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Background Neoadjuvant chemoradiation (nCRT) followed by esophagectomy is the standard treatment for locally advanced esophageal cancer. Older patients are often felt to be poor candidates for nCRT. Limited data is available to guide the use of nCRT in this population. Methods A retrospective review of patients treated at a tertiary cancer center between 2002 and 2014 was conducted grouping patients by age (≥ 65 or Results 125 patients were identified for this study (67 aging Conclusions Older patients who underwent nCRT followed by esophagectomy had similar toxicities and outcomes as younger patients suggesting that nCRT before esophagectomy is safe in select older adults with esophageal cancer. PLR and NLR may serve as prognostic markers of aging, toxicity, and outcomes. Further research is warranted to optimize the therapy of older patients with this disease.

Background: Patients with esophageal cancer (EC) have high rates of malnutrition due to tumor location and treatment-related toxicity. Various strategies are used to improve nutritional status in patients with EC including oral and enteral support. Methods: We conducted a retrospective analysis to determine the impact of malnutrition and prophylactic feeding jejunostomy tube (FJT) placement on toxicity and outcomes in patients with localized EC who were treated with neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy. Results: We identified 125 patients who were treated with nCRT between 2002 and 2014. Weight loss and hypoalbuminemia occurred frequently during nCRT and were associated with multiple adverse toxicity outcomes including hematologic toxicity, nonhematologic toxicity, grade &ge, 3 toxicity, and hospitalizations. After adjusting for relevant covariates including the specific nCRT chemotherapy regimen received and the onset of toxicity, there were no significant associations between hypoalbuminemia, weight loss, or FJT placement and relapse-free survival (RFS) or overall survival (OS). FJT placement was associated with less weight loss during nCRT (p = 0.003) but was not associated with reduced toxicity or improved survival. Conclusions: Weight and albumin loss during nCRT for EC are important factors relating to treatment toxicity but not RFS or OS. While pretreatment FJT placement may reduce weight loss, it may not impact treatment tolerance or survival.

Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (−SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with −SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p

OBJECTIVE The objective of this study was to characterize patients at an increased risk of distant metastasis (DM) following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS We identified patients undergoing SBRT for stage I NSCLC between 2005 and 2016. Patients with a prior lung cancer diagnosis, receiving a biological effective dose

Purpose Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity. Methods and Materials The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer–specific survival, and distant metastasis–free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding. Results The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P Conclusions To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.

Freedom from biochemical failure (FFBF) is a common primary outcome of randomized-controlled trials of prostate cancer (PCa). We aimed to determine how increasing the PCa biologically equivalent dose (BED) of external radiation therapy (RT) is correlated with FFBF and overall patient outcomes: overall survival (OS), distant metastasis (DM), and cancer-specific mortality (CSM); as well as genitourinary (GU), and gastrointestinal toxicities. We performed a meta-analysis of 6884 PCa patients from 12 randomized-controlled trials of external beam RT. Mixed effects regression models were used to estimate weighted linear relationships between BED and observed percentages of 5- and 10-year outcomes. For toxicities, a subset analysis of using 3-dimensional conformal RT (3D-CRT) versus intensity-modulated RT (IMRT) was performed. Increasing BED correlated with improved FFBF: 10-year absolute improvement of 9.6% and 7.2% for low-risk and intermediate-risk patients, respectively (P

BackgroundThe long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons.ObjectiveTo compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP.Design, setting, participantsRetrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy.Outcome measurements and statistical analysisKaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS).Results and limitationsThe median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p

Lung cancer is the leading cause of cancer death worldwide. Majority of newly diagnosed lung cancers are non-small cell lung cancer (NSCLC), of which up to half are considered locally advanced at the time of diagnosis. Patients with locally advanced stage III NSCLC consists of a heterogeneous population, making management for these patients complex. Surgery has long been the preferred local treatment for patients with resectable disease. For select patients, multi-modality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone. For patients with unresectable disease, concurrent chemoradiation is the preferred treatment. More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life. The array of treatment approaches for locally advanced NSCLC is large and constantly evolving. An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage III NSCLC patients are presented.

There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy.We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χA total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P.001), 10 Gy (P.001), 20 Gy (V20; P.001), and 30 Gy (P.001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP.Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning.

The purpose of the study was to identify the effect of final surgical margin (SM) status and re-excision on outcomes in patients with ductal carcinoma in situ (DCIS) who underwent breast conservation therapy (BCT).The study population consisted of women diagnosed with DCIS who underwent BCT between 1989 and 2014. All women received adjuvant whole breast radiation and a boost. The primary end point was local control (LC). Final SMs were defined according to margin width: negative SM was defined as2 mm, close SM was defined as0 to ≤ 2 mm, and a positive SM was defined as tumor on ink. The Cox proportional hazards model was used to determine predictors of outcomes on multivariable analysis. Actuarial incidence of LC was estimated using the Kaplan-Meier method.A total of 498 patients were included; 400 patients had a final negative SM, 87 had a close SM, and 11 had a positive SM. A total of 172 patients received adjuvant hormonal therapy, 265 patients required ≥ 1 re-excision. Patients with positive or close SMs were more likely to receive a radiation dose60 Gy (P .001) and undergo re-excision (P .01). The 10-year LC rates were not significantly different between patients with a negative (93.5%), close (91.8%), or positive (100%) SM (P = .57). There was no difference in LC in patients who underwent re-excision for initial close or positive SMs (P = .55).This single-institution experience showed that risks of local recurrence remain poorly characterized. Re-excision and whole breast radiation with boost resulted in excellent LC for women with DCIS. Trials aimed at personalized deintensified local therapy are warranted.

Purpose This study was undertaken to identify parameters associated with hematologic toxicity or chemotherapy dose modification in patients undergoing concurrent chemoradiation (CRT) with gemcitabine for localized pancreatic cancer. Methods and materials We reviewed patients with localized pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of nongemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. The T11-L3 vertebrae were contoured as bone marrow region at risk. Linear and logistic regression models were used to test associations between dosimetric parameters and gemcitabine dose modification or hematologic toxicity during or within 3 months following CRT. Receiver operator curves were generated to identify threshold doses for hematologic toxicity. Results Forty-nine patients were included. During CRT, the maximum thoracolumbar dose was associated with grade 2+ neutropenia during CRT ( P = .017) and the volume receiving 5 Gy (V5) was associated with grade 2+ leukopenia ( P = .041). Post-CRT, thoracolumbar mean dose ( P = .015), V5 ( P = .01), and V10 ( P = .012) were associated with increased grade 2+ neutropenia. On multivariable analysis, the thoracolumbar maximum dose ( P = .045) and V5 ( P = .045) were associated with grade 2+ neutropenia and grade 2+ leukopenia during CRT, respectively. Post-CRT, the mean dose ( P = .046), V5 ( P = .019), and V10 ( P = .037) were associated with increased grade 2+ neutropenia. A maximum dose of 48.02 Gy and V5 of 57.6% were identified as predictors of toxicity during CRT. A V5 of 56.6%, V10 of 47.05%, and mean dose of 11.67 Gy were identified as predictors of post-CRT hematologic toxicity. Post-CRT, there was a trend toward increased dose modifications with increased V5 ( P = .065). Conclusions In our dataset, the thoracolumbar mean dose, maximum dose, V5, and V10 correlated with hematologic toxicity during CRT and post-CRT in patients with localized pancreatic cancer. Because of the high rates of distant failure and importance of systemic therapy in these patients, this may be an important consideration during treatment planning.

Our study sought to characterize the presentation, local management and outcomes of invasive cervical cancer with regard to patient insurance status.We queried the NCI-SEER database for invasive cervical cancer cases in patients aged 18-64 from 2007 to 2011. We analyzed clinical and socioeconomic data with regard insurance status (insured, Medicaid, or uninsured). We tested for associations between patient insurance status and treatment with definitive surgery for FIGO IA2-IB1 patients, and treatment with suboptimal radiation therapy (RT) for FIGO IB2-IVA patients (other than combination external beam and brachytherapy). We evaluated overall and cause specific survival according to insurance status.11,714 cases were analyzed: 60% insured, 31% Medicaid, and 9% uninsured. FIGO III/IV stage at presentation was more frequent with Medicaid (40%) and uninsured (42%) compared to insured patients (28%) (p0.001). For FIGO IA2-IB1 patients, receipt of definitive surgery was inversely associated with uninsured status (OR [95%CI]=0.65 [0.47-0.90], p0.001) in univariable analysis; however the relationship lost significance after multivariable adjustment. For FIGO IB2-IVA patients, the use of suboptimal RT was associated with uninsured status (OR [95%CI]=1.33 [1.07-1.65], p=0.011) in adjusted analyses. Among all patients, overall mortality was increased with Medicaid (HR [95%CI]=1.16 [1.05-1.28], p=0.003) and uninsured status (HR [95%CI]=1.17 [1.01-1.34], p=0.031) in multivariable analysis. Cancer specific mortality survival trended towards significance in multivariable analyses for both Medicaid (HR [95%CI]=1.11 [1.00-1.24] and uninsured status (HR [95%CI]=1.14 [0.98-1.33]).Disparities in cervical cancer treatment with regard to insurance status are apparent in a recent cohort of American patients. Later stage at presentation and differences in management partially account for the inferior prognostic outcomes associated with Medicaid and uninsured status.

We used an electronic survey to quantify knowledge about radiation therapy among first and fourth year medical students, and primary care physician attendings (PCPs) at 7 academic US hospitals. We found that, although medical knowledge of radiation therapy principles improves from first to fourth years, large knowledge gaps still exist between students, PCPs, and radiation oncology attendings. Basic misconceptions persist among a minority of students and PCPs. PURPOSE: The purposes are: (1) to assess the exposure that medical students (MSs) have to radiation oncology (RO) during the course of their medical school career, as evidenced by two time points in current medical training (i.e. 1st vs. 4th year; MS1s and MS4s, respectively); and, (2) to assess the knowledge of MS1s, MS4s, and primary care physicians (PCPs) about the appropriateness of RT in cancer management as compared to RO attendings. METHODS: We developed and beta tested an electronic survey, divided into 3 parts: (1) RO job descriptions, (2) appropriateness of RT, and (3) toxicities of RT. Surveys were distributed to 7 US medical schools. A concordance of >90% (either “yes” or “no”) among RO attendings in an answer was necessary to determine the “correct” answer; and to compare to other subgroups using a chi-squared test (p < 0.05 was significant). RESULTS: The overall response rate for ROs, MS1s, MS4s, and PCPs was 26%; n: (22 + 315 + 404 + 43)/3,004. RT misconceptions decreased with increasing level of training. More than 1 of 10 MSs did not believe RT alone could cure cancer. Emergent oncologic conditions for RT (e.g. spinal cord compression, superior vena cava syndrome) could not be identified by > 1 of 5 respondents. Multiple non-toxicities of RT (e.g. emitting low-level radiation from the treatment site), were incorrectly identified as toxicities by > 1 of 5 respondents. MS4s/PCPs with an RO rotation in medical school had improved scores in all prompts. CONCLUSIONS: Although MS knowledge of general RT principles improves from 1st to 4th year, a large knowledge gap still exists between MSs, current PCPs, and ROs. Some basic misconceptions of RT persist among a minority of MSs and PCPs. We recommend implementing formal education in RO fundamentals during the core curriculum of medical school.

