Pattern of recurrence after interval cytoreductive surgery and HIPEC following neoadjuvant chemotherapy in primary advanced stage IIIC/IVA epithelial ovarian cancer

ObjectiveThe aim of this study was to evaluate the patterns of recurrence and factors affecting the same after interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in primary stage IIIC and IV A epithelial ovarian cancer.MethodsIn this retrospective multicentric study, all patients with FIGO stages III-C and IV-A epithelial ovarian carcinoma were treated with CRS and HIPEC after receiving neoadjuvant chemotherapy. Relevant clinical and demographic data were captured. Multivariable logistic regression was performed to evaluate the factors affecting recurrence after CRS and HIPEC.ResultsFrom January 2017 to Jan 2020, 97, consecutive patients of Stage IIIC/IVA epithelial ovarian cancer underwent interval cytoreductive surgery and HIPEC after receiving neoadjuvant chemotherapy. The median duration of follow up duration was 20 months [1–36months]. 21/97 (21.6%) patients presented with disease recurrence. Visceral recurrences involving the lungs, liver and brain were seen in 8/21 (38%) of cases and comprised the commonest sites. On multivariable analysis, nodal involvement (p = 0.05), selective peritonectomy (p = 0.001) and leaving behind residual disease <0.25 mm (CC1) (p = 0.01) was associated with increased risk of disease recurrence. Extent of peritonectomy (OS,p = 0.56, PFS p = 0.047, Log Rank test) and nodal positivity (OS, p = 0.13,PFS,p = 0.057, Log Rank test) were found to impact progression free survival but had no impact on overall survival.ConclusionThere is a higher incidence of systemic recurrences in patients with Stage IIIC/IVA epithelial ovarian carcinoma after CRS and HIPEC. Extent of peritonectomy and nodal clearance impacts patterns of recurrence and progression free survival.     

间歇性肿瘤细胞减灭术与初始肿瘤细胞减灭术对晚期上皮性卵巢癌的疗效评价

目的探讨间歇性肿瘤细胞减灭术(IDS)与初始肿瘤细胞减灭术(PDS)对晚期上皮性卵巢癌(EOC)的疗效。方法根据手术方法的不同将132例晚期EOC患者分为PDS组(n=87例)和IDS组(n=45)。PDS组患者行PDS手术后接受6~8个疗程的化疗。IDS组患者行PDS手术后接受3个疗程的化疗,然后再行IDS手术后化疗3~5个疗程。观察两组患者的PDS切除范围,比较两组患者的减瘤满意率、疗效、血清CA125水平和不良反应发生情况。结果IDS组患者的PDS切除范围明显小于PDS组(P﹤0.01)。IDS组患者的减瘤满意率高于PDS组(P﹤0.05)。IDS组患者的临床疗效明显优于PDS组(P﹤0.01)。术前和第3次化疗后,两组患者的血清CA125水平比较,差异均无统计学意义(P﹥0.05)。IDS组患者PDS后的血清CA125水平高于PDS组,完成化疗后的血清CA125水平低于PDS组(P﹤0.05)。IDS组患者的不良反应总发生率低于PDS组(P﹤0.05)。结论IDS有助于提高晚期EOC患者的手术减瘤满意率和近期疗效,且不会显著增加不良反应。     

Clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery in advanced ovarian cancer patients

Objective

To investigate the clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) patients.

Methods

We retrospectively reviewed the medical records of 124 advanced EOC patients and analyzed the details of neoadjuvant chemotherapy (NACT), IDS, postoperative treatment, and prognoses.

Results

Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual disease sized <1 cm (optimal), and 11 had residual disease sized ≥1 cm (suboptimal). Two-year overall survival (OS) and progression-free survival (PFS) rates were 88.8% and 39.8% in the NGRD group, 40.0% and 13.3% in the optimal group (p<0.001 vs. NGRD for both), and 36.3% and 0% in the suboptimal group, respectively. Five-year OS and 2-year PFS rates were 62% and 56.1% in the lymph node-negative (LN-) group and 26.2% and 24.5% in the lymph node-positive (LN+) group (p=0.0033 and p=0.0024 vs. LN-, respectively). Furthermore, survival in the LN+ group, despite surgical removal of positive nodes, was the same as that in the unknown LN status group, in which lymphadenectomy was not performed (p=0.616 and p=0.895, respectively). Multivariate analysis identified gross residual tumor during IDS (hazard ratio, 3.68; 95% confidence interval, 1.31 to 10.33 vs. NGRD) as the only independent predictor of poor OS.

