Showing papers on "Debulking published in 2017"
TL;DR: Reversion mutations can be detected in an unbiased analysis of cfDNA, suggesting clinical utility for predicting chemotherapy response in recurrent HGSC and from a rapid autopsy of a patient with multiple independent reversions indicated that reversion-allele frequency in metastatic sites is an important determinant of assay sensitivity.
Abstract: PurposeGermline BRCA1 or BRCA2 mutations in patients with high-grade serous ovarian cancer (HGSC) are associated with favorable responses to chemotherapy. However, secondary intragenic (reversion) mutations that restore protein function lead to clinically significant rates of acquired resistance. The goal of this study was to determine whether reversion mutations could be found in an unbiased manner in circulating cell-free DNA (cfDNA) to predict treatment response in HGSC.Patients and MethodsPlasma and tumor samples were obtained from 30 patients with HGSC with either BRCA1 or BRCA2 germline mutation. Two cohorts were ascertained: patients with a malignancy before undergoing primary HGSC debulking surgery (n = 14) or patients at disease recurrence (n = 16). Paired tumor and plasma samples were available for most patients (24 of 30). Targeted amplicon, next-generation sequencing was performed using primers that flanked germline mutations, whose design did not rely on prior knowledge of reversion sequences...
134 citations
TL;DR: This review summarizes all AMN classifications and proposes a treatment algorithm based on stage and histology of disease, a reference to guide gastroenterologists, pathologists, surgeons, and oncologists in the management of appendiceal mucinous neoplasms.
Abstract: Objective Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding modalities of treatment to guide the management of AMNs. Methods and review criteria We conducted a PubMed search in February 2016 for English-language publications, using the terms "appendiceal," "appendix," "carcinoma," "cancer," "mucinous," "treatment," "genes," "target," "genomic," and terms listed in the articles' subheadings. Published reports and abstracts from the American Society of Clinical Oncology meetings were also searched. Results In this review, we summarize current data and controversies in AMN classification, clinical presentation, molecular alterations, treatment outcomes with regard to cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and the role of systemic chemotherapy. Conclusion Appendiceal mucinous neoplasms are a heterogeneous group of tumors with a rising incidence. Treatment is based on stage and histology. Low-grade tumors are treated surgically with resection of the primary site in early stage disease, or peritoneal debulking and HIPEC in patients with advanced stage disease. Treatment of high-grade tumors requires further prospective trials, and options include debulking surgery and HIPEC with or without preoperative chemotherapy. Trials evaluating novel therapies based on the molecular profiling of AMN tumors are needed to evaluate therapeutic options in patients who are not surgical candidates. Implications for practice This review provides a reference to guide gastroenterologists, pathologists, surgeons, and oncologists in the management of appendiceal mucinous neoplasms (AMNs), a rare and heterogeneous disease with no consensus on histologic classification or guidelines for treatment algorithms. This review summarizes all AMN classifications and proposes a treatment algorithm based on stage and histology of disease.
117 citations
TL;DR: The role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation.
114 citations
TL;DR: The consensus statements regarding first-line therapies in women with ovarian cancer, reached at the Fifth Ovarian Cancer Consensus Conference held in Tokyo, Japan, in November 2015 are reported.
109 citations
TL;DR: PMP is challenging, complex but nevertheless the most rewarding peritoneal malignancy amenable to cure by CRS and HIPEC.
Abstract: Pseudomyxoma peritonei (PMP) is an uncommon disease characterised by mucinous ascites, classically originating from a ruptured low grade mucinous neoplasm of the appendix. The natural history of PMP revolves around the "redistribution phenomenon", whereby mucinous tumour cells accumulate at specific sites with relative sparing of the motile small bowel and to a lesser extent other parts of the gastrointestinal tract. Peritoneal tumour accumulates due to gravity and at the sites of peritoneal fluid absorption, namely, the greater and lesser omentum and the under-surface of the diaphragm, particularly on the right. The optimal treatment is complete macroscopic tumour excision termed cytoreductive surgery (CRS) combined with Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC). Total operating time for complete CRS and HIPEC for extensive PMP is around 10 h and generally involves bilateral parietal and diaphragmatic peritonectomies, right hemicolectomy, radical greater omentectomy with splenectomy, cholecystectomy and liver capsulectomy, a pelvic peritonectomy with, or without, rectosigmoid resection and bilateral salpingo-oophorectomy with hysterectomy in females. A unique feature of low grade PMP, which differs from other peritoneal malignancies, includes slow disease progression, which may be asymptomatic until advanced stages. Additionally, very extensive disease with a high "PCI" (Peritoneal Carcinomatosis Index) may still be amenable to complete excision and cure. In cases where complete tumour removal is not feasible, maximum tumour debulking can still result in long-term survival in PMP. PMP is challenging, complex but nevertheless the most rewarding peritoneal malignancy amenable to cure by CRS and HIPEC.