BACKGROUND. Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. MATERIALS AND METHODS. We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher’s exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. RESULTS. A total of 132 patients met the inclusion criteria with a median age of 62 (range 36–80) and median follow-up of 28 months (range 4–128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p = 0.01) and close/positive margins (p13 LN evaluated (p = 0.003). Distant recurrence was correlated with higher pathologic nodal stage (p

Background and Objectives To identify the impact of the interval between chemoradiation to surgery on morbidity and mortality in patients undergoing tri-modality therapy for esophageal cancer. Methods Eighty-five patients completed chemoradiation followed by esophagectomy between 2006 and 2011. The interval between completion of chemoradiation and surgery was calculated for each patient. We evaluated the association of quartiles and 3-week groups with morbidity and mortality using logistic regression. Other treatment and clinical factors were also assessed. Results A total of 59 patients(69%) experienced at least one complication. When examining specific complications, patients with pulmonary complications had a longer mean time interval from chemoradiation to surgery (P = 0.02). Linear regression showed an association between longer interval between chemoradiation to surgery and hospital length of stay (LOS) >14 days when analyzing by both interval quartile (P = 0.04) and 3-week intervals (P = 0.04). On multivariable analysis, increased time interval predicted for pulmonary complications (P 14 days (P = 0.03). When examining other treatment factors, squamous cell histology (P = 0.02) also predicted for a hospital length of stay >14 days. Conclusions Factors such as interval between completion of chemoradiation and surgery and squamous cell histology may be associated with surgical morbidity. Further data is warranted to confirm these findings. J. Surg. Oncol. 2015;112:629–633. © 2015 Wiley Periodicals, Inc.

Purpose Patients with pancreatic adenocarcinoma (PAC) are often treated with neoadjuvant chemoradiation (NACRT) in hopes of downstaging their disease for potential surgical resection. We hypothesized that increasing the radiation dose to the area of the tumor abutting the vessel(s) of concern would increase the rate of surgical resection in patients with borderline resectable PAC (BRPAC) and locally advanced PAC (LAPAC) treated with NACRT. Methods and materials We retrospectively reviewed consecutive cases of BRPAC and LAPAC treated with NACRT from January 2006 to December 2013, with or without a vessel boost (VB), at a single institution. The primary endpoints were rate of R0/R1 potentially curative surgical resection and acute toxicity. Univariate analysis with the Fisher exact test was performed to evaluate the effect of each variable. Multiple logistic regression was used to adjust for the following covariates: year of diagnosis, age, sex, carbohydrate antigen 19-9 (CA19-9) level at diagnosis, and BRPAC or LAPAC. Results Of the 104 patients identified, 22% (n = 23) received a VB (median, 54 Gy; range, 54-64 Gy), and 78% (n = 81) received no boost (median, 50.4 Gy; range, 48.6-52.2 Gy). More patients in the VB group were treated from 2010 to 2013 ( P P = .002). Other baseline characteristics were balanced. After adjustment for covariates, there was a statistical trend toward increased surgical resection in patients who received a VB (odds ratio [OR], 2.77; 95% confidence interval [CI], 0.89-8.57; P = .077). Age (≥70 years; OR, 0.42; 95% CI, 0.16-1.05; P = .064) and LAPAC (OR, 0.32; 95% CI, 0.09-1.09; P = .068) also trended toward significance. CA19-9 ≥47.9 U/mL (OR, 0.24; 95% CI, 0.08-0.71; P = .010) was significant on multivariate analysis. There was no significant difference in acute or late toxicity between groups. Conclusions In our retrospective series, dose escalation was associated with an improved surgical resection rate in BRPAC and LAPAC patients treated with NACRT, although this improvement was not statistically significant.

Purpose To determine whether computed tomography/magnetic resonance imaging–based day 0 (d0) dosimetry is a meaningful predictor of day 21 (d21) dosimetry in low-dose-rate brachytherapy for localized prostate cancer. Methods and Materials The study population consisted of 277 men with localized (T1-2 N0 M0), low-/intermediate-risk prostate cancer treated with low-dose-rate brachytherapy. Computed tomography/magnetic resonance imaging fusion was used for postimplant dosimetry at d0 and d21. Logistic regression was used to construct receiver operating characteristic curves for achieving each constraint at d21, based on d0 D90 and V100, and Youden’s index was used to evaluate cutpoints. Freedom from biochemical failure (FBCF) was estimated with the Kaplan-Meier method. Results The median d0 D90 increased from 133 to 150 Gy at d21, and median d0 V100 increased from 87% to 91%. For achieving the D90 constraint at d21, the optimal cut-point for d0 D90 was 135 Gy, with 84% of these patients maintaining a d21 D90 > 145 Gy. For achieving the D90 constraint at d21, the optimal cut-point for d0 V100 was 87%, with 83% of these patients maintained a d21 V100 > 90%. There was no improvement in FBCF in patients with a d0 D90 > 135 Gy or D90 > 145 Gy. Similarly, there was no improvement in FBCF in patients with a d0 V100 > 87% or V100 > 90%. Conclusions Meeting dosimetric constraints on d0 does not obviate d21 dosimetric analysis. Constraints used for dose prescriptions on d0 are not the ideal predictors of d21 dosimetry.

