Cytoreductive Surgery For Ovarian Cancer Research Articles

Role of MRI in Pre-Operative Assessment of Patients with Advanced Ovarian Cancer Candidate for Cytoreductive Surgery, A Brief Review

When it comes to gynecologic cancer, ovarian cancer with no doubt is the deadliest and most challenging. The reason often falls into the late presentation, in fact the clinical symptoms are not prominent until the disease is disseminated In patients with advanced ovarian cancer cytoreductive surgery procedure is the key element in treatment plan. One of the best tools to predict successful and complete cytoreductive surgery is using prior imaging. Magnetic resonance imaging is one of the newly described imaging modality for advanced ovarian cancer patients selected for cytoreductive surgery. Here we discussed the application of MRI in advanced ovarian cancer underwent cytoreductive surgery.

Factors predicting postoperative morbidity after cytoreductive surgery for ovarian cancer: a systematic review and meta-analysis.

ObjectiveAdvances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable.MethodsElectronic databases were searched. Meta-analysis was conducted using random-effects models.ResultsFifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001).ConclusionOur study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS.Trial RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42021282770

Outcomes of splenectomy during primary cytoreductive surgery in ovarian cancer

Objectives: Most splenectomies performed in ovarian cancer (OC) debulking are for disease resection; the impact of splenectomy on 30-day complication and oncologic outcomes is unclear. We aimed to determine the association of splenectomy with postoperative complications, overall survival (OS), and progression-free survival (PFS) in the setting of primary debulking surgery (PDS) for OC. Methods: We retrospectively evaluated women who underwent PDS or surgical staging for OC from 1/2003-07/2016. Perioperative variables and 30-day complications defined by ACS-NSQIP were abstracted. Among those with advanced stage (IIIC/IV) disease, complications were graded using the modified Accordion grading scale; severe was defined as grade 3 or 4. A propensity score (PS) matched cohort was evaluated to limit the effect of bias due to confounding variables between patients who did and did not have a splenectomy. The severe complication rate was compared between matched pairs using McNemar's test and time-to-event outcomes were compared using stratified Cox proportional hazards models. Results: Among 1311 patients in the cohort, 153 (11.7%) underwent splenectomy. Patients with splenectomy were more likely to have advanced stage disease (96.1 vs 60.6%), serous histology (89.5 vs 68.8%), ascites (83.0 vs 45.3%), higher median preoperative CA-125 (737 vs 388 U/mL), and residual disease (52.9 vs 31.3%), compared to patients without splenectomy (all p Download : Download high-res image (74KB) Download : Download full-size image Conclusions: We observed that splenectomy during PDS was associated with increased risk of progression and death compared to those not undergoing splenectomy but this risk was no longer observed with a PS-matched cohort. Splenectomy appears to be a marker for disease extent but does not increase the risk of progression or decreased survival in and of itself. Splenectomy was associated with a higher risk of severe postoperative complications including a 9% risk of pancreatic leak. These findings underscore the importance of preoperative surgical risk/benefit assessment and expertise in management of complications.

Quaternary and beyond cytoreduction: An updated and expanded analysis

ObjectiveWe sought to describe the clinicopathologic features and outcomes of patients undergoing quaternary, quinary, or senary cytoreductive surgery for ovarian cancer. MethodsWe retrospectively identified patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who underwent quaternary or beyond cytoreduction at our institution between 1/1/1989 and 12/31/2020. Kaplan-Meier curves were used to estimate survival and compared using the log-rank test. Cox-proportional hazards regression was used to detect variables associated with survival. ResultsTwenty patients underwent 24 quaternary (n = 20), quinary (n = 3), or senary (n = 1) cytoreductive surgeries. Most patients had high-grade (89.5%) and serous (75.0%) tumors. At the time of quaternary cytoreduction, 44.7% of patients had single-site disease and 85.0% achieved a complete gross resection. After quaternary cytoreduction, 34.8% of patients developed a surgical complication, most of which were grade 1 or 2. Postoperatively, 80.0% of patients received additional medical treatment and 20.0% underwent observation alone. On univariate analysis, factors associated with progression-free survival included prolonged treatment-free interval (TFI), platinum sensitivity, and complete gross resection. Factors associated with disease-specific survival included platinum sensitivity and complete gross resection. Quinary and senary surgeries were associated with similar safety profiles, with no surgical complications reported. After quinary surgery, progression-free survival ranged from 5.0 to 216.0 months. ConclusionsIn carefully selected patients, quaternary cytoreduction may be associated with acceptable morbidity and a relatively robust disease-specific survival. Patients who present to surgery with a prolonged TFI and achieve a complete gross resection likely derive the greatest benefit from quaternary surgery.

