Proton radiotherapy for recurrent or metastatic sarcoma with palliative quad shot

Abstract

Patients with previously treated, recurrent or metastatic sarcomas who have progressed on multiples lines of systemic therapy may have limited options for local control. We evaluated outcomes of palliative proton therapy with the quad shot regimen to unresectable disease for patients with recurrent and/or metastatic sarcoma. From 2014 to 2018, 28 patients with recurrent or metastatic sarcomas were treated to 40 total sites with palliative proton RT with quad shot (14.8 Gy/4 twice daily). Outcomes included toxicity, ability to receive further systemic therapy, and subjective palliative response. Univariate analysis was performed for local progression‐free survival (LPFS) and overall survival (OS). Of the 40 total sites, 25 (62.5%) received ≥3 cycles with median follow up of 12 months (IQR 4–19). The most common histologies were GIST (9; 22.5%) and leiomyosarcoma (7; 17.5%). A total of 27 (67.5%) sites were located in the abdomen or pelvis. Seventeen (42.5%) treatments involved concurrent systemic therapy and 13 (32.5%) patients received further systemic therapy following proton therapy. Overall subjective palliative response was 70%. Median LPFS was 11 months and 6‐month LPFS was 66.1%. On univariate analysis, receipt of four cycles of quad shot (HR 0.06, p = 0.02) and receipt of systemic therapy after completion of radiation therapy (HR 0.17, p = 0.02) were associated with improved LPFS. Three grade 3 acute toxicities were observed. The proton quad shot regimen serves as a feasible alternative for patients with previously treated, recurrent or metastatic sarcomas where overall treatment options may be limited.

Rapid and Durable Symptom Palliation With Quad Shot Radiation Therapy to Nonosseous Metastatic/Recurrent Cancer in Elderly or Frail Patients in a Rural Community Clinic

“…Such rapid subjective symptom response after QS1 can be explained by a significant objective response (42.7% of mean GTV reduction) after QS1 ( Fig 2 ). Like the results of quad shot to advanced pelvic or head and neck cancer, 3 , 4 , 5 , 6 , 9 we observed further reduction of residual symptoms and GTVs with additional quad shots (QS2-QS3) to nonosseous metastatic/recurrent sites in our elderly or frail patients. Of the 8 sites that received QS3, all achieved objective radiographic response, including interval stability (RECIST SD, 2 sites) and shrinkage (RECIST PR, 6 sites) after QS1.…”

“…Although the number of cases is small and there is heterogeneity in the histology, the responses from quad shots for such low alpha-beta ratio cancers in this case series are comparable to the published data. 9 Lee et al reported results from palliative quad shot using proton beam to 40 recurrent or metastatic sarcomas in various sites (lung, trunk, abdomen, and extremities) showing a 70% subjective palliative response and durable local sarcoma control (11 months of median local progression-free survival). 9 Radiobiologic experiments have suggested that increasing the dose per fraction using hypofractionation may treat those low alpha-beta ratio cancers more effectively than delivering smaller conventionally fractionated doses (1.8∼2.0 Gy/fx).…”

“… 9 Lee et al reported results from palliative quad shot using proton beam to 40 recurrent or metastatic sarcomas in various sites (lung, trunk, abdomen, and extremities) showing a 70% subjective palliative response and durable local sarcoma control (11 months of median local progression-free survival). 9 Radiobiologic experiments have suggested that increasing the dose per fraction using hypofractionation may treat those low alpha-beta ratio cancers more effectively than delivering smaller conventionally fractionated doses (1.8∼2.0 Gy/fx). 10 , 11 Thus, radiobiologic advantages from hypofractionated doses (3.5-3.7 Gy/fx) in accelerated schedule (twice daily for 2 consecutive days) of quad shot RT can account for rapid subjective and objective responses in low alpha-beta ratio cancers after QS1 in this report.…”

“…Radiobiologic effectiveness of 3 or more cycles of quad shot is reportedly comparable to that of protracted definitive RT regimens, and hypofractionation may provide particular benefit to radio-resistant low alpha-beta ratio cancers. 7 , 8 , 9 , 10 Herein, we report responses from palliative RT using quad shot in elderly or frail patients with nonosseous metastatic/recurrent cancer in various anatomic sites with varying histology.…”

Diagnosis of pulmonary leiomyosarcoma extending into the main bronchus using repeated transbronchial cryobiopsy

“…Nevertheless, several studies on proton therapy show good overall survival and focal control for unresectable malignant soft tissue sarcomas, including leiomyosarcomas. 4 Further exploration of the effectiveness of proton therapy will be possible when more cases are definitively diagnosed using TBCB.…”