Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer: A phase I and III open label randomized controlled registry-based clinical trial protocol.

Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15-30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal Cancer-An Overview of Current Status and Future Perspectives.

Peritoneal metastases (PM) are observed in approximately 8% of patients diagnosed with colorectal cancer, either synchronously or metachronously during follow-up. PM often manifests as the sole site of metastasis. PM is associated with a poor prognosis and typically shows resistance to systemic chemotherapy. Consequently, there has been a search for alternative treatment strategies. This review focuses on the global evolution of the combined approach involving cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of PM. It encompasses accepted clinical guidelines, principles for patient selection, surgical and physiological considerations, biomarkers, pharmacological protocols, and treatment outcomes. Additionally, it integrates the relevant literature and findings from previous studies. The role of CRS and HIPEC, in conjunction with other therapies such as neoadjuvant and adjuvant chemotherapy, is discussed, along with the management of patients presenting with oligometastatic disease. Furthermore, potential avenues for future development in this field are explored.

The effect of cognitive behavioral therapy on chemotherapy-induced side effects and immune function in colorectal cancer patients undergoing chemotherapy: study protocol for a randomized controlled trial.

Background: Colorectal cancer (CRC) was one of the most widely diagnosed cancers in the United States in 2021. CRC patients may experience significant psychological stress and are susceptible to depression and anxiety. Previous studies have shown that cognitive behavioral therapy (CBT) can reduce fatigue and improve quality of life among breast cancer patients. However, as a non-pharmaceutical treatment, it remains unclear whether CBT improves chemotherapy-induced side effects and immune function in CRC patients. In this study, we will conduct a randomized controlled trial (RCT) among CRC patients undergoing chemotherapy to determine whether CBT can reduce the side effects of chemotherapy and improve the immune function of CRC patients. Methods: The study will be a single-center RCT. CRC patients undergoing chemotherapy will receive either eight sessions of group-based CBT (every 2-3 weeks) or usual care (usual oncology care). Each participant will undergo assessments at baseline (T0), immediately post-intervention (T1), 3 months post-intervention (T2), and 6 months post-intervention (T3). The primary outcome will include chemotherapy-induced side effects in CRC patients. The secondary outcome will be immune function (measured by levels of inflammatory cytokines). Other outcomes will include the levels of tumor markers, assessments of psychological status (perception of stress, depression and anxiety, self-efficacy, sleep quality, quality of life, social support condition, and cognitive function), and necessary laboratory examinations (biochemical index and blood cell counts) among CRC patients undergoing chemotherapy. Discussion: Our study will provide clinical evidence regarding whether CBT should be generalized in clinical treatment and the extent to which CBT reduces chemotherapy-induced side effects for CRC patients. Trial Registration: ClinicalTrials.gov registration number NCT04741308.

External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. METHODS: Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open-close laparotomy-those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility-those who underwent open-close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS). RESULTS: Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open-close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open-close prediction was 0.78 (95% confidence interval, CI: 0.68-0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52-0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination. CONCLUSION: While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study.

Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM. Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed. Findings: Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy. Interpretation: Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting. Funding: None.

Surgical treatment of rectovaginal fistula-predictors of outcome and effects on quality of life.

PURPOSE: To determine the results after rectovaginal fistula (RVF) repair and find predictors of outcome. Primary objective was fistula healing. Secondary outcomes were morbidity and patient health-related quality of life (HRQoL). METHOD: An observational study of 55 women who underwent RVF repair including both local procedures and tissue transposition 2003-2018 was performed. Baseline patient and fistula characteristics were registered, combined with a prospective HRQoL follow-up and a general questionnaire describing fistula symptoms. RESULTS: Healing rate after index surgery was 25.5% (n = 14) but the final healing rate was 67.3% (n = 37). Comparing the etiologies, traumatic fistulas (iatrogenic and obstetric) had the highest healing rates after index surgery (n = 11, 45.9%) and after repeated operations at final follow-up (n = 22, 91.7%) compared with fistulas of inflammatory fistulas (Crohn's disease, cryptoglandular infection, and anastomotic leakage) that had inferior healing rates after both index surgery (n = 7, 7.1%) and at final follow-up (n = 13, 46.4%). Fistulas of the category others (radiation damage and unknown etiology) included a small amount of patients with intermediate results at both index surgery (n = 1, 33.3%) and healing rate at last follow-up (n = 2, 66.7%). The differences were statistically significant for both index surgery (p = 0.004) and at final follow-up (p = 0.001). Unhealed patients scored lower than both healed patients and the normal population in 6/8 Rand-36 domains, but the differences were not statistically significant. CONCLUSIONS: Most traumatic rectovaginal fistulas closed after repeated surgery whereas inflammatory fistulas had a poor prognosis. Low healing rates after local repairs suggest that tissue transfer might be indicated more early in the treatment process. Unhealed fistulas were associated with reduced quality of life. Trial registration Clinicaltrials.gov No. NCT05006586.

Validating the PSOGI classification of peritoneal disease from non-carcinoid epithelial appendiceal neoplasms in the curative and palliative setting: an observational retrospective study.

Background: Few studies on long-term survival have been published since the new updated pseudomyxoma peritonei (PMP) classification was published in 2016. The aim was to investigate long-term survival according to the Peritoneal Surface Oncology Group International (PSOGI) classification and compare prognostic factors. Methods: From Uppsala University Hospital, consecutive patients referred for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from 2004 to 2017 with peritoneal disease from non-carcinoid mucinous epithelial appendiceal neoplasms were included in the study. The peritoneal disease was divided into four groups: mucin only, low-grade mucinous carcinoma peritonei (MCP-1), high-grade (MCP-2), and high-grade with signet ring cells (MCP-3). Survival curves were rendered, and prognostic factors were compared. Results: The study included 223 patients: 36 with mucin only, 112 with MCP-1, 70 with MCP-2, and 5 with MCP-3. Thirty-eight patients had a palliative debulking or open/close procedure. The 5- and 10-year overall survival was 97% and 97% for mucin only, 83% and 70% for MCP-1, 69% and 49% for MCP-2, with no patients still under follow-up after 5 years in the MCP-3 group. In a multivariable analysis, completeness of cytoreduction (CC) score 2-3 and PSOGI class MCP-3 were significantly associated with lower survival. The 5-year overall survival in the palliative setting was 40% vs. 44% (MCP-1 vs. MCP-2, P>0.05) with median survival 51 vs. 53 months, respectively. Conclusions: The PSOGI classification of PMP provides a solid differentiation of prognostic groups after CRS/HIPEC treatment, but not in the palliative setting.

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI).

INTRODUCTION: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. MATERIALS AND METHODS: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. RESULTS: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. CONCLUSION: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.

Sequential postoperative intraperitoneal chemotherapy for colorectal cancer with peritoneal metastases: a narrative review.

Sequential postoperative intraperitoneal chemotherapy (SPIC) is a chemotherapy abdominal infusion given as a postoperative adjuvant treatment for 6 months after cytoreductive surgery (CRS) for peritoneal surface malignancies. It has most commonly been used in conjunction with ovarian cancer where the SPIC treatment has been integrated with adjuvant systemic chemotherapy. This review investigates the role of SPIC in the setting of colorectal cancer with peritoneal metastases. The focus is on the CRS+SPIC combination treatment with no systemic chemotherapy component. Several cohort studies, several comparative studies, and one randomized trial have been reported with several important endpoints. The following aspects will be covered in this review: overall survival, disease-free survival, morbidity, quality-of-life, and cost-effectiveness. In comparison to systemic chemotherapy alone for isolated resectable colorectal peritoneal metastases, CRS+SPIC is superior concerning overall survival, has no difference in morbidity, is similar in quality-of-life, and SPIC is cost-effective. In comparison to HIPEC, results are conflicting in multivariate analysis; but in a univariate analysis HIPEC (most often combined with systemic adjuvant therapy) appears superior to SPIC alone (no systemic component). The future of SPIC is uncertain. However, a combination of HIPEC and SPIC ± a systemic chemotherapy component is a possible direction to explore further.

Oxaliplatin-based hyperthermic intraperitoneal chemotherapy with single drug versus multiple drug treatment for colorectal cancer with peritoneal metastases: an observational cohort study.

BACKGROUND: Long-term survival for selected patients with peritoneal metastases (PM) from colorectal cancer (CRC) is possible when treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The objective of this study was to compare three different oxaliplatin-based (OX)-HIPEC regimens. Primary end-point was disease-free survival (DFS), and secondary endpoints, morbidity and overall survival (OS). METHODS: This is a retrospective study of all patients with colorectal PM treated with CRS and HIPEC between 2004 and 2015 from the prospectively maintained Uppsala HIPEC database. One hundred and thirty-three patients were identified. Three HIPEC regimens were included: OX-HIPEC, OX-HIPEC + post-operative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil (5-FU), and oxaliplatin-irinotecan-based (OXIRI)-HIPEC. Multivariable Cox regression for DFS was performed. RESULTS: Sixty-one patients received OX-HIPEC, 24 patients received OX-HIPEC + 5-FU EPIC, and 48 patients received OXIRI-HIPEC. The DFS for the OX-HIPEC group was 10.5 months, OX-HIPEC + EPIC 11.9 months, and OXIRI-HIPEC 13.4 months (OX-HIPEC vs. OXIRI HIPEC, P=0.049). The morbidity and OS did not differ between the groups. In the multivariable analysis, low peritoneal cancer index (PCI), absence of liver metastases, low completeness of cytoreduction (CC) score, and multiple drug (EPIC or OXIRI) HIPEC regimen were independent prognostic factors for DFS. CONCLUSIONS: This study showed improved DFS with an intensification of HIPEC by adding irinotecan or EPIC compared to oxaliplatin alone without an increase in morbidity or mortality.

