Response to first line platinum-based chemotherapy in mismatch repair deficient (MMRd)/ microsatellite instability high (MSI-high) endometrial carcinoma.

BACKGROUND: Around 15% of metastatic endometrial carcinoma (EC) are MMRd/MSI-H improving response to immune checkpoint inhibitors (ICI). So far, few data existed considering the chemotherapy (CT) sensitivity in MMRd/MSI-H EC, especially response to first-line platinum-based treatment. PATIENTS AND METHODS: We performed a multicentric retrospective analysis reporting the response to first line platinum CT in MMRd/MSI-H EC patients. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) with first line platinum-based CT. RESULTS: A total of 112 patients MMRd/MSI-H EC from 8 centers were identified. Median overall survival was 58.0 months (95% CI: 45.3-95.1). Among them, 78 patients received first line platinum CT in recurrent/metastatic setting. With a median follow up of 32.6 months (min: 0.03; max: 135.0), ORR and DCR (disease control rate) were 50% (95% CI: 38.5-61.5) and 68% (95% CI: 56.4-78.1), respectively. Median PFS and OS from first line platinum-based CT was 7.8 months (95% CI: 6.0-9.0) and 51.9 months (95% CI: 28.0-NE), respectively. Median PFS with ICI in second line (n = 48) was 10.7 months (95% CI: 3.4-NE) from ICI initiation. CONCLUSION: ORR in first line metastatic MMRd/MSI-H EC is consistent with efficacy in an all comer metastatic EC population.

Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial.

AIM: The oral anti-angiogenic therapy nintedanib prolongs progression-free survival (PFS) when combined with chemotherapy after primary surgery for advanced epithelial ovarian cancer. The randomized phase II CHIVA trial evaluated the impact of combining nintedanib with neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer. METHODS: Patients with newly diagnosed unresectable FIGO stage IIIC-IV epithelial ovarian cancer received 3-4 cycles of carboplatin plus paclitaxel every 3 weeks as NACT before interval debulking surgery (IDS), followed by 2-3 post-operative cycles. Patients were randomized 2:1 to receive either nintedanib 200 mg twice daily or placebo on days 2-21 every 3 weeks during NACT (omitting peri-operative cycles), and then as maintenance therapy for up to 2 years. The primary endpoint was PFS. RESULTS: Between January 2013 and May 2015, 188 patients were randomized (124 to nintedanib, 64 to placebo). PFS was significantly inferior with nintedanib (median 14.4 versus 16.8 months with placebo; hazard ratio 1.50, p = 0.02). Overall survival (OS) was also inferior (median 37.7 versus 44.1 months, respectively; hazard ratio 1.54, p = 0.054). Nintedanib was associated with increased toxicity (grade 3/4 adverse events: 92% versus 69%, predominantly hematologic and gastrointestinal), lower response rate by RECIST (35% versus 56% before IDS), and lower IDS feasibility (58% versus 77%) versus placebo. CONCLUSIONS: Adding nintedanib to chemotherapy and in maintenance as part of NACT for advanced epithelial ovarian cancer cannot be recommended as it increases toxicity and compromises chemotherapy efficacy (IDS, PFS, OS). CLINICALTRIALS: govregistration: NCT01583322.

Prognostic impact of cytoreductive surgery conducted with primary intent, versus cytoreductive surgery after neoadjuvant chemotherapy, in the management of patients with advanced epithelial ovarian cancers: a multicentre, propensity score-matched study from the FRANCOGYN group.

OBJECTIVE: To compare survival and morbidity rates between primary cytoreductive surgery (pCRS) and interval cytoreductive surgery (iCRS) for epithelial ovarian cancer (EOC), using a propensity score. DESIGN: We conducted a propensity score-matched cohort study, using data from the FRANCOGYN cohort. SETTING: Retrospective, multicentre study of data from patients followed in 15 French department specialized in the treatment of ovarian cancer. SAMPLE: Patients included were those with International Federation of Gynaecology and Obstetrics (FIGO) stage III or IV EOC, with peritoneal carcinomatosis, having undergone CRS. METHODS: The propensity score was designed using pre-therapeutic variables associated with both treatment allocation and overall survival (OS). MAIN OUTCOME MEASURES: The primary outcome was OS. Secondary outcomes included recurrence-free survival (RFS), quality of CRS and other variables related to surgical morbidity. RESULTS: A total of 513 patients were included. Among these, 334 could be matched, forming 167 pairs. No difference in OS was found (hazard ratio, HR = 0.8, p = 0.32). There was also no difference in RFS (median = 26 months in both groups) nor in the rate of CRS leaving no macroscopic residual disease (pCRS 85%, iCRS 81.4%, p = 0.76). The rates of gastrointestinal tract resections, stoma, postoperative complications and hospital stay were significantly higher in the pCRS group. CONCLUSIONS: Analysis of groups of patients made comparable by propensity score matching showed no difference in survival, but lower postoperative morbidity in patients treated with iCRS.

