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ObjectiveRetrospective series have shown minimally invasive secondary cytoreductive surgery is a feasible approach in selected cases of recurrent ovarian cancer. However, no predictors of minimally invasive secondary cytoreductive surgery feasibility are currently available. This study aims to identify predictive factors of minimally invasive secondary cytoreductive surgery feasibility and to compare perioperative and survival outcomes in a matched series of recurrent ovarian cancer patients who underwent secondary cytoreduction via an open or minimally invasive surgical approach.MethodsWe retrospectively identified all platinum-sensitive recurrent epithelial ovarian cancer patients who underwent minimally invasive or laparotomic secondary cytoreductive surgery between January 2013 and July 2020. Each patient underwent a preoperative positron emission tomography (PET) computerized tomography (CT) scan and diagnostic laparoscopy before secondary cytoreductive surgery. A 1:2 propensity score-matched analysis was performed to balance predictive factors of minimally invasive secondary cytoreductive surgery.ResultsOverall, 276 patients were identified (62 minimally invasive and 214 open), and a complete gross resection was achieved in 262 (94.9%) patients. At multivariate analysis, predictive factors for minimally invasive secondary cytoreductive surgery were neoadjuvant chemotherapy at first diagnosis (p=0.007), site of recurrence (p=0.031), and number of lesions (p=0.001). In the 1:2 propensity-matched population (39 minimally invasive and 78 open), complete gross resection was similar for both groups (p=0.082). Early post-operative complications were significantly higher in the laparotomy (33.3%) than in the minimally invasive surgery (10.3%) group (p=0.004). Only one (2.6%) patient experienced a grade >3 early post-operative complication in the minimally invasive surgery group compared with 13 (16.7%) patients in the open cohort (pConclusionsPatients with single or oligometastatic recurrences can be offered minimally invasive secondary cytoreductive surgery, mainly if localized in the lymph-nodes, and/or if they received neoadjuvant chemotherapy at primary diagnosis. Minimally invasive secondary cytoreductive surgery is associated with favorable perioperative outcomes with no differences in terms of post-recurrence survival with respect to open approach.

ObjectiveTo evaluate the role of different specific types of germline breast cancer susceptibilityBRCAmutations on the age of onset of high grade serous ovarian cancer.MethodsThis was a multicenter, international, retrospective cohort of 474 patients diagnosed with recurrent or newly diagnosed high grade serous ovarian cancer, with known germline mutations inBRCA1/2genes, treated between January 2011 and December 2020 in three academic centers in Europe. Patients were classified into four groups related to the type ofBRCA1/2genes mutation: frameshift, missense, nonsense, and splicing. Data from patients with splicing mutations were removed from the analysis because of the small numbers. The other three groups were compared.ResultsExcluding the 29 patients with a splicing mutation, 474 patients were enrolled: 309 (65.2%) with frameshift mutations, 102 (21.5%) with nonsense mutations, and 63 (13.3%) with missense mutations. TheBRCA1gene was affected in 324 (68.4%) cases, whileBRCA2was involved in 150 (31.6%) women (p=0.06). We found a difference of more than 5 years in the age of onset of high grade serous ovarian cancer betweenBRCA1andBRCA2patients (mean 53.3 years vs 58.4 years; p=0.001), with a mean age of 55.1 years. Patients with nonsense germline mutations had the youngest age of onset, while women with frameshift mutations had the oldest age of onset of high grade serous ovarian cancer (mean 52.2 years vs mean 55.9 years), both in theBRCA1andBRCA2subgroups. There was no statistically significant difference in age of onset between early and advanced groups (mean 55.8 years vs 55.0 years; p=0.55).ConclusionDifferent types of germlineBRCAmutations could determine different ages for onset of high grade serous ovarian cancer. If confirmed in larger series, this finding might have a clinical impact, potentially leading to a more tailored approach for risk reducing surgery for the prevention of high grade serous ovarian cancer.

