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Purpose: The benefit of local consolidative therapy (LCT) for oligometastasis across histologies remains uncertain. EXTernal beam radiation to Eliminate Nominal metastatic Disease (EXTEND; NCT03599765) is a randomized phase 2 basket trial evaluating the effectiveness of LCT for oligometastatic solid tumors. We report here the prospective results of the single-arm "lead-in" phase intended to identify histologies most likely to accrue to histology-specific endpoints in the randomized phase., Methods and Materials: Eligible histologies included colorectal, sarcoma, lung, head and neck, ovarian, renal, melanoma, pancreatic, prostate, cervix/uterine, breast, and hepatobiliary. Patients received LCT to all sites of active metastatic disease and primary/regional disease (as applicable) plus standard-of-care systemic therapy or observation. The primary endpoint in EXTEND was progression-free survival (PFS), and the primary endpoint of the lead-phase was histology-specific accrual feasibility. Adverse events were graded by Common Terminology Criteria for Adverse Events version 4.0., Results: From August 2018 through January 2019, 50 patients were enrolled and 49 received definitive LCT. Prostate, breast, and kidney were the highest enrolling histologies and identified for independent accrual in the randomization phase. Most patients (73%) had 1 or 2 metastases, most often in lung or bone (79%), and received ablative radiation (62%). Median follow-up for censored patients was 38 months (range, 16-42 months). Median PFS was 13 months (95% confidence interval, 9-24), 3-year overall survival rate was 73% (95% confidence interval, 57%-83%), and local control rate was 98% (93 of 95 tumors). Two patients (4%) had Common Terminology Criteria for Adverse Events grade 3 toxic effects related to LCT; no patient had grade 4 or 5 toxic effects., Conclusions: The prospective lead-in phase of the EXTEND basket trial demonstrated feasible accrual, encouraging PFS, and low rates of severe toxic effects at mature follow-up. The randomized phase is ongoing with histology-based baskets that will provide histology-specific evidence for LCT in oligometastatic disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The current distribution of radiation therapy (RT) facilities in the United States is not well established. A comprehensive inventory of U.S. RT facilities was last assessed in 2005, based on data from state regulatory agencies and dosimetric quality assurance bodies. We updated this database to characterize population-level measures of geographic access to RT and analyze changes over the past 15 years., Methods and Materials: We compiled data from regulatory and accrediting organizations to identify U.S. facilities with linear accelerators used to treat humans in 2018 to 2020. Addresses were geocoded and analyzed with Geographic Information Services software. Geographic access was characterized by assessing the Euclidian distance between ZIP code tabulation areas/county centroids and RT facilities. Populations were assigned to each county to estimate the effect of facility changes at the population level. Logistic regressions were performed to identify features associated with increased distance to RT and associated with regions that gained an RT facility between the 2 time points studied., Results: In 2020, a total of 2313 U.S. RT facilities were reported, compared with 1987 in 2005, representing a 16.4% growth in facilities over nearly 15 years. Based on population attribution to the centroids of ZIP Code Tabulation Areas, 77.9% of the U.S. population lives within 12.5 miles of an RT facility, and 1.8% of the U.S. population lives more than 50 miles from an RT facility. We found that increased distance to RT was associated with nonmetro status, less insurance, older median age, and less populated regions. Between 2005 and 2020, the population living within 12.5 miles from an RT facility increased by 2.1 percentage points, whereas the population living furthest from RT facilities decreased 0.6 percentage points. Regions with improved geographic RT access are more likely to be higher income and better insured., Conclusions: The percentage of the U.S. population with limited geographic access to RT is 1.8%. We found that people benefiting from improved access to RT facilities are more economically advantaged, suggesting disparities in geographic access may not improve without intervention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Numerous publications during the COVID-19 pandemic recommended the use of hypofractionated radiation therapy. This project assessed aggregate changes in the quality of the evidence supporting these schedules to establish a comprehensive evidence base for future reference and highlight aspects for future study., Methods and Materials: Based on a systematic review of published recommendations related to dose fractionation during the COVID-19 pandemic, 20 expert panelists assigned to 14 disease groups named and graded the highest quality of evidence schedule(s) used routinely for each condition and also graded all COVID-era recommended schedules. The American Society for Radiation Oncology quality of evidence criteria were used to rank the schedules. Process-related statistics and changes in distributions of quality ratings of the highest-rated