Association between access to accelerated partial breast irradiation and use of adjuvant radiotherapy.

BACKGROUND: The current study was performed to determine whether access to facilities performing accelerated partial breast irradiation (APBI) is associated with differences in the use of adjuvant radiotherapy (RT). METHODS: Using the National Cancer Data Base, the authors performed a retrospective study of women aged ≥50 years who were diagnosed with early-stage breast cancer between 2004 and 2013 and treated with breast-conserving surgery (BCS). Facilities performing APBI in ≥10% of their eligible patients within a given year were defined as APBI facilities whereas those not performing APBI were defined as non-APBI facilities. All other facilities were excluded. The authors identified independent factors associated with RT use using multivariable logistic regression with clustering in the overall sample as well as in subsets of patients with standard-risk invasive cancer, low-risk invasive cancer, and ductal carcinoma in situ. RESULTS: Among 222,544 patients, 76.6% underwent BCS plus RT and 23.4% underwent BCS alone. The likelihood of RT receipt in the overall sample did not appear to differ significantly between APBI and non-APBI facilities (adjusted odds ratio [AOR], 1.02; P = .61). Subgroup multivariable analysis demonstrated that among patients with standard-risk invasive cancer, there was no association between evaluation at an APBI facility and receipt of RT (AOR, 0.98; P = .69). However, patients with low-risk invasive cancer were found to be significantly more likely to receive RT (54.4% vs 59.5%; AOR, 1.22 [P<.001]), whereas patients with ductal carcinoma in situ were less likely to receive RT (56.9% vs 55.3%; AOR, 0.89 [P = .04]) at APBI facilities. CONCLUSIONS: Patients who were eligible for observation were more likely to receive RT in APBI facilities but no difference was observed among patients with standard-risk invasive cancer who would most benefit from RT. Cancer 2017;123:502-511. © 2016 American Cancer Society.

Concurrent chemoradiotherapy versus radiotherapy alone for "biopsy-only" glioblastoma multiforme.

BACKGROUND: Combined temozolomide and radiotherapy (RT) is the standard postoperative therapy for glioblastoma multiforme (GBM). However, the clearest benefit of concurrent chemoradiotherapy (CRT) observed in clinical trials has been among patients who undergo surgical resection. Whether the improved survival with CRT extends to patients who undergo "biopsy only" is less certain. The authors compared overall survival (OS) in a national cohort of patients with GBM who underwent biopsy and received either RT alone or CRT during the temozolomide era. METHODS: The US National Cancer Data Base was used to identify patients with histologically confirmed, biopsy-only GBM who received either RT alone or CRT from 2006 through 2011. Demographic and clinicopathologic predictors of treatment were analyzed using the chi-square test, the t test, and multivariable logistic regression. OS was evaluated using the log-rank test, multivariable Cox proportional hazard regression, and propensity score-matched analysis. RESULTS: In total, 1479 patients with biopsy-only GBM were included, among whom 154 (10.4%) received RT alone and 1325 (89.6%) received CRT. The median age at diagnosis was 61 years. CRT was associated with a significant OS benefit compared with RT alone (median, 9.2 vs 5.6 months; hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.54-0.76; P < .001). CRT was independently associated with improved OS compared with RT alone on multivariable analysis (HR, 0.71; 95% CI, 0.60-0.85; P < .001). A significant OS benefit for CRT persisted in a propensity score-matched analysis (HR, 0.72; 95% CI, 0.56-0.93; P = .009). CONCLUSIONS: The current data suggest that CRT significantly improves OS in patients with GBM who undergo biopsy only compared with RT alone and should remain the standard of care for patients who can tolerate therapy. Cancer 2016;122:2364-2370. © 2016 American Cancer Society.

Production of 1-decanol by metabolically engineered Yarrowia lipolytica.

Medium-chain alcohols are used to produce solvents, surfactants, lubricants, waxes, creams, and cosmetics. In this study, we engineered the oleaginous yeast Yarrowia lipolytica to produce 1-decanol from glucose. Expression of a fatty acyl-CoA reductase from Arabidopsis thaliana in strains of Y. lipolytica previously engineered to produce medium-chain fatty acids resulted in the production of 1-decanol. However, the resulting titers were very low (<10mg/mL), most likely due to product catabolism. In addition, these strains produced small quantities of 1-hexadecanol and 1-octadecanol. Deleting the major peroxisome assembly factor Pex10 was found to significantly increase 1-decanol production, resulting in titers exceeding 500mg/L. It also increased 1-hexadecanoland and 1-octadecanol titers, though the resulting increases were less than those for 1-decanol. These results demonstrate that Y. lipolytica can potentially be used for the industrial production of 1-decanol and other fatty alcohols from simple sugars.

Engineering Rhodosporidium toruloides for increased lipid production.

Oleaginous yeast are promising organisms for the production of lipid-based chemicals and fuels from simple sugars. In this work, we explored Rhodosporidium toruloides for the production of lipid-based products. This oleaginous yeast natively produces lipids at high titers and can grow on glucose and xylose. As a first step, we sequenced the genomes of two strains, IFO0880, and IFO0559, and generated draft assemblies and annotations. We then used this information to engineer two R. toruloides strains for increased lipid production by over-expressing the native acetyl-CoA carboxylase and diacylglycerol acyltransferase genes using Agrobacterium tumefaciens mediated transformation. Our best strain, derived from IFO0880, was able to produce 16.4 ± 1.1 g/L lipid from 70 g/L glucose and 9.5 ± 1.3 g/L lipid from 70 g/L xylose in shake-flask experiments. This work represents one of the first examples of metabolic engineering in R. toruloides and establishes this yeast as a new platform for production of fatty-acid derived products.

Who benefits from chemoradiation in stage III-IVA endometrial cancer? An analysis of the National Cancer Data Base.

OBJECTIVE: Adjuvant therapy for advanced endometrial cancer (AEC) is not standardized. We investigated whether regional radiotherapy with chemotherapy (CRT) compared to chemotherapy alone (CT) was associated with improved overall survival (OS) in an AEC cohort and among subgroups by stage and histologic grade. METHODS: Women who received CT or CRT after hysterectomy and bilateral salpingo-oophorectomy for FIGO stage III-IVA AEC diagnosed in 2004-2012 were identified in the National Cancer Data Base. Multilevel modeling was used to identify covariates associated with treatment selection. OS was compared using Kaplan-Meier estimates, the log-rank test, Cox proportional hazards regression, and propensity score matching. RESULTS: We identified 9837 patients, of whom 6358 (65%) received CT and 3479 (35%) received CRT. Median follow-up was 59.6months. OS was higher in patients receiving CRT compared to CT (70% v 55% at 5years, log-rank P<0.001). Controlling for stage, histologic grade, tumor size, age, comorbidity and race, CRT remained independently associated with improved OS (HR 0.63, 95% CI 0.57-0.70, P<0.001). When stratified by stage and histologic grade, there was a significant OS benefit for stage IIIA, IIIB, IIIC, grade 2, and grade 3 (all P<0.001), a trend for stage IVA (P=0.06), but no benefit for grade 1 (P=0.91). On multivariable subgroup analyses, these findings persisted, including lack of benefit in grade 1 patients (HR 0.72, P=0.14). These results were further confirmed after propensity score matching. CONCLUSIONS: Adjuvant CRT for AEC was associated with improved OS, except for patients with well-differentiated disease, who fared equally well with CT alone.

Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base.

BACKGROUND: The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness. METHODS: Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base. Overall survival (OS) was compared for CT and CRT groups with Cox regression and propensity score matching. Subset analyses by clinicopathologic characteristics were performed. RESULTS: This study identified 6165 patients treated with CT (n = 2334 or 38%) or CRT (n = 3831 or 62%). Most were classified as pT3 (72%), pN1 (67%), and status-post R0 resection (84%). For CRT patients, the median radiotherapy dose was 50.4 Gy. Compared with CT, CRT was associated with improved OS in a univariate analysis (median, 20.0 vs 22.3 months; at 5 years, 16.5% vs 19.6%; P < .001) and a multivariate analysis (hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.837-0.953; P = .001). CRT remained associated with improved OS after propensity score matching (HR, 0.851; 95% CI, 0.793-0.913; P < .001). Subset analyses showed that CRT was associated with improved OS among patients with pT3 (HR, 0.892; 95% CI, 0.828-0.962; P = .003) or pN1 disease (HR, 0.856; 95% CI, 0.793-0.924; P < .001) and both R0 resection (HR, 0.901; 95% CI, 0.839-0.969; P = .005) and R1 resection (HR, 0.842; 95% CI, 0.722-0.983; P = .030). CONCLUSIONS: CRT was independently associated with improved OS after the resection of pancreatic adenocarcinoma in a large national cohort and particularly among patients with R1 resection and pN1 disease. Well-designed randomized comparisons of CRT and CT are urgently needed.

The evolving role of adjuvant radiotherapy for elderly women with early-stage breast cancer.

BACKGROUND: Elderly patients with early-stage breast cancer (ESBC) derive a local control benefit from radiotherapy (RT) after lumpectomy, without any apparent effect on overall survival. Therefore, the use of RT is controversial. In the current study, the authors characterized updated trends in RT for elderly patients with estrogen receptor (ER)-positive ESBC. METHODS: Patients aged ≥70 years with ER-positive ESBC measuring ≤2 cm after lumpectomy with negative resection margins and known RT details were identified in the National Cancer Data Base. Patients were classified by year of diagnosis and segregated into 3 groups relative to the initial publication and updated presentation of the Cancer and Leukemia Group B (CALGB) 9343 trial. RT use overall, prescription of hypofractionated RT, and use of boost RT were compared between groups using logistic regression analysis, and the influence of clinicopathologic covariates was determined with multivariable logistic regression analysis. RESULTS: A total of 122,796 elderly patients with ER-positive ESBC who were diagnosed between 1998 and 2011 were identified. Overall, 84,649 patients (68.9%) received adjuvant RT, with a decline observed between successive cohorts (71.3% in the pre-initial publication cohort, 69.5% in the pre-update cohort, and 64.7% in the post-update cohort; P <.001). Hypofractionated RT use increased among treated patients over time (P<.001). Boost RT was used in 67.5% of patients, with a decline noted between the pre-update and post-update cohorts (68.7% vs 57.7%; P<.001). Overall RT use as well as use of boost RT were found to be lower among older patients and those with lower-grade or smaller tumors (P<.001), whereas hypofractionated RT was used more commonly in these groups (P<.001). CONCLUSIONS: RT use appears to have declined in elderly patients with ER-positive ESBC, a finding that is reflective of evidence-based practice integrating mature trial data. Further research is needed to develop tools to aid in the decision-making process regarding the delivery or avoidance of RT in this setting.

Growing Use of Mastectomy for Ductal Carcinoma-In Situ of the Breast Among Young Women in the United States.

BACKGROUND: Ductal carcinoma-in situ (DCIS) is a preinvasive form of breast cancer associated with excellent outcomes after either mastectomy or breast conservation therapy. Previous studies have demonstrated declining rates of mastectomy. However, it is unclear how this pattern has changed in recent years. METHODS: Women with DCIS were identified within the National Cancer Data Base. Patients treated with lumpectomy with or without radiotherapy were compared to women treated with mastectomy on the basis of demographic, clinicopathologic, and reporting facility details using χ (2) tests and multivariable logistic regression modeling to identify factors that may influence surgical choice. Changes in the proportion of women receiving contralateral prophylactic mastectomy (CPM) were assessed in a similar fashion. RESULTS: We identified 212,936 women diagnosed with DCIS between 1998 and 2011. Lumpectomy was performed in 68 % (144,681) of patients. Mastectomy rates initially declined from 1998 (36 %) through 2004 (28 %), before increasing again through 2011 (33 %). Younger patient age, greater medical comorbidity, more extensive disease, higher tumor grade, treatment at an academic facility, and greater distance from the reporting facility were associated with heightened use of mastectomy (all p < 0.001). CPM also increased over time, particularly among younger patients, on multivariate analysis (p < 0.001). CONCLUSIONS: Mastectomy utilization appears to be rising between 2004 and 2011, particularly among younger patients and those with higher-risk histopathologic features. CPM is increasing in a similar fashion. Further research is needed to understand the drivers of this change.

Engineering Yarrowia lipolytica for production of medium-chain fatty acids.

Lipids are naturally derived products that offer an attractive, renewable alternative to petroleum-based hydrocarbons. While naturally produced long-chain fatty acids can replace some petroleum analogs, medium-chain fatty acid would more closely match the desired physical and chemical properties of currently employed petroleum products. In this study, we engineered Yarrowia lipolytica, an oleaginous yeast that naturally produces lipids at high titers, to produce medium-chain fatty acids. Five different acyl-acyl carrier protein (ACP) thioesterases with specificity for medium-chain acyl-ACP molecules were expressed in Y. lipolytica, resulting in formation of either decanoic or octanoic acid. These novel fatty acid products were found to comprise up to 40 % of the total cell lipids. Furthermore, the reduction in chain length resulted in a twofold increase in specific lipid productivity in these engineered strains. The medium-chain fatty acids were found to be incorporated into all lipid classes.