103 citations
TL;DR: The ability of preoperative computed tomography scan and CA-125 to predict gross residual disease (RD) at primary cytoreduction in advanced ovarian cancer was assessed and a multivariate model predictive of RD was developed.
89 citations
TL;DR: Bvacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision, as the CRR with BCP was significantly higher than the reference rate.
78 citations
TL;DR: This review comprehensively describes recent advances in the management of malignant central airway obstruction and assesses the risks and benefits of interventions in each individual patient during the decision-making process.
Abstract: This review comprehensively describes recent advances in the management of malignant central airway obstruction (CAO). Malignant CAO can be a dramatic and devastating manifestation of primary lung cancer or metastatic disease. A variety of diagnostic modalities are available to provide valuable information to plan a therapeutic intervention. Clinical heterogeneity in the presentation of malignant CAO provides opportunities to adapt and utilize endoscopic technology and tools in many ways. Mechanical debulking, thermal tools, cryotherapy and airway stents are methods and instruments used to rapidly restore airway patency. Delayed bronchoscopic methods, such as photodynamic therapy (PDT) and brachytherapy can also be utilized in specific non-emergent situations to establish airway patency. Although data regarding the success and complications of therapeutic interventions are retrospective and characterized by clinical and outcome measure variability, the symptoms of malignant CAO can often be successfully palliated. Assessment of risks and benefits of interventions in each individual patient during the decision-making process forms the critical foundation of the management of malignant CAO.
76 citations
TL;DR: Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery and future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival.
Abstract: Background Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Methods Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm2/m2). Cox-regression and Kaplan–Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Results Kaplan–Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105–2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968–1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Conclusion Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival.
72 citations
TL;DR: AL rate was mainly influenced by rectosigmoid resection and only marginally increased by additional bowel resections and was independently associated with shortened overall survival.
61 citations
TL;DR: BRCA testing might be a reliable tool to personalize treatment in patients with high‐grade serous ovarian cancer, thus giving novel points of discussion to the ongoing debate regarding the best initial treatment approach.
TL;DR: It is reported that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 from dendritic cells.
Abstract: Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211-21. ©2017 AACR.
TL;DR: The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety, and median PFS is the longest reported for frontline bevacsuzumab-containing therapy.
Abstract: Objective The aim of this study was to assess the safety and efficacy of extending bevacizumab therapy beyond 15 months in nonprogressive ovarian cancer. Patients and Methods In this multinational prospective single-arm study (ClinicalTrials.gov NCT01239732), eligible patients had International Federation of Gynecology and Obstetrics stage IIB to IV or grade 3 stage I to IIA ovarian cancer without clinical signs or symptoms of gastrointestinal obstruction or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the preceding 6 months. Prior neoadjuvant chemotherapy was permitted. After debulking surgery, patients received bevacizumab 15 (or 7.5) mg/kg every 3 weeks (q3w) with 4 to 8 cycles of paclitaxel (investigator’s choice of 175 mg/m2 q3w or 80 mg/m2 weekly) plus carboplatin AUC 5 to 6 q3w. Single-agent bevacizumab was continued until progression or for up to 24 months. The primary end point was safety. Results Between December 2010 and May 2012, 1021 patients from 35 countries began study treatment. Bevacizumab was administered at 15 mg/kg in 89% of patients and for more than 15 months in 53%. Median follow-up duration was 32 months (range, 1–50 months). The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%). The most common grade 3 or higher-grade adverse events were neutropenia (27%) and hypertension (25%). Bevacizumab was discontinued because of proteinuria in 5% of patients and hypertension in 3%. Median progression-free survival (PFS) was 25.5 months (95% confidence interval, 23.7–27.6 months). Conclusion Extended bevacizumab demonstrated increased incidences of proteinuria and hypertension compared with 12 or 15 months of bevacizumab in previous trials, but these rarely led to bevacizumab discontinuation. Median PFS is the longest reported for frontline bevacizumab-containing therapy. The longer bevacizumab duration beyond 15 months in this study may improve PFS without substantially compromising safety.
