European Groundshot-addressing Europe's cancer research challenges: a Lancet Oncology Commission.

Cancer research is a crucial pillar for countries to deliver more affordable, higher quality, and more equitable cancer care. Patients treated in research-active hospitals have better outcomes than patients who are not treated in these settings. However, cancer in Europe is at a crossroads. Cancer was already a leading cause of premature death before the COVID-19 pandemic, and the disastrous effects of the pandemic on early diagnosis and treatment will probably set back cancer outcomes in Europe by almost a decade. Recognising the pivotal importance of research not just to mitigate the pandemic today, but to build better European cancer services and systems for patients tomorrow, the Lancet Oncology European Groundshot Commission on cancer research brings together a wide range of experts, together with detailed new data on cancer research activity across Europe during the past 12 years. We have deployed this knowledge to help inform Europe's Beating Cancer Plan and the EU Cancer Mission, and to set out an evidence-driven, patient-centred cancer research roadmap for Europe. The high-resolution cancer research data we have generated show current activities, captured through different metrics, including by region, disease burden, research domain, and effect on outcomes. We have also included granular data on research collaboration, gender of researchers, and research funding. The inclusion of granular data has facilitated the identification of areas that are perhaps overemphasised in current cancer research in Europe, while also highlighting domains that are underserved. Our detailed data emphasise the need for more information-driven and data-driven cancer research strategies and planning going forward. A particular focus must be on central and eastern Europe, because our findings emphasise the widening gap in cancer research activity, and capacity and outcomes, compared with the rest of Europe. Citizens and patients, no matter where they are, must benefit from advances in cancer research. This Commission also highlights that the narrow focus on discovery science and biopharmaceutical research in Europe needs to be widened to include such areas as prevention and early diagnosis; treatment modalities such as radiotherapy and surgery; and a larger concentration on developing a research and innovation strategy for the 20 million Europeans living beyond a cancer diagnosis. Our data highlight the important role of comprehensive cancer centres in driving the European cancer research agenda. Crucial to a functioning cancer research strategy and its translation into patient benefit is the need for a greater emphasis on health policy and systems research, including implementation science, so that the innovative technological outputs from cancer research have a clear pathway to delivery. This European cancer research Commission has identified 12 key recommendations within a call to action to reimagine cancer research and its implementation in Europe. We hope this call to action will help to achieve our ambitious 70:35 target: 70% average 10-year survival for all European cancer patients by 2035.

Sodium Thiosulfate Reduces Acute Kidney Injury in Patients Undergoing Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy with Cisplatin: A Single-Center Observational Study.

BACKGROUND: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a multimodal treatment concept for patients with peritoneal surface malignancies. The use of intraperitoneal cisplatin (CDDP) is associated with a risk of acute kidney injury (AKI). The aim of this study is to evaluate the protective effect of perioperative sodium thiosulfate (STS) administration on kidney function in patients undergoing CRS and CDDP-based HIPEC. PATIENTS AND METHODS: We retrospectively analyzed clinical data of all patients who underwent CRS and CDDP-based HIPEC at our hospital between March 2017 and August 2020. Patients were stratified according to the use of sodium thiosulfate (STS vs. no STS). We compared kidney function and clinical outcome parameters between both groups and determined risk factors for postoperative AKI on univariate and multivariate analysis. AKI was classified according to acute kidney injury network (AKIN) criteria. RESULTS: Of 238 patients who underwent CRS and CDDP-based HIPEC, 46 patients received STS and 192 patients did not. There were no significant differences in baseline characteristics. In patients who received STS, a lower incidence (6.5% vs. 30.7%; p = 0.001) and severity of AKI (p = 0.009) were observed. On multivariate analysis, the use of STS (OR 0.089, p = 0.001) remained an independent kidney-protective factor, while arterial hypertension (OR 5.283, p < 0.001) and elevated preoperative urea serum level (OR 5.278, p = 0.032) were predictors for postoperative AKI. CONCLUSIONS: The present data suggest that STS protects patients from AKI caused by CRS and CDDP-based HIPEC. Further prospective studies are needed to validate the benefit of STS among kidney-protective strategies.

