Pharmacogenomic predictor of long-term residual chemotherapy-induced peripheral neuropathy in ovarian cancer survivors: A substudy of the GINECO Vivrovaire study.

BACKGROUND: Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors. METHODS: Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated. RESULTS: 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176). CONCLUSIONS: Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.

Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial.

BACKGROUND: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. PATIENTS AND METHODS: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. RESULTS: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). CONCLUSIONS: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.

Breast Cancer Patients' Experience and Wishes Regarding Communication on Sexual Health: The BEROSE Study.

BEROSE is a single-center observational study, which aimed to determine the proportion of women with breast cancer who received information on sexual health from health professionals throughout their whole care pathway. A total of 318 women with all stages of breast cancer (30% metastatic) and at different time interval from diagnosis (up to 7 years) participated to the survey. Sixty-five percent of women reported that they had not received any information about sexual health over the whole care. Increased awareness among the healthcare professionals and particularly the oncology community is needed to discuss sexual health in women with breast cancer.

Oncologic results of fertility sparing surgery of cervical cancer: An updated systematic review.

BACKGROUND: Several techniques can be proposed as fertility sparing surgery in young patients treated for cervical cancer but uncertaincies remain concerning their outcomes. Analysis of oncological issues is then the first aim of this review in order to evaluate the best strategy. RESULTS: Data were identified from searches of MEDLINE, Current Contents, PubMed and from references in relevant articles from January 1987 to 15th of September 2021. We carry out an updated systematic review involving 5862 patients initially selected for fertility-sparing surgery in 275 series. FINDINGS: In patients having a stage IB1 disease, recurrence rate/RR in patients undergoing simple conisation/trachelectomy, radical trachelectomy/RT by laparoscopico-vaginal approach, laparotomic or laparoscopic approaches are respectively: 4.1%, 4.7%, 2.4% and 5.2%. In patients having a stage IB2 disease, RR after neoadjuvant chemotherapy or RT by laparotomy are respectively 13.2% and 4.8% (p = .0035). After neoadjuvant treatment a simple cone/trachelectomy was carried out in 91 (30%) patients and a radical one in 210 (70%) cases. But the lowest pregnancy rate is observed in patients undergoing RT by laparotomy (36%). CONCLUSIONS: The choice between these treatments should be based above all, on objective oncological data that strike a balance for each procedure between the best chances for cure and the fertility results. In patients having a stage IB1 disease, oncological results are quite similar according to the procedure used. In patients having a stage IB2 disease, RT by open approach has the lowest RR. Anyway the lowest pregnancy rate is observed in patients undergoing RT by laparotomy.

Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.

BACKGROUND: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population. RESULTS: A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy. CONCLUSIONS: In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.

Menopausal symptoms in epithelial ovarian cancer survivors: a GINECO VIVROVAIRE2 study.

OBJECTIVE: We have previously shown that epithelial ovarian cancer (EOC) and its treatments have negative effects on long-term quality of life (QoL) and fatigue. The present multicenter study investigated the main menopausal symptoms and gynecological management of EOC survivors (EOCS). METHODS: 166 patients with relapse-free ≥3 years after the end of treatment attended a consultation with a gynecologist, including a questionnaire related to vasomotor symptoms (VMS) and sexuality, a clinical examination, a blood sample and an osteodensitometry. QoL, fatigue, insomnia and mood disorders were measured with validated questionnaires and correlated to VMS. VMS and QoL were assessed according to natural menopause (NM) or surgical menopause (SM). RESULTS: Mean age at the survey was 62 [21-83] years and stage III/IV (48%). Mean delay since the end of treatment was 6 years. Fifty-nine patients (36%) had SM. Half of patients reported VMS. Seventy-two percent of EOCS with SM had VMS compared to 41% with NM (P < .001). VMS were not associated with poor global QoL, fatigue, insomnia or mood disorders. Two-thirds of EOCS reported a decrease in libido. Patients with SM showed a greater decrease in libido than NM (P < .02). Fourteen percent of them had osteoporosis and 50% osteopenia. Among the 85 patients with VMS, 80 did not receive HRT after cancer treatment. At the time of the survey, only 7 (4%) patients were receiving hormone replacement therapy (HRT). CONCLUSIONS: VMS and sexual disorders are frequently reported by EOCS, particularly among patients with SM. Most EOCS with menopausal symptoms could benefit from HRT to improve these symptoms.