Stoma creation at the time of large bowel resection during ovarian cytoreductive surgery does not improve 30-day postoperative surgical outcomes

Objectives: Large bowel resections (LBR) are occasionally required to achieve optimal resection during cytoreductive surgery for ovarian cancer. Stoma creation (SC) has been proposed as a protective measure to reduce the incidence and potential consequences of an anastomotic leak after LBR; however there is conflicting data on whether this does indeed reduce rates of leak. The objectives of this study were to evaluate the rate of SC at time of LBR during ovarian cytoreductive surgery (OCS), and to determine whether SC reduces the rates of sepsis and reoperation. Methods: Women who underwent LBR at time of OCS from 2013 to 2018 were identified in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database using corresponding CPT, ICD-9, and ICD-10 codes. SC was determined based on CPT codes. Comparative analyses were then stratified by SC to evaluate demographics, preoperative and intraoperative variables, and surgical outcomes. Statistical tests were performed with R Studio v.1.1.456. Results: A total of 8,750 women who underwent OCS were identified, and 1,603 (18.3%) of these women underwent a concurrent LBR. Among the women who had a LBR, 1,418 (88.5%) had one bowel resection and 185 (11.5%) had multiple bowel resections performed. At the time of LBR, 1,003 (62.6%) had a primary anastomosis without SC, 272 (17.0%) had a colostomy, and 190 (11.8%) had an ileostomy. SC data was not available for 138 (8.6%) women, and these women were excluded from analysis. Preoperatively, women with SC tended to be of older age, and have a higher body mass index (BMI), higher American Society of Anesthesiology (ASA) class, higher White blood cell count, and lower albumin level. Women who had multiple bowel resections were more likely to have SC at time of OCS (17.3% vs. 8.4%, p Download : Download high-res image (120KB) Download : Download full-size image Conclusions: Over a quarter of women who had a concurrent LBR at time of OCS underwent SC. These women tended to be older with higher BMI and ASA class. Although the specific indications for SC are not captured in the NSQIP database, SC was associated with higher rates surgical site infection, organ space infection, sepsis, and hospital readmission during the 30-day postoperative period.

Peri-operative Variables Associated With Prolonged Intensive Care Stay Following Cytoreductive Surgery for Ovarian Cancer.

Peri-operative variables associated with prolonged Intensive Care Unit (ICU) admission following cytoreductive surgery for ovarian cancer were investigated. A retrospective review was carried out of patients admitted to the ICU following cytoreductive surgery for ovarian cancer in a single tertiary referral centre from 2015-2019. Patients were categorized according to length of ICU stay (<48 h and ≥48 h), and peri-operative variables were compared across the two groups. A total of 56 patients were admitted to the ICU post-operatively, 37 for <48 h and 19 for ≥48 h (range=3-11 days). Greater duration of procedure and estimated blood loss, bowel resection, higher post-operative lactate level, lower post-operative albumin level and requirement for post-operative blood products were associated with prolonged ICU stay. Increased intraoperative fluid requirement was an independent predictor of extended ICU stay. Utilizing identified intra-operative risk factors to perform individualized risk assessments might improve planning of ICU resources. Optimizing intraoperative fluid management may improve short-term patient outcomes.

Poor anaerobic threshold and VO2 max recorded during cardiopulmonary exercise testing (CPET) prior to cytoreductive surgery in advanced (stage 3/4) ovarian cancer (AOC) is associated with suboptimal cytoreduction but does not preclude maximum effort cytoreduction

This study assessed Cardiopulmonary Exercise Testing (CPET) in predicting oncological outcomes, post-operative recovery and complications in advanced ovarian cancer (AOC) cytoreductive surgery. We reviewed all patients who had CPET prior to AOC cytoreductive surgery with evidence of upper abdominal disease on preoperative imaging at the University Hospitals of Derby and Burton (UHDB) between August 2016 and July 2019. Patients were stratified by AT and maximum VO2 levels. 43 patients were identified. AT showed no relationship with major complications. 100% of patients in the AT ≥11 group received R0 (n = 21, 91.30%), or R1 (n = 2, 8.70%) cytoreduction, whereas in the AT <11 group, only 75.00% achieved and R0 or R1 resection (p = .02). Surgical complexity was higher in the AT ≥11 group (p = .001) and the VO2 ≥15 group (p = .0006). No other correlations were seen between AT or VO2 max and complications or readmissions. No difference in overall survival was seen if R0 resection was achieved. IMPACT STATEMENT What is already known on this subject? CPET testing allows pre-operative assessment of functional capacity to generate variables that can be used as a risk-stratification tool for major surgery. Whilst CPET testing has been shown to predict morbidity in non-gynaecological surgery, it remains unproven in cytoreductive surgery for ovarian cancer surgery despite being increasingly utilised. What do the results of study add? Our data suggest that CPET testing does not predict complication rates or survival in AOC. Patients with poor CPET performance are more likely to receive suboptimal cytoreductive outcomes from surgery. What are the implications of these findings for clinical practice and/or further research? CPET results should not be used to discount patients from cytoreductive surgery further research should address the interplay with nutrition, haematological markers, neoadjuvant chemotherapy and CPET performance.

