Impact of neoadjuvant chemotherapy on the immune microenvironment in advanced epithelial ovarian cancer: Prognostic and therapeutic implications

Over the last decade, increasing evidence highlights the role of the host immune system in the control of tumor growth and the prognostic implications of tumor infiltrating lymphocytes (TILs) in ovarian cancer. Most data support a better prognosis with accumulation of CD3+ and CD8 + TILs and a poor outcome associated with increased regulatory T cells. However, only a small number of studies have focused on the effect of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment. This review will provide an update on the prognostic value of TIL subpopulations at diagnosis and a comprehensive overview of the recent studies evaluating the impact of neoadjuvant chemotherapy on TILs and their relationship to clinical outcome in advanced ovarian cancer. This information could help in future investigations of immunotherapy as maintenance following primary treatment.     

Intraperitoneal chemotherapy in patients with advanced ovarian cancer: the con view

OBJECTIVES: In this paper we wish to present the reasons why i.p. chemotherapy cannot be accepted as standard of care for first-line systemic treatment of advanced ovarian carcinoma. METHODS: The recent literature on i.p. chemotherapy is critically reviewed. All possible arguments against i.p. chemotherapy are reviewed. CONCLUSIONS: Intraperitoneal chemotherapy is associated with a higher toxicity rate than i.v. chemotherapy. For this reason, none of the regimens investigated in the three Gynecologic Oncology Group (GOG) studies can be used as standard treatment outside clinical protocols. The trials on i.p. chemotherapy have suggested a survival difference. However, in the two most recent trials, i.p. chemotherapy or not was not the only research question because different schedules and dosages were used. In addition, the significance of the most recent GOG 172 study was only weak (p = .03), and the result was nonsignificant for progression-free survival. Intraperitoneal chemotherapy should be used only in the context of properly designed clinical trials. These trials must either assess i.p. therapy in comparison with the standard treatment or address the issue of route of administration for equivalent dosages and schedules of the same drugs, and not a mosaic of these questions. In addition, these trials should investigate i.p. regimens that are less toxic than the regimens used in the three GOG trials, and which can be combined with molecular targeted therapies.     

晚期卵巢癌化疗联合放疗的临床研究

目的探讨化疗联合放疗综合治疗晚期卵巢癌的疗效和毒性。方法随机将不能手术的晚期卵巢癌患者分为两组,即化疗组和化放疗组,两组各36例,均使用IPA方案,IF01.2g/m2,i.vdripd1~5,Mesna0.4gi.v(0、4、8h)d1~5,DDP60~80mg/m2,i.vd1,ADM40~60mg/m2,i.vd1。化疗组用该方案连续化疗3个周期,每3周重复1次;化放疗组先用该方案化疗1周期,接着用6MV-X线全盆腔外照射DT40GY/4W,再缩野至癌灶局部加量DT10~20GY/1~2W,放疗结束后,休息1周,再化疗2个周期,每3周重复1次。结果化疗组和化放疗组有效率(CR PR)为77.8%和100%,1、3年生存率分别为60.1%,32.7%和73.1%,48.2%。毒性反应以骨髓抑制和消化道反应为主。结论化疗联合放疗综合治疗晚期卵巢癌能提高局控率和生存率,且并发症发生率较低,是一种安全、有效、较理想的治疗方法。     

Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study.

PURPOSE: Since 1986, the recommended therapy for patients with ovarian cancer has included surgery and chemotherapy with a platinum compound (cisplatin or carboplatin). The purpose of this study is to assess the use of chemotherapy in elderly patients with advanced ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database represents approximately 14% of the United States population and provides clinical and demographic information on cancer patients covered by Medicare, along with health care-utilization data from Medicare claims files. We analyzed the association of demographic and clinical factors with treatment among patients diagnosed from 1992 to 1996 with stage III or IV ovarian cancer, who survived > or = 120 days beyond diagnosis, and were > or = 65 years of age (N = 1,775). RESULTS: Approximately 83% of elderly patients received some form of chemotherapy within 4 months of diagnosis. In a multiple logistic regression model with patients aged 65 to 69 years as the reference, the odds ratios of receiving chemotherapy were 0.96 (95% confidence interval [CI], 0.63 to 1.46) for ages 70 to 74, 0.65 (95% CI, 0.43 to 1.00) for 75 to 79, 0.24 (95% CI, 0.15 to 0.37) for 80 to 84, and 0.12 (95% CI, 0.07 to 0.19) for 85+. Hispanic patients were less likely to receive chemotherapy than non-Hispanic white patients. Since 1992, paclitaxel has gradually replaced cyclophosphamide as the drug most commonly used with platinum. CONCLUSION: Despite its proven efficacy in treating ovarian cancer, chemotherapy seems to be used less among patients over age 65, especially those who are nonwhite and/or in the oldest age groups. Further research is needed to elucidate to what degree this represents appropriate clinical judgment and to what degree other factors, such as patient choice, play a role.     

Cisplatin-based chemotherapy in advanced ovarian cancer: initial experience in an Indian set-up

Forty patients of advanced ovarian carcinoma were treated with monthly cycles of cyclophosphamide, adriamycin and cisplatin. Debulking surgery was done in 29 cases. Clinical complete response was seen in 70 percent and an overall response in 85 percent of cases. The median follow-up was 30 months. The actuarial overall survival was 45 percent and the disease free survival was 35 percent at 3 years. The present protocol appears to have an important influence on initial control of disease but relapses continue to occur following the treatment. Cytoreductive surgery before or after three cycles of chemotherapy has a favourable influence on disease free survival (DFS). Prolonged follow up will be necessary to determine the overall influence on long term survival.     

High-dose chemotherapy in advanced epithelial ovarian cancer

Since more than thirty years, ovarian cancer is wellknown to be chemosensitive. However, long term results of advanced stages remain low with 5 years overall survival around 20%. That's why high-dose chemotherapy in this chemosensitive disease has to be considered. Here, authors report the french, european and american experiences in three clinical settings: first in consolidation after complete or very good partial response, second after relapse or for refractory disease, third as first line treatment to increase clinical and pathological complete responses and improve prognosis. The more promising results concern high-dose chemotherapy as consolidation setting. The preliminary results of the french multicentric randomized phase III study (high-dose versus conventional dose) gives a favorable trend for high-dose approach as consolidation. This unique trial would definitively establish the place of high-dose chemotherapy in the first line treatment of advanced epithelial ovarian cancer.     

Combination chemotherapy and immune capacity in advanced ovarian carcinoma

The effects of chemotherapy with either Chap-5 (a drug regimen consisting of adriamycin, cis-dichlorodiammine platinum (II), hexamethylmelamine and cyclophosphamide) or Hexa CAF (a drug regimen consisting of methotrexate, 5-fluorouracil, hexamethylmelamine and cyclophosphamide) on the immunocompetence of 22 patients with advanced ovarian carcinoma were studied. Both primary and secondary humoral and cellular immune responses in vivo were studied. In addition, the numbers of granulocytes, lymphocytes and monocytes in peripheral blood were determined, as well as the levels of immunoglobulins and complement proteins. Furthermore, the proliferative capacity of lymphocytes, cytotoxic T-cell function, and K- and NK-cell activities were measured. The results indicate a depression of the primary humoral immune response in vivo in patients receiving Chap-5. Furthermore, a decrease of several parameters in vitro was observed. However, these alterations were only moderate and rapidly reversible.     

Alternating multiagent chemotherapy for advanced ovarian cancer

A chemotherapy regimen consisting of hexamethylmelamine (H) 150 mg/m2 orally days 1-14, cyclophosphamide (C) 500 mg/m2 IV day 1 of a 28-day cycle with Adriamycin (A) 40 mg/m2 IV day 1 alternating with cis-diamminechloroplatinum (C-P) 50 mg/m2 IV day 1 every other cycle was administered to 29 patients with advanced epithelial ovarian cancer. Toxicity to this regimen included alopecia, nausea, and vomiting in all patients. Mild paresthesias occurred in four patients. Hematologic toxicity required only minimal dose modification. There was no cardiac, renal, or auditory toxicity. The clinical response rate of 55% and median survival of 14 months compare favorably with that of other reported series. This chemotherapy regimen seems to be well tolerated without jeopardizing the patients' response.     

Primary chemotherapy-associated effect of second-line chemotherapy on survival of patients with advanced ovarian cancer

Background The current treatment of patients with recurrent ovarian cancer who have received initial platinum- or taxane-based chemotherapy depends on the results of the initial chemotherapy. The purpose of this study was to evaluate how to make the selection of second-line agents for patients with recurrent ovarian carcinoma initially diagnosed as stage II to IV. Methods We conducted a retrospective crossover study in patients who received second-line chemotherapy at Jikei University School of Medicine. We evaluated the responses, progression-free survivals, survivals of second-line chemotherapy, and overall survivals after primary surgery for 51 patients. The treatment cohorts were defined as follows: TC1, patients who were given paclitaxel and carboplatin as first-line chemotherapy and who, upon recurrence, were treated with a platinum-based combination as second-line; and TC2, patients who were given a non-taxane-based platinum combination as first-line chemotherapy, followed, at the time of recurrence, with paclitaxel and carboplatin. Results The response rates of the second-line chemotherapy for the TC1 and TC2 groups were 44% and 25% (P = 0.09). The median progression-free survivals of TC1 and TC2 were 12.9 and 6.4 months (P = 0.018; hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.16–5.04). The median survivals after second-line chemotherapy for the two groups were 16.8 and 10.4 months (P = 0.007; HR, 2.78; 95% CI, 1.33–5.84) and overall survivals after primary surgery were 36.6 and 27.9 months (P = 0.007; HR, 2.36; 95% CI, 1.07–5.21). Conclusion The TC1 group demonstrated a significantly better response and extension of progression-free survival, as well as significantly better survival after crossover and overall survival after primary surgery. As this was a retrospective analysis, this effect should be considered as hypothesis-generating and assessed prospectively in other trials comparing these two chemotherapy schedules.     

晚期卵巢癌行热灌注化疗患者的生活质量现状分析

目的 调查晚期卵巢癌行热灌注化疗患者的生活质量。方法 采用一般资料调查问卷、生活质量核心问卷（QLQ-C30）、卵巢癌治疗功能评价量表（FACT-O）、自我感受负担量表（SPBS）、疼痛数字评价量表（NRS）及社会支持评定量表（SSRS）对本院300例晚期卵巢癌行热灌注化疗患者进行调查。结果 晚期卵巢癌行热灌注化疗患者QLQ-C30总分为（66.28±17.72）分,FACT-O 总分为（94.07±8.80）分,SPBS总分为（39.82±7.61）分;NRS评分为（5.68±1.24）分,SSRS得分为（23.96±6.57）分;Pearson相关分析结果显示,自我感受负担、社会支持和疼痛与生活质量相关（r=0.807,0.458,0.604）。结论 晚期卵巢癌行热灌注化疗患者的生活质量较差,自我感受负担、疼痛及社会支持可影响患者生活质量。     

Comparison of adjuvant and neoadjuvant chemotherapy in the management of advanced ovarian cancer: a retrospective study of 574 patients

Background  

There is a lack of clinical data on the validity of neoadjuvant chemotherapy in the treatment of ovarian cancer. The aim of this study was to compare the impact of the adjuvant and neoadjuvant chemotherapy regimens on the clinical outcomes in patients with advanced ovarian cancer.     

先期化疗在晚期卵巢癌中的临床应用与疗效评价

目的 探讨在晚期卵巢癌患者中行先期化疗的临床疗效.方法 130例晚期卵巢癌患者随机分为新辅助化疗组及术后化疗组,各65例,比较两组患者临床资料差异性.结果 新辅助化疗组手术时间(180±15)分钟,术后化疗组(240±25)分钟;新辅助化疗组出血量(380±55)mL,术后化疗组(610±80)mL;新辅助化疗组较术后化疗组术后并发症少8例,新辅助化疗组较术后化疗组缓解满意率高29.2％,1年生存率高15.4％,3年生存率高21.6％,差异均有统计学意义(P＜0.05).结论 先期化疗具有手术时间短、出血量少、术后并发症少、提高缓解率、延长生存率的优点.     

Neoadjuvant chemotherapy for advanced epithelial ovarian cancer]

Primary surgical cytoreduction followed by paclitaxel/carboplatin combination chemotherapy currently is the treatment of choice for advanced epithelial ovarian cancer. Aggressive surgery is widely accepted as a valid approach to initial cytoreduction of stage III disease, but suboptimal residual disease following primary surgical resection is one of the most important adverse prognostic factors in these patients. Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery for initial management of bulky ovarian cancer, with the goal of improving surgical quality. General acceptance of neoadjuvant chemotherapy as an alternative to primary surgery for patients who are not ideal surgical candidates remains limited, because equivalent or superior survival has not yet been demonstrated in a prospective randomized study. A large-scale, prospective, randomized study is being conducted by the European Organization for Research and Treatment of Cancer (EORTC) Gynecologic Cancer Cooperative Group and Gynecologic Oncology Group (GOG) to compare outcomes (overall and progression-free survival, quality of life, treatment complications) of neoadjuvant chemotherapy/interval debulking surgery versus primary cytoreductive surgery/adjuvant chemotherapy in patients with advanced epithelial ovarian carcinoma.     

