Patient Reported Outcomes From CCTG CX.5 (SHAPE): Randomized Trial Comparing Radical Hysterectomy (RH) And Pelvic Node Dissection (PND) Vs Simple Hysterectomy (SH) And PND In Women With Low-Risk Early-Stag

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La grossesse chez les patientes dialysées (étude rétrospective à propos de 25 cas dans la région Nord-Pas-de-Calais)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Détection de l'envahissement ganglionnaire dans les cancers du col utérin

Le cancer du col de l'utérus occupe le second rang des cancers de la femme dans le monde. En France, son incidence se situe autour de 3500 nouveaux cas par an. Le principal facteur pronostic est l'atteinte ganglionnaire. Dix à 15% des patientes présentent une récidive alors que leurs ganglions étaient histologiquement indemnes. La détection de micrométastases ou de cellules tumorales isolées non diagnostiquée par l'examen anatomopathologique pourrait améliorer la connaissance de l'évolution tumorale. Les techniques de biologie moléculaire (RT-PCR) se sont révélées très sensibles pour mettre en évidence un envahissement ganglionnaire par des cellules tumorales, mais peu spécifiques. Nous avons testé différents marqueurs biologiques caractéristiques des cellules épithéliales (CK19, MUC1, HER 1-4), des cellules cancéreuses du col utérin (HVP16-E6) ou impliqués dans le cycle cellulaire (Cycline D1, p16, p21, p27), l'angiogénèse (VEGF et VEGF-C) et l'invasion (uPA et MMP9). Nous avons caractérisé l'expression de ces marqueurs sur des échantillons humains de cols sains, de tumeurs de col de l'utérus et de ganglions lombo-aortiques et scaléniques. CK19, HPV16-E6 et MUC1 ont des niveaux d'expression significativement plus élevés dans les ganglions histologiquement envahis par des cellules tumorales que dans les ganglions indemnes. L'étude concomitante de CK19 et HPV16-E6 permet de détecter la totalité des ganglions histologiquement atteint. D'autre part, ces biomarqueurs étaient exprimés dans 6% des ganglions histologiquement indemnes d'envahissement tumoral et pour lesquels une étude rétrospective en immunohistochimie a révélé la présence de cellules tumorales. L'utilisation de CK19 et HPV16-E6 en RT-PCR est fiable et plus sensible que les techniques histologiques classiques. Notre étude conduit à proposer l'utilisation de la RT-PCR pour diagnostiquer l'envahissement ganglionnaire dans le cancer du col de l'utérus.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Primary malignant melanoma of the vagina: A case report

Malignant primary melanoma of the vagina (PMV) is a rare type of non-cutaneous melanoma often discovered in postmenopausal women. PMV has a very aggressive disease course and a poor prognosis. The best course of treatment is not presently agreed upon. In this report, we describe the case of a 68-year-old woman presenting with a malignant PMV and its subsequent management. The patient presented with right vaginal pain, abnormal vaginal bleeding and a new vaginal mass. A PET scan identified a 28 × 38 mm hypermetabolic vaginal lesion, without nodal involvement or distant metastasis. A posterior exenteration type 2B was performed, including the anal mucosa. Sentinel lymph node dissection, vaginal and rectal resection as well as a terminal colostomy were also carried out. Final staging was FIGO stage III and T4bN1. Four months later, the patient presented with a recurrent vaginal bleed and intra-vaginal induration. Imaging revealed loco-reginal recurrence at the site of the primary malignancy with countless metastases. The patient opted for palliative care given the early disseminated recurrence and her multiple comorbidities. We review the treatment options for PMV, mainly the importance of surgery as the mainstay of treatment as well as the interest of adding checkpoint inhibitor immunotherapy or targeted therapy to the treatment plan. We also summarize the characteristics of PMV and its main prognostic factors

A Plain Language Summary of Results from the GARNET Study of Dostarlimab in Patients with Endometrial Cancer.

What is this summary about?: Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study What were the results? The results from the GARNET study published in 2022 showed how well dostarlimab worked for people participating in the study. Dostarlimab was found to reduce the size of tumors in patients with certain types of endometrial cancer. The patients treated with dostarlimab had side effects that could be managed and few severe side effects. What do the results mean?: The results of the GARNET study led to dostarlimab being approved to treat patients with certain types of endometrial cancer. For patients with advanced-stage endometrial cancer, or endometrial cancer that has come back after chemotherapy (recurrent), there are few treatment options. The results suggest that dostarlimab may provide long-term benefits for these patients. Clinical Trial Registration: NCT02715284 (ClinicalTrials.gov)

An International Randomized Phase III Trial Comparing Radical Hysterectomy and Pelvic Node Dissection (RH) vs Simple Hysterectomy and Pelvic Node Dissection (SH) in Patients with Low-Risk Early-Stage Cervical Cancer (LRESCC). A Gynecologic Cancer Intergroup Study led by Canadian Cancer Trials Group (CCTG CX.5-SHAPE).

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Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET—a phase I, single-arm study

International audienceBackground Dostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab. Methods GARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review. Results Screening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5–22.1) for cohort A1 and 11.5 months (IQR 11.0–25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1–2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab. Conclusion Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile. Trial registration number NCT02715284

Oncologic Outcomes of Surgically Treated Cervical Cancer with No Residual Disease on Hysterectomy Specimen: A 4C (Canadian Cervical Cancer Collaborative) Working Group Study

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan–Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted