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.     

Role of aggressive surgical cytoreduction in advanced ovarian cancer

Ovarian cancer is the eighth most frequent cancer in women and is the most lethal gynecologic malignancy worldwide. The majority of ovarian cancer patients are newly diagnosed presenting with advanced-stage disease. Primary cytoreductive surgery and adjuvant taxane- and platinum-based combination chemotherapy are the standard treatment for advanced ovarian cancer. A number of studies have consistently shown that successful cytoreductive surgery and the resultant minimal residual disease are significantly associated with survival in patients with this disease. Much has been written and even more debated regarding the competing perspectives of biology of ovarian cancer versus the value of aggressive surgical resection. This review will focus on the current evidences and outcomes supporting the positive impact of aggressive surgical effort on survival in the primary management of ovarian cancer.     

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.     

Treatment of ovarian metastases of colorectal and appendiceal carcinoma in the era of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Aim

To compare outcome of women with ovarian metastasis who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to outcome of women without ovarian metastasis who underwent CRS-HIPEC.

Methods

A prospective CRS-HIPEC database was searched to identify women with surgically treated colorectal carcinoma between 2000 and 2012. Patients with ovarian metastasis were identified and patients with peritoneal carcinomatosis but without ovarian metastasis were included as control cases.

Results

75 patients with macroscopic ovarian metastasis underwent CRS-HIPEC with curative intent, while 50 female patients without ovarian metastasis were identified who underwent CRS-HIPEC. Patients with ovarian metastasis more often had a primary appendiceal tumour and had a more extensive intra-abdominal tumour load compared to patients without ovarian metastases. Median follow-up time was 45 months (95% confidence interval (CI): 37–53 months). Overall survival (OS) did not differ significantly between the two groups with a median OS in the ovarian metastasis group of 40 months (95% CI 26–54) compared to 64 months (95% CI 17–111, P = 0.478) in the non-ovarian metastasis group. Recurrence patterns did not differ significantly between groups (p = 0.183).

Conclusions

Patients with ovarian metastasis of colorectal and appendiceal origin who underwent CRS-HIPEC had similar outcome compared to patients without ovarian metastasis. Given the findings of high coincidence of peritoneal metastases with ovarian metastases and ovarian metastases not being an independent factor for survival after CRS-HIPEC, this procedure should be recommended for patients with peritoneal metastases and ovarian metastases of colorectal and appendiceal carcinoma.     

提高复发性卵巢上皮癌手术切除率的探讨

背景与目的:复发性卵巢上皮癌能否手术切除对预后影响较大,提高复发性卵巢上皮癌的手术切除率有助于改善其预后。本研究旨在探讨如何提高复发性卵巢上皮癌的手术切除率。方法:回顾性分析1997年3月1日至2003年3月31日期间因复发性卵巢上皮癌在我院行第二次细胞减灭术的54例病例的临床资料。其中病灶部位局限于盆腔19例,超出盆腔35例。病灶数目为1个者16例,≥2个者38例。无腹水38例,有腹水16例。接受术前化疗20例,有效12例,无效8例。以 Logistic多因素回归,分析年龄、复发间隔时间、复发病灶部位、数目、有无腹水及复发术前化疗对复发术后残留灶的影响。结果:肿瘤的满意切除率为81.5％(44/54),其中无残留灶者占53.7％(29/54),残留灶≤2 cm者占27.8％(15/54)。Logistic分析显示,病灶部位及有无腹水是影响复发术后残留灶的显著性因素(P<0.05);复发术前化疗有效和无效患者的满意切除率分别为100％(12/12)和37.5％(3/8),卡方检验显示两者有非常显著性差异(P<0.01)。本组40.7％(22/54)的患者手术较复杂,涉及胃肠道、泌尿道或肝脾。术后并发症发生率为16.6％(9/54),手术死亡率1.9％(1/54)。结论:根据患者瘤灶的边界、部位、有无腹水及术前化疗的疗效,对复发患者进行适当的选择,并作好充分的术前准备有助于提高复     

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.     