TL;DR: The CRS system for assessing NAC response was a reproducible prognostic tool in an external cohort of tubo-ovarian HGSC patients and can improve survival estimation in HG SC patients.
Abstract: OBJECTIVE The chemotherapy response score (CRS) system based on histopathological examination has been recently proposed for tubo-ovarian high-grade serous carcinoma (HGSC) to assess response to neoadjuvant chemotherapy (NAC). This study was aimed at validating the CRS system in an external cohort of tubo-ovarian HGSC patients. METHODS This study included 110 tubo-ovarian HGSC patients who underwent NAC followed by interval debulking surgery. The 3-tiered CRS of the omental and adnexal tissue sections was determined by 3 independent pathologists. Differences in patient outcomes according to CRS were analyzed. RESULTS The CRS system was highly reproducible among the 3 pathologists. Fleiss' kappa value and Kendall's coefficient of concordance for the omental CRS were 0.656 and 0.669, respectively. The omental CRS significantly predicted progression-free survival (PFS). The median PFS of patients whose tumors exhibited the omental CRS 1-2 (15 months) was significantly shorter than that of patients with an omental CRS of 3 (19 months; p=0.016). In addition, after adjusting for age, stage, and debulking status, the omental CRS was an independent prognostic factor for PFS of tubo-ovarian HGSC patients who were treated with NAC (adjusted hazard ratio [HR]=1.74; 95% confidence interval [CI]=1.05-2.87). CONCLUSION The CRS system for assessing NAC response was a reproducible prognostic tool in our cohort. The application of the CRS system after NAC can improve survival estimation in HGSC patients.
TL;DR: For selected patients, laparoscopy is a feasible and safe approach to optimal cytoreduction for patients with recurrent ovarian cancer.
TL;DR: Ovarian cancer patients selected for laparoscopic interval debulking surgery after neoadjuvant chemotherapy have 3-year survival rates similar to women who undergo intervaldebulking by laparotomy, whereas readmission rates and risk of perioperative death are similar for the surgeries.
TL;DR: MI-IDS seems to play an important role in the quality of life and oncologic outcomes and more experience with larger groups of patients is desirable to deeply investigate and assess the results.
TL;DR: NACT is associated with superior optimal cytoreduction, lower peri-operative morbidity as well as post-surgical mortality, and better QOL compared to initial surgery in patients with advanced EOC.
Abstract: Objective
To assess whether neoadjuvant chemotherapy (NACT) is superior to primary debulking surgery (PDS) with regard to optimal cytoreduction, peri-operative morbidity, mortality, and quality of life (QOL) in advanced epithelial ovarian cancer (EOC).
Methods
We searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Registers of Clinical Trials for randomized controlled trials (RCTs) comparing NACT to PDS in women with Federation of International Gynaecologists and Obstetricians stage Ⅲ-Ⅳ EOC. RevMan 5.3 software was utilized for statistical analysis.
Results
Four RCTs involving 1,607 women with advanced EOC were included. Compared with PDS, NACT provided a higher rate of complete cytoreduction (risk ratio [RR], 1.95; 95% confidence interval [CI], 1.33 to 2.87), optimal cytoreduction (RR: 1.61 [95%CI: 1.05 to 2.47]), but there was no significant difference in residual disease 0–1 cm (p = 0.49). NACT was associated with lower peri-operative morbidity with respect to infection (RR: 0.30 [95% CI: 0.16 to 0.56]), gastrointestinal fistula (RR: 0.24 [95% CI: 0.06 to 0.95]), any grade 3 or 4 adverse event (RR: 0.29 [95% CI: 0.11 to 0.78]), and less post-surgical death within 28 days (RR: 0.14 [95% CI: 0.04 to 0.49]). NACT provided better QOL in terms of fatigue (weight mean difference [WMD], -3.28; [95% CI: -3.99 to -2.57]), role functioning (WMD: 5.29 [95% CI: 4.44 to 6.14]), emotional functioning (WMD: 6.19 [95% CI: 5.57 to 6.82]), and cognitive functioning (WMD: 1.02 [95% CI: 0.43 to 1.61]) at 6-month follow-up compared with PDS.