Conclusion

NGRD after IDS improved prognosis in advanced EOC patients treated with NACT-IDS. However, while systematic retroperitoneal lymphadenectomy during IDS may predict outcome, it does not confer therapeutic benefits.     

The significance of the site of recurrence to subsequent breast cancer survival.

AIM: To investigate differences in the 3-year survival of patients with recurrent breast cancer dependent on recurrence site. METHODS: The study was a review of 294 patients from a breast cancer database, who were treated for operable breast cancer and subsequently developed a recurrence between 1989 and 2003. Patients were divided into four groups according to the site of first recurrence (local, lymph node, bone or visceral). Breast Cancer Specific Survival (BCSS) was compared using Kaplan-Meier life table analysis and the log rank test. RESULTS: Patient and tumour characteristics were comparable between the four groups. Survival rates between the recurrence site groups were significantly different. Patients in whom first recurrence was local had the best prognosis with a 3-year BCSS of 83% compared to 33% for patients with first node recurrence (p<0.001), 23% for patients with first bone recurrence (p=0.03) and 13% for patients with first visceral recurrence (p=0.004). CONCLUSION: Survival of patients with recurrent breast cancer is associated with the site of first recurrence. The prognosis from recurrence is progressively worse with local, regional, bone and visceral metastasis.     

新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的探讨

目的：探讨新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的效果。方法：对我院在1998年1月至2003年12月间收治的51例晚期卵巢癌进行回顾性分析,先行新辅助化疗,CP方案全身化疗3疗程后行间隔减瘤术,术后继续化疗6疗程,分析3年及5年生存率。结果：明显提高肿瘤细胞减灭术的满意率,3年生存率80．4％,5年生存率58．8％。结论：新辅助化疗结合间隔减瘤术治疗晚期卵巢癌可以明显提高晚期卵巢癌患者手术满意率和生存率。     

新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的探讨

目的:探讨新辅助化疗结合间隔减瘤术治疗晚期卵巢癌的效果.方法: 对我院在1998年1月至2003年12月间收治的51例晚期卵巢癌进行回顾性分析,先行新辅助化疗,CP方案全身化疗3疗程后行间隔减瘤术,术后继续化疗6疗程,分析3年及5年生存率.结果: 明显提高肿瘤细胞减灭术的满意率,3年生存率80.4%,5年生存率58.8%.结论: 新辅助化疗结合间隔减瘤术治疗晚期卵巢癌可以明显提高晚期卵巢癌患者手术满意率和生存率.     

Results of interval debulking surgery in advanced stage ovarian cancer: an exposed-non-exposed study.

BACKGROUND: To study the results of interval debulking surgery (IDS) in patients treated for 'unresectable' advanced stage ovarian cancer compared with primary debulking surgery (PDS) followed by chemotherapy. PATIENTS AND METHODS: An exposed-non-exposed study including a group of 34 patients who underwent an IDS and were matched to an historic control group of 34 patients treated with PDS. RESULTS: Optimal cytoreductive surgery was achieved in 94% (32 out of 34) of patients in both groups. The rates of post-operative morbidity, blood transfusion and median length of hospitalisation were significantly reduced in the study (IDS) group, but survival did not differ in both groups. CONCLUSIONS: IDS in patients with advanced stage ovarian cancer offers the same chance of survival as PDS, but it is better tolerated.     

Pattern of recurrence in patients with endometrial cancer: A retrospective study

IntroductionEndometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule.Methods758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate.ResultsHigher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01).ConclusionTo identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.     

Impact of interval debulking surgery on clinical outcome in primary unresectable FIGO stage IIIc ovarian cancer patients

OBJECTIVES: To report the results of neoadjuvant chemotherapy (NACT) and the impact of interval debulking surgery (IDS) on clinical outcomes of patients considered unresectable at primary surgery. METHODS: Retrospective analysis was carried out on 73 consecutive stage IIIc ovarian cancer patients treated with platinum-based NACT followed by IDS. Their clinical outcomes were compared with those of 111 consecutive stage IIIc ovarian cancer patients treated with primary cytoreduction followed by platinum-based adjuvant chemotherapy. RESULTS: Patients who underwent successful IDS had a more favorable prognosis than those who did not in terms of time to progression (TTP) (p = 0.00001), and overall survival (OS) (p = 0.0001). On the other hand, in the group of patients that underwent successful IDS, no differences in survival outcomes were observed between patients with no residual disease and patients with macroscopic residual disease <2 cm after IDS (p = n.s.). CONCLUSIONS: NACT followed by successful IDS can achieve good results in terms of survival outcomes in a high percentage of chemoresponsive IIIc ovarian cancer patients classified as unresectable at primary surgery. These results are in fact inferior to those achievable with optimal primary cytoreduction; however, they were quite similar to those seen with suboptimal primary cytoreduction.     

