Search

Purpose/Objective(s) Metastasis-directed radiotherapy (RT) may improve disease free and overall survival (OS) in select patients with lung metastases (LM). Long-term toxicity and cancer outcome data in patients with LM treated with ablative RT is limited, particularly in patients treated concurrently with novel systemic therapies. This is a retrospective, multi-hospital analysis of ablative RT for LM. Materials/Methods From 2015-2020, 343 LM-directed ablative RT treatment courses were delivered in 301 patients. Second primary lung cancers and non-parenchymal lesions were excluded. Medical records were reviewed retrospectively, and local progression (LP) was determined by evaluation of serial CT and/or PET scans. Univariate associations of clinical and radiographic parameters with clinical outcomes were evaluated using Cox proportional hazard models. Acute and late adverse events (AEs) were defined using CTCAE v.4.0. Results Median age was 64 years with 51% of patients being female. Median lesion size was 1.6 cm (range 0.3-9.4 cm). Seventy-four (22%) courses involved treatment of > 1 LM. Most common primary tumor histologies included melanoma (18%), colorectal adenocarcinoma (15%), urothelial/renal cell carcinoma (11%), and sarcoma (9%). Median physical dose was 5000 cGy. Median number of fractions delivered was 5, and 27 (8%) courses were > 5 fractions. Concurrent systemic therapies included immuno-, targeted, hormone, and cytotoxic therapy in 16%, 8%, 2%, and 1% of courses, respectively. Treatment to prior lung LM included surgery, RT, and ablation in 25%, 22%, and 2% of courses, respectively. With a median follow-up of 2.8 years, median and 5-year estimated OS were 3.0 years and 43% (95% confidence interval [CI] 34-52%), respectively. Factors associated with shorter OS included larger lesion size (P 2 LM (P = 0.016; HR 1.6), and > 5 fraction treatment (P = 0.024; HR 2.0). Fifteen patients experienced LP with a 5-year estimated cumulative incidence of 5.7% (95% CI 3.4-9.3%). Factors associated with increased risk of LP included larger lesion size (P = 0.004; HR 1.4 per cm), > 5 fraction treatment (P = 0.040; HR 3.8), and colorectal histology (P = 0.011; HR 3.9). Acute and late grade 2-3 AEs were 13% and 5%, respectively. There were no grade 4+ AEs. Increased toxicity was associated with larger size (P = 0.007; odds ratio 1.3 per cm) but not concurrent systemic therapy (P = 0.546) or prior treatment to other LM (P = 0.694). Conclusion These data confirm the efficacy and safety of ablative RT for LM in well-selected patients. 5-year OS and LP were 43% and 6%, respectively. AEs were infrequent, even in the setting of 24% of courses delivered concurrently with systemic therapy and 40% of courses delivered subsequent to other local therapies for LM. Given the excellent OS, these data are suggestive of improved local control as a factor for improved OS.

8569 Background: Immune checkpoint inhibitor (atezolizumab or durvalumab) combined with platinum-etoposide is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The phase III clinical trials that led to the approval of chemoimmunotherapy in ES-SCLC, excluded patients with an Eastern Cooperative Group (ECOG) Performance Status (PS) of Two or Greater. Therefore, data on efficacy of this combination in this subgroup of ES-SCLC patients whose performance status two or greater is limited. Methods: A retrospective analysis was performed of patients diagnosed with ES-SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. Cases were identified from clinical databases at Mayo Clinic. Data on demographics, ECOG-PS, date of diagnosis, date of progression, whole brain radiation, CNS involvement, liver involvement, stereotactic body radiation, chest consolidation, platinum sensitivity, lines of therapy and last follow up date were extracted. Overall Survival (OS) and progression free survival (PFS) for ECOG-PS 2-3 were compared to patients with an ECOG-PS 0-1. Results: A total of 84 patients were identified with a median age of 68.2 (48-88) years old. Of these, 54 patients were identified with an ECOG-PS 0-1 and 30 patients with an ECOG-PS 2-3. The median PFS for the ECOG PS 0-1 cohort was 5.2 months (95% CI 4.6-6.1) while the median PFS for the ECOG-PS 2-3 cohort was 6.0 months (95% CI 4.2-7.7; logrank p = 0.93). The median OS for the ECOG-PS 0-1 cohort was 10.8 months (95% CI 8.5-12.9) while the median OS for the ECOG-PS 2-3 cohort was 10.3 months (95% CI 6.0-14.1; logrank p = 0.39). Hazard ratios of ECOG-PS 0-1 versus 2-3 showed no tendency of increased PFS or OS for either group within cox proportional hazards models. Forty-three percent of ECOG-PS 0-1 achieved a partial response (PR) and 57% of patients who had ECOG-PS 2-3 also achieved a PR (Fisher’s exact p = 0.23). A complete response was found in 4% of ECOG-PS 0-1 compared to 3% in the ECOG-PS 2-3 cohort. For patients who responded to initial therapy, 46% of ECOG-PS 2-3 patients had a platinum sensitive relapse while only 33% of ECOG-PS 0-1 were still platinum sensitive at the time of relapse. Five ECOG-PS 2-3 patients were able to receive a second-line therapy. Conclusions: To our knowledge, this is the first study to evaluate chemoimmunotherapy in the subgroup of ES-SCLC patients with an ECOG-PS 2 or greater. This retrospective study demonstrated no significant difference in PFS, OS, and ability to achieve a least a PR in ECOG-PS 2-3 cohort when compared to ECOG-PS 0-1. Therefore, chemoimmunotherapy should not be reserved for only an ECOG-PS of 0-1 but should be considered for all treatment eligible patients.