ObjectivePoly (ADP-ribose) polymerase (PARP) inhibitor resistance is problematic in epithelial ovarian cancer management and sequencing strategies may be performed to overcome this issue. In this context, our study evaluated the role of non-platinum doublet pegylated liposomal doxorubicin/trabectedin in ovarian cancer platinum-sensitive patients who experienced disease progression under PARP inhibitor maintenance.MethodsThis case–control study includes patients with recurrent epithelial ovarian cancer treated between March 2016 and April 2021 who progressed under PARP inhibitor maintenance. Data of patients treated with pegylated liposomal doxorubicin/trabectedin (experimental group) were matched 1:1 with a series of patients who received platinum-based treatment (control group). The study outcomes were overall clinical benefit (including complete, partial, and stable response), progression-free survival, and overall survival. The safety of both treatments was also evaluated.ResultsA total of 26 patients in both groups were analyzed. Clinical benefit was achieved in 15 (57%) patients in the study group and 17 (65%) patients in the control group (p=0.38). Patients receiving pegylated liposomal doxorubicin/trabectedin had 5 months of progression-free survival, compared with 5 months in patients treated with platinum-based treatment (p=0.62). Patients in the experimental group achieved a median overall survival of 16 months compared with 19 months in the control group (p=0.26) There was no difference concerning severe toxicities (G3-G4) between groups, except for hepatic toxicity, which was experienced in 30% of the patients receiving pegylated liposomal doxorubicin/trabectedin and none in the control group (pConclusionsPegylated liposomal doxorubicin/trabectedin might be an alternative option to platinum-based treatment in patients experiencing disease progression during PARP inhibitor maintenance with an acceptable toxicity profile. This might be a therapeutic option in this setting, sparing platinum compounds for subsequent relapse.

Background Few studies analyzed the prognostic role of systemic inflammatory markers in early-stage ovarian cancer. The primary endpoint of the present study was to assess the prognostic impact of baseline inflammatory markers in early-stage ovarian cancer. The secondary endpoints were to compare the disease-free survival (DFS) of inflammatory markers with standard risk factors and to correlate these with BRCA mutational status. Methods Retrospective, single-center, observational study. Patients with FIGO-stage I–II and IIIA1 epithelial ovarian cancer undergoing primary surgery between 10/2012 and 12/2019 were included. Inflammatory markers were evaluated on the results of the complete blood count and coagulation tests, performed before ovarian cancer surgery. The Receiver Operating Characteristic curve was used to determine the optimal cut-off value of different baseline inflammatory biomarkers for the DFS analysis. Results Three hundred fifty-nine patients were included in the study period. Baseline neutrophil–lymphocyte ratio (NLR) ≥ 3 and systemic immune inflammation index (SII, defined as platelet x neutrophil–lymphocyte ratio) ≥ 1000 were associated with worse 3 year DFS and baseline SII ≥ 1000 was associated with worse 3 year OS. BRCA-mutated patients with SII ≥ 1000 and with NLR ≥ 3 had significantly worse DFS compared to SII I was the only independent risk factor for higher risk of recurrence. Conclusion SII ≥ 1000 and NLR ≥ 3 were associated with worse 3 year DFS and SII ≥ 1000 was associated with worse 3 year OS. The subgroups of BRCA-mutated patients with higher inflammation markers (SII ≥ 1000 and NLR ≥ 3) were associated with worse DFS. These findings might be helpful to design personalized treatment and more intensive surveillance.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

ObjectiveCurrently, there is no clear guidance defining the ideal candidate for minimally invasive interval debulking surgery. This study aimed to identify predictive factors for a minimally invasive approach in patients with advanced ovarian cancer who are candidates for interval debulking surgery after neoadjuvant chemotherapy.MethodsThis was a single institution retrospective study conducted between January 2014 and June 2020 Perioperative variables were used to predict the likelihood of minimally invasive interval debulking surgery using multivariable models. A nomogram was developed, and internal validation was performed using the bootstrapping correction technique. This nomogram was built to visualize the effect of perioperative variables on the estimated probability of minimally invasive interval debulking surgery in patients with a clinical response after neoadjuvant chemotherapy. We used the four significant perioperative variables according to logistic regression.ResultsA total of 108 (28.4%) and 272 (71.6%) patients underwent interval debulking surgery by a minimally invasive or open approach, respectively. Absence of omental cake (odds ratio (OR) 9.15, 95% confidence interval (CI) 4.26 to 19.64, pConclusionsOur nomogram may serve as a useful tool to choose the surgical approach in patients with advanced ovarian cancer undergoing interval debulking surgery.

