Cytoreduction For Ovarian Cancer Research Articles

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

ObjectiveTo 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 DesignThis 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. ResultsOut 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. ConclusionIn 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.

Efficacy and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy with secondary cytoreduction for platinum resistant recurrent ovarian cancer: A single-center retrospective cohort study

Background/purposeThis retrospective study evaluated the efficacy and adverse effects of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) with secondary cytoreductive surgery (CRS) in patients with recurrent ovarian cancer. MethodsPatients diagnosed with recurrent epithelial ovarian cancer, including fallopian tube and peritoneal origin, who underwent oxaliplatin-based HIPEC with secondary CRS, were enrolled. The primary outcome was progression-free survival (PFS), and the secondary outcomes were overall survival (OS) and adverse events. ResultsA total of 33 patients were included in the analysis. The mean PFS and OS were 20.4 months (95% CI 16.3–24.5 months) and 26.7 months (95% CI 23.7–29.7), respectively. Furthermore, the OS and PFS between platinum-sensitive and resistant recurrence showed no significant difference. Univariate and multivariate analysis of PFS identified a pre-operative peritoneal carcinomatosis index (PCI) score of ≥5 as a poor prognostic factor. Among them, the incidence of acute kidney injury was 9.0 % & none had grade ≧3 adverse events. ConclusionOxaliplatin-based HIPEC with secondary CRS might provide a survival benefit for patients with recurrent ovarian cancer with a decreased incidence of renal toxicity compared to cisplatin-based regimens. It might be effective and feasible in selected recurrent ovarian cancer patients, regardless of platinum-sensitive or resistant.

Diaphragmatic stripping in epithelial ovarian cancer at first diagnosis: Impact on morbidity and survival outcomes

ObjectivesDiaphragmatic stripping is a standard procedure that is performed in a significant proportion of patients undergoing surgical cytoreduction for advanced ovarian cancer. The objective of the present study is to evaluate morbidity and survival outcomes among patients offered diaphragmatic surgery for primary diagnosed optimally resected ovarian cancer. Study designWe conducted a retrospective cohort study, identifying patients that were offered surgery between 2016 and 2021 for primary diagnosis of ovarian cancer. Cases that had diaphragmatic stripping or partial diaphragmatic resection were selected and compared to cases that did not require this procedure. Kaplan-Meier and Cox-regression analyses were applied to evaluate survival outcomes. ResultsOverall, 61 patients that had diaphragmatic stripping were identified. Severe postoperative complications (Clavien-Dindo 3 + ) were noted in 19 patients (31 %). Survival analyses denoted that the stage of the disease at the time of diagnosis, as well as the timing of the surgical procedure (PDS vs IDS) and the completion of tumor debulking were factors that significantly affected the recurrence free and overall survival of patients. Severe postoperative morbidity was a significant predictor of the overall survival. Multivariate cox-regression analysis that was adjusted for the stage of the disease revealed that preoperative pleural effusion, optimal (compared to complete) tumor resection and the occurrence of postoperative complications significantly affected the overall survival of patients. Compared to patients that did not have diaphragmatic surgery, patients submitted to diaphragmatic stripping or resection had improved progression free and overall survival rates, irrespective of the stage of the disease at diagnosis or the adequacy of resection status. ConclusionsDiaphragmatic surgery is feasible in advanced ovarian cancer patients with acceptable morbidity that mainly refers to postoperative pleural effusion. Its positive impact on patients‘ survival requires further investigation.

Risk Prediction Model for Surgical Complications and Predictors of Delay/Omission of Adjuvant Chemotherapy Post Primary Cytoreduction in Epithelial Ovarian Cancer

Risk Prediction Model for Surgical Complications and Predictors of Delay/Omission of Adjuvant Chemotherapy Post Primary Cytoreduction in Epithelial Ovarian Cancer

Trends in specific procedures performed at the time of cytoreduction for ovarian cancer: Is interval debulking surgery truly less radical? A Memorial Sloan Kettering Cancer Center Team Ovary study

