Primary debulking surgery before initiation of chemotherapy has been the standard of care for patients with advanced ovarian cancer.
We randomly assigned patients with stage IIIC or IV epithelial ...ovarian carcinoma, fallopian-tube carcinoma, or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery (so-called interval debulking surgery).
Of the 670 patients randomly assigned to a study treatment, 632 (94.3%) were eligible and started the treatment. The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery (metastatic lesions that were larger than 5 cm in diameter in 74.5% of patients and larger than 10 cm in 61.6%). The largest residual tumor was 1 cm or less in diameter in 41.6% of patients after primary debulking and in 80.6% of patients after interval debulking. Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking. The hazard ratio for death (intention-to-treat analysis) in the group assigned to neoadjuvant chemotherapy followed by interval debulking, as compared with the group assigned to primary debulking surgery followed by chemotherapy, was 0.98 (90% confidence interval CI, 0.84 to 1.13; P=0.01 for noninferiority), and the hazard ratio for progressive disease was 1.01 (90% CI, 0.89 to 1.15). Complete resection of all macroscopic disease (at primary or interval surgery) was the strongest independent variable in predicting overall survival.
Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study. Complete resection of all macroscopic disease, whether performed as primary treatment or after neoadjuvant chemotherapy, remains the objective whenever cytoreductive surgery is performed. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003636.)
There is limited information about the relative effectiveness of cervical cancer screening with primary human papillomavirus (HPV) testing alone compared with cytology in North American populations.
...To evaluate histologically confirmed cumulative incident cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) detected up to and including 48 months by primary HPV testing alone (intervention) or liquid-based cytology (control).
Randomized clinical trial conducted in an organized Cervical Cancer Screening Program in Canada. Participants were recruited through 224 collaborating clinicians from January 2008 to May 2012, with follow-up through December 2016. Women aged 25 to 65 years with no history of CIN2+ in the past 5 years, no history of invasive cervical cancer, or no history of hysterectomy; who have not received a Papanicolaou test within the past 12 months; and who were not receiving immunosuppressive therapy were eligible.
A total of 19 009 women were randomized to the intervention (n = 9552) and control (n = 9457) groups. Women in the intervention group received HPV testing; those whose results were negative returned at 48 months. Women in the control group received liquid-based cytology (LBC) testing; those whose results were negative returned at 24 months for LBC. Women in the control group who were negative at 24 months returned at 48 months. At 48-month exit, both groups received HPV and LBC co-testing.
The primary outcome was the cumulative incidence of CIN3+ 48 months following randomization. The cumulative incidence of CIN2+ was a secondary outcome.
Among 19 009 women who were randomized (mean age, 45 years 10th-90th percentile, 30-59), 16 374 (8296 86.9% in the intervention group and 8078 85.4% in the control group) completed the study. At 48 months, significantly fewer CIN3+ and CIN2+ were detected in the intervention vs control group. The CIN3+ incidence rate was 2.3/1000 (95% CI, 1.5-3.5) in the intervention group and 5.5/1000 (95% CI, 4.2-7.2) in the control group. The CIN3+ risk ratio was 0.42 (95% CI, 0.25-0.69). The CIN2+ incidence rate at 48 months was 5.0/1000 (95% CI, 3.8-6.7) in the intervention group and 10.6/1000 (95% CI, 8.7-12.9) in the control group. The CIN2+ risk ratio was 0.47 (95% CI, 0.34-0.67). Baseline HPV-negative women had a significantly lower cumulative incidence of CIN3+ at 48 months than cytology-negative women (CIN3+ incidence rate, 1.4/1000 95% CI, 0.8-2.4; CIN3+ risk ratio, 0.25 95% CI, 0.13-0.48).
Among women undergoing cervical cancer screening, the use of primary HPV testing compared with cytology testing resulted in a significantly lower likelihood of CIN3+ at 48 months. Further research is needed to understand long-term clinical outcomes as well as cost-effectiveness.
isrctn.org Identifier: ISRCTN79347302.
2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer. This report provides the outcomes from the Fourth Ovarian Cancer Consensus Conference.
In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC ...followed by hr-HPV triage with > or = CIN3 as the outcome.
HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases
To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program.
International Standard Randomised Controlled Trial Number Register, ISRCTN79347302.
HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high‐risk human papillomavirus (HPV) and the control arm received ...liquid‐based cytology (LBC) at baseline and 24 months. Both arms received 48‐month exit HPV and LBC cotesting. Exit results are presented for per‐protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow‐up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25–65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56–1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43–1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14–65) and intervention 43 (95% CI: 25–73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1–0.7). This per‐protocol analysis found that screening with HPV using a 4‐year interval is as safe as LBC with a 2‐year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.
What's new?
Human papillomavirus (HPV) testing is a sensitive approach for detecting cervical intraepithelial neoplasia grade 2 and higher (CIN2+). However, whether HPV testing alone, with extended intervals between visits, is more effective than HPV testing and liquid‐based cytology (LBC) combined for cervical screening remains uncertain. Here, HPV testing every four years was found to be at least as effective as LBC every two years for CIN2+ identification. Moreover, women were more likely to comply with screening protocol when four‐year intervals were used, compared to two‐year intervals. Women with CIN1 at colposcopy and women initially HPV‐positive may require screening with both methods.
First-line therapy in ovarian cancer trials Thigpen, Tate; duBois, Andreas; McAlpine, Jessica ...
International journal of gynecological cancer
21, Issue:
4
Journal Article
Peer reviewed
Open access
At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying ...gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today?
Clinical trials in recurrent ovarian cancer Friedlander, Michael; Trimble, Edward; Tinker, Anna ...
International journal of gynecological cancer
21, Issue:
4
Journal Article
Peer reviewed
Open access
The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic ...cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?
The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus ...meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer.
Quality of surgery is a proven prognostic factor in many tumors. It is critical to ensure that an effective method is in place to evaluate surgery accurately.
A provincial Cancer Surgery Working ...Group designed and piloted a computerized synoptic operative report template (WebSMR) in rectal cancer surgery, to replace the standard narrative operative record (NR). This included a precise description of the procedure, data on demographics, diagnostic evaluation, staging, and functional measures. A total of 70 items for anterior resection (AR) and 63 items for abdominoperinal excision (APR) were included. The WebSMR was assessed for comparison with 40 NR randomly selected from seven hospitals in Southern Alberta from 2001 to 2003.
The NR contained 45.9% of the specified data elements and the WebSMR captured 99%. The most complete NR data (68.8% to 97%) concerned hospital and patient data, anesthetist and surgeon information, approach, and closure details. The important details of laparotomy and tumor resection were the next most complete data (33.5% to 47.5%) and the least complete (0 to 25%) concerned preoperative treatment, comorbidity, and metastatic and local assessment. All differences among these groups were statistically different (P < .001). No statistically significant differences were seen in the completeness of the NR according to the type of surgery (AR vs. APR; P = .1) or the dictating surgeon (colorectal vs. general vs. resident; P = .175). The time needed to complete the WebSMR test was only 6 minutes.
The science of surgical technique can be better measured by this unique instrument and will create accountability in surgery.
Current first-line management for advanced ovarian cancer consists of cytoreductive surgery followed by chemotherapy, usually with a platinum/taxane combination. Although this approach has been shown ...to achieve overall response rates of 70–80% in clinical trials, the majority of patients relapse. A number of different approaches have been investigated to improve the efficacy of therapy, including the introduction of newer agents, such as topotecan, into chemotherapy regimens and the use of consolidation therapy. Encouraging results have been obtained in clinical trials of topotecan administered using a variety of different approaches, including replacement regimens, triplet regimens, and sequential doublet regimens. Other treatment modalities have included the use of drug resistance modifiers and intraperitoneal delivery of treatment. A variety of approaches to consolidation therapy have also been investigated, including radiotherapy, cytotoxic therapy, and intraperitoneal therapy. The use of topotecan has also shown promise in this setting, although further data from large, controlled trials are required. In summary, while good response rates are obtained using current first-line treatments, the high relapse rate indicates the need to develop more effective and durable treatment regimens including new agents with, perhaps, an increased emphasis on maintaining remission through the use of consolidation therapy.
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