Jose M. Pimiento

Outcomes of a Clinical Pathway for Borderline Resectable Pancreatic Cancer

AbstractBackgroundWithout prospective data establishing a consensus multimodality approach to borderline resectable pancreatic adenocarcinoma, institutional treatment regimens vary. This study investigated the outcomes of the clinical pathway at the author’s institution, which consists of neoadjuvant gemcitabine, docetaxel, capecitabine, and stereotactic radiotherapy followed by surgery.MethodsThe study reviewed all cases that met the National Comprehensive Cancer Network (NCCN) diagnostic criteria for borderline resectable pancreatic adenocarcinoma from 1 January 2006, to 31 December 2013. nPancreatectomy rates, margin status, pathologic response, disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were retrospectively examined. Standard statistical methods and Kaplan–Meier survival analysis were used for statistical comparisons.ResultsOf 121 patients who met criteria, 101 entered the clinical pathway, and 94 (93.1xa0%) completed neoadjuvant chemotherapy and radiation therapy. Of the 101 patients, 55 (54.5xa0%) underwent pancreatectomy, with 53 patients (96.4xa0%) having microscopically negative margins (R0) and 2 patients (3.6xa0%) having microscopically positive margins (R1). Vascular resection was required for 22 patients (40xa0%), with rates of 95.5xa0% for R0 (nxa0=xa021) and 4.5xa0% for R1 (nxa0=xa01). A pathologic response to treatment was demonstrated by 45 patients (81.8xa0%) and a complete response by 10 patients (14.5xa0%). Pancreatectomy resulted in a median DFS of 23xa0months (95xa0% conflidence interval [CI] 14.5–31.5), a median DSS of 43xa0months (95xa0% CI, 25.7–60.3), and a median OS of 33xa0months (95xa0% CI, 25.0–41.0) versus a median DSS and OS of 14xa0months (95xa0% CI, 10.9–17.1) for patients without pancreatectomy (DSS: Pxa0=xa03.5xa0×xa010−13; OS: Pxa0=xa04.7xa0×xa010−10).ConclusionsThe study demonstrated high rates for neoajduvant therapy completion (93.1xa0%) and pancreatectomy (54.5xa0%). After pancreatectomy, DSS was significantly improved (43xa0months), with a pathologic response demonstrated by 81.8xa0% and a complete response by 14.5xa0% of the patients. The results support further study of this borderline resectable pancreatic adenocarcinoma clinical pathway.

The prognostic value of residual nodal disease following neoadjuvant chemoradiation for esophageal cancer in patients with complete primary tumor response

The prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) to neoadjuvant chemoradiation (nCRT) for esophageal cancer is unknown.

The role of radical amputations for extremity tumors: a single institution experience and review of the literature.

Major amputations are indicated for advanced tumors when limb‐preservation techniques have been exhausted. Radical surgery can result in significant palliation and possible cure.

Tumor regression grade in gastric cancer: Predictors and impact on outcome.

The clinical value and prognostic implications of histologic response to neoadjuvant chemotherapy in gastric cancer is unknown.

Correlation Between Standardized Uptake Value in Preneoadjuvant and Postneoadjuvant Chemoradiotherapy and Tumor Regression Grade in Patients With Locally Advanced Esophageal Cancer.

Purpose: To investigate whether positron emission tomography/computed tomography (PET/CT) initial and restaging imaging predicts for pathologic response measured by tumor regression grade (TRG) after preoperative chemoradiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: A retrospective review of 220 patients with stage II-III esophageal cancer treated with neoadjuvant CRT followed by surgery was performed. In total, 187 patients were eligible for statistical analysis. Pretreatment and posttreatment PET/CT scans were reviewed. Maximum standard uptake value (SUV) at the site of the primary tumor was recorded before and 6 weeks after neoadjuvant therapy. Upon completion of surgery, TRG was determined by a specialized site-specific gastrointestinal pathologist. Spearman correlation was used to compare pre, post, and change in maximum SUV, TRG, and overall survival. Results: The median follow-up was 24 months. Although no significant correlation was found between pretreatment SUV and TRG (r=0.073, P=0.32), post-CRT SUV, however, showed a significant positive correlation with TRG (r=0.374, P<0.01). There was no significant correlation between the absolute change in fluorodeoxyglucose uptake after CRT and TRG (r=0.057, P=0.44); however, the rate of SUV change showed a significant correlation with TRG (r=0.178, P=0.017). Similar to previous studies, our study showed a significant difference in overall survival between TRG groups (log-rank test, P=0.019). Patients with TRG 3 showed prominently worse survival with median survival of 27.4 months. Patients with favorable pathologic responses were those whose scans demonstrated a metabolic response defined as a decrease in SUV≥70%. Conclusions: Changes in SUV uptake on PET/CT scans after CRT have prognostic value in predicting pathologic response of esophageal cancer after neoadjuvant therapy. Further studies are needed to validate the integration of PET/CT as a decision-making tool.