ObjectivesTo evaluate procedures performed during primary debulking surgery (PDS) and interval debulking surgery (IDS) for ovarian cancer. MethodsPatients surgically treated at our institution for newly diagnosed stage IIIC/IV epithelial ovarian cancer between 6/1/2015–12/31/2021 were identified using a prospectively collected database. Patients were triaged to PDS or neoadjuvant chemotherapy (NACT) followed by IDS using an institutional algorithm. Data on specific procedures performed, including consultants called, were collected from operative and pathology reports. Appropriate statistical analyses were applied. ResultsOverall, 467 patients underwent PDS and 434 underwent IDS; 76% (PDS) and 71% (IDS) of cases achieved complete gross resection. Comparing PDS vs IDS cohorts, median age was 63 years (range, 23–86) vs 67 years (range, 35–95), 79% vs 86% of patients had high-grade serous histology, and 38% vs 70% had stage IV disease. Most procedures (except ostomy, distal pancreatectomy) were more common during PDS (P < .05). Bowel surgery was performed during 65% of PDS and 33% of IDS, and upper abdominal surgery during 72% of PDS and 52% of IDS; both were more common during PDS (P < .001). Estimated blood loss (median, 500 mL [PDS] vs 300 mL [IDS]) and operative time (median, 362 min [PDS] vs 267 min [IDS]) were higher for PDS (P < .001). A consulting surgeon was utilized during 31% of PDS and 18% of IDS, with hepatopancreaticobiliary as the most commonly called service (61% and 65%, respectively). ConclusionsIn our study of patients with advanced-stage ovarian cancer, while most procedures were more often performed during PDS, NACT did not obviate the need for radical surgical resection. Thus, advanced surgical skills remain essential.

Splenectomy as Part of Maximal-Effort Cytoreductive Surgery in Advanced Epithelial Ovarian Cancer.

A splenectomy is frequently performed during debulking surgery for advanced ovarian cancer. Its impact on perioperative and survival outcomes remains questionable as current evidence is conflicting. In the present study, we sought to determine the factors that affect survival rates in ovarian cancer patients that undergo a splenectomy as part of maximal-effort cytoreduction. A retrospective chart review was conducted that included all epithelial ovarian cancer patients that had surgical cytoreduction for advanced epithelial ovarian cancer. Differences among splenectomized and non splenectomized patients were evaluated as well as the impact of known risk factors on survival outcomes of splenectomized patients. Overall, 245 patients were identified and 223 were included in the present series, of whom 91 had a splenectomy. Recurrence rates as well as death rates were comparable among splenectomized and non-splenectomized patients; however, both the disease-free survival (log-rank = 0.001), as well as the overall survival of splenectomized patients (log-rank = 0.006), was shorter. Thrombotic events as well as rates of pulmonary embolism were comparable. Sepsis was more common among splenectomized patients. The site of splenic metastases did not influence patients' survival. Among splenectomized patients, those offered primary debulking had longer progression-free survival (log-rank = 0.042), although their overall survival did not differ compared to patients submitted to interval debulking. Complete debulking significantly improved the overall survival compared to optimal debulking (log-rank = 0.047). Splenectomized patients that developed sepsis had worse overall survival (log-rank = 0.005). The findings of our study support the feasibility of splenectomy in advanced epithelial ovarian cancer; however, its impact on patients' survival is considerable. Therefore, every effort should be made to avoid splenic injury which will result in unintended splenectomy for non-oncological reasons.

Primary vs. interval cytoreduction for high-grade serous ovarian cancer: oncological outcomes from a retrospective study at a single tertiary referral center

Primary vs. interval cytoreduction for high-grade serous ovarian cancer: oncological outcomes from a retrospective study at a single tertiary referral center

"Things Have Changed"-Laparoscopic Cytoreduction for Advanced and Recurrent Ovarian Cancer: The Experience of a Referral Center on 108 Patients.

