Shaakir Hasan

OBJECTIVE: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. BACKGROUND: We utilized the National Cancer Database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. METHODS: We analyzed 5086 patients between 2010 and 2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional-hazard ratios were used for survival. RESULTS: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher-grade tumors (P < 0.05).The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (odds ratio 0.65, 95% confidence interval 0.43-0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared with 73% without it (<0.001). CONCLUSION: Microsatellite instability was independently associated with a reduction in pCR for locally advanced rectal cancer after neoadjuvant chemoradiation in this NCDB-based analysis.

Objective: A systematic review of the literature was undertaken to investigate whether adjuvant radiotherapy and/or chemotherapeutics offered any additional benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC). Methods: A PubMed, MEDLINE search was conducted between 1995-2013, to identify reported cases of surgically treated MCC followed by either observation, radiation, or chemoradiation. Patient demographics and outcomes were recorded and compared in a systematic fashion. Results: Thirty-four studies (n = 4475) were included. The median age was 73 years, median follow-up was 36 months and there was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no further treatment, 1689 received postoperative RT, and 301 received postoperative chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most common clinical stage at diagnosis (57%). Three-year LC was 20% [median 10%] in the observation cohort, compared to 65% [62%] with postoperative RT and 67% [75%] with postoperative chemoRT; these findings were statistically significant (P

BACKGROUND: Stereotactic body radiation therapy (SBRT) and proton beam therapy (PBT) generally are safe and effective for non-operative hepatocellular carcinoma (HCC). To date, data comparing the two modalities are limited. We aimed to identify the practice patterns and outcomes of nonsurgical HCC cases treated definitively with either SBRT or PBT. METHODS: We queried the National Cancer Database for T1-2N0 HCC patients receiving PBT or SBRT from 2004 to 2015. Patients were excluded for any treatment other than non-palliative external beam radiotherapy. A multivariable binomial regression model identified patterns of SBRT/PBT use, and propensity-matched multivariable Cox regression assessed correlates of survival. RESULTS: A total of 71 patients received PBT and 918 patients received SBRT (median follow-up 45 months). SBRT was used in 1.8% of nonoperative early stage HCC cases in 2004 and 4.2% of cases in 2015, whereas PBT was used in 0.1-0.2% of cases every year. The median biologically effective dose (BED) for SBRT and PBT was 100 Gy10 and 98 Gy10, respectively (OR =0.70, P=0.17). Factors predictive of receiving PBT included: white race, higher comorbidity score, higher education, metropolitan residence, tumors >5 cm and recent treatment (all P<0.05). Both PBT (HR =0.48, 95% CI: 0.29-0.78) and BED ≥100 Gy10 (HR =0.61, 95% CI: 0.38-0.98) were independent predictors for longer survival. CONCLUSIONS: Although not implying causation and requiring prospective corroboration, PBT was independently associated with longer survival than SBRT, despite being delivered to HCC patients with multiple poor prognostic factors. PBT may also allow for safer BED escalation, which also independently associated with outcomes.