Postmastectomy Radiotherapy: Barriers to Implementation in a Disparate Population.

Appalachian Kentucky (AK) has a disproportionally high breast cancer mortality rate. Postmastectomy radiotherapy (PMRT) in N2/N3 nodal disease improves survival and locoregional recurrence. We evaluated Kentucky patient compliance to the quality measure of PMRT received within one year of diagnosis. A population-based retrospective review of patients who received mastectomy with N2/N3 nodal disease from 2006 to 2015 was obtained through the Kentucky Cancer Registry. A total of 1489 patients met the inclusion criteria. Of these, 1104 (66.6%) received PMRT. AK patients were less likely to receive PMRT (58.3%) than non-AK patients (70%, P < 0.001). After adjusting for significant factors, private insurance, education level, treatment center, and receipt of adjuvant chemotherapy were independently associated with PMRT compliance. Patients who received PMRT had improved overall survival (OS, P < 0.0001) and disease-free survival (DFS, P < 0.0001). Appalachian status was not a major factor in OS (P= 0.1929) or DFS (P = 0.5840). Nearly two decades after the recommendation of PMRT, compliance remains poor in Kentucky. PMRT continues to be a major factor in survival and recurrence in this population. Interventions focusing on improving insurance coverage, education level, and guideline adherence in nonacademic centers are needed to improve compliance.

Effect of complications on oncologic outcomes after pancreaticoduodenectomy for pancreatic cancer.

BACKGROUND: Although adjuvant therapy (AT) is a necessary component of multimodality therapy for pancreatic ductal adenocarcinoma (PDAC), its application can be hindered by post-pancreaticoduodenectomy (PD) complications. The primary aim of this study was to evaluate the impact of post-PD complications on AT utilization and overall survival (OS). METHODS: Patients undergoing PD without neoadjuvant therapy for stages I-III PDAC at a single institution (2007-2015) were evaluated. Ninety-day postoperative major complications (PMCs) were defined as grade ≥3. Records were linked to the Kentucky Cancer Registry for AT/OS data. Early AT was given <8 wk; late 8-16 wk. Initiation >16 wk was not considered to be AT. Complication effects on AT timing/utilization and OS were evaluated. RESULTS: Of 93 consecutive patients treated with surgery upfront with AT data, 64 (69%) received AT (41 [44%] early; 23 [25%] late). There were 32 patients (34%) with low-grade complications and 24 (26%) with PMC. With PMC, only six of 24 patients (25%) received early AT and 13 of 24 (54%) received any (early/late) AT versus 35 of 69 (51%) early AT and 51 of 69 (74%) any AT without PMC. PMCs were associated with worse median OS (7.1 versus 24.6 mo, without PMC, P < 0.001). Independent predictors of OS included AT (hazard ratio [HR]: 0.48), tumor >2 cm (HR: 3.39), node-positivity (HR: 2.16), and PMC (HR: 3.69, all P < 0.02). CONCLUSIONS: Independent of AT utilization and biologic factors, PMC negatively impacted OS in patients treated with surgery first. These data suggest that strategies to decrease PMC and treatment sequencing alternatives to increase multimodality therapy rates may improve oncologic outcomes for PDAC.

Defining the optimal timing of adjuvant therapy for resected pancreatic adenocarcinoma: A statewide cancer registry analysis.

BACKGROUND: Long-term results of the ESPAC-3 trial suggest that while completing adjuvant therapy (AT) is necessary after resection of pancreatic ductal adenocarcinoma (PDAC), early initiation (within 8 weeks) may not be associated with improved overall survival (OS). The primary aim of this study was to evaluate the OS impact of early versus late AT in a statewide analysis. METHODS: Patients with stages I-III PDAC in the Kentucky Cancer Registry (KCR) from 2004 to 2013, were evaluated. Those undergoing pancreatectomy were stratified into two groups ("early," <8 weeks, vs. "late," 8-16 weeks). RESULTS: Of 2,221 diagnosed patients with stages I-III, 831 (37.4%) underwent pancreatectomy upfront. Of these, only 420 (50.5%) received AT. Initiation date of AT was not associated with OS (median OS: early, 20.2 vs. late, 19.0 months, P = 0.97). On multivariate analysis, factors that affected OS included stage (II, HR-1.82, P = 0.017; III, HR-3.77, P < 0.001), node positivity (HR-1.51, P = 0.004), poorly/undifferentiated grade (HR-1.34; P = 0.011), but not AT initiation date. CONCLUSIONS: In this statewide analysis, there was no difference in OS between early and late AT initiation for resected PDAC. The ideal window for AT initiation remains unknown as tumor biology continues to trump regimens from the past decade. J. Surg. Oncol. 2016;114:451-455. © 2016 Wiley Periodicals, Inc.

