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Background: 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. Objective: 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. Methods: 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). Results: 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 < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04–4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00–1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72–1.65; p = 0.70). Conclusion: Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of rheumatoid arthritis (RA) on toxicity and cosmesis in women undergoing radiotherapy for breast cancer. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives: To know the serum ferritin and vitamin B12 levels in relation to C reactive protein in individuals using smokeless tobacco in Hyderabad, sindh, Pakistan. Study Design: Cross sectional study. Place of Study: Private clinics of consultants of Hyderabad, Sindh, Pakistan. Duration of Study: January 2016 to February 2017. Methodology: One hundred eighty three individuals were selected from different clinics of physicians, dental surgeons of sadder Hyderabad sindh Pakistan by judgmental sampling. Patients were young subjects, mean age was 21.4±7.4 years, mean BMI was 22.1±3.8 and mean duration of chewing tobacco was 2±1.5 years. All types and forms of gutaka, manpuri and flavored betel nut were included like bombart, zafri and panparag. The dose was 30-100grams once or two times. SPSS 16 was used as statical software and Chai square test was used to calculate p value. P value was taken <0.05 statically significant. Results: Frequency of use of gutka was 32%, Betel nut 38% and 29% had habit of chewing manpuri. Serum ferritin was low and c reactive protein was high, p value was <0.05 in gutaka and manpuri users. Vitamin B12 was reduced significantly in gutaka user p value was <0.05. In betel nut chewers significant finding was only high C reactive protein, p value <0.04. Conclusion: Smokeless tobacco has significant negative impact on serum ferritin and vitamin B12 levels. These chewing agents also increased inflammatory markers like c reactive protein. [ABSTRACT FROM AUTHOR]

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 (p < 0.01). Regional nodal failure was correlated with fewer LN assessed (p < 0.01) and larger pretreatment tumor size (p = 0.04). Patients with ≤13 LN evaluated had an inferior locoregional RFS versus patients with >13 LN evaluated (p = 0.003). Distant recurrence was correlated with higher pathologic nodal stage (p < 0.001), ulceration (p = 0.017), perineural invasion (p = 0.029), residual disease (p = 0.004), and higher post-treatment PET SUV max (p = 0.049). Patients with a pathologic complete response (OR 0.19, 95% CI 0.05–0.68) were less likely to experience distant recurrence.Conclusion.Tumor and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience" by Brandon Fisher and colleagues is presented.

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 ≥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. [ABSTRACT FROM AUTHOR]

BACKGROUND: The role of adjuvant radiation for T4 colon adenocarcinoma is controversial. We assessed the impact of adjuvant radiation on treatment outcomes in a large national dataset. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was queried from 1988–2012 for patients aged > 18 years diagnosed with T4 colon adenocarcinoma who underwent curative surgery. The primary endpoints were overall survival (OS) and cancer-specific survival (CSS) for patients treated with or without adjuvant radiation. Survival was assessed utilizing the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: A total of 29,830 patients were identified; 1,877 (6.3%) patients received adjuvant radiation. There was no difference in OS (P = .384) with adjuvant radiation. Patients receiving radiation had a worse CSS than patients who received no adjuvant radiation (P < .001). On examination of a modern cohort of patients treated from 2004–2012, patients receiving adjuvant radiation had an improvement in OS compared with patients receiving no radiation (P < .001), and there was a trend toward improved CSS in patients receiving adjuvant radiation (P = .053). On multivariable analysis, adjuvant radiation remained associated with OS (hazard ratio [HR], 0.88 [95% CI, 0.78–0.99]; P = .034). Subgroup analysis demonstrated an OS benefit with radiation in patients with distal tumors (P = .002), grade 3/4 disease (P = .006), grade 2 disease (P = .012), negative lymph nodes (P < .001), and tumor size > 5 cm (P < .001). CONCLUSION: In this large population dataset, adjuvant radiation was associated with an improvement in OS in a modern cohort of patients. Patients with distal tumors, higher-grade disease, negative lymph nodes, and larger tumors may derive a greater benefit with radiation. [ABSTRACT FROM AUTHOR]