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Background: Recent HIV infection surveillance can help to identify populations and geographies with active transmission. We compared risk factors among recent and long-term infections from the initial ten months of [...]

Background: Cervical cancer (CxCa) is mainly a locally invading disease that metastasizes to loco-regional lymph node basins before involving distant organs in more advanced stages. Local immune potentiation of tumor-draining lymph nodes (TDLN) may thus protect against tumor progression. Methods: To identify therapeutic targets for local immune modulation, multi-parameter flow cytometric T-cell profiling of primary cervical tumors (PT) and TDLN (n = 37) was performed. The in-vitro effect of PD-1 blockade on T-cell reactivity to HPV16 E6 oncoproteins was determined in cultures of TDLN and PT single cell suspensions (n = 19). Also, intracellular cytokine staining (ICS) upon anti-CD3 stimulation was performed in metastatic TDLN (LN+) and PT (n = 7), as well as multiplexed immunofluorescence histochemistry staining (n = 8). Results: Our data revealed elevated rates of activated regulatory T cells (aTregs) and of central or effector memory CD8+ T cells in metastatic TDLN (LN+) as compared to tumor-free TDLN (LN-), and equally high or even higher rates of these subsets in PT. Both memory subsets co-expressed multiple immune checkpoints. PD-1 blockade significantly enhanced detectable E6-specific T-cell responses in 4/5 HPV16+ LN+ and in 1/5 HPV16+ PT. Whereas aTreg rates were higher in anti-PD-1 non-responders, in responders elevated levels of CD8+FoxP3+CD25+ T cells were observed, which correlated with the efficacy of PD-1 blockade (P = 0.018). This subset was characterized by an early effector memory phenotype with particularly high levels of co-expressed PD-1, CTLA-4, TIM-3 and LAG-3 checkpoints, but, rather than exhausted, was shown upon polyclonal activation to produce higher levels of Granzyme-B and effector cytokines as compared to its CD8+FoxP3- counterparts. Conclusion: These observations support local PD-(L)1 blockade to interrupt loco-regional immune suppression in CxCa and control metastatic spread to TDLN. Furthermore, our data identify CD8+FoxP3+CD25+ T cells as therapeutic targets, which may also serve as predictive biomarker for PD-(L)1 checkpoint blockade. [ABSTRACT FROM AUTHOR]

Background: Treatment with programmed cell death receptor (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors is a promising strategy to lift tumour-induced immune response suppression. However, the current systemic treatment often causes autoimmune side effects. In more than 50% of squamous cell cervical cancer, PD-L1 expression is detected. Moreover, we observed high and interrelated rates of PD-L1 positive macrophages and regulatory T cells in metastatic lymph nodes of cervical cancer patients. As cervical cancer in general initially metastasizes to regional lymph nodes, local administration of durvalumab (a PD-L1 checkpoint inhibitor) at an early stage will deliver these antibodies exactly where they are needed, facilitating immune protection. This may result in a clinical benefit while reducing undesirable side effects.Methods: DURVIT is a non-randomized, single-arm, open-label, phase I study. Three escalating dose levels of intratumourally (i.t.) injected durvalumab will be tested, i.e. 5, 10 and 20 mg (three patients per dose level, with an additional three at the highest tolerated dose). The primary endpoint of this phase-I study is safety. Immune monitoring will consist of flow cytometric, immunohistochemical and functional T cell reactivity testing. The first patient has been included in this trial in November 2017.Discussion: Evidence of safety and biological efficacy of this locally administered checkpoint blockade may expand adjuvant therapy options for cervical cancer patients. Early metastatic spread of cervical cancer cells may thus be controlled in the draining lymph node basin, and beyond, and hopefully delay or even prevent the onset of disease recurrence.Trial Registration: NTR6119 , 1-nov-2016. [ABSTRACT FROM AUTHOR]