Prognostic significance of CA-125 re-elevation after interval debulking surgery in patients with advanced-stage ovarian cancer undergoing neoadjuvant chemotherapy

AimsWe evaluated the prognostic significance of postoperative re-elevation of cancer antigen-125 (CA-125) levels in patients with ovarian cancer and preoperative normalization of CA-125 levels after neoadjuvant chemotherapy (NAC).MethodsThe data of 103 patients with preoperative CA-125 normalization after NAC at the Yonsei Cancer Hospital (2006–2017) were analyzed. We compared the clinical characteristics and survival outcomes among patients with normal postoperative CA-125 levels and those with re-elevated CA-125 levels after interval debulking surgery (IDS). CA-125 elevation was defined as levels >35 U/mL.ResultsAmong 103 patients, 52 (50.5%) and 51 (49.5%) had normal and re-elevated CA-125 levels after IDS, respectively. Patients with CA-125 re-elevation underwent more radical surgeries during IDS than those with normal CA-125 levels (p = 0.018). We found no significant differences in progression-free survival (PFS; p = 0.726) or overall survival (OS; p = 0.293) between the two groups. Moreover, patients with persistent CA-125 elevation (3 weeks after IDS) did not have inferior PFS (p = 0.171 and p = 0.208, respectively) or OS (p = 0.128 and p = 0.095, respectively) compared to patients with early normalization (within 3 weeks of IDS) or normal CA-125 levels. Multivariate regression showed that CA-125 re-elevation had no effect on recurrence (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.43–1.30) or death (HR, 0.99; 95% CI, 0.33–2.98).ConclusionAmong patients with preoperative CA-125 normalization after NAC, postoperative CA-125 re-elevation had no prognostic value. Novel and reliable biomarkers reflecting the tumor response after IDS should be identified.     

Prognostic impact of initial tumor load and intraperitoneal disease dissemination patterns in patients with advanced ovarian cancer undergoing complete cytoreductive surgery

IntroductionComplete removal of disease is the most important prognostic factor for patients with advanced epithelial ovarian carcinoma. However, the influence of carcinomatosis distribution on prognosis is unknown and the prognostic impact of implant size according to their location is poorly studied. Our objective was to assess the impact of peritoneal carcinomatosis quantitative and qualitative localizations on progression free survival (PFS) in patients with advanced epithelial ovarian carcinoma (AEOC) after complete cytoreductive surgery.MethodsWe conducted a monocentric cohort study, retrospective from October 2001 to July 2014. Inclusion criteria were high-grade AEOC patients without residual disease (CC0) after primary debulking surgery (PDS) or after interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT). Peritoneal carcinomatosis was assessed according to qualitative criteria and quantitative criteria.ResultsOne hundred and one patients were included. Median PFS was 21·2 months and median OS was 62·2 months. On the whole population, involvement of adipocytes-enriched areas tended to be associated with a decreased PFS and was significantly associated with a decreased OS. Any localization was associated with PFS or OS in the “IDS” subgroup. In the “PDS” subgroup, PCI score and involvement of the right mesocolic area were associated with a decreased PFS.ConclusionInitial tumor load has not been found associated with PFS after complete surgery. Adipocytes-enriched areas and right mesocolic areas involvement were associated with poor prognosis in patients receiving primary debulking surgery. Larger-scale studies are needed to assess whether initial tumor load has a prognostic impact even after complete cytoreductive surgery is achieved.     

Influence of the primary tumour location in patients undergoing surgery for colorectal liver metastases

Background

The prognosis of patients undergoing liver resection for colorectal liver metastases (CLM) seems to be altered when the primary tumour is right-sided. However, data are lacking and conflicting. We aimed to evaluate the influence of the primary tumour location on oncologic outcomes following such surgery.

