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      Dose-Escalated Preoperative Proton Therapy for Retroperitoneal Sarcomas: Initial Outcomes of a New Treatment Paradigm

      brief-report
      , MD a , , MD a , , MD b , , PhD, MPH c , , MD, MBA a , , MD d , , MD, MBA a , *
      Advances in Radiation Oncology
      Elsevier

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          Abstract

          Purpose

          Retroperitoneal sarcomas (RPS) have varied treatment practices with regard to the use of radiation therapy (RT). Preoperative RT ∼50 Gy is commonly used, but the Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma (STRASS-1) randomized trial demonstrated no improvement in abdominal recurrence-free survival with preoperative RT. Dose escalation has been proposed to improve the efficacy of preoperative RT. We analyzed RPS treated with preoperative intensity modulated proton therapy (IMPT) to an escalated dose of 63 Gy at a single institution.

          Methods and Materials

          Patients who received preoperative RT with IMPT with RPS between January 2015 and October 2021 were reviewed. IMPT 63 Gy in 28 fractions to the clinical target volume high-risk and 50.4 Gy in 28 fractions to clinical target volume low-risk was used. Patient baseline characteristics, RT dose parameters, toxicities, margin status, and recurrence patterns were recorded. Local control was computed by Fine-Gray analysis and overall survival by Kaplan-Meier analysis.

          Results

          Sixteen patients met the study criteria (n = 16): 12 primary and 4 isolated local recurrences. Median age was 62 years (IQR, 43.5-66 years) and 62.5% were male; 10 were liposarcoma. The median maximum tumor diameter was 19.9 cm (IQR, 12-24 cm). With a median follow-up of 18 months (IQR, 11.5-37 months), the estimated 3-year freedom from local failure rate was 68.2% (95% CI, 41.7%-94.7%); 3-year overall survival (OS) rate was 68.8% (95% CI, 41.9%-95.8%). No Radiation Therapy Oncology Group grade ≥3 acute or late toxicities were noted.

          Conclusions

          In our RPS cohort, preoperative dose-escalated RT to 63 Gy demonstrated comparable local control without G3 acute toxicities. Given the high local recurrence rates of RPS, this approach warrants further study to validate these results and identify patients most likely to benefit from therapy.

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          Most cited references17

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          Cancer statistics, 2022

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC)

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              Retroperitoneal soft-tissue sarcoma: analysis of 500 patients treated and followed at a single institution.

              To analyze treatment and survival of a large cohort of patients with retroperitoneal soft-tissue sarcomas (STS) treated and prospectively followed at a single institution. Retroperitoneal STS are relatively uncommon and constitute a difficult management problem. Although surgical resection is often difficult or impossible, current chemotherapy is not effective and radiation is limited by toxicity to adjacent structures. Thus, complete surgical resection remains the most effective modality for selected primary and recurrent disease. Five hundred patients with retroperitoneal STS were admitted and treated between July 1, 1982, and September 30, 1997, and prospectively followed. Patient, tumor, and treatment variables were analyzed for disease-specific and disease-free survival. Survival was determined with the Kaplan-Meier method. Statistical significance was evaluated using the logrank test for univariate influence and Cox model stepwise regression for multivariate influence. Two hundred seventy-eight patients (56%) had primary disease and 222 (44%) recurrent disease. Median follow-up was 28 months (range 1 to 172 months), 40 months for survivors. Median survival was 72 months for patients with primary disease, 28 months for those with local recurrence, and 10 months for those with metastasis. For patients with primary or locally recurrent tumors, unresectable disease, incomplete resection, and high-grade tumors significantly reduced survival time. In this study of patients with retroperitoneal STS, stage at presentation, high histologic grade, unresectable primary tumor, and positive gross margin are strongly associated with the tumor mortality rate. Patients approached with curative intent should undergo aggressive attempts at complete surgical resection. Incomplete resection should be undertaken only for symptom relief.
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                Author and article information

                Contributors
                Journal
                Adv Radiat Oncol
                Adv Radiat Oncol
                Advances in Radiation Oncology
                Elsevier
                2452-1094
                30 December 2023
                April 2024
                30 December 2023
                : 9
                : 4
                : 101431
                Affiliations
                [a ]Department of Radiation Oncology
                [b ]Department of Surgical Oncology
                [c ]Department of Biostatistics
                [d ]Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida
                Author notes
                [* ]Corresponding author: Noah S. Kalman, MD, MBA NoahK@ 123456baptisthealth.net
                Article
                S2452-1094(23)00259-2 101431
                10.1016/j.adro.2023.101431
                10884413
                647f5dd7-0f40-4b64-8323-024f9d0a497f
                © 2024 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 28 April 2023
                : 14 December 2023
                Categories
                Research Letter

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