Association of radiation dose intensity with overall survival in patients with distant metastases.

BACKGROUND: Patients with metastatic cancer referred to radiation oncology have diverse prognoses and there is significant interest in personalizing treatment. We hypothesized that patients selected for higher biologically equivalent doses have improved overall survival. METHODS: The study population consists of 355 consecutive adult patients with distant metastases treated by a single radiation oncologist from 2014 to 2018. The validated NEAT model was used to prospectively stratify patients into four distinct cohorts. Radiation dose intensity was standardized using the equivalent dose in 2 Gy fractions (EQD2) model with an α/ß of 10. Radiation dose intensity on survival was assessed via Cox regression models and propensity score match pairing with Kaplan-Meier analysis. RESULTS: The median survival was 9.3 months and the median follow-up for surviving patients was 18.3 months. The NEAT model cohorts indicated median survivals of 29.5, 11.8, 4.9, and 1.8 months. Patients receiving an EQD2 of ≥40 Gy had a median survival of 16.0 months versus 3.8 months for patients receiving an EQD2 of <40 Gy (p < 0.001). On multivariable analysis, performance status, primary tumor site, radiation dose intensity, albumin, liver metastases, and number of active tumors were all independent predictors of survival (p < 0.05 for all). Propensity score matching was performed for performance status, albumin, number of active tumors, primary tumor site, and liver metastasis, finding higher EQD2 to remain significantly associated with improved survival within the matched cohort (p = 0.004). CONCLUSION: Higher radiation dose intensity was used in patients with better prognosis and was associated with improved survival for patients with metastatic disease.

Tumor Directed, Scalp Sparing Intensity Modulated Whole Brain Radiotherapy for Brain Metastases.

Despite significant technical advances in radiation delivery, conventional whole brain radiation therapy (WBRT) has not materially changed in the past 50 years. We hypothesized that IMRT can selectively spare uninvolved brain and scalp with the goal of reducing acute and late toxicity. MRI/CT simulation image registration was performed. We performed IMRT planning to simultaneously treat the brain tumor(s) on MRI + 5 mm margin to 37.5 Gy in 15 fractions while limiting the uninvolved brain + 2 mm margin to 30 Gy in 15 fractions and the mean scalp dose to #18 Gy. Three field IMRT plans were compared to conventional WBRT plans. Symptomatic patients were started on conventional WBRT for 2 to 3 fractions while IMRT planning was performed. Seventeen consecutive patients with brain metastases with RPA class I and II disease with no leptomeningeal spread were treated with IMRT WBRT. Compared to conventional WBRT, IMRT reduced the mean scalp dose (26.2 Gy vs. 16.4 Gy, p < 0.001) and the mean PTV30 dose (38.4 Gy vs. 32.0 Gy, p < 0.001) while achieving similar mean PTV37.5 doses (38.3 Gy vs. 38.0 Gy, p = 0.26). Using Olsen hair loss score criteria, 4 of 15 assessable patients preserved at least 50% of hair coverage at 1 to 3 months after treatment while 6 patients preserved between 25 and 50% hair coverage. At a median follow-up of 6.8 months (range: 5 to 15 months), the median overall survival was 5.4 months. Four patients relapsed within the brain, one within the PTV37.5 and three outside the PTV37.5. Tumor directed, scalp sparing IMRT is feasible, achieves rational dose distributions and preserves partial hair coverage in the majority of patients. Further studies are warranted to determine whether the increased utilization of resources needed for IMRT are appropriate in this setting.