Ward Hofhuis

Response to Systemic Therapies in Patient-Derived Cell Lines from Primary and Recurrent Adult Granulosa Cell Tumors

Abstract In patients with the rare adult-type granulosa cell tumor (aGCT), surgery is the primary treatment for both primary and recurrent disease. In cases of inoperable disease, systematic therapy is administered, but variable response rates and drug resistance complicate predicting the most effective therapy. Drug screen testing on patient-derived cell lines may offer a solution. In a national prospective study on aGCT, fresh tissue was cultured into 2D cell lines, testing 27 clinical and experimental drugs. Dose–response curves and synergy were calculated using GraphPad Prism and CompuSyn software. We established 34 patient-derived cell lines from tissue of 20 patients with aGCT. Of these, seven patients had a primary diagnosis of aGCT and 13 patients had recurrent disease. In eight patients, multiple tumor locations were cultured. On each cell line, 10 monotherapies and 17 combinations of drugs were tested. Carboplatin/gemcitabine showed efficacy and synergy in almost all patient-derived cell lines. Synergy could not be detected in the regular carboplatin/paclitaxel and carboplatin/etoposide combinations. Experimental combinations alpelisib/fulvestrant and alpelisib/gemcitabine showed efficacy of more than 75%. Drug screens on patient-derived tumor cell lines reflect the reality of the variable response of systemic therapy in patients with aGCT. In future research, this technique may be used to personalize the systemic treatment of patients with aGCT in a clinical study. The good response to carboplatin/gemcitabine in our patient-derived cell lines can then be confirmed in a clinical setting.

Serous endometrial intraepithelial carcinoma (SEIC): Current clinical practice in The Netherlands

Serous endometrial intraepithelial carcinoma (SEIC) is a rare diagnosis, defined as an intraepithelial lesion with cells identical to serous type endometrial carcinoma. SEIC is considered to be potentially metastatic, however clear and robust data on prognosis are lacking, potentially leading to variability in clinical management. The aim is to establish the opinion of gynecologists on the optimal management of patients with SEIC. An online questionnaire with 15 multiple choice questions was sent to all gynecologists with expertise in gynecological oncology in 19 expert centers in The Netherlands. A total of 24 gynecologists participated. The majority of respondents (n = 18/24, 75%) do not consult a guideline regarding the treatment of SEIC. In current practice, 14 of the 24 respondents perform surgical staging in women with SEIC (58.3%) while seven choose hysterectomy with bilateral salpingo-oophorectomy (29.2%), and three (12.5%) have no firm preference. Eleven of the 14 respondents who perform a surgical staging procedure believe that this is certainly the optimal treatment. The majority of respondents have no firm opinion on whether lymph node sampling or lymph node dissection is preferable during surgical staging (n = 15/23, 65.2%). Most respondents do not give adjuvant therapy (n = 15/24, 62.5%), 25.0% recommend brachytherapy (n = 6/24). Follow-up is for 5 years in almost all cases (n = 23/24). There is no consensus on the optimal surgical treatment and the use of adjuvant therapy for patients with SEIC. Our research team is therefore conducting a nationwide cohort study in which treatment modality, morbidity and survival will be evaluated.

High acceptability of point‐of‐care HIV testing at the colposcopy outpatient clinic in hospitals in the Netherlands

AbstractObjectiveCervical cancer and its precursor are labeled as HIV indicator conditions, justifying the recommendation of HIV testing for all patients. This study aimed to assess the acceptance and patients' and gynecologists' perceptions on HIV testing in patients with cervical dysplasia at the colposcopy outpatient clinic in hospitals in the Netherlands.MethodsA cross‐sectional study was conducted between May 2021 and February 2023 to implement point‐of‐care HIV testing in five hospitals in the Rotterdam region, the Netherlands. We included patients aged 18 years and older, without documented HIV, presenting with cervical dysplasia. The primary outcome was the HIV test acceptance rate. Secondary outcomes were the HIV positivity rate and the association between dysplasia severity and test acceptance. We also assessed patients' and gynecologists' perspectives on this testing strategy with a questionnaire.ResultsOf 563 patients, 523 accepted HIV testing, resulting in a test acceptance rate of 92.9% (95% confidence interval, 90.45%–94.88%). Testing rates were consistent among participating hospitals (91.6%–100.0%) None of the patients tested positive for HIV. Severity of dysplasia was not associated with test acceptance (P = 0.768). Most patients (n = 500, 96.0%) reported good or higher experience with this testing strategy. The main barriers for gynecologists to offer HIV testing were lack of time (n = 22, 33.9%) and fear to offend a patient (n = 7, 12.5%). Less than half (n = 19, 39.3%) of gynecologists believed an HIV test should be offered to all patients with cervical dysplasia.ConclusionPoint‐of‐care HIV testing at colposcopy outpatient clinics was well accepted by patients. The data indicate that the primary barrier lies with the physicians to offer such testing.