[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery.

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.

Clinical study on simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy for synchronous colorectal cancer liver metastasis.

PURPOSE: This study aimed to analyze the clinical effect of simultaneous resection of liver metastases combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on synchronous colorectal cancer liver metastasis. METHODS: A total of 144 patients with synchronous colorectal cancer liver metastasis who were admitted to our hospital between January 2018 and January 2019 were randomly assigned into a control group and an intervention group. The patients in the control group received simultaneous resection of liver metastases. The patients in the intervention group obtained simultaneous resection of liver metastases combined with HIPEC. The recent total effective rate of the 2 groups was compared, and the disease control rate of the 2 groups was calculated at 3 months after treatment. The patients were followed up for 3 years. The survival time of the 2 groups was observed and compared. Fasting venous blood was collected from patients in the 2 groups, and the carcinoembryonic antigen (CEA) level was compared. The level of quality of life scale (Short Form 36-item Health Survey) and the occurrence of adverse reactions were compared between the 2 groups. RESULTS: The R0 complete resection rate in the intervention group was significantly higher than that in the control group (P < .05). The recent total effective rate in the intervention group (87.50%) was significantly higher than that in the control group (59.72%) (P < .05). The negative change of CEA in the intervention group was 72.22%, which was prominently higher than that in the control group of 43.06% (χ2 = 12.542, P < .001). After a 36-month follow-up, the overall survival rate of the observation group was significantly higher than that of the control group (hazard ratio, 2.54; 95% CI, 1.05-5.48; P < .001). The patients in the intervention group had significantly higher life quality scores of health status, social function, emotional function, physical function, and mental health than in the control group (P < .05). There was no significant difference in the incidence of complications between the 2 groups (P > .05). Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were risk factors affecting the occurrence of complications after treatment and were closely correlated with the prognosis and survival of patients (P < .05). Patients with age ≤ 60 years, no preoperative comorbidities, low tumor differentiation, intraoperative blood loss ≤ 150 mL, more experienced surgeons, and complete R0 resection had a longer survival time. Age > 60 years, preoperative comorbidities, moderate and high differentiation of tumors, intraoperative blood loss > 150 mL, and less experienced surgeons were independent risk factors affecting the prognosis of patients with colorectal cancer liver metastases (P < .05), whereas R0 surgery was an independent protective factor for the prognosis (P < .05). CONCLUSION: In the treatment of synchronous colorectal cancer liver metastases, simultaneous resection of liver metastases in conjunction with HIPEC demonstrated superior efficacy. This approach may potentially extend patient survival and enhance quality of life and deserve to be extensively used in clinical practice.

Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre.

BACKGROUND: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. METHODS: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. RESULTS: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. CONCLUSION: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results.

The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany.

PURPOSE: Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS: A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS: Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION: Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.

The Potential of Integrative Cancer Treatment Using Melatonin and the Challenge of Heterogeneity in Population-Based Studies: A Case Report of Colon Cancer and a Literature Review.

Melatonin is a multifunctional hormone regulator that maintains homeostasis through circadian rhythms, and desynchronization of these rhythms can lead to gastrointestinal disorders and increase the risk of cancer. Preliminary clinical studies have shown that exogenous melatonin alleviates the harmful effects of anticancer therapy and improves quality of life, but the results are still inconclusive due to the heterogeneity of the studies. A personalized approach to testing clinical parameters and response to integrative treatment with nontoxic and bioavailable melatonin in patient-centered N-of-1 studies deserves greater attention. This clinical case of colon cancer analyzes and discusses the tumor pathology, the adverse effects of chemotherapy, and the dynamics of markers of inflammation (NLR, LMR, and PLR ratios), tumors (CEA, CA 19-9, and PSA), and hemostasis (D-dimer and activated partial thromboplastin time). The patient took melatonin during and after chemotherapy, nutrients (zinc, selenium, vitamin D, green tea, and taxifolin), and aspirin after chemotherapy. The patient's PSA levels decreased during CT combined with melatonin (19 mg/day), and melatonin normalized inflammatory markers and alleviated symptoms of polyneuropathy but did not help with thrombocytopenia. The results are analyzed and discussed in the context of the literature on oncostatic and systemic effects, alleviating therapy-mediated adverse effects, association with survival, and N-of-1 studies.

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.

Doxorubicin as Risk Factor for Fascial Dehiscence After CRS-HIPEC for Peritoneal Metastases.

