Prognostic Relevance of Recurrent Sites of Gastric Cancer Treated With Curative Resection: A Single Center Retrospective Study.

PURPOSE: Gastric cancer treated with curative resection exhibits several recurrence patterns. The peritoneum is the most common site of recurrence. Some reports have indicated different prognostic influences according to the recurrence sites in other cancers, such as esophageal and colorectal cancers. This study investigated whether the recurrence sites influenced the prognosis of patients with recurrent gastric cancer. MATERIALS AND METHODS: The data of 115 patients who experienced tumor recurrence after curative gastrectomy were retrospectively reviewed. The sites of recurrence were divided into 4 groups: lymph node (LN), peritoneum, other single organs, and multiple lesions. Clinicopathological features were compared between the sites of recurrence. Prognosis after resection and recurrence were also compared. RESULTS: The peritoneum was the primary site of recurrence in 38 patients (33%). The tumor differentiation and pathological stages were significantly different. Survival after surgery did not show a statistically significant difference (hazard ratio [HR] of LN: 1, peritoneum: 1.083, other single organs: 1.025, and multiple lesions: 1.058; P=1.00). Survival after recurrence was significantly different (HR of LN, 1; peritoneum, 2.164; other single organs, 1.092; multiple lesions, 1.554; P=0.01), and patients with peritoneal and multiple lesion recurrences had worse prognosis. Furthermore, peritoneal recurrence seemed to occur later than that at other sites; the median times to recurrence in LN, peritoneal, other single-organ, and multiple lesions were 265, 722, 372, and 325 days, respectively. CONCLUSIONS: The sites of gastric cancer recurrence may have different prognostic effects. Peritoneal recurrence may be less sensitive to chemotherapy and occur during the late phase of recurrence.

Survival Difference of Endometrial Cancer Patients with Peritoneal Metastasis Receiving Cytoreductive Surgery (CRS) with and without Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Systematic Review and Meta-Analysis.

Although several studies have been completed to investigate the effect of cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in endometrial cancer with peritoneal metastasis (ECPM), a direct comparison was not performed previously. A meta-analysis was performed to investigate the suspected additional survival benefits of CRS plus HIPEC over CRS only. Twenty-one and ten studies with a total number of 1116 and 152 cases investigating CRS only and CRS plus HIPEC were identified, respectively. When all articles were analyzed, the 1-year survival rate was 17.60% higher for CRS plus HIPEC (82.28% vs. 64.68%; p = 0.0102). The same tendency was observed for the 2-year (56.07% vs. 36.95%; difference: 19.12%; p = 0.0014), but not for the 5-year (21.88% vs. 16.45%; difference: 5.43%; p = 0.3918) survival rates. The same clinical significance, but statistically less strong observations, could be made if only the studies published after 2010 were investigated (1-year survival rate: 12.08% and p = 0.0648; 2-year survival rate: 10.90% and p = 0.0988). CRS remains one of the core elements of ECPM treatment, but the addition of HIPEC to CRS can increase the positive clinical outcome, especially in the first 2 years.

Intraoperative urinary tract resection and construction in CRS + HIPEC procedures: a single center retrospective analysis.

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.

Risk Scoring System to Predict Mortality in Gastric Cancer with Peritoneal Carcinomatosis.

Gastric cancer (GC) with peritoneal carcinomatosis (PC) has a particularly unfavorable prognosis. This limited survival raises doubts about which factors confer an extremely worse outcome and which patients could benefit from more aggressive treatments, in an attempt to improve survival and better control the disease. This study aimed to evaluate the survival outcomes of patients with PC due to GC and develop a prognostic score to predict 6-month mortality. We performed an analysis of clinical stage IV GC with PC. Scores were assigned to risk factors and calculated for each patient from nine variables. Among 326 IVB GC, 211 (64.7%) had PC and were included. After calculating the score, 136 (64.5%) GCs were classified as a low-risk group and 75 (35.5%) as a high-risk group. Median OS was 7.9 and 1.9 months for low- and high-risk patients (p < 0.001). In the high-risk group, 77.3% of the patients died in <6 mo (p < 0.001). Palliative surgery and chemotherapy were associated with better survival, and the prognostic groups maintained statistical significance even when the same type of treatment was performed. In conclusion, the scoring system developed with variables related to patient performance status and clinical data was able to distinguish GC with PC with a high risk of 6-month mortality. Accordingly, verifying and validating our findings in a large cohort of patients is necessary to confirm and guarantee the external validation of the results.

Exosomal ROR1 in peritoneal fluid identifies peritoneal disseminated PDAC and is associated with poor survival.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and peritoneal dissemination is one major cause for this poor prognosis. Exosomes have emerged as promising biomarkers for gastrointestinal cancers and can be found in all kinds of bodily fluids, also in peritoneal fluid (PF). This is a unique sample due to its closeness to gastrointestinal malignancies. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) has been identified as a potential biomarker in human cancers and represents a promising target for an immunotherapy approach, which could be considered for future treatment strategies. Here we prospectively analyzed the exosomal surface protein ROR1 (exo-ROR1) in PF in localized PDAC patients (PER-) on the one hand and peritoneal disseminated tumor stages (PER+) on the other hand followed by the correlation of exo-ROR1 with clinical-pathological parameters. Methods: Exosomes were isolated from PF and plasma samples of non-cancerous (NC) (n = 15), chronic pancreatitis (CP) (n = 4), localized PDAC (PER-) (n = 18) and peritoneal disseminated PDAC (PER+) (n = 9) patients and the surface protein ROR1 was detected via FACS analysis. Additionally, soluble ROR1 in PF was analyzed. ROR1 expression in tissue was investigated using western blots (WB), qPCR, and immunohistochemistry (IHC). Exosome isolation was proven by Nano Tracking Analysis (NTA), WB, Transmission electron microscopy (TEM), and BCA protein assay. The results were correlated with clinical data and survival analysis was performed. Results: PDAC (PER+) patients have the highest exo-ROR1 values in PF and can be discriminated from NC (p <0.0001), PDAC (PER-) (p <0.0001), and CP (p = 0.0112). PDAC (PER-) can be discriminated from NC (p = 0.0003). In plasma, exo-ROR1 is not able to distinguish between the groups. While there is no expression of ROR1 in the exocrine pancreatic tissue, PDAC and peritoneal metastasis show expression of ROR1. High exo-ROR1 expression in PF is associated with lower overall survival (p = 0.0482). Conclusion: With exo-ROR1 in PF we found a promising diagnostic and prognostic biomarker possibly discriminating between NC, PDAC (PER-) and PDAC (PER+) and might shed light on future diagnostic and therapeutic concepts in PDAC.

Hyperthermic intraperitoneal chemotherapy in colorectal cancer.

BACKGROUND: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. PATIENTS AND METHODS: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. RESULTS: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. CONCLUSIONS: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

Long-term survival outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma with peritoneal metastasis (HCC-PM) has a poor outlook. Traditional treatments have limited effect on survival. The safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) have been shown in other peritoneal cancers. This study evaluates the role of CRS + HIPEC in HCC-PM. METHODS: A retrospective analysis of HCC-PM patients treated with CRS + HIPEC at Beijing Shijitan Hospital from March 2017 to December 2023 was conducted, assessing clinical features, severe adverse events (SAEs), and overall survival (OS) rates. RESULTS: The study population comprised 10 HCC-PM patients who underwent CRS + HIPEC. The median peritoneal cancer index (PCI) was 25, and complete cytoreduction (CC0 ~ 1) was achieved in half of the patients. Three patients experienced SAEs within 30 days postoperatively. The 1-year, 3-year, and 5-year OS rates were recorded as 89.0%, 89.0%, and 21.0% respectively, with a median OS1 of 107.8 months and OS2 of 49.9 months. The median progression-free survival (PFS) was 5.0 months. CONCLUSION: The application of CRS + HIPEC offers significant benefits to patients with HCC-PM. A selected group of patients may achieve prolonged PFS. Incorporating CRS + HIPEC into the treatment paradigm can thus be considered a strategic therapeutic option for patients with HCC-PM.

Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis.