Conclusions
NACT is associated with superior optimal cytoreduction, lower peri-operative morbidity as well as post-surgical mortality, and better QOL compared to initial surgery in patients with advanced EOC. Future research should focus on improving the efficacy of NACT.
TL;DR: Hepatic debulking for patients with NELM is a reasonable therapeutic option for patientsWith grossly unresectable disease that may provide a survival benefit.
Abstract: Background Management of neuroendocrine liver metastasis (NELM) in the setting of unresectable disease is poorly defined and the role of debulking remains controversial. The objective of the current study was to define outcomes following non-curative intent liver-directed therapy (debulking) among patients with NELM. Methods 612 patients were identified who underwent liver-directed therapy of NELM from a multi-institutional database. Outcomes were stratified according to curative (R0/R1) versus non-curative ≥ 80% debulking (R2). Results 179 (29.2%) patients had an R2/debulking procedure. Patients undergoing debulking more commonly had more aggressive high-grade tumors (R0/R1: 12.8% vs. R2: 35.0%; P Conclusion Debulking operations for NELM provided reasonable long-term survival. Hepatic debulking for patients with NELM is a reasonable therapeutic option for patients with grossly unresectable disease that may provide a survival benefit.
TL;DR: The results indicated that surgical resection combined with anti-CD47 blocking immunotherapy promoted an inflammatory response and prolonged survival in animals, and is therefore an attractive strategy for clinical translation.
Abstract: // Huaiyang Zhu 1, 2 , Lina Leiss 1, 5 , Ning Yang 3, 4 , Cecilie B. Rygh 1 , Siddhartha S. Mitra 6 , Samuel H. Cheshier 7 , Irving L. Weissman 6 , Bin Huang 3, 4 , Hrvoje Miletic 1, 8 , Rolf Bjerkvig 1 , Per O. Enger 1, 9 , Xingang Li 3, 4 , Jian Wang 1, 3, 4 1 Department of Biomedicine, University of Bergen, Bergen, Norway 2 Department of Oncology, Shandong Chest Hospital, Jinan, China 3 Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China 4 Brain Science Research Institute, Shandong University, Jinan, China 5 Neuro Clinic, Haukeland University Hospital, Bergen, Norway 6 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, USA 7 Division of Pediatric Neurosurgery, Department of Neurosurgery, Stanford University, USA 8 Department of Pathology, Haukeland University Hospital, Bergen, Norway 9 Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway Correspondence to: Jian Wang, email: Jian.Wang@uib.no Keywords: glioblastoma, CD47, signal regulatory protein-α, phagocytosis, macrophage Received: April 20, 2016 Accepted: December 26, 2016 Published: January 06, 2017 ABSTRACT Surgical resection is a standard component of treatment in the clinical management of patients with glioblastoma multiforme (GBM). However, experimental therapies are rarely investigated in the context of tumor debulking in preclinical models. Here, a surgical debulking GBM xenograft model was developed in nude rats, and was used in combination with CD47 blocking immunotherapy, a novel treatment strategy that triggers phagocytosis of tumor cells by macrophages in diverse cancer types including GBM. Orthotopic patient–derived xenograft tumors expressing CD47 were resected at 4 weeks after implantation and immediately thereafter treated with anti-CD47 or control antibodies injected into the cavity. Debulking prolonged survival (median survival, 68.5 vs 42.5 days, debulking and non-debulking survival times, respectively; n = 6 animals/group; P = 0.0005). Survival was further improved in animals that underwent combination treatment with anti-CD47 mAbs (median survival, 81.5 days vs 69 days, debulking + anti-CD47 vs debulking + control IgG, respectively; P = 0.0007). Immunohistochemistical staining of tumor sections revealed an increase in recruitment of cells positive for CD68, a marker for macrophages/immune cell types, to the surgical site (50% vs 10%, debulking vs non-debulking, respectively). Finally, analysis of tumor protein lysates on antibody microarrays demonstrated an increase in pro-inflammatory cytokines, such as CXCL10, and a decrease in angiogenic proteins in debulking + anti-CD47 vs non-debulking + IgG tumors. The results indicated that surgical resection combined with anti-CD47 blocking immunotherapy promoted an inflammatory response and prolonged survival in animals, and is therefore an attractive strategy for clinical translation.