To report the feasibility of laparoscopic cytoreduction surgery for primary and recurrent ovarian cancer in a select group of patients. A retrospective analysis was conducted on a cohort of patients with FIGO stage IIIA-IV advanced ovarian cancer who underwent laparoscopic primary debulking surgery (PDS), interval debulking surgery (IDS), or secondary debulking surgery (SDS) between June 2008 and January 2020. The primary endpoint was achieving optimal cytoreduction, defined as residual tumor less than 1 cm. Secondary endpoints included evaluating surgical complications and long-term survival, assessed at three-month intervals during the initial two years and then every six months. This study included a total of 108 patients, among whom, 40 underwent PDS, 44 underwent IDS, and 24 underwent SDS. Optimal cytoreduction rates were found to be 95.0%, 97.7%, and 95.8% for the PDS, ISD, and SDS groups, respectively. Early postoperative complications (<30 days from surgery) occurred in 19.2% of cases, with 7.4% of these cases requiring reintervention. One patient died following postoperative respiratory failure. Late postoperative complications (<30 days from surgery) occurred in 9.3% of cases, and they required surgical reintervention only in one case. After laparoscopic optimal cytoreduction with a median follow-up time of 25 months, the overall recurrence rates were 45.7%, 38.5%, and 39.3% for PDS, ISD, and SDS, respectively. The three-year overall survival rates were 84%, 66%, and 63%, respectively, while the three-year disease-free survival rates were 48%, 51%, and 71%, respectively. Laparoscopic cytoreduction surgery is feasible for advanced ovarian cancer in carefully selected patients, resulting in high rates of optimal cytoreduction, satisfactory peri-operative morbidity, and encouraging survival outcomes. Future studies should focus on establishing standardized selection criteria and conducting well-designed investigations to further refine patient selection and evaluate long-term outcomes.

Exploring the Potential Role of Upper Abdominal Peritonectomy in Advanced Ovarian Cancer Cytoreductive Surgery Using Explainable Artificial Intelligence.

The Surgical Complexity Score (SCS) has been widely used to describe the surgical effort during advanced stage epithelial ovarian cancer (EOC) cytoreduction. Referring to a variety of multi-visceral resections, it best combines the numbers with the complexity of the sub-procedures. Nevertheless, not all potential surgical procedures are described by this score. Lately, the European Society for Gynaecological Oncology (ESGO) has established standard outcome quality indicators pertinent to achieving complete cytoreduction (CC0). There is a need to define what weight all these surgical sub-procedures comprising CC0 would be given. Prospectively collected data from 560 surgically cytoreduced advanced stage EOC patients were analysed at a UK tertiary referral centre.We adapted the structured ESGO ovarian cancer report template. We employed the eXtreme Gradient Boosting (XGBoost) algorithm to model a long list of surgical sub-procedures. We applied the Shapley Additive explanations (SHAP) framework to provide global (cohort) explainability. We used Cox regression for survival analysis and constructed Kaplan-Meier curves. The XGBoost model predicted CC0 with an acceptable accuracy (area under curve [AUC] = 0.70; 95% confidence interval [CI] = 0.63-0.76). Visual quantification of the feature importance for the prediction of CC0 identified upper abdominal peritonectomy (UAP) as the most important feature, followed by regional lymphadenectomies. The UAP best correlated with bladder peritonectomy and diaphragmatic stripping (Pearson's correlations > 0.5). Clear inflection points were shown by pelvic and para-aortic lymph node dissection and ileocecal resection/right hemicolectomy, which increased the probability for CC0. When UAP was solely added to a composite model comprising of engineered features, it substantially enhanced its predictive value (AUC = 0.80, CI = 0.75-0.84). The UAP was predictive of poorer progression-free survival (HR = 1.76, CI 1.14-2.70, P: 0.01) but not overall survival (HR = 1.06, CI 0.56-1.99, P: 0.86). The SCS did not have significant survival impact. Machine Learning allows for operational feature selection by weighting the relative importance of those surgical sub-procedures that appear to be more predictive of CC0. Our study identifies UAP as the most important procedural predictor of CC0 in surgically cytoreduced advanced-stage EOC women. The classification model presented here can potentially be trained with a larger number of samples to generate a robust digital surgical reference in high output tertiary centres. The upper abdominal quadrants should be thoroughly inspected to ensure that CC0 is achievable.