Comprehensive analysis of patient outcome after local recurrence of locally advanced cervical cancer treated with concomitant chemoradiation and image-guided adaptive brachytherapy.

INTRODUCTION: Since dose escalation allowed by image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer (LACC), local relapses have become a rare event. Only scarce data are available on the outcome of patients experiencing a local relapse after IGABT. METHODS: Between 2004 and 2016, all consecutive patients treated at Gustave Roussy Institute for LACC and receiving concomitant chemoradiation and IGABT were analysed. Clinical and treatment-related prognostic factors for survival after local relapse were searched, in order to potentially identify patients requiring salvage treatment. RESULTS: Two hundred and fifty-nine patients were treated during this period. With a median follow-up of 4.1 years, 10.8% (n = 28) had a local relapse. Among these patients, 53.6% had synchronous lymph nodes or distant metastatic relapse and only 13 patients (5% of all patients) had isolated local relapse. After local relapse, median survival was 47 months and three patients were alive at last follow-up. Only three patients with local relapse could receive salvage surgery (10.7%). Metastases occurrence and pelvic wall involvement were the main contraindications (67.9%) for salvage surgery. Among the three patients treated with surgery, two are still alive at last follow-up without significant complication. Improved survival was observed among the two patients who could have surgery (p = .02). Local progression led to serious symptoms in 75% of patients. Only the time interval between brachytherapy and relapse (<1 year) was prognostic for 2-year overall survival (p = .005). CONCLUSION: Salvage surgery is feasible in a very low number of highly selected patients with local relapse following IGABT. Local failure is a major cause of severe local symptoms, confirming that every effort should be done to achieve long-term local control through dose escalation.

Implementation of image-guided brachytherapy as part of non-surgical treatment in inoperable endometrial cancer patients.

OBJECTIVE: This study assessed outcomes of inoperable endometrial cancer (IEC) patients treated with definitive external beam radiation therapy (EBRT) followed by a 3D image-guided brachytherapy boost. METHODS: All consecutive patients treated with EBRT followed by 3D image-guided brachytherapy for IEC were retrospectively included. EBRT delivered a dose of 45Gy. Then, patients had an uterovaginal brachytherapy guided by 3D imaging. Clinical target volume (CTVBT) included the whole uterus and the initial disease extent. Gross tumour volume (GTVres) included the residual disease at time of brachytherapy. RESULTS: Twenty-seven patients were identified. Causes of inoperability were comorbidities (37%) or tumour loco regional extent (63%). Including EBRT and brachytherapy, the median D90 (minimal dose delivered to 90% of the volume) was 60.7 GyEQD2 (IQR = 56.4-64.2) for the CTVBT, and was 73.6 GyEQD2 (IQR = 64.1-83.7) for the GTVres. The median overall treatment time was 50 days (IQR = 46-54). The mean follow-up was 36.5 months (SD = 30.2). The cumulative incidence of local, pelvic and distant failures was 19% (n = 5), 7% (n = 2) and 26% (n = 7), respectively. Five-year overall survival was 63% (95% CI = 43-91). Late urinary and gastro intestinal toxicities ≥ grade 2 were reported in four (15%) and two patients (7%) respectively. No vaginal toxicity ≥ grade 2 was reported. CONCLUSIONS: EBRT followed by intracavitary brachytherapy seems to be an effective option for IEC. The implementation of 3D concepts at time of brachytherapy may contribute to high local control probability and low toxicity profile. Large scale retrospective or prospective data are needed to confirm these early data.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.

