Background

Cervical cancer ranks the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths among women globally. In LMIC, most women with cervical cancer are diagnosed at an advanced stage because they have limited access to proper diagnosis. Treatment options are limited due to limited access to radiation therapy. Thus, survival outcomes are poor. There is no data on this issue in Cameroon so we undertook to determine the survival outcomes for women who present with cervical cancer to the CBCHS.

Methods

Data was extracted Women’s Health Program (WHP) database. Outcomes were categorized as alive with disease, alive without disease, or dead. Kaplan-Meier (KM) curves for survival were plotted stratified by age, HIV status, and histologic subtype. Cox regression model for survival analysis was used to determine the impact of some variables on the mean time of patient survival after diagnosis.

Results

Between 2013 and 2018, 752 women were diagnosed with cervical cancer. The average age at cervical cancer diagnosis was 53.33 (+/-13.82) with a mean survival time of 2.34 years (+/-2.00). Within five years of diagnosis, the overall survival for women diagnosed with cervical cancer was 27.1%. 285 (37.5%) of cases diagnosed did not go in for treatment. 387 (51.5%) went in for treatment, including 205 who did not complete their treatment. Age at diagnosis (HR 1.007 (95% Cl ( 1.000-1.013), p=0.035), a positive HIV status (HR 1.032 (95%Cl (0.930-1.145)) p = 0.558), and histologic subtype of adenocarcinoma (HR 1.026 (95% Cl (0.705-1.493), p=0.894) were associated with lower survival (although these associations were not statistically significant).

Conclusions

A diagnosis of cervical cancer is a serious threat to the health of women, especially in LMIC like Cameroon. Survival from the disease is extremely poor in this country, consistent with data from other LMICs. Most cases present late with symptoms, and the majority cannot afford treatment reflected by the very few who attend recommended forms of treatment or are unable to complete it. Education, and creating awareness around primary and secondary prevention and universal health care funding are necessary steps to strengthen cervical cancer control in Cameroon

Background

Fallopian tube cancer is a rare tumor which accounts for only 1% of all gynaecological cancers. It is closely related and generally treated with a similar approach to ovarian cancer. We used the publicly available databases to provide a description of epidemiological patterns, clinical outcomes, and mutational landscape of fallopian tube cancer and compare it with that of ovarian cancer.

Methods

We extracted clinical and epidemiological data of fallopian tube and ovarian cancers from the SEER database [13 reg; Nov 2020 Submission]. The average annual percentage change (AAPC) of incidence rates was calculated using The NIH’s Joinpoint Regression Program. Sequencing data were obtained through The American Association of Cancer Research (AACR) project GENIE database.

Results

We included 4,240 cases of fallopian tube cancer and 74,837 cases of ovarian cancer diagnosed between 1992 and 2018. The overall incidence of fallopian tube cancer was 0.39 [95% CI, 0.38-0.40], whereas the overall incidence of ovarian cancer was 6.97 [95% CI, 6.92-7.02]. Between 1992 and 2018, there was a significant increase in the incidence of fallopian tube cancer (AAPC = 6.1% 95% CI, [4.6, 7.9], p<0.001) and a decrease in the incidence of Ovarian cancer (AAPC = -1.7% 95% CI, [-2, -1.4], p<0.001). The median overall survival of fallopian tube cancer was significantly higher than ovarian cancer (80 months vs 43 months, P<0.001). A presentation with stage IV disease was significantly less frequent in fallopian tube cancer compared to ovarian cancer (50% vs 70%, P<0.001). In 166 patients with fallopian tube cancer and 5,303 patients with ovarian cancer in GENIE, the most frequently mutated genes were TP53, SPTA1, LRP1B, FAT3, and NF1; and TP53, CSMD3, DNAH9, ARID1A, and PDE4DIP; for fallopian tube cancer and ovarian cancer respectively.

Conclusions

Fallopian tube cancer is a distinct disease entity different in genetic, epidemiological, and clinical characteristics from ovarian cancer. Cases with fallopian tube cancer are less likely to present with distant metastasis and have longer overall survival compared to cases with ovarian cancer. The most frequently mutated genes of both cancers are different.

Background

Detection of residual tumor after radio-chemotherapy(RCX) in patients with locally advanced cervical cancer creates problems in clinical management. The aim of study is to evaluate the survival effect and prognostic importance of the residual tumor limited to the uterus in patients with advanced cervical cancer who received primary RCX.

Methods

125 cases of inoperable cervix cancer applied to our clinic between June 2012 and December 2018. Patients undergo magnetic resonance imaging of the pelvis to evaluate residual tumor before brachytherapy treatment, and positron emulsion tomography (PET-CT) to evaluate treatment response at 6 months after radical treatment.

Results

The median age was 50 and 111 patients (88.8% were diagnosed with squamous cell carcinoma and 14(11.2% with adenocarcinoma. Median tumor size was 5 cm and 71 patients were stage IIB (56.8%, and lymphnodes(LN) were detected in PET-CT before treatment in 70 patients. Residual tumor was found in 47 patients (37.6% median follow-up after external RCX 45 months (7-91) , and in 10 patients at 6 months.Three-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 86.9%, 89.1%, and 76.4%, respectively. In the univariate analysis, it was seen that the presence of residual tumor detected at 6 months was an unfavorable prognostic factor on LRFS (p=0.01), OS (p=0.001), and DMFS (p=0.01.Pre-treatment evaluation, presence of pelvic LN in PET-CT (p=0.05) and detection of residual tumor after external pelvic radiotherapy (p=0.015) were unfavorable prognostic factors on LRFS and DMFS.Local control (LC) was better in patients < 60 years (p=0.001), and distant metastases were more common in tumors > 5 cm (p=0.02. LC was better in <60 years (p=0.001), and distant metastases were more common in > 5 cm (p=0.02. Presence of residual tumor on PET-CT 6 months after treatment was determined in multivariate analysis as an important prognostic factor on OS and LRFS.

Conclusions

Treatment is controversial in patients with residual tumor after RCX.. Survival is worse in patients with residual tumor at 6-month follow-ups after treatment. The need for adjuvant therapy should be considered in these patients.

Editorial acknowledgement

Bedriye Doğan¹, Özlem Yetmen Doğan¹, Makbule Doğan Eren¹, Evrim Amodor²

¹Istanbul Kartal Dr Lutfi Kırdar City Hospital, Radiation Oncology Department

²Istanbul Kartal Dr Lutfi Kırdar City Hospital, Nuclear Medicine Department

Background

Inflammation is a hallmark of cancer. In our recent Umbrella systematic review of systematic reviews, we demonstrated that inflammatory biomarkers based on peripheral blood count impact both progression-free survival and overall survival (OS) in ovarian cancer. Pan-Immune-Inflammation Value (PIIV) is a new prognostic factor that was studied in breast cancer and other malignancies, but never in ovarian cancer. In this study, we provide the first results of the prognostic value of PIIV in a Moroccan cohort of ovarian cancer patients based on a biomarker-analysis of OVANORDEST-1 study.

Methods

An exploratory biomarker set from our OVANORDEST-1 database was included in the final analysis with OS as a primary endpoint. PIIV was calculated as previously described: (neutrophil count × platelet count × monocyte count)/lymphocyte count. Receiver operating characteristic (ROC) was used to evaluate the optimal cut-off of PIIV. Cox proportional hazard model was used for multivariable analysis and Kaplan-Meier method to estimate OS.

Results

A total number of 158 patients treated for epithelial ovarian cancer with a median age of 55 years were included in the survival analysis. A ROC-based cut off of 991.7 of PIIV was used for patients’ stratification. Survival analysis using Log rank test showed a significant association of PIIV with OS (p<0.0001). Women with high PIIV had the worst outcomes as compared to those with low PIIV (median OS: 16 months versus 35.4 months, respectively). On Cox proportional hazard model, PIIV was an independent predictor of OS (HR=2.38, CI:1.47-3.85; p<0.0001).

Conclusions

High PIIV is associated with an increased risk of death in women with epithelial ovarian cancer. A validation set of this study is ongoing and a prospective enrollment to develop a nomogram based on PIIV is being planned.

Background

In the PAOLA-1/ENGOT-ov25 trial, adding maintenance ola to bev improved progression-free survival in homologous recombination deficiency-positive (HRD+; tumour BRCA1/2 mutation [tBRCAm] and/or genomic instability) pts with newly diagnosed AOC at higher and lower risk of progression by disease stage and surgical status. Greatest benefits were seen in lower-risk pts (Harter et al. Gynecol Oncol 2022). Here, we analysed 5-y OS according to clinical risk and HRD status.

Methods

Pts in response after first-line platinum-based chemotherapy + bev were randomized 2:1 to ola (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; up to 15 mo) or placebo [pbo] + bev. This post hoc exploratory analysis evaluated OS in pts classified as higher risk (stage III with upfront surgery and residual disease or neoadjuvant chemotherapy; stage IV) or lower risk (stage III with upfront surgery and no residual disease), and by HRD status.

Results

537 pts were randomized to ola + bev and 269 to pbo + bev (median OS follow-up 61.7 and 61.9 mo, respectively). Of 806 randomized pts, 595 (74%) were classified as higher risk and 211 (26%) as lower risk. At final data cutoff (22 March 2022), OS events had occurred in 377 higher-risk pts (data maturity 63%) and 69 lower-risk pts (data maturity 33%). OS was prolonged with ola + bev in higher- and lower-risk pts with a tBRCAm or who were HRD+ (Table). No OS benefit was seen in HRD− pts in any clinical risk subgroup (Table). Subsequent PARP inhibitor therapy was received by 19.5% and 19.6% of ola + bev pts, and 45.9% and 45.2% of pbo + bev pts, in higher- and lower-risk groups, respectively.

Conclusions

This post hoc analysis of 5-y OS suggests that adding maintenance ola to bev should be considered for all HRD+ pts with newly diagnosed AOC, irrespective of their clinical risk status. Particular benefit was observed in HRD+ lower-risk pts who achieved 5-y OS rates of 88.3%.

Clinical trial identification

NCT02477644

Editorial acknowledgement

Medical writing assistance was provided by Helen Speedy, PhD, at Seques, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Background

The prognosis for patients with platinum-resistant ovarian High Grade Serous Carcinoma (HGSC) remains poor. BriTROC-1 data indicate that genomic alterations alone cannot explain acquired platinum resistance. We investigate epigenetic changes that may drive platinum resistance in HGSC.

Methods

Using in an in vitro two-dimensional model, we recreated multiple cycles of chemotherapy. We utilised both established cell lines and primary cultures derived from HGSC ascites. Following cell characterisation (p53, PAX8 IHC), carboplatin sensitivity was assessed (sulforhodamine B assay). Cells were then pulsed with four cycles of carboplatin (50μM for 6 hours) with a week of recovery between each cycle. Methylation (Illumina 850k array), transcriptomic (RNAseq) and chromatin accessibility (ATACseq) assays were performed. Cells were also imaged using Stochastic Optical Reconstruction Microscopy.

Results

Firstly, we focused on RNAseq analysis to evaluate genes (and related biological processes) that are consistently enriched following carboplatin cycles and the unique genes that are conversely enriched at cycle level. We attempted to identify uniformly up-/down-regulated pathways across the different cultures. These data were compared with the same results obtained from the OvCar4, an established HGSC cell line and IVR01, an in-vivo resistant OvCar4 derivative. The ATACseq and methylation analyses are still ongoing, aiming to identify possible concordant changes in the chromatin accessibility and the methylation patterns that will allow us to clarify the changes observed in transcriptomic. The preliminary data obtained from the RNAseq analysis show that the highest number of enriched genes seems to occur after the first Carboplatin cycle, with a lower number of progressively enriched genes across all other ones. No constant biological processes were identified for the moment, across the different primary cell cultures. Further comparisons will be certainly needed.

Conclusions

Understanding the epigenetic landscape of HGSC using physiologically relevant models will allow us to identify possible therapeutic targets that could eventually prevent platinum resistance.

Background

NOVA was a randomized Phase 3 trial assessing the efficacy of niraparib maintenance for patients (pts) with platinum-sensitive recurrent ovarian cancer (OC); overall survival (OS) was the secondary endpoint. The aim of this real-world (RW) study was to compare OS in BRCA wild-type (BRCAwt) pts with recurrent OC receiving second-line maintenance (2Lm) niraparib monotherapy or active surveillance (AS) to complement NOVA trial results.

Methods

This study used the US nationwide Flatiron Health de-identified electronic health record-derived database. Pts diagnosed with epithelial OC from 1 Jan 2011–31 May 2021 and completed 2L therapy from 1 Jan 2017–2 Mar 2022 were eligible for inclusion. Pts were assigned to niraparib 2Lm or AS cohorts according to their treatment scenario after end of 2L therapy (≤120 days). Follow-up was measured from index date (end of 2L non-maintenance therapy) until end of study (31 May 2022), last activity or death, whichever came first. A target trial emulation cloned inverse probability of censoring weighting (IPCW) methodology was selected a priori to minimize bias. IPCW median OS and hazard ratios (HR) for 2Lm vs AS were estimated with Kaplan-Meier curves and Cox regression models.

Results

Overall, 199 and 707 BRCAwt pts received niraparib 2Lm or were under AS, respectively. Most pt characteristics were similar across cohorts (Table). Median follow-up was 15.6 and 9.3 months, and median OS was 24.1 (95% confidence interval [CI]: 20.9, 29.5) and 18.4 (95% CI: 15.1, 22.8) months for niraparib 2Lm and AS cohorts, respectively (HR: 0.77 [95% CI: 0.66, 0.89]).

Table. Patient characteristics and follow-up before adjustment

HRp, HR proficient; NR, not reported

Conclusions

This RW study provides supportive evidence of niraparib's OS benefit in BRCAwt pts in the 2Lm setting. Homologous recombination deficiency (HRD) testing in the RW is limited and prevented examination of BRCAwt + HR deficient (HRd) subgroup.

Editorial acknowledgement

Editorial support provided by Claire Kelly, Fishawack Health, funded by GSK.

Background

Current guidelines suggest endometrial biopsy in women ³40 years old with abnormal uterine bleeding (AUB) as they are at greater risk of endometrial hyperplasia (EH) or cancer (EC). In women under 40 years old, there are no clear recommendations regarding endometrial biopsy. This should be carefully considered in younger women due to the associated risks that may affect fertility. We aim to study the profile of younger women with EH/EC in our population, to optimise endometrial biopsy in these high-risk patients.

Methods

This is an observational retrospective study that included women under 40 years old with AUB (according to the International Federation of Gynaecology and Obstetrics definition) who had endometrial biopsy in KK Women’s and Children’s Hospital Singapore in 2020. Institutional review board approval was not required for this study. Women with persistent intermenstrual bleeding > 3months or postcoital bleeding were also included. Women who had endometrial sampling on a known background of EH were excluded. Data on patient characteristics, ultrasound findings, histology and treatment were collected. Odds ratio (OR) for EH/EC as a measure of relative risk were computed.

Results

In 2020, 128 women under 40 years old underwent endometrial biopsy for AUB. The median age was 34 years old. 40.6% were nulliparous, 21.1% had polycystic ovarian syndrome, 5.5% had diabetes mellitus, and 49.2% had a BMI > 30. The median endometrial thickness was 10mm and 18.3% had cystic spaces reported on ultrasound. Majority of histology were benign (79.0%). 13.3% had EH without atypia, 2.3% had EH with atypia, and 1.6% had EC. 75% of women with EH were treated with oral progestogen and 10% had Mirena inserted. Nulliparity (OR 6.53, 95% confidence interval (CI) 1.96-21.78) and cystic spaces (OR 7.20, 95% CI 1.87-27.64) were associated with an increased likelihood of EH/EC in these women.

Conclusions

The risk of EH/EC in women <40 years old is low. Endometrial biopsy should be carefully considered in younger women with AUB, and reserved for those with risk factors.