To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eight patients were enrolled. Dose levels were 10, 20, 30, 45, 70, 85, and 100 mg. At 100 mg dose-limiting toxicity (DLT) (common toxicity criteria grade 3 skin rash and grade 3 diarrhoea despite treatment with loperamide) occurred in two patients. In the next-lower dose of 70 mg, DLT (grade 3 fatigue and ALAT elevation) occurred in one of six patients. An intermediate dose level of 85 mg was studied. Here DLT occurred in two patients (grade 3 diarrhoea despite treatment and grade 2 diarrhoea lasting more than 7 days despite treatment). An additional 12 patients were treated at 70 mg. BIBW 2992 PK after single and multiple doses revealed moderately fast absorption, and no deviation from dose proportionality. Pharmacodynamics analysis in skin biopsies did not show significant changes in EGFR-associated biomarkers. However, a significant inhibitory effect on the proliferation index of epidermal keratinocytes was observed. No partial or complete responses were observed, stable disease lasting more than four cycles was seen in seven patients. The recommended dose for studies with BIBW 2992 for 14 days followed by 14 days off medication is 70 mg OD.British Journal of Cancer (2008) 98, 80–85. doi:10.1038/sj.bjc.6604108 www.bjcancer.com Published online 20 November 2007 [ABSTRACT FROM AUTHOR]

Objective: Several European and American guidelines recommend to perform an additional hysterectomy in patients with cervical adenocarcinoma in situ (AIS), who initially received conservative treatment and who completed childbearing during follow-up. This study aimed to evaluate cost-effectiveness of performing an additional hysterectomy in comparison to expectative management., Methods: This post-hoc analysis was based on a retrospective cohort of patients diagnosed with AIS, who were conservatively treated by a radical (i.e., negative surgical margins) large loop excision of the transformation zone (LLETZ) or cold-knife conisation (CKC) in the Netherlands between 1990 and 2021. Based on these data, we estimated and compared the harms, benefits, and costs in 1000 simulated patients, both with and without an additional hysterectomy five years after conservative treatment for AIS. In the sensitivity analyses, we varied the timing of the additional hysterectomy, the risk of recurrent high-grade cervical dysplasia and cervical cancer risk after AIS treatment, and the utility loss for hysterectomy., Results: Less than 2 % of the patients who did not receive an additional hysterectomy after AIS developed cervical cancer. When an additional hysterectomy was performed, no quality adjusted life-years (QALYs) were gained and costs were 863 % higher (€6203,485 versus €644,238). Only when assuming no utility loss for a hysterectomy, QALYs were gained resulting in a cost-effectiveness ratio of €144,273, which is far above the cost-effectiveness threshold of €20,000., Conclusion: It is not cost-effective to perform an additional hysterectomy after completion of childbearing in patients who were primarily treated by a radical LLETZ or CKC., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RB: gives lectures for MSD. All other authors declare that they have no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood., Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing., Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months)., Conclusion: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: [ 18 F]FDG-PET/CT is used for staging and treatment planning in patients with locally advanced cervical cancer (LACC). We studied if a PET-based prediction model could provide additional risk stratification beyond International Federation of Gynaecology and Obstetrics (FIGO) staging in our population with LACC to aid treatment decision making., Methods: In total, 183 patients with LACC treated with chemoradiation between 2013 and 2018 were included. Patients were treated according to FIGO 2009 and retrospectively reclassified according to FIGO 2018 staging system. After validation of an existing PET-based prediction model, the predicted recurrent free survival (RFS), disease specific survival (DSS) and overall survival (OS) at 1, 3, and 5 years, based on metabolic tumor volume (MTV), maximum standardized uptake value (SUV max ) and highest level of [ 18 F]FDG-positive node was calculated. Then the observed survival was compared to the predicted survival. An area under the curve (AUC) close to or higher than 0.7 was considered adequate for accurate prediction. The Youden (J) index defined survival chance cutoff values for low and high risk groups., Results: All AUC values for the comparison between predicted and observed outcomes were > 0.7 except for 5-year RFS and for 5-year OS which were close to 0.7 (0.684 and 0.650 respectively). Cutoff values for low and high risk survival chance were 0.44 for the 3-year RFS and 0.47 for the 5-year OS. The FIGO 2009 system could not differentiate between the risk profiles. After reclassification according to FIGO 2018, all patients with stage IIIC2 and IVB fell in the high risk and almost all patients with stages IB2-IIIB and IVA in the low risk group. In patients with stage IIIC1 disease the FIGO stage cannot discriminate between the risk profiles., Conclusions: Low and high risk patients with LACC can be identified with the PET-based prediction model. In particular patients with stage IIIC1 need additional risk stratification besides the FIGO 2018 staging. The Kidd model could be a useful tool to aid treatment decision making in these patients. Our results also support the choice of [ 18 F]FDG-PET/CT imaging in patients with LACC., (© 2024. The Author(s).)

Objectives: The aim of this study was to analyze morbidity and survival after pelvic exenteration for gynecologic malignancies and evaluate prognostic factors influencing postoperative outcome., Methods: We retrospectively reviewed all patients who underwent a pelvic exenteration at the departments of gynecologic oncology of three tertiary care centers in the Netherlands, the Leiden University Medical Centre, the Amsterdam University Medical Centre, and the Netherlands Cancer Institute, during a 20-year period. We determined postoperative morbidity, 2- and 5-year overall survival (OS) and 2- and 5-year progression free survival (PFS), and investigated parameters influencing these outcomes., Results: A total of 90 patients were included. The most common primary tumor was cervical cancer (n = 39, 43.3%). We observed at least one complication in 83 patients (92%). Major complications were seen in 55 patients (61%). Irradiated patients had a higher risk of developing a major complication. Sixty-two (68.9%) required ≥1 readmission. Re-operation was required in 40 patients (44.4%). Median OS was 25 months and median PFS was 14 months. The 2-year OS rate was 51.1% and the 2-year PFS rate was 41.5%. Tumor size, resection margins and pelvic sidewall involvement had a negative impact on OS (HR = 2.159, HR = 2.376, and HR = 1.200, respectively). Positive resection margins and pelvic sidewall involvement resulted in decreased PFS (HR = 2.567 and HR = 3.969, respectively)., Conclusion: Postoperative complications after pelvic exenteration for gynecologic malignancies are common, especially in irradiated patients. In this study, a 2-year OS rate of 51.1% was observed. Positive resections margins, tumor size, and pelvic sidewall involvement were related to poor survival outcomes. Adequate selection of patients who will benefit from pelvic exenteration is important., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The "intermediate-risk" (IR) group of early-stage cervical cancer patients is characterized by negative pelvic lymph nodes and a combination of tumor-related prognostic risk factors such as tumor size ≥2 cm, lymphovascular space invasion (LVSI), and deep stromal invasion. However, the role of adjuvant treatment in these patients remains controversial. We investigated whether adjuvant (chemo)radiation is associated with a survival benefit after radical surgery in patients with IR cervical cancer., Methods: We analyzed data from patients with IR cervical cancer (tumor size 2-4 cm plus LVSI OR tumor size >4 cm; N0; no parametrial invasion; clear surgical margins) who underwent primary curative-intent surgery between 2007 and 2016 and were retrospectively registered in the international multicenter Surveillance in Cervical CANcer (SCCAN) study., Results: Of 692 analyzed patients, 274 (39.6%) received no adjuvant treatment (AT-) and 418 (60.4%) received radiotherapy or chemoradiotherapy (AT+). The 5-year disease-free survival (83.2% and 80.3%; P DFS = 0.365) and overall survival (88.7% and 89.0%; P OS = 0.281) were not significantly different between the AT- and AT+ groups, respectively. Adjuvant (chemo)radiotherapy was not associated with a survival benefit after adjusting for confounding factors by case-control propensity score matching or in subgroup analyses of patients with tumor size ≥4 cm and <4 cm. In univariable analysis, adjuvant (chemo)radiotherapy was not identified as a prognostic factor in any of the subgroups (full cohort: P DFS = 0.365; P OS = 0.282)., Conclusion: Among patients with IR early-stage cervical cancer, radical surgery alone achieved equal disease-free and overall survival rates to those achieved by combining radical surgery with adjuvant (chemo)radiotherapy., Competing Interests: Declaration of Competing Interest The authors declared no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer., Methods: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort., Results: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy., Conclusions: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited., Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer., Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery., Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study., Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO., Trial Registration: ClinicalTrials.gov NCT03835793; https://clinicaltrials.gov/ct2/show/NCT03835793., International Registered Report Identifier (irrid): DERR1-10.2196/24414., (©Lara Terra, Maartje J Hooning, Bernadette A M Heemskerk-Gerritsen, Marc van Beurden, Jeanine E Roeters van Lennep, Helena C van Doorn, Joanne A de Hullu, Constantijne Mom, Eleonora B L van Dorst, Marian J E Mourits, Brigitte F M Slangen, Katja N Gaarenstroom, M Carola Zillikens, Tim Leiner, Lizet van der Kolk, Margriet Collee, Marijke Wevers, Margreet G E M Ausems, Klaartje van Engelen, Lieke PV Berger, Christi J van Asperen, Encarna B Gomez-Garcia, Irma van de Beek, Matti A Rookus, Michael Hauptmann, Eveline M Bleiker, Sanne B Schagen, Neil K Aaronson, Angela H E M Maas, Flora E van Leeuwen. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 22.01.2021.)

Background: In 2014-2015, 242 individuals aged 2-89 years were newly diagnosed with human immunodeficiency virus type 1 (HIV-1) in Roka, a rural commune in Cambodia. A case-control study attributed the outbreak to unsafe injections. We aimed to reconstruct the likely transmission history of the outbreak., Methods: We assessed in 209 (86.4%) HIV-infected cases the presence of hepatitis C virus (HCV) and hepatitis B virus (HBV). We identified recent infections using antibody (Ab) avidity testing for HIV and HCV. We performed amplification, sequencing, and evolutionary phylogenetic analyses of viral strains. Geographical coordinates and parenteral exposure through medical services provided by an unlicensed healthcare practitioner were obtained from 193 cases and 1499 controls during interviews., Results: Cases were coinfected with HCV (78.5%) and HBV (12.9%). We identified 79 (37.8%) recent (<130 days) HIV infections. Phylogeny of 202 HIV env C2V3 sequences showed a 198-sample CRF01&#95;AE strains cluster, with time to most recent common ancestor (tMRCA) in September 2013 (95% highest posterior density, August 2012-July 2014), and a peak of 15 infections/day in September 2014. Three geospatial HIV hotspots were discernible in Roka and correlated with high exposure to the practitioner (P = .04). Fifty-nine of 153 (38.6%) tested cases showed recent (<180 days) HCV infections. Ninety HCV NS5B sequences formed 3 main clades, 1 containing 34 subtypes 1b with tMRCA in 2012, and 2 with 51 subtypes 6e and tMRCAs in 2002-2003., Conclusions: Unsafe injections in Cambodia most likely led to an explosive iatrogenic spreading of HIV, associated with a long-standing and more genetically diverse HCV propagation.

Background: Assessment of virological outcomes among HIV-infected patients receiving protease (PR) inhibitor-based second-line regimen are uncommon in Cambodia. The objective of this study is to assess the virological effectiveness of this regimen as well as impact of adherence boosting for patients experiencing virological failure., Methods: The 2PICAM study (Clinicaltrial: NCT01801618) is a cross-sectional study of HIV-infected adults on PR inhibitor-based second-line regimen since at least 6 months, conducted in 13 representative sites, comprising more than 90% of the target population. Adults with HIV RNA above 250 copies/mL (threshold of the assay) at inclusion received boosted adherence counseling during 3 months followed by HIV RNA control. For confirmed virological failure, genotype resistance test was performed and expert committee used results for therapeutic decision., Results: Among the 1,317 adults enrolled, the median duration of second-line regimen was 5 years. At inclusion, 1,182 (89.7%) patients achieved virological success (<250 copies/mL) and 135 (10.3%) experienced a virological failure (>250 copies/mL). In multivariable analysis, factors associated with virological success were: CD4 cell count between 201 and 350/mm 3 (OR: 4.66, 95% CI: 2.57-8.47, p  < 0.0001) and >350/mm 3 (OR: 6.67, 95% CI: 4.02-11.06, p  < 0.0001), duration of PI-based regimen >2 years (OR: 1.64, 95% CI: 1.03-2.62, p  = 0.037), ATV-containing regimen (0R: 1.65, 95% CI: 1.04-2.63, p  = 0.034) and high level of adherence (OR: 2.41, 95% CI: 1.07-5.41, p  = 0.033). After adherence counseling, 63 (46.7%) patients were rescued while 72 (53.3%) were not. For the 54 patients with genotype resistance tests available, high or intermediate levels of resistance to lopinavir, atazanavir, and darunavir were reported for 13 (24%), 12 (22.2%), and 2 (3.7%) patients, respectively. Change to an alternative PR inhibitor-based regimen was recommended for 17 patients and to third-line regimen, including integrase inhibitors for 12., Conclusion: This study reports high rate of virological suppression of second-line regimen and importance of adherence boosting prior to deciding any change of ART regimen. Genotype resistance tests appear necessary to guide decisions. Such information was of great importance for National HIV Program to adapt guidelines and program needs for third-line regimen.

Objectives: Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years., Methods: Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed., Results: Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014., Conclusion: While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Pre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival., Methods: Patients diagnosed with EC within the first 6 months of the years 2005-2014 were selected from the Netherlands Cancer Registry (N = 7875). Pre- and post-operative risk stratifications were determined based on grade and/or histological subtype for 3784 eligible patients., Results: A discordant risk stratification was found in 10% of patients: 4% (N = 155) had high pre- and low post-operative risk and 6% (N = 215) had low pre- and high post-operative risk. Overall survival of patients with high pre- and low post-operative risk was less favourable compared to those with a concordant low risk (80% versus 89%, p = 0.002). This difference remained significant when correcting for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95% confidence interval 1.28-2.53, p = 0.001). Survival of patients with low pre- and high post-operative risk did not differ from those with a concordant high risk (64% versus 62%, p = 0.295)., Conclusion: Patients with high pre- and low post-operative risk have a less favourable prognosis compared to patients with a concordant low risk. Pre-operative risk stratifications contain independent prognostic information and should be incorporated into clinical decision-making., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Objectives of this study were to evaluate the effect of changes in patterns of care, for example centralization and treatment sequence, on surgical outcome and survival in patients with epithelial ovarian cancer (EOC)., Methods: Patients diagnosed with FIGO stage IIB-IV EOC (2004-2013) were selected from the Netherlands Cancer Registry. Primary outcomes were surgical outcome (extent of macroscopic residual tumor after surgery) and overall survival. Changes in treatment sequence (primary debulking surgery and adjuvant chemotherapy (PDS+ACT) or neo-adjuvant chemotherapy and interval debulking surgery (NACT+IDS)), hospital type and annual hospital volume were also evaluated., Results: Patient and tumor characteristics of 7987 patients were retrieved. Most patients were diagnosed with stage III-IV EOC. The average annual case-load per hospital increased from 8 to 28. More patients received an optimal cytoreduction (tumor residue≤1cm) in 2013 (87%) compared to 2004 (55%, p<0.001). Complete cytoreduction (no macroscopic residual tumor), registered since 2010, increased from 42% to 52% (2010 and 2013, respectively, p<0.001). Optimal/complete cytoreduction was achieved in 85% in high volume (≥20 cytoreductive surgeries annually), 80% in medium (10-19 surgeries) and 71% in small hospitals (<10 surgeries, p<0.001). Within a selection of patients with advanced stage disease that underwent surgery the proportion of patients undergoing NACT+IDS increased from 28% (2004) to 71% (2013). Between 2004 and 2013 a 3% annual reduction in risk of death was observed (HR 0.97, p<0.001)., Conclusion: Changes in pattern of care for patients with EOC in the Netherlands have led to improvement in surgical outcome and survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case-control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure.

Objectives: In patients with a granulosa cell tumor of the ovary, the value of serum inhibin A and B concentrations for the assessment of disease status was investigated., Methods: In 30 consecutive patients with a stage I-III granulosa cell tumor, inhibin A and B concentrations were measured in pre- and post-treatment serum samples. Clinical data concerning diagnosis, treatment and follow-up of these patients were related to serum inhibin A and B concentrations. Serum samples from 41 premenopausal females with cervical dysplasia served as controls., Results: In 30 patients, 13 (43%) recurrences were observed during a median follow-up of 10 years (range 1-31 years). Serum inhibin A and B concentrations were elevated in respectively 67% and 89% of the patients at diagnosis, and in 58% and 85% at recurrence. Inhibin A and B concentrations were normal in all controls. Sensitivity of inhibin A testing for the diagnosis of granulosa cell tumor was 67% with a specificity of 100%, compared to 89% and 100% respectively for inhibin B (ns). Elevations in serum inhibin B concentrations predated recurrences by a median of 11 months. None of the patients in remission showed increased concentrations of inhibin A and B., Conclusion: Inhibin B seems to be the predominant form of inhibin secreted by granulosa cell tumors and appears to reflect disease status more accurately than inhibin A. Measurement of serum inhibin B concentrations may be preferred for the follow-up of granulosa cell tumors.