Step-by-step procedure of visceral serosal segmentectomy during cytoreductive surgery for ovarian cancer

Step-by-step procedure of visceral serosal segmentectomy during cytoreductive surgery for ovarian cancer

Extrapelvic bowel resection and anastomosis in cytoreductive surgery for ovarian cancer.

Ovarian cancer is known as the second most common cause of death among gynecologic cancers. Survival outcome has been reported to be significantly associated with the efforts to minimize residual disease after cytoreductive surgery. As ovarian cancer often invades the small and large bowel without boundary, bowel surgery has been a crucial part of the cytoreductive surgery to achieve complete tumor removal. The scope of surgical resections has progressively expanded to include small and large bowel resections, making advanced surgical skills essential for gynecologic oncologists. In this review, we discuss the extra-pelvic bowel resection in cytoreductive surgery, with a focus on the regional anatomy and surgical techniques.

Modified intestinal isolation bag as promising tool in promoting bowel resumption after ovarian cancer cytoreductive surgery: a randomized clinical trial.

Postoperative ileus (POI) impairs patient recovery, prolonging hospital stay after major surgery in ovarian cancer (OvCa) patients. Thus, intraoperative bowel isolation is expected to reduce manipulation-related impairment. The aim of this study was to investigate the impact of intraoperative intestinal isolation bag on POI in OvCa patients submitted to primary surgery. A randomized trial including patients managed with or without isolation bag during OvCa primary surgery was conducted. Patients were selected by consecutive randomization. Primary endpoints were the time between surgery and resumption of bowel motility (as passage of first/continued flatus), assessing of postoperative nausea or vomiting and return to regular diet. Secondary endpoint was the impact of intestinal isolation bag on length of hospitalization in the two groups. Ninety-two patients respecting inclusion criteria were eligible to be enrolled in the study (48 patients as Group 1 and 44 patients as Group 2). Thirty-eight (79.2%) patients, in which intraoperative isolation bag was used, experienced first/continued flatus within 3days from surgery and they were susceptible to be discharged within 5days, compared, respectively, to 34.3% of Group 2 (n = 15). Advantages were more evident in patients whose surgery took over 220min (OR 0.02, CI 95% 0.001-0.57; p < 0.001) despite the type of surgical effort made. Despite the small sample size, our study showed that the use of intestinal isolation bag can reduce incidence of POI and length of stay in OvCa patients submitted to primary cytoreductive surgery.

Intraperitoneal hemorrhage following primary cytoreductive surgery for ovarian cancer: Successful treatment with superior epigastric artery embolization.

Hemoperitoneum often occurs due to abdominal trauma, abdominal tumors, gastro-intestinal perforation and more rarely it’s spontaneous due to coagulopathies. Superior epigastric artery (SEA) iatrogenic damage is rarer than the Inferior epigastric artery injury, it may occur during laparotomy and, in most cases, it causes a rectus muscle hematoma. We present the case of a caucasian 44 years-old-woman with hemoperitoneum after cytoreductive surgery for ovarian cancer. Active bleeding from the distal branch of the SEA was diagnosed at computed tomography and coil embolization followed by surgical laparotomic drainage of the hemoperitoneum was performed. After initial resolution, active bleeding from the same vessel was observed. Further embolization of the same vessel was necessary to stop bleeding. Ultrasound follow-up showed a complete resolution of the hemoperitoneum. (www.actabiomedica.it)

Effect of tumor burden and radical surgery on survival difference between upfront, early interval or delayed cytoreductive surgery in ovarian cancer.

ObjectiveWe sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0).MethodsThis retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC–IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3–4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score.ResultsFive hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score <8. Among patients with PCI ≤10, median OS after PDS was significantly higher than after early IDS or DDS. In women with PCI >10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS.ConclusionThe benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome.