Discovery and validation of a transcriptional signature identifying homologous recombination-deficient breast, endometrial and ovarian cancers.

BACKGROUND: Molecular alterations leading to homologous recombination deficiency (HRD) are heterogeneous. We aimed to identify a transcriptional profile shared by endometrial (UCEC), breast (BRCA) and ovarian (OV) cancers with HRD. METHODS: Genes differentially expressed with HRD genomic score (continuous gHRD score) in UCEC/BRCA/OV were identified using edgeR, and used to train a RNAseq score (ridge-regression model) predictive of the gHRD score (PanCanAtlas, N = 1684 samples). The RNAseq score was applied in independent gynaecological datasets (CARPEM/CPTAC/SCAN/TCGA, N = 4038 samples). Validations used ROC curves, linear regressions and Pearson correlations. Overall survival (OS) analyses used Kaplan-Meier curves and Cox models. RESULTS: In total, 656 genes were commonly up/downregulated with gHRD score in UCEC/BRCA/OV. Upregulated genes were enriched for nuclear/chromatin/DNA-repair processes, while downregulated genes for cytoskeleton (gene ontologies). The RNAseq score correlated with gHRD score in independent gynaecological cancers (R² = 0.4-0.7, Pearson correlation = 0.64-0.86, all P < 10-11), and was predictive of gHRD score >42 (RNAseq HRD profile; AUC = 0.95/0.92/0.78 in UCEC/BRCA/OV). RNAseq HRD profile was associated (i) with better OS in platinum-treated advanced TP53-mutated-UCEC (P < 0.001) and OV (P = 0.013), and (ii) with poorer OS (P < 0.001) and higher benefit of adjuvant chemotherapy in Stage I-III BRCA (interaction test, P < 0.001). CONCLUSIONS: UCEC/BRCA/OV with HRD-associated genomic scars share a common transcriptional profile. RNAseq signatures might be relevant for identifying HRD-gynaecological cancers, for prognostication and for therapeutic decision.

Potential competing risk of death in older high-risk endometrial carcinoma patients: Results from a multicentric retrospective cohort.

INTRODUCTION: Adjuvant therapeutic decisions in older endometrial carcinoma (EC) patients are challenged by a balance between more frequent aggressive EC and comorbidities. We assessed whether EC and comorbidities are competing or cumulative risks in older EC patients. METHODS: All consecutive patients treated for FIGO stage I-IV EC in two University Hospitals in Paris between 2010 and 2017 were retrospectively included. Patients were categorized as: <70 years (y), >70y without comorbidity (fit), and > 70y with a Charlson comorbidity index>3 (comorbid). Association between high-risk EC (2021-ESGO-ETRO-ESP) or comorbidity, and disease-specific-survival (DSS), was evaluated using Cox model (estimation of cause-specific hazard ratio (CSHR), and Fine-Gray model (subdistribution HR) to account for competing events (death unrelated with EC). RESULTS: Overall, 253 patients were included (median age = 67y, IQR[59-77], median follow-up = 61.5 months, [44.4-76.8]). Among them, 109 (43%) were categorized at high-risk (proportion independent of age), including 67 (26%) who had TP53-mutated tumors. Comorbidity and high-risk group were both associated with all-cause mortality (HR = 4.09, 95%CI[2.29; 7.32] and HR = 3.21, 95%CI [1.69; 6.09], respectively). By multivariate analysis, patients with high-risk EC exhibited poorer DSS, regardless of age/comorbidity (Adjusted-CSHR = 6.62, 95%CI[2.53;17.3]; adjusted-SHR = 6.62 95%CI[2.50;17.5]). Patients>70y-comorbid with high-risk EC had 5-years cumulative incidences of EC-related and EC-unrelated death of 29% and 19%, respectively. In patients <70y, 5-years cumulative incidence of EC-related and EC-unrelated death were 25% and < 1% (one event), respectively. CONCLUSION: High-risk EC patients are exposed to poorer DSS regardless of age/comorbidities, comorbidities and cancer being two cumulative rather than competing risks. Our results suggest that age/comorbidity alone should not lead to underestimate EC-specific survival.

