General practice at work : its contribution to epidemiology and health policy

The purpose of this thesis is to show how general practice can be a source of information for epidemiological and health policy questions, especially those relating to socio-economic health differences. Such use of general practice based information differs in several respects from use of information for individual patient care. High requirements regarding uniformity in registration procedures, availability of background information and compatibility of datasystems apply and analysis and interpretation generally demands much effort and expertise. In this thesis, we have examined the methods of data collection in general practice, the quality of the information, how the information has been used and the available information relating to socio-economic and area-based differences. Four specific themes will be explored

Treatment of bulky lymph nodes in locally advanced cervical cancer:boosting versus debulking

Objective: Treatment strategies for bulky lymph nodes in patients with locally advanced cervical cancer scheduled for definitive chemoradiation include nodal boosting with radiotherapy, surgical debulking, or both. The aim of this retrospective cohort study was to compare survival and toxicity in patients receiving these treatments and to compare them with a group that received neither form of treatment. Methods: Women diagnosed between January 2009 and January 2017 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2, IIA2-IVA cervical cancer with lymph nodes ≥1.5 cm without upper limit on pretreatment imaging and treated with definitive chemoradiation were selected from the Netherlands Cancer Registry. Patients were categorized by intention-to-treat strategy: boosting, debulking, or neither treatment, with subgroup analysis for patients receiving both treatments, that is, debulking with boosting. Overall and relapse-free survival outcomes were compared by Kaplan-Meier and Cox regression analyses and toxicity by logistic regression analysis. Results: Of 190 patients, 101 (53%) received only nodal boosting, 31 (16%) debulking alone, 29 (15%) debulking combined with boosting, and 29 (15%) received neither treatment. The 5 year overall and relapse-free survival for the treatment groups were 58%, 45% and 45% (p=0.19), and 47%, 44% and 46% (p=0.87), respectively. Multivariable Cox regression analyses demonstrated no differences in overall and relapse-free survival. Combination of debulking with boosting was associated with decreased overall and relapse-free survival compared with debulking alone (HR 2.47, 95% CI 1.22 to 5.00; and HR 2.37, 95% CI 1.14 to 4.93). Nodal boosting was independently associated with a decreased toxicity risk compared with debulking strategy (OR 0.37, 95% CI 0.16 to 0.83). Conclusions: This study showed no survival benefit from either nodal boosting or debulking strategy in patients with suspicious bulky nodes. Nodal boosting might, however, be associated with less toxicity. Dual treatment with debulking and boosting showed a worse survival outcome because this group probably represents patients with poor prognostic factors

European Society of Gynaecological Oncology Guidelines for the Management of Patients With Vulvar Cancer

Objective The aim of this study was to develop clinically relevant and evidence-based guidelines as part of European Society of Gynaecological Oncology's mission to improve the quality of care for women with gynecologic cancers across Europe. Methods The European Society of Gynaecological Oncology Council nominated an international development group made of practicing clinicians who provide care to patients with vulvar cancer and have demonstrated leadership and interest in the management of patients with vulvar cancer (18 experts across Europe). To ensure that the statements are evidence based, the current literature identified from a systematic search has been reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group (expert agreement). The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 181 international reviewers including patient representatives independent from the development group. Results The guidelines cover diagnosis and referral, preoperative investigations, surgical management (local treatment, groin treatment including sentinel lymph node procedure, reconstructive surgery), radiation therapy, chemoradiation, systemic treatment, treatment of recurrent disease (vulvar recurrence, groin recurrence, distant metastases), and follow-up

Tailoring radicality in early cervical cancer: how far can we go?

Today, the patient who is diagnosed with early cervical cancer is offered a variety of treatments apart from standard therapy. Patients can be treated with a less radical hysterectomy (RH) regarding parametrectomy, a trachelectomy either vaginal or abdominal, and this can be performed through a minimal invasive or open procedure. All this in combination with nerve sparing and/or sentinel node technique. Level 1 evidence for the oncological safety of all these modifications is only available from 3 randomized controlled trials (RCTs). Two RCTs on more or less radical parametrectomy both showed that oncological safety was not compromised by doing less radical surgery. Because of the heterogeneity of the patient population and the high frequency of adjuvant radiotherapy, the true impact of surgical radicality cannot be assessed. Regarding the issue of oncological safety of fertility sparing treatments, case-control and retrospective case series suggest that trachelectomy is safe as long as the tumor diameter does not exceed 2 cm. Recently, both a RCT and 2 case-control studies showed a survival benefit for open surgery compared to minimally invasive surgery, whereas many previous case-control and retrospective case series on this subject did not show impaired oncological safety. In a case-control study the survival benefit for open surgery was restricted to the group of patients with a tumor diameter more than 2 cm. Although modifications of the traditional open RH seem safe for tumors with a diameter less than 2 cm, ongoing prospective RCTs and observational studies should give the final answer