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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.
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PURPOSE/OBJECTIVES: NRG/RTOG 0436 evaluated cetuximab added to chemoradiation (CRT) for non-operative esophageal cancer management. PRO objectives assessed improvement in the FACT-Esophageal cancer subscale (ECS), version 4, with cetuximab, and if improved ECS correlated with clinical complete response (cCR). MATERIALS/METHODS: Patients were randomized to cisplatin/paclitaxel/radiation ± cetuximab. Overall survival (OS) was the primary endpoint, with a 420 patient target, which also provided 82% power to detect ≥ 15 increase in the proportion of cetuximab patients with ECS improvement from baseline to 6-8 weeks post-CRT; α = 0.05, using a χ2 test. Improvement in ECS and its Swallowing and Eating Indices (SI, EI) was defined as 5, 4 and 2 point increases, respectively, from baseline to 6-8 weeks post-CRT. Univariate logistic regression assessed if cCR was associated with improved ECS. RESULTS: This study was stopped early for not meeting a pre-specified OS endpoint and did not show survival benefit. Of 420 planned patients, 344 enrolled and 281 consented to PROs. ECS was completed by 261 (93%) at baseline, 173 (66%) 6-8 weeks post-CRT, and 117 (64%) at 1 year. At 6-8 weeks, patients receiving CRT + Cetuximab didn't have improved ECS; they experienced a lower proportion of improvement compared to standard CRT (37% vs. 53%; P = 0.04). The proportion of CRT patients with improvement in SI was 9% higher than with cetuximab, but not statistically significant (39% vs. 30%, P = 0.22). There was no association between treatment and EI. When examining ECS scores at 1 year by cCR vs. residual disease, a higher proportion of cCR patients improved, but not statistically significant (48% vs. 45%, P = 0.74). CONCLUSIONS: The addition of cetuximab to CRT for the nonoperative management of esophageal cancer did not improve PROs.
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Purpose: Myxofibrosarcoma (MFS) is a subtype of soft tissue sarcoma with a highly infiltrative growth pattern that leads to a higher risk of inadvertent positive surgical margins and local relapse. Poorly defined tumor margins also pose a challenge for radiation therapy (RT) planning, in terms of treatment volumes and administration of pre- versus postoperative RT. This study aims to evaluate local control and patterns of recurrence in patients with MFS treated with neoadjuvant RT followed by definitive surgical excision. Methods and Materials: Multiple institutional databases were retrospectively searched for patients diagnosed with MFS between 2013 and 2021 who were exclusively treated with preoperative RT followed by definitive surgery at our institution. The endpoints of the study were defined as local tumor recurrence, distant metastasis, and death after the date of definitive surgery. Results: Forty-nine patients met the inclusion criteria and were included in the final study. The median age at diagnosis was 67 years, and 71% of patients were male. The tumor was superficially located in 63% of patients, and the mean tumor size at presentation was 7.8 cm. All patients received neoadjuvant RT and completed their planned course of treatment. Neoadjuvant chemotherapy was administered in 22% of patients. Inadvertent excision (IE) before definitive treatment was performed in 25 patients (51%), 84% of which had superficially located tumors. All margins were assessed using frozen section analysis at the time of definitive surgery, and 100% of patients had negative surgical margins, with 25% having no residual tumor. With a median follow-up of 4.7 years, the 5-year local control rate was 87%, and 5-year overall survival was 98%. Tumor depth was associated with distant metastasis (P < .01). Conclusions: Despite the infiltrative nature of MFS, preoperative RT followed by definitive surgical excision, especially in the setting of a reliable frozen section margin analysis, was associated with excellent local control.
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Purpose: Spatially fractionated radiation therapy (SFRT) is a recognized technique for enhancing tumor response in radioresistant and bulky tumors. We analyzed clinical and treatment outcomes in patients with bone and soft tissue sarcomas treated with modern SFRT techniques. Methods and Materials: Patients with metastatic or unresectable sarcoma treated with brass collimator, volumetric modulated arc therapy lattice, or proton SFRT from December 2019 to June 2022 were retrospectively reviewed. Consolidative external beam radiation therapy (EBRT) was delivered at the physician's discretion. Patient and treatment characteristics, treatment response (symptom improvement, local control, and imaging response), and toxicity data were collected. Results: The cohort consisted of 53 patients treated with 61 SFRT treatments. Median age at treatment was 60.0 years. The primary location was soft tissue in 46 courses (75%) and bone in 15 (25%). Fifty-three courses (87%) were treated for symptom relief. The most used SFRT technique was volumetric modulated arc therapy lattice (n = 52, 85%) to a dose of 20 Gy (n = 48, 79%; range, 16-20 Gy). EBRT was delivered post-SFRT in 55 (90%) treatment courses with a median time interval from SFRT to EBRT of 5 days (range, 0-14 days). Median physical EBRT dose and fractionation was 40 Gy (range, 9-73.5 Gy) and 10 fractions (range, 3-33 fractions). Median follow up was 7.4 months (range, 0.2-30 months). One-year overall survival and local control rates were 53% and 82%. Symptom relief was documented with 32 treatment courses (60%). Stable or partial response was observed with 47 treatment courses (90%). Four grade 3 to 4 acute and subacute toxicities were attributable to SFRT (8%). Conclusions: The current series is the largest to date documenting outcomes for SFRT in sarcomas. Our results suggest combined SFRT with EBRT is associated with a favorable toxicity profile and high rates of symptomatic and radiographic responses for metastatic or unresectable sarcomas.
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Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.