FIRE-9 - PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer.

BACKGROUND: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. METHODS: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. DISCUSSION: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18).

Decision-Making Analysis for Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer: A Survey by the Executive Committee of the Peritoneal Surface Oncology Group International (PSOGI).

OBJECTIVES: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. METHODS: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. RESULTS: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. DISCUSSION AND CONCLUSION: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.

Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma - the phase III "PREVENT"- (FLOT9) trial of the AIO /CAOGI /ACO.

BACKGROUND: The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40-50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published. METHODS: This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens's classification) adenocarcinoma of the stomach and Type II/III GEJ. All enrolled pts. will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life. The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed. Recruitment has already started and first patient in was on January 18th, 2021. DISCUSSION: If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery. TRIAL REGISTRATION: The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .

Peritoneal metastasis in gastric cancer: results from the German database.

BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis with a median survival of 7 months. A benefit of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) could be shown in several selected patient cohorts but remains controversial. The aim of this study was, to reflect the results of a national German HIPEC registry initiated by the German Society of General and Visceral Surgery (DGAV). METHODS: The DGAV HIPEC registry StuDoQ|Peritoneum documents patients with peritoneal malignancy contributed from 52 hospitals. All consecutive documented patients from 2011 until 2016 (n = 3078) were treated with CRS and HIPEC and were analysed. A total of 315 (10%) suffered from gastric cancer and were analysed. RESULTS: A complete data set of 235 patients was available for this study, including 113 male (48.1%) and 122 female (51.9%) patients with a median age of 53.4 years (SD ± 11.9). The median PCI was 8.0 (range 1-30). A complete cytoreduction was achieved in 121 patients (71.6%). Postoperative complications (Clavien-Dindo grades 3-4) occurred in 40 patients (17%). The median overall survival (OS) time was 13 months. The 5-year survival rate was 6%. According to the PCI from 0-6 (n = 74); 7-15 (n = 70) and 16-39 (n = 24) the median OS differs significantly (18 months vs. 12 months vs. 5 months; p = 0.002). CONCLUSIONS: CRS and HIPEC in selected patients with gastric cancer and peritoneal spread can improve survival when they are treated in centers. An accurate staging and patient selection are of major importance to achieve long-term survival.

Gender comparison of clinical, histopathological, therapeutic and outcome factors in 185,967 colon cancer patients.

INTRODUCTION: Colorectal carcinomas represent the third most common cause of cancer-related deaths in Germany. Although the incidence is significantly higher in men compared with women and gender is a well-established crucial factor for outcome in other diseases, detailed gender comparisons for colon cancer are lacking. METHODS: This retrospective population-based cohort study included all patients diagnosed with colon cancer in Germany between 2000 and 2016 who were included in the common dataset of colorectal cancer patients from the quality conference of the German Cancer Society. We compared clinical, histopathological, and therapeutic characteristics as well as overall and recurrence-free survival. RESULTS: A total of 185,967 patients were included in the study, of which 85,685 were female (46.1%) and 100,282 were male (53.9%). The proportion of women diagnosed with colon cancer decreased from 2000 to 2016 (f: 26.6 to 40.1%; m: 24.9 to 41.9%; p < 0.001), and the proportion of very old patients was especially high in women (f: 27.3%; m: 15.6%; p < 0.001). The localization in women was more right-sided (f: 45.0%, m: 36.7%; p < 0.001), and women had a higher tumor grading and a higher UICC stage (especially stage III nodal-positive) at diagnosis of primary colon cancer (UICC III: f: 22.7%, m: 21.0%; p < 0.001). We could detect a significantly better overall (hazard ratio: 0.853, lower 95%: 0.841, upper 95%: 0.864; p < 0.001) and recurrence-free survival (hazard ratio: 0.857, lower 95%: 0.845, upper 95%: 0.868; p < 0.001) in women compared with men, even though women received chemotherapy less frequently compared with men (f: 26.1%, m: 28.1%; p < 0.001). CONCLUSION: We could detect several variables that differed significantly between men and women regarding clinical, histopathological, therapeutic, and outcome factors. We believe that it is crucial to consider gender as a key factor in the diagnosis and treatment of colon cancer. Sex-specific diagnostic tools could lead to an earlier diagnosis of colon cancer in women, and ways to increase the rate of chemotherapy in women should be evaluated. Furthermore, we recommend stratifying randomized trials by gender.

