The prognostic value of KRAS mutation in locally advanced rectal cancer.

BACKGROUND: The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). METHODS: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. RESULTS: Of the 784 eligible patients, 506 were KRAS-negative (KRAS -) and 278 were KRAS-positive (KRAS +). Median survival was 63.6 months and 76.3 months for KRAS + and KRAS - patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses. CONCLUSIONS: Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.

Utilization of Adjuvant Radiotherapy for Resected Colon Cancer and Its Effect on Outcome.

BACKGROUND: Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios [advanced local disease (pT4) and/or positive margins]. Guidelines in this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome. METHODS: We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy. Multivariable logistic regression was used to identify predictors of adjuvant radiation. A propensity score was used to perform matched Kaplan-Meier analysis. Propensity-adjusted Cox regression was used to identify predictors of overall survival. RESULTS: We identified 23,325 patients meeting criteria, of whom 1711 (7%) received adjuvant radiation. Median follow-up was 36 months. The majority of patients were pT4 alone (65%). Predictors of adjuvant radiation were lower comorbidity score, younger age, more remote year of treatment, and both pT4 and positive margins. Kaplan-Meier analysis revealed improved overall survival (OS) in patients with both pT4 and positive margins treated with radiation (median OS: 66 versus 47 months, p = 0.02). Receipt of adjuvant radiation was associated with improved OS [hazard ratio (HR): 0.86 (0.80-0.93) p = 0.0002] on Cox regression analysis. Increased age, higher comorbidity score, lower income, government insurance, and combined pT4/positive margins were indicative of worse survival. CONCLUSIONS: Expectedly, adjuvant radiation use was relatively low but was associated with improved OS in patients with both pT4 and positive margins.

Definitive Chemoradiation for Rectal Cancer: Is There a Role for Dose Escalation? A National Cancer Database Study.

BACKGROUND: Surgery remains the standard of care in rectal cancer. Select patients will not undergo surgery for reasons such as medical inoperability or a watch-and-wait approach and instead are managed with definitive chemoradiation. OBJECTIVE: We used the National Cancer Database to identify overall survival and predictors thereof in the nonoperative management of patients with rectal cancer. DESIGN: This was a retrospective review. SETTINGS: This study used deidentified data from the National Cancer Database. PATIENTS: We queried the national cancer database from 2004 to 2014 for stage 1 to 3 rectal adenocarcinoma treated with only chemotherapy and radiation to definitive doses. Dose escalated therapy was defined as >54 Gy. MAIN OUTCOME MEASURES: Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of dose escalation and overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Among the 6311 patients eligible for the study, 11% were treated with doses >54 Gy. Earlier stage and increased age/comorbidity patients were more likely to receive dose escalation, and patients with more recent treatment and treatment at an academic facility were less likely. The median follow-up time was 31 months (range, 2-154 mo). Three- and 5-year overall survival rates for all patients were 60% and 46%. Patients treated with dose escalation had a median survival of 33 months compared with 56 months for those treated with ≤54 Gy (p < 0.0001). LIMITATIONS: The main limitation is the inherent selection bias present in National Cancer Database studies. Important treatment details and outcomes as they relate to a definitive chemoradiation approach in rectal cancer are lacking. Salvage therapy was also not recorded, which in this population could be surgery. CONCLUSIONS: In this analysis, dose escalation in the nonoperative management of rectal cancer was associated with a lower overall survival compared with more conventional doses. Careful patient selection and enrollment on appropriate clinical trials may be warranted in the nonoperative setting. See Video Abstract at http://links.lww.com/DCR/B15. LA QUIMIORRADIACIÓN DEFINITIVA PARA EL CÁNCER RECTAL: ¿HAY LUGAR PARA EL AUMENTO DE LA DOSIS? UN ESTUDIO DE BASE DE DATOS NACIONAL DEL CÁNCER:: La cirugía sigue siendo el estándar en el tratamiento del cáncer rectal. Algunos pacientes no son quirúrgicos por razones como, no ser operables o con el enfoque de ver y esperar, y en su lugar son tratados con la quimiorradiación definitiva.Utilizamos la base de datos nacional del cáncer para identificar la supervivencia general y los factores predictivos de la misma, en el tratamiento no quirúrgico de pacientes con cáncer rectal.Esta fue una revisión retrospectiva.Utilizamos los datos identificados en la base de datos nacional del cáncer.Se consultó la base de datos nacional del cáncer del 2004-2014, para adenocarcinoma rectal en estadio 1-3, tratada únicamente con quimioterapia y radiación hasta la dosis definitiva. La terapia de aumento de la dosis se definió como >54 Gy.Se realizaron análisis univariables y multivariables para identificar características sociodemográficas, de tratamiento y predictivas del aumento de la dosis y supervivencia en general. Los índices de riesgo proporcionales de Cox ajustados a la propensión para la supervivencia, se utilizaron para tener en cuenta el sesgo de indicación.Entre los 6311 pacientes elegibles para el estudio, el 11% fue tratado con dosis >54 Gy. Los pacientes en estadios tempranos y con mayor edad/comorbilidad, tenían más probabilidades de recibir aumento de la dosis, y menos propensos los pacientes con tratamientos recientes y de centros académicos. El tiempo medio de seguimiento fue de 31 meses (2-154 meses). Las tasas de supervivencia global de tres y cinco años para todos los pacientes, fueron respectivamente del 60% y 46%. Los pacientes tratados con aumento de la dosis, tuvieron una supervivencia media de 33 meses, en comparación con los 56 meses para los pacientes tratados con ≤54 Gy (p < 0,0001).La principal limitación es el inherente sesgo en la selección, presente en los estudios de la base de datos nacional del cáncer. Faltan los detalles importantes del tratamiento y los resultados en relación con el enfoque definitivo de quimiorradiación en cáncer rectal. Tampoco se registró la terapia de rescate, que en esta población podría ser la cirugía.En este análisis, el aumento de la dosis en el manejo no quirúrgico del cáncer rectal, se asoció con una menor supervivencia global, en comparación con la dosis más convencional. La cuidadosa selección del paciente y la inscripción en los apropiados ensayos clínicos, pueden estar justificados en el entorno no quirúrgico. Vea el Resumen del Video en http://links.lww.com/DCR/B15.

Radiomodulating Properties of Superparamagnetic Iron Oxide Nanoparticle (SPION) Agent Ferumoxytol on Human Monocytes: Implications for MRI-Guided Liver Radiotherapy.

Superparamagnetic iron oxide nanoparticles (SPION) have attracted great attention not only for therapeutic applications but also as an alternative magnetic resonance imaging (MRI) contrast agent that helps visualize liver tumors during MRI-guided stereotactic body radiotherapy (SBRT). SPION can provide functional imaging of liver parenchyma based upon its uptake by the hepatic resident macrophages or Kupffer cells with a relative enhancement of malignant tumors that lack Kupffer cells. However, the radiomodulating properties of SPION on liver macrophages are not known. Utilizing human monocytic THP-1 undifferentiated and differentiated cells, we characterized the effect of ferumoxytol (Feraheme®), a carbohydrate-coated ultrasmall SPION agent at clinically relevant concentration and therapeutically relevant doses of gamma radiation on cultured cells in vitro. We showed that ferumoxytol affected both monocytes and macrophages, increased the resistance of monocytes to radiation-induced cell death and inhibition of cell activity, and supported the anti-inflammatory phenotype of human macrophages under radiation. Its effect on human cells depended on the duration of SPION uptake and was radiation dose-dependent. The results of this pilot study support a strong mechanism-based optimization of SPION-enhanced MRI-guided liver SBRT for primary and metastatic liver tumors, especially in patients with liver cirrhosis awaiting a liver transplant.

Concepts and Outcomes of Perioperative Therapy in Stage IA-III Pancreatic Cancer-A Cross-Validation of the National Cancer Database (NCDB) and the German Cancer Registry Group of the Society of German Tumor Centers (GCRG/ADT).

(1) Background: The aim of this study is to assess perioperative therapy in stage IA-III pancreatic cancer cross-validating the German Cancer Registry Group of the Society of German Tumor Centers-Network for Care, Quality, and Research in Oncology, Berlin (GCRG/ADT) and the National Cancer Database (NCDB). (2) Methods: Patients with clinical stage IA-III PDAC undergoing surgery alone (OP), neoadjuvant therapy (TX) + surgery (neo + OP), surgery+adjuvantTX (OP + adj) and neoadjuvantTX + surgery + adjuvantTX (neo + OP + adj) were identified. Baseline characteristics, histopathological parameters, and overall survival (OS) were evaluated. (3) Results: 1392 patients from the GCRG/ADT and 29,081 patients from the NCDB were included. Patient selection and strategies of perioperative therapy remained consistent across the registries for stage IA-III pancreatic cancer. Combined neo + OP + adj was associated with prolonged OS as compared to neo + OP alone (17.8 m vs. 21.3 m, p = 0.012) across all stages in the GCRG/ADT registry. Similarly, OS with neo + OP + adj was improved as compared to neo + OP in the NCDB registry (26.4 m vs. 35.4 m, p < 0.001). (4) Conclusion: The cross-validation study demonstrated similar concepts and patient selection criteria of perioperative therapy across clinical stages of PDAC. Neoadjuvant therapy combined with adjuvant therapy is associated with improved overall survival as compared to either therapy alone.