TL;DR: It is suggested that among women with no residual disease, survival is better among those who undergo primary debulking surgery than treatment with neoadjuvant chemotherapy, and the latter should be reserved for women who are deemed not to be candidates for primary debULking surgery.
Abstract: Objective The management of women with advanced-stage serous ovarian cancer includes a combination of surgery and chemotherapy. The choice of treatment with primary debulking surgery or neoadjuvant chemotherapy varies by institution. The objective of this study was to report 5-year survival outcomes for ovarian cancer patients treated at a single institution with primary debulking surgery or neoadjuvant chemotherapy. Methods This study included a retrospective chart review of 303 patients with stage IIIC or IV serous ovarian carcinoma diagnosed in Calgary, Canada. The patients were categorized into 1 of the 2 treatment arms: primary debulking surgery or neoadjuvant chemotherapy. The 5-year ovarian cancer–specific survival rates were estimated using Kaplan-Meier curves. Results Among the 303 eligible patients, 142 patients (47%) underwent primary debulking surgery, and 161 patients (53%) were treated with neoadjuvant chemotherapy. Five-year survival was better for patients undergoing primary debulking surgery (39%) than for patients who received neoadjuvant chemotherapy (27%; P = 0.02). Women with no residual disease experienced better overall survival than those with any residual disease (47% vs. 26%, respectively; P = 0.0002). This difference was significant for those who had primary debulking surgery (P = 0.0004) but not for the patients who received neoadjuvant chemotherapy (P = 0.09). Women who received intraperitoneal chemotherapy had better overall survival as compared with patients who received intravenous chemotherapy (44% vs 30%, respectively; P = 0.002). Conclusions Our findings suggest that among women with no residual disease, survival is better among those who undergo primary debulking surgery than treatment with neoadjuvant chemotherapy. The latter should be reserved for women who are deemed not to be candidates for primary debulking surgery.
TL;DR: Current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated, unless a curative approach is feasible or a debulking procedure is planned.
Abstract: Surgical extraction of as much tumour mass as possible is considered the first step of treatment in acromegaly in many centers. In this article the potential benefits, disadvantages and limitations of operative acromegaly treatment are reviewed. Pertinent literature was selected to provide a review covering current indications, techniques and results of operations for acromegaly. The rapid reduction of tumour volume is an asset of surgery. To date, in almost all patients, minimally invasive, transsphenoidal microscopic or endoscopic approaches are employed. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. The radicality of adenoma resection essentially depends on localization, size and invasive character of the tumour. The normalization rates of growth hormone and IGF-1 secretion, respectively, depend on tumour-related factors such as size, extension, the presence or absence of invasion and the magnitude of IGF-1 and growth hormone oversecretion. However, also surgeon-related factors such as experience and patient load of the centers have been shown to strongly affect surgical results and the rate of complications. As compared to most medical treatments, surgery is relatively cheap since the costs occur only once and not repeatedly. There are several new technical gadgets which aid in the surgical procedure: navigation and variants of intraoperative imaging. For the mentioned reasons, current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated. A few suggestions are made when a re-operation could be considered.
TL;DR: A survival benefit may be achieved by consistently starting chemotherapy between 21 and 35days from primary debulking surgery, and women at higher risk for chemotherapy delay may be targeted for close follow-up.
TL;DR: The data underline the potential implication of number of cycles of NACT before IDS and suggest that only Eastern Cooperative Oncology Group performance status correlated with overall survival.