Improved cellobiose utilization in E. coli by including both hydrolysis and phosphorolysis mechanisms.

Cellobiose is a major intermediate from cellulase hydrolysis of pretreated plant biomass. Engineering biocatalysts for direct use of cellobiose could eliminate the need for exogenous ß-glucosidase. Additionally, rapid removal of cellobiose in a simultaneous saccharification and fermentation facilitates enzymatic hydrolysis as cellobiose is a potent inhibitor for cellulases. We report here improved cellobiose utilization by engineering Escherichia coli to assimilate the disaccharide both hydrolytically and phosphorolytically (shorter fermentation time). Additionally, we demonstrate that engineering intracellular cellobiose utilization circumvents catabolite repression allowing simultaneous fermentation of xylose and cellobiose. Using meso-2,3-butanediol as model product, we further demonstrate that the accelerated carbon metabolism led to improved product formation (higher titers and shorter fermentation times), illustrating the utility of the engineered biocatalysts in biorefinery applications.

Periplasmic expression of a Saccharophagus cellodextrinase enables E. coli to ferment cellodextrin.

Metabolic engineering has been successful in generating highly efficient Escherichia coli catalysts for production of biofuels and other useful products. However, most of these engineered biocatalysts are only effective when glucose is used as the starting substrate. Strategies to overcome this limitation in the past almost exclusively relied on extracellular secretion or surface display of a ß-glucosidase. We show here, for the first time, a periplasmic expression of a Sacchrophagus degradans cellodextrinase (Ced3A) as a successful strategy to enable E. coli to use cellodextrin. The engineered strain was able to grow with cellodextrin as sole carbon source. Additionally, we show that penetration of cellodextrin into periplasmic space was enhanced by using a mutant with leaky outer membrane. Furthermore, we demonstrate that the catalyst can efficiently ferment cellodextrin to lactic acid with about 80 % yield. The ability of a biocatalyst to use cellodextrin should make it useful in consolidated bioprocessing of cellulose.

Implementation Strategies to Increase Clinical Trial Enrollment in a Community-Academic Partnership and Impact on Hispanic Representation: An Interrupted Time Series Analysis.

PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

Factors impacting volumetric white matter changes following whole brain radiation therapy.

Whole brain radiation therapy (WBRT) is one of the most effective modalities for treatment of brain metastases. With increasing cancer control there is growing concern regarding the long-term effects of treatment. These effects are seen as white matter change (WMC) on brain MRI. Severity of WMC is implicated in cognitive and functional decline in many patient groups. Our objective was to identify clinical factors associated with greater accumulation of WMC following WBRT. Through retrospective review of serial MRIs obtained from 30 patients surviving greater than 1 year after WBRT, treated at a single institution between 2002 and 2007, we calculated volumetric WMC over time using segmentation software. Changes related to tumor, secondary effects, surgery or radiosurgery were excluded. Factors that influenced the rate of WMC accumulation were identified through multivariate analysis. Following WBRT, patients accumulated WMC at an average rate of 0.07% of total brain volume per month. In multivariate analyses, greater rates of accumulation were independently associated with older age (ß = 0.004, p < .0001), poor levels of glycemic control (ß = 0.048, p < .0001) and hypertension diagnosis (ß = 0.084, p < .0001). Long-term survivors of cancer allow assessment of late effects of treatment modalities. Radiation injury appears to be related to a steady rate of white matter damage over time, as indicated by progressive accumulation of WMC. Our results suggest that rate of WMC accumulation is enhanced by parameters such as hyperglycemia and hypertension. This has significant clinical impact by clearly identifying hyperglycemia, steroid-induced hyperglycemia, and other vascular risk factors as targets for intervention to decrease WMC in patients receiving WBRT.

Linear accelerator-based single-fraction stereotactic radiosurgery versus hypofractionated stereotactic radiotherapy for intact and resected brain metastases up to 3 cm: A multi-institutional retrospective analysis.

INTRODUCTION: Single-fraction stereotactic radiosurgery (SF-SRS) is typically used to provide local control of brain metastases. Recently, hypofractionated stereotactic radiotherapy (HF-SRT) has been utilized for large brain metastases. Data comparing these two modalities are limited for brain metastases ≤3 cm. METHODS: Patients with brain metastases receiving linear accelerator-based SF-SRS or HF-SRT were identified at three institutions. Local progression-free survival (LPFS), intracranial progression-free survival (ICPFS), overall survival (OS), and radionecrosis-free survival (RNFS) were determined from time of treatment. RESULTS: 108 patients (76 intact, 32 resected) with 184 brain metastases (142 intact, 42 resected) were included. There were no significant differences between SF-SRS and HF-SRT for intact metastases in 1-year LPFS (62.8% vs. 58.5%, p=0.631), ICPFS (56.9% vs. 55.3%, p=0.300), and OS (71.6% vs. 70.6%, p=0.096), or for resected metastases in 1-year LPFS (67.3% vs. 57.8%, p=0.288), ICPFS (64.8% vs. 57%, p=0.291), and OS (64.8% vs. 66.1%, p=0.603). There were also no significant differences in 1-year RNFS between SF-SRS and HF-SRT (92% vs. 92%, p=0.325). CONCLUSIONS: There were no significant differences in LPFS, ICPFS, OS, and RNFS between SF-SRS and HF-SRT for brain metastases ≤3 cm suggesting SF-SRS may be preferred due to similar outcomes and reduced number of fractions.

Impact of Health Insurance Status on Prostate Cancer Treatment Modality Selection in the United States.

OBJECTIVES: A variety of treatment modalities are available for the management of clinically localized prostate cancer in the United States. In addition to clinical factors, treatment modality choice may be influenced by a patient's insurance status. Using a national data set, we investigated the relationship between insurance status and prostate cancer treatment modality selection among nonelderly men in the United States. METHODS: Nonelderly men age 18 to 64 years treated for localized prostate cancer from 2010 to 2014 were identified within the National Cancer Database. Patients with no insurance, Medicaid, or private insurance were included. The χ and multivariable logistic regression analyses were used to evaluate the association of insurance status, other demographic and facility factors, and D'Amico risk classification with treatment modality. RESULTS: We identified 135,937 patients with either no insurance (2.8%), Medicaid (4.2%), or private insurance (92.9%) treated for prostate cancer who underwent cancer-directed treatment or active surveillance between 2010 and 2014. Patients with private insurance were more likely to receive minimally invasive surgery (61.4% vs. 35.4%, respectively; P<0.001) and less likely to receive external beam radiotherapy (10.9% vs. 26.9%, respectively; P<0.001) than patients with no insurance. On multivariable analysis, among patients with no insurance and private insurance, private insurance was the strongest predictor of receipt of minimally invasive surgery (adjusted odds ratio, 2.61; 95% confidence interval, 2.44-2.79; P<0.001). CONCLUSION: Insurance status is a strong predictor of prostate cancer treatment modality among nonelderly men in the United States.

Chemoradiation after FOLFIRINOX for borderline resectable or locally advanced pancreatic cancer.

BACKGROUND: The safety and efficacy of FOLFIRINOX (FX) followed by consolidative chemoradiation (CRT) in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) has not been extensively studied. We sought to evaluate outcomes and toxicities of this regimen. METHODS: A retrospective review was performed of 33 patients with BRPC or LAPC treated with FX followed by CRT. Radiotherapy was directed at the primary tumor and any involved nodes (84.8% received 50-50.4 Gy with standard fractionation and concurrent capecitabine, while 15.2% of patients received 36 Gy in 15 fractions with weekly gemcitabine). Toxicities of FX and CRT were graded using Common Terminology Criteria for Adverse Events (CTCAE v4.0), and radiographic response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). Overall survival (OS), distant metastasis-free survival (DMFS), and local control (LC) were calculated using Kaplan-Meier analyses, and a Cox proportional hazards model was used to assess the impact of clinicopathologic factors on OS. RESULTS: Median follow-up was 19.9 months and patients received a median of 6.4 months of chemotherapy (range, 2.2-12.0 months). There were more T4 tumors than T3 tumors (70% vs. 30%). Grade ≥3 toxicities were low, including fatigue (9.1%), diarrhea (6.1%), neuropathy (6.1%), and dehydration (6.1%). R0 surgical resection was achieved in 5 patients (15.2%) after CRT. Median OS was 22.0 months (91% at 1 year and 45% at 2 years). Median DMFS was 17.8 months (69% at 1 year and 35% at 2 years). LC was 84% at 1 year and 55% at 2 years. CONCLUSIONS: OS is promising with the use of FX in BRPC and LAPC, and consolidative CRT was well tolerated in this cohort. Therefore, the role of radiation after multi-agent chemotherapy should be further evaluated in prospective trials.

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

BACKGROUND: The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN+ disease stratified by margin status. METHODS: We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. RESULTS: Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. CONCLUSIONS: Among cT1-2 N0 pN+ esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results.

Post-operative radiotherapy is associated with improved survival in esophageal cancer with positive surgical margins.

BACKGROUND: The optimal treatment for early-stage esophageal cancer with positive surgical margins after an upfront esophagectomy is not well-defined. This study investigates the effect of post-operative radiotherapy (PORT) on overall survival (OS) in clinical stage I-II patients with positive margins. METHODS: We identified patients diagnosed between 2004 and 2012 with clinical stage I-II esophageal carcinoma from the National Cancer Data Base (NCDB) who underwent an upfront esophagectomy. For those patients with positive margins, administration of PORT was recorded, and OS was compared by the Kaplan-Meier estimator and log-rank test. Multivariable Cox regression analysis was performed to identify variables associated with improved survival. RESULTS: Among the 3,490 patients identified, 209 (5.8%) had positive margins. One hundred forty-two (67.9%) patients did not receive PORT while 67 (32.1%) did receive PORT. Compared to those receiving PORT, patients who did not receive PORT were significantly older (68.5 vs. 64.0 years, P=0.003), more likely to have pN0 disease (50.7% vs. 35.4%, P=0.026), and less likely to receive postoperative chemotherapy (21.1% vs. 86.6%, P<0.001). On multivariable logistic regression, only receipt of chemotherapy predicted for receipt of PORT (OR: 25.6, 95% CI: 9.9-65.8, P<0.001). OS was significantly higher for patients receiving PORT compared to those who did not (median OS: 32.2 vs. 16.9 months, log-rank P=0.008). Multivariable analysis confirmed an association with PORT and improved OS (HR: 0.39, 95% CI: 0.27-0.60, P<0.001). Subset analysis demonstrated that the OS benefit of PORT persisted in those patients who received adjuvant chemotherapy (HR: 0.33, 95% CI: 0.19-0.57, P<0.001). CONCLUSIONS: PORT is associated with improved OS in clinical stage I-II esophageal cancer patients after an upfront esophagectomy with positive margins. In the absence of prospective randomized data, our findings suggest that PORT should be strongly considered in the setting of early-stage esophageal cancer resected with positive margins.

Patterns of care and outcomes for use of concurrent chemoradiotherapy over radiotherapy alone for anaplastic gliomas.

BACKGROUND AND PURPOSE: The role of concurrent chemoradiotherapy (CRT) for anaplastic gliomas is undefined and patterns of care are under-reported. To address the knowledge gap, we examined use of CRT for grade III gliomas compared to radiotherapy (RT) alone. MATERIAL AND METHODS: In an observational study design cohort from the National Cancer Database, we identified 4437 adult patients receiving surgery followed by either CRT or RT for supratentorial anaplastic glioma in 2003-2011. Univariable and multivariable logistic regression analyses were used to assess factors associated with use of CRT. Overall survival (OS) was assessed by the Kaplan-Meier analysis with log-rank tests, Cox proportional hazards regression modeling, and propensity score matching. RESULTS: Receipt of CRT (vs. RT) was associated with recent year of diagnosis (OR for 2011 (vs. 2003) 3.36, 95% CI 2.49-4.54) and having astrocytoma (vs. oligodendroglioma) (OR 1.37, 95% CI 1.15-1.63). Patients receiving CRT had a lower adjusted hazard of death (hazard ratio 0.72, 95% CI 0.65-0.79). Outcomes were worse for patients ≥60 (HR 6.94, 95% CI 6.09-7.91) and astrocytomas (HR 2.08, 95% CI 1.85-2.34). CONCLUSION: Use of concurrent CRT is associated with more recent year of diagnosis and improved survival relative to RT alone.