494 Background: Our aim was to compare survival between patients receiving neoadjuvant chemoradiation and orthotopic liver transplantation (OLT group) versus definitive chemoradiation (CRT group) for extrahepatic or hilar cholangiocarcinoma. Methods: 49 patients (20 in OLT group vs. 29 in CRT group) with unresectable hilar/extrahepatic cholangiocarcinoma were treated at Mayo Clinic Arizona between Feb. 1998–Sep. 2019. Treatment included external beam radiation therapy (median 4500cGy) and boost (median 900cGy) with either continuous 5-flurouracil (dose range 180–225 mg/m2) or capecitabine (dose range 825–1000 mg/m2 BID) prior to or without OLT. Radiation boosts were delivered with EBRT or bile duct brachytherapy. Patients were between 27.9–84.3 years (median 64.3) at diagnosis. 18 patients had previous diagnosis of PSC. Results: Between Feb. 1998–Sep. 2019, 31(63%) of 49 patients died by the end of follow-up. Of patients treated with neoadjuvant therapy and OLT, 7(35%) of 20 patients died. 24(86%) of 28 patients treated with definitive therapy died. The OLT cohort were younger (mean age 56.5 vs. 69.0 years), more likely to have PSC and UC (65% vs. 17%), and had a lower CA 19-9 (median 43 vs. 535)(P < 0.003). From the end date of radiation, median overall survival was 76.8 months vs. 15.6 months for the OLT and CRT groups, respectively. Survival rates at 3 and 5 years were 78% and 69% in the OLT group compared to 19% and 6% in the CRT group (HR 7.73; 3.04-19.65:(P < 0.0001)). Progression-free survival (89% vs. 30% at 3 years), and distant metastasis-free survival (88% vs. 66% at 3 years) favored OLT versus CRT alone (HR 5.74;1.12-29.34:(P < 0.02)). Univariate analysis demonstrated that the method of treatment (OLT vs. CRT) was the only variable associated with better clinical outcomes. Conclusions: In patients with unresectable extrahepatic/hilar cholangiocarcinoma, survival was higher in those who underwent chemoradiation and OLT. Patients who received definitive chemoradiation in the absence of OLT were expected to have worse overall, progression-free, and metastasis-free survival.

159 Background: Intensity-modulated proton therapy (IMPT) with small spot size has the potential to reduce dose to normal tissues but also introduces new confounding factors such as setup uncertainty, range uncertainty, and interplay effects due to breathing motion. We investigated plan quality and robustness of IMPT with small spot size for distal esophageal adenocarcinoma (DEA). Methods: 19 patients with DEA treated by IMPT were retrospectively evaluated. Spot sizes ranged from 2 to 6mm, with spot spacing of 5mm. All plans were generated using a commercial treatment planning system. In-house-developed dose-evaluation software modeled time-dependent spot delivery to incorporate interplay effects. Dose-volume-histogram (DVH) indices were used to evaluate plan quality and robustness was evaluated using the DVH band method. Results: For plan quality, median values of clinical target volume D95% and D5%-D95% (normalized to the prescribed doses), total lung mean dose, heart mean dose, and cord Dmax were 1.014, 0.035, 3.82Gy[RBE], 7.73Gy[RBE], 39.16Gy[RBE], respectively. For plan robustness, median band widths of the aforementioned DVH indices were 0.018, 0.048, 0.60Gy[RBE], 4.17Gy[RBE], and 2.36Gy[RBE], respectively. For interplay effects, median values of the aforementioned DVH indices were 0.99, 0.061, 4.07Gy[RBE], 7.87Gy[RBE], and 39.66Gy[RBE], respectively. Seven patients underwent esophagectomy after neoadjuvant chemoradiation, and five, three, and one of them achieved downstaging, near complete response, and pathologic complete response, respectively; R0 resection was achieved in all cases. For all patients, acute side effects were mostly limited to grades 1-2 only. The only grade 3 adverse events were related to feeding tube placement (8 patients); there were no RT-induced pneumonitis or other lung-related toxicities. Conclusions: IMPT plans with small spot size for DEA have good target dose coverage, homogeneity and normal tissue protection. Treatment plans are also robust to uncertainties and interplay effects. Early clinical results demonstrate low acute toxicity and encouraging clinical and pathologic response.