Synergy Effect of Combined Near and Mid-Infrared Fibre Spectroscopy for Diagnostics of Abdominal Cancer.

Cancers of the abdominal cavity comprise one of the most prevalent forms of cancers, with the highest contribution from colon and rectal cancers (12% of the human population), followed by stomach cancers (4%). Surgery, as the preferred choice of treatment, includes the selection of adequate resection margins to avoid local recurrences due to minimal residual disease. The presence of functionally vital structures can complicate the choice of resection margins. Spectral analysis of tissue samples in combination with chemometric models constitutes a promising approach for more efficient and precise tumour margin identification. Additionally, this technique provides a real-time tumour identification approach not only for intraoperative application but also during endoscopic diagnosis of tumours in hollow organs. The combination of near-infrared and mid-infrared spectroscopy has advantages compared to individual methods for the clinical implementation of this technique as a diagnostic tool.

Morbidity and Mortality Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Data from the DGAV StuDoQ Registry with 2149 Consecutive Patients.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are performed for well-selected patients with peritoneal surface malignancies. This combined treatment is potentially associated with an increased rate of complications. OBJECTIVE: The aim of this paper was to analyze the morbidity and mortality of CRS and HIPEC in the German national registry. METHODS: We present a retrospective analysis of 2149 consecutive patients from 52 hospitals. The data were prospectively documented in the DGAV StuDoQ Registry between February 2011 and December 2016. RESULTS: Almost two-thirds of all patients had a colorectal malignancy; therefore, the most frequently performed resections were colectomies (54%) and rectal resections (30%). Only 36.2% of all patients had no anastomosis, and fewer than 20% of all patients were older than 70 years of age (16.4%). Enteric fistula and anastomotic leaks occurred in 10.5% of all cases. The reoperation rate was 14.6% (95% confidence interval [CI] 11.51-18.1). Major grade 3 and 4 complications (Clavien-Dindo classification) occurred in 19.3% of all patients, half of which were due to surgical complications. The overall 30-day postoperative hospital mortality was 2.3% (95% CI 1.02-3.85). Multivariate analysis showed an increased risk for morbidity associated with pancreatic resections (odds ratio [OR] 2.4), rectal resection (OR 1.5), or at least one anastomosis (OR 1.35), and mortality with reoperation (OR 8.7) or age > 70 years (OR 3.35). CONCLUSIONS: CRS and HIPEC are associated with acceptable morbidity and low mortality. These results show that CRS and HIPEC can be safely performed nationwide when close mentoring by experienced centers is provided.

The efficacy of treatment options for patients with gastric cancer and peritoneal metastasis.

BACKGROUND: Patients with peritoneal metastases of gastric cancer have a poor prognosis and median survival of 7 months. This study compared treatment options and outcomes based on the Peritoneal Cancer Index (PCI). METHODS: This retrospective analysis included patients with gastric cancer treated between August 2008 and December 2017 with synchronous peritoneal metastases only diagnosed by laparoscopy. The three treatments were as follows: (1) cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in combination with pre- and postoperative systemic chemotherapy (n = 58), (2) laparotomy/laparoscopy without CRS, but HIPEC in combination with pre- and postoperative systemic chemotherapy (n = 11), and (3) systemic chemotherapy only (n = 19). RESULTS: A total of 88 patients aged 54.6 ± 10.9 years with mean PCI of 14.3 ± 11.3 were included. The PCI was significantly lower in group 1 (8.3 ± 5.7) than in group 2 (23.9 ± 11.1, p < 0.001) and group 3 (27.3 ± 9.3, p < 0.001). Mean time from diagnosis to laparoscopy was 5.2 ± 2.9 months. The median overall survival was 9.8 ± 0.7 for group 1, 6.3 ± 3.0 for group 2 and 4.9 ± 1.9 months for group 3 (p < 0.001). Predictors for deteriorated overall patient survival included > 4 cycles of preoperative chemotherapy (HR 4.49, p < 0.001), lymph-node metastasis (HR 3.53, p = 0.005), PCI ≥ 12 (HR 2.11, p = 0.036), and incompleteness of cytoreduction (HR 4.30, p = 0.001) in patients treated with CRS and HIPEC. CONCLUSION: CRS and HIPEC showed convincing results in selected patients with PCI < 12 and complete cytoreduction. Prolonged duration (> 4 cycles) of preoperative intravenous chemotherapy reduced patient survival in patients suitable for CRS and HIPEC.

Safety of extraperitoneal rectal resection and ileo- or colorectal anastomosis without loop ileostomy in patients with peritoneal metastases treated with CRS and HIPEC.

AIM: Extraperitoneal rectal resection combined with complete peritonectomy of the pelvis in patients with peritoneal metastases is associated with a high rate of morbidity and mortality due to anastomotic leakage (AL). Therefore, many centers tend to perform loop ileostomy to reduce the clinical impact of AL. The aim of this study was to analyze the need for protective stoma creation in this patient group to avoid major complications and mortality in the case of AL. METHOD: We analyzed 53 patients who underwent extraperitoneal rectal resection from 409 consecutive patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) at our department between January 1997 and December 2016. RESULTS: Mean age of the patients was 56.7 (SD 12.2) years and the mean Peritoneal Cancer Index was 24.6 (SD 12.0). Complete cytoreduction was achieved in 33 patients (62.3%). Six patients received an ileostomy or a colostomy, 5 of 6 with permanent intention. One patient (2.1%) developed AL postoperatively. Overall, 21 patients (39.6%) developed surgical complications, while 41 (77.3%) developed medical complications. The mortality rate was 7.5% (n = 4). In total, 26 patients (49.1%) developed Clavien-Dindo class-III/IV complications. CONCLUSIONS: These results demonstrate the safety of colorectal anastomosis in combination with HIPEC in the absence of loop ileostomy. Loop ileostomy may be omitted for patients with low risk for AL in experienced centers with adequate post-operative care, possibilities for post-operative assessment and radiological intervention to avoid stoma related complications and increase the quality of life of patients with peritoneal metastases. This article is protected by copyright. All rights reserved.

Predictive value of peritoneal cancer index for survival in patients with mucinous peritoneal malignancies treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a single centre experience.

