreas in the setting of cranio-spinal irradiation for medulloblastoma: implications for reduced risk of diabetes mellitus in long-term survivors.

Many pediatric cancer patients require cranio-spinal irradiation (CSI) as part of curative treatment for various childhood central nervous system malignancies. Notably, medulloblastoma represents the most common malignant pediatric brain tumor requiring CSI. Aggressive treatment regimens in this setting result in relatively high cure rates, with fi ve-year overall survival (OS) ranging from 72% to 85% [1]. As a result of long-term survival following comprehensive treatment, many patients are at risk for the development of late effects [2]. Standard photon beam irradiation of the craniospinal axis has been associated with late effects to include vertebral growth arrest, cardiac dysfunction, restrictive lung disease and gonadal dysfunction [3]. Furthermore, pediatric patients receiving central nervous system (CNS) irradiation may be subject to a number of well-characterized treatment-related late effects to include neurocognitive defi cits, endocrine dysfunction, secondary malignancy and hearing defi cits [4]. The capacity for increased target conformality of proton beam therapy (PBT) has been proposed to reduce late effects, with ongoing investigation into clinical outcomes [5,6]. Accumulating evidence from the literature demonstrates a linkage between the development of diabetes mellitus (DM) and total body/abdominal irradiation [7,8]. A recent multi-institution study, by deVathaire et al. demonstrated a dose-response relationship between radiation dose to the pancreatic tail and risk of subsequent DM in childhood cancer survivors [9]. deVathair et al. reported on the long-term follow-up of pediatric patients treated with radiation, involving dose to the pancreas. An 11.5-fold relative increased risk of DM was noted with doses greater than 10 Gy to the pancreas, specifi cally the tail of the pancreas. Another recent study by van Nimwegen et al. contributed further support to a relationship between pancreatic and pancreatic tail radiation and the increased risk of developing DM [10]. Here the authors demonstrated that a mean dose to the pancreatic tail of x03 36 Gy resulted in a 2.58-fold increased risk of developing DM [10]. Collectively these data suggest the potential radiosensitivity of pancreatic islet cells responsible for insulin secretion [11]. These fi ndings support identifying the pancreas as a radiosensitive organ at risk (OAR) during CSI, which has not previously been standard practice. To better assess pancreatic dosimetry using conventional photon techniques and the differential capacity for pancreatic sparing with techniques of increased conformality, this study compares CSI approaches using conventional three-dimensional conformal photon therapy (3DCRT), inverse-planned intensity-modulated radiotherapy using helical tomotherapy (HT), and PBT.

Image-guided hypofractionated proton beam therapy for low-risk prostate cancer: Analysis of quality of life and toxicity, PCG GU 002.

AIMnThis interim analysis evaluated changes in quality of life (QOL), American Urological Association Symptom Index (AUA), or adverse events (AEs) among prostate cancer patients treated with hypofractionation.nnnBACKGROUNDnResults for hypofractionated prostate cancer with photon therapy are encouraging. No prior trial addresses the role of proton therapy in this clinical setting.nnnMATERIALS AND METHODSnForty-nine patients with low-risk prostate cancer received 38-Gy relative biologic effectiveness in 5 treatments. They received proton therapy at 2 fields a day, magnetic resonance imaging registration, rectal balloon, and fiducial markers for guidance pre-beam. We evaluated AEs, Expanded Prostate Index Composite (EPIC) domains, and AUA at pretreatment and at 3, 6, 12, 18, and 24 months. An AUA change >5 points and QOL change of half a standard deviation (SD) defined clinical significance.nnnRESULTSnMedian follow-up was 18 months; 17 patients reached follow-up of ≥24 months. For urinary function, statistically and clinically significant change was not seen (maximum change, 3). EPIC urinary QOL scores did not show statistically and clinically significant change at any end point (maximum, 0.45 SD). EPIC bowel QOL scores showed small but statistically and clinically significant change at 6, 12, 18, and 24 months (SD range, 0.52-0.62). EPIC sexual scores showed small but statistically and clinically significant change at 24 months (SD, 0.52). No AE grade ≥3 was seen.nnnCONCLUSIONSnPatients treated with hypofractionated proton therapy tolerated treatment well, with excellent QOL scores, persistently low AUA, and no AE grade ≥3.

Low Levels of Acute Toxicity Associated With Proton Therapy for Low-Grade Glioma: A Proton Collaborative Group Study.