versus recommended COVID-19 era schedules were described by disease groups and for specific clinical scenarios., Results: From January to May 2020 there were 54 relevant publications, including 233 recommended COVID-19-adapted dose fractionations. For site-specific curative and site-specific palliative schedules, there was a significant shift from established higher-quality evidence to lower-quality evidence and expert opinions for the recommended schedules (P = .022 and P < .001, respectively). For curative-intent schedules, the distribution of quality scores was essentially reversed (highest levels of evidence "pre-COVID" vs "in-COVID": high quality, 51.4% vs 4.8%; expert opinion, 5.6% vs 49.3%), although there was variation in the magnitude of shifts between disease sites and among specific indications., Conclusions: A large number of publications recommended hypofractionated radiation therapy schedules across numerous major disease sites during the COVID-19 pandemic, which were supported by a lower quality of evidence than the highest-quality routinely used dose fractionation schedules. This work provides an evidence-based assessment of these potentially practice-changing recommendations and informs individualized decision-making and counseling of patients. These data could also be used to support radiation therapy practices in the event of second waves or surges of the pandemic in new regions of the world., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the last few years there have been dramatic changes in the management of patients with melanoma with locally advanced disease. Previously, standard therapy for melanoma patients with nodal disease involved completion lymph node dissection followed by adjuvant radiation therapy for high-risk features, as defined by TROG 02.01. Adjuvant systemic therapy with interferon could be offered, but many eligible patients did not receive this agent in the context of significant toxicity. New, effective, and often well-tolerated systemic therapies, such as immune checkpoint inhibitors and targeted MAPK pathway inhibitors, have shown impressive responses in metastatic disease and are now being applied to the locally advanced setting. Currently, for patients with occult nodal disease found at sentinel lymph node biopsy, completion lymph node dissection is uncommon with adjuvant anti-PD1 therapy often recommended. For patients with clinically apparent nodal disease, neoadjuvant immunotherapy has shown impressive pathologic response rates, which thus far have correlated well with longer term disease outcomes. However, not all patients exhibit a robust pathologic response. In circumstances of either occult nodal disease or clinically evident nodal disease without a robust pathologic response to neoadjuvant immunotherapy, there is a dearth of evidence regarding the optimal use of radiation therapy. Prospective studies investigating the role of adjuvant nodal radiation therapy for melanoma patients in the modern immunotherapy era are much needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To update our experience with long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT) and to characterize factors associated with increased risk of local recurrence., Methods and Materials: We reviewed the records of 209 consecutive patients with desmoid fibromatosis treated with RT, either alone or as combined-modality therapy (CMT) with surgery, at our institution from 1965 to 2015., Results: Median follow-up time was 98 months (range, 1-509 months). The 5- and 10-year local control (LC) was 71% and 69%, respectively. Fifty-nine patients (28%) experienced a local recurrence at a median time of 23 months (interquartile range, 15-38 months). Among all patients, on multivariable analysis, adjusting for anatomic site, size, age, treatment era (>2005 vs ≤2005), treatment approach (RT alone vs CMT), and an interaction between age and treatment, we found only age ≤30 years (hazard ratio [HR], 2.94; P = .005; 95% confidence interval [CI], 1.38-6.27) and large tumor size >10 cm (HR, 2.51; P = .03; 95% CI, 1.09-5.78) to be correlated with poorer LC. Notably, for patients receiving RT alone, the 5-year LC was 43% for patients ≤30 years old versus 75% for >30 years old (P < .001). On multivariable analyses, for patients receiving RT alone, the only factor associated with inferior LC was age ≤30 years (HR, 2.87; P = .001; 95% CI, 1.51-5.47). The same was true for patients treated with CMT; age ≤30 years was the only factor associated with inferior LC (HR, 5.36; P = .01; 95% CI, 1.40-20.58)., Conclusions: Among all patients with desmoid fibromatosis, RT is an effective local therapy for tumor control. However, young patients ≤ 30 years have notably high rates of local recurrence regardless of treatment strategy, which requires further study. Treatment decisions should be risk-adapted by large referral centers with multidisciplinary expertise in desmoid management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Trimodality therapy (chemoradiation and surgery) is the standard of care for stage II/III rectal cancer but nearly one third of patients do not receive radiation therapy (RT). We examined the relationship between the density of radiation oncologists and the travel distance to receipt of RT., Methods and Materials: A retrospective study based on the National Cancer Data Base identified 