Development and validation of a RNAseq signature for prognostic stratification in endometrial cancer.

BACKGROUND: Despite recent advances in endometrial carcinoma (EC) molecular characterization, its prognostication remains challenging. We aimed to assess whether RNAseq could stratify EC patient prognosis beyond current classification systems. METHODS: A prognostic signature was identified using a LASSO-penalized Cox model trained on TCGA (N = 543 patients). A clinically applicable polyA-RNAseq-based work-flow was developed for validation of the signature in a cohort of stage I-IV patients treated in two Hospitals [2010-2017]. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated by multivariable Cox model, adjusted on high-risk prognostic group (2021 ESGO-ESTRO-ESP guidelines: non-endometrioid histology or stage III-IVA orTP53-mutated molecular subgroup). RESULTS: Among 209 patients included in the external validation cohort, 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC = 0.80). Most disease-related deaths occurred in high-risk patients (5-years DSS = 78% (95% CI = [68%-89%]) versus 99% [97%-100%] in patients without high-risk). A composite classifier accounting for the TP53-mutated subgroup and the RNAseq signature identified three classes independently associated with DSS: RNAseq-good prognosis (reference, 5-years DSS = 99%), non-TP53 tumors but with RNAseq-poor prognosis (adjusted-hazard ratio (aHR) = 5.75, 95% CI[1.14-29.0]), and TP53-mutated subgroup (aHR = 5.64 [1.12-28.3]). The model accounting for the high-risk group and the composite classifier predicted DSS with AUC = 0.84, versus AUC = 0.76 without (p = 0.01). CONCLUSION: RNA-seq profiling can provide an additional prognostic information to established classification systems, and warrants validation for potential RNAseq-based therapeutic strategies in EC.

What can we learn from the 10 mm lymph node size cut-off on the CT in advanced ovarian cancer at the time of interval debulking surgery?

INTRODUCTION: The benefit of a systematic lymphadenectomy is still debated in patients undergoing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in ovarian cancer (OC). The objective of this study was to evaluate the predictive value of the pre-NACT and post-NACT CT in predicting definitive histological lymph node involvement. The prognostic value of a positive node on the CT was also assessed. MATERIEL AND METHODS: A retrospective, unicentric cohort study was performed including all patients with ovarian cancer who underwent NACT and IDS with a lymphadenectomy between 2005 and 2018. CT were analyzed blinded to pathology, and nodes with small axis ≥ 10 mm on CT were considered positive. Sensitivity (Se), specificity (Sp), and negative (NPV) and positive predictive values (PPV) and their CI95% were calculated. The 2-year recurrence free survival (RFS) and 5-year overall survival (OS) was compared. RESULTS: 158 patients were included, among which 92 (58%) had histologically positive lymph nodes. CT had a Se, Sp, NPV and PPV of 35%, 82%, 47% and 73% before NACT and 20%, 97%, 47% and 91% after NACT, respectively. Patients with nodes considered positive had a non-significant lower 2-year RFS and 5-year OS on the pre-NACT and post-NACT CT. Patients at 'high risk' (nodes stayed positive on the CT or became positive after NACT) also had a non-significant lower 2-year RFS and 5-year OS. CONCLUSION: Presence of enlarged lymph nodes on CT is a weak indicator of lymph node involvement in patients with advanced ovarian cancer undergoing NACT. However, it could be used to assess prognosis.

Cabazitaxel schedules in metastatic castration-resistant prostate cancer: a review.

Cabazitaxel (25 mg/m2 every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules. Based on this review, the use of prophylactic granulocyte colony-stimulating factor from cycle 1 appears crucial to maximize the benefit-risk ratio of cabazitaxel in metastatic castration-resistant prostate cancer. Preliminary data with alternative schedules look promising, especially for frail patients. Results of the ongoing Phase III CABASTY trial (ClinicalTrials.gov: NCT02961257) are awaited.

Pharmaceutical consultation to detect drug interactions in patients treated with oral chemotherapies: A descriptive cross-sectional study.