Outcomes Associated with Surgery for T4 Esophageal Cancer

BackgroundT4 esophageal cancer often portends a dismal prognosis even after surgical resection. Historical incomplete resections and poor survival rates often make surgery palliative rather than curative.MethodsUsing a comprehensive esophageal cancer database, we identified patients who underwent an esophagectomy for T4 tumors between 1994 and 2011. Neoadjuvant treatment (NT) and pathologic response variables were recorded, and response was denoted as complete response (pCR), partial response (pPR), and nonresponse (NR). Clinical and pathologic data were compared. Survival was calculated using Kaplan–Meier curves with log-rank tests for significance.ResultsWe identified 45 patients with T4 tumors all who underwent NT. The median age was 60xa0years (range, 31–79xa0years) with a median follow-up of 27xa0months (range, 0–122xa0months). There were 19 pCR (42xa0%), 22 pPR (49xa0%), and 4 NR (9xa0%). R0 resections were accomplished in 43 (96xa0%). There were 18 recurrences (40xa0%) with a median time to recurrence of 13.5xa0months (2.2–71xa0months). In this group pCR represented 7 (38.9xa0%), whereas pPR and NR represented 10 (55.5xa0%), and 1 (5.5xa0%) respectively. The overall and disease-free survival for all patients with T4 tumors were 35 and 36xa0%, respectively. Patients achieving a pCR had a 5xa0year overall and disease-free survival of 53 and 54xa0%, compared with pPR 23 and 28xa0%, while there were no 5xa0year survivors in the NR cohort.ConclusionWe have demonstrated that neoadjuvant therapy and downstaging of T4 tumors leads to increased R0 resections and improvements in overall and disease-free survival.

Systematic Review and Case Series Report of Acinar Cell Carcinoma of the Pancreas.

BACKGROUNDnAcinar cell carcinoma of the pancreas is a rare malignancy representing less than 1% of all pancreatic malignancies.nnnMETHODSnWe report on a case series of 21 patients with acinar cell carcinoma of the pancreas treated at a high-volume quaternary center. A systematic review of the medical literature was performed that described typical therapeutic management approaches for acinar cell carcinoma of the pancreas and reported on disease control and survival rates. Data for the case series were obtained from a prospective database.nnnRESULTSnIn our systematic review of 6 articles, study patients had a median age of 61 years, 66% were male, 52% had stage I/II disease, and 55% of lesions were located in the pancreatic head. The rates of median survival were approximately 47 months after resection with adjuvant therapy, 38 months for nonmetastatic, locally unresectable disease, and 17 months for metastatic disease treated with chemotherapy. Combination fluoropyrimidine-based chemotherapy regimens had better rates of disease control than other therapies. Our case series included 21 study patients, 14 of whom required resection and 7 who had metastatic disease. The rates of median survival were 40.2 ± 31.9 months in those who underwent surgery and were treated with adjuvant therapy and 13.8 ± 11.3 months for patients with metastatic disease.nnnCONCLUSIONSnMultidisciplinary treatment for acinar cell carcinoma of the pancreas should be considered due to the rarity of the disease and its lack of high-level therapeutic data. Progress in the molecular analysis of this tumor may improve outcomes through the use of personalized therapy based on underlying tumor mutations.

TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma.

The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene. Average log2 mRNA expression of TGFβ1 in patients with high expression was 11.6 ± 0.2 and 10.5 ± 0.6 in patients with low expression (P<0.001). Low TGFβ1 expression is associated with shorter median survival compared with high TGFβ1 expression (17 versus at least 60 months; P=0.005). Patients with tumors demonstrating high MKI67 (the gene encoding Ki-67) expression have shorter median survival versus those with lowerMKI67 expression (16 versus 20 months; P=0.026). TGFβ1 and MKI67 are inversely associated (P=0.009). On multivariate analysis, improved survival is associated with TGFβ1 overexpression (P=0.017), adjuvant chemotherapy (P=0.001), and adjuvant radiotherapy (P=0.017), whereas positive surgical margins are associated with worse survival (P=0.002). In patients who undergo pancreaticoduodenectomy for PDAC, high TGFβ1 expression may counteract the worse survival associated with high proliferation.

Adjuvant chemotherapy and outcomes in esophageal carcinoma

BackgroundnStandard treatment for locally advanced esophageal cancer is neoadjuvant chemoradiation followed by surgery. The role of postoperative chemotherapy is unclear. We sought to determine the indications, patterns, and outcomes for adjuvant chemotherapy in esophageal carcinoma.nnnMethodsnThis single institution retrospective review included patients with esophageal cancer who received neoadjuvant chemoradiation and surgery at Moffitt. We identified patients in this cohort who additionally received adjuvant chemotherapy. Medical records were reviewed for demographic/clinical information. Survival was estimated using the Kaplan-Meier method and compared by log-rank. Case-control analysis was performed using a 2:1 nearest neighbor propensity score matching algorithm, which included 92 without adjuvant chemotherapy and 46 with adjuvant chemotherapy.nnnResultsnWe identified 382 patients, 46 of whom received adjuvant chemotherapy. Patients who received adjuvant chemotherapy were younger (60.2 vs. 63.8 years; P=0.047), more likely to have adenocarcinoma (91% vs. 85%; P=0.034), had more advanced ypT and ypN classifications (P<0.001), less response to neoadjuvant therapy (P<0.001), and more margin positivity (15% vs. 4%; P=0.007). With propensity score matching analysis, no variables were significantly different between the two matched groups. Median follow-up times for the entire cohort and for case-control analysis were 2.9 and 2.4 years, respectively. There were no significant differences in overall or recurrence-free survival (RFS) between groups in either analysis.nnnConclusionsnThe role of adjuvant chemotherapy following neoadjuvant chemoradiation and surgery in esophageal cancer is unclear. We found no significant difference in survival based on adjuvant chemotherapy. Future prospective studies should further investigate potential survival benefits and morbidity.

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

BackgroundnTotal psoas area (TPA), a marker of sarcopenia, has been used as an independent predictor of clinical outcomes in gastrointestinal (GI) cancers as a proxy for frailty and nutritional status. Our study aimed to evaluate whether TPA, in contrast to traditional measurements of nutrition like body mass index (BMI) and body surface area (BSA), was predictive of outcomes in borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients receiving stereotactic body radiation therapy (SBRT).nnnMethodsnRetrospective analysis of an institutional review board approved database of 222 BRPC and LAPC treated with SBRT from 2009-2016 yielded 183 patients that met our selection criteria of pre-SBRT computed tomography (CT) imaging with an identifiable L4 vertebra. Once the L4 vertebral level was identified, the bilateral psoas muscles were manually contoured. This area was normalized by patient height, with units described in mm2/m2. Receiver operating characteristic (ROC) curves were generated for TPA, BMI, and BSA to elicit clinically relevant cutoffs. Regression and Kaplan-Meier analyses were used to correlate toxicity with survival functions.nnnResultsnLow TPA (OR =1.903, P=0.036) was predictive of acute toxicities, and only TPA was predictive of Grade 3 or higher acute toxicities (OR =10.24, P=0.007). Both findings were independent of tumor resectability. Pain (P=0.003), fatigue (P=0.040), and nausea (P=0.039) were significantly associated with low TPA. No association was identified between any measurement of nutritional status and the development of late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median =21.98 months) than their LAPC (median =16.2 months) counterparts (P=0.002), independent of nutritional status.nnnConclusionsnTPA measurement is readily available and more specific than BMI or BSA as a predictor of acute radiotoxic complications following SBRT in BRPC/LAPC patients. A TPA of <500 mm2/m2 is a clinically relevant cutoff that can direct physicians to address expected complications of pain, fatigue, and nausea. However, tumor resectability remains as the only predictor of overall survival in this cohort.