The French national network dedicated to rare gynecological cancers diagnosis and management could improve the quality of surgery in daily practice of granulosa cell tumors. A TMRG and GINECO group Study.

OBJECTIVE: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs). METHODS: This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines. RESULTS: Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p < 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p < 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery. CONCLUSION: Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.

Long-term fatigue and quality of life among epithelial ovarian cancer survivors: a GINECO case/control VIVROVAIRE I study.

BACKGROUND: Few data are available on long-term fatigue (LTF) and quality of life (QoL) among epithelial ovarian cancer survivors (EOCS). In this case-control study, we compared LTF, symptoms and several QoL domains in EOCS relapse-free ≥3 years after first-line treatment and age-matched healthy women. PATIENTS AND METHODS: EOCS were recruited from 25 cooperative GINECO centers in France. Controls were randomly selected from the electoral rolls. All participants completed validated self-reported questionnaires: fatigue (FACIT-F), QoL (FACT-G/O), neurotoxicity (FACT-Ntx), anxiety/depression (HADS), sleep disturbance (ISI), and physical activity (IPAQ). Severe LTF (SLTF) was defined as a FACIT-F score <37/52. Univariate and multivariate logistic regressions were conducted to analyze SLTF and its influencing factors in EOCS. RESULTS: A total of 318 EOCS and 318 controls were included. EOCS were 63-year-old on average, with FIGO stage I/II (50%), III/IV (48%); 99% had received platinum and taxane chemotherapy, with an average 6-year follow-up. There were no differences between the two groups in socio-demographic characteristics and global QoL. EOCS had poorer FACIT-F scores (40 versus 45, P < 0.0001), lower functional well-being scores (18 versus 20, P = 0.0002), poorer FACT-O scores (31 versus 34 P < 0.0001), and poorer FACT-Ntx scores (35 versus 39, P < 0.0001). They also reported more SLTF (26% versus 13%, P = 0.0004), poorer sleep quality (63% versus 47%, P = 0.0003), and more depression (22% versus 13%, P = 0.01). Fewer than 20% of EOCS and controls exercised regularly. In multivariate analyses, EOCS with high levels of depression, neurotoxicity, and sleep disturbance had an increased risk of developing SLTF (P < 0.01). CONCLUSION: Compared with controls, EOCS presented similar QoL but persistent LTF, EOC-related symptoms, neurotoxicity, depression, and sleep disturbance. Depression, neuropathy, and sleep disturbance are the main conditions associated with severe LTF.

Early tumor regrowth is a contributor to impaired survival in patients with completely resected advanced ovarian cancer. An exploratory analysis of the Intergroup trial AGO-OVAR 12.

OBJECTIVE: Surgical assessment of residual tumor provides the strongest prognostic information in advanced ovarian cancer (AOC), with the best outcome observed after complete resection. Postoperative radiological assessment before initiation of chemotherapy can supplement the information obtained by surgical assessment; however, it may also reveal conflicting findings. METHODS: Patients with AOC enrolled in the AGO-OVAR 12 trial underwent baseline imaging before the first chemotherapy cycle. The findings from surgical and radiologic assessment for disease extend were compared. Additionally, an integrated approach was assessed. RESULTS: Complete data from all 3 assessment methods were available for 1345 patients. Of 689 patients with complete resection, tumor was observed in 28% and 22% of patients undergoing radiologic and integrated assessment, respectively. Patients with surgical- radiological and surgical-integrated concordant findings showed a 5-year overall survival (5Y-OS) of 72% and 71%, whereas patients with surgical-radiological and surgical-integrated discordant results showed inferior 5Y-OS of 47% and 49%, respectively. Patients with surgically assessed residual disease had a 5-YOS of 37%. The interval between surgery and baseline assessment was independently associated with discordance between assessment methods, which might reflect early tumor regrowth. CONCLUSIONS: Baseline tumor assessment before chemotherapy provides information that stratifies patients with complete resection into different prognostic groups. Integrating the data from different assessment methods might lead to improved definitions of prognostic groups. Further investigation to determine if earlier initiation of chemotherapy after debulking surgery could increase survival of patients with early tumor regrowth is warranted.

Localized high grade endometrial stromal sarcoma and localized undifferentiated uterine sarcoma: a retrospective series of the French Sarcoma Group.

OBJECTIVE: High grade endometrial stromal sarcoma and undifferentiated uterine sarcomas are associated with a very poor prognosis. Although large surgical resection is the standard of care, the optimal adjuvant strategy remains unclear. METHODS: A retrospective analysis of patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas (stages I-III) treated in 10 French Sarcoma Group centers was conducted. RESULTS: 39 patients with localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas treated from 2008 to 2016 were included. 24/39 patients (61.5%) were stage I at diagnosis. 38/39 patients underwent surgical resection, with total hysterectomy and bilateral oophorectomy completed in 26/38 (68%). Surgeries were mostly resection complete (R0, 23/38, 60%) and microscopically incomplete resection (R1, 6/38, 16%). 22 patients (58%) underwent postoperative radiotherapy (including brachytherapy in 11 cases), and 11 (29%) underwent adjuvant chemotherapy. After a median follow-up of 33 months (range 2.6-112), 17/39 patients were alive and 21/39 (54%) had relapsed (9 local relapses and 16 metastases). The 3 year and 5 year overall survival rates were 49.8% and 31.1%, respectively, and 3 year and 5 year disease free survival rates were 42.7% and 16.0%, respectively. Median overall survival and disease free survival were 32.7 (95% CI 16.3-49.1) and 23 (4.4-41.6) months, respectively. Medians were, respectively, 46.7 months and 39.0 months among those who underwent adjuvant radiotherapy and 41.0 months and 10.3 months for those who underwent adjuvant chemotherapy. In multivariate analysis, adjuvant radiotherapy was an independent prognostic factor for overall survival (P=0.012) and disease free survival (P=0.036). Chemotherapy, International Federation of Gynecology and Obstetrics I-II stages, and Eastern Cooperative Oncology Group-performance status 0 correlated with improved overall survival (P=0.034, P=0.002, P=0.006), and absence of vascular invasion (P=0.014) was associated with better disease free survival. CONCLUSIONS: The standard treatment of primary localized high grade endometrial stromal sarcoma and undifferentiated uterine sarcomas is total hysterectomy and bilateral oophorectomy. The current study shows that adjuvant radiotherapy and adjuvant chemotherapy appear to improve overall survival. A prospective large study is warranted to validate this therapeutic management.

Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC).

Background: Lymphocytic infiltration at diagnosis is prognostic in EOC, however, the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. Patients and methods: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2. A smaller number were available for PD-L1 evaluation, cut-off for positivity was ≥5% staining. Results: sTILs were detected in all tumours at diagnosis (range 2-90%, median 20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT samples (N = 83), an overall increase in median sTILs from 20% to 30% was seen following NACT (P = 0.0005); individually the impact of NACT varied with sTILs increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs were predictive of platinum-free interval (PFI), patients with PFI ≥6 months had significantly higher post-NACT sTILs (sTILs 28% versus 18% for PFI <6 months, P = 0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs, and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1-positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P = 0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell lines. On multivariate analysis, high sTILs both pre- and post-NACT were independent prognostic factors for progression-free survival (PFS) (HR 0.49, P = 0.02 and HR 0.60, P = 0.05, respectively). No prognostic impact of ieTILs or PD-L1 expression was detected. Conclusions: In EOC, sTILs levels are prognostic at diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase following NACT. Evaluation of immune parameters in the post-NACT tumour may help select patients for immunotherapy trials.

Networking for ovarian rare tumors: a significant breakthrough improving disease management.

BACKGROUND: Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. METHODS: Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. RESULTS: Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. CONCLUSION: Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research.

Fertility-sparing surgery in epithelial ovarian cancer: a systematic review of oncological issues.

Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in early-stage epithelial ovarian cancer (EOC) has been explored by several teams and is reconsidered in this systematic review undertaken using the PRISMA guidelines. Borderline ovarian tumours and non-EOCs were excluded. This review comprises 1150 patients and 139 relapsing patients reported by 21 teams. This conservative treatment can be safely carried out for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. Nevertheless, the number of patients reported with grade 2 disease is too small to definitively confirm whether FSS is safe in this subgroup. For patients with 'less favourable' prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be confirmed, but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome, because the poorest survival observed could be related to the natural history of the disease itself and not specifically to the use of conservative therapy. FSS could probably be considered in stage I clear-cell tumours but should remain contraindicated for stage II/III disease (whatever the histologic subtype). As the disease stage and the histologic data (tumour type and grade) are crucial to patient selection for this treatment, this implies careful and mandatory complete surgical staging surgery in this context and a pathological analysis (or review) of the tumour by an expert pathologist.

A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group.

BACKGROUND: There is no proven benefit of adjuvant treatment of uterine sarcoma (US). SARCGYN phase III study compared adjuvant polychemotherapy followed by pelvic radiotherapy (RT) (arm A) versus RT alone (arm B) conducted to detect an increase ≥ 20% of 3-year PFS. METHODS: Patients with FIGO stage ≤ III US, physiological age ≤ 65 years; chemotherapy: four cycles of doxorubicin 50 mg/m² d1, ifosfamide 3 g/m²/day d1-2, cisplatin 75 mg/m² d3, (API) + G-CSF q 3 weeks. Study was stopped because of lack of recruitment. RESULTS: Eighty-one patients were included: 39 in arm A and 42 in arm B; 52 stage I, 16 stage II, 13 stage III; 53 leiomyosarcomas, 9 undifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 patients): thrombopenia (76%), febrile neutropenia (22%) with two toxic deaths; renal gr 3 (1 patient). After a median follow-up of 4.3 years, 41/81 patients recurred, 15 in arm A, 26 in arm B. The 3 years DFS is 55% in arm A, 41% in arm B (P = 0.048). The 3-year overall survival (OS) is 81% in arm A and 69% in arm B (P = 0.41). CONCLUSION: API adjuvant CT statistically increases the 3 year-DFS of patients with US.

[Fertility preservation in cervical cancer, analysis of 30 years of practice and immersion in future developments]. / La préservation de fertilité en cas de cancer du col, analyse de 30 ans de pratique et immersion dans les évolutions à venir.

OBJECTIVES: The strategy of fertility preservation (FP) in cervical cancer has been challenged for several years and a therapeutic de-escalation seems to be necessary. In this context, we evaluated the oncological, fertility and obstetric outcomes of surgical techniques performed in our centre for FP. METHODS: This retrospective uni centric trial included 75 patients, managed at the Gustave Roussy Institute between 1995 and 2020, for cervical cancer (stage IB1 FIGO 2018) and having conducted a fertility preservation project after a complete pre-therapy work-up. The objective of this study was to understand our results on fertility and obstetrical outcomes and to correlate them with oncological data and finally to evaluate the evolution of our surgical practices. RESULTS: 54 patients benefited from an extended trachelectomy and no lymph node involvement was found. 1 patient received a complementary treatment postoperatively which did not allow to preserve her fertility. The recurrence rate was 4.8% (4/75) with one death described. 31 pregnancies were obtained, representing a pregnancy rate of 50%. 74% of pregnancies were obtained spontaneously and 60% of pregnancies were carried to term. CONCLUSION: Our results are similar to those in the literature. Despite a fertility preservation project, only half of the patients were able to achieve a pregnancy.