OBJECTIVE: The development of oral chemotherapy (OC) has led to the recent establishment of multidisciplinary programmes involving pharmacists. We evaluated the utility of our local programme for detecting potential interactions with OCs, particularly drug-drug interactions (DDIs) and herbal-drug interactions (HDIs). METHODS: We performed a single-centre retrospective descriptive study of patients on OC attending a pharmaceutical consultation (PC) during a seven-month period. These consultations included the use of various complementary tools/databases to search for interactions. RESULTS: We analysed 308 treatments taken by 42 consecutive patients. Fifty-four potential interactions with OCs were detected in 26% (n = 79) of the treatments taken by patients: 46 DDIs (32 minor, 12 major, 2 contraindicated) and eight HDIs. Five interventions associated with interactions were suggested by pharmacists during the consultations (4 were taken into account by oncologists). The total mean time spent on each PC for an individual patient was 80 minutes (36 minutes of preparation, 44 minutes with the patient). CONCLUSION: This pilot study highlights the importance of studying interactions in such patients, and of the expertise of pharmacists for detecting interactions, which were found in more than one in four treatment lines. The further development of such activities, which already take up considerable amounts of time, is therefore warranted.

[Hereditary breast and ovarian cancer syndrome: Diagnosis and therapeutic implications]. / Syndrome héréditaire de prédisposition au cancer du sein et de l'ovaire : diagnostic et implications thérapeutiques.

Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification. BRCA1/2 carriers have to be followed up regularly and may justify breast and/or adnexal prophylactic surgery, according to the French National Cancer Institute guidelines (INCa). Poly- (DNA-riboses) polymerases inhibitors, notably olaparib, have a major role in the management of epithelial ovarian cancer in patients with BRCA mutation and many studies are ongoing to expand their indications in a near future.

The impact of the Paris terrorist attacks on the mental health of resident physicians.

BACKGROUND: On November 13, 2015, terrorist attacks took place in Paris. One hundred and twenty-nine people were immediately killed and 302 needed emergency care. Many resident physicians were on the front line of the medical response. Our aim was to report the frequency of symptoms of post-traumatic stress disorder (PTSD), anxiety and depression among resident physicians after the Paris terrorist attacks. METHODS: Anonymous questionnaires, including the Impact of Event Scale- Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS), were emailed two months after the attacks to 2413 Parisian resident physicians. Exposure to the attacks was defined as having direct clinical contact with one of the victims up to one week after the attacks, being one of the victims, or having one among close relatives. RESULTS: The questionnaire was completed by 680 (28.2%) residents. Eighty-four (12.4%) reported symptoms of PTSD (IES-R ≥ 33), 76 (11.2%) reported symptoms of anxiety (HADS anxiety score > 10) and 16 (2.4%) reported symptoms of depression (HADS depression score > 10). Exposed residents had higher IES-R scores than non-exposed residents (18.8 ± 16.6 versus 14.2 ± 12.0, p = 0.001), and 40 (18.5%) of them reported symptoms of PTSD, compared to 44 (9.5%) of the non-exposed residents (p = 0.001). CONCLUSIONS: There was a high frequency of symptoms of mental distress among our respondents. Dedicated screening and care strategies must be considered in the event of new attacks.

Bleomycin-Induced Pneumonitis in the Treatment of Ovarian Sex Cord-Stromal Tumors: A Systematic Review and Meta-analysis.

OBJECTIVE: Adult ovarian sex cord-stromal tumors (SCSTs) are a rare histological subtype of ovarian cancer associated with a favorable prognosis. Bleomycin-containing regimens are standards of care, although pneumonitis may cause potentially fatal dose-limiting toxicity. We aimed to evaluate the safety of bleomycin in SCST treatment. METHODS: We performed a systematic literature review of all studies of bleomycin therapy for SCSTs that were referenced in MEDLINE (PubMed), EMBASE, and Cochrane Central Register of Controlled Trials and published from 1986 to 2014. RESULTS: Eight studies totaling 221 patients were included. Rates of pneumonitis (7.7%; 95% confidence interval, 4.2-11.2) and mortality (1.8%; 95% confidence interval, 0.1-3.6) related to bleomycin were significant. However, these results were very similar to those reported for men who were treated with bleomycin for a male germ cell tumor, suggesting that women with ovarian SCSTs are not particularly vulnerable to bleomycin lung toxicity. The main risk factors of bleomycin-induced pneumonitis are high cumulative bleomycin dose (>400 U or mg), age older than 40 years, and impaired renal function. Whether granulocyte colony-stimulating factor is a risk factor remains controversial. CONCLUSIONS: Bleomycin-induced pneumonitis frequently occurs in patients with SCSTs and lacks effective treatment. Prevention lies in limiting cumulative bleomycin dose, monitoring pulmonary function during treatment, discontinuing bleomycin at the onset of pulmonary symptoms or if pulmonary function is impaired, and avoiding bleomycin in older patients.