Multifocal and multicentric breast cancers have been correlated with poor prognostic factors and worse outcomes versus unifocal disease. We evaluated the impact of multifocal and multicentric disease versus case controls with unifocal disease, matching for age, grade, T-, and N-stage. A total of 110 patients with multifocal (n = 93) or multicentric (n = 17) disease and 263 matched case controls were identified with a median follow-up of 53 months and 64 months, respectively. The actuarial local control rates for the multifocal/multicentric and unifocal group were 88% and 97%, respectively at both 5 and 10 years (p < 0.001). On multivariate analysis, multifocal/multicentric disease remained associated with higher local recurrence after controlling for other covariates including surgery type. The disease-free survival rates in the multifocal/multicentric group at 5 and 10 years were 75% and 71%, respectively, versus 87% and 78% at 10 years (p = 0.01). On multivariate analysis, multifocal/multicentric disease was no longer associated with worse disease-free survival. There was no difference in the cohorts in terms of regional control, overall survival, or cancer specific survival. Our findings suggest that multifocal/multicentric disease may be associated with worse outcomes versus unifocal disease regardless of type of surgery. This suggests a more biologically aggressive cancer and may be an important consideration when managing these patients. Further studies are needed to better understand the impact of multifocal/multicentric breast cancers on outcomes.

Stereotactic body radiotherapy is the preferred treatment modality for patients with inoperable early stage lung cancer. Chest wall toxicity is a potentially dose limiting side effect and may include fractures or pain secondary to treatment. The pathophysiology of these symptoms is unclear although it is presumed that radiation may alter the bone's normal tissue environment, affecting maintenance and remodeling. Chest wall pain is likely neuropathic secondary to injury to the intercostal nerves. Identifying patients with chest wall toxicity can be difficult due to the varying definitions of toxicity as well as heterogeneous contouring guidelines. Multiple studies have demonstrated a correlation between treatment factors and the incidence of chest wall toxicity. An increase in dose and treatment volume appear to be the most consistent radiation factors associated with toxicity. Patient factors such as body mass index, female gender, tumor location, and age have also been correlated with an increased likelihood of developing side effects. Management of chest wall toxicity is typically conservative using analgesic medications although surgical intervention may be required for displaced fractures. In this review, we examine the treatment, patient, and tumor factors predictive for chest wall toxicity and the implications for the treating physician.

Mismatch repair (MMR) deficiency of DNA has been observed in up to 15% of sporadic colorectal cancers (CRCs) and is a characteristic feature of Lynch syndrome, which has a higher incidence in young adults (age,50 years) with CRC. Mismatch repair deficiency can be due to germline mutations or epigenetic inactivation, affects prognosis and response to systemic therapy, and results in unrepaired repetitive DNA sequences, which increases the risk of multiple malignant tumors.To evaluate the utilization of MMR deficiency testing in adults with CRC and analyze nonadherence to long-standing testing guidelines in younger adults using a contemporary national data set to help identify potential risk factors for nonadherence to newly implemented universal testing guidelines.Adult (age,30 to ≥70 years) and, of these, younger adult (30 to 49 years) patients with invasive colorectal adenocarcinoma diagnosed between 2010 and 2012 and known MMR deficiency testing status were identified using the National Cancer Database. The study was conducted from March 16, 2016, to March 1, 2017.Patient sociodemographic, facility, tumor, and treatment characteristics.The primary outcome of interest was receipt of MMR deficiency testing. Multivariable logistic regression was used to identify independent predictors of testing in adult and/or young adult patients.A total of 152 993 adults with CRC were included in the study (78 579 [51.4%] men; mean [SD] age, 66.9 [13.9] years). Of these patients, only 43 143 (28.2%) underwent MMR deficiency testing; the proportion of patients tested increased between 2010 and 2012 (22.3% vs 33.1%; P.001). Among 17 218 younger adult patients with CRC, only 7422 (43.1%) underwent MMR deficiency testing; the proportion tested increased between 2010 and 2012 (36.1% vs 48.0%; P .001). Irrespective of age, higher educational level (OR, 1.38; 95% CI, 1.15-1.66), later diagnosis year (OR, 1.81; 95% CI, 1.65-1.98), early stage disease (OR, 1.24; 95% CI, 1.18-1.30), and number of regional lymph nodes examined (≥12) (OR, 1.44; 95% CI, 1.34-1.55) were independently associated with MMR deficiency testing, whereas older age (OR, 0.31; 95% CI, 0.26-0.37); Medicare (OR, 0.89; 95% CI, 0.84-0.95), Medicaid (OR, 0.83; 95% CI, 0.73-0.93), or uninsured (OR, 0.78; 95% CI, 0.66-0.92) status; nonacademic vs academic/research facility type (OR, 0.44; 95% CI, 0.34-0.56); rectosigmoid or rectal tumor location (OR, 0.76; 95% CI, 0.68-0.86); unknown grade (OR, 0.61; 95% CI, 0.53-0.69); and nonreceipt of definitive surgery (OR, 0.33; 95% CI, 0.30-0.37) were associated with underuse of MMR deficiency testing.Despite recent endorsement of universal use of MMR deficiency testing in patients with CRC and well-established guidelines aimed at high-risk populations, overall utilization of testing is poor and significant underuse of testing among young adults persists. Interventions tailored to groups at risk for nonadherence to guidelines may be warranted in the current era of universal testing.