The Cukurova score in the prediction of primary cytoreduction in ovarian cancer

ObjectivePrimary debulking surgery has been the preferred surgical route and is still considered a quality indicator for advanced ovarian cancer surgery. However, a significant number of patients are not amenable...

The peritoneal cancer index as a predictor of complete cytoreduction at primary and interval cytoreductive surgery in advanced ovarian cancer

ObjectiveThe peritoneal cancer index quantitatively assesses cancer distribution and tumor burden in the peritoneal cavity. The aim of this study is to evaluate the association between the peritoneal cancer index...

Minimally-Invasive Secondary Cytoreduction in Recurrent Ovarian Cancer.

The role of secondary cytoreductive surgery (SCS) in the treatment of recurrent ovarian cancer (ROC) has been widely increased in recent years, especially in trying to improve the quality of life of these patients by utilising a minimally-invasive (MI) approach. However, surgery in previously-treated patients may be challenging, and patient selection and surgical planning are crucial. Unfortunately, at the moment, validated criteria to select patients for MI-SCS are not reported, and no predictors of its feasibility are currently available, probably due to the vast heterogeneity of recurrence patterns. The aim of this narrative review is to describe the role of secondary cytoreductive surgery and, in particular, minimally-invasive procedures, in ROC, analyzing patient selection, outcomes, criticisms, and future perspectives.

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis developed after ovarian cancer cytoreduction surgery: a case report and literature review

BackgroundAnti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis (AE), is often found associated with tumors such as thymoma, lung cancer, ovarian tumors, and breast cancer, and the tumors were generally detected during the screening process after the encephalitis initiated. The tumor is considered a trigger of AE, but the mechanism remains unclear.Case PresentationA 53-year-old woman presented short-term memory loss two days after the primary cytoreduction for high-grade serous ovarian cancer (HGSOC, FIGO stage IC3). Cell-based assay found AMPAR CluA2 IgG positive in both serum (1:3.2) and cerebrospinal fluid (1:32). Moreover, mild AMPAR GluA1 and strong GluA2 expressions were also found positive in the paraffin sections of ovarian tumor tissue, indicating the ovarian cytoreduction surgery might stimulate the release of receptor antigens into the circulation system. The patient’s condition deteriorated within two weeks, developing consciousness and autonomic dysfunction, leading to ICU admission. With oral steroids, intravenous immunoglobulin, plasmapheresis, and rituximab treatment, the patient’s consciousness markedly improved after three months.ConclusionWe presented the first case of anti-AMPAR encephalitis developed right after the primary cytoreduction of a patient with HGSOC and retrieved paraneoplastic anti-AMPAR encephalitis cases (n = 66). Gynecologists should pay attention to patients who develop cognitive dysfunction or psychiatric symptoms shortly after the ovarian tumor resection and always include AE in the differentiation diagnosis.

'First do no harm' revisited in ovarian cancer cytoreduction.

Linked article: This is a mini commentary on Marchetti et al., pp.1579–1588 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17558.

Minimizing futile laparotomies at primary cytoreduction for advanced ovarian cancer: A feasibility study comparing management algorithms (023)

Minimizing futile laparotomies at primary cytoreduction for advanced ovarian cancer: A feasibility study comparing management algorithms (023)

Complete Cytoreduction in Advanced Epithelial Ovarian Cancer: The Time Has Come to Define a Standard Boundary

Complete Cytoreduction in Advanced Epithelial Ovarian Cancer: The Time Has Come to Define a Standard Boundary

Role of Serum CA125 and HE4 in Predicting Optimal Cytoreduction in Advanced Epithelial Ovarian Cancer After Neoadjuvant Chemotherapy

Role of Serum CA125 and HE4 in Predicting Optimal Cytoreduction in Advanced Epithelial Ovarian Cancer After Neoadjuvant Chemotherapy

Secondary cytoreduction in platinum sensitive relapsed ovarian cancer: an individual patient level meta-analysis

ObjectiveTo synthesize the role of secondary cytoreduction in recurrent ovarian cancer from the results of randomized studies.MethodsWe conducted a meta-analysis of randomized controlled trials which compared secondary cytoreductive surgery versus...