BACKGROUND: Gastric cancer with peritoneal metastases is associated with a dismal prognosis. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver chemotherapy intraperitoneally leading to higher intraperitoneal concentrations of cytotoxic drugs compared to intravenous administration. We reviewed the effectiveness and safety of different methods of palliative intraperitoneal chemotherapy. METHODS: Embase, MEDLINE, Web of Science and Cochrane were searched for articles studying the use of repeated administration of palliative intraperitoneal chemotherapy in patients with gastric cancer and peritoneal metastases, published up to January 2024. The primary outcome was overall survival. RESULTS: Twenty-three studies were included, representing a total of 999 patients. The pooled median overall survival was 14.5 months. The pooled hazard ratio of the two RCTs using intraperitoneal paclitaxel and docetaxel favoured the intraperitoneal chemotherapy arm. The median overall survival of intraperitoneal paclitaxel, intraperitoneal docetaxel and PIPAC with cisplatin and doxorubicin were respectively 18.4 months, 13.2 months and 9.0 months. All treatment methods had a relatively safe toxicity profile. Conversion surgery after completion of intraperitoneal therapy was performed in 16% of the patients. CONCLUSIONS: Repeated intraperitoneal chemotherapy, regardless of method of administration, is safe for patients with gastric cancer and peritoneal metastases. Conversion surgery after completion of the intraperitoneal chemotherapy is possible in a subset of patients.

Critical reappraisal of prognostic indicators for 949 mucinous appendiceal neoplasm patients.

BACKGROUND AND OBJECTIVES: The standard of care for treatment of an appendiceal mucinous neoplasm with peritoneal dissemination is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). These two treatments are combined in the operating room. A crucial requirement for benefit long-term is proper patient selection. Clinical and histopathologic prognostic indicators are used, along with the patient's fitness for surgery, to select patients to receive CRS and HIPEC. METHODS: This study seeks to identify the reliable prognostic indicators for four different groups of patients. They are (1) the low-grade appendiceal mucinous neoplasms (LAMN) with a complete CRS, (2) the mucinous appendiceal adenocarcinomas (MACA) with complete CRS, (3) MACA with lymph node metastases (MACA-LN) with complete CRS, and (4) all histologic subtypes with incomplete cytoreduction. The prognostic indicators were evaluated for their impact on overall survival in these four groups of patients. RESULTS: The completeness of cytoreduction (CC) score statistically significantly showed survival differences in all three histologic subtypes. The peritoneal cancer index (PCI) showed significance with LAMN and MACA-LN but not with MACA and not with incomplete CRS. The prior surgical score (PSS) was a prognostic indicator that predicted the outcome with LAMN, MACA-LN, and incomplete CRS patients but not with the MACA group. Patients who were symptomatic or who had extensive systemic chemotherapy before CRS had a significantly reduced survival. CONCLUSION: The utility of prognostic indicators varied greatly within our four different groups of appendiceal mucinous neoplasms. CC score was always a reliable prognosticator. Surprisingly, PCI was not.

Perioperative intraperitoneal plus systemic chemotherapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gastric cancer: phase Ib/II single-arm prospective study.

BACKGROUND: In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis or even after reducing peritoneal tumor burden by upfront IP chemotherapy. METHOD: Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II. RESULTS: The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively. CONCLUSION: A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.

Different Frequency and Clinical Role for MTAP Loss in Pleural and Peritoneal Mesothelioma.