Post-Operative Morbidity and Mortality Following Total Neoadjuvant Therapy Versus Conventional Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

BACKGROUND: Standard of care for locally advanced rectal cancer (LARC) (stage II/III) includes preoperative chemoradiation (CRT) followed by resection and adjuvant chemotherapy. Total neoadjuvant therapy (TNT) is a new treatment paradigm that delivers systemic therapy prior to CRT aimed at improving outcomes for high-risk patients. Here we analyzed the national cancer database (NCDB) comparing short-term post-operative outcomes between patients receiving TNT and CRT. METHODS: The NCDB was queried to identify patients with LARC between the 2004 and 2014 treated with TNT or CRT. Primary outcomes included post-operative 30-day mortality and readmissions between TNT and CRT which were analyzed via logistic regression. Secondary outcomes included post-operative length of stay (LOS) and OS which were compared with two-tailed t-test and Kaplan-Meier with log rank testing, respectively. RESULTS: A total of 9066 patients met inclusion criteria with a median age at diagnosis that was 57 years (IQR, 19-65); 62.3% were male and 87.8% white. Neoadjuvant therapy consisted of either standard CRT (97.2%) or TNT (2.8%). Patients treated at academic programs and those with N1 [p < 0.001, OR 2.34, 95%CI 1.71-3.19] or N2 [p < 0.001, OR 3.29, 95%CI 2.19-4.94] disease were associated with increased utilization of TNT. TNT was not significantly associated with either 30-day mortality (p = 1.0) or readmissions (p = 0.82). Further, there was no significant difference identified between CRT and TNT for hospital LOS or OS (p = 0.18). CONCLUSION: This large-scale analysis of patients with LARC demonstrates increased utilization of TNT in patients harboring node-positive disease. Further, TNT does not appear to increase 30-day post-operative mortality, readmissions, or hospital LOS.

Chemotherapy use in early stage anal canal squamous cell carcinoma and its impact on long-term overall survival,,.

BACKGROUND: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy. It is postulated that chemotherapy could be omitted for the earliest stages without worsening outcomes. METHODS: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation, with and without chemotherapy, and at least two months of follow-up. Of the 2,959 patients meeting eligibility, 92% received chemotherapy (n = 2722) and 8% (n = 237) did not. Most patients were white (n = 2676), female (n = 2019), had private insurance (n = 1507) and were treated in a comprehensive cancer center (n = 1389). Average age was 58.5 years. RESULTS: Predictors of chemotherapy omission were age > 58 years (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and treatment at the start of the study period (OR 1 for years 2004-2006). HR for single-agent chemotherapy was 0.70 (95% CI [0.50-0.96], P = 0.0288) and 0.48 for multi-agent (95% CI [0.38-0.62], P <0.0001). Overall survival was 86% in those that received chemotherapy vs 65% in those who did not (P <0.0001). CONCLUSIONS: In conclusion, patients with early-stage squamous cell cancer of the anus who are treated with combination chemoradiation continue to demonstrate better overall survival than those who undergo radiotherapy alone.

Effect of Daily and Every Other Day Stereotactic Body Radiation Therapy Schedules on Treatment-Related Fatigue in Patients With Hepatocellular Carcinoma.

PURPOSE: We compared the rate and severity of fatigue in patients who completed stereotactic body radiation therapy (SBRT) to the liver daily (QD) compared with every other day (QOD). METHODS AND MATERIALS: From 2010 to 2017, 91 patients with Child Pugh (CP) A (n = 57) or CP-B (n = 34) cirrhosis who completed 100 SBRT sessions to 110 hepatocellular carcinoma (HCC) lesions were analyzed in this study. Confounding variables with fatigue such as CP-C cirrhosis, Eastern Cooperative Oncology Group score >2, or a history of ascites or encephalopathy were excluded. Fatigue was assessed against several treatment- and patient-related variables with univariate and propensity score-matched multivariate analysis. The median follow-up time was 18 months. RESULTS: Patients with HCC and Barcelona-Clinic Liver Cancer stages 0 (n = 10), A (n = 32), and B (n = 58), and a median age of 62 years were analyzed. The median tumor diameter was 3 cm (1.1-11 cm). The Eastern Cooperative Oncology Group performance status score was 0 (n = 44), 1 (n = 43), or 2 (n = 13). The median dose was 45 Gy in 5 fractions, and 65 treatments were QD and 45 QOD. Grades 1 and 2 fatigue developed in 49% and 14% of treatments, respectively. Among the patients who were treated daily, 78% developed Grade 1 or 2 fatigue compared with 44% who were treated QOD (odds ratio: 4.52; P = .001). Grade 2 fatigue occurred in 22% of patients compared with 7.3% for QD and QOD treatment, respectively (odds ratio: 3.83; P = .048). There was no difference in fatigue rate for time of treatment (morning or afternoon), dose, treated volume, CP score, Barcelona-Clinic Liver Cancer stage, or performance status, which were not associated with any level of fatigue. There was no difference in local control between QD and QOD treatments. CONCLUSIONS: Compared with traditional daily treatment fractions, SBRT that is delivered QOD to cirrhotic patients with HCC may reduce the risk of fatigue.

Anal adenocarcinoma: Treatment outcomes and trends in a rare disease entity.

IMPORTANCE: Primary Adenocarcinoma of the anus is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to 2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage. OBJECTIVE: We conducted this National Cancer Database (NCDB)-driven retrospective study to analyze treatment trends and outcomes in the current time from 2004 to 2015 with respect to chemoradiation and surgery. DESIGN: Retrospective NCDB tumor registry data review-using propensity score-adjusted multivariable analyses for survival. SETTING: Database review. PARTICIPANTS: We selected for patients listed in the NCDB with AJCC stage 1-3 anal adenocarcinoma diagnosed between 2004 and 2015 and selected out patients with undocumented/stage 4 disease, those with radiation outside the pelvis, not treated with systemic therapy and patients lost to follow-up. EXPOSURE(S): None. MAIN OUTCOMES AND MEASURES: Overall survival and use of surgery in the up-front management of anal adenocarcinoma. RESULTS: Of the 1729 patients eligible in this study, 1028 were treated with surgery as up-front management and 701 had definitive chemoradiation. Median overall survival for all patients was 55 months with a 5-year survival rate of 55%. Patients treated without surgery had worse overall survival, median survival of 45 months compared to 87 months (P < 0.0001) with 5-year survival rates of 42% and 55% in favor of incorporation of surgery. Analysis across patients treated with surgery alone, surgery followed by adjuvant chemoradiation, neoadjuvant chemoradiation followed by surgery, and chemoradiation alone had median survival rates of 78, 83, 92, and 46 months, respectively. Propensity score-adjusted multivariable analysis identified older age, grade 3, high comorbidity score, and lack of surgery as predictive of worse outcome. CONCLUSIONS AND RELEVANCE: The results of the NCDB analysis indicate improved overall survival with the incorporation of surgery into the initial management of anal adenocarcinoma when compared to chemoradiation alone, despite the omission of surgery in up to 50% of the cases logged. Our results corroborate earlier studies published prior to the year 2000 for surgery to be included in the definitive management of anal adenocarcinoma.

Incidence and risk factors for post-operative mortality, hospitalization, and readmission rates following pancreatic cancer resection.

BACKGROUND: The only potentially curative approach for pancreatic cancer is surgical resection, but this technically challenging procedure carries risks for postoperative morbidities and mortality. This study of a large, contemporary national database illustrates incidences of, and risk factors for, post-procedural mortality, prolonged hospital stay, and 30-day readmission. METHODS: From the National Cancer Database (NCDB), stage I-III pancreatic adenocarcinomas were identified [2004-2015]. Surgical techniques included pancreaticoduodenectomy, partial pancreatectomy (selective removal of the pancreatic body/tail), total pancreatectomy (removal of the entire pancreas) with or without subtotal resection of the duodenum and/or stomach, and extended pancreatectomy. Predictors of 30/90-day post-operative mortality, 30-day readmission rates, and prolonged hospital stay (>17 days per receiver operating curve analysis) were identified via multivariable logistic regression. RESULTS: Overall, 24,798 patients were analyzed (median age of 66). The majority of cases were T3 (47%), N0 (65%), pancreatic head lesions (83%), and treated with pancreaticoduodenectomy (57%). Only 16% received neoadjuvant therapy. Overall unadjusted risk of 30- and 90-day mortality ranged from 1.3-2.5% and 4.1-7.1%, respectively, depending on extent of surgery. Independent predictors of 30-/90-day mortality included preoperative therapy, increasing age, higher comorbidity score, lower income, case volume, and more extensive surgery. Similar findings were demonstrated regarding prolonged hospital stay and 30-day readmission. Age ≥70 was most associated with 30-day mortality, whereas age ≥60 was most associated with 90-day mortality and prolonged hospital stay. CONCLUSIONS: Quantitation of incidences and risk factors for postoperative outcomes following resection for pancreatic cancer is essential for judicious patient selection and shared decision-making between providers and patients.

