The Value of Decision Analytical Modeling in Surgical Research: An Example of Laparoscopic Versus Open Distal Pancreatectomy.

OBJECTIVE: To illustrate how decision modeling may identify relevant uncertainty and can preclude or identify areas of future research in surgery. SUMMARY BACKGROUND DATA: To optimize use of research resources, a tool is needed that assists in identifying relevant uncertainties and the added value of reducing these uncertainties. METHODS: The clinical pathway for laparoscopic distal pancreatectomy (LDP) versus open (ODP) for nonmalignant lesions was modeled in a decision tree. Cost-effectiveness based on complications, hospital stay, costs, quality of life, and survival was analyzed. The effect of existing uncertainty on the cost-effectiveness was addressed, as well as the expected value of eliminating uncertainties. RESULTS: Based on 29 nonrandomized studies (3.701 patients) the model shows that LDP is more cost-effective compared with ODP. Scenarios in which LDP does not outperform ODP for cost-effectiveness seem unrealistic, e.g., a 30-day mortality rate of 1.79 times higher after LDP as compared with ODP, conversion in 62.2%, surgically repair of incisional hernias in 21% after LDP, or an average 2.3 days longer hospital stay after LDP than after ODP. Taking all uncertainty into account, LDP remained more cost-effective. Minimizing these uncertainties did not change the outcome. CONCLUSIONS: The results show how decision analytical modeling can help to identify relevant uncertainty and guide decisions for future research in surgery. Based on the current available evidence, a randomized clinical trial on complications, hospital stay, costs, quality of life, and survival is highly unlikely to change the conclusion that LDP is more cost-effective than ODP.

Para-aortic lymphadenectomy in advanced stage cervical cancer, a protocol for comparing safety, feasibility and diagnostic accuracy of surgical staging versus PET-CT; PALDISC trial.

BACKGROUND: Currently, a PET-CT is used to assess the need for extended field radiotherapy of para-aortic lymph nodes (PALN) in International Federation of Gynaecology and Obstetrics (FIGO) stage IB2, IIA2-IVA (locally advanced stage) cervical cancer. A small study established a sensitivity and specificity estimate for PALN metastases of 50% (95% CI; 7-93%) and 83% (95% CI; 52-98%), respectively. Surgical staging of PALN may lead to a higher diagnostic accuracy. However, surgical staging of para-aortic lymph nodes in locally advanced stage cervical cancer is not common practice. Therefore, a phase 2 randomised controlled trial is needed to assess its safety and feasibility. METHODS/DESIGN: In addition to standard imaging (MRI or CT scan) with PET-CT, 30 adult women with FIGO stage IB2, IIA2-IVA cervical cancer will be randomised to receive either surgical staging or usual PET-CT staging. Administering extended field radiotherapy will be based on lymphadenectomy results for the intervention group and on the PET-CT results for the control group. Follow-up visits at 0, 3, 6, 9 and 12 months will assess health-related quality of life and progression-free survival.Primary safety and feasibility outcomes of surgical staging will be assessed by calculating means with 95% confidence intervals for duration of surgery, number of complications, blood loss, nodal yield after para-aortic lymphadenectomy and treatment delay due to surgical staging. Secondary patient-centred outcomes on quality of life and first year survival will be documented and compared between the two groups. Estimates of sensitivity, specificity and negative and positive predictive values of MRI, PET-CT and surgical staging will be presented with 95% CI.. All analysis will be performed according to the intention to treat principle. DISCUSSION: This study will assess safety and feasibility, expressed as the number and severity of complications, effect on quality of life and the treatment delay due to surgically staging para-aortic lymph nodes in locally advanced cervical cancer. It will provide insight in the diagnostic accuracy of the PET-CT and detection rate of missed (micro)metastases due to surgical staging. This information will be used to assess the necessity for a phase 3 study on the diagnostic accuracy of the PET-CT and surgical staging. If a phase 3 study is deemed necessary, current data can be used for sample size calculation of such a phase 3 study. TRIAL REGISTRATION: Nederlands Trial Register/Dutch Trial Registry (www.trialregister.nl), NTR4922. Registered on 24 November 2014.

Measuring health-related quality of life in cervical cancer patients: a systematic review of the most used questionnaires and their validity.

BACKGROUND: Data on health-related quality of life (HRQoL) is paramount for shared and evidence based decision-making. Since an overview of cervical cancer HRQoL tools and their validity appears to be lacking, we performed a systematic review on usage of disease specific HRQoL instruments in cervical cancer patients and their psychometric properties to identify the most suitable cervical cancer specific HRQoL tool. METHODS: We searched Pubmed, EMBASE and PsycINFO from inception up to 18 October 2016 for studies on quality of life in cervical cancer patients. Data extraction and HRQoL identification was performed by two independent reviewers. Validation studies of the identified cervical cancer specific HRQoL tools were retrieved and assessed on psychometric properties using the COSMIN checklist. All used cervical cancer specific HRQoL instruments were scored and ranked according to their psychometric properties. RESULTS: We included 156 studies (20,690 patients) and identified 31 HRQoL tools. The EORTC QLQ-CX24 (35 studies; 5,556 patients) and FACT-Cx (22 studies; 4,224 patients) were the only cervical cancer specific tools. The EORTC QLQ-CX24 had 4 out of 9 positive rated psychometric properties; internal consistency, content and construct validity, and agreement. Criterion validity, reliability, and interpretability scored doubtful. Responsiveness and floor- and ceiling effects were not reported. The FACT-Cx had 2 out of 9 positive rated psychometric properties; internal consistency and agreement. Content validity, reliability, and interpretability scored doubtful while criterion and construct validity scored negative. Responsiveness and floor- and ceiling effects were not reported. CONCLUSION: The validity of the often used EORTC QLQ-CX24 questionnaire for cervical cancer patients remains uncertain as 5 out of 9 psychometric properties were doubtful or not reported in current literature. Cervical cancer specific HRQoL tools should therefore always be used in conjunction with validated generic cancer HRQoL tools until proper validity has been proven, or a more valid tool has been developed.

The sentinel node procedure in early stage cervical cancer, taking the next step; a diagnostic review.

OBJECTIVE: Recent reviews on the sentinel lymph node (SLN) procedure in cervical cancer have shown that bilateral SLN detection and ultra staging are safe and superior options compared to a unilateral detection, frozen section and H&E analysis. So far, nobody identified a subgroup of patients in whom a SLN procedure may replace pelvic lymph node dissection (PLND). METHODS: We searched PubMed, Embase, CINAHL and Cochrane from inception up to November 26, 2014. Studies reporting SLN detection, and/or histological outcome of the SLN were included. Methodological quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool by two independent reviewers. Data to complete 2×2 contingency tables were obtained, and patient-, study- and technique characteristics were extracted. Results were pooled and plotted in forest plots. RESULTS: Forty-seven studies (4130 patients) were analyzed. Pooled data of diagnostic accuracy on ultra staging (18 studies; 1275 patients) showed a sensitivity of 94% (95% CI 80-99%) and negative predictive values ranging between 91 and 100%. After ultra staging, 19 false negative results remained. Prerequisites such as early FIGO stage (IA2, IB1, IIA primary tumor size <40mm), no suspicious pre-, and per-operative lymph nodes, and bilateral negative SLNs after ultra staging resulted in 1 remaining false negative result among 1257 patients (0.08%). Pooled data on a combined tracer in early stage cervical cancer patients with primary tumor size <20mm (6 studies; 276 patients) resulted in 87% bilateral SLN detection. CONCLUSIONS: Early stage cervical cancer patients (FIGO IA2, IB1, IIA primary tumor size <40mm) who have no suspicious pre-, and per-operative lymph nodes, and have bilateral negative SLNs after ultra staging, have a residual risk of 0.08% (1/1257) on occult metastases. On the basis of these results we recommend not to perform a full PLND in these patients.

[IDEAL as a model for the evaluation of implants]. / Het IDEAL-framework.

Medical devices have to be tested for safety before they can be brought onto the market; effectiveness does not have to be demonstrated. The 'IDEAL model' is in place for the development and evaluation of new surgical interventions and procedures; 'IDEAL' stands for the 5 phases of the model: Idea, Development, Exploration, Assessment and Long-term study. The model is based on the assumption that innovation and evaluation should be interwoven from concept through to the, preferably randomised, clinical trial phase. Prospective registration of new interventions from the pre-clinical development phase onwards can prevent waste of money and effort, as unsuccessful 'new' registered interventions will not have to be developed again in the same manner. The IDEAL model, with a few adaptations, also seems to be a practically useful and suitable model for new medical devices. It will allow patients efficient access to new interventions and medical devices for which the safety and effectiveness has been sufficiently clinically established.