Abstract: Objectives Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) may be a valuable treatment option in advanced ovarian cancer when primary cytoreduction is not feasible. However, a consensus on the ideal number of NACT cycles is still lacking. In the present investigation, we aimed to evaluate how number of cycles of NACT influenced patients9 outcomes. Methods Data of consecutive patients undergoing NACT and IDS were retrospectively reviewed in 4 Italian centers, and survival outcomes were evaluated. Results Overall, 193 patients were included. Cycles of NACT were 3, 4, and at least 5 in 77 (40%), 74 (38%), and 43 (22%) patients, respectively. Patients undergoing 3 cycles experienced a similar disease-free survival (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.89–1.65; P = 0.20) but an improved overall survival (HR, 1.64; 95% CI, 1.05–2.4; P = 0.02) in comparison to patients receiving at least 4 cycles. Five-year overall survival was 46% and 31% for patients having 3 and at least 4 cycles. Ten-year overall survival was 26% and 18% for patients having 3 and at least 4 cycles (HR, 1.70; 95% CI, 1.13–2.55; P = 0.009). Using multivariate analysis, we observed that only Eastern Cooperative Oncology Group performance status correlated with overall survival (HR, 1.76; 95% CI, 1.2–2.49; P = 0.001). In addition, a trend toward worse overall survival was observed for patients with residual disease at IDS (HR, 1.29; 95% CI, 0.98–1.70; P = 0.06) and patients receiving at least 4 cycles (HR, 1.76; 95% CI, 0.95–3.22; P = 0.06). Conclusion Our data underline the potential implication of number of cycles of NACT before IDS. Further prospective studies are warranted to assess this correlation.
TL;DR: NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved clinical complete response (CCR).
Abstract: No consensus exists on the number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced stage epithelial ovarian cancer. The present study aims to explore the optimal number of cycles of neoadjuvant chemotherapy (NAC) and post-operation chemotherapy to treat the International Federation of Gynecology and Obstetrics stage IIIc–IV high-grade serous ovarian cancer (HG-SOC). A total of 129 IIIc–IV stage HG-SOC cases were retrospectively analyzed. Cases were comprised of patients who underwent NAC followed by IDS and who achieved clinical complete response (CCR) at the end of primary therapy. Patients were recruited from the Jiangsu Institute of Cancer Research between 1993 and 2013. Optimal IDS-associated factors were explored with logistic regression. The association between progression-free survival (PFS), overall survival (OS) duration, and covariates was assessed by Cox proportional hazards model and log-rank test. The median number of NAC cycle was 3 (range 1–8). CA-125 decreasing kinetics (p = 0.01) was independently associated with optimal IDS. CA-125 decreasing kinetics, optimal IDS, and NAC cycles was independently associated with OS (p < 0.01, p < 0.01, p = 0.03, respectively) and PFS (p < 0.01, p < 0.01, p = 0.04, respectively). The PFS of patients who underwent ≥5 NAC cycles was shorter than those of patients who underwent <5 NAC cycles (12.3 versus 17.2 months). The PFS and OS of patients who underwent <5 cycles of adjuvant chemotherapy post-IDS were shorter than those of patients who underwent ≥5 cycles (14.2 and 20.3 versus 21.2 and 28.8 months). NAC cycles, CA-125 decreasing kinetics, and optimal debulking are independently associated with the prognosis of patients with advanced stage HG-SOC who underwent NAC/IDS and achieved CCR. The number of administered NAC cycles should not exceed 4.
TL;DR: For primary EOC where resection to residual disease of 1cm or less is unlikely, NACT/IDS is associated with improved survival and reduced perioperative morbidity compared to PDS, and more reliable predictors of resectability would be valuable.
TL;DR: The current study suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC.
Abstract: Objective: In patients with advanced stage epithelial ovarian cancer (EOC) the volume of residual tumor after debulking is known as prognostic factor for survival. We wanted to examine the relationship between postoperative decline in serum CA125 and residual disease after cytoreductive surgery and evaluate perioperative changes in serum CA125 levels as predictor for disease-specific survival. Methods: A retrospective study was conducted of patients with FIGO stage IIb-IV EOC treated with cytoreductive surgery, followed by chemotherapy between 1996 and 2010 in three hospitals in the Southeastern region of the Netherlands. Data were analyzed with the use of multilevel linear regression and Cox-proportional hazard regression models. Results: A postoperative decline in serum CA125 level of ≥80% was associated with complete primary cytoreduction (p=0.035). Univariate analyses showed favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction. In multivariate analyses the decline in serum CA125 but not the outcome of surgery remained significantly associated with better survival (HR50%–79%=0.52 [95% CI: 0.28–0.96] and HR≥80%=0.26 [95% CI: 0.13–0.54] vs. the serum CA125 decline of <50% [p<0.001]). Conclusion: The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons’ estimation of residual tumor volume.