26,845 patients aged 18 to 80 years with stage II/III rectal cancer diagnosed from 2007 to 2010. Radiation oncologists were identified through the Physician Compare dataset. Generalized estimating equations clustering by hospital service area was used to examine the association between geographic access and receipt of RT, controlling for patient sociodemographic and clinical characteristics., Results: Of the 26,845 patients, 70% received RT within 180 days of diagnosis or within 90 days of surgery. Compared with a travel distance of <12.5 miles, patients diagnosed at a reporting facility who traveled ≥50 miles had a decreased likelihood of receipt of RT (50-249 miles, adjusted odds ratio 0.75, P<.001; ≥250 miles, adjusted odds ratio 0.46; P=.002), all else being equal. The density level of radiation oncologists was not significantly associated with the receipt of RT. Patients who were female, nonwhite, and aged ≥50 years and had comorbidities were less likely to receive RT (P<.05). Patients who were uninsured but self-paid for their medical services, initially diagnosed elsewhere but treated at a reporting facility, and resided in Midwest had an increased the likelihood of receipt of RT (P<.05)., Conclusions: An increased travel burden was associated with a decreased likelihood of receiving RT for patients with stage II/III rectal cancer, all else being equal; however, radiation oncologist density was not. Further research of geographic access and establishing transportation assistance programs or lodging services for patients with an unmet need might help decrease geographic barriers and improve the quality of rectal cancer care., Competing Interests: or conflict of interest: All authors did not have potential conflicts of interest to disclose., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with aggressive surgery and radiation therapy (RT) for retroperitoneal sarcomas (RPS)., Methods and Materials: We reviewed the medical records of 121 consecutive patients treated for RPS with surgery and RT between 1965 and 2012. The most common histology was liposarcoma (n = 42; 35%). The median follow-up was 100 months (range: 20-467 months). Eighty-six patients (71%) were treated for initial presentation of RPS, and 35 patients (29%) presented with and were treated for RPS recurrence. RT was preoperative in 88 patients (73%; median dose: 50.4 Gy) and postoperative in 33 patients (27%; median dose: 55 Gy)., Results: Five-year local control and overall survival rates were 56% and 57%, respectively. Two factors were associated with higher risk of any intra-abdominal recurrence at 5 years: positive or uncertain margins (58% vs 30% for negative margins, P < .001; hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.6-4.8) and disease recurrence after previous resection (76% vs 31% for de novo RPS, P < .001; HR: 4.4; 95% CI: 2.5-7.5). The 10-year complication rate was 5%, and RT-related complications were associated with postoperative RT (P < .001) and RT dose of ≥ 60 Gy (P < .001)., Conclusions: Intra-abdominal RPS recurrence continues to be a significant challenge despite the use of aggressive surgery and radiation therapy. Given the complications associated with postoperative radiation therapy, we recommend that preoperative radiation therapy is the preferred strategy when combined modality therapy is recommended., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to investigate local control, survival outcomes, and complication rates of patients treated with limb-sparing surgery and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet., Methods and Materials: We reviewed the medical records of 85 consecutive patients treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and 2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven patients (79%) received postoperative RT after resection of their tumor (median dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64 Gy)., Results: Median follow-up was 140 months (range, 24-442 months). Five-year local control, overall survival, and disease-specific survival rates were 86%, 89%, and 89%, respectively. Positive or uncertain surgical margin status was the only factor adversely associated with local recurrence (19% vs 6% for negative margins, P=.046) but this lost significance on multivariate analysis when adjusting for RT dose ≥64 Gy. Of the 12 patients who had local relapses, 6 (50%) were salvaged, and only 2 of those required salvage amputation. Five patients had grade ≥3 late RT sequelae, with 2 patients (2%) having moderate limitations of limb function and 3 patients (4%) having severe limitations requiring procedures for skin ulceration., Conclusions: Limb-sparing surgery combined with RT provides excellent local control outcomes for sarcomas arising in the hands or feet. In patients who have local recurrence, salvage without amputation is possible. The excellent cancer control outcomes observed, considering the minimal impact on limb function, support use of combined modality, limb-sparing local therapy for STS arising in the hands or feet., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS., Methods and Materials: An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended that these clinical practice guidelines be updated as pertinent data become available., Results: Treatment guidelines for preoperative RT for RPS are presented., Conclusions: An international panel of radiation oncologists who specialize in sarcoma reached consensus guidelines for preoperative RT for RPS. Many of the recommendations are based on expert opinion because of the absence of higher level evidence and, thus, are best regarded as preliminary. We emphasize that the role of preoperative RT for RPS has not been proven, and we await data from the European Organization for Research and Treatment of Cancer (EORTC) study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS. Further data are also anticipated pertaining to normal tissue dose constraints, particularly for bowel tolerance. Nonetheless, as we await these data, the guidelines herein can be used to establish treatment uniformity to aid future assessments of efficacy and toxicity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes of conservative surgery and radiation therapy (RT) treatment in patients with dermatofibrosarcoma protuberans., Methods and Materials: We retrospectively reviewed the medical records of 53 consecutive dermatofibrosarcoma protuberans patients treated with surgery and preoperative or postoperative radiation therapy between 1972 and 2010. Median tumor size was 4 cm (range, 1-25 cm). Seven patients (13%) were treated with preoperative RT (50-50.4 Gy) and 46 patients (87%) with postoperative RT (60-66 Gy). Of the 46 patients receiving postoperative radiation, 3 (7%) had gross disease, 14 (30%) positive margins, 26 (57%) negative margins, and 3 (7%) uncertain margin status. Radiation dose ranged from 50 to 66 Gy (median dose, 60 Gy)., Results: At a median follow-up time of 6.5 years (range, 0.5 months-23.5 years), 2 patients (4%) had disease recurrence, and 3 patients (6%) had died. Actuarial overall survival was 98% at both 5 and 10 years. Local control was 98% and 93% at 5 and 10 years, respectively. Disease-free survival was 98% and 93% at 5 and 10 years, respectively. The presence of fibrosarcomatous change was not associated with increased risk of local or distant relapse (P=.43). One of the patients with a local recurrence had gross residual disease at the time of RT and despite RT to 65 Gy developed both an in-field recurrence and a nodal and distant recurrence 3 months after RT. The other patient with local recurrence was found to have in-field recurrence 10 years after initial treatment. Thirteen percent of patients had an RT complication at 5 and 10 years, and 9% had a moderate or severe complication at 5 and 10 years., Conclusions: Dermatofibrosarcoma protuberans is a radioresponsive disease with excellent local control after conservative surgery and radiation therapy. Adjuvant RT should be considered for patients with large or recurrent tumors or when attempts at wide surgical margins would result in significant morbidity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF])., Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF., Results: At a median follow-up of 59 months, 111 patients (56%) had sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications., Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.

Purpose: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery., Methods and Materials: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy)., Results: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size (< or =5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age (< or = 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age < or =30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01)., Conclusions: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.

Purpose: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT)., Patients and Methods: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment., Results: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at > or =5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver., Conclusion: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.

Purpose: To evaluate prognostic factors and treatment outcomes in patients with localized synovial sarcoma treated with conservation surgery and radiotherapy (RT)., Methods and Materials: Between 1960 and 2003, 150 patients with nonmetastatic synovial sarcoma were treated with conservation surgery and RT. The majority of patients (81%) were aged >20 years. Sixty-eight percent received postoperative RT, and 32% received preoperative RT. Forty-eight percent received adjuvant chemotherapy., Results: Median follow-up was 13.2 years. Overall survival (OS) rates at 5, 10, and 15 years were 76%, 57%, and 51%, respectively. Corresponding disease-free survival (DFS) rates were 59%, 52%, and 52%, respectively. Tumor size >5 cm predicted worse OS, DFS, disease-specific survival (DSS), and higher rate of distant metastases (DM). Age >20 years predicted worse DFS and DSS but not OS. Local control (LC) was 82% at 10 years. Positive or unknown resection margins predicted inferior LC rates. Forty-four percent developed DM by 10 years. Only 1% developed nodal metastases. Analysis of outcomes by treatment decade showed no significant differences with respect to LC and DM rates., Conclusions: Synovial sarcoma is adequately controlled at the primary site by conservation surgery and RT. Elective nodal irradiation is not indicated. Rates of development of DM and subsequent death from disease remain high, with no significant improvement in outcomes for this disease in the past four decades.