The objective of this study was to analyze the expression and prognostic role of methylthioadenosine phosphorylase (MTAP) in mesothelioma. MTAP protein expression by immunohistochemistry was analyzed in 113 mesotheliomas (60 pleural and 53 peritoneal), consisting of 36 effusions and 77 surgical specimens. MTAP expression was fully lost in 38 tumors and partially lost in 8 tumors. Loss of expression was significantly more common in effusions compared with biopsies/surgical resection specimens (20/36 vs. 26/77; P =0.017), and in pleural compared with peritoneal mesotheliomas (35/60 vs. 11/53; P <0.001). MTAP performed less robustly than BAP1 in comparative analysis of 57 tumors previously analyzed for expression of the latter protein (46 vs. 25 cases with loss of expression). In survival analysis for 69 patients with partial clinical data, male gender was significantly associated with shorter overall survival (OS; P =0.042), whereas loss of MTAP was associated with a trend for shorter OS ( P =0.058), with no prognostic role for patient age ( P =0.379) or anatomic site ( P =0.381). The association between loss of MTAP and poor OS became significant when survival analysis was limited to patients with pleural mesothelioma ( P =0.018). In conclusion, loss of MTAP expression is more frequent in pleural compared with peritoneal mesothelioma and has limited diagnostic relevance at the latter anatomic site. More frequent loss in effusion specimens suggests a role for this marker in effusion cytology. MTAP loss in pleural mesothelioma is associated with poor survival.

Bile Spillage as a Prognostic Factor for Gall Bladder Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Biliary spillage (BS) is a common complication following initial cholecystectomy for gall bladder cancer (GBC). Few studies have explored the importance of BS as a long-term prognostic factor. We perform a meta-analysis of the association between BS and survival in GBC. METHODS: A systematic literature search was performed in February 2023. Studies evaluating the incidence of BS and its association with long-term outcomes in patients undergoing initial laparoscopic or open cholecystectomy for either incidental or resectable GBC were included. Overall survival (OS), disease-free survival (DFS), and rate of peritoneal carcinomatosis (RPC) were the primary end points. Forest plot analyses were used to calculate the pooled hazard ratios (HRs) of OS, DFS, and RPC. Metaregression was used to evaluate study-level association between BS and perioperative risk factors. RESULTS: Of 181 published articles, 11 met inclusion criteria with a sample size of 1116 patients. The rate of BS ranged between 9% and 67%. On pooled analysis, BS was associated with worse OS (HR = 1.68, 95% confidence interval [CI] = 1.32-2.14), DFS (pooled HR= 2.19, 95% CI = 1.30-3.68), and higher RPC (odds ratio = 9.37, 95% CI = 3.49-25.2). The rate of BS was not associated with higher T stage, lymph node metastasis, higher grade, positive margin status, reresection, or conversion rates. CONCLUSIONS: Our meta-analysis shows that BS is a predictor of higher peritoneal recurrence and poor survival in GBC. BS was not associated with tumor characteristics or conversion rates. Further research is needed to identify other potential risk factors for BS and investigate the ideal treatment schedule to improve survival.

Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis.

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC. METHODS: We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts. RESULTS: Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy. CONCLUSIONS: Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Has time to chemotherapy from primary debulking surgery in advanced ovarian cancer an impact on survival? - A population-based nationwide SweGCG study.

OBJECTIVE: The aim of the study was to investigate if time to start chemotherapy (TTC) after primary debulking surgery (PDS) impacted relative survival (RS) in advanced epithelial ovarian/fallopian tube/primary peritoneal cancer (EOC). METHODS: Nationwide population-based study of women with EOC FIGO stages IIIC-IV, registered 2008-2018 in the Swedish Quality Register for Gynecologic Cancer, treated with PDS and chemotherapy. TTC was categorized into; ≤21 days, 22-28 days, 29-35 days, 36-42 days and > 42 days. Relative survival (RS) was estimated using the Pohar-Perme estimate of net survival. Multivariable analyses of excess mortality rate ratios (EMRRs) were estimated by Poisson regression models. RESULTS: In total, 1694 women were included. The median age was 65.0 years. Older age and no residual disease were more common in TTC >42 days than 0-21 days. The RS at 5-years was 37.9% and did not differ between TTC groups. In the R0 (no residual disease) cohort (n = 806), 2-year RS was higher in TTC ≤21 days (91.6%) and 22-28 days (91.4%) than TTC >42 days (79.1%). TTC >42 days (EMRR 2.33, p = 0.026), FIGO stage IV (EMRR 1.83, p = 0.007) and non-serous histology (EMRR 4.20, p < 0.001) were associated with 2-year worse excess mortality compared to TTC 0-21 days, in the R0 cohort. TTC was associated with 2-year survival in the R0 cohort in FIGO stage IV but not in stage IIIC. TTC was not associated with RS in patients with residual disease. CONCLUSIONS: For the entire cohort, stage IV, non-serous morphology and residual disease, but not TTC, influenced 5-year relative survival. However, longer TTC was associated with a poorer 2-year survival for those without residual disease after PDS.

Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases: A Nationwide Population-Based Study.

BACKGROUND: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. METHODS: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009-2015 and 2016-2021). RESULTS: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009-2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016-2021 (30.2% in expert centers, 22.6% in referring centers). In 2009-2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02-2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66-0.96). In 2016-2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76-2.13) and survival (HR 1.00, 95% CI 0.76-1.32). CONCLUSION: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.

Correlation between peritoneal cancer index and survival in advanced epithelial ovarian cancer with complete resection.

OBJECTIVE: The aim of this study was to investigate the relation between the peritoneal cancer index, overall survival, and recurrence free survival, in patients with epithelial ovarian cancer. METHODS: Patients treated at the Gustave-Roussy Institute between December 2004 and November 2017 for advanced epithelial ovarian cancer in complete resection were included. The correlation between the peritoneal cancer index and survival was studied using statistical modeling. Multivariate analysis was performed with a logistic regression model. RESULTS: Of the 351 patients included, 94 (27%) had initial surgery and 257 (73%) had interval surgery. Median follow-up was 52.7 months (range 47.6-63.9). Median peritoneal cancer index was 10 (range 0-32). The linear model best represented the relationship between peritoneal cancer index and overall survival. Patients with neoadjuvant chemotherapy had a greater instantaneous risk of baseline death than those with initial surgery, as well as a more rapid increase in this risk as the peritoneal cancer index increased. Overall survival and recurrence free survival were better in the initial surgery group (103.4 months (79.1-not reached (NR)) vs 66.5 months (59.1-95.3) and 31.8 months (23.7-48.7) vs 25.9 months (23.2-29), respectively). Risk factors for death were body mass index, peritoneal cancer index, and need for neoadjuvant chemotherapy. CONCLUSION: The peritoneal cancer index is a prognostic indicator, but its linear relationship with survival precluded setting a unique peritoneal cancer index cut-off. Moreover, the prognostic impact of peritoneal cancer index was stronger in the setting of neoadjuvant chemotherapy.

Retrospective Evaluation of the Prognostic Value of Histological Growth Pattern in Patients with Colorectal Peritoneal Metastases Undergoing Curative-Intent Cytoreductive Surgery.

BACKGROUND: Two distinct histological growth patterns (HGPs) were described in patients with peritoneal metastasis of colorectal cancer origin (PMCRC) with limited Peritoneal Cancer Index (PCI) ≤ 6 who did not receive neoadjuvant chemotherapy (NAC) and were treated with cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC): pushing HGP (P-HGP) and infiltrating HGP (I-HGP). Patients with dominant P-HGP (> 50%) had significantly better disease-free survival (DFS) and overall survival (OS). OBJECTIVE: We aimed to determine whether these previous observations regarding the prognostic value of HGP in patients with PMCRC with low PCI (≤ 6) are also valid in all operable patients, regardless of whether they received NAC or not and regardless of PCI score. METHODS: This was a retrospective study including 76 patients who underwent complete CRS ± HIPEC for PMCRC between July 2012 and March 2019. In each patient, up to five of the largest excised peritoneal nodules were analyzed for their tumor-to-peritoneum interface. Correlations between NAC, HGP, and prognosis were further explored. RESULTS: Thirty-seven patients (49%) had dominant P-HGP and 39 (51%) had dominant I-HGP. On univariate analysis, patients with P-HGP ≤ 50% had significantly lower OS than those with dominant P-HGP > 50% (39 versus 60 months; p = 0.014) confirmed on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5; p = 0.006). There were no significant associations between NAC and type of HGP. CONCLUSIONS: This study confirms the prognostic value and reproducibility of the two previously reported HGPs in PMCRC. Dominant P-HGP is associated with better DFS and OS in patients undergoing curative-intent CRS ± HIPEC compared with I-HGP, independently of the extent of peritoneal disease burden.