Taxanes Versus Androgen Receptor Therapy as Second-Line Treatment for Castrate-Resistant Metastatic Prostate Cancer After First-Line Androgen Receptor Therapy.

BACKGROUND: The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer (mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line ART. PATIENTS AND METHODS: This retrospective study included all consecutive chemo-naive mCRPC patients who have received first-line ART treatment. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with second-line ART or TAX. RESULTS: Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone (ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received second-line TAX and ART, respectively, while 76 (43%) patients did not receive further treatment. From the start of first-line therapy, the median PFS and OS were 13 months (95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant difference between ENZA and ABI. From the start of second-line therapy, the median PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively. Compared with ART, docetaxel was associated with significantly higher prostate-specific antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95% CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months, P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART. CONCLUSION: In the second-line setting, TAX provides higher PSA and radiological responses than does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar. This study provides new elements to help deciding the best treatment sequence.

Real-world dostarlimab use in advanced/recurrent endometrial cancer in France.

INTRODUCTION: In October 2020, the French Health Authority granted early access outside of the clinical trial setting for dostarlimab, a programmed death-1 inhibitor. Dostarlimab was approved by the European Medicines Agency (in April 2021) as monotherapy for patients with post-platinum mismatch repair deficient/microsatellite instability-high advanced/recurrent endometrial cancer, based on the results of the GARNET trial (NCT02715284). METHODS: This was a real-world descriptive analysis of patients granted cohort temporary authorization of use to receive dostarlimab between November 2020 and June 2021. Physicians could complete follow-up forms at each treatment cycle to provide clinical information, safety, and efficacy data. Safety and disease progression data were also captured through pharmacovigilance reports. RESULTS: Of 95 temporary authorization of use requests made by 80 oncologists in 59 French hospitals, 87 patients were eligible, and 80 received≥1 dose of dostarlimab. Based on treatment response assessments received (n=43), the mean (standard deviation) time from treatment initiation to response evaluation was 11 (6) weeks. The disease control rate (complete plus partial responses plus stable disease rates) was 56% (n=24/43), and the overall response rate was 35% (n=15/43); both consistent with those reported in the GARNET trial. No new safety signals were reported. DISCUSSION: The enrolment of 80 patients in an 8-month period highlights the need for access to novel treatment regimens in France for these patients post-platinum. Prospective randomized studies are ongoing to assess the efficacy and safety of dostarlimab and other checkpoint inhibitors as first-line treatment in patients with endometrial cancer.

Patterns of recurrence in surgically treated women for TP53-mutated endometrial carcinomas.

OBJECTIVE: To describe the patterns of recurrence and the prognosis of patients with a recurrent TP53 mutated endometrial carcinoma treated initially by surgery. METHODS: All patients with endometrial carcinoma, treated at hospital European Georges Pompidou between 2001 and 2021 were retrospectively included. Patients were separated into two groups: TP53-mutated and not TP53-mutated (POLE/ultramutated-like (POLEmut), dMMR (mismatch repair-deficient) and NSMP (No specific molecular profile)). We estimated survival using recurrence free survival, overall survival and overall survival from recurrence. The risk of recurrence according to TP53 status and the type of recurrence (locoregional recurrence, peritoneal recurrence, and metastasis) were also compared between the two groups. RESULTS: Two hundred and ninety-one patients with endometrial carcinoma were included. Of these, 57 were TP53-mutated and 234 patients were not TP53-mutated. TP53 mutated patients had the worst recurrence free survival and overall survival (p < 0.001 for each). The hazard rate of recurrence was higher during the first three years for TP53 mutated endometrial carcinoma then tend to join the one of no TP53 mutated. There was a statistical difference between the two groups in terms of cumulative incidence of peritoneal recurrence (p = 0.002). There was, however, no statistical difference in overall survival from recurrence. CONCLUSIONS: TP53-mutated endometrial carcinoma were more likely to experience a recurrence during the first three years and most often peritoneal recurrence compared to not TP53-mutated. TP53 status in endometrial carcinoma could be useful to define follow-up. Further prospective studies are required to assess the predictive impact of TP53 mutation on chemotherapy benefit.