Coagulopathy and Venous Thromboembolic Events Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Coagulopathy after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recognized but few details have been studied. OBJECTIVES: The aim of this study was to investigate changes in coagulation biomarkers and their predictive ability for venous thromboembolism (VTE). METHODS: Patients undergoing CRS and HIPEC at Uppsala University Hospital, Sweden, from 2004 to 2014 were included in a prospective study of coagulation biomarkers. Prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, D-dimer, and platelets were sampled on postoperative days 1, 2, 5, and 10. Logistic regression analysis was used to evaluate predictive capacity for coagulation-related complications. RESULTS: Overall, 380 patients were included (214 females, mean age 56 years); 38 patients had a history of thromboembolism and 57 were active smokers. Mean perioperative blood loss was 1228 mL and 231 (61%) received perioperative blood transfusions. PT-INR and APTT were elevated directly after surgery but returned to normal levels on postoperative day 5. Conversely, fibrinogen, platelet count, D-dimer, and antithrombin increased by postoperative day 5 and continued to increase up to day 10. There were 23 radiologically verified cases of VTE within 6 months. The multivariate analysis identified a completeness of cytoreduction score of 2-3 (p = 0.047) and day 2 D-dimer (p = 0.0082) as independent risk factors for postoperative VTE. CONCLUSION: Significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery and elevated D-dimer on day 2 were independent risk factors for postoperative VTE.

Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study.

BACKGROUND: The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment have never been investigated. AIM: To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival. METHODS: All patients with colorectal peritoneal metastases (1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a bi-institutional database (Uppsala and Sydney) were included in the study. Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs non-neutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for disease-free survival were implemented. RESULTS: Two hundred and forty-six patients were identified - 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the non-neutropenia group (66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P = 0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02. Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio: 0.58, 95% confidence interval: 0.36-0.95, P = 0.03. CONCLUSION: 13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity.

Readmissions after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy-a national population-based study.

BACKGROUND: Comprehensive readmission morbidity studies after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are scarce. This study aimed to investigate readmissions and in-hospital morbidity after CRS and HIPEC. METHODS: The national in-hospital patient register was used to identify patients via the HIPEC ICD code JAQ10 2004-2014. Data were retrieved from the index CRS/HIPEC treatment and from all HIPEC-related readmissions within 6 months. Univariate/multivariate logistical analyses were performed to identify risk factors for reinterventions and readmissions. RESULTS: A total of 519 patients (mean age 56 years) had a mean hospital stay of 27 days. Within 6 months, 150 readmissions for adverse events were observed in 129 patients (25%) with 67 patients requiring an intervention (13%). Totally 179 patients (34%) required a reintervention during the first 6 months with 85 (16%) requiring a reoperation. Of these 179 patients, 83 patients (46%) did not undergo the intervention at the HIPEC centre. Gastric resection was the only independent risk factor for in-hospital intervention, and advanced age for readmission. CONCLUSION: Morbidity causing HIPEC-related readmission was higher than expected with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and high age are independent predictors of morbidity and readmission.

Prognostic Impact of BRAF and KRAS Mutation in Patients with Colorectal and Appendiceal Peritoneal Metastases Scheduled for CRS and HIPEC.

BACKGROUND: KRAS and BRAF mutations are prognostic and predictive tools in metastatic colorectal cancer, but little is known about their prognostic value in patients scheduled for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Therefore, we analyzed the prognostic impact of KRAS and BRAF mutations in patients with peritoneal metastases scheduled for CRS and HIPEC. PATIENTS AND METHODS: In a consecutive series of 399 patients scheduled for CRS and HIPEC between 2009 and 2017, 111 subjects with peritoneal metastases from primaries of the appendix, colon, or rectum were analyzed for KRAS mutation and 92 for BRAF mutation. RESULTS: Mutation in KRAS was present in 51/111 (46%), and mutated BRAF was found in 10/92 (11%). There was no difference in overall survival between KRAS mutation tumors and KRAS wild type, whereas BRAF mutation was associated with short survival. No subject with BRAF mutation survived 2 years. On multivariate analysis, completeness of cytoreduction score (CCS, p = 0.000001), presence of signet cell differentiation (p = 0.000001), and BRAF mutation (p = 0.0021) were linked with poor prognosis. CONCLUSIONS: BRAF mutation is a marker of poor prognosis in patients with appendiceal and colorectal peritoneal metastases scheduled for CRS and HIPEC, whereas survival outcome in subjects with mutated KRAS does not differ from wild-type KRAS. This finding suggests that those with BRAF mutation should be considered for alternative treatment options.

Peritoneal mesothelioma in Sweden: A population-based study.

The study aim was to report survival and morbidity of all patients in Sweden with peritoneal mesothelioma treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as well as investigate whether the survival has increased on a population level since this treatment was nationalized 2011. Study data were collected from the Swedish HIPEC registry and the Swedish National Cancer Registry. All patients with peritoneal mesothelioma scheduled for CRS/HIPEC treatment in Sweden January 2011 to March 2018 were retrieved from the Swedish HIPEC registry. Clinicopathological and survival data were collected. For population-level analysis, all patients with diffuse malignant peritoneal mesothelioma (DMPM) were identified from the Swedish National Cancer Registry and data were retrieved from two separate 5-year time periods: 1999-2003 and 2011-2015. Thirty-two patients were accepted for CRS/HIPEC. Four were open/close cases. Two-year survival rate was 84% or 59% when excluding borderline peritoneal mesotheliomas (n = 17). Median overall survival was not reached. Grade III-IV Clavien-Dindo events occurred in 22% with no mortality. From the national cancer registry, 102 DMPM cases were retrieved: 40 cases between 1999 and 2003, and 62 cases between 2011 and 2015 (corresponding to an increase from 0.9 to 1.24/million/year, P = .04). Six patients (10%) received CRS/HIPEC in the second period. Median OS increased between periods from 7 to 15 months and 5-year survival from 14% to 29% (P = .03). Peritoneal mesothelioma of both borderline and DMPM subtypes undergoing CRS/HIPEC have good long-term survival. The incidence of DMPM in Sweden has increased. Overall survival has increased alongside the introduction of CRS/HIPEC, which may be a contributing factor.

Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy treatment of colorectal peritoneal metastases: cohort analysis of high volume disease and cure rate.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) treatment of colorectal peritoneal metastases (PM) is an established treatment alternative. The study aim was, first, to investigate the outcome of high-volume disease defined by the peritoneal cancer index (PCI) 20; second, to report the long-term disease-free survival of patients with >5 years observation. METHODS: Consecutive patients with colorectal PM from a prospective HIPEC database between 2004 and 2010 were included, 67 patients. Clinicopathological and outcome parameters were compared between low PCI (n = 40) and high PCI (n = 27). A subgroup analysis on patients with >5 years observation was performed (n = 32). Disease-free survival after 5 years defined cure. RESULTS: Median overall survival (OS) was 28 months, low PCI-group 33 months versus high PCI-group 17 months (P = 0.03). Median OS of patients with complete CRS (n = 56) was 30 months, low PCI-group 37 months versus high PCI-group 27 months (P = 0.2), with 5-year survival of 31% and 21%, respectively. No difference in morbidity/mortality. The cure rate was 22% in the subgroup (7/32) and 28% in those with complete CRS (7/25). Two patients in the cured group had PCI 29 and 34. DISCUSSION: Treatment of high-volume disease may result in long-term survival and even cure. The key is to reach a complete CRS. The overall cure rate is 22%.

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal and hepatic metastases: a case-control study.

BACKGROUND: Concomitant treatment of colorectal peritoneal metastases (PM) and hepatic metastases (HM) remains controversial. This study compares the cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal metastases (PM) with the CRS/IPC/hepatic resection treatment of colorectal PM and HM. METHODS: All patients from a prospective PM registry at the Uppsala institution treated concomitantly for PM/HM with CRS/IPC/hepatic resections were included in a PM/HM-group, n=11. They were matched 1(:)2 with patients from the registry being treated only for PM with CRS/IPC, n=22. Overall survival (OS), disease-free survival (DFS), morbidity, mortality, and recurrences were compared. RESULTS: The PM/HM-group had median OS of 15 months (95% CI: 6-46 months) and the PM-group had a median OS of 34 months (95% CI: 19-37 months), P=0.2. The DFS was 10 months (95% CI: 3-14 months) and 24 months (95% CI: 10-32 months) respectively, P=0.1. Morbidity was 27% in both groups and one postoperative death in the PM/HM-group. Currently, 1/10 (10%) patients with an R1 resection are disease-free in the PM/HM group while 9/20 (45%) are disease-free in the PM group (P=0.05). CONCLUSIONS: Concomitant treatment of PM and HM with CRS/IPC/hepatic resections is feasible with no significant increase in morbidity compared to CRS/IPC. The risk of recurrences is higher in the PM/HM group with a tendency towards worse DFS.

Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer.

BACKGROUND: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis (PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC from colorectal cancer (CRC). METHODS: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. RESULTS: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. CONCLUSIONS: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. In the CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.