Retrospective review of total neoadjuvant therapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer. Using this approach, maChT administration can be delayed for several months, leading to concern for distant metastases. To counteract this, a novel treatment approach known as total neoadjuvant therapy (TNT) has gained popularity, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database to examine temporal trends in TNT usage, and any potential effect on survival. AIM: To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation. METHODS: We queried the National Cancer Database for patients with locally advanced rectal cancer, Stage II-III, from 2004-2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 d prior to nCRT initiation. Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival, with log-rank statistics to assess significance. Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias. RESULTS: We identified 9066 eligible patients, with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT, respectively. Nodal involvement, stage III disease, and treatment in recent years were predictive of TNT use. There was greater use of TNT with more advanced stage, specifically > 1 node involved (odds ratio [OR] = 2.88, 95% confidence interval [CI]: 2.11-3.93, P < 0.01) and stage III disease (OR = 2.88, 95%CI: 2.11-3.93, P < 0.01). From 2010 to 2012 the use of TNT increased (OR = 2.41, 95%CI: 1.27-4.56, P < 0.01) with a greater increase from 2013 to 2015 (OR = 6.62, 95%CI: 3.57-12.25, P < 0.01). Both the TNT and neoadjuvant chemoradiation arms had a similar 5-year survival at 76% and 78% respectively. Multivariable analysis with propensity score demonstrated that increased age, high comorbidity score, higher grade, African American race, and female gender had worse overall survival. CONCLUSION: Our data demonstrates a rising trend in TNT use, particularly in patients with worse disease. Patients treated with TNT and nCRT had similar survival. Randomized trials evaluating TNT are underway.

Time to Adjuvant Systemic Therapy Following Pancreatic Cancer Resection and Effect on Outcome.

OBJECTIVES: The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy postresection and correlated with outcome. METHODS: We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy. Receiver operator curve analysis identified an interval of 66 days as the a priori value for largest discrepancy in outcome. Multivariable logistic regression analysis identified variables associated with increased time to chemotherapy postoperatively (>66 days). Propensity matching was performed to account for indication bias. RESULTS: In total, 6873 and 3348 patients received chemotherapy before and after the 66-day cutoff, respectively. Predictors of expedited chemotherapy included lower comorbidity, treatment outside a community program in an urban location, having insurance, white race, and treatment after 2009. Propensity-matched median survival was 21.8 months for all patients, and of these, 6462 were stage 1. Five-year survival was 20% in patients receiving chemotherapy within 66 days and 18% in those not (P = 0.0266). In stage 1 patients, 5-year survival was 23% versus 21% (P = 0.0116) in favor of expedited chemotherapy. CONCLUSIONS: The present propensity-matched analysis showed a significant association with survival for earlier delivery of chemotherapy in the adjuvant setting.

Trends in Radiation Dose and Technique For Anal Canal Squamous Cell Carcinoma.

BACKGROUND: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemoradiation, reserving surgery for salvage. The dosage of radiation has varied from 30 Gy to in excess of 60 Gy. RTOG 0529 established intensity modulated radiation therapy (IMRT) as standard of care for anal canal SCC with doses of 50.4 to 54 Gy. We sought to use the National Cancer Database to examine trends in dose selection and radiation technique over time. METHODS: We queried the National Cancer Database from 2004 to 2015 for cases of anal cancer stage groups 1 to 3, treated with definitive doses of radiation with chemotherapy. Dose escalation was defined as >54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of dose, IMRT, and overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: We identified 7792 patients meeting the eligibility criteria, with 4269 treated to doses of 45 to 54 Gy and 3163 treated to doses >54 Gy. Patients who were older, had government or private insurance, IMRT treatment, treatment at an academic center, or more recent years were less likely to get dose escalation. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. IMRT use increased over time from 2% to 63%. On multivariable analysis with propensity score included it was found that increased age, higher comorbidity score, lower income, shorter distance to facility, and male sex were predictive of decreased overall survival. In addition, escalated dose was associated with a lower survival (hazard ratio: 1.10, 95% confidence interval: 1.01-1.20, P=0.03). CONCLUSIONS: The results of this analysis show a steady increase in the use of IMRT, with corresponding decrease in dose escalation. These findings correlate with the results of RTOG 0529 establishing IMRT as standard of care for anal SCC, using doses of 50.4 to 54 Gy.