Predictors of 30-day Readmission among Ovarian Cancer Patients Undergoing Surgery

Background: Cytoreductive surgery in ovarian cancer remains a complex and invasive procedure with elevated risks of postoperative complications and readmission. We aimed to characterize the rate and predictors of 30-day readmission in patients undergoing ovarian cancer surgery. Methods: Women undergoing ovarian cancer surgery between 2010 and 2015 were identified in the Nationwide Readmissions Database (NRD). Baseline demographics and clinical features of patients readmitted within 30 days were analyzed. Multivariable logistic regression analysis was used to identify significant perioperative factors associated with readmission. Results: Of 94,077 patients undergoing surgery for ovarian malignancy, 12,806 (13.6%) were readmitted within 30 days. The proportion of 30-day readmissions has significantly decreased from 15.2% in 2010 to 12.5% in 2015 (p<.001). Readmitted patients were more likely to have large bowel resection during initial surgery (18.9 vs. 11.5%, p<.001), and experience a postoperative complication, including bowel perforation and infection (11.2 vs. 7.7%, p<.001). The primary reasons for 30-day readmission included postoperative infection (10.6%) and gastrointestinal dysfunction or infection (9.0%). In multivariable analysis, Medicaid (OR 1.18 [95% Confidence Interval 1.04-1.35]), age < 50 years old (OR 1.35 [1.17-1.56]), large (OR 1.35 [1.20-1.51]) or small bowel (OR 1.34 [1.14-1.57]) resection, and discharge to a skilled nursing facility (SNF; OR 1.53 [1.34-1.75]) were significantly associated with 30-day readmission. For readmitted patients, index hospitalization cost was higher ($25,021 vs. $19,587, p<.001) and length of stay (LOS) was longer (8.7 vs 6.4 days, p<.001). Discussion: Rates of 30-day readmission are declining, however, continued optimization of perioperative pathways for patients at highest risk of readmission, including those undergoing bowel resections and those discharged to a SNF, is warranted.

Modified fragility index and surgical complexity score are able to predict postoperative morbidity and mortality after cytoreductive surgery for advanced ovarian cancer

ObjectiveThe aim of this study was to assess the impact of surgical complexity on postoperative complications and mortality, according to patient's frailty (mFI) following surgery for ovarian cancer. MethodsPatients undergoing cytoreductive surgery for ovarian cancer from 2008 to 2018 were identified from our database. A surgical complexity score from 1 to 3 was used to assess the extent of surgery (simple to complex, respectively). mFI with 11 variables, based on mapping the Canadian Study of Health and Aging Frailty Index to the NSQIP comorbidities was evaluated. Data were analyzed using Fisher exact test, independent sample t-test, and logistic regression. ResultsOf 263 patients identified, 33% reported at least one postoperative complication and 6% had severe complications. BMI ≥ 30 (p = 0.04) increased mFI (p = 0.04) and high-complexity surgery (p < 0.001) were independent predictors of severe complications (G3-G5). Patients with high frailty index score (mFI ≥ 3) who underwent intermediate or high-complexity surgery were at higher risk of severe complications ranging from 29.4% to 50. ConclusionsThe combined evaluation of mFI and surgical complexity expected may identify patients at higher risk for severe morbidity allowing to stratify patients who are less likely to tolerate a surgical extensive treatment.

The Ability Pre-operative Serum (Cancer Antigen-125, Fatty Acid Synthase, and Glucose Transporter) to Predict Primary Suboptimal Cytoreduction in Epithelial Ovarian Cancer

BACKGROUND: The incidence of ovarian cancer ranks 8th in the world, with 295,414 cases and 184,799 death in 2018. Management in ovarian cancer is surgery and chemotherapy. Some studies state that patients who underwent optimal cytoreduction surgery have better survival rates than suboptimal cytoreduction surgery. The pre-operative serum assessed in this study was Cancer Antigen-125 (CA-125), Fatty Acid Synthase (FASN), and Glucose Transporter (GLUT) to predict suboptimal cytoreduction in epithelial ovarian cancer (EOC).&#x0D; AIM: We aimed to use FASN and GLUT1 as other biomarkers, besides CA-125, to predict suboptimal cytoreduction surgery in epithelial ovarian cancer. &#x0D; METHODS: This observational-analytic cross-sectional study included 109 women diagnosed with epithelial ovarian cancer (EOC) between 2017 and 2019, who had serum CA-125, FASN, and GLUT measured preoperatively and underwent cytoreductive surgery.&#x0D; RESULTS: The results of the statistical analysis test in this study obtained p values at CA-125 (p = 0.0001), FASN (p = 0.017), and at GLUT (p = 0.013). While the cutoff point (COP) on CA-125 was 248.55, FASN was 0.445, and GLUT was 0.1980. The value of area under curve (AUC) obtained by the ROC method at CA-125 76.7%, FASN 65.3%, and GLUT 63.8%. The combination of CA-125 and FASN shows AUC value 76.9%, the combination of CA-125 and GLUT shows AUC value 72.2%, and the combination of the three shows AUC value 75.2%.&#x0D; CONCLUSION: The use of CA-125 as a predictor of cytoreduction surgery is still considered to be the best predictor compared to serum biomarkers in this study.

