Comparison of survival for metastatic pancreatic cancer patients treated with CPI-613 versus resected borderline-resectable pancreatic cancer patients.

INTRODUCTION: Treatment of advanced pancreatic adenocarcinoma remains suboptimal. Therapeutic agents with a novel mechanism of action are desperately needed; one such novel agent is CPI-613 targets. We here analyze the outcomes of 20 metastatic pancreatic cancer patients treated with CPI-613 and FOLFIRINOX in our institution and evaluate their outcomes to borderline-resectable patients treated with curative surgery. METHODS: A post hoc analysis was performed of the phase I CPI-613 trial data (NCT03504423) comparing survival outcomes to borderline-resectable cases treated with curative resection at the same institution. Survival was measured by overall survival (OS) for all study cases and disease-free survival (DFS) for resected cases with progression-free survival for CPI-613 cases. RESULTS: There were 20 patients in the CPI-613 cohort and 60 patients in the surgical cohort. Median follow-up times were 441 and 517 days for CPI-613 and resected cases, respectively. There was no difference in survival times between CPI-613 and resected cases with a mean OS of 1.8 versus 1.9 year (p = 0.779) and mean PFS/DFS of 1.4 versus 1.7 years (p = 0.512). There was also no difference in 3-year survival rates for OS (hazard ratio [HR] = 1.063, 95% confidence interval [CI] 0.302-3.744, p = 0.925) or DFS/PFS (HR = 1.462, 95% CI 0.285-7.505, p = 0.648). CONCLUSION: The first study to evaluate the survival between metastatic patients treated with CPI-613 versus borderline-resectable cases undergoing curative resection. Analysis revealed no significant differences in survival outcomes between the cohorts. Study results are suggestive that there may be potential utility with the addition of CPI-613 to potentially resectable pancreatic adenocarcinoma, although additional research with more comparable study groups are required.

Conditional Survival After Hepatectomy for Colorectal Liver Metastasis: Results from the Colorectal Liver Operative Metastasis International Collaborative (COLOMIC).

INTRODUCTION: Complete resection of colorectal liver metastasis (CLM) improves long-term survival in colorectal cancer. However, there is limited recent data on conditional survival (CS) as postoperative survival milestones are achieved post-hepatectomy. METHODS: A retrospective analysis was performed on the penta-institutional Colorectal Liver Operative Metastasis International Collaborative (COLOMIC), with 906 consecutive CLM hepatectomy cases. CS was calculated using Bayes' theorem and Kaplan-Meier analysis. Additional CS analyses were performed on additional clinicopathologic risk factors, including colon cancer laterality, KRAS mutation status, and extrahepatic disease. RESULTS: The 5-year CS was 40.6%, 45.3%, 52.8%, and 65.3% at 0, 1, 2, and 3 years postoperatively, with significant improvements each year (p < 0.005). CS was not significantly different between right-sided and left-sided colorectal cancers by 3 years postoperatively. Patients with KRAS mutations had worse CS at all timepoints (p < 0.001). Extrahepatic disease was a poor prognostic factor for OS and CS (p < 0.001). However, CS for patients with KRAS mutations or extrahepatic disease improved significantly as 2-year, postoperative survival was achieved (p < 0.05). CONCLUSIONS: Five-year CS after hepatectomy for CLM improved with each passing year of survival postoperatively. Although extrahepatic disease and KRAS mutations are poor prognostic factors for OS, these populations still had improved CS after 2 years postoperatively.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. METHODS: Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. RESULTS: The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, and the perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection status at first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. CONCLUSIONS: This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Exposure to Neoadjuvant Oxaliplatin-Containing Chemotherapy, Does it Effect Intraperitoneal Hyperthermic Chemotherapy Perfusion?

INTRODUCTION: Patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are commonly exposed to oxaliplatin neoadjuvant chemotherapy (NAT) regimens. The impact of systemic exposure to oxaliplatin prior to HIPEC with oxaliplatin is unknown. METHODS: We conducted a retrospective review of our institutional registry of CRS/HIPEC cases who received oxaliplatin-containing NAT, and compared patients who underwent HIPEC with oxaliplatin versus cases perfused with mitomycin C. The primary outcome was survival, defined by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was performed based on primary tumor etiology and completeness of cytoreduction. RESULTS: A total of 333 cases satisfied the selection criteria-159 appendiceal primaries (all high-grade disease) and 174 colorectal cases. Thirty-one cases (9.3%) underwent HIPEC with oxaliplatin, with the remaining 302 cases (90.7%) receiving mitomycin C. Both cohorts were identical in regard to baseline characteristics, and both groups were alike in regard to NAT regimens and oxaliplatin exposure. There was no difference in survival outcomes. OS times were 2.9 (± 2.8) and 2.8 ( ± 3.6) years for oxaliplatin and mitomycin C perfusions, respectively (p = 0.94), and the 5-year OS rates were also similar at 9.7 and 18.5% (odds ratio [OR] 0.49, 95% confidence interval [CI] 0.14-1.67, p = 0.24) for oxaliplatin and mitomycin cases, respectively. Likewise, DFS findings were similar, with survival of 2.5 (± 4.5) and 1.8 (± 2.4) years for oxaliplatin and mitomycin perfusions, respectively (p = 0.21). There was no difference in 5-year DFS rates, at 10.5 and 7.8% (OR 1.39, 95% CI 0.30-6.56, p = 0.68) for oxaliplatin and mitomycin C, respectively. Subgroup analysis found minimal discordant findings from the main results. CONCLUSION: This analysis found no discernable association with NAT oxaliplatin exposure in regard to survival outcomes following CRS/HIPEC stratified out by perfusion agent.

Impact of myometrium invasion on survival outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective surgical intervention for peritoneal surface malignancy. The effect of myometrium invasion on outcomes is unknown. METHODS: Retrospective review of our institutional registry with analysis of CRS-HIPEC cases involving a hysterectomy. Compared cases with myometrium invasion versus those without invasion. Primary outcome was survival as measured by overall survival (OS) and disease-free survival (DFS). Secondary outcome was the evaluation of risk factors for myometrium invasion based on multivariate analysis. RESULTS: A total of 126 cases of CRS-HIPEC involving a hysterectomy were identified. Ninety-seven cases (76.9%) had no myometrium invasion and the remaining 29 cases (23.1%) had malignant invasion. The presence of myometrial invasion was a significant negative survival prognostic factor. The OS was halved with mean survival times of 2.8 (±2.3) versus 5.8 (±4.7) years for cases with and without invasion, respectively (p = 0.002). Five-year OS rates were also inferior with myometrium invasion at 17.4% versus 53.8% (odds ratio [OR] = 0.181, 95% confidence interval [CI]: 0.057-0.580, p = 0.002). A similar trend was present with DFS with mean survival times of 1.4 (±0.9) versus 3.7 (±3.9) years for noninvasion and invasion cases (p = 0.009). The 5-year DFS rates were 0% versus 34.8% (OR = 0.652, 95% CI: 0.549-0.775, p = 0.004). Secondary analysis significantly associated several risk factors with myometrium invasion to include lymph node positivity (OR = 2.539, 95% CI: 1.074-6.003, p = 0.012), colorectal primary tumors (OR = 2.248, 95% CI: 1.094-5.161, p = 0.035), and high-grade tumors (OR = 2.160, 95% CI: 1.080-4.820, p = 0.038). CONCLUSION: Myometrium invasion is a significant negative prognostic factor for survival following CRS-HIPEC. Several risk factors are potentially predictive of identifying those at high-risk for myometrium invasion.

Switching Perfusion Agents for Repeat Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Surgical Dogma or Evidence-Based Practice?

BACKGROUND: A common practice is to switch chemotherapy perfusion agents for repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). However, there is a paucity of objective benefit with this practice. METHODS: A retrospective review of our institutional registry involving repeat CRS-HIPEC cases was conducted, comparing cases that underwent a perfusion agent switch versus those cases with no switch. The primary outcome of this study was survival, measured by overall survival (OS) and disease-free survival (DFS). A subgroup analysis was performed on the basis of primary etiology. RESULTS: A total of 101 cases met selection criteria. Mitomycin C was used as the index perfusion agent in 84% of cases, while oxaliplatin was utilized in the remaining 16% of cases. In total, 66 cases underwent a perfusion switch, with 35 cases using the same agent. Analysis revealed no survival benefit with HIPEC perfusion switch. For OS, there were similar mean survival times of 5.2 (± 4.1) years and 5.1 (± 3.6) years for cases with perfusion switch and no perfusion switch, respectively (P = 0.985). The 5-year OS rates were also similar at 61.4% and 53.3% for switch and non-switch cases, respectively [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.54-3.56, P = 0.49]. Mean DFS was 4.0 (± 4.2) years and 3.6 (± 3.8) years for switch and non-switch cases, respectively (P = 0.74). The 5-year DFS rates had a greater difference with statistical trend, with rates of 53% versus 28% for switch and non-switch cases, respectively (OR 2.91, 95% CI 0.86-9.86, P = 0.081). Subgroup analysis had a similar trend to the main results. CONCLUSIONS: The study findings revealed no survival benefit with switching perfusion agents. Analysis suggests that the practice of perfusion switch is ineffective.