Impact of Age on Overall Survival Among Children With Wilms Tumor: A Population-based Registry Analysis.

OBJECTIVES: International trials have reported conflicting findings on whether the association between age and worse overall survival (OS) among children with Wilms tumor (WT) is due to age as an independent prognostic factor or the observation of more advanced disease at older ages. We sought to further elucidate this relationship using a population-based registry analysis. METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with WT under the age of 20. The association between age and OS was assessed using multivariable Cox proportional hazards regression. RESULTS: In this study, 3463 patients (54% female) were diagnosed with WT between 1975 and 2016. More advanced stage, larger primary tumor size, lymph node involvement, disease requiring radiotherapy, and omission of surgery were associated with worse OS ( P <0.05). More advanced stage, larger primary tumor size, and disease requiring radiotherapy were also associated with older age, whereas bilateral disease was associated with younger age ( P <0.001). On average, each year of age conferred an incremental hazard ratio (HR) of 1.07 (95% CI, 1.01 to 1.12, P =0.018) independent of relevant covariates. The rise in adjusted OS HR was most pronounced after the transitions in diagnosis age from 2 to 3 (HR age 3-15 vs. 0-2 1.77, 95% CI, 1.11 to 2.82, P =0.016) and from 15 to 16 (HR age 16-19 vs. 3-15 2.58, 95% CI, 1.06 to 6.25, P =0.036). CONCLUSIONS: Diagnosis of pediatric WT at an older age was found to be independently associated with worse OS. Although additional prospective studies are warranted to examine tumor biology and other potential correlates, more aggressive treatment of older children based on age, especially as they approach early adulthood, may be considered in the multidisciplinary management of WT.

Ninety-day mortality following transoral robotic surgery or radiation at Commission on Cancer-accredited facilities.

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown. METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities. RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality. CONCLUSIONS: There is minimal difference between 90-day mortality in patients treated with TORS or radiotherapy for early-stage OPSCC. While overall rates are low, for patients with expectation of cure, work is needed to identify optimal treatment.

Development and validation of a prognostic gene expression signature for lower-grade glioma following surgery and adjuvant radiotherapy.

BACKGROUND AND PURPOSE: Standard of care for lower-grade glioma (LGG) is maximal safe resection and risk-adaptive adjuvant therapy. While patients who benefit the most from adjuvant chemotherapy have been elucidated in prospective randomized studies, comparable insights for adjuvant radiotherapy (RT) are lacking. We sought to identify and validate patterns of gene expression that are associated with differential outcomes among LGG patients treated by RT from two large genomics databases. MATERIALS AND METHODS: Patients from The Cancer Genome Atlas (TCGA) with LGG (WHO grade II-III glioma) treated by surgery and adjuvant RT were randomized 1:1 to a discovery cohort or an internal validation cohort. Using the discovery cohort only, associations between tumor RNA-seq expression and progression-free survival (PFS) as well as overall survival (OS) were evaluated with adjustment for clinicopathologic covariates. A Genomic Risk Score (GRS) was then constructed from the expression levels of top genes also screened for involvement in glioma carcinogenesis. The prognostic value of GRS was further assessed in the internal validation cohort of TCGA and a second distinct database, compiled by the Chinese Glioma Genome Association (CGGA). RESULTS: From TCGA, 289 patients with LGG received adjuvant RT alone (38 grade II, 30 grade III) or chemoradiotherapy (CRT) (51 grade II, 170 grade III) between 2009 and 2015. From CGGA, 178 patients with LGG received adjuvant RT alone (40 grade II, 13 grade III) or CRT (41 grade II, 84 grade III) between 2004 and 2016. The genes comprising GRS are involved in MAP kinase activity, T cell chemotaxis, and cell cycle transition: MAP3K15, MAPK10, CCL3, CCL4, and ADAMTS1. High GRS, defined as having a GRS in the top third, was significantly associated with poorer outcomes independent of age, sex, glioma histology, WHO grade, IDH mutation, 1p/19q co-deletion, and chemotherapy status in the discovery cohort (PFS HR 1.61, 95% CI 1.10-2.36, P = 0.014; OS HR 2.74, 95% CI 1.68-4.47, P < 0.001). These findings were replicated in the internal validation cohort (PFS HR 1.58, 95% CI 1.05-2.37, P = 0.027; OS HR 1.84, 95% CI 1.13-3.00, P = 0.015) and the CGGA external validation cohort (OS HR 1.72, 95% CI 1.27-2.34, P < 0.001). Association between GRS and outcomes was observed only among patients who underwent RT, in both TCGA and CGGA. CONCLUSION: This study successfully identified an expression signature of five genes that stratified outcomes among LGG patients who received adjuvant RT, with two rounds of validation leveraging independent genomics databases. Expression levels of the highlighted genes were associated with PFS and OS only among patients whose treatment included RT, but not among those with omission of RT, suggesting that expression of these genes may be predictive of radiation treatment response. While additional prospective studies are warranted, interrogation of these genes may be considered in the multidisciplinary management of LGG.

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Stereotactic body radiotherapy used as a bridge to liver transplant in patients with hepatocellular carcinoma and Child-Pugh score ≥8 cirrhosis.

INTRODUCTION: To report on SBRT as a bridge to OLT for patients with HCC and Child-Pugh ≥8 cirrhosis. METHODS: Retrospective review of 15 patients, treated from 2010-2017. Three patients excluded secondary to delisting from prohibitive substance. Twelve patients (17 lesions) included for final analysis. Hepatic SPECT functional treatment planning utilized. RESULTS: The median age of 60 years with a median CP 9 and MELD 14. The median SBRT dose was 40 Gy in 5 fractions, and median tumor size was 2.3cm (1.2-5.3cm). Median follow-up and survival was 40-months and 46-months, respectively. One patient succumbed to renal/hepatic failure before OLT. Radiographic response was 80%. pCR at explant was 46%. No grade ≥ 3 acute toxicities. Median time to progression of CP ≥ 2 was 9.7-months and MELD progression was not met before OLT. CONCLUSION: SBRT with functional treatment planning can be used safely as a bridge to OLT in select patients with CP ≥8 cirrhosis.