Anastomotic leakage following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: A clinical cohort study.

BACKGROUND: Extended oncological resections for colorectal cancer surgery are associated with a high rate of complications, especially anastomotic leakage (AL). This study determines the incidence of risk factors for postoperative complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer (CRC). METHODS: In this cohort study, the clinical data of all patients with CRC, treated with CRS and HIPEC, from 2011 to 2021 was analyzed. We considered patients' characteristics, tumor-specific features, postoperative complications, and hospital stay using Chi-Square-test or Fisher's exact test. The Mann-Whitney-U-test was used to measure the probability of differences between two sets of data. RESULTS: Of 1089 HIPEC procedures performed in the study center, 185 patients with CRC and peritoneal metastasis were treated with CRS and HIPEC after formation of at least one anastomosis and therefore included in this study. This included synchronous and metachronous peritoneal metastasis with a mean peritoneal cancer index of 8.67 ± 5.22. In this cohort, AL occurred in 12 (6.5 %) patients. There was no correlation between the number of anastomoses and the occurrence of an AL (p = 0.401). CONCLUSION: This study reports a low risk of AL after CRS with HIPEC for CRC, comparable to other published data. If a complete cytoreduction seems possible, the risk of anastomotic leakage should not negatively influence the decision to resect. Further studies on this subject are essential to validate our findings.

Peritoneal Metastatic Gastric Cancer: Local Treatment Options and Recommendations.

Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.

Prioritization and resource allocation in the context of the COVID-19 pandemic. Recommendations for colorectal and pancreatic cancer in Germany.

In the context of the COVID-19 pandemic, there has been a scarcity of resources with various effects on the care of cancer patients. This paper provides an English summary of a German guideline on prioritization and resource allocation for colorectal and pancreatic cancer in the context of the pandemic. Based on a selective literature review as well as empirical and ethical analyses, the research team of the CancerCOVID Consortium drafted recommendations for prioritizing diagnostic and treatment measures for both entities. The final version of the guideline received consent from the executive boards of nine societies of the Association of Scientific Medical Societies in Germany (AWMF), 20 further professional organizations and 22 other experts from various disciplines as well as patient representatives. The guiding principle for the prioritization of decisions is the minimization of harm. Prioritization decisions to fulfill this overall goal should be guided by 1. the urgency relevant to avoid or reduce harm; 2. the likelihood of success of the diagnostic or therapeutic measure advised; and 3. the availability of alternative treatment options. In the event of a relevant risk of harm as a result of prioritization, these decisions should be made by means of a team approach. Gender, age, disability, ethnicity, origin and other social characteristics, such as social or insurance status, as well as the vehemence of a patient's treatment request and SARS-CoV-2 vaccination status should not be used as prioritization criteria. The guideline provides concrete recommendations for 1. diagnostic procedures, 2. surgical procedures for cancer, and 3. systemic treatment and radiotherapy in patients with colorectal or pancreatic cancer within the context of the German healthcare system.

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.

[The Association of Surgical Oncology (ACO) curriculum "Surgical oncology"-Prerequisites for participation, registration and course]. / Das ACO-Kurrikulum "Chirurgische Onkologie" ­ Voraussetzungen zur Teilnahme, Anmeldung und Ablauf.

For solid malignancies of the gastrointestinal tract, surgical removal is a central pillar of treatment and often the only possibility to achieve a long-term cure. While there are additional qualifications for an oncological subspecialization in other surgical disciplines, such as gynecology or urology nothing comparable exists for visceral surgery in Germany, despite the fact that interdisciplinary cancer treatment strategies are becoming increasingly more complex. The Association of Surgical Oncology (ACO) in cooperation with the European Union of Medical Specialists (UEMS) has created the curriculum for surgical oncology, a structured further education concept, which concludes with the European Board of Surgical Qualification (EBSQ) examination. This results in a standardization and improvement in surgical and oncological treatment in Germany. Furthermore, successful graduates receive an ACO as well as a UEMS certificate and are Fellows of the European Board of Surgery (FEBS).