Robotic surgery in ovarian cancer.

Ovarian cancer (OC) represents one of the most lethal cancers in women. The aim of surgical treatment is complete cytoreduction in advanced stages and a surgical staging in early stages. Although the guidelines still suggest laparotomy as the standard approach, in recent years minimally invasive surgery (MIS) has become increasingly popular in the treatment of OC, especially in early stages, because the 5-year relative survival exceeds 90% and the patients' quality of life cannot be overshadowed. However, MIS has been demonstrated to have a role even in advanced stages, in the prediction of optimal cytoreduction, identification patients who may benefit from neoadjuvant chemotherapy, and, more recently, in the interval debulking surgery, as in selected cases of secondary cytoreduction for recurrent ovarian cancer. The aim of this review is to describe the MIS (especially robotic surgery), with its advantages and pitfalls, in the treatment of OC.

Circulating tumor DNA (ctDNA) as a marker of residual disease and recurrence in resected stage I-IV epithelial ovarian cancer (EOC).

5553 Background: The management of EOC remains challenging, with a high risk of relapse despite surgery, chemotherapy and maintenance therapy. Detection of ctDNA after surgery and adjuvant chemotherapy (CT) may identify patients (pts) at highest risk of recurrence suitable for treatment escalation. Our primary aim was to investigate the use of ctDNA as a marker of residual disease following both surgery and adjuvant CT that might predict later recurrence. Methods: In this multi-centre observational study, we collected blood samples post-op and 6-8 weeks post-CT completion from pts with debulked stage I-IV EOC planned for adjuvant CT. Pre-cycle 1 CT and pre-op blood was also collected from some pts who received neoadjuvant CT. We used a tumor-informed approach for ctDNA analysis with whole exome sequencing of tumor tissue followed by detection of up to 50 variants in the plasma with the SaferSeqS assay. The primary outcome was recurrence-free survival (RFS), calculated using the Cox proportional-hazards model. Results: 81 pts who had post-op ctDNA results were included. 84% had high grade serous histology and 23% had BRCA mutations. Median number of tumor-informed variants analyzed in the plasma was 44 (range 3-60). Overall, post-operative ctDNA was detected in 63 of 81 (78%) of pts, 18 of 26 (69%) in Stage I-II and 45 of 55 (82%) in Stage III-IV. Pts who were ctDNA negative post-surgery had longer RFS versus who were ctDNA positive (HR 3.28, 95% CI 1.39 to 7.72, p = 0.007). Estimated RFS at 2 years was 78% among pts who were ctDNA negative post-surgery and 44% among the ctDNA positive group. Pts with BRCA mutations were less likely to have positive post op ctDNA (OR 0.12, 95% CI 0.036 to 0.39, p &lt; 0.001). For post-CT ctDNA, estimated RFS at 2 years was 74% in the ctDNA negative pts versus 43% in the ctDNA positive group but this was not statistically significant (HR 1.64, 95% CI 0.84 to 3.18, p = 0.15). Pts with zero residual disease were more likely to be ctDNA negative post-surgery (OR 12.36, 95% CI 1.54 to 99.4, p = 0.018). Post-op ctDNA outperformed post-op CA-125 in predicting recurrence; pts with elevated CA-125 post-surgery had shorter RFS compared to those with normal CA-125 post-surgery (HR 1.99, 95% CI 1.15 to 3.42, p = 0.013). Of 18 pts who had neoadjuvant CT, pre-treatment ctDNA was detected in 17 (94%). Only two pts had clearance of ctDNA post neoadjuvant CT and both had zero residual disease at surgery. For the pts that maintained positive ctDNA results post-op, 7/15 (47%) pts had zero residual disease. Conclusions: ctDNA detection after ovarian cancer cytoreduction identifies pts at very high risk of recurrence. Pts with BRCA mutations were more likely to have negative ctDNA post-op. The role of ctDNA in guiding neoadjuvant and adjuvant therapy to improve outcomes, warrants further investigation. Clinical trial information: ACTRN12617001119381 .