OBJECTIVES: This study investigated the correlation between the peritoneal carcinomatosis index (PCI) and patient outcome depending on the tumour type. BACKGROUND: Peritoneal surface malignancy (PSM) treatment depends on tumour type. Mucinous PSM (m-PSM) is associated with a better prognosis than non-mucinous PSM (nm-PSM). The PCI's predictive ability has not yet been evaluated. METHODS: We analysed 123 patients with PSM treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) between 2008 and 2015. The m-PSM group (n = 75) included patients with appendiceal cancer (n = 15), colorectal cancer (n = 21), or low-grade appendiceal mucinous neoplasm (n = 39); the nm-PSM group (n = 48) included patients with gastric (n = 18) or colorectal (n = 30) cancer. The PCI's predictive ability was evaluated by multiple Cox-proportional hazard regression analysis and Kaplan-Meier curves. RESULTS: The 5-year survival and PCI were higher in m-PSM patients (67.0%; 20.5 ± 12.1) than in nm-PSM patients (32.6%; p = 0.013; 8.9 ± 6.0; p < 0.001). Colorectal nm-PSM patients with PCI ≥16 had a worse 2-year survival (25.0%) vs. patients with PCI <16 (79.1%; log rank = 0.009), but no significant effect was observed in patients with m-PSM (66.7% vs. 68.1%; p = 0.935). Underlying disease (HR 5.666-16.240), BMI (HR 1.109), and PCI (HR 1.068) significantly influenced overall survival in all patients. CONCLUSIONS: PCI is prognostic in nm-PSM, but not in m-PSM. CRS and HIPEC may benefit not only patients with low PCI, but also those with high PCI and m-PSM.

Registries on peritoneal surface malignancies throughout the world, their use and their options.

AIM: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries. METHODS: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected. RESULTS: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year. CONCLUSIONS: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

Can hyperthermic intraperitoneal chemotherapy efficiency be improved by blocking the DNA repair factor COP9 signalosome?

PURPOSE: A frequently used chemotherapeutic agent in hyperthermic intraperitoneal chemotherapy (HIPEC) is mitomycin C (MMC) which induces DNA damage and apoptosis in tumor cells. In addition, MMC activates DNA damage response (DDR) leading to repair mechanisms counteracting the effect of chemotherapy. COP9 signalosome (CSN) positively influences the DDR pathway by its intrinsic deneddylating and associated kinase activities. In an in vitro HIPEC model, we studied the impact of curcumin, an inhibitor of CSN-associated kinases, and of the microRNA (miRNA) let-7a-1, an inhibitor of CSN subunit expression, on the MMC-induced apoptosis in human HT29 colon cancer cells. METHODS: Cells were incubated at 37 °C and indicated concentrations of MMC in a medium preheated to 42 °C as under HIPEC conditions for 1 or 4 h. HT29 cells were cotreated with 50 µM curcumin or transfected with let-7a-1 miRNA mimic. After incubation, cells were analyzed by Western blotting, densitometry, and caspase-3 ELISA. RESULTS: An increase of CSN subunits in response to MMC treatment was detected. Apoptosis was only measured after 4 h with 50 µM MMC. MMC-induced apoptosis was elevated by cotreatment with curcumin. Transfection of HT29 cells with let-7a-1 reduced the expression of tested CSN subunits associated with the accumulation of the pro-apoptotic factors p27 and p53. CONCLUSIONS: In response to MMC treatment, the CSN is elevated as a regulator of DDR retarding apoptosis in tumor cells. The therapeutic effect of HIPEC can be increased by inhibiting CSN-associated kinases via curcumin or by blocking CSN expression with let-7a-1 miRNA.

Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial.