Increased morbidity and mortality of a concomitant colectomy during a pancreaticoduodenectomy: an NSQIP propensity-score matched analysis.

BACKGROUND: Select patients with peri-ampullary cancers require concomitant colon resection (CR) during a pancreaticoduodenectomy (PD) for margin-negative resections. This study analysed the impact of concomitant CR on major morbidity (MM) and mortality. METHODS: National Surgical Quality Improvement Program (NSQIP) patients undergoing PD for peri-ampullary cancers were identified from 2005 to 2012. A 4 : 1 propensity-score matched analysis isolated the impact of CR upon PD. Risk factors for 30-day MM and mortality were analysed to determine post-operative sequelae of PD+CR. RESULTS: From 10 965 PD and 159 PD+CR patients, 624 and 156, respectively, were selected for 4 : 1 matched analysis. PD+CR resulted in a higher MM and mortality (50.0% and 9.0%) versus PD alone (28.8% and 2.9%, respectively, P < 0.001). Multivariate analysis identified risk factors for MM after PD: concomitant CR [odds ratio (OR)-3.19, P < 0.001], smoking (OR-1.92, P = 0.005), a lack of functional independence (OR-3.29, P = 0.018), cardiac disease (OR-2.39, P = 0.011), decreased albumin (per g/dl, OR-1.38, P = 0.033) and a longer operative time (versus median time, OR-1.56, P = 0.029). Independent predictors of mortality included concomitant CR (OR-3.16, P = 0.010), ventilator dependence (OR-13.87, P < 0.001) and septic shock (OR-6.02, P < 0.001). CONCLUSIONS: CR was an independent predictor of MM and mortality after a PD. Patients requiring PD+CR should be identified pre-operatively, maximally optimized and referred to experienced surgeons at expert centres.

Should gastric cardia cancers be treated with esophagectomy or total gastrectomy? A comprehensive analysis of 4,996 NSQIP/SEER patients.

BACKGROUND: Category 1 guidelines emphasize multimodality therapy (MMT) for patients with gastric cardia cancer (GCC). These patients are often referred to thoracic surgeons for "esophagogastric junction" cancers rather than to abdominal surgeons for "proximal gastric" cancers. This study sought to determine the ideal surgical approach using national datasets evaluating morbidity/mortality (M/M) and overall survival (OS). STUDY DESIGN: Patients with resected GCC were identified from the 2005 to 2012 ACS-NSQIP dataset and the 1998 to 2010 SEER dataset. Multivariate 30-day M/M analyses were performed using NSQIP. Survival analyses were derived from SEER and stratified by surgical approach. RESULTS: There were 1,181 NSQIP patients with GCC included; 81.8% had esophagectomies and 18.1% had gastrectomies. Major postoperative M/M occurred in 33.2%/3.7% patients after gastrectomy vs 35.0%/2.4% after esophagectomy (p = 0.260). Although a major postoperative complication (odds ratio 12.8, p < 0.001) was an independent predictor of mortality on multivariate analysis, surgical approach was not. Of the 3,815 SEER patients included, 71.1% had esophagectomies and 28.9% had gastrectomies. Radiation use (surrogate for MMT) was administered more often with esophagectomy vs gastrectomy (42.9% vs 29.6%, p < 0.001). Unadjusted median overall survival (OS) favored esophagectomy (26.0 vs 21.0 months, p = 0.025). However, multivariate analysis confirmed age (hazard ratio [HR] 1.01), T/N stages (HR 1.12/1.91), and radiation use (HR 0.83, all p ≤ 0.018), but not surgical approach (HR 0.95, p = 0.259), as independent predictors of OS. CONCLUSIONS: Tumor biology and MMT, rather than surgical approach, dictate oncologic outcomes for GCC. Therefore, the decision of esophagectomy vs gastrectomy for GCC should be based on proximal and distal tumor extent and the multidisciplinary strategy with the lower rate of complications and the higher rate of MMT completion.

Should Histologic Grade Be Incorporated into the TNM Classification System for Small (T1, T2) Node-Negative Breast Adenocarcinomas?

