A Prospective Pilot Study of Pencil Beam Scanning Proton Radiation Therapy as a Component of Trimodality Therapy for Esophageal Cancer.

Purpose: To evaluate the safety and efficacy of pencil beam scanning (PBS) proton radiation therapy (RT) in trimodality therapy for esophageal cancer. Methods and Materials: This prospective pilot study was planned to accrue 30 patients with locally advanced esophageal or gastroesophageal junction carcinoma medically suitable for chemoradiation therapy (CRT) followed by esophagectomy. PBS proton RT consisted of 25 fractions, 50 Gy to tumor + 1 cm and 45 Gy to a 3.5 cm mucosal expansion and regional lymph nodes. Chemotherapy included weekly carboplatin (area under the curve, 2 mg/mL/min) and paclitaxel (50 mg/m2). At 4 to 8 weeks after CRT, patients underwent restaging and potential esophagectomy. The primary endpoint was acute grade 3+ adverse events (AEs) attributed to CRT. Overall survival and progression-free survival were assessed using the Kaplan-Meier methodology; local-regional recurrence and distant metastases rates were assessed using the cumulative incidence methodology. The Functional Assessment of Cancer Therapy-Esophagus assessed quality of life. Results: Thirty eligible patients were enrolled from June 2015 to April 2017. Median age was 68 years. Histology was adenocarcinoma in 87%, and location was distal esophagus/gastroesophageal junction in 90%. Stage was T3 to T4 in 87% and N1 to N3 in 80%. All patients completed the planned RT dose. Acute grade 3+ AEs occurred in 30%, most commonly leukopenia and neutropenia. Acute grade 3+ nonhematologic AEs occurred in 3%. Esophagectomy was performed in 90% of patients (R0 in 93%). Pathologic complete response rate was 40%. Major postoperative complications (Clavien-Dindo score, ≥3) occurred in 34%. Postoperative mortality at 30 days was 3.7%. Median follow-up was 5.2 years. Five-year outcome estimates were overall survival at 46%, progression-free survival at 39%, local-regional recurrence at 17%, and distant metastases at 40%. Functional Assessment of Cancer Therapy-Esophagus scores (medians) at baseline, at the end of CRT, before esophagectomy, at 12 months, and at 24 months were 145, 136 (p = .0002 vs baseline), 144, 146 and 157, respectively. Conclusions: PBS proton RT is feasible and safe as a component of trimodality therapy for esophageal cancer.

Vaginal Sparing Radiotherapy Using IMPT and Daily Dilator Placement for Women with Anal Cancer.

Sexual dysfunction is a common toxicity and detrimental for the quality of life of women treated with chemoradiotherapy for anal cancer. Sexual dysfunction occurs because the vagina is closely approximated to the anal canal and typically receives substantial doses of radiation. Strategies for mitigation have largely been focused on posttreatment therapy and symptom management. The use of daily vaginal dilator placement during radiotherapy to mitigate dose to the vagina has been previously explored with modest gains, while proton therapy is under active investigation for the treatment of anal cancer. Use of proton therapy for anal cancer reduces dose to some organs at risk but may inadvertently increase vaginal toxicity if the proton beam terminates in the vaginal tissue. Herein, we present the case histories of 2 women treated for squamous cell carcinoma of the anal canal with the novel combination of intensity-modulated proton therapy and daily vaginal dilator placement to maximally reduce dose to the vagina and protect it from areas of increased energy deposition at the end of the proton range.

Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer.

PURPOSE: For treatment of rectal cancer, pencil beam scanning proton therapy (PBS-PT) may reduce radiation exposure to normal tissues compared with 3-dimensional conformal photon radiation therapy (3DCRT) or volumetric modulated arc photon radiation therapy (VMAT). The purpose of this study was to report the clinical implementation and dosimetric analysis of preoperative short-course PBS-PT for rectal cancer. METHODS AND MATERIALS: Eleven patients with stage IIA-IVB rectal cancer received preoperative short-course (25 Gy in 5 fx) PBS-PT between 2018 and 2019 preceding curative-intent total mesorectal excision. PBS-PT plans were generated using single-field optimization with 2 posterior-oblique fields. Verification computed tomography scans were performed on the first 3 days of treatment. Each patient had a backup 3DCRT and VMAT plan. RESULTS: Clinical target volume coverage was similar between PBS-PT, 3DCRT, and VMAT. PBS-PT had statistically significant reductions in dose to the small bowel, large bowel, bladder, and femoral heads across multiple dosimetric parameters. All patients completed PBS-PT as planned without need for replanning. All computed tomography verification scans demonstrated good target coverage with clinical target volume V100 > 95%. CONCLUSIONS: Preoperative short-course PBS-PT has been successfully implemented and offers a significant reduction of dose to normal tissues. Prospective studies are warranted to evaluate if dosimetric advantages translate into clinical benefit.

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes.

PURPOSE: Pencil-beam scanning intensity modulated proton therapy (IMPT) may allow for an improvement in the therapeutic ratio compared with conventional techniques of radiation therapy delivery for pancreatic cancer. The purpose of this study was to describe the clinical implementation of IMPT for intact and clinically localized pancreatic cancer, perform a matched dosimetric comparison with volumetric modulated arc therapy (VMAT), and report acute adverse event (AE) rates and patient-reported outcomes (PROs) of health-related quality of life. METHODS AND MATERIALS: Between July 2016 and March 2017, 13 patients with localized pancreatic cancer underwent concurrent capecitabine or 5-fluorouracil-based chemoradiation therapy (CRT) utilizing IMPT to a dose of 50 Gy (radiobiological effectiveness: 1.1). A VMAT plan was generated for each patient to use for dosimetric comparison. Patients were assessed prospectively for AEs and completed PRO questionnaires utilizing the Functional Assessment of Cancer Therapy-Hepatobiliary at baseline and upon completion of CRT. RESULTS: There was no difference in mean target coverage between IMPT and VMAT (P > .05). IMPT offered significant reductions in dose to organs at risk, including the small bowel, duodenum, stomach, large bowel, liver, and kidneys (P < .05). All patients completed treatment without radiation therapy breaks. The median weight loss during treatment was 1.6 kg (range, 0.1-5.7 kg). No patients experienced grade ≥3 treatment-related AEs. The median Functional Assessment of Cancer Therapy-Hepatobiliary scores prior to versus at the end of CRT were 142 (range, 113-163) versus 136 (range, 107-173; P = .18). CONCLUSIONS: Pencil-beam scanning IMPT was feasible and offered significant reductions in radiation exposure to multiple gastrointestinal organs at risk. IMPT was associated with no grade ≥3 gastrointestinal AEs and no change in baseline PROs, but the conclusions are limited due to the patient sample size. Further clinical studies are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.

Proton Therapy for Stage IIA-B Seminoma: A New Standard of Care for Treating Retroperitoneal Nodes.

Currently there has been no published report describing the use of proton beam therapy for stage II testicular seminoma. A 31-year-old man presenting with a right testicular mass and a 2.7-cm aortocaval lymph node received a diagnosis of stage IIB testicular seminoma. He was treated with scanning proton beam therapy, as a means of improving the therapeutic ratio of radiation therapy over conventionally used x-ray radiation therapy. The patient achieved a complete response and remained free of relapse at 15 months post proton beam therapy. The advantageous dose deposition characteristics of proton beam, allowing much lower radiation doses to normal tissues, should be exploited when radiation therapy is applied for stage II testicular seminoma or for an isolated retroperitoneal lymph node relapse of stage I disease initially managed with surveillance.