Tyrosine-kinases inhibitors in recurrent platinum-resistant ovarian cancer patients

For many decades, ovarian cancer (OC) has been one of the most common gynecological cancer.Despite advances in OC diagnosis and treatment, the risk of recurrence is ever present and approximately 85% of patients will experience relapse. Recurrent OC after first-line therapy is almost always incurable. Multiple novel therapies, including tyrosine-kinases inhibitors (TKI), have shown promising results, but their role needs to be clarified.In this review we describe the rationale and the clinical evidence regarding the use of TKI for the treatment of recurrent platinum-resistant OC patients.     

Comparison of diaphragmatic surgery at primary or interval debulking in advanced ovarian carcinoma: an analysis of 163 patients

Aims of the study and methods

Survival, complications and recurrences after diaphragmatic surgery at primary or interval debulking surgery were compared. One hundred and sixty three consecutive patients with stage III/IV ovarian cancer underwent diaphragmatic surgery between September 1993 and December 2007. Primary debulking was performed in group 1 (89) patients and interval debulking was performed in group 2 (74) patients. Cytoreductive outcome, overall survival (OS), disease-free survival (DFS) and post-operative complications were analysed.

Results

Despite differences in baseline mean age (p = 0.015), in FIGO stage III/IV (p = 0.036) and in mean largest diameter of metastatic disease at the beginning of debulking surgery (p = 0.037), the optimal debulking rates (residual tumour less than 1 cm) were similar (p = 0.065). Excision of diaphragmatic metastases was most frequently performed in group 1 (77.53%) and coagulation was most frequently performed in group 2 (58.10%). Similar overall survival and disease-free survival rates were found. After the propensity matching procedure, the largest diameter of metastatic disease at the time of debulking and no residual tumour (complete debulking) were demonstrated as independent prognostic factors for OS. Plaque-like lesions on the diaphragm metastases were significantly (p = 0.015) more associated with diaphragm recurrence than papillary lesions. Minor and major complications related to diaphragmatic surgery as well as mean operating time, post-operative care in intensive care unit and length of hospitalisation were significantly higher in group 1 rather than in group 2 (p = 0.043).

Conclusions

Diaphragmatic dissemination resulted in similar survival and cytoreductive rates after primary and interval debulking. However, the morbidity was less after interval debulking as fewer surgical procedures were performed.     

Systematic lymph node dissection during interval debulking surgery for advanced epithelial ovarian cancer: a systematic review and meta-analysis

ObjectiveTo evaluate the efficacy and safety of systematic lymph node dissection (SyLND) at the time of interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC).MethodsSystematic literature review of studies including AEOC patients undergoing SyLND versus selective lymph node dissection (SeLND) or no lymph node dissection (NoLND) after neoadjuvant chemotherapy (NACT). Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included severe postoperative complications, lymphocele, lymphedema, blood loss, blood transfusions, operative time, and hospital stay.ResultsNine retrospective studies met the eligibility criteria, involving a total of 1,660 patients: 827 (49.8%) SyLND, 490 (29.5%) SeLND, and 343 (20.7%) NoLND. The pooled estimated hazard ratios (HR) for PFS and OS were, respectively, 0.88 (95% confidence interval [CI]=0.65–1.20; p=0.43) and 0.80 (95% CI=0.50–1.30; p=0.37). The pooled estimated odds ratios (ORs) for severe postoperative complications, lymphocele, lymphedema, and blood transfusions were, respectively, 1.83 (95% CI=1.19–2.82; p=0.006), 3.38 (95% CI=1.71–6.70; p<0.001), 7.23 (95% CI=3.40–15.36; p<0.0001), and 1.22 (95% CI=0.50–2.96; p=0.67).ConclusionDespite the heterogeneity in the study designs, SyLND after NACT failed to demonstrate a significant improvement in PFS and OS and resulted in a higher risk of severe postoperative complications.Trial RegistrationPROSPERO Identifier: CRD42022303577     