To evaluate the impact of rheumatoid arthritis (RA) on toxicity and cosmesis in women undergoing radiotherapy for breast cancer. We queried an institutional database for women with RA treated with external beam radiotherapy for breast cancer between 1981 and 2016. Matching each patient to three controls without RA was attempted. Radiation toxicity was graded using CTCAE 4.0. Cosmesis was graded using the Global Harris Scoring System of Excellent, Good, Fair, or Poor. Grade 2+ (G2+) acute and late toxicities were compared between women with RA and their matched pairs using a generalized estimating equation (GEE). Wilcoxon test and mixed effects model were used to compare the cosmesis between two groups. Forty women with RA at time of radiation were matched to 117 controls. The median radiation dose was 60 Gy (50–66 Gy) and the median follow-up was 94 months (1–354 months). When comparing the women with RA to their matched pairs, there was no significant difference in the rates of G2+ acute toxicity (25.0 vs. 13.7%, O 2.1, CI 0.91–4.9) or G2+ late toxicity (7.5 vs. 4.3%, OR 1.8, CI 0.48–6.8). Mean cosmesis was between Good and Excellent for both groups of patients, although women with RA were less likely to get Excellent cosmesis compared to their matched pairs (OR 0.35, CI 0.15–0.84). Among women with RA, radiation for breast cancer was well tolerated without significantly increased toxicity. Their cosmesis was generally Good to Excellent, although they might be less likely to get Excellent cosmesis compared to their matched pairs.

A 58-year Caucasian woman with a 45-pack year smoking history underwent a computed tomography (CT) scan of the chest due to a persistent respiratory infection. Imaging revealed extensive mediastinal and hilar lymphadenopathy on the right. Fine needle aspiration of the right paratracheal and subcarinal lymph nodes revealed small cell lung carcinoma. She was treated with definitive concurrent chemoradiation (with Cisplatin and Etoposide) therapy to the primary tumor and the mediastinum using intensity modulated radiation therapy. Post-treatment repeat CT of the chest showed complete radiographic response and she was offered prophylactic cranial irradiation which the patient refused. Within six months of completing treatment, the patient developed brain metastases and was treated with a course of palliative radiation to the whole brain. One month after completion, she noticed painful swelling of the left submandibular gland and a CT showed an enlarged submandibular gland. FNA revealed metastatic SCLC. She was treated with urgent palliative RT to the left submandibular gland with significant improvement in her symptoms.

During the breast lumpectomy procedure, surgeons traditionally elect to use either a superficial or full-thickness closure when sealing the wound depending on surgeon preference as well as desired outcomes. The purpose of this study was to examine dosimetric endpoints in patients with superficial versus full-thickness closures with accelerated partial breast irradiation (APBI). Patients who underwent breast conservation surgery followed by 3D conformal external-beam APBI were identified (n = 45) and were separated according to the type of cavity closure performed: superficial and full thickness. Data gathered from the retrospective review of patient charts was analyzed according to criteria in the NSABP B-39 protocol in order to quantify the amount of radiation delivered to organs at risk. The patient seroma cavity was further given a cavity visualization score to assess the impact of wound closure on treatment planning. There was no significant difference in the mean CVS score for the 2 groups. There were no statistical differences in all dosimetric endpoints compared for the 2 types of closure, and both groups met NSABP B-39 guidelines for the ipsilateral breast, heart, and ipsilateral lung dosimetry. We found no significant difference in dosimetric outcomes in either the superficial or deep closure treatment groups. Breast surgeons should not alter their preferred closure strategy in anticipation of 3D-CRT APBI.

Background The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy. Patients and Methods We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer-specific survival, and toxicities. Kaplan–Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used. Results Of the 3217 patients, 1295 (40%) were low-risk, 1192 (37%) were intermediate-risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow-up time was 50 (range, 1-190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66-1.54), BF (sHR, 2.14; 0.88-1.83), and cause-specific mortality (sHR, 3.87; 95% CI, 1.31-11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%-14% vs. 2%-6%; P Conclusion Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients.

Purpose To assess the impact of radiation treatment time (RTT) in head and neck cancers on overall survival (OS) in the era of chemoradiation. Methods and Materials Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or tonsil cancer were identified by use of the National Cancer Database. RTT was defined as date of first radiation treatment to date of last radiation treatment. In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT was defined as 49 days, accelerated RTT was defined as 2 tests to identify predictors of RTT. The Kaplan-Meier method was used to compare OS among groups. Cox proportional hazards model was used for OS analysis in patients with known comorbidity status. Results 19,531 patients were included; 12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165 (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a worse OS relative to standard RTT. When the 9,200 (47%) patients receiving definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95% CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas there was no significant association between accelerated RTT and OS (HR 0.76; 95% CI 0.57-1.01). Conclusion Prolonged RTT is associated with worse OS in patients receiving radiation therapy for head and neck cancer, even in the setting of chemoradiation. Expeditious completion of radiation should continue to be a quality metric for the management of head and neck malignancies.

Objectives The purpose of this study was to assess the trends in use of clinical diagnosis and its impact on treatment outcomes in patients receiving radiation therapy for early-stage lung cancer. Methods The Surveillance, Epidemiology, and End Results registry was queried from 2004 to 2012 for patients at least 18 years old in whom stage I (clinical stage T1a–T2a) lung cancer had been diagnosed and who underwent radiation therapy alone. Trends in diagnostic confirmation patterns were characterized. A Cox proportional hazards model was used to assess overall survival, and competing risk regression analysis was used to assess cancer-specific survival (CSS). Results A total of 7050 patients were included; the disease of 6399 of them (90.8%) was pathologically diagnosed and that of 651 (9.2%) was clinically diagnosed. There was no significant change in the utilization of clinical versus pathologic diagnosis ( p = 0.172) over time. Patients with T1 disease ( p p p = 0.004) were more likely to have been clinically diagnosed. On multivariable analysis, clinical diagnosis was associated with an improved CSS (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.71–0.96) but was not associated with an improved overall survival (HR = 1.01, 95% CI: 0.90–1.13). When stratified by T stage, patients whose disease had been clinically diagnosed as stage T1a had an improved CSS (HR = 0.75, 95% CI: 0.58–0.96, p = 0.022). There was a trend toward improved CSS in patients with clinical stage T1b tumors (HR = 0.74, 95% CI: 0.55–1.00, p = 0.052). Conclusions The improved CSS in patients with a clinical diagnosis suggests treatment of benign disease, particularly in smaller tumors. Prudent patient selection is needed to reduce the potential for overtreatment.

