European Network of Gynaecological Oncological Trial Groups' Requirements for Trials Between Academic Groups and Industry Partners--First Update 2015.

The first version of ENGOT's Requirements for Trials Between Academic Groups and Industry Partners in Europe was published 2010. This first update integrates the experiences made by the ENGOT network and the cooperative group studies while performing, analyzing, and publishing -among others - three large phase III trials. Furthermore, progress in European legislation and its impact on clinical studies in Europe have been considered in this update process.

Laparoscopic hysterectomy is preferred over laparotomy in early endometrial cancer patients, however not cost effective in the very obese.

BACKGROUND: Total laparoscopic hysterectomy (TLH) is safe and cost effective in early stage endometrial cancer when compared to total abdominal hysterectomy (TAH). In non-randomised data it is often hypothesised that older and obese patients benefit most from TLH. Aim of this study is to analyse whether data support this assumption to advice patients, clinicians and policy makers. METHODS: Data of 283 patients enrolled in a randomised controlled trial comparing TAH versus TLH in early stage endometrial cancer were re-analysed. Randomisation by sequential number generation was done centrally, with stratification by trial centre. Using multivariate analysis, predictors of major complications and conversions to laparotomy were assessed. For the cost effectiveness analysis, subgroups of patients were constructed based on age and body mass index (BMI). For each subgroup, costs per major complication-free patient were estimated, using incremental cost effect ratios (extra costs per additional effect). RESULTS: Older (odds ratio (OR): 1.05; 1.01-1.09) and obese (OR: 1.05; 1.01-1.10) patients had a higher risk to develop complications, for both groups. In obese (OR: 1.17; 1.09-1.25) patients and patients with a previous laparotomy (OR: 3.45; 1.19-10.04) a higher risk of conversion to laparotomy was found. For patients>70 years of age and patients with a BMI over 35 kg/m2, incremental costs per major complication-free patients were €16 and €54 for TLH compared to TAH, respectively. CONCLUSION: In general, TLH should be recommended as the standard surgical procedure in early stage endometrial cancer, also in patients>70 years of age. In obese patients with a BMI>35 kg/m2 TLH is not cost effective because of the high conversion rate. A careful consideration of laparoscopic treatment is needed for this subgroup. Surgeon experience level may influence this choice.

Assessment of gene promoter hypermethylation for detection of cervical neoplasia.

Current cervical cancer screening is based on morphological assessment of Pap smears and associated with significant false negative and false positive results. Previously, we have shown that detection of hypermethylated genes in cervical scrapings using quantitative methylation-specific PCR (QMSP) is a promising tool for identification of squamous cell cervical cancer. Aim of the present pilot-study was to evaluate presence of hypermethylated genes in cervical carcinogenesis, both in squamous cell as well as adenocarcinomas. Cervical scrapings were obtained from 30 patients diagnosed with cervical cancer (20 squamous cell carcinomas and 10 adenocarcinomas) and 19 women with histologically normal cervices. The scraped cells were used for determination of promoter hypermethylation by QMSP for 12 genes and for morphological assessment. Overall, CALCA, DAPK, ESR1, TIMP3, APC and RAR-beta2 promoters were significantly more often hypermethylated in cancers than in controls, while adenocarcinomas were more often hypermethylated above the highest control ratio for APC, TIMP3 and RASSF1A promoters. Combining 4 genes (CALCA, DAPK, ESR1 and APC) yielded a sensitivity of 89% (with all adenocarcinomas identified), equal to cytomorphology (89%) and high-risk human papilloma virus (Hr-HPV; 90%). The 4-gene QMSP proved theoretically superior to cytomorphology as well as Hr-HPV in specificity (100% vs. 83 and 68%, respectively), because cytology identified 3 controls as moderate or severe dyskaryosis and 6 controls were positive for Hr-HPV. In conclusions, QMSP of 4 gene promoters combined appears to have comparable sensitivity and potentially better specificity in comparison to "classic" cytomorphological assessment and Hr-HPV detection. QMSP holds promise as a new diagnostic tool for both squamous cell carcinoma and adenocarcinoma of the cervix.

Vulvar carcinoma. The price of less radical surgery.

BACKGROUND: The objective of this study was to determine whether modifications in the treatment of patients with vulvar carcinoma influence the rates of recurrence and survival. METHODS: Between 1982 and 1997, 253 patients with T1 and T2 invasive squamous cell carcinoma of the vulva were treated by essentially the same team of gynecologic oncologists, and 168 patients (Group I) underwent radical vulvectomy with en bloc inguinofemoral lymphadenectomy. Standard therapy was changed in 1993, and 85 patients (Group II) underwent wide local excision with inguinofemoral lymphadenectomy through separate incisions. The rates of recurrence and survival were compared between both groups. RESULTS: In Group II, the overall recurrence rate (33.3%) within 4 years was increased compared with Group I (19.9%; P = 0.03). In Group II, 5 of 79 patients (6.3%) developed fatal groin or skin bridge recurrences compared with 2 of 159 patients (1.3%) in Group I (P = 0.029); this did not result in a difference in overall survival. In Group II, 40 of 79 patients had tumor free margins measuring 8 mm, resulting in no local recurrences (P = 0.002). CONCLUSIONS: The current study showed that fatal recurrences in either the groin or the skin bridge were more frequent after wide local excision and inguinofemoral lymphadenectomy through separate incisions; however, probably due to lack of power, this did not result in shorter survival. In 40 of 79 patients, the histologic margins measured