PURPOSE: In patients with peritoneal metastasis (PM) from gastric cancer (GC), chemotherapy is the treatment of choice. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are still being debated. This randomized, controlled, open-label, multicenter phase III trial (EudraCT 2006-006088-22; ClinicalTrials.gov identifier: NCT02158988) explored the impact on overall survival (OS) of HIPEC after CRS. PATIENTS AND METHODS: Adult patients with GC and histologically proven PM were randomly assigned (1:1) to perioperative chemotherapy and CRS alone (CRS-A) or CRS plus HIPEC (CRS + H). HIPEC comprised mitomycin C 15 mg/m2 and cisplatin 75 mg/m2 in 5 L of saline perfused for 60 minutes at 42°C. The primary end point was OS; secondary endpoints included progression-free survival (PFS), other distant metastasis-free survival (MFS), and safety. Analyses followed the intention-to-treat principle. RESULTS: Between March 2014 and June 2018, 105 patients were randomly assigned (53 patients to CRS-A and 52 patients to CRS + H). The trial stopped prematurely because of slow recruitment. In 55 patients, treatment stopped before CRS mainly due to disease progression/death. Median OS was the same for both groups (CRS + H, 14.9 [97.2% CI, 8.7 to 17.7] months v CRS-A, 14.9 [97.2% CI, 7.0 to 19.4] months; P = .1647). The PFS was 3.5 months (95% CI, 3.0 to 7.0) in the CRS-A group and 7.1 months (95% CI, 3.7 to 10.5; P = .047) in the CRS + H group. The CRS + H group showed better MFS (10.2 months [95% CI, 7.7 to 14.7] v CRS-A, 9.2 months [95% CI, 6.8 to 11.5]; P = .0286). The incidence of grade ≥3 adverse events (AEs) was similar between groups (CRS-A, 38.1% v CRS + H, 43.6%; P = .79). CONCLUSION: This study showed no OS difference between CRS + H and CRS-A. PFS and MFS were significantly better in the CRS + H group, which needs further exploration. HIPEC did not increase AEs.

Current trends in the management of Gastro-oEsophageal cancers: Updates to the ESSO core curriculum (ESSO-ETC-UGI-WG initiative).

Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.

Quality of life in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is it worth the risk?

OBJECTIVE: To investigate the course of health-related quality of life (HQL) over time in patients with peritoneal carcinomatosis (PC) after complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Prospective, single-center, nonrandomized cohort study using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: Ninety patients who underwent CRS and HIPEC for PC in our institution were enrolled in the study. Mean age was 56 years (range 27-77 years) (61% female). Primary tumor was colorectal in 21%, ovarian in 19%, pseudomyxoma peritonei in 16%, an appendix tumor in 16%, gastric cancer in 10%, and peritoneal mesothelioma in 13% of cases. Mean peritoneal carcinomatosis index was 22 (range 2-39). Mean global health status score was 69±25 preoperatively and 55±20, 66±22, 66±23, 71±23, and 78±21 at months 1, 6, 12, 24, and 36, respectively. Physical and role function recovered significantly at 6 months and were close to baseline at the 24-month measurement. Emotional function starting from a low baseline recovered to baseline by month 12. Cognitive and social function had slow recovery on follow-up. Fatigue, diarrhea, dyspnea, and sleep disturbance were symptoms persistent at 6-month follow-up, improving later on in survivors. CONCLUSIONS: Survivors after CRS and HIPEC have postoperative quality of life similar to preoperatively, with most of the reduced elements recovering after 6-12 months. We conclude that reduced quality of life of patients after CRS and HIPEC should not be used as an argument to deny surgical therapy to these patients.

Synchronous Pleural and Peritoneal Mesothelioma: a Case Report and Narrative Review.

Malignant mesotheliomas most often affect the pleura and tend to spread locally within the originating cavity. Mesotheliomas are already rare diseases, and cases with synchronous pleural and peritoneal involvement are scarce in the literature. Mesothelioma in children is a rare disease representing only 0.9% of all mesotheliomas. They exhibit similar distribution and characteristics as mesotheliomas in adults and generally, a poor prognosis. Due to the rarity, there is no standardized treatment recommendation for children with mesothelioma. Though the malignant mesothelioma tends to spread locally within the originating cavity, pleuM have been reported to metastasize into the peritoneal cavity and vice versa. As there are only few studies concerning the metastatic spread of mesothelioma, it is difficult to define a precise incidence and risk factors for patients to develop metastases of the other mesothelium. There is no standardized therapeutic recommendation for patients with synchronous pleuM and perM. Our patient proved to profit from a radical two-stage surgical approach in combination with locoregional chemotherapy; she showed no sign of tumor recurrences 9 years after tumor resection. In conclusion, clinical studies are needed to confirm the benefit of this treatment and to determine its limitations and selection criteria.