ObjectiveCorrelation betweenBRCA1/2 (BRCA) pathogenic variants and the response to poly (ADP-ribose) polymerase inhibitors (PARPi) has been recognized in patients with ovarian cancer. Moreover, data on the clinical implications of variants of unknown significance are lacking. The aim of this study was to evaluate differences in survival outcomes in patients withBRCAvariants of unknown significance, mutated, and wild type relapsed ovarian cancer treated with PARPi.MethodsPatients with ovarian cancer whose somaticBRCAtesting was available and who were receiving PARPi as maintenance treatment at the first recurrence between January 2014 and January 2021 were included in the present study and analyzed. Patients were divided into three groups according toBRCAmutational status (variant of unknown significance, mutated, and wild type). Progression-free survival was assessed in each study group.ResultsOf 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients withBRCAmutation was significantly longer than for those with BRCA wild type or variant of unknown significance (not reached vs 4 months vs 7 months, respectively; pBRCAwild type andBRCAvariant of unknown significance (p=0.50).ConclusionOur study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients withBRCAwild type and shorter progression-free survival than women harboringBRCApathogenic variants.

Intensity modulated radiotherapy (IMRT) is the standard of care for oropharyngeal cancer management. IMRT can be applied using either the sequential boost or simultaneous integrated boost (SIB-IMRT) techniques. The purpose of the study was to assess the efficacy of sequential boost technique or SIB-IMRT) in locally advanced p16-negative oropharyngeal squamous cell carcinoma.Baseline characteristics and treatment outcomes were compared between patients with locally advanced p16-negative oropharyngeal squamous cell carcinoma, who received sequential RT (n=40) and those who received SIB-IMRT (n=38).In total, 78 patients with locally advanced p16-negative oropharyngeal cancer were identified. Mean age was 63 years. Patients treated with SIB-IMRT had better 5-year overall survival (OS; 78.7% vs. 52.5%, p=0.023) and 5-year disease-free survival (DFS; 87.4% versus 63.5%, p=0.046) compared to sequential group. There was no difference of total severe acute and late toxicity (grade ≥3) incidences. Patients treated with SIB technique had higher rates of mild to moderate late xerostomia (73.7% vs. 52.5%), dysgeusia (63.2% vs. 20%), and dysphagia (44.7% vs. 17.5%).Compared to sequential technique, SIB-IMRT improved both OS and DFS, but higher mild to moderate late toxicity was observed. As long as RT dose constraints to surrounding normal organs can be maintained, SIB technique should be the technique of choice for locally advanced p16-negative oropharyngeal squamous cell carcinoma treatment.

Laboratory-markers of the systemic inflammatory-response, such as neutrophil/lymphocyte-ratio (NLR) have been studied as prognostic factors in several tumors but in OC-patients their role is still controversial and no data about the possible correlation with the BRCA-status has been ever reported. We consecutively enrolled a series of 397 newly diagnosed high-grade serous-advanced OC-patients. All patients were tested for BRCA-mutational-status and blood-parameters have been collected 48 h before staging-surgery. A significant correlation of NLR with disease distribution (p 4 (BRCA-mutated: 35 vs 23 months, p = 0.03; BRCA-wt: 19 vs 16 months, p = 0.05). At multivariate-analysis, independent factors of prolonged PFS were BRCA mutational status, having received complete cytoreduction and NLR

Guidelines and expert consensus are lacking on fertility preservation in BRCA mutation carriers and in patients with Lynch syndrome. The safety of fertility preservation in this setting is still a topic of debate and multiple factors need to be carefully considered. The aim of this review was to analyze the reproductive potential of women harboring a genetic mutation affecting the DNA repair system and explore the efficacy and safety of existing fertility preservation strategies in these patients.