Prognostic value of complete metabolic response on 18F-FDG-PET/CT after three cycles of neoadjuvant chemotherapy in advanced high-grade serous ovarian cancer

ObjectiveWe investigated the prognostic value of complete metabolic response (CMR) on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) after 3 cycles of neoadjuvant chemotherapy (NAC) in advanced high-grade serous ovarian cancer (HGSC).MethodsPET/CT at baseline and after 3 cycles of NAC were performed; peak standardized uptakes were measured. PET parameters were compared with NAC parameter: cancer antigen-125 (CA-125) normalization before interval debulking surgery (IDS) and chemotherapy response score (CRS) to predict platinum-sensitivity. Kaplan-Meier analysis was used to determine correlations between PET parameters and survival. Prognostic factors were obtained by multivariate Cox regression analysis.ResultsBetween 2007 and 2020, 102 patients were recruited: 19 (18.6%) were designated as CMR group and 83 (81.4%) as non-CMR group. CMR after 3 cycles of NAC showed the highest accuracy in predicting platinum-sensitivity (area under the curve [AUC]=0.729; 95% confidence interval [CI]=0.552–0.823; p=0.017), compared with CA-125 normalization before IDS (AUC=0.626; 95% CI=0.542–0.758; p=0.010) and CRS (AUC=0.613; 95% CI=0.490–0.735; p=0.080). CMR demonstrated better prognosis than non-CMR in progression-free survival (PFS) (median PFS, 23.9 months vs. 16.4 months; p=0.021) and overall survival (OS) (median OS, not reached vs. 69.7 months; p=0.025). In multivariate analysis, CMR was associated with a lower risk of recurrence (adjusted hazard ratio [aHR]=0.50; 95% CI=0.27–0.92; p=0.027) and death (aHR=0.23; 95% CI=0.05–0.99; p=0.048).ConclusionCMR after 3 cycles of NAC can be a prognostic factor for both recurrence and death in advanced HGSC.     

Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian,tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602

BackgroundWe conducted a phase III, non-inferiority trial comparing upfront primary debulking surgery (PDS) and interval debulking surgery (IDS) following neoadjuvant chemotherapy (NAC) for stage III/IV ovarian, tubal, and peritoneal cancers (JCOG0602). Two earlier studies, EORTC55971 and CHORUS, demonstrated non-inferior survival of patients treated with NAC. However, they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30% of both arms of EORTC55971 and in 16% of NAC arm of CHORUS.MethodsPatients were randomised into the standard arm (PDS followed by eight cycles of paclitaxel and carboplatin [TC]) and NAC arm (four cycles of TC, IDS, and four cycles of TC). In the standard arm, IDS was optional for patients who had undergone suboptimal or incomplete PDS. Treatment invasiveness was compared between arms (UMIN000000523).ResultsBetween November 2006 and October 2011, 301 patients were randomised. In the standard arm, 147/149 underwent PDS and 49 underwent IDS. In the NAC arm, 130/152 underwent IDS. The NAC arm required fewer surgeries (mean 0.86 versus 1.32, p < 0.001) and shorter total operation time (median 273 min versus 341 min, p < 0.001) than the standard arm and required a lower frequency of abdominal organ resection (23.7% versus 37.6%, p = 0.012) or distant metastases resection (3.9% versus 10.7%, p = 0.027). In the NAC arm IDS, blood/ascites loss was smaller (median 787 ml versus 3235 ml, p < 0.001) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent (26.2% versus 58.5%, p < 0.001; 4.6% versus 15.0%, p = 0.005, respectively).ConclusionOur findings demonstrated that NAC treatment is less invasive than standard treatment. NAC treatment may become the new standard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017.     

放疗对宫颈癌根治术患者卵巢功能影响

目的 在保留并移位卵巢的ⅠB1-ⅡA2期根治术后需辅助放疗的年轻宫颈癌患者中,评估移位卵巢剂量学参数与临床不同卵巢功能状态之间相关性。方法 回顾2015-2017年间86例患者疗前和疗后2年内移位卵巢功能和临床相关症状,并评价放疗技术中移位卵巢的剂量学参数以及移位卵巢的功能状态之间的相关性。术后放疗采用不同体外保护移位卵巢,68例IMRT或VMAT,18例二维等中心放疗。结果 卵巢和PTV最近距离与卵巢剂量≥V5Gy呈负相关(P=0.025)。V8Gy、Dmean与疗后FSH(为卵巢血清卵泡刺激素,FSH)呈正相关(P=0.011、0.020)。即V8Gy体积越大Dmean越高,疗后FSH越高卵巢功能越差。二维技术中≥V5Gy低于三维技术,剂量降低明显。疗后卵巢功能正常者平均年龄33.4岁,而卵巢功能衰竭者平均年龄39.6岁(P=0.007)。不同卵巢状态患者间保留卵巢数目、是否同步化疗均相近,但与疗前FSH、E2(雌二醇)水平相关,即疗前FSH水平越高E2越低,疗后卵巢FSH水平越高E2越低。疗前保留卵巢但功能衰竭者均进行了新辅助化疗且年龄略高。结论 年龄,卵巢 V_{8 Cy}、D_mean,悬吊卵巢与 PTV 最近距离,疗前有无新辅助化疗及放疗技术均会影响移位卵巢功能的保护。     

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group

IntroductionThe aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery.Materials and methodsData from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival.ResultsThe median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16–3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01–2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC.ConclusionIn this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.     

Health-related quality of life after interval cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with stage III ovarian cancer

IntroductionThe addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improves recurrence-free (RFS) and overall survival (OS) in patients with FIGO stage III ovarian cancer. We evaluated the effect of HIPEC on patient's health-related quality of life (HRQoL) in the OVHIPEC trial.Materials and methodsOVHIPEC was a multicentre, open-label, randomized phase III trial for patients with stage III ovarian cancer. Patients were randomly assigned (1:1) to receive interval CRS with or without HIPEC with cisplatin. HRQoL was assessed using the EORTC QLQ-C30, and the ovarian (QLQ-OV28) and colorectal cancer (QLQ-CR38) modules. HRQoL questionnaires were administered at baseline, after surgery, after end of treatment, and every three months thereafter. HRQoL was a secondary endpoint, with the prespecified focus on the QLQ-C30 summary score and symptom scores on fatigue, neuropathy and gastro-intestinal symptoms. HRQoL was analysed using linear and non-linear mixed effect models.ResultsIn total, 245 patients were randomized. One-hundred-ninety-seven patients (80%) completed at least one questionnaire. No significant difference over time in the QLQ-C30 summary scores was observed between the study arms (p-values for linear and non-linear growth: p > 0.133). The pattern over time for fatigue, neuropathy and gastro-intestinal symptoms did not significantly differ between treatment arms.ConclusionThe addition of HIPEC to interval CRS does not negatively impact HRQoL in patients with stage III ovarian cancer who are treated with interval CRS due to the extent of disease. These HRQoL results, together with the improvement in RFS and OS, support the viability of HIPEC as an important treatment option in this patient population.ClinicalTrials.gov numberNCT00426257.EudraCT number2006-003466-34.     

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.     

新辅助化疗对晚期卵巢癌患者带瘤状态、手术效果及预后的影响

目的：探讨新辅助化疗对晚期卵巢癌患者带瘤状态、手术效果及预后的影响。方法选取80例晚期卵巢癌患者,实施新辅助化疗联合减瘤术治疗的40例患者为研究组,仅实施减瘤术治疗的40例患者为对照组,比较两组临床疗效、手术效果及预后情况。结果研究组患者治疗的总有效率为87.5%（35/40）,高于对照组的65.0%（26/40）,差异有统计学意义（P﹤0.05）;研究组患者的腹腔积液量、术中出血量、总瘤灶直径、转移灶数均少于对照组,手术时间短于对照组,差异均有统计学意义（P﹤0.05）;研究组副损伤发生率低于对照组,最佳减灭率高于对照组,差异有统计学意义（P﹤0.05）;研究组患者的1年、3年生存率分别为92.5%（37/40）、57.5%（23/40）,与对照组的90.0%（36/40）、52.5%（21/40）比较,差异均无统计学意义（P﹥0.05）;研究组中位生存时间为（42±5）个月,与对照组的（37±5）个月比较,差异无统计学意义（P﹥0.05）。结论新辅助化疗能够有效改善晚期卵巢癌患者带瘤状态、手术效果,但对预后影响不大。     

新辅助化疗联合中间性肿瘤细胞减灭术治疗晚期上皮性卵巢癌的疗效及对HE4、VEGF、CA125水平的影响

目的 探讨新辅助化疗联合中间性肿瘤细胞减灭术治疗晚期上皮性卵巢癌的疗效及其对血清人附睾蛋白4(HE4)、血管内皮细胞生长因子(VEGF)、糖类抗原125(CA125)水平的影响.方法 回顾性分析68例晚期上皮性卵巢癌患者的病历资料,根据治疗方法不同将患者分为联合组与对照组,每组34例.联合组患者采用新辅助化疗联合中间性肿瘤细胞减灭术治疗,对照组患者仅接受卵巢肿瘤细胞减灭术治疗.观察并比较两组患者的近期疗效,手术相关指标,血清HE4、VEGF、CA125水平及预后情况.结果 联合组患者的治疗总有效率为79.4%,高于对照组的52.9%(P﹤0.05);联合组患者的手术时间明显短于对照组(P﹤0.01);联合组患者的术中失血量、腹腔积液量均明显低于对照组(P﹤0.01);治疗后,联合组患者的血清HE4、VEGF、CA125水平均明显低于对照组(P﹤0.01);治疗后,两组患者的1年、2年、3年生存率比较,差异均无统计学意义(P﹥0.05).联合组和对照组患者的中位生存时间分别为32.0个月(95%CI:25.3~35.6)和28.0个月(95%CI:22.1~33.9),两组患者的生存情况比较,差异无统计学意义(χ2=1.96,P﹥0.05).结论 新辅助化疗联合中间性肿瘤细胞减灭术治疗晚期上皮性卵巢癌可以缩短手术时间,减少术中出血量,降低血清肿瘤相关标志物水平,但该方法对改善患者的远期生存意义不大.     

Greater-omentum lesion-score (GOLS) as a predictor of residual disease in different regions of the peritoneal cavity in patients undergoing interval cytoreductive surgery for advanced ovarian cancer and its potential clinical utility

Background and aimThe greater omentum(GO) is a common site of residual disease in patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer. The presence of tumor in the GO could predict presence of disease in other peritoneal regions. The goal of this study was to perform a correlation between the greater-omentum lesion-score(GOLS) and presence of disease in different peritoneal regions and determine its potential utility in guiding interval cytoreductive surgery(CRS).MethodsThis prospective study included 134 patients undergoing interval CRS from July 1, 2018 to June 30, 2020.Each region of Sugarbaker's Peritobneal Cancer Index(PCI) was given a lesion score(LS) from 0 to 3 according to the diameter of the largest tumor in the region. The GOLS was recorded separately from other structures in the region. Correlation between the GOLS and surgical and pathological LS in each region was performed.ResultsAs the GOLS increased, the incidence of disease(surgical LS) in other regions of the peritoneal cavity increased. Receiver operating characteristic(ROC) curves showed area under curve more than 80% for regions 1–2 and 7–8 indicating a high probability of disease in these regions in patients with GOLS 1–3. The positive predictive value(PPV) of preoperative imaging for GOLS was 95.7%. No cut-off of the GOLS could predict presence of disease on pathology with more than 70% accuracy.ConclusionsPresence of disease in the GO warrants performing upper abdominal exploration and/or cytoreduction and interval CRS should be planned accordingly in these patients. Imaging has a high PPV in detecting disease in the GO.     

卵巢恶性肿瘤、宫颈癌白细胞体外药敏与临床疗效探讨

 目的：评价白细胞和癌细胞体外药敏相关性,并在卵巢恶性肿瘤、宫颈癌中进行临床疗效观察。方法：用MTT法体外药敏试验检测卵巢恶性肿瘤、宫颈癌的癌细胞、白细胞对10种常用化疗药物的敏感性。结果：卵巢恶性肿瘤的白细胞和癌细胞药敏相关性好,无统计学差异;宫颈癌的白细胞在DDP等六种药物的敏感率和阳性率非常显著低于癌细胞（P＜0.05～0.01）。卵巢恶性肿瘤、宫颈癌病人化疗时尽量选择癌细胞敏感、白细胞不敏感的药物化疗,其有效率与单用癌细胞敏感的药物化疗结果一样好,但前者化疗后白细胞下降程度明显低于后者,（P＜0.05～0.0）。结论：白细胞、癌细胞药敏结果为卵巢恶性肿瘤、宫颈癌病人化疗提供了理想的参考方案。     

