Cytoreduction For Ovarian Cancer Research Articles

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.

"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 .

Validation of the Integrated Prediction Model algorithm for outcome of cytoreduction in advanced ovarian cancer

BackgroundWe previously developed the Integrated Prediction Model using a 4-step algorithm of unresectable stage IVB, patient factors, surgical resectability, and surgical complexity to predict outcome of <1 cm cytoreduction in...

Splenectomy in epithelial ovarian cancer surgery

ObjectiveSplenectomy is performed in 4–32% of cytoreductive surgeries for ovarian cancer. The objective of our study was to assess splenectomy and evaluate its impact on overall and disease-free survival.MethodsWe conducted...

Comparison of the Contracted Accordion, Expanded Accordion, and Clavien-Dindo complication grading scales after ovarian cancer cytoreduction

ObjectiveTo compare the ability of current complication reporting scales (Contracted Accordion Scale, Expanded Accordion Scale, Clavien-Dindo Scale) to reflect the severity of patient outcomes after cytoreductive surgery for ovarian cancer.MethodsWe...

Development of a Novel Intra-Operative Score to Record Diseases' Anatomic Fingerprints (ANAFI Score) for the Prediction of Complete Cytoreduction in Advanced-Stage Ovarian Cancer by Using Machine Learning and Explainable Artificial Intelligence.

The Peritoneal Carcinomatosis Index (PCI) and the Intra-operative Mapping for Ovarian Cancer (IMO), to a lesser extent, have been universally validated in advanced-stage epithelial ovarian cancer (EOC) to describe the extent of peritoneal dissemination and are proven to be powerful predictors of the surgical outcome with an added sensitivity of assessment at laparotomy of around 70%. This leaves room for improvement because the two-dimensional anatomic scoring model fails to reflect the patient's real anatomy, as seen by a surgeon. We hypothesized that tumor dissemination in specific anatomic locations can be more predictive of complete cytoreduction (CC0) and survival than PCI and IMO tools in EOC patients. (2) Methods: We analyzed prospectively data collected from 508 patients with FIGO-stage IIIB-IVB EOC who underwent cytoreductive surgery between January 2014 and December 2019 at a UK tertiary center. We adapted the structured ESGO ovarian cancer report to provide detailed information on the patterns of tumor dissemination (cancer anatomic fingerprints). We employed the extreme gradient boost (XGBoost) to model only the variables referring to the EOC disseminated patterns, to create an intra-operative score and judge the predictive power of the score alone for complete cytoreduction (CC0). Receiver operating characteristic (ROC) curves were then used for performance comparison between the new score and the existing PCI and IMO tools. We applied the Shapley additive explanations (SHAP) framework to support the feature selection of the narrated cancer fingerprints and provide global and local explainability. Survival analysis was performed using Kaplan-Meier curves and Cox regression. (3) Results: An intra-operative disease score was developed based on specific weights assigned to the cancer anatomic fingerprints. The scores range from 0 to 24. The XGBoost predicted CC0 resection (area under curve (AUC) = 0.88 CI = 0.854-0.913) with high accuracy. Organ-specific dissemination on the small bowel mesentery, large bowel serosa, and diaphragmatic peritoneum were the most crucial features globally. When added to the composite model, the novel score slightly enhanced its predictive value (AUC = 0.91, CI = 0.849-0.963). We identified a "turning point", ≤5, that increased the probability of CC0. Using conventional logistic regression, the new score was superior to the PCI and IMO scores for the prediction of CC0 (AUC = 0.81 vs. 0.73 and 0.67, respectively). In multivariate Cox analysis, a 1-point increase in the new intra-operative score was associated with poorer progression-free (HR: 1.06; 95% CI: 1.03-1.09, p < 0.005) and overall survival (HR: 1.04; 95% CI: 1.01-1.07), by 4% and 6%, respectively. (4) Conclusions: The presence of cancer disseminated in specific anatomical sites, including small bowel mesentery, large bowel serosa, and diaphragmatic peritoneum, can be more predictive of CC0 and survival than the entire PCI and IMO scores. Early intra-operative assessment of these areas only may reveal whether CC0 is achievable. In contrast to the PCI and IMO scores, the novel score remains predictive of adverse survival outcomes.

Maximal Effort Cytoreduction in Epithelial Ovarian Cancer: Perioperative Complications and Survival Outcomes from a Retrospective Cohort.

Background: Rates of maximal effort cytoreductive surgery in ovarian cancer patients increase gradually the last decade. The purpose of the present study is to evaluate factors that contribute to survival and morbidity outcomes in this group of patients. Methods: We retrospectively reviewed patient records of epithelial ovarian cancer patients with an intermediate and high Mayo Clinic surgical complexity score, operated between January 2010 and December 2018. Results: Overall, 107 patients were enrolled in the present study with a median age of 62 years (23-84) and a follow-up of 32 months (2-156). Thirteen Clavien-Dindo grade IIIa complications were documented in 10 patients (9.3%). Of all the investigated factors, only stage IVb (p = 0.027) and interval debulking surgery (p = 0.042) affected overall survival rates. Overall survival outcomes of patients operated on a primary setting started to differentiate compared to those that received neo-adjuvant chemotherapy after the 4th postoperative year. Conclusions: Maximal effort cytoreductive procedures should be considered feasible in the modern surgical era, as they are accompanied by acceptable rates of perioperative morbidity. Hence, every effort should be made to perform them in the primary setting, rather than following neoadjuvant chemotherapy as current evidence favor increased survival rates of patients that will likely surpass an interval of observation of more than 4 years.

Intrathoracic surgery as part of primary cytoreduction for advanced ovarian cancer: Going to the next level – A Memorial Sloan Kettering Cancer Center study

ObjectiveWe investigated the feasibility, safety, and survival outcomes of intrathoracic cytoreduction during primary debulking surgery (PDS) for advanced ovarian cancer. MethodsWe conducted a database review of patients with stage IIIB-IV ovarian (including fallopian tube and primary peritoneal) carcinoma who underwent PDS at our institution from 01/01/2006–9/30/2021. Patients who underwent intrathoracic cytoreduction as part of primary treatment were included. Patients who received neoadjuvant chemotherapy or surgery for reasons other than cytoreduction were excluded. ResultsAmong 178 patients identified for inclusion, complete gross resection (CGR) in the abdomen and thorax was achieved in 131 (74%); 45 (25%) had optimal cytoreduction, and 2 (1%) had suboptimal cytoreduction. Thirty-one patients (17%) had at least one grade ≥ 3 complication; 8 were possibly related to intrathoracic cytoreduction. There were no deaths within 30 days following surgery. Median length of follow-up among survivors was 53.4 months. Among all patients, the median PFS was 33.6 months (95% CI: 24.7–61.9) and the 3-year PFS rate was 48.9% (95% CI: 41.2%–56.2%). Median OS was 81.3 months (95% CI: 68.9–103). When stratified by residual disease status, median PFS was 51.8 months when CGR was achieved versus 16.7 months with residual disease (HR: 2.17; P < .001) and median OS was 97.6 months when CGR was achieved versus 65.9 months with residual disease (HR: 2.05; P = .003). ConclusionsIntrathoracic cytoreduction during PDS for advanced ovarian cancer is both safe and feasible. CGR can be achieved in patients with intrathoracic disease if properly selected, and could significantly improve both PFS and OS.