Trends in intensity-modulated radiation therapy use for rectal cancer in the neoadjuvant setting: a National Cancer Database analysis.

PURPOSE: Traditionally, three-dimensional conformal radiation therapy (3D-CRT) is used for neoadjuvant chemoradiation in locally advanced rectal cancer. Intensity-modulated radiation therapy (IMRT) was later developed for more conformal dose distribution, with the potential for reduced toxicity across many disease sites. We sought to use the National Cancer Database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. MATERIALS AND METHODS: We queried the NCDB from 2004 to 2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to standard doses followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. RESULTS: Among 21,490 eligible patients, 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, higher comorbidity score, more recent year, treatment at an academic facility, increased income, and higher educational level. On propensity-adjusted, multivariable analysis, male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African-American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. CONCLUSION: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique, more often reserved for higher disease burden.

Hepatocellular carcinoma with child Pugh-A Cirrhosis treated with stereotactic body radiotherapy.

AIM: To evaluate the control, survival, and hepatic function for Child Pugh (CP)-A patients after Stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC). METHODS: From 2009 to 2016, 40 patients with Barcelona Liver Clinic (BCLC) stages 0-B HCC and CP-A cirrhosis completed liver SBRT. The mean prescription dose was 45 Gy (40 to 50 Gy in 4-5 fractions). Local relapse, defined as recurrence within the planning target volume was assessed with intravenous multiphase contrast computed tomography or magnetic resonance imaging every 4-6 mo after completion of SBRT. Progression of cirrhosis was evaluated by CP and Model for End Stage Liver Disease scores every 3-4 mo. Toxicities were graded per the Common Terminology Criteria for Adverse Events (v4.03). Median follow-up was 24 mo. RESULTS: Forty-nine HCC lesions among 40 patients were analyzed in this IRB approved retrospective study. Median tumor diameter was 3.5 cm (1.5-8.9 cm). Six patients with tumors ≥ 5 cm completed planned selected transarterial chemoembolization (TACE) in combination with SBRT. Eight patients underwent orthotropic live transplant (OLT) with SBRT as a bridging treatment (median time to transplant was 12 mo, range 5 to 23 mo). The Pathologic complete response (PCR) rate in this group was 62.5%. The 2-year in-field local control was 98% (1 failure). Intrahepatic control was 82% and 62% at 1 and 2 years, respectively. Overall survival (OS) was 92% and 60% at 1 and 2 years, with a median survival of 41 mo per Kaplan Meier analysis. At 1 and 2 years, 71% and 61% of patients retained CPA status. Of the patients with intrahepatic failures, 58% developed progressive cirrhosis, compared to 27% with controlled disease (P = 0.06). Survival specific to hepatic failure was 92%, 81%, and 69% at 12, 18, and 24 mo. There was no grade 3 or higher toxicity. On univariate analysis, gross tumor volume (GTV) < 23 cc was associated with freedom from CP progression (P = 0.05), hepatic failure-specific survival (P = 0.02), and trended with OS (P = 0.10). CONCLUSION: SBRT is safe and effective in HCC with early cirrhosis and may extend waiting time for transplant in patients who may not otherwise be immediate candidates.

Consequences and countermeasures in a nuclear power accident: Chernobyl experience.

Despite the tragic accidents in Fukushima and Chernobyl, the nuclear power industry will continue to contribute to the production of electric energy worldwide until there are efficient and sustainable alternative sources of energy. The Chernobyl nuclear accident, which occurred 26 years ago in the former Soviet Union, released an immense amount of radioactivity over vast territories of Belarus, Ukraine, and the Russian Federation, extending into northern Europe, and became the most severe accident in the history of the nuclear industry. This disaster was a result of numerous factors including inadequate nuclear power plant design, human errors, and violation of safety measures. The lessons learned from nuclear accidents will continue to strengthen the safety design of new reactor installations, but with more than 400 active nuclear power stations worldwide and 104 reactors in the Unites States, it is essential to reassess fundamental issues related to the Chernobyl experience as it continues to evolve. This article summarizes early and late events of the incident, the impact on thyroid health, and attempts to reduce agricultural radioactive contamination.