Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our ...study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners.
From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a “gold standard."
Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists).
Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers.
This work was carried out under the aegis of the CNGOF (Collège national des gynécologues et obstétriciens français) and proposes guidelines based on the evidence available in the literature. The ...objective was to define the diagnostic and surgical management strategy, the fertility preservation and surveillance strategy in Borderline Ovarian Tumor (BOT). No screening modality can be proposed in the general population. An expert pathological review is recommended in case of doubt concerning the borderline nature, the histological subtype, the invasive nature of the implant, for all micropapillary/cribriform serous BOT or in the presence of peritoneal implants, and for all mucinous or clear cell tumors (grade C). Macroscopic MRI analysis should be performed to differentiate the different subtypes of BOT: serous, seromucinous and mucinous (intestinal type) (grade C). If preoperative biomarkers are normal, follow up of biomarkers is not recommended (grade C). In cases of bilateral early serous BOT with a desire to preserve fertility and/or endocrine function, it is recommended to perform a bilateral cystectomy if possible (grade B). In case of early mucinous BOT, with a desire to preserve fertility and/or endocrine function, it is recommended to perform a unilateral adnexectomy (grade C). Secondary surgical staging is recommended in case of serous BOT with micropapillary appearance and uncomplete inspection of the abdominal cavity during initial surgery (grade C). For early-stage serous or mucinous BOT, it is not recommended to perform a systematic hysterectomy (grade C). Follow up after BOT must be pursued for more than 5 years (grade B). Conservative treatment involving at least the conservation of the uterus and a fragment of the ovary in a patient wishing to conceive may be proposed in advanced stages of BOT (grade C). A new surgical treatment that preserves fertility after a first non-invasive recurrence may be proposed in women of childbearing age (grade C). It is recommended to offer a specialized consultation for Reproductive Medicine when diagnosing BOT in a woman of childbearing age. Hormonal contraceptive use after serous or mucinous BOT is not contraindicated (grade C).
PTEN hamartoma tumour syndrome (PHTS) encompasses several clinical syndromes with germline mutations in the PTEN tumour suppressor gene, including Cowden syndrome