BACKGROUND/AIM: Among postoperative complications, fascial dehiscence (FD) is registered in up to 10% of patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aimed to evaluate the risk factors related to FD after CRS-HIPEC. PATIENTS AND METHODS: A retrospective analysis of a prospectively maintained database of consecutive patients who underwent CRS-HIPEC between 2015 and 2023 was performed. For each patient, risk factors for postoperative fascial dehiscence were identified using multivariate analysis. RESULTS: During the study period (2018-2023), 217 patients were treated with CRS-HIPEC. The incidence of FD was observed in seven cases (3.2%), which were reoperated with direct fascial closure. In three cases, FD was associated with other grade III-IV complications. Body mass index, (BMI; p=0.024), doxorubicin-based HIPEC (p=0.005), and open technique (p=0.004) were identified as risk factors for FD in univariate analysis. Systemic chemotherapy, prior surgical score, and peritoneal cancer index (PCI) were not associated with an increased risk of FD. In multivariable regression analysis, doxorubicin-based HIPEC and open technique were confirmed as risk factors for FD. CONCLUSION: Although FD is a relatively rare event after CRS-HIPEC, open technique and doxorubicin-based HIPEC were significant predictors of this complication. Specific fascial closure techniques and proper wound care should be considered in high-risk patients.

Complexity of surgery and treatment burden in patients with peritoneal malignancy is not determined by addition of hyperthermic intraperitoneal chemotherapy.

BACKGROUND: This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves. RESULTS: 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed. CONCLUSIONS: The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding.

Application Evaluation of Fluorouracil Intraperitoneal Perfusion Chemotherapy in Combination with Intravenous Chemotherapy in Patients after Radical Resection of Colorectal Cancer.

BACKGROUND: Colorectal cancer stands as one of the most prevalent malignant tumors affecting the digestive tract, posing a significant threat to human health. Its incidence and fatality rates rank third and second, respectively, among malignant tumors. This study seeks to analyze the efficacy of combining fluorouracil intraperitoneal perfusion chemotherapy with intravenous chemotherapy in patients following radical resection of colorectal cancer. METHODS: This retrospective study analyzed the medical records of 65 patients who underwent radical resection of colorectal cancer at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2011 to January 2013. These patients were divided into two groups based on their treatment methods: the control group (CG, n = 31, receiving intravenous chemotherapy) and the observation group (OG, n = 32, receiving fluorouracil intraperitoneal perfusion chemotherapy + intravenous chemotherapy). After 6 cycles of treatment, the study compared clinical symptoms, Karnofsky score, body weight, adverse reactions, local recurrence, and liver metastasis between the two groups. RESULTS: The OG demonstrated superior efficacy in controlling recurrence and metastasis compared to the CG (p < 0.05). However, there were no significant differences observed in clinical symptoms, quality of life, body weight, and drug safety between the two groups (p > 0.05). CONCLUSION: Intraperitoneal infusion chemotherapy with fluorouracil significantly impacts the control of recurrence and metastasis following radical resection of colorectal cancer. It also offers valuable references for developing clinical treatment protocols for these patients.

Outcomes following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies: 10 ​Year experience.

INTRODUCTION: The treatment of peritoneal malignancies has evolved and select patients can undergo effective surgical therapies. Access to innovative oncology procedures can be improved if programs are developed within and outside of academic cancer centers. We report the creation of a high volume, comprehensive peritoneal malignancy program developed in a community center. METHODS: A retrospective single-site study was conducted using registry data comprising all patients who underwent Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC) between October 2011-December 2021. RESULTS: 353 patients underwent CRS and HIPEC. 208 patients experienced in-hospital morbidity (58.9 â€‹%). Group comparison by disease site, PCI, and the completeness of cytoreduction demonstrated survival differences in mean overall survival and disease-free survival in 1-, 3- and 5-year ranges. CONCLUSIONS: This study demonstrates that with a standardized protocol and a surgeon-led multidisciplinary team it is possible to offer safe outcome driven, complex oncologic surgery in a community-based cancer program.

Efficacy and safety of neoadjuvant sintilimab in combination with FLOT chemotherapy in patients with HER2-negative locally advanced gastric or gastroesophageal junction adenocarcinoma: an investigator-initiated, single-arm, open-label, phase II study.