A phase 1b,open-label study of trebananib in combination with paclitaxel and carboplatin in patients with ovarian cancer receiving interval or primary debulking surgery

AimTo evaluate the tolerability, pharmacokinetics and tumour response of first-line trebananib plus paclitaxel and carboplatin followed by trebananib maintenance in high-risk or advanced ovarian cancer.MethodsIn this open-label phase 1b study, patients received intravenous (IV) trebananib 15 mg/kg administered weekly (QW) plus paclitaxel 175 mg/m² once every 3 weeks (Q3W) and carboplatin 6 mg/mL·min Q3W followed by trebananib 15 mg/kg QW monotherapy for 18 months. End-points were dose-limiting toxicities (DLTs; primary); treatment-emergent adverse events (AEs), anti-trebananib antibodies, pharmacokinetics and tumour response (secondary).ResultsTwenty seven patients (interval debulking surgery [IDS], n = 13) were enrolled. No DLTs occurred. During the combination therapy phase, AEs (>50%) in patients with IDS were nausea, diarrhoea, fatigue, decreased appetite and thrombocytopenia. In patients with primary debulking surgery (PDS), they were nausea, diarrhoea, fatigue and localised oedema. Grade 4 AEs were neutropenia (IDS, PDS; all n = 3) and thrombocytopenia (IDS, PDS; all n = 1). No deaths occurred. Toxicity results pertaining to trebananib maintenance were immature. The treatment combination did not markedly affect the pharmacokinetics across agents. In patients with IDS (n = 14 after one patient was reassigned from PDS to IDS), 12 patients had a partial response (PR), two patients had stable disease. In patients with PDS (n = 4), three patients had a complete response, one patient had a PR.ConclusionsIn women with ovarian cancer receiving IDS or PDS, IV trebananib 15 mg/kg QW plus paclitaxel and carboplatin appears tolerable. Results suggest that the treatment combination followed by trebananib 15 mg/kg monotherapy is associated with antitumour activity.     

Effect of antiangiogenic therapy on tumor growth, vasculature and kinase activity in basal- and luminal-like breast cancer xenografts

Several clinical trials have investigated the efficacy of bevacizumab in breast cancer, and even if growth inhibiting effects have been registered when antiangiogenic treatment is given in combination with chemotherapy no gain in overall survival has been observed. One reason for the lack of overall survival benefit might be that appropriate criteria for selection of patients likely to respond to antiangiogenic therapy in combination with chemotherapy, are not available. To determine factors of importance for antiangiogenic treatment response and/or resistance, two representative human basal- and luminal-like breast cancer xenografts were treated with bevacizumab and doxorubicin alone or in combination. In vivo growth inhibition, microvessel density (MVD) and proliferating tumor vessels (pMVD = proliferative microvessel density) were analysed, while kinase activity was determined using the PamChip Tyrosine kinase microarray system. Results showed that both doxorubicin and bevacizumab inhibited basal-like tumor growth significantly, but with a superior effect when given in combination. In contrast, doxorubicin inhibited luminal-like tumor growth most effectively, and with no additional benefit of adding antiangiogenic therapy. In agreement with the growth inhibition data, vascular characterization verified a more pronounced effect of the antiangiogenic treatment in the basal-like compared to the luminal-like tumors, demonstrating total inhibition of pMVD and a significant reduction in MVD at early time points (three days after treatment) and sustained inhibitory effects until the end of the experiment (day 18). In contrast, luminal-like tumors only showed significant effect on the vasculature at day 10 in the tumors having received both doxorubicin and bevacizumab. Kinase activity profiling in both tumor models demonstrated that the most effective treatment in vivo was accompanied with increased phosphorylation of kinase substrates of growth control and angiogenesis, like EGFR, VEGFR2 and PLCγ1. This may be a result of regulatory feedback mechanisms contributing to treatment resistance, and may suggest response markers of value for the prediction of antiangiogenic treatment efficacy.