We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, stereotactic body RT [SBRT]) and brachytherapy (BT), with an emphasis on the outcomes, toxicities, and contraindications for therapies. PICOS/PRISMA methods were used to identify published English-language comparative studies on PubMed (from 1980 to 2015) that included men treated on prospective studies with a primary endpoint of patient outcomes, with ≥ 70 patients, and ≥ 5 year median follow up. Twenty six studies met inclusion criteria; of these, 16 used EBRT, and 10 used BT. Long-term freedom from biochemical failure (FFBF) rates were roughly equivalent between conventional and hypofractionated RT with intensity modulation (evidence level 1B), with 10-year FFBF rates of 45–90%, 40–60%, and 20–50% (for low-, intermediate-, and high-risk groups, respectively). SBRT had promising rates of BF, with shorter follow-up (5-year FFBF of >90% for low-risk patients). Similarly, BT (5-year FFBF for low-, intermediate-, and high- risk patients have generally been >85%, 69–97%, 63–80%, respectively) and BT + EBRT were appropriate in select patients (evidence level 1B). Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82–97%, 1–14%, 0–8%, respectively) have not been detected in randomized trials of dose escalation or in studies comparing RT modalities. Studies did not use patient-reported outcomes, through grade 3–4 toxicities were rare (

The purpose of this study was to examine the impact of adjuvant radiation on overall survival (OS) and cancer specific survival (CSS) in patients with lymph node (LN) positive endometrial cancer.We analyzed all women diagnosed with FIGO stage IIIC endometrial adenocarcinoma in the Surveillance, Epidemiology, and End Results database from 2004 to 2012 (n=2177). Patients not undergoing surgery or with missing treatment information were excluded. Chi-squared tests were used to compare predictors of treatment received. Cox proportional hazards model and Kaplan-Meier method were used to assess OS and CSS.The median age was 60 (27-84) and the median follow-up was 31months (2-107). Adjuvant radiation was administered to 1248 (60.3%) patients. A total of 1363 (65.9%) patients had pelvic LN involvement while 658 (31.8%) had para-aortic involvement. The 3-year actuarial OS for patients with and without radiation was 80.5% and 67.6%, respectively (p0.001). The 3-year actuarial CSS for patients with and without radiation was 83.4% and 73%, respectively (p0.001). On multivariable analysis, receipt of radiotherapy remained associated with OS (HR 0.61 95% CI 0.51-0.74) and CSS (HR 0.65, 95% CI 0.53-0.80). After propensity matching, radiotherapy continued to be associated with an improved OS (HR 0.65 95% CI 0.54-0.78) and CSS (HR 0.65 95% CI 0.53-0.81). The addition of brachytherapy was not associated with OS or CSS.In this large population registry analysis, adjuvant radiation was associated with improved OS and CSS in patients with LN positive endometrial cancer. Prospective data is needed to confirm these findings.

Importance The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer–specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer–specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer–specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer–specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Intensity-modulated radiation therapy (IMRT) has been shown to decrease abdominal toxicity in patients undergoing chemoradiation (CRT) for pancreatic cancer. We evaluated whether IMRT impacts the rates of hematologic toxicity and chemotherapy dose intensity in patients undergoing CRT. We retrospectively reviewed patients with borderline resectable or locally advanced pancreatic cancer undergoing CRT between 2006 and 2012. Exclusion criteria included receipt of non-gemcitabine therapy, chemotherapy before CRT, or abnormal baseline hematologic indices. Endpoints included total gemcitabine dose received, dose intensity, unplanned dose reductions, and hematologic toxicity (WBC, ANC, platelet, and hemoglobin). Patient/treatment factors were evaluated for their relationship to the above endpoints during CRT and within the first 3 months post-CRT. Statistical analysis was performed using the Fisher exact test and regression models. Because of the multiple comparisons in the presented analysis, a false discovery rate adjustment was performed at the 5% false discovery rate level. Eighty-five patients met the inclusion criteria. Fifty-eight (68.2%) patients received treatment with IMRT, and 27 (31.8%) patients were treated with 3D-conformal radiation. During CRT, there was no relationship between radiation technique and gemcitabine dose received, dose intensity, or hematologic grade 3+ toxicity. Post-CRT, there was no relationship between radiation technique and total gemcitabine dose received, dose intensity, or dose reduction. Patients receiving IMRT were more likely to have ANC grade 3+ toxicity (P=0.007) post-CRT, although this was no longer statistically significant after correction. There were no other relationships between treatment technique and hematologic toxicity. IMRT technique may be associated with higher hematologic toxicity in patients undergoing CRT for pancreatic cancer. Given the expanding use of CRT, additional study is needed to identify the impact of IMRT on myelosuppression in these patients.

Purpose To determine the impact of fellow, resident, or medical student (MS) involvement on outcomes in patients undergoing permanent 125 I prostate seed implant. Methods and Materials The study population consisted of men with clinically localized low/intermediate-risk prostate cancer treated with low-dose-rate permanent interstitial brachytherapy. Cases were stratified according to resident, fellow, MS, or attending involvement. Outcomes were compared using analysis of variance, logistic regression, and log rank tests. Results A total of 291 patients were evaluated. Fellows, residents, and MS were involved in 47 (16.2%), 231 (79.4%), and 34 (11.7%) cases, respectively. Thirteen (4.4%) cases were completed by an attending physician alone. There was no difference in freedom from biochemical failure when comparing the resident, fellow, or attending alone groups ( p = 0.10). There was no difference in V 100 (volume of the prostate receiving 100% of the prescription dose) outcomes when comparing resident cases to fellow cases ( p = 0.72) or attending alone cases ( p = 0.78). There was no difference in D 90 (minimum dose covering 90% of the postimplant volume) outcomes when comparing resident cases to fellow cases ( p = 0.74) or attending alone cases ( p = 0.58). When examining treatment toxicity, fellow cases had higher rates of acute Grade 2 + GU toxicity ( p = 0.028). With the exception of higher urethra D 90 among PGY 2–3 cases ( p = 0.02), dosimetric outcomes were similar to cases with PGY 4–5 resident participation. There was no difference in outcomes for cases with and without MS participation. Conclusions Interstitial prostate seed implants can be safely performed by trainees with appropriate supervision. Hands-on brachytherapy training is effective and feasible for trainees.

