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 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.
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.
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.
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.
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.
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).
API adjuvant CT statistically increases the 3 year-DFS of patients with US.
Évaluer l’évolution des cancers du col utérin avec atteinte ganglionnaire diagnostiquées à la tomographie par émission de positons au (18F)-fluoro-désoxy-glucose (TEP-FDG) et traités à visée ...curative.
Les dossiers des patientes atteintes d’un carcinome du col utérin avec atteinte ganglionnaire à la TEP-FDG pelvienne et/ou lomboaortique, qui ont reçu un traitement à visée curative entre 2003 et 2007, ont été rétrospectivement étudiés. Le traitement a consisté en une radiothérapie pelvienne (éventuellement lomboaortique) associée à une chimiothérapie concomitante, puis d’une curiethérapie utérovaginale, puis éventuellement une chirurgie. La rechute initiale a été classée en fonction de la topographie comme locale (centropelvienne), ganglionnaire régionale (pelvienne ou lomboaortique) ou métastatique.
Quarante patientes ont été incluses dans cette étude. L’âge médian était de 47ans (28–78). Trente atteintes ganglionnaires étaient uniquement pelviennes et dix étaient lomboaortiques. Le suivi médian était de 42,5 mois (11–85). Il y a eu 22 rechutes et 21 décès, 20 secondaires à une rechute, un imputable à une toxicité iatrogénique tardive. La probabilité de survie à troisans était de 50 % (intervalle de confiance à 95 % IC : 36–65). La rechute initiale était métastatique chez 33 % des patientes (13/40), locale chez 20 % (8/40) et ganglionnaire isolée chez 5 % (2/40). En analyse multifactorielle, seul le stade selon la Fédération internationale de gynécologie-obstétrique (Figo) et l’atteinte lomboaortique avaient un impact significatif sur la survie globale. La survie à troisans sans et avec atteinte lomboaortique était respectivement de 58 % (IC : 39–74) et de 24 % (IC : 7–57) (p=0,009).
L’atteinte lomboaortique sur la TEP-FDG est un facteur pronostique indépendant de survie globale. Le contrôle tumoral local centropelvien ne doit pas être négligé : la curiethérapie reste donc primordiale. Les rechutes ganglionnaires isolées sont peu fréquentes.
To assess the outcome of cervical carcinoma with positive nodes on fluorodesoxyglucose positon emission tomography scans (FDG-PET).
Patients with cervical carcinoma who had pelvic and/or para-aortic lymph nodes involvement by FDG-PET and treated with a curative intent from 2003 to 2007 were retrospectively studied. All patients received pelvic (and possibly para-aortic) radiotherapy with chemotherapy, followed by brachytherapy, and possibly surgery. The first site of relapse was classified as follows: local, nodal (pelvic or para-aortic) or metastatic.
Forty patients were included the study. Median age was 47 years (range: 28–78). Thirty patients had nodal involvement limited to pelvic area and ten had a para-aortic involvement. Median follow-up was 42.5 months (range: 11–85). There were 22 relapses and 20 deaths: 20 due to relapse and one due to late toxicity. Three-year survival is 50 % (95 % confidence interval CI: 36–65). First relapse was: metastatic for 33 % (13/40), local for 20 % (8/40) and isolated nodal for 5 % (2/40). Multivariate analysis has revealed that only staging according to International Federation of Gynecology and Obstetrics (FIGO) and para-aortic involvement had a significant impact on survival. Three-year survival was 58 % (CI: 39–74) and 24 % (CI: 7–57) (P=0.009) in patient without and with para-aortic involvement, respectively.
Para-aortic involvement by FDG-PET is a significant prognostic factor for overall survival. Local control at primary site remains of paramount importance for patient with nodal involvement. Isolated nodal failures are scarce.
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 ≥3years after first-line treatment and age-matched healthy women.
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.
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).
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.
Infectious complications of parietal mesh after prosthetic abdominal wall repair are rare. Their management is complex. Furthermore, the emergence of bacterial resistance, the presence of a foreign ...material, the need to continue an extended antibiotic therapy, and the choice of an appropriate treatment are crucial. The objective of this study is to access the microbiological epidemiology of infected parietal meshes in order to optimize the empirical antibiotic therapy.
Between January 2016 and December 2021, a monocentric and retrospective study was performed in patients hospitalized for infected parietal meshes at Avicenne hospital, in Paris area. Clinical and microbiological data such as antibiotic susceptibility were collected.
Twenty-six patients with infected parietal meshes have been hospitalized during this period. Meshes were in preaponevrotic positions (n=10; 38%), retromuscular (n=6; 23%) and intraperitoneal (n=10; 38%). Among the 22 (84.6%) documented cases of infections, 17 (77.3%) were polymicrobial. A total of 54 bacteria were isolated, 48 of which had an antibiogram available. The most frequently isolated bacteria were: Enterobacterales (n=19), Enterococcus spp. (n=11) and Staphylococcus aureus (n=6), whereas anaerobes were poorly isolated (n=3). Concerning these isolated bacteria, amoxicillin-clavulanic acid, metronidazole-associated cefotaxime, piperacillin-tazobactam and meropenem were susceptible in 45.5%, 68.2%, 63.6%, 77.2%, of cases, respectively.
This work highlights that infections of abdominal parietal meshes may be polymicrobial and the association amoxicillin-clavulanic acid cannot be used as a probabilist antibiotic therapy because of the high resistance rate in isolated bacteria. The association piperacillin-tazobactam appears to be a more adapted empirical treatment to preserve carbapenems, a broad-spectrum antibiotic class.
Ovarian yolk sac tumor (YST) is a very rare malignancy arising in young women. Chemotherapy has dramatically improved the prognosis. Current treatment consists of surgery followed by bleomycin, ...etoposide, and cisplatin (BEP) chemotherapy. However, given the rarity of this tumor, ovarian YST-specific survival and outcome after such treatment are not precisely known.
This report concerns prospectively recorded cases that were either treated at Institut Gustave Roussy (Villejuif, France) or referred there for advice about therapy. From 1990 to 2006, 52 patients underwent surgery followed by BEP chemotherapy. Data on patient characteristics, treatment, survival, and fertility outcome were analyzed to assess treatment efficacy and gonadal toxicity after achieving a complete remission.
Thirty-five patients had stage I/II tumors while 17 patients presented with stage III/IV disease. With a median follow-up of 68 months, the overall 5-year survival and disease-free survival rates were 94% and 90%, respectively. Forty-one women underwent fertility-sparing surgery. Pregnancy was achieved in 12 of 16 (75%) women who attempted conception. Overall, 19 pregnancies have been recorded.
BEP chemotherapy following fertility-sparing surgery is a very effective treatment of ovarian YSTs. Most of the patients who attempt conception after complete remission will have children.
Based on registries, the European experience has been that <50% of patients are treated according to protocols and/or benefit from the minimum required surgery for ovarian cancer. The French Cancer ...Plan 2009–2013 considers the definition of qualitative indicators in ovarian cancer surgery in France. This endeavour was undertaken by the French Society of Gynaecologic Oncology (SFOG) in partnership with the French National College of Obstetricians and Gynecologists and all concerned learned societies in a multidisciplinary mindset.
The quality indicators for the initial management of patients with ovarian cancer were based on the standards of practice determined from scientific evidence or expert consensus.
The indicators were divided into structural indicators, including material (equipment), human (number and qualification of staff), and organizational resources, process indicators, and outcome indicators.
The enforcement of a quality assurance programme in any country would undoubtedly promote improvement in the quality of care for ovarian cancer patients and would result in a dramatic positive impact on their survival. Such a policy is not only beneficial to the patient, but is also profitable for the healthcare system.
Abstract Background Patients with high-risk gestational trophoblastic neoplasia (GTN) need multi-agent chemotherapy to be cured. The most common regimen is etoposide (E), methotrexate (M) and ...actinomycin D (A), alternating weekly with cyclophosphamide (C) plus vincristine (O) (EMA/CO). Cisplatin (P) is a very active drug, but it is usually restricted to second-line therapies. Herein, we report the results of a cisplatin-based therapy: APE (actinomycin D, cisplatin, and etoposide). Patients and methods The efficacy and safety of APE for high-risk GTN (defined by Institut Gustave-Roussy (IGR) criteria and/or an International Federation of Gynaecology and Obstetrics (FIGO) score >6) are reported. Patients with brain metastasis or placental-site trophoblastic tumour were excluded. Results Between 1985 and 2013, 95 patients were treated with APE for high-risk GTN: 59 patients as first-line, 36 as ⩾2nd-line therapy. There was 94.7% complete remission, though five patients relapsed. One patient died from GTN after multiple lines of chemotherapy. The five-year overall survival rate (median follow-up 5.7 years) was 97% (95% confidence interval (CI): 91–99%). No death from toxicity occurred. Long-term, six grade-1 neuro-toxicities, three grade-1 and two grade-2 oto-toxicities, and one grade-1 renal toxicity were recorded. One patient developed AML-M4 after APE and EMA/CO. Thirty-four of 35 women, who wished to become pregnant, succeeded and all had at least one live birth. Conclusion With a 97% long-term overall survival rate, limited long-term toxicity, and an excellent reproductive outcome, APE could be regarded as an alternative option to EMA/CO as a standard therapy for high-risk GTN.
Purpose: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in ...addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination.
Patients and methods: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out.
Results: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005).
Conclusions: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.
The evaluation of first-line intensive combination therapy in small cell carcinoma of the ovary (SCCO).
Debulking surgery; four to six cycles of chemotherapy with cisplatin (P) 80 mg/m2 day 1, ...adriamycin (A) 40 mg/m2 day 1, vepeside (V) 75 mg/m2/day days 1–3, cyclophosphamide (EP) 300 mg/m2/day days 1–3, every 3 weeks and granulocyte colony-stimulating factor with, in case of a complete remission, high-dose chemotherapy with carboplatin, vepeside, cyclophosphamide and stem-cell support.
Twenty-seven patients (median age 25 years); International Federation of Gynecology and Obstetrics stage: five I, four IIC, 17 IIIC–IV and one unknown. Twenty patients underwent complete surgery. Eight patients progressed under chemotherapy. Among 18 patients in complete response (CR), 10 received high-dose chemotherapy (CT) (three stem-cell collection failures, two protocol violations, two disease progression and one refusal). The main grade 3–4 toxic effects were hematologic. There were eight relapses among the 18 CR, four of which were pelvic alone. Among the 27 patients, 13 died and 10 patients are in CR1, three in CR2. The median follow-up is 37 months (8–166) and the median duration of the 18 CR is 30 months (5–111). Overall survival at 1 and 3 years is 58% confidence interval (CI) 40% to 75% and 49% (CI 30% to 67%).
Initial dose-intensive therapy achieves interesting overall survival in SCCO.
PDF