ObjectiveThe benefit of surgery and maintenance treatment with PARP inhibitors (PARPi) has been clearly demonstrated in ovarian cancer. Also, the efficacy and safety of stereotactic body radiotherapy has been shown in patients with metastatic, persistent, and recurrent disease. The aim of this study is to evaluate the management of oligometastatic progression during PARPi maintenance treatment.MethodsThis is an observational, retrospective, single-arm study conducted from June 2017 to December 2020 in patients with recurrent ovarian cancer with oligometastatic progression under PARPi maintenance treatment and receiving surgery or stereotactic body radiotherapy for such recurrence. PARPi treatment was continued until further progression of the disease. The primary objective of the study was the median prolongation of the treatment-free interval-p (without platinum) after local treatment.ResultsA total of 186 patients with ovarian cancer were treated with PARPi at recurrence. Of these, 30 (16%) developed oligometastatic progression. The median age was 49.5 years (range 35–73). Olaparib, niraparib and rucaparib were administered to 33%, 60%, and 7% of patients, respectively. The median prolongation of the treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy was 6 and 10 months, respectively (p=0.53). The median treatment-free interval-p of patients treated with surgery or stereotactic body radiotherapy at the time of oligometastatic progression was 32 and 29 months, respectively (p=0.44). At the time of this publication, 50% of patients are still on treatment with PARPi following progression.ConclusionsPatients with recurrent ovarian cancer who have oligometastic progression during PARPi maintenance may continue to benefit from PARPi if combined with local treatment.

Introduction: Pembrolizumab is an immune checkpoint inhibitor with high specificity for binding to the programmed cell death 1 (PD-1) receptor. It has been approved by the FDA in patients with recu...

Objective The aim of this study was to investigate the correlation between BRCA mutational status and response to bevacizumab in a large advanced ovarian cancer (AOC) series. Methods This is a multicenter, retrospective case-control study including upfront AOC treated between January 2015 and June 2019. The main inclusion criteria were: having received three weekly carboplatin-paclitaxel as first-line treatment, with or without Bevacizumab maintenance, knowledge of the BRCA mutational status. Results Overall, 441 patients were included; 183 (41.5%) patients received bevacizumab (Cases), and 258 (58.5%) did not receive it (Controls). The BRCA mutated patients (BRCAmut) were 58 (39%) in the Cases group and 90 (34.9%) in the Controls group (p = .77). Patients who received bevacizumab had a significant 4-months increase in median progression free survival (mPFS: 21 vs. 17 months, p = .033). Concerning BRCAmut patients, no differences were shown between those who received bevacizumab or not in terms of mPFS (24 vs. 22 months, p = .3). Conversely, in BRCA wild-type (BRCAwt) population bevacizumab administration significantly prolonged mPFS (20 vs 15 months, p = .019). At multivariate analysis, independent factors of prolonged PFS were BRCA status (OR = 0.60), having received PDS (OR = 0.69), and complete cytoreduction (OR = 0.50), but not the bevacizumab administration (OR = 0.83, p = .22). Conclusions No evidence of oncological benefit in terms of PFS and OS related to bevacizumab maintenance therapy was found in BRCAmut patients. Differently, BRCAwt patients seem to benefit from antiangiogenic treatment in terms of mPFS.

A single-institution prospective study was conducted to evaluate hearing loss rate after intensity modulated radiotherapy with concomitant cisplatin-based chemotherapy (CRT) for locally advanced head and neck cancer and identify cochlear dosimetric parameters associated with hearing loss risk.Hearing assessment, patients' characteristics, tumor-related variables, and cochlear quantitative dosimetric factors for adults with locally advanced head and neck cancer treated with CRT were prospectively collected. Each patient repeated audiometry at baseline (pre-CRT), 1 month after CRT, and then every 3 to 6 months. For each cochlea minimum dose (DBetween January 2016 and December 2018, 35 patients (70 cochleae) were included. Most patients (n=29; 82.9%) had primary cancer in a low-risk region (oral cavity, oropharynx, larynx). All patients completed the programmed CRT. During follow-up, significant hearing loss was recorded in 13 cases (37.1%). The ROC areas for significant hearing loss in relation to DD

Purpose: To evaluate the role of upper-neck irradiation versus standard whole-neck irradiation in patients with N0-1 nasopharyngeal carcinoma. Methods: We conducted a PRISMA guideline based systematic review and meta-analysis. Randomized clinical trials assessing upper-neck irradiation versus whole-neck irradiation with or without chemotherapy in non-metastatic N0-1 nasopharyngeal carcinoma patients were identified. The studies were searched on the PubMed, Embase and Cochrane library up to March 2022. Survival outcomes, including overall survival, distant metastasis-free survival and relapse-free survival, and toxicities rate were evaluated. Results: There were two randomized clinical trials with 747 samples finally included. Upper-neck irradiation had similar overall survival (hazard ratio = 0.69, 95% confidence interval = 0.37-1.30), distant metastasis-free survival (hazard ratio = 0.92, 95% confidence interval = 0.53-1.60) and relapse-free survival (risk ratio = 1.03, 95% confidence interval = 0.69-1.55) compared to whole-neck irradiation. No differences in both acute and late toxicities were recorded between upper-neck irradiation and whole-neck irradiation. Conclusion: This meta-analysis supports the potential role of upper-neck irradiation in this population of patients. Further research is needed to confirm results.

The aims of the present study were to assess the oncological outcomes of platinum-sensitive recurrent ovarian cancer patients undergoing secondary cytoreduction (SCS) after treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) at diagnosis and to compare the performance of different selection models in these patients.Retrospective, observational, single-center cohort study including patients with platinum-sensitive recurrent epithelial ovarian cancer with abdominal/inguinal/cardiophrenic disease between November 2012 and November 2020. Patients were selected as surgical candidates with PET/CT-scan and with diagnostic laparoscopy.272 patients were included in the study. Of these, 165 (60.7%) patients were treated with PDS at diagnosis and 107 (39.3%) with IDS. SCS was performed in 178 (65.4%) cases, with complete gross resection achieved in 155/178 (87.1%). No progression-free survival (PFS) difference was demonstrated when patients treated with PDS were compared with those treated with NACT+IDS at first diagnosis (median 21 versus 21 months; p = 0.684); no post-recurrence survival (PRS) difference was evident between the two groups (median 81 versus 77 months, respectively; p = 0.574). Current selection models to candidate patients to SCS adequately performed in patients treated with IDS at diagnosis, as well as in the PDS group, with combination of PET/CT-scan and laparoscopy being an accurate tool in prediction of no gross residual disease at SCS in this pre-selected population.Patients with platinum-sensitive recurrent epithelial ovarian cancer treated with NACT/IDS as primary treatment have similar post-recurrence survival outcomes of those treated with PDS. Current models to select patients for SCS can be safely applied to IDS patients.

To investigate the role of needleoscopic-assisted laparoscopy in terms of surgical impact and psychological outcomes in RR-BSO for BRCA1/2 patients.Prospective monocentric trial conducted at the Division of Gynecologic Oncology, "Fondazione Policlinico Universitario A. Gemelli" IRCSS in Rome. Between March 2016 and March 2018, 26 consecutive patients were prospectively enrolled in the study and underwent RR-BSO. Peri-operative surgical variables were collected. The psychological interview was performed at the discharge and during the first post-operative follow-up visit (between 30 and 60 days after surgery).We reported a median OT of 18.5 min (range, 15-37), a median EBL of 0 mL (0-20), and no conversion to laparoscopy or laparotomy. The median VAS score was "at rest" of 2, 3, and 1; while under "Valsalva maneuver" was 4, 3, 2, respectively at 2, 4, and 24 h. 77% (20/26) of the whole population had a previous diagnosis of breast cancer. All patients expressed great cosmetic satisfaction both at discharge and after 30/60 days, with an 84.6% of score 5 and a 15.4% of score 4. The highest number of "score 5", concerning the cosmetic outcomes, were clustered in the subgroup of breast cancer survivors with a 95% of score 5 versus 50% of score 5 in patients with no previous breast cancer (p = 0.0073). Similarly, the maximal psychological advantage of the ultra-MIS approach was revealed in the breast cancer survivors (70% of score 5 versus 16% of score 5, p = 0.02).The use of 2.4 mm instruments raises the possibility of decreasing post-operative incisional pain, reducing hospitalization, and ensuring better cosmetic and psychological outcomes without increasing complications. The full psychosomatic benefit of ultra-MIS within BRCA mutation carriers is revealed in breast cancer survivors, probably due to the comparison with the mutilating and invasive previous breast surgery.

International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO.Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected.A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed.Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.

Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status.In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis.A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 - 1.86, P = 0.54). Heterogeneity was significant (IAlthough no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.

ObjectiveTo evaluate a relation between BRCA1/2 status and the Chemotherapy Response Score in patients with epithelial ovarian cancer undergoing neoadjuvant chemotherapy and interval debulking surgery.MethodsData were retrospectively collected on patients with unresectable disease undergoing three or four cycles of neoadjuvant chemotherapy and interval debulking surgery at the Gynecologic Oncology Unit of the Catholic University of the Sacred Heart from January 2016 to December 2020. All patients were assessed for BRCA1/2 somatic mutation at diagnosis. The omental specimens obtained at the interval surgery were evaluated according to Bohm’s Chemotherapy Response Score System.ResultsA total of 172 patients were included in the analysis, 69 (40%) patients were BRCA1/2 mutation carriers and 103 (60%) patients were wild type. In the wild-type group (BRCAwt), 73 (70.9%) patients had a Chemotherapy Response Score of 1 or 2 and 30 (29.1%) patients had a score of 3. In the BRCA1/2 carriers group (BRCAmut), 39 (56.5%) patients had a score of 1 or 2 and 30 (43.5%) patients had a score of 3. Among the BRCAwt group, those with a Chemotherapy Response Score of 3 had a prolonged median progression-free survival (22 vs 15 months, p=0.003). Among the BRCAmut carriers group, no differences were found (30 vs 27 months, p=0.55). No difference in overall survival was observed in either the BRCAmut carriers population (p=0.23) or the BRCAwt population (60 vs 44 months, p=0.06).ConclusionsPatients with BRCA1/2mut seem to achieve a score of 1, 2 or 3 with the same frequency. In contrast, patients with BRCAwt seem to have a score of 1 or 2 more frequently than a score of 3. In patients with BRCA1/2mut, this score may not be an indicator of chemosensitivity.

ObjectiveBRCA1/2 (BRCA) genetic testing allows patients with high-grade serous ovarian cancer to receive appropriate medical management with molecular target therapy and prevention strategies. Most of theBRCAsequencing methods use blood as the primary source of germline DNA. Buccal swab emerged as an alternative collection device due to its convenient and non-invasive characteristics. This study assessed the suitability of buccal swabs as the DNA source in next-generation sequencing-basedBRCAgenotyping.MethodsMatched buccal swabs and blood samples were collected from 51 patients with high-grade serous ovarian cancer, including 29BRCA-mutated patients, from June to December 2021. Buccal swabs were self-collected using COPAN FLOQSwabs hDNA Free.BRCAgenes were amplified using Devyser’sBRCAnext-generation sequencing kit and sequenced on the Illumina MiSeq platform. We evaluated collection and extraction procedures, amplification and sequencing performances, coverage data, blood/swab variant calling concordance, and interpretation.ResultsComparable sequencing parameters were observed between the two sample types in term of mean total number of reads passing filter for indexed sample (p>0.05) and sequencing coverage distribution, with a widespread overlap of mean depth of coverage/target region between blood and swab samples. An overall concordance of 100% in both polymorphisms and pathogenic variants calling between the two DNA sources were observed, including the copy number variation prediction.ConclusionsData from this study support the use of buccal swabs as an alternative source of DNA forBRCAevaluation. The use of this alternative delivery mode ofBRCAtesting may facilitate access to care without compromising patient outcomes.