1Willis-Knighton Cancer Center, Shreveport, LA; 2Louisiana State University Health Sciences Center, Shreveport, LA; 3Northwestern Medicine Chicago Proton Center, Warrenville, IL; 4Procure Proton Therapy Center, Oklahoma City, OK; 5University of Washington Medical Center and SCCA Proton Therapy Center, SeaYle, WA; 6Mayo Clinic Arizona, ScoYsdale, AZ 7University of Texas MD Anderson Cancer Center, Houston, Texas; 8MassachuseYs General Hospital, Boston, MA; 9Miami Cancer Instute, Bapst Health South Florida, Miami, FL

Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiation: results from the proton collaborative group REG001-09 trial

Abstract Background: Proton beam therapy (PBT) reduces normal organ dose compared to intensity modulated radiation therapy (IMXT) for prostate cancer patients who receive pelvic radiation therapy. It is not known whether this dosimetric advantage results in less gastrointestinal (GI) and genitourinary (GU) toxicity than would be expected from IMXT. Material and methods: We evaluated treatment parameters and toxicity outcomes for non-metastatic prostate cancer patients who received pelvic radiation therapy and enrolled on the PCG REG001-09 trial. Patients who received X-ray therapy and/or brachytherapy were excluded. Of 3210 total enrolled prostate cancer patients, 85 received prostate and pelvic radiation therapy exclusively with PBT. Most had clinically and radiographically negative lymph nodes although 6 had pelvic nodal disease and one also had para-aortic involvement. Pelvic radiation therapy was delivered using either 2 fields (opposed laterals) or 3 fields (opposed laterals and a posterior beam). Median pelvic dose was 46.9 GyE (range 39.7–56) in 25 fractions (range 24–30). Median boost dose to the prostateu2009+/− seminal vesicles was 30 GyE (range 20–41.4) in 16 fractions (range 10–24). Results: Median follow-up was 14.5 months (range 2.8–49.2). Acute grade 1, 2, and 3 GI toxicity rates were 16.4, 2.4, 0%, respectively. Acute grade 1, 2, and 3 GU toxicity rates were 60, 34.1, 0%, respectively. Conclusions: Prostate cancer patients who receive pelvic radiation therapy using PBT experience significantly less acute GI toxicity than is expected using IMXT. Further investigation is warranted to confirm whether this favorable acute GI toxicity profile is related to small bowel sparing from PBT.

An update from the Pediatric Proton Consortium Registry

Background/objectives The Pediatric Proton Consortium Registry (PPCR) was established to expedite proton outcomes research in the pediatric population requiring radiotherapy. Here, we introduce the PPCR as a resource to the oncology community and provide an overview of the data available for further study and collaboration. Design/methods A multi-institutional registry of integrated clinical, dosimetric, radiographic, and patient-reported data for patients undergoing proton radiation therapy was conceived in May 2010. Massachusetts General Hospital began enrollment in July of 2012. Subsequently, 12 other institutions joined the PPCR and activated patient accrual, with the latest joining in 2017. An optional patient-reported quality of life (QoL) survey is currently implemented at six institutions. Baseline health status, symptoms, medications, neurocognitive status, audiogram findings, and neuroendocrine testing are collected. Treatment details of surgery, chemotherapy, and radiation therapy are documented and radiation plans are archived. Follow-up is collected annually. Data were analyzed 25 September, 2017. Results A total of 1,854 patients have consented and enrolled in the PPCR from October 2012 until September 2017. The cohort is 55% male, 70% Caucasian, and comprised of 79% United States residents. Central nervous system (CNS) tumors comprise 61% of the cohort. The most common CNS histologies are as follows: medulloblastoma (n = 276), ependymoma (n = 214), glioma/astrocytoma (n = 195), craniopharyngioma (n = 153), and germ cell tumors (n = 108). The most common non-CNS tumors diagnoses are as follows: rhabdomyosarcoma (n = 191), Ewing sarcoma (n = 105), Hodgkin lymphoma (n = 66), and neuroblastoma (n = 55). The median follow-up is 1.5u2009years with a range of 0.14 to 4.6u2009years. Conclusion A large prospective population of children irradiated with proton therapy has reached a critical milestone to facilitate long-awaited clinical outcomes research in the modern era. This is an important resource for investigators both in the consortium and for those who wish to access the data for academic research pursuits.