Perioperative Chemotherapy and Chemoradiotherapy for Patients With Resectable and Borderline Resectable Pancreatic Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS. METHODS: A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS). RESULTS: Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR). CONCLUSIONS: Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.

Outcomes After Adjuvant Hyperthermic Intraperitoneal Chemotherapy for High-Risk Primary Appendiceal Neoplasms After Complete Resection.

INTRODUCTION: Appendiceal neoplasms are uncommon tumors. Optimal treatment for patients with perforation or high-grade pathology after initial resection is unknown. This study evaluated patients with increased risk for peritoneal dissemination after primary resection, but no evidence of peritoneal disease, who underwent adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This multi-institutional cohort study evaluated 56 patients with high-risk (HR) appendiceal neoplasms with a peritoneal carcinomatosis index of 0 who underwent HIPEC. The patients were divided into two groups: perforated low-grade appendiceal (LGA) carcinoma and HR neoplasms, which included perforated high-grade appendiceal carcinoma, positive margins after initial resection, minimal macroscopic peritoneal disease that was previously resected or completely responded to systemic chemotherapy prior to HIPEC, goblet cell carcinoma, and adenocarcinoma with signet ring cell features. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier analysis. RESULTS: Thirty-eight percent of patients had perforated LGA and 68% had HR features. Five-year OS probability was 82.1% for the entire cohort, and 100% and 70.1% for patients with perforated LGA and HR features, respectively (p = 0.024). Five-year RFS probability was 79.3% for the entire cohort, and 90.0% and 72.4% for patients with perforated LGA and HR features, respectively (p = 0.025). Eight patients recurred after HIPEC and their OS was significantly worse (p < 0.001). CONCLUSION: While adjuvant HIPEC is both safe and feasible, there appears to be little benefit over close surveillance when outcomes are compared with historical and prospective studies, especially for perforated LGA carcinoma.

Elevated brain natriuretic peptide (BNP) is an early marker for patients at risk for complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).

BACKGROUND: Elevated BNP is associated with adverse cardiac outcomes after noncardiac surgery. We assessed BNP values as markers of perioperative fluid status and their correlation with major/cardiopulmonary (CP) complications following CRS + HIPEC. METHODS: Fluid balance, BNP levels, and morbidity data were collected for all patients undergoing CRS + HIPEC between 6/2014 and 2/2016. RESULTS: One hundred and twenty-nine patients underwent CRS + HIPEC for appendiceal adenocarcinoma (n = 99), mesothelioma (n = 16), and colon cancer (n = 14). Less than 10% had CP comorbidities. The median PCI was 14 (range 4-39); 89% underwent CC0/1 resection (n = 115). Median blood loss (EBL) was 497 mL (50-2700). Major complications (Clavien III-V) occurred in 16 (12%), CP in 17 (13%), and major/CP in 24 (18%). Thirty-day mortality occurred in 2 (1.5%). Elevated BNP on POD1 correlated with increased risk of major/CP complications (OR 2.2, P = 0.052). This was most pronounced in the 25 patients receiving cisplatin: for each 100 unit increase in POD1 BNP the OR for major/CP complication was 7.4 versus 1.2 for the remaining patients, P = 0.083. Multivariate analysis identified increased EBL (OR 4.1 P = 0.011) and a trend toward increased BNP on POD1 (OR for each 100 unit increase 2.0, P = 0.10) as risk factors for major/CP complications. CONCLUSIONS: Postoperative BNP measurement after CRS + HIPEC may guide postoperative fluid resuscitation and facilitate identification of patients at risk for major and/or cardiopulmonary complications.

Adherence to National Comprehensive Cancer Network Guidelines is Associated with Improved Survival for Patients with Stage 2A and Stages 2B and 3 Extremity and Superficial Trunk Soft Tissue Sarcoma.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) has instituted treatment guidelines for stage 2A and stages 2B and 3 extremity and superficial trunk soft tissue sarcomas (ETSTS). This study examined adherence to the NCCN guidelines and factors associated with nonadherent treatment and survival outcomes. METHODS: Patients with stage 2A and stages 2B and 3 ETSTS (n = 15,957) were categorized as undergoing adherent or nonadherent treatment based on the 2014 NCCN guidelines. Multivariate logistic regression models were used to determine factors associated with nonadherent treatment. Overall survival (OS) and disease-specific survival (DSS) were calculated, and Cox models were used to generate adjusted survival curves and hazard ratios (HRs). RESULTS: The findings showed that 87.2% of the patients with stage 2A disease and 58.3% of the patients with stage 2B or 3 disease received adherent treatment. Community treatment facilities and uninsured or unknown insurance status were associated with nonadherent treatment for both stage groups. Adherent treatment was associated with higher 5-year adjusted OS and DSS for stage 2A and stage 2B or 3 patients. In Cox models, nonadherent treatment was associated with worse survival for both stage 2A disease (HR, 2.31; 95% confidence interval [CI], 2.02-2.63) and stages 2B and 3 disease (HR, 1.63; 95% CI, 1.53-1.73). Increasing age and non-private insurance were associated with poorer outcomes. For stages 2B and 3 disease, treatment at a community center and African American race were associated with worse survival. CONCLUSIONS: Adherence to NCCN guidelines is excellent for stage 2A and poor for stages 2B and 3 ETSTS. Adherent treatment was associated with improved survival outcomes, highlighting the importance of adherence to NCCN guidelines.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Moderately and Poorly Differentiated Appendiceal Adenocarcinoma: Survival Outcomes and Patient Selection.

BACKGROUND: Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death. METHODS: Overall, 178 patients with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes. RESULTS: Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio [HR] 0.52, p = 0.04) and PCI (HR 1.054, p = 0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR 0.352, p = 0.018), signet ring cells (HR 3.34, p = 0.02), positive peritoneal cytology (HR 0.081, p = 0.04), and PCI (HR 1.076, p = 0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44 months, compared with 21 months for those with progressive disease (p = 0.011). CONCLUSIONS: In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI ≤ 20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.

High-quality results of cytoreductive surgery and heated intraperitoneal chemotherapy perfusion for carcinomatosis at a low volume institution.

BACKGROUND AND OBJECTIVES: Maximal cytoreductive surgery (CS) with heated intraperitoneal chemotherapy perfusion (HIPEC) for peritoneal carcinomatosis can improve oncologic outcomes, but is associated with significant morbidity. Whether low-volume experience with CS/HIPEC results in acceptable outcomes is unknown. METHODS: A retrospective review of all patients undergoing CS/HIPEC by a single surgeon. Experience was divided into first versus second 50 cases, and patient characteristics, operative details, and outcomes were compared. RESULTS: Ninety patients underwent 100 CS/HIPEC procedures (mean age 57 years, 68% female). -Compared to the initial experience, the second 50 cases included more high grade tumors (68 vs. 52%) and greater disease burden (PCI 14.2 vs. 12.4). Operative times remained unchanged and mean blood loss decreased (978 vs. 684 ml). Hospital stay (mean 18.1 vs. 12.6 days), major complications (24 vs. 16%), and perioperative mortality (8 vs. 2%) declined. Overall median survival was 18 months and was longer with low grade tumors (26 vs. 16 months, P = 0.03). CONCLUSIONS: Patients experienced reduced EBL, fewer major complications, and shorter hospital stay, despite having higher disease burden and higher grade tumors. This suggests that even low-volume experience with CS/HIPEC can lead to a trend in reduction of adverse perioperative events with acceptable oncologic outcomes.