TL;DR: Treatment with NACT-IDS improves perioperative outcomes and optimal cytoreduction rates, but it may not improve OS, and future studies should focus on candidate selection for NACT.
Abstract: // Meng Qin 1 , Ying Jin 1 , Li Ma 2 , Yan-Yan Zhang 1 and Ling-Ya Pan 1 1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 2 Department of Interventional Radiology and Vascular Surgery, Taiyuan Center Hospital, Taiyuan 030009, China Correspondence to: Ying Jin, email: jinypumc@aliyun.com Keywords: neoadjuvant chemotherapy; debulking surgery; ovarian cancer; survival Received: July 15, 2017 Accepted: November 15, 2017 Published: December 27, 2017 ABSTRACT Objective: We aimed to performed a meta-analysis and systematic review on the role of neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) in advanced ovarian cancer (AOC) patients. Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library for relevant articles. All statistical analyses were performed in Review Manager 5.3.5. Results: In two randomized controlled trials (RCTs), there was no significant difference in overall survival (OS) (HR = 0.93, 95% CI: 0.81–1.06) or progression-free survival (PFS) (HR = 0.97, 95% CI: 0.86–1.09). Few adverse events (HR = 0.37, 95% CI: 0.19–0.72) and a high optimal debulking surgery rate (HR = 1.69, 95% CI: 1.50–1.91) were observed with NACT. In 22 observational studies, primary debulking surgery (PDS) yielded better OS (HR = 1.38, 95% CI: 1.19–1.60) but not progression-free survival (PFS) (HR = 1.03, 95% CI: 0.86–1.23). An increased optimal cytoreduction rate (HR = 1.17, 95% CI: 1.12–1.22) was observed with NACT. Irrespective of the degree of residual disease, OS was longer in the PDS group than that in the NACT group. Patients with FIGO stage III (HR = 1.43, 95% CI: 1.05–1.95) and IV (HR = 1.14, 95% CI: 1.06–1.23) disease had better survival with PDS. Conclusions: Treatment with NACT-IDS improves perioperative outcomes and optimal cytoreduction rates, but it may not improve OS. NACT-IDS is not inferior to PDS-CT in terms of survival outcomes in selected AOC patients. Future studies should focus on candidate selection for NACT.
TL;DR: Even with the small sample size and short term use of the drug, perioperative propranolol was effective in reducing tumor burden (as measured by CA 125) suggesting its potential benefits in decreasing peri operative tumor growth.
Abstract: Objective This study was done to evaluate whether perioperative propranolol (s-blocker) in ovarian cancer patients undergoing debulking surgery reduced perioperative tumor growth induced by surgical stress. Methods This was a prospective randomized single institution analysis. The primary objective was to compare the changes in CA 125 level (changes between preoperation day 2 and postoperative day 7). As a study arm, patients received a low dose of propranolol 40 mg/day (4×10 mg) starting two days before surgery and 40 mg twice daily for three days following surgery. Results Twenty-two patients were enrolled and 16 were evaluable for efficacy. The drug was well tolerated. The mean decrease of CA 125 during the seven perioperative days was 83.1±8.9% in the propranolol group and 72.4±14.7% in the placebo group. The difference was statistically significant (P=0.044). The change of C-reactive protein, cortisol, and anxiety score (State-Trait Anxiety Inventory-X1) were not different between the two groups. Conclusion This preliminary result is the first to directly test the role of perioperative propranolol on tumor growth. Even with the small sample size and short term use of the drug, perioperative propranolol was effective in reducing tumor burden (as measured by CA 125) suggesting its potential benefits in decreasing perioperative tumor growth.
TL;DR: The clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups.
Abstract: Objective The objective of this retrospective study was to assess the clinical outcome of patients with advanced epithelial ovarian cancer in complete response after primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (IDS]). Methods The authors reviewed the hospital records of 384 patients who underwent PDS (n = 322) or IDS (n = 62) and who were in complete response after primary treatment. Results Optimal (residual disease [RD] Conclusions The clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups.