John M. Stahl

Trends in stereotactic body radiation therapy for stage I small cell lung cancer

OBJECTIVES We aimed to report trends in stereotactic body radiation therapy (SBRT) utilization, dose prescriptions, and chemotherapy administration for stage I small cell lung cancer (SCLC) in the United States. MATERIALS AND METHODS The National Cancer Data Base (NCDB) was used to identify patients with cT1-2 N0 SCLC treated with SBRT between 2004 and 2013. Trends in SBRT use and dose prescription were analyzed over time. Multivariable logistic regression was used to determine factors associated with the administration of chemotherapy with SBRT. The Kaplan-Meier method was used to estimate overall survival. RESULTS Of 9265 patients with clinical stage I SCLC who were examined for initial treatment allocation, 285 were treated with SBRT and represented the subject of the primary analysis. SBRT utilization increased from 2004 (0.4% of all stage I patients diagnosed that year) to 2013 (6.4%). During this same time period, definitive surgical management also increased from 14.9% of all patients in 2004 to 28.5% in 2013. The median SBRT biologically effective dose (BED10) was 112.5Gy (range, 72-290) and only 33 out of 285 (11.6%) received a BED10<100Gy. Nearly half of all patients (130/285, 45.6%) received chemotherapy, with 42.7% of those patients receiving their chemotherapy prior to SBRT. On multivariable logistic regression, only age<75 (the median) vs. ≥75years (OR 4.97, 95% CI 2.96-8.35, p<0.001) and year of diagnosis 2004-2008 vs. 2009-2013 (OR 2.58, 95% CI 1.27-5.26, p=0.009) were predictive of chemotherapy use with SBRT. After median follow up of 45 months, the median survival was 23.5 months. CONCLUSIONS Our findings suggest that SBRT utilization for stage I SCLC has increased between 2004 and 2013, highlighting the need for additional research to validate the feasibility of this management approach for inoperable patients.

Multi-institutional experience of stereotactic body radiotherapy for large (≥5 centimeters) non-small cell lung tumors.

Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early‐stage non–small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single‐institution reports. The current multi‐institutional study reported outcomes evaluating the largest such population reported to date.

The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma

Extranodal (or extracapsular) extension (ENE) is an adverse prognostic factor in patients with head and neck cancers who undergo primary surgery. However, the significance of ENE in human papillomavirus (HPV)‐positive oropharyngeal squamous cell carcinoma (OPSCC) is not well established, and single‐institution studies have not established that ENE predicts inferior outcome. The authors investigated the prognostic value of ENE in HPV‐positive patients who underwent primary surgery and whether adjuvant chemoradiation improved overall survival (OS) compared with radiation alone in ENE‐positive patients.

Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival

Background: Radiotherapy alone is often used to treat early-stage glottic cancer (ESGC); however, the optimal radiation treatment schedule remains unknown. The National Comprehensive Cancer Network (NCCN) guidelines recommend both hypofractionated radiotherapy (HFX) and conventionally fractionated radiotherapy (CFX). We compared overall survival (OS) and treatment patterns among patients treated with HFX vs CFX for ESGC using a large national database. Methods: We identified patients diagnosed with stage I–II (cT1-2N0M0) glottic cancer from 2004 to 2013 within the National Cancer Data Base who were treated with either HFX (2.25 Gy/fraction to 63–65.25 Gy) or CFX (2.0 Gy/fraction to 66–70 Gy). The overall survival of patients receiving HFX vs CFX was compared using the log-rank test, multivariable Cox proportional hazards regression, and propensity score matching. All statistical tests were two-sided. Results: Among 10 212 included patients, 4030 patients (39.5%) received HFX and 6182 patients (60.5%) received CFX. Predictors for receipt of HFX included clinical T1 disease, recent year of diagnosis, and treatment at academic and higher-volume centers (all P < .001). Patients treated with HFX increased from 22.1% in 2004 to 58.0% in 2013. HFX was associated with improved OS compared with CFX on univariate (five-year OS = 77.1%, 95% CI = 75.2% to 78.8%, vs 73.5%, 95% CI = 72.1% to 74.8%, respectively, log-rank P < .001) and multivariable analysis (HR = 0.89, 95% CI = 0.81 to 0.98, P = .02), a finding confirmed on propensity score matching. Conclusions: HFX is associated with improved survival compared with CFX among patients treated with definitive radiotherapy for ESGC, particularly among patients with cT2 disease. HFX utilization increased over the study period; however, 40% of patients in our cohort did not receive HFX in the most recent year of our analysis.

Impact of vaginal cylinder diameter on outcomes following brachytherapy for early stage endometrial cancer

Objective To examine the outcomes (tolerability, toxicity, and recurrence) of vaginal brachytherapy (VBT) among endometrial cancer (EC) patients treated with small cylinder size. Methods Patients with EC who received adjuvant VBT between September 2011 and December 2015 were reviewed. Patients were fitted with the largest vaginal cylinder they could comfortably accommodate, from 2.0–3.0 cm diameter. Small cylinders were defined as size 2.3 cm or less. Patient, tumor, or treatment characteristics were correlated with need for small cylinders. Treatment tolerability, measures of gastrointestinal (GI), genitourinary (GU), and vaginal toxicity, and rates of recurrence were analyzed. Results Three hundred four patients were included. Small cylinders were used in 51 patients (17%). Normal body mass index (BMI; p<0.001), nulligravidity (p<0.001), and shorter vaginal length (p<0.001) were associated with small cylinder size. There was no acute or late grade 3 toxicity. Rates of acute (grade 1–2) GI, GU, or vaginal symptoms were low (10%, 11%, and 19%, respectively). Small cylinder size was associated with increased likelihood of reporting acute GI (p<0.05) but not GU or vaginal symptoms. Small cylinder size was associated with higher risk of grade 1–2 vaginal stenosis (odds ratio [OR]=4.7; 95% confidence interval [CI]=1.5–14.7; p=0.007). There was no association between cylinder size and recurrence rate (p=0.55). Conclusion VBT is generally very well tolerated, however, patients fitted with smaller cylinders (commonly nulligravid and low BMI) may have increased side effects. Further study to improve the dosimetry of VBT for patients requiring small cylinders may be worthwhile.

Influence of robotic-assisted laparoscopic hysterectomy on vaginal cuff healing and brachytherapy initiation in endometrial carcinoma patients

PURPOSE The purpose of this study was to examine the impact of robotic-assisted laparoscopic hysterectomy (RALH) compared with total abdominal hysterectomy by laparotomy (TAH) on vaginal cuff healing in early-stage endometrial carcinoma patients receiving adjuvant intravaginal brachytherapy (IVBT). METHODS AND MATERIALS We included 137 consecutive patients who underwent adjuvant IVBT without external beam radiation therapy or chemotherapy for stage I-II endometrial carcinoma. All patients underwent either RALH or TAH. Vaginal cuff healing status as assessed by inspection and palpation at initial evaluation by radiation oncology (VC1) was the primary outcome, with secondary outcomes including vaginal cuff healing status at first scheduled IVBT (VC2), time interval from hysterectomy to initiation of IVBT, and local recurrence. RESULTS Among 137 patients, 74 (54.0%) underwent RALH and 63 (46.0%) underwent TAH. There was no significant difference in mean time from hysterectomy to initial radiation oncology evaluation between RALH and TAH patients (approximately 30 days in both groups). RALH was the only covariate associated with protracted vaginal cuff healing time at both VC1 (P = .003) and VC2 (P = .038). There was a significantly increased mean interval between hysterectomy and start of IVBT for patients undergoing RALH from 47.7 to 55.0 days (P < .001). Vaginal cuff healing was more likely to contribute to delay in delivery of IVBT in RALH patients, whereas abdominal or other nonvaginal wound healing was more likely to contribute to delay in TAH patients. There were no vaginal cuff recurrences detected after 16 months median follow-up. CONCLUSIONS RALH for early-stage endometrial carcinoma was associated with longer vaginal cuff healing time and a mean increase in interval from hysterectomy to IVBT of 1 week compared with TAH.

Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma

ABSTRACT Soft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50–50.4 Gy in 25–28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio – 0.16, 95% confidence interval: 0.034–0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.