BACKGROUND: The addition of immune checkpoint inhibitors to neoadjuvant chemotherapy in operable advanced gastric or gastroesophageal junction (G/GEJ) cancer aroused wide interest. This study was designed to assess the efficacy and safety of neoadjuvant sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, in combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy for HER2-negative locally advanced G/GEJ cancer. METHODS: Eligible patients with clinical stage cT4 and/or cN+M0 G/GEJ cancer were enroled in this phase II study. Patients received neoadjuvant sintilimab (200 mg every 3 weeks) for three cycles plus FLOT (50 mg/m 2 docetaxel, 80 mg/m 2 oxaliplatin, 200 mg/m 2 calcium levofolinate, 2600 mg/m 2 5-fluorouracil every 2 weeks) for four cycles before surgery, followed by four cycles of adjuvant FLOT with same dosages after resection. The primary endpoint was the pathological complete response (pCR) rate. RESULTS: Thirty-two patients were enroled between August 2019 and September 2021, with a median follow-up of 34.8 (95% CI, 32.8-42.9) months. Thirty-two (100%) patients received neoadjuvant therapy, and 29 underwent surgery with an R0 resection rate of 93.1%. The pCR (TRG0) was achieved in 5 (17.2%; 95% CI, 5.8-35.8%) patients, and the major pathological response was 55.2%. Twenty-three (79.3%) patients had T downstaging, 21 (72.4%) had N downstaging, and 19 (65.5%) had overall TNM downstaging. Six (20.7%) patients experienced recurrence. Patients achieving pCR showed better event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) than non-pCR. The estimated 3-year EFS rate, 3-year DFS rate, and 3-year OS rate were 71.4% (95% CI, 57.2-89.2%), 78.8% (95% CI, 65.1-95.5%), and 70.9% (95% CI, 54.8-91.6%), respectively. The objective response rate and disease control rate were 84.4% (95% CI, 68.3-93.1%) and 96.9% (95% CI, 84.3-99.5%), respectively. Twenty-five (86.2%) received adjuvant therapy. The main grade ≥3 treatment-related adverse events (TRAEs) were lymphopenia (34.4%), neutropenia (28.1%), and leukopenia (15.6%). no patients died from TRAE. The LDH level exhibited a better predictive value to pathological responses than PD-L1 and MSI status. CONCLUSIONS: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant sintilimab plus FLOT in HER2-negative locally advanced G/GEJ cancer, which suggested a potential therapeutic option for this population.

[Contribution of intraperitoneal chemotherapy in the treatment of colorectal peritoneal carcinoma. HIPEC, PIPAC, state of the art and future directions]. / La chimiothérapie intra-péritonéale dans le traitement de la carcinose péritonéale d'origine colorectale. CHIP, PIPAC, état des lieux et perspectives.

After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.

Appendiceal adenocarcinoma, diagnosed after acute perforated appendicitis: Potential contribution of HIPEC.

INTRODUCTION: Treatment of peritoneal metastasis from appendicular adenocarcinoma consists of cyto-reductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC). In case of acute appendicular syndrome (AAS) the tumor is likely to be perforated. In that case, there is no treatment recommendation. We propose CRS and HIPEC. MATERIALS AND METHOD: We listed 21 consecutive patients who were addressed for discovery of appendiceal adenocarcinoma. The emergency surgery was performed in a primary-care hospital. We evaluated the therapeutic algorithms, per operative decision, survival and recurrent rate. RESULTS: Among the 21 patients, 4 patients were diagnosed as synchronous appendicular peritoneal metastasis, and underwent CRS and HIPEC. The other 17 patients with diagnosis of adenocarcinoma on anatomopathological samples, without peritoneal metastasis during appendectomy, were addressed. Between them 2 patients were denied CRS. Among the 15 operated patients, 8 patients had no peritoneal metastasis discovery during surgery, and therefore underwent prophylactic CRS and HIPEC. Peritoneal metastasis were discovered for the other 7 patients, who also underwent CRS and HIPEC. For the prophylactic group, the recurrence rate is 12,5 %, overall survival (OS) is 100 %. The rate of grade III-IV surgical complications after CRS and HIPEC was 36 % among the 19 patients who underwent surgery. CONCLUSION: In case of appendectomy in emergency situations for perforated adenocarcinoma, half of the patients may have peritoneal metastasis. In case of non-identified peritoneal metastasis during CRS, performing a prophylactic HIPEC seems to be associated with an encouraging rate of peritoneal disease free situation at 5 years.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Risk factors of chronic kidney disease in cisplatin-based hyperthermia intraperitoneal chemotherapy.

