Utilization of Primary Cytoreductive Surgery for Advanced-Stage Ovarian Cancer.

This cohort study examines changes in surgical approach for patients with stage III and IV epithelial ovarian cancer from 2010 to 2021.

Targeted Genetic Sequencing Analysis of 223 Cases of Pseudomyxoma Peritonei Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Shows Survival Related to GNAS and KRAS Status.

BACKGROUND AND AIM: Pseudomyxoma peritonei (PMP) is an unusual condition with unique behaviour caused by a mucinous neoplasm, usually arising from the appendix. The aim of this study was to evaluate the prevalence of genomic alterations in clinical specimens of PMP using a targeted assay and correlate the findings with clinical, pathological and outcome data. Sequencing data from 223 patients were analysed. RESULTS: The median follow-up interval was 48 months. The primary neoplasm was appendiceal in 216 patients, ovarian in 4, urachal in 2 and renal in one. We confirmed common mutations in GNAS and KRAS (42% each) with significant co-occurrence of variants in these genes. TP53 mutations were found in 8%. Other mutations were rare but included novel mutations in BAP1 and ERBB4. Of 17 patients with acellular peritoneal mucin, 6 (35%) were positive for DNA mutations. The non-appendiceal cases generally showed a similar mutational landscape to the appendiceal lesions with GNAS and KRAS commonly mutated, although one urachal lesion showed multi-hit TP53 mutation without variants in either GNAS or KRAS. Survival was significantly associated with the grade of the primary neoplasm, the grade of the peritoneal disease, the completeness of cytoreduction score and with mutation in either GNAS, KRAS or both. The hazard ratio (HR) associated with mutation in GNAS and/or KRAS was 1.87 (p = 0.004). CONCLUSIONS: Survival outcome was more closely associated with the grade of the peritoneal disease than with the grade of the primary neoplasm. Our findings support the developing concept that mutational analysis may provide prognostic information in patients with PMP.

Side-Effects on the Renal function of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Background: Acute kidney injury (AKI) is a frequent complication in patients undergo-ing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) due to a combination of several factors: increased intra-abdominal pressure, heat stress and drug tox-icity. Methods: Patients admitted to Intensive Care Unit after CRS and HIPEC during 129 months. Data recorded were: demographic characteristics; severity of illness, haematology and basic chemistry panels (renal function and electrolytes), type of cancer and extension, HIPEC drug and temperature, fluid balance, ICU and hospital stay and mortality. Results: 123 patients were included, only 4.9% developed AKI. AKI was more frequent on patients with ovarian cancer or in those who received doxorubicina as intraperitoneal chemotherapy; also, among those who had higher positive fluid balance during surgery, had higher SOFA or were under mechanical ventilation at ICU admission. There were not differences in mortality according to the development of AKI. Electrolyte disorders appeared in 95.8% of the patients, mainly hypocalcemia and hypokalemia. Conclusion: In our study, the incidence of AKI has been low. The presence of hydroelectrolytic alterations and polyuria was very frequent. The type of cancer, no mitomycin-based regimens and positive fluid balance during surgery were factors that suggest increased risk of AKI. However, although patients with AKI were clinically worse it was not associated with higher mortality.

Risk factors for postoperative complications in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: A meta-analysis and systematic review.

OBJECTIVE: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is one of the most effective treatments for intraperitoneal malignancies. However, current research on risk factors for postoperative complications needs to be more consistent. This study aimed to conduct a meta-analysis of the risk factors for postoperative complications in CRS + HIPEC patients. METHODS: Studies meeting the inclusion criteria were screened by searching the Embase, PubMed, Cochrane and Web of Science databases. RevMan and STATA software were used to analyze the data extracted from the included articles. RESULTS: A total of 15 articles with 4021 patients were included in the meta-analysis. The results revealed that sex, elevated peritoneal cancer index, prolonged duration of surgery and smoking habits were risk factors for postoperative complications in CRS + HIPEC patients. In contrast, BMI, eGFR, age, history of preoperative chemotherapy, history of preoperative surgery, and history of neoadjuvant therapy had no significant effect on postoperative complications in the CRS + HIPEC group. The effects of diabetes, hypertension, preoperative albumin level, tumor location and chemotherapy regimen on the occurrence of complications need to be further investigated. CONCLUSIONS: We identified several risk factors for postoperative complications after CRS + HIPEC, which should help clinicians minimize the incidence of postoperative complications and make more beneficial decisions for cancer patients who need treatment.