Prognosis of invasive ductal carcinoma (IDC) strongly correlates with tumor grade as determined by Nottingham combined histologic grade. While reporting grade as low grade/favorable (G1), intermediate grade/moderately favorable (G2), and high grade/unfavorable (G3) is recommended by American Joint Committee on Cancer (AJCC) staging system, existing TNM (Primary Tumor/Regional Lymph Nodes/Distant Metastasis) classification does not directly incorporate these data. For large tumors (T3, T4), significance of histologic grade may be clinically moot as those are nearly always candidates for adjuvant therapy. However, for small (T1, T2) node-negative (N0) tumors, grade may be clinically relevant in influencing treatment decisions, but data on outcomes are sparse and controversial. This retrospective study analyzes clinical outcome in patients with small N0 IDC on the basis of tumor grade. Our results suggest that the grade does not impact clinical outcome in T1N0 tumors. In T2N0 tumors, however, it might be prognostically significant and relevant in influencing decisions regarding the need for additional adjuvant therapy and optimal management.

Breast reduction as an alternative treatment option for early breast cancer in women with macromastia.

Macromastia has been considered a relative contraindication to breast conservation therapy because of difficulties with postoperative radiation therapy and cosmesis. This study evaluates the feasibility of the inferior pedicle reduction mammaplasty as a component of breast conservation therapy for patients with early breast cancer. A retrospective review identified 6 patients with macromastia receiving oncologic treatment of breast cancer and simultaneous breast reduction. Mean age was 43.5 +/- 8.7 (mean +/- SD) years, and all breast cancers were stage I or II, averaging 2.3 +/- 1.5 cm in size. All patients underwent a Wise-pattern inferior pedicle breast reduction after cancer extirpation and received postoperative radiation as part of their treatment. They were evaluated for postoperative complications, esthetic outcome of the breasts, and local recurrence. Patients in this series were followed for an average of 30.3 months, with no significant postoperative complications and recurrences. Breast reduction incisions healed primarily and adjuvant radiation was completed without a delay. All patients were pleased with the esthetic result and had improvement of their symptoms related to macromastia. Thus, we believe that breast reduction is a reasonable and safe option for early breast cancer patients with macromastia who desire breast conservation therapy. Our combined oncologic and reconstructive approach may improve the outcome of this group of patients with early breast cancers.

Concurrent infusional gemcitabine and radiation in the treatment of advanced unresectable GI malignancy: a phase I study.

PURPOSE: Preclinical studies have demonstrated significant synergistic tumor cell death when gemcitabine is combined with radiation therapy. The optimal mode for concomitant delivery of drug and radiation therapy remains to be determined. A phase I/II study was undertaken to establish the maximum tolerated dose of infusional gemcitabine when combined with radiation therapy in advanced gastrointestinal malignancies and to assess the response to treatment. MATERIALS AND METHODS: Twenty-five patients with advanced or recurrent gastrointestinal malignancy were entered in this dose-escalation study. The initial dose of gemcitabine was 50 mg/m2 as a 24-hour continuous intravenous infusion given weekly x 3 with concurrent radiation therapy. The patients were given a week off chemotherapy after the third injection. The radiation therapy was continued during that week. Gemcitabine was thereafter resumed weekly for another 3 weeks or until the patient completed the radiation therapy (whichever was earlier). Five patients were treated at each dose level. The dose of the drug was escalated in increments of 50 mg/m2 if the toxicity was acceptable at the previous level until the maximum tolerated dose was established. Thirteen patients with advanced unresectable colorectal cancer and 12 patients with advanced unresectable pancreaticobiliary cancers were enrolled on the study. Radiation was delivered at 180 cGy/fraction to a total dose of 4000 cGy +/- boost. Because toxicity was severe at the 150 mg/m2 dose level, three additional patients were entered at this dose level. The dose was then dropped to 125 mg/m2, and five more patients were entered at this dose level. Two additional patients were then added in order to assess toxicity. Patient follow-up ranged from 4 to 22 months, and the median was 8 months. RESULTS: All patients were evaluable for toxicity. The doses of 50 and 100 mg/m2 were well tolerated, but at 150 mg/m2, six of eight patients experienced grade 3 or greater toxicity. The dose was de-escalated to 125 mg/m2, and three of seven patients showed grade 3 diarrhea and weight loss. Clinical tumor response was evaluable in 20 patients. Ten patients had a complete clinical response (50%), five patients had a partial response (25%), three patients had no response, and two patients had progression of disease. No patients experienced late toxicities related to either gemcitabine administration or radiation therapy. Twelve patients are currently alive. CONCLUSION: Based on these results, it appears that the maximum tolerated dose for weekly 24-hour infusion of gemcitabine combined with radiation therapy is 100 mg/m2. Gemcitabine appears to be a potent radiation sensitizer, and when combined with radiation therapy, it has shown encouraging tumor responses. In this study, we found an overall response rate of 75% in patients with locally advanced stage of disease. Further evaluation of gemcitabine at 100 mg/m2 is being undertaken in preparation for a confirmatory multi-institutional phase II study.