Early postoperative CRP predicts major complications following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Objectives: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is associated with significant postoperative complications. Early detection of at-risk patients may lead to improved outcomes. The role of C-reactive protein (CRP) in predicting postoperative complications has only been recently investigated. Methods: Postoperative complications were categorized according to Clavien-Dindo classification and further divided into minor (Grade <3) and major complications (Grade ≥3A). Absolute CRP counts (mg/L) on postoperative days (POD) 1-7, and proportional change in CRP was compared and the area under (AUC) receiver operating characteristics (ROC) curve was calculated. Univariate and multivariate analysis was performed. Significant findings were externally validated. Results: Twenty-five percent of patients experienced one or more major complications. A CRP level of ≥106 mg/L on POD 2 and 65.5 mg/L on POD 4 were significantly associated with an increased risk of major complications with an AUC of 0.658 and 0.672, respectively. The proportional increase in CRP between POD 1 and 4 (ΔCRP POD 1/4) at a cut-off of 30 % had the best AUC of 0.744 and was the only independent risk factor for major complications (p<0.0001) on multivariate analysis. ∆CRP had an AUC of 0.716 (p=0.002) when validated in an independent database. Conclusions: CRP can be used in a variety of ways to predict major complications after CRS and HIPEC. However, the ∆CRP POD 1/4>30 % is the best indicator of major complications. Serial CRP measurements in the early postoperative period may lead to early detection of patients at risk of major complications allowing for alternative management strategies to improve outcomes.

Treatment of Colorectal Cancer in Certified Centers: Results of a Large German Registry Study Focusing on Long-Term Survival.

(1) Background: The WiZen study is the largest study so far to analyze the effect of the certification of designated cancer centers on survival in Germany. This certification program is provided by the German Cancer Society (GCS) and represents one of the largest oncologic certification programs worldwide. Currently, about 50% of colorectal cancer patients in Germany are treated in certified centers. (2) Methods: All analyses are based on population-based clinical cancer registry data of 47.440 colorectal cancer (ICD-10-GM C18/C20) patients treated between 2009 and 2017. The primary outcome was 5-year overall survival (OAS) after treatment at certified cancer centers compared to treatment at other hospitals; the secondary endpoint was recurrence-free survival. Statistical methods included Kaplan-Meier analysis and multivariable Cox regression. (3) Results: Treatment at certified hospitals was associated with significant advantages concerning 5-year overall survival (HR 0.92, 95% CI 0.89, 0.96, adjusted for a broad range of confounders) for colon cancer patients. Concentrating on UICC stage I-III patients, for whom curative treatment is possible, the survival benefit was even larger (colon cancer: HR 0.89, 95% CI 0.84, 0.94; rectum cancer: HR 0.91, 95% CI 0.84, 0.97). (4) Conclusions: These results encourage future efforts for further implementation of the certification program. Patients with colorectal cancer should preferably be directed to certified centers.

Effects of the Pandemic on the Care of Patients With Colorectal Cancer.

BACKGROUND: During the COVID-19 pandemic, there was a decrease in the rates of diagnosis and treatment of cancer. However, only a few detailed analyses have been made to date regarding the effect of the pandemic on the care of cancer patients in Germany. Such studies are needed as the basis for well-founded recommendations on health-care delivery priorities during pandemics and other, comparable situations of crisis. METHODS: This review is based on publications that were retrieved by a selective search of the literature for controlled studies from Germany on the effects of the pandemic on colonoscopies, first diagnoses of colorectal cancer (CRC), surgical procedures for CRC, and CRC-related mortality. RESULTS: Compared to 2019, the rate of screening colonoscopies performed by physicians in private practice was 1.6% higher in 2020 and 4.3% higher in 2021. On the other hand, the rate of diagnostic colonoscopies in the inpatient setting was 15,7% lower in 2020, while that of therapeutic colonoscopies was 11.7% lower. According to the data evaluated here, first diagnoses of CRC were 2.1% less common in January to September in 2020 than they had been in 2019; according to routine data collected by the statutory health insurance provider GRK, surgery for CRC was 10% less common in 2020 than in 2019. With regard to mortality, sufficient data from Germany were lacking to draw definite conclusions. International modeling data suggest an increase in mortality due to decreased colorectal screening rates during the pandemic that may at least be partially compensated for by intensified screening strategies following the pandemic. CONCLUSION: Three years after the onset of the COVID-19 pandemic, there is still only a limited evidence base for an evaluation of the effects of the pandemic on medical care and on the outcomes of patients with CRC in Germany. The implementation of central data and research infrastructures will be necessary for further study of the long-term effects of this pandemic, as well as to enable optimal preparedness for future crisis situations.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases.

BACKGROUND: Advanced gastric cancer with synchronous peritoneal metastases (GC-PM) is associated with a poor prognosis. Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising approach, only a limited number of Western studies exist. AIM: To investigate the clinicopathological outcomes of patients who underwent CRS-HIPEC for GC-PM. METHODS: A retrospective analysis of patients with GC-PM was conducted. All patients were seen at the Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany between January 2011 and July 2021 and underwent CRS-HIPEC. Preoperative laboratory results, the use of neoadjuvant trastuzumab, and the details of CRS-HIPEC, including peritoneal carcinomatosis index, completeness of cytoreduction, and surgical procedures were recorded. Disease-specific (DSS), and overall survival (OS) of patients were calculated. RESULTS: A total of 73 patients were included in the study. Patients treated with neoadjuvant trastuzumab (n = 5) showed longer DSS (P = 0.0482). Higher white blood cell counts (DSS: P = 0.0433) and carcinoembryonic antigen levels (OS and DSS: P < 0.01), and lower hemoglobin (OS and DSS: P < 0.05) and serum total protein (OS: P = 0.0368) levels were associated with shorter survival. Longer HIPEC duration was associated with more advantageous median survival times [60-min (n = 59): 12.86 mo; 90-min (n = 14): 27.30 mo], but without statistical difference. To obtain additional data from this observation, further separation of the study population was performed. First, propensity score-matched patient pairs (n = 14 in each group) were created. Statistically different DSS was found between patient pairs (hazard ratio = 0.2843; 95% confidence interval: 0.1119-0.7222; P = 0.0082). Second, those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity (median survival: 12.68 mo vs 24.02 mo), or had to undergo the procedure before 2016 (median survival: 12.68 mo vs 27.30 mo; P = 0.0493) were removed from the original study population. CONCLUSION: Based on our experience, CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients. Prolonged HIPEC duration may serve as a good therapy for these patients.

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Primary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. METHODS: Clinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. RESULTS: The median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan-Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). CONCLUSIONS: With multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Prognostic Factors in Pseudomyxoma Peritonei with Emphasis on the Predictive Role of Peritoneal Cancer Index and Tumor Markers.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and by the extent of the disease. METHODS: Prognostic relevance of tumor markers CA19-9 and CEA, gender, Peritoneal Cancer Index (PCI), and completeness of cytoreduction (CC) after cytoreductive surgery were evaluated on 193 consecutive PMP patients, based on a retrospective analysis of prospectively gathered data from a German tertial referral center. RESULTS: We demonstrated that low PCI, CC0 status, low-grade histology, and female gender were independent positive prognostic factors for both overall survival (OS) and progression-free survival (PFS). Furthermore, LAMN patients with achieved CC0 status show significantly better OS and PFS compared to those with CC1 status (p = 0.0353 and p = 0.0026 respectively). In contrast, the duration and drug of hyperthermic intraperitoneal chemotherapy (HIPEC) were not prognostic in any comparison. Increased CA19-9 and CEA levels were significantly associated with HAMN cases, but also predicted recurrence in patients with low-grade histologies. CONCLUSION: Our study confirmed the prognostic role of tumor markers and emphasized the importance of CC status and PCI in a large cohort of PMP- and LAMN patients.

Role of HIPEC after Complete Cytoreductive Surgery (CRS) in Peritoneal Recurrence of Platinum-Sensitive Recurrent Ovarian Cancer (OC): The Aim for Standardization at Two Reference Centers for CRS.

BACKGROUND: This bicentric study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for platinum-sensitive recurrent ovarian cancer patients. METHODS: The data of 88 patients with the first peritoneal recurrence of platinum-sensitive epithelial ovarian cancer who underwent CRS and HIPEC from a prospective HIPEC registry were retrospectively investigated. Endpoints were feasibility, chemotherapeutic compound, time of exposure, complications, and overall survival. RESULTS: The median follow-up was 4.7 years (95%-CI 4.6-5.5). The median age was 55.8 years (IQR: 50.3-66.2). Eighty-four patients (95.5%) had high-grade serous histology. The median peritoneal cancer index was 12.0 (IQR: 7.0-20.5). Sixty-five patients (73.9%) had complete cytoreduction (CCR 0). Thirty-eight patients (43.2%) received HIPEC for 60 min, and fifty patients (56.8%) for 90 min. Eighteen patients (20.5%) had grade III to IV complications. One patient (1.1%) died perioperatively. The overall median survival was 43.1 months (95%-CI 34.1-52.2), and the 5-year survival rate was 39.7%. Only 90 min HIPEC and cisplatin were associated with survival. CONCLUSION: In well-selected patients with platinum-sensitive recurrent ovarian cancer, survival may correlate with complete CRS and 90 min cisplatin-based HIPEC. We confirmed the results of primary OC studies; therefore, this combination should be used for further analysis in the recurrent situation.

Clinical outcome after total neoadjuvant treatment (CAO/ARO/AIO-12) versus intensified neoadjuvant and adjuvant treatment (CAO/ARO/AIO-04) a comparison between two multicenter randomized phase II/III trials.

BACKGROUND: Total neoadjuvant therapy (TNT) can enhance local tumor regression, but its survival benefits compared to intensified chemoradiotherapy (CRT) followed by adjuvant chemotherapy (CT) remain unclear. METHODS: This is a secondary comparison between 607 patients treated with intensified 5-FU/Oxaliplatin neoadjuvant CRT and adjuvant CT within the experimental arm of the CAO/ARO/AIO-04 phase III trial, and 306 patients treated with TNT within the CAO/ARO/AIO-12 phase II trial. Comparison between clinical-pathological characteristics, surgical quality, and post-surgical complications were analyzed using the Pearson's Chi-squared or Mann-Whitney U test. Oncological outcome was examined with log-rank, Gray's test, and multivariate cox regression. In addition, further subgroup analyses and propensity score matching were performed to optimize the balance of baseline covariates. FINDINGS: Patients treated with CRT followed by consolidation CT had a significantly higher rate of pathological complete remission (pCR) compared to patients treated within the experimental arm of the CAO/ARO/AIO-04 trial (25.3 % vs 17.3 %, P = 0.04). Post-surgical complications were less common in the CAO/ARO/AIO-12 trial. After a median follow-up of 46 months, clinical outcome did not differ significantly in the overall cohort, in any subgroup or after propensity score matching. In multivariate analysis, disease-free survival (DFS) was similar between the experimental arm of the CAO/ARO/AIO-04 trial and treatments arms of the CAO/ARO/AIO-12 trial (vs arm A: HR 0.92 [95 % CI 0.62-1.37], P = 0.69; vs arm B: HR 1.06 [95 % CI 0.72-1.58], P = 0.76). INTERPRETATION: Notwithstanding the limitations of intertrial comparison, TNT did not improve long term oncological outcome in our study compared to the intensified neoadjuvant CRT and adjuvant CT treatment in the CAO/ARO/AIO-04 trial. Improved response rates after TNT offers an attractive option to explore organ preservation in selective patients with locally advanced rectal cancer.

Radiotherapy dose escalation using endorectal brachytherapy in elderly and frail patients with rectal cancer unsuitable for surgery: Lessons from studies in fit patients and future perspectives.

Epidemiological data indicate that more than 50 % of patients with newly-diagnosed rectal cancer are older than 70 years, with rising numbers expected over the next decades. Treatment decision-making is challenging in elderly and frail patients with rectal cancer, whereas standardized treatment guidelines for this patient cohort are lacking. Elderly and frail rectal cancer patients are often considered by surgeons as unfit to undergo radical surgery as the risk of surgical complications and postoperative mortality rises with increasing age and comorbidity. Furthermore, these patients often receive no treatment at all, resulting in local and/or systemic disease progression with associated symptoms and impaired quality of life (QoL). Recent data from randomized trials in young fit patients with early stage rectal cancer indicate that RT dose escalation can be safely delivered using external beam (chemo)radiotherapy (EBRT) followed by endoluminal radiotherapeutic modalities, such as contact X-ray brachytherapy (CXB) or high-dose rate endorectal brachytherapy (HDR-BT). However, prospective studies testing this therapeutic concept in elderly and frail patients remain limited. Here, we review the current evidence in the epidemiology and the management of elderly and frail patients with rectal cancer. We summarize the potential of RT dose escalation to achieve long-term local control of the primary tumour, prevent disease-related morbidity, improve QoL and even organ preservation. Future perspectives and open questions will be discussed as well.

Patients with Metachronous Peritoneal Metastatic Mucinous Colorectal Adenocarcinoma Benefit More from Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) than Their Synchronous Counterparts.

BACKGROUND: Mucinous adenocarcinoma is a frequent subtype in colorectal cancer (CRC). A higher initial T-stage, poorer differentiation, worse response to anti-tumor therapies, and shorter survival are characteristic of mucinous CRC. Moreover, the therapeutic benefit of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) in mucinous CRC has not been significantly investigated. METHODS: A retrospective analysis of 218 CRC patients with synchronous or metachronous peritoneal metastases was conducted. RESULTS: 129 and 89 patients had synchronous and metachronous metastases, and 36 (27.8%) and 22 (24.8%) of these were mucinous CRC, respectively. Mucinous CRC was more frequent in the proximal colon, with a higher T-stage and N-stage and with an average peritoneal carcinomatosis index that was 2 values higher. Disease-specific survival was significantly worse in the synchronous mucinous group (median survival: 22.4 months vs. 36.3 months, p = 0.0229). In contrast, no such difference was observed in the metachronous cohort (32.6 months vs. 34.4 months, p = 0.6490). CONCLUSIONS: In the case of synchronous peritoneal metastases originating from mucinous CRC, the positive effect of CRS+HIPEC cannot be verified, and the added value of this highly invasive treatment is therefore somewhat questioned. However, CRS + HIPEC is recommended for metachronous metastases, since no difference between the two CRC-subtypes could be verified.

Total Neoadjuvant Therapy for Rectal Cancer in the CAO/ARO/AIO-12 Randomized Phase 2 Trial: Early Surrogate Endpoints Revisited.

BACKGROUND: Early efficacy outcome measures in rectal cancer after total neoadjuvant treatment are increasingly investigated. We examined the prognostic role of pathological complete response (pCR), tumor regression grading (TRG) and neoadjuvant rectal (NAR) score for disease-free survival (DFS) in patients with rectal carcinoma treated within the CAO/ARO/AIO-12 randomized phase 2 trial. METHODS: Distribution of pCR, TRG and NAR score was analyzed using the Pearson's chi-squared test. Univariable analyses were performed using the log-rank test, stratified by treatment arm. Discrimination ability of non-pCR for DFS was assessed by analyzing the ROC curve as a function of time. RESULTS: Of the 311 patients enrolled, 306 patients were evaluable (Arm A:156, Arm B:150). After a median follow-up of 43 months, the 3-year DFS was 73% in both groups (HR, 0.95, 95% CI, 0.63-1.45, p = 0.82). pCR tended to be higher in Arm B (17% vs. 25%, p = 0.086). In both treatment arms, pCR, TRG and NAR were significant prognostic factors for DFS, whereas survival in subgroups defined by pCR, TRG or NAR did not significantly differ between the treatment arms. The discrimination ability of non-pCR for DFS remained constant over time (C-Index 0.58) but was slightly better in Arm B (0.61 vs. 0.56). CONCLUSION: Although pCR, TRG and NAR were strong prognostic factors for DFS in the CAO/ARO/AIO-12 trial, their value in selecting one TNT approach over another could not be confirmed. Hence, the conclusion of a long-term survival benefit of one treatment arm based on early surrogate endpoints should be stated with caution.

[Surgical treatment of adenocarcinoma of the esophagogastric junction type II : Comparison between transhiatal extended gastrectomy and thoracoabdominal esophagectomy]. / Chirurgische Therapie des Adenokarzinoms des ösophagogastralen Übergangs Typ II : Vergleich zwischen transhiatal erweiterter Gastrektomie und thorakoabdomineller Ösophagektomie.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction (AEG) has significantly increased. However, the best surgical treatment for AEG type II is still the subject of current research. The goal of this retrospective cohort study is to compare survival and recurrence rates in patients, who underwent either thoracoabdominal esophagectomy (TAE) or transhiatal extended gastrectomy (TEG). MATERIAL AND METHODS: The study is based on a cohort of 272 patients diagnosed with AEG type II between 2002 and 2020, recorded by a population-based clinical cancer registry. Of the included patients 63 underwent TAE and 209 TEG. In order to compare overall survival, recurrence rates, and recurrence free survival, we applied the Kaplan-Meier method, univariable and multivariable Cox regression. RESULTS: Our analysis showed no statistically significant difference concerning overall survival (p = 0.333). However a tendency towards higher survival rates after TAE for the period from 2016-2020 (p = 0,058) is possible. In contrast a significant difference concerning higher cumulative recurrence rates after TAE was found after Kaplan-Meier analysis (p = 0.049). This trend was not observed for the time after 2016 (p = 0.993), in which over 50% of TAE were performed. No differences were found regarding recurrence-free survival (p = 0.772). CONCLUSION: Our findings in a rather small cohort are concordant with most studies showing no differences or a trend towards better survival after TAE. Other studies found no significant difference regarding recurrence-free survival as well. In conclusion, no significant differences were found between TEG and TAE in surgical treatment of AEG type II.

Prolonged Exposition with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) May Provide Survival Benefit after Cytoreductive Surgery (CRS) in Advanced Primary Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer.

Background: The usage of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gynecological cancers is increasing. Methods: Prospectively collected data of 85 advanced primary ovarian/fallopian tube cancer and peritoneal carcinoma patients of a single center were investigated. Results: A total 48, 37, 62, and 25 patients were enrolled into the HIPEC with/without neoadjuvant chemotherapy (upfront vs. interval) and into the 60 min and 90 min long HIPEC groups, respectively. Better overall survival (OS) was observed in the 90 min HIPEC group (p = 0.0330), compared to the 60 min HIPEC group. Neither OS (p = 0. 2410), disease-specific (p = 0. 3670), nor recurrence-free survival (p = 0.8240) differed between upfront and interval HIPEC. Higher peritoneal carcinomatosis index (PCI) values were associated with worse disease-specific survival (p = 0.0724). Age (p = 0.0416), body mass index (p = 0.0044), PCI (p < 0.0001), the type (p = 0.0016) and duration (p = 0.0012) of HIPEC, and increased perioperative morbidity (p < 0.0041) had the greatest impact on OS. Conclusions: Increasing data support the value of HIPEC in the treatment of advanced ovarian cancer. Ongoing prospective studies will definitively clarify the role and timing of this additional therapeutic approach.

Rare Histologies and Infrequent Indications for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

AIM: This single-centre study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with rare histologies and uncommon tumour origins. PATIENTS AND METHODS: Prospectively collected data from the data registry of a single institution was retrospectively investigated. We present a series of selected patients who underwent CRS and HIPEC between 2011 and 2021 for peritoneal metastases arising from infrequent tumour entities. RESULTS: The study included 76 patients. From the wide range of histologies, seven groups were formed: Cancer of unknown primary, uncommon ovarian cancer types, other gynaecological tumours (endosalpingiosis, endometrial and cervical cancer), small bowel carcinoma, recurrent peritoneal mesothelioma, desmoplastic small round-cell tumour, and other rare malignancies. The median peritoneal cancer index was 8. Fifty-five patients with primary and 22 patients with recurrent disease were examined. Complete macroscopic tumour resection was achieved in 84% of cases. The median survival was 68.53 months considering the entire cohort, whilst the longest survival rate was registered in the group with rare ovarian cancer, and the shortest in the group of patients with small round-cell tumour, at 112.3 and 11.4 months, respectively (small round-cell tumour versus rare ovarian cancer, hazard ratio=15.6817; 95% confidence interval=2.6585-92.5030; p=0.0024). CONCLUSION: Based on the encouraging results in some test groups, especially in rare ovarian cancer, CUP, small bowel cancer and recurrent mesothelioma, multicenter prospective studies examining such rare tumour histologies are needed to reach a higher number of cases and, thus, explore the impact of multimodal therapy on these patients.