Aging affects regrowth of stealthperitoneal dissemination of advanced ovarian cancer: a multicenter retrospective cohort study.

Ovarian cancer (OvCa) is one of the most lethal gynecological malignancies, and most patients are diagnosed at advanced stage with peritoneal dissemination. Although age at diagnosis is considered an independent prognostic factor, its impact on peritoneal recurrence after combined cytoreductive surgery and chemotherapy is not clear. The objective of this study was to investigate the impact of aging on peritoneal recurrence from stealth dissemination and gain insight of the pathophysiology of OvCa in elderly patients. A total of 243 patients with pT2b-pT3 epithelial ovarian who achieved complete surgery, no-residual tumor at first surgery, were selected to be analyzed the risk of peritoneal seeding and recurrence. We found that age over 65 years was independently associated with an increased risk of peritoneum-specific (PS) recurrence (. Furthermore, pT3 stages and positive ascites cytology also worsen the PS-relapse-free survival. Collectively, our findings suggest that age, especially over 65 years, predicts reduced peritoneum-specific tumor recurrence in patients with advanced ovarian cancer after complete cytoreduction surgery, particularly those with pT3 tumors and positive ascites cytology.

A rare case of aggressive uterine leiomyosarcoma: a case report.

Uterine leiomyosarcoma is a rare aggressive uterine malignancy that arises from a smooth muscle of the uterus which accounts for 2-5% of all uterine malignancies. Definitive treatment is surgery with a high rate of recurrences. Our patient presented with lower abdominal pain and mass per abdomen which was diagnosed to be uterine leiomyosarcoma. A 56-year-old woman of East Indian origin presented with abdominal pain and a huge rapidly growing suprapubic abdominal mass with an almost monthly doubling. Her CA 125 and Lactate dehydrogenase (LDH) level was elevated and Computed Tomography (CT) scan showed a large irregular-shaped abdominopelvic solid heterogeneously enhanced lesion with focal central hyperdensity and areas of necrosis causing mass effect. A primary cytoreductive surgery was performed and the histopathology report confirmed the diagnosis of uterine leiomyosarcoma. A combination chemotherapy of six cycles was given to prevent recurrence. No recurrence was detected during her more than two years follow-up period. As the cases are rare in nature, screening is impractical. Hence, the diagnosis of uterine leiomyosarcoma is done by histopathologic examination after surgery.

Effect of glucose-insulin-potassium on lactate levels at the end of surgery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a randomized controlled trial.

INTRODUCTION: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications. METHODS AND ANALYSIS: The modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization. ETHICS AND DISSEMINATION: The trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals. TRIAL REGISTRATION: ChiCTR2200057258. Registered on March 5, 2022.

Prognostic factors and overall survival among patients with ovarian cancer in the pre-PARP inhibitor era: the OCRWE-Finland study.

BACKGROUND: Despite recent treatment advances in ovarian cancer (OC), more real-world evidence studies investigating patient outcomes are needed. OCRWE-Finland was an observational cohort study investigating OC outcomes in Finland during the pre-PARP inhibitor era. PATIENTS: Patients were diagnosed with OC between 2014 and 2019 in Finland. This analysis reports baseline characteristics of all patients, patients with high-grade serous OC (HGSOC), and overall survival (OS) for patients with HGSOC. RESULTS: Among 1,711 patients diagnosed with OC, 867 (51%) had HGSOC. The absence versus presence of visible residual disease post-debulking surgery was associated with improved OS for patients at stage III (n = 303; median: NR vs. 43 months; p = 0.005), but not stage IV (n = 118; median: 37 months vs. 40 months; p = 0.96). Bevacizumab treatment at any line at stages III/IV improved OS in the short-term only. Receiving versus not receiving bevacizumab at first-line for patients with visible residual disease post-debulking surgery was associated with improved OS at stage III (median: 48 months vs. 36 months; p = 0.003), but not stage IV (median: 42 months vs. 37 months; p = 0.26). Multivariate Cox regression analyses showed that stage IV at initial diagnosis and the presence of R2 classification post-debulking surgery resulted in poorer OS. INTERPRETATION: In the pre-PARP inhibitor era, the absence versus presence of visible residual disease post-debulking surgery was associated with improved OS in stage III, but not stage IV HGSOC. First-line bevacizumab seemed to be beneficial in patients with stage III HGSOC and visible residual disease.

Is There a Correlation Between Platelet Count, Mesenteric Lymph Node Involvement, and Hematogenous Metastases in Advanced Stage Ovarian Cancer?

BACKGROUND/AIM: Ovarian cancer remains a major cause of death in women worldwide, mainly due to late diagnosis and the lack of a reliable screening test for early detection of the disease. In this context, attention has been focused on the identification of other prognostic factors that might allow a better identification of cases with worse long-term outcome. PATIENTS AND METHODS: Data of patients who underwent cytoreductive surgery between 2014-2019 were retrospectively reviewed and 57 patients were considered eligible for this study. These cases were further classified according to preoperative platelet count, with a cut-off value of 335,000/µl as a positive predictive value for long-term survival. RESULTS: According to this value, there were 27 cases with a preoperative platelet count lower than 335,000/µl and 30 cases with a preoperative platelet count higher than 335,000/µl. Cases in the second group had a significantly higher peritoneal carcinomatosis index (p=0.002), a higher proportion of digestive serosa involvement (p<0.001), and a higher proportion of mesenteric lymph node involvement and hematogenous metastases (p=0.005 and p=0.001, respectively). When analyzing long-term outcomes, all these factors had a significant impact on overall survival. CONCLUSION: Preoperative thrombocytosis appears to be positively associated with gastrointestinal serosa involvement, mesenteric lymph node invasion, and the presence of hematogenous metastases, thus significantly influencing the long-term outcome of patients with advanced ovarian cancer.

Ovarian carcinosarcoma with lung metastasis characterized by persistent fever: A case report and literature review.

RATIONALE: Ovarian carcinosarcoma (OCS) is a rare malignant tumor prone to distant metastasis. Primary manifestations include pelvic and/or abdominal pain, bloating, and compression. Nevertheless, it is uncommon for OCS to present primarily with persistent fever. This is the first reported case of OCS with lung metastasis characterized by persistent fever. PATIENT CONCERNS: A 61-year-old female patient complaining of abdominal pain and fever was admitted to our hospital. Computed tomography showed an irregular, slightly low-density mass on the left side of the uterus and multiple solid nodules in both lungs. DIAGNOSES: She underwent cytoreductive surgery for pathologically confirmed stage IVB OCS. INTERVENTIONS: She was administered chemotherapy after cytoreductive surgery. Given the patient's history of persistent fever and progressively enlarged pulmonary nodules, a pulmonary abscess was considered as a possible diagnosis. Following antibiotic therapy, the patient's high body temperature did not decrease; however, following nonsteroidal anti-inflammatory drug therapy, it quickly decreased. These symptoms were eventually considered the consequence of neoplastic fever caused by lung metastases. OUTCOMES: Owing to the rapid progression of the disease, the patient ultimately died. LESSONS: This study suggests that, for patients with pelvic and/or abdominal pain, bloating, and pelvic masses, especially those with suspicious lesions in other organs accompanied by fever of unknown origin, a diagnosis of cancer or sarcoma with metastasis should be considered after ruling out infectious fever.

Ultra-radical surgery versus standard-radical surgery for the primary cytoreduction of advanced epithelial ovarian cancer; long-term tertiary center experiences.

OBJECTIVE: To compare overall survival (OS) and morbidity outcomes in patients with advanced epithelial ovarian/tubal/peritoneal cancer undergoing standard-radical (SR) and ultra-radical (UR) surgical procedures based on NICE classification. STUDY DESIGN: This retrospective study analyzed data from 282 patients with 2014 FIGO stage III-IV epithelial ovarian cancer operated on between January 2006 and January 2019. The study compared OS, progression-free survival (PFS), and morbidity between SR and UR surgeries. Parameters influencing OS, including preoperative, postoperative, and post-adjuvant chemotherapy CA-125 values, surgical procedures, post-surgical residual tumor, histopathological grade, and FIGO surgical stage, were assessed. RESULTS: Out of 282 patients, 256 met the inclusion criteria. SR surgery was performed in 48 %, and UR surgery in 52 %. The mean preoperative CA-125 value was 1200 ± 1914.83, decreasing to 240.32 ± 373.87 postoperatively. The mean follow-up period was 63.01 ± 47.56 months. UR surgery correlated with significantly higher postoperative complications (p < 0.001), histopathological grade (p = 0.023), FIGO stage (p < 0.001), three-year death rates, and overall mortality rates (p = 0.035). FIGO stage and total metastatic lymph nodes emerged as independent prognostic factors for overall and PFS. CONCLUSION: In the treatment of epithelial ovarian cancer, evaluating the extent of the tumor before the surgery and showing maximal effort to minimize the residual tumor volume instead of applying UR procedures as the first choice seems to be the most important factor that can affect survival.

Triphasic Learning Curve of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective but costly procedure for select patients with peritoneal malignancies. The impact of progression along a learning curve on the cost of these procedures is unknown. PATIENTS AND METHODS: We performed a retrospective cohort study of patients undergoing CRS-HIPEC from 2016 to 2022 at a single quaternary center. Our study cohort was temporally divided into four equally sized volume quartiles (A, B, C, and D). We utilized cumulative sum plots and split-group analysis to characterize the institutional learning curve based on cost, operative time, length of stay, and morbidity. Multivariable linear regression was performed to estimate costs after adjusting for covariates. Bivariate analysis was performed using a Kruskal-Wallis test to compare continuous variables and a χ2 test to compare categorical variables. RESULTS: Of 201 patients, the median age [interquartile range (IQR)] was 57 (47-65) years, 113 (56%) patients were female, 143 (71%) were white, and 107 (53%) had private insurance. Median operating room charge [US$42,639 (US$32,477-54,872), p < 0.001] varied between volume quartiles, peaking in quartile C. Stabilization was achieved for 86 cases for operating room cost, 88 cases for routine cost, 96 cases for length of stay, 103 cases for operative time, 120 cases for intensive care unit length of stay, and 150 cases for overall and serious morbidity. The actual operating room and routine costs were similar to predicted costs at the end of the study period. CONCLUSIONS: The CRS-HIPEC learning curve is triphasic, with cost stability achieved relatively early compared with other markers of surgical proficiency.

Pathological Response and Outcomes in Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Immunotherapy-Based Therapies and Undergoing Deferred Cytoreductive Nephrectomy (CN).

In this study we evaluated outcomes of patients with metastatic renal cell carcinoma who received immunotherapy before surgery. We found that receiving immunotherapy combinations before surgery can offer patients benefits in reducing tumor size and improving disease control. BACKGROUND: Immunotherapy (IO) has improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, the timing of surgical intervention for cytoreductive nephrectomy (CN) is still controversial for this group of patients. PATIENTS AND METHODS: We identified patients with mRCC receiving IO-based therapies and undergoing CN. Patients were divided into 2 cohorts: those who underwent upfront CN and those who underwent deferred CN. Pathologic and radiographic features along with clinical outcomes were systematically collected. Comparisons were performed using Chi-square test, paired t-Test or Mann-Whitney-U test. Progression Free survival (PFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Fifty-one patients with mRCC were included, with a median follow-up of 21 months. 38 (74.5%) patients received IO-based therapies prior to CN, while 13 (25.5%) patients underwent up-front CN. IO-based therapies reduced median tumor size from pretreatment 10 cm to 8.6 cm post-treatment when given prior to CN. IO-TKI had a trend toward higher tumor shrinkage (-2.3 vs -1.2 cm). Pathologic T downstaging occurred in 42% (n=16) of patients, 11% (n=4) of whom had pT0 disease. Thrombus downstaging occurred in 13% (n=6) of patients, all with either partial response (PR) or complete response (CR) in metastases. PFS (HR=0.7, 95% CI 0.29-1.98, p=0.58) and OS (HR 0.4, 95% CI 0.13-1.57, p=0.21) were not statistically significant between 2 cohorts. CONCLUSIONS: IO-based therapies, particularly IO-TKIs, resulted in pathologic necrosis and reductions in tumor size prior to deferred CN. PFS and OS were similar for patients who received either upfront IO-based therapy or after CN.

Portal vein thrombosis and hepatic infarction due to hepatic mobilization after primary debulking surgery for advanced ovarian cancer: A case report.

Hepatic mobilization is essential in debulking surgery for resecting diaphragmatic lesions in advanced ovarian cancer. However, hepatic mobilization potentially induces postoperative portal vein thrombosis and hepatic infarction. No reports exist regarding these postoperative complications of gynecological surgeries. Thus, we reported a case of portal vein thrombosis and hepatic infarction after ovarian cancer surgery with upper abdominal surgery. The 51-year-old female patient who had been diagnosed with advanced ovarian and early endometrial cancer underwent primary debulking surgery. Ultimately, she underwent the following surgical procedures: a hysterectomy, bilateral salpingo-oophorectomy, total parietal peritonectomy, low anterior resection, ileostomy, and appendicectomy. The hepatic enzymatic and D-dimer levels were elevated, postoperatively. Contrast-enhanced computed tomography revealed portal vein thrombosis and an infarction of the hepatic S3 region. The portal vein thrombosis resolved post-administration of unfractionated heparin. The hepatic infarction improved. Meticulous intra- and postoperative management should encompass the deliberation of the potential risk of these postoperative complications.

Survival Dynamics in Advanced Ovarian Cancer: R2 Resection Versus No-Surgery Paths Explored.

BACKGROUND: Cytoreductive surgery is critical for optimal tumor clearance in advanced epithelial ovarian cancer (EOC). Despite best efforts, some patients may experience R2 (>1 cm) resection, while others may not undergo surgery at all. We aimed to compare outcomes between advanced EOC patients undergoing R2 resection and those who had no surgery. METHODS: Retrospective data from 51 patients with R2 resection were compared to 122 patients with no surgery between January 2015 and December 2019 at a UK tertiary referral centre. Progression-free survival (PFS) and overall survival (OS) were the study endpoints. Principal Component Analysis and Term Frequency - Inverse Document Frequency scores were utilized for data discrimination and prediction of R>2 cm from computed tomography pre-operative reports, respectively. RESULTS: No statistical significance was observed, except for age (73 vs 67 years in the no- surgery vs R2 group, P: .001). Principal Components explained 34% of data variances. Reasons for no surgery included age, co-morbidities, patient preference, refractory disease, patient deterioration or disease progression, and absence of measurable intra- abdominal disease). The median PFS and OS were 12 and 14 months for no-surgery, vs 14 and 26 months for R2 (P: .138 and P: .001, respectively). Serous histology and performance status independently predicted PFS in both no-surgery and R2 cohorts. In the no-surgery cohort, serous histology independently predicted OS, while in the R2 cohorts, both serous histology and adjuvant chemotherapy were independent prognostic features for OS. The bi-grams "abdominopelvic ascites" and "solid omental" were amongst those best discriminating between R>2 cm and R1-2 cm. CONCLUSIONS: R2 resection and no-surgery cohorts displayed unfavourable prognosis with a notable degree of uniformity. When cytoreduction results in suboptimal results, the survival benefit may still be higher compared to those who underwent no surgery.

The study examined outcomes in advanced epithelial ovarian cancer (EOC) patients who underwent either R2 (suboptimal) surgical resection or received no surgery at all at a UK tertiary referral center. Sophisticated machine learning methodolgies were used to analyze data patterns and predict the extent of resection (>2 cm) from pre-operative CT reports. Reasons for not undergoing surgery included older age, presence of other medical conditions, patient preference, progressive disease, patient decline, or lack of detectable intra-abdominal disease. Factors like serous histology and performance status iinfluenced the risk of recurrence in both groups, while serous histology and adjuvant chemotherapy predicted the risk of death in the R2 group. Word sequences like "omental disease" and "reduced bulk" helped differentiate between R>2 cm and less extensive resections (R1-2 cm). In summary, both R2 resection and no-surgery groups had poor outcomes, but patients who underwent R2 resection generally had better survival compared to those who received no surgery, even when complete tumor removal was not achieved.

Ovarian Carcinoma - A Single Centre Case-Series Descriptive Analysis of Surgical Procedures.

Background: Ovarian surface epithelial cancer (OSEC) are an entity in which, according to genomics and pathology data accumulated in the last couple of decades, several different nosological entities with distinct etiologies are aggregated. In ovarian cancer, surgery is the pivot of treatment, to which medical oncological treatment is added by recommendation in most cases. Material and Methods: This is a single centre sample of 263 cases with OSEC operated from January 2014 until December 2021 with a 28-month period of follow-up, until 30th April 2024. OSEC surgical procedures in stages IIB to III and IV of the disease are complex interventions in order to have the R0/optimal cytoreduction achieved, so we summarised and coded them as follows: 1 = biopsy (of the tumour/peritoneum); 2 = bilateral/unilateral adnexectomy (BA/UA) total hysterectomy (TH) omentectomy +- peritoneal biopsies; 3 = (2) with total hysterectomy with bilateral adnexectomy (THBA) +- by extraperitoneal/subperitoneal route+peritonectomies (exclusively diaphragmatic) and electrocauterization of peritoneal carcinomatous lesions; 4 = (3) with visceral (multiple) resections +- stoma; 5 = (4) with diaphragmatic peritonectomies/stripping/partial resection of the diaphragm; 6 = palliative surgery. Results: Debulking surgery (DS) was carried out for n = 182 patients with no residual tissue = R0 being registered in n = 41. Results for patients with residual tissue (n = 141) after DS recorded the following findings: 1 cm (49% cases), 1.1-2 cm (29%) and 2 cm (22%). Recorded results for endometrial ovarian carcinoma (EC) n = 27 shown a tumour free survival probability estimate (%) at 60 months of 66% as both surgery and platinum based chemotherapy are efficient. For clear cell ovarian carcinoma (CCC) n = 7 recorded results shown a tumour free estimate (%) at 60 months of 14%, being known the controversy as to whether or not paclitaxel is an active drug for CCC. Major complications were recorded in 25 patients with a fatality ratio of 5/25. Conclusion: Considering OSEC is a relatively rare disease and the importance of collecting substantial numbers of samples by histotypes to further knowledge about ovarian cancer it comes crucial to establish collaborative endeavour of tertiary centers with standardised and quality control strategies.

Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis.

Background: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis. Methods: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results: The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations: We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions: In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work: More randomised controlled trials are necessary. Study registration: This study is registered as PROSPERO CRD42019130504. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

Cancers of the bowel, ovary or stomach can spread to the lining of the abdomen ('peritoneal metastases'). Chemotherapy (the use of drugs that aim to kill cancer cells) given by injection or tablets ('systemic chemotherapy') is one of the main treatment options. There is uncertainty about whether adding cytoreductive surgery (cytoreductive surgery; an operation to remove the cancer) and 'hyperthermic intraoperative peritoneal chemotherapy' (warm chemotherapy delivered into the lining of the abdomen during cytoreductive surgery) are beneficial. We reviewed all the information from medical literature published until 14 April 2022, to answer the above uncertainty. We found the following from eight trials, including about 1000 participants. In people with peritoneal metastases from bowel cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably does not provide any benefits and increases harm compared to cytoreductive surgery + systemic chemotherapy, while cytoreductive surgery + systemic chemotherapy appears to increase survival compared to systemic chemotherapy alone. There is uncertainty about the best treatment for people with peritoneal metastases from stomach cancer. In women with peritoneal metastases from ovarian cancer who require systemic chemotherapy before cytoreductive surgery to shrink the cancer to allow surgery ('advanced ovarian cancer'), hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably increases survival compared to cytoreductive surgery + systemic chemotherapy. In people who can withstand a major operation and in whom cancer can be removed, cytoreductive surgery + systemic chemotherapy should be offered to people with peritoneal metastases from bowel cancer, while hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered to women with peritoneal metastases from 'advanced ovarian cancer'. Uncertainty in treatment continues for gastric cancer. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.

A nomogram to predict platinum-sensitivity and survival outcome in women with advanced epithelial ovarian cancer.

OBJECTIVE: This study presents the development and validation of a nomogram aimed at predicting platinum-sensitivity and survival outcomes in women with advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Data from a retrospective cohort of women diagnosed with stage III/IV EOC between Jan 2011 and Dec 2021 treated at our institute were collected. Clinical and pathological characteristics were analyzed using logistic regression analysis to identify independent predictors of platinum-sensitivity. Impact on progression-free (PFS) and overall survival (OS) was determined by Kaplan-Meier and Cox regression analysis. A nomogram was constructed based on the significant predictors, and its performance was evaluated using calibration, discrimination, and validation analyses. RESULTS: Of the 210 patients, 139 (66.19%) had platinum-sensitive and 71 (33.81%) were platinum-resistant disease. On multivariate analysis, platinum-resistance correlated with neoadjuvant chemotherapy (OR 2.15; 95% CI 1.10-4.21), clear cell/mucinous histology (OR 5.04; 95% CI 2.20-11.54), and sub-optimal debulking status (OR 3.37; 95% CI 1.44-7.91). Median PFS and OS were also significantly shorter for patients with neoadjuvant chemotherapy (23 vs. 10 months and 69 vs. 29 months, respectively), clear cell/mucinous histology (15 vs. 3 months and 63 vs. 11 months, respectively), and suboptimal debulking (26 vs. 5 months and 78 vs. 24 months, respectively). The nomogram demonstrated good predictive accuracy for platinum-sensitivity in the cohort as indicated by high concordance index of 0.745. Calibration plots showed excellent agreement and internal validation further confirmed the reliability of the nomogram's performance. CONCLUSION: A novel predictive nomogram based on type of initial treatment, histology, and debulking status was developed, which provides a friendly and reliable tool for predicting platinum-sensitivity and survival outcomes in women with advanced EOC. Its application may assist clinicians in individualizing treatment decisions.