Chemokine Ligand 5 to Predict Optimal Cytoreduction in Ovarian Cancer.

PurposeThe ultimate goal of cytoreduction surgery is the complete removal of all visible tumors (complete cytoreductive surgery) or tumor residues <1 cm (optimal cytoreduction surgery). Following cytoreduction surgery in ovarian cancer, tumor residue is one of the most important prognostic factors. Oncologists strive to be able to predict the outcome of cytoreduction surgery during the presurgical period. The purpose of this study was to assess CCL5 as a modality for determining whether a patient could perform optimal cytoreduction surgery or not.Materials and MethodsThis was an observational, analytic, and cross-sectional study of patients with ovarian cancer who underwent surgery at the Dr. Hasan Sadikin Bandung from 2019 to 2020. All of the patients had stage I–IV disease based on the International Federation of Gynecology and Obstetrics (FIGO) score.ResultsIn total, 72 patients were enrolled in this study, 31 of whom underwent suboptimal cytoreduction surgery and 41 underwent optimal cytoreduction surgery. The mean serum CCL5 level at suboptimal cytoreduction was 70,920.87 ± 36,362.966, while that at optimal cytoreduction was 43,244.95 ± 21,983.887. CCL5, as a predictor of suboptimal cytoreduction surgery, had a sensitivity of 61.3%, a specificity of 68.3%, and an accuracy of 65.7% (p = 0.012).ConclusionPreoperative CCL5 serum levels can predict suboptimal cytoreduction surgery outcomes in patients with ovarian cancer.

How far should we go in optimal cytoreductive surgery for ovarian cancer?

The treatment of ovarian cancer should be appropriate, since clinical and surgical decisions may affect the prognosis; the surgery must be performed by an expert oncological surgeon or gynecological oncologist, it's fundamental roles are cancer staging and cytoreduction. The concept of staging surgery in early stages has its justification in the fact that up to 11% of "early ovarian cancers" will have metastasis in different sites of the peritoneal cavity at the time of diagnosis. In advanced stages of epithelial ovarian cancer, the goal is the complete cytoreduction of all visible macroscopic disease, since this variable is the most strongly associated with increased overall survival and disease-free period. The ideal time for cytoreductive surgery in relation to chemotherapy (before or after) is still under debate. In 2010 a randomized trial (EORTC) was published, comparing 310 patients initially operated (followed by adjuvant chemotherapy) versus 322 patients initially treated with neoadjuvant chemotherapy (followed by cytoreductive surgery); no significant differences in overall survival between groups were found. Another important factor playing a role in survival and in the probability of surgical cytoreductive success is tumor biology; there has been described a clear difference between serous and mucinous tumors, but some groups advocate that maximal surgical effort in mucinous tumors may compensate morbidity with an increase in survival. The extension of resection in cytoreduction is still controversial; some authors have confirmed that the most important factor is the residual disease and that radical surgery is superior to non-radical surgery in terms of overall survival. The need and extent of lymphadenectomy in advanced cancer will be treated in another chapter of this issue. Undoubtedly, an important factor is to perform procedures in specialized centers.

Lebanese experience with cytoreductive surgery in ovarian cancer: A single institution series

Lebanese experience with cytoreductive surgery in ovarian cancer: A single institution series

Predictive factors of postoperative complications after cytoreductive surgery for ovarian cancer

Objective: Ovarian cancer is the leading cause of death from gynecological cancer for women. The standard treatment consists of extensive cytoreductive surgery followed with adjuvant chemotherapy. This study aims to identify the common postoperative complications as well as to define predictive factors of their occurrence.

Systemic and intratumoral stress responses to primary debulking surgery in patients with epithelial ovarian cancer

Objective: There is evidence suggesting that surgical procedures may facilitate tumor growth and promote metastases because of paracrine and neuroendocrine stress response, which increases proangiogenic factors, suppresses antitumor immunity, and facilitates malignant cell invasion and proliferation. We sought to determine whether a protumorigenic stress response occurs in the course of ovarian cancer (OC) cytoreductive surgery and to define its impact on the tumor and tumor microenvironment.