新辅助化疗对比初始肿瘤细胞减灭术治疗Ⅲ-Ⅳ期卵巢癌的荟萃分析

目的:比较Ⅲ-Ⅳ期卵巢癌（International Federation of Gynecology and Obstetrics,FIGO）新辅助化疗（neoadjuvant chemotherapy,NACT)联合间隔减瘤手术与初始肿瘤细胞减灭术（primary debulking surgery,PDS）联合化疗两种治疗模式有效性及安全性差异。方法:计算机检索Pubmed、Cochrane Library、Embase、Web of Science、中国生物医学文献数据库、万方数据库和中国知网等数据库,查找NACT对比PDS治疗Ⅲ-Ⅳ期卵巢癌随机对照研究相关文献,应用Review Manager 5.3软件进行统计分析。结果:纳入4项研究,共计1 631例患者。NACT组与PDS组总生存期（HR=0.95,95％CI为0.84～1.07,P=0.38）和无进展生存期相似（HR=0.97,95%CI为0.88～1.08,P＝0.61）;NACT组肿瘤完整切除率较PDS组提高（RR=2.47,95%CI为1.50～4.05,P=0.000 4）。在不良反应和安全性方面,NACT组患者≥3级静脉血栓发生率（RR＝0.25,95％CI为0.10～0.62,P=0.003）、≥3级感染发生率（RR＝0.30,95％CI为0.16～0.56,P=0.000 2）和围手术期死亡率（RR＝0.17,95％CI为0.06～0.48,P=0.000 9）均降低。结论:在Ⅲ-Ⅳ期卵巢癌治疗中,两种治疗模式生存获益相当,但新辅助化疗联合间隔减瘤手术可以提高肿瘤完整切除率,具有更好的安全性。新辅助化疗联合间隔减瘤手术可作为Ⅲ-Ⅳ期卵巢癌患者一种推荐治疗方式。     

原发性肝癌射频消融术后复发预测模型的建立及评价

目的 构建和评价用于预测原发性肝癌（primary liver cancer,PLC）患者射频消融（radiofrequency ablation,RFA） 术后无瘤生存率的列线图模型。 方法 回顾性分析2009年6月至2017年5月于广西医科大学附属肿瘤医院接受射频消融治疗的213例PLC患者的临床资料。ＰＬＣ患者被随机分为训练组（n=133）和验证组（n=80）。采用Cox回归模型分析射频消融术后复发的因素,并建立复发的列线图模型。通过校准曲线评估模型的预测符合度,Kaplan-Meier 曲线评估模型的实用性,一致性指数（C-index）评估模型的准确度。结果 训练组1年、3年、5年无瘤生存率分别为65.25%、40.91%、26.99%,验证组分别为66.29%、48.10%、24.59%,两组生存曲线比较差异无统计学意义（P=0.785）。Cox回归分析结果显示,肿瘤数目（HR=1.921, 95%CI：1.136~3.251）、丙肝抗体阳性（HR=4.545,95%CI：1.700~12.149）、HBV-DNA≥10² IU/mL（HR=1.993,95%CI：1.209~3.284）及血清前白蛋白（HR=0.996,95%CI：0.993~0.999）为无瘤生存率的影响因素。基于肿瘤数目、HBV-DNA和血清前白蛋白等因素建立列线图模型,训练组和验证组的 C-index 分别为 0.649（95%CI：0.588~0.710）、0.641（95%CI：0.556~0.724）,校准图形中标准曲线与预测校准曲线贴合良好。采用列线图将患者分为高风险组和低风险组,高风险组无瘤生存率低于低风险组（P<0.05）。结论 基于肿瘤数目、HBV-DNA和血清前白蛋白等因素建立的列线图测模型可预测PLC射频消融术后的无瘤生存率,对患者辅助治疗具有一定指导价值。     

原发性肝癌患者术后细胞免疫功能状况与复发的相关性

目的探讨原发性肝癌（primarylivercancer，PLC，简称肝癌）患者术后细胞免疫功能动态变化与复发的相关性。方法对2001～2010年在我院行肝癌根治性切除术后1个月以上的42例患者进行动态随访、追踪观察。每隔2个月对患者进行T淋巴细胞亚群检测。其中16例出现复发，26例未复发。同期检测10例健康志愿者为健康对照组。结果复发组与未复发组PLC患者术后CD3＋、CD4＋、CD8＋T淋巴细胞均明显低于健康对照组，差异比较有统计学意义（P〈0．05），复发组患者T淋巴细胞较未复发组低，以复发时最为明显，与未复发组比较差异有统计学意义（P〈0．05）。随着术后无瘤生存时间的延长，复发组的CD4＋和CD4＋／CD8＋的比值逐渐升高，CD8＋、CD3＋T淋巴细胞逐渐下降，而未复发组的CD4＋、CD3＋T淋巴细胞则随着术后时间的延长逐渐升高。结论PLC患者术后普遍且比较持续地存在细胞免疫功能低下，患者细胞免疫功能低下可能是影响肝癌术后复发的重要因素。动态监测PLC患者术后的细胞免疫功能，可作为评估肝癌根治术后预后和潜在复发风险评估的指标之一。