A Suggested Modification to FIGO Stage IV Epithelial Ovarian Cancer.

International Federation of Gynecology and Obstetrics (FIGO) staging classification for stage IV epithelial ovarian cancer (EOC) separates stages IVA (pleural effusion) and IVB (parenchymal and/or extra-abdominal lymph node metastases). We aimed to evaluate its prognostic impact and to compare survival according to the initial metastatic location. We conducted a multicenter study between 2000 and 2020, including patients with a FIGO stage IV EOC. Primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and recurrence rates. We included 307 patients: 98 (32%) had FIGO stage IVA and 209 (68%) had FIGO stage IVB. The median OS and PFS of stage IVA patients were significantly lower than those of stage IVB patients (31 versus 45 months (p = 0.02) and 18 versus 25 months (p = 0.01), respectively). Recurrence rate was higher in stage IVA than IVB patients (65% versus 47% (p = 0.004)). Initial pleural involvement was a poor prognostic factor with a median OS of 35 months versus 49 months for patients without initial pleural involvement (p = 0.024). Patients with FIGO stage IVA had a worse prognosis than patients with FIGO stage IVB EOC. Pleural involvement appears to be relevant for predicting survival. We suggest a modification of the current FIGO staging classification.

Identifying homogeneous healthcare use profiles and treatment sequences by combining sequence pattern mining with care trajectory clustering in kidney cancer patients on oral anticancer drugs: A case study.

OBJECTIVE: We evaluated the ability of a coupled pattern-mining and clustering method to identify homogeneous groups of subjects in terms of healthcare resource use, prognosis and treatment sequences, in renal cancer patients beginning oral anticancer treatment. METHODS: Data were retrieved from the permanent sample of the French medico-administrative database. We applied the CP-SPAM algorithm for pattern mining to healthcare use sequences, followed by hierarchical clustering on principal components (HCPC). RESULTS AND CONCLUSION: We identified 127 individuals with renal cancer with a first reimbursement of an oral anticancer drug between 2010 and 2017. Clustering identified three groups of subjects, and discrimination between these groups was good. These clusters differed significantly in terms of mortality at six and 12 months, and medical follow-up profile (predominantly outpatient or inpatient care, biological monitoring, reimbursement of supportive care drugs). This case study highlights the potential utility of applying sequence-mining algorithms to a large range of healthcare reimbursement data, to identify groups of subjects homogeneous in terms of their care pathways and medical behaviors.

Risks and benefits of systematic lymphadenectomy during interval debulking surgery for advanced high grade serous ovarian cancer.

BACKGROUND: Lymphadenectomy is debated in patients with ovarian cancer. The aim of our study was to evaluate the impact of lymphadenectomy in patients with high-grade serous ovarian cancer receiving neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). METHODS: A retrospective, unicentric study including all patients undergoing NACT and IDS was carried out from 2005 to 2018. Patients with and without lymphadenectomy were compared in terms of recurrence free survival (RFS), overall survival (OS), and complication rates. RESULTS: We included 203 patients. Of these, 133 had a lymphadenectomy (65.5%) and 77 had involved nodes (57.9%). Patients without a lymphadenectomy were older, had a more extensive disease and less complete CRS. No differences were noted between the lymphadenectomy and no lymphadenectomy group concerning 2-year RFS (47.4% and 48.6%, p = 0.87, respectively) and 5-year OS (63.2% versus 58.6%, p = 0.41, respectively). Post-operative complications tended to be more frequent in the lymphadenectomy group (18.57% versus 31.58%, p = 0.09). In patients with a lymphadenectomy, survival was significantly altered if the nodes were involved (positive nodes: 2-year RFS 42.5% and 5-year OS 49.4%, negative nodes: 2-year RFS 60.7% and 5-year OS 82.2%, p = 0.03 and p < 0.001, respectively). CONCLUSION: Lymphadenectomy during IDS does not improve survival and increases post-operative complications.

[Place of PARP inhibitors in the treatment of endometrial and cervical cancers]. / Place des inhibiteurs de PARP dans le traitement des cancers de l'endomètre et du col de l'utérus.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.