PURPOSE: Cisplatin is commonly prescribed in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Acute kidney injury (AKI) is regarded as a common complication after HIPEC combined with cytoreductive surgery (CRS). However, post-HIPEC chronic kidney disease (CKD) is scarce and less investigated. This study aims to investigate the incidence of CKD following cisplatin-based HIPEC and to analyse the associated risk factors. MATERIALS AND METHODS: From January 2016 to August 2021, a total of 55 patients treated with CRS and cisplatin-based HIPEC for peritoneal carcinomatosis were categorized retrospectively into groups, with and without CKD. Demographics, comorbidity, surgery, postoperative management, and complications were collected to evaluate risk factors for cisplatin-based HIPEC-related CKD. Univariate and multivariate analyses were conducted to confirm the correlation between different variables and CKD occurrence. RESULTS: Of the 55 patients, 24 (43.6%) patients developed AKI and 17 (70.8%) patients of these AKI patients progressed to CKD. Multivariate regression analysis identified intraoperative use of parecoxib (Odds Ratio (OR) = 4.39) and intraoperative maximum temperature > 38.5°C (OR = 6.40) as major risk factors for cisplatin-based HIPEC-related CKD occurrence. Though type II diabetes mellitus and intraoperative complications were the independent risk factors of AKI following cisplatin-based HIPEC, but they were not shown in CKD analysis. CONCLUSION: Intraoperative use of parecoxib during cisplatin-based HIPEC emerged as a significant risk factor for postoperative CKD. Clinicians should exercise caution in prescribing parecoxib during HIPEC procedures. Additionally, maintaining intraoperative body temperature below 38.5°C might be crucial to mitigate the risk of CKD development. This study underscores the importance of identifying and preventing specific risk factors to improve long-term renal outcomes in patients undergoing cisplatin-based HIPEC.

Preoperative CA 19-9 Predicts Disease Progression in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC. METHODS: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome. RESULTS: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125. CONCLUSIONS: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.

Determination of enzalutamide long-term safety and efficacy for castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy: a multicenter prospective DELC study.

BACKGROUND: Alternative anti-androgen therapy has been widely used as a first-line treatment for castration-resistant prostate cancer, and it may affect treatment outcome of subsequent agents targeting the androgen receptor axis. We conducted the prospective observational DELC (Determination of Enzalutamide Long-term safety and efficacy for Castration-resistant prostate cancer patients after combined anti-androgen blockade followed by alternative anti-androgen therapy) study to evaluate the efficacy of enzalutamide in patients with castration-resistant prostate cancer who underwent prior combined androgen blockade with bicalutamide and then alternative anti-androgen therapy with flutamide. METHODS: The DELC study enrolled 163 Japanese patients with castration-resistant prostate cancer who underwent alternative anti-androgen therapy with flutamide following failure of initial combined androgen blockade with bicalutamide in multiple institutions between January 2016 and March 2019. Primary endpoint was overall survival. Administration of enzalutamide was started at 160 mg orally once daily in all patients. RESULTS: The rate of decline of prostate-specific antigen by 50% or more was 72.2%, and median overall survival was 42.05 months. Multivariate analysis revealed that higher pretreatment serum levels of prostate-specific antigen (≥11.3 ng/mL; P = 0.004), neuron-specific enolase (P = 0.014) and interleukin-6 (≥2.15 pg/mL; P = 0.004) were independent risk factors for overall survival. Fatigue (30.0%), constipation (19.6%) and appetite loss (17.8%) were the most common clinically relevant adverse events. The enzalutamide dose was not reduced in any patient under the age of 70, but adherence was decreased in those over 70. CONCLUSIONS: In the DELC study, the safety of enzalutamide was comparable to that in previous reports. Serum levels of neuron-specific enolase and interleukin-6 were suggested as prognostic factors for castration-resistant prostate cancer with potential clinical utility.

Impacts of hyperthermic chemotherapeutic agent on cytotoxicity, chemoresistance-related proteins and PD-L1 expression in human gastric cancer cells.

Objective: Gastric cancer with peritoneal metastasis is considered to be final stage gastric cancer. One current treatment approach for this condition is combined cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the therapeutic mechanisms of HIPEC remain largely undescribed. Method: In order to assess the cellular effects of HIPEC in vitro, we treated AGS human gastric adenocarcinoma cells with or without 5-fluorouracil (5-Fu) at 37 °C or at 43 °C (hyperthermic temperature) for 1 h followed by incubation at 37 °C for 23 h. The impacts of hyperthermia/5-Fu on apoptosis, cell survival signals, oxidative stress, chemoresistance-related proteins and programmed death-ligand 1 (PD-L1) expression were measured. Results: Our results showed that hyperthermia potentiates 5-Fu-mediated cytotoxicity in AGS cells. Furthermore, the combination of 5-Fu and hyperthermia reduces levels of both phosphorylated STAT3 and STAT3, while increasing the levels of phosphorylated Akt and ERK. In addition, 5-Fu/hyperthermia enhances reactive oxygen species and suppresses superoxide dismutase 1. Chemoresistance-related proteins, such as multidrug resistance 1 and thymidylate synthase, are also suppressed by 5-Fu/hyperthermia. Interestingly, hyperthermia enhances 5-Fu-mediated induction of glycosylated PD-L1, but 5-Fu-mediated upregulation of PD-L1 surface expression is prevented by hyperthermia. Conclusion: Taken together, our findings provide insights that may aid in the development of novel therapeutic strategies and enhanced therapeutic efficacy of HIPEC.