热疗联合静脉化疗在晚期卵巢癌患者中的效果观察

目的探讨热疗联合静脉化疗在晚期卵巢癌患者中的应用效果。方法选取2017年1月至2019年1月间乐山市人民医院收治的88例晚期卵巢癌患者,采用随机数表法分为观察组与对照组,每组44例。对照组患者采用静脉化疗,观察组患者采用局部热疗联合静脉化疗,分析两组患者的腹水症状改善程度。结果治疗后,观察组患者有效率为90. 9%,优于对照组的63. 6%,差异有统计学意义(P <0. 05)。结论晚期卵巢癌患者采用热疗联合静脉化疗,能有效改善患者症状,控制腹腔积液,值得临床推广。     

以大剂量顺铂为主腹腔内化疗治疗晚期卵巢癌临床观察

目的　评价大剂量顺铂和常规剂量顺铂腹腔化疗对晚期卵巢癌的疗效。方法　将 1994年至1998年在我院住院治疗的晚期卵巢癌患者 5 3例随机分为大剂量顺铂组 2 8例 ,常规剂量顺铂组 2 5例。每周腹腔化疗一次 ,3～ 6周为一疗程。结果　大剂量顺铂组和常规剂量顺铂组其有效率和中位生存期分别为 89 2 9%、6 4 0 0 %和 13月、8 5月 (P <0 .0 5 )。如果腹腔内化疗加全身化疗 ,则疗效优于单纯腹腔化疗组。结论　大剂量顺铂腹腔化疗治疗晚期卵巢癌其疗效明显优于常规剂量顺铂组。     

Impact of secondary cytoreductive surgery on survival of patients with advanced epithelial ovarian cancer

Aims To investigate the impact on survival of secondary cytoreduction for advanced epithelial ovarian cancer and variables influencing redebulking surgical outcome. Methods Between 1986 and 1997, 106 patients who received secondary cytoreductive surgery and consequent second-line chemotherapy for stages III and IV epithelial ovarian cancer were retrospectively reviewed. The optimal residual disease cut-off was 1.0 cm. The Cox proportional regression model and logistic stepwise regression were used in statistical processing of the data. Results The median age of the patients was 50 years (range, 26–77 years). Optimal secondary cytoreduction was achieved in 46 of 106 patients (43.4%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimaly cytoreduced, with an estimated median survival in the optimal group of 20 months vs 8 months in the suboptimal group (²=42.03, P=0.0000). When factorized, patients had significant survival benefit from optimal secondary cytoreduction for recurrent disease and interval cytoreduction. Survival was adversely influenced by progression-free interval ≤12 months (P=0.0078), residual disease >1 cm (P=0.0001) and presence of refractory ascites (P=0.0001). The probability of successful redebulking surgery was affected by presence of refractory ascites (P=0.0023) in all 106 patients and by the ascites (P=0.0072) and residual disease at initial operation in recurrent disease (P=0.0096). Conclusion Secondary surgical cytoreduction surgery significantly lengthened survival for patients with recurrent epithelial ovarian cancer or those receiving interval cytoreduction. Patients with refractory ascites, however, were not suitable for aggressive secondary surgery, and redebulking surgery for those with residual disease of >1.0 cm after primary operation should be considered prudently in recurrent disease.     

腹腔热灌注联合静脉化疗治疗晚期卵巢癌的疗效观察

目的:探讨晚期卵巢癌行腹腔热灌注联合静脉化疗的临床疗效及不良反应。方法:2008年12月-2012年12月收治 的100例晚期卵巢癌并大、中量腹腔积液患者采用信封法随机分为治疗组和对照组。治疗组60例,行腹腔热灌注联合静脉化疗;对照组40例,行单纯的静脉化疗。治疗组采用顺铂腹腔热灌注联合紫杉醇静脉化疗,对照组采用紫杉醇联合顺铂 静脉化疗,观察两组的腹水控制率及不良反应。结果:治疗组的腹水控制率为78.3%,对照组为42.5%,差异具有统计学 意义（P＜0.01）。两组的不良反应比较无统计学差异（P＞0.05）。结论:腹腔热灌注联合静脉化疗可有效的控制卵巢 癌患者恶性腹腔积液,不良反应能够耐受。