To examine the utilization of radiation therapy (RT) in patients with renal cell carcinoma (RCC) using a large national tumor registry.Patients diagnosed with RCC were identified using the National Cancer Data Base. Our primary objective was to assess temporal trends in the utilization of RT. Our secondary objective was to identify patient and treatment factors associated with receipt of RT. The Cochran-Armitage test was used for trend analysis. Multivariable logistic regression was performed to identify factors associated with RT use.A total of 279,427 patients were diagnosed with RCC from 1998 to 2010. A total of 233,572 (83.6%) had localized or locally advanced disease, whereas the remaining 45,855 (16.4%) had metastatic disease. There was a decrease in radiotherapy across all patients during this period (1.5%-0.6%, P .001); as salvage or adjuvant therapy with surgery (1.3%-0.3%, P .001), and in patients with metastatic disease (33.3%-28.5%, P .001). Factors associated with increased RT use in patients with nonmetastatic RCC included male gender, receipt of systemic therapy, higher stage, higher grade, nonacademic treatment facility, facility location, and sarcomatoid or other histology.In the National Cancer Data Base, we observed a decrease in the use of RT for patients with RCC from 1998 to 2010. Patients with more aggressive disease characteristics were more likely to receive RT. Well-designed clinical trials are needed to clarify the role of RT in the management of these patients.

Purpose/Objective(s) To assess the effect on clinical outcomes of the addition of whole pelvis radiation (WPRT) to definitive prostate external beam radiation therapy (EBRT) or external beam radiation therapy plus brachytherapy boost (EBRT-BT) for patients with Gleason Score (GS) 9-10 prostate cancer (PCa), who are at high risk of having occult nodal metastases. Materials/Methods Nine-hundred-forty-two patients with biopsy-proven GS 9-10 PCa treated between 2000 and 2013 at 10 institutions (506 with EBRT and 436 with EBRT+BT) were included. 299 EBRT patients (59%) and 320 EBRT+BT patients (73.4%) received WPRT. A cohort of surgically-treated patients from the same multi-institutional database had a pathologic node positivity rate of 17%. Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM) were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated as the conditional probability of receiving WPRT given age, tumor stage, GS, and initial PSA. Results The median follow-up was 5.6 years. The median doses were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions in the EBRT and EBRT-BT groups, respectively. The median WPRT dose was isoeffective to 50.4 Gy in 1.8 Gy fractions. In the EBRT group 94% of patients receiving WPRT and 96% of patients not receiving WPRT received ADT (median duration 23 months), and in the EBRT-BT group, 80% of patients receiving WPRT received ADT, and 98% not receiving WPRT received ADT (median duration 12 months). WPRT did not significantly improve PCSM in the EBRT group (HR = 0.76, 95% CI 0.45-1.3, p = .3), though it trended towards improvement in the EBRT-BT group (HR 0.46, 0.19-1.11, p = .08). Similar results were seen in a competing risks regression model, treating other cause mortality as a competing risk. WPRT improved bRFS among patients treated with EBRT-BT (HR = 0.4, 95% CI 0.29-0.54, p < .001) but not in those treated with EBRT (HR 1.1, 95% CI 0.67-1.68, p = 0.8). There was borderline improvement in DMFS in the EBRT-BT group (HR 0.64, 95% CI .40-1.03, p = .065), but not the EBRT group (HR = 1.21, 95% CI 0.76-1.93, p= .4). Conclusion WPRT offered a trend towards improved DMFS and PCSM in this large cohort of patients with biopsy GS 9-10 PCa, but only in those treated with EBRT+BT. This trend did not reach statistical significance. WPRT did significantly improve bRFS, but again only in patients treated with EBRT+BT. These results are hypothesis-generating in suggesting that a long-term clinical benefit to WPRT, if present, might only be seen in the setting of extreme dose-escalation to the prostate itself.

7 Background: To compare the outcomes of a modern cohort of patients with Gleason Score (GS) 9-10 prostate adenocarcinoma (CaP) following treatment with external beam radiotherapy (EBRT), extremely dose-escalated radiotherapy (as exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP). Methods: One-thousand-and-one patients with biopsy GS 9-10 CaP who received definitive treatment between 2000 and 2013 were included (347 treated with EBRT, 330 with EBRT+BT, and 324 with RP). Kaplan-Meier analysis and multivariate Cox regression compared 5- and 10-year rates of distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). Prostate cancer-mortality (PCSM) rates were compared with a competing risk analysis. Results: The median followup periods were 4.8, 6.4, and 5.1 years among patients receiving EBRT, EBRT + BT, and RP. The median doses among EBRT and EBRT+BT patients were equivalent to 78 Gy and 90 Gy in 2 Gy fractions. Over 90% of patients treated with EBRT or EBRT+BT received ADT (median durations of 18 months and 12 months, respectively). Nearly 40% of RP patients received postoperative RT, primarily in the salvage setting. Five- and 10-year DMFS rates were significantly higher with EBRT+BT (91.6% and 81.3%) than with EBRT (79.6% and 65.8%; p < 0.0001) or RP (77.9% and 60.1%; p < 0.0001). Five- and 10-year PCSM rates were significantly lower with EBRT+BT (3.8% and 14.1%) than with EBRT (10.3% and 25.2%; 5- and 10-year hazard ratios of 0.38 and 0.47; p = 0.003) or RP (8.9% and 20.3%; 5- and 10-year hazard ratios of 0.39 and 0.55; p = 0.02). Overall 5- and 10-year OS rates were 85.7% and 64.7% and were similar between cohorts (p > 0.1). Conclusions: Extremely dose-escalated radiotherapy offered improved systemic control and reduced PCSM when compared with either EBRT or RP. Notably, this was achieved despite a significantly shorter median duration of ADT than in the EBRT arm. This is hypothesis generating as it suggests that improved local control via dose-escalation may have systemic control and survival implications even for patients with very high risk disease.

204 Background: Trimodality therapy (TMT) for EC is associated with significant toxicity. Limited data are available on the safety of nCRT in vulnerable populations such as older pts. We evaluated the associations between age and toxicity as well as survival in pts treated with nCRT as part of TMT. Methods: A retrospective review of pts with EC treated with nCRT as part of TMT at an academic cancer center between 2002-2014 was conducted. We assessed the impact of age (

191 Background: EC is associated with significant MN. Resultant weight loss (WL) can be further exacerbated by toxicity of nCRT. We evaluated the association of surrogates of MN and T during nCRT for EC. Methods: A retrospective analysis of EC patients (pts) treated with nCRT as part of tri-modality therapy between 2002-2014 was performed. The following pre and post-CRT factors were assessed: presence of jejunostomy tube (J-tube), weight change (gain, loss of < 5%, 5-10%, ≥ 10%) and albumin change (decrease by < 0.5 or ≥ 0.5). We recorded rates of chemotherapy (ctx) dose reduction/interruption (DRI), hospitalizations (H), grade 3/4 T (G3+T), any grade non-hematologic (NHT) or hematologic T (HT). Multivariate regression analyses (MVA) were used to determine associations between MN and T, adjusting for age, gender, smoking status, stage, CRT regimen, performance status, and co-morbidities. Results: 125 patients were identified. Median age was 63 (range 35-80). Pre-CRT body mass index ranged from 17-45 kg/m2, with 74% overweight or obese. Mean WL during nCRT was 10 lbs (5%). Increased WL was noted in pts who received cisplatin/5-FU as compared to other ctx (p < 0.001) or ≥ 50 Gy (p = 0.025). In MVA, increased NHT was noted in pts with ≥ 5% WL (p < 0.05) and more G3+T was noted in pts with ≥ 10% WL (p = 0.002). A decrease in albumin by ≥ 0.5 was associated with increased DRI (p = 0.043), NHT (p = 0.004), HT (p = 0.002), and G3+T (p = 0.004). Sixty-three pts (50%) had a J-tube prior to nCRT. Pts with a J-tube had reduced mean WL (8 lbs vs 13 lbs) during nCRT. No differences in T were noted based on J-tube status. No associations between MN and H rates were observed. Conclusions: Hypoalbuminemia and WL during nCRT were associated with multiple T endpoints. The presence of a prophylactic J-tube did not reduce T rates. Other methods to prevent MN and reduce T during nCRT should be studied.

534 Background: The purpose was to identify predictors of non-adherence to MSI testing in young CRC patients and identify factors associated with an increased risk of high microsatellite instability (MSI-H) disease. Methods: Patients 18-49 years old diagnosed with invasive colorectal adenocarcinoma between 2010-2012 and known MSI testing status were identified using the National Cancer Data Base. Multivariable logistic regression was used to identify independent predictors of receipt of MSI testing, as well as MSI-H status among those tested. Results: Among 17,218 patients identified, only 7,422 (43%) underwent MSI testing; the proportion of patients tested increased between 2010 (36%) and 2012 (48%; p < 0.001). Higher educational level, early stage disease, and number of regional lymph nodes examined > 12 were independently associated with MSI testing, whereas older age (40-49), Hispanic ethnicity, non-private insurance status, non-academic/research facility, facility location, rectosigmoid/rectal tumor location, non-mucinous histology, unknown grade, non-receipt of definitive surgery were associated with underuse. Among 6,358 tested patients with known MSI status, 531 (8%) patients had MSI-H disease. Lower income, previous cancer history, and stage II disease were independently associated with MSI-H status, whereas older age (40-49), female sex, advanced comorbidity, non-metropolitan facility status, facility location, distal tumor location, non-mucinous histology, unknown/lower tumor grade, and non-receipt of chemotherapy were inversely associated with MSI-H status. Conclusions: Despite national guidelines, significant underuse of routine MSI testing in young patients diagnosed with colorectal cancer persists. Interventions are warranted to improve adherence to guideline-based care in these patients, particularly among those at increased risk of MSI-H disease. [Table: see text]

Background The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer. Methods Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed. Results Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% ( p = 0.03). Results for 3-week intervals were similar ( p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks. Conclusions A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.

Since it was first described by Wiseman and Lao, primary breast lymphoma (PBL) has remained an intriguing and elusive disease [1]. The malignancy itself although rare, accounting for less than 0.5% of all breast cancers, is common enough to be the subject of several case reports and retrospective analysis. Common enough to be seen at tertiary care centers but rare enough to not have any definitive guidelines for therapy.

Purpose/Objective(s): To compare outcomes of patients with Gleason score (GS) 9-10 prostate adenocarcinoma (CaP) following external beam radiation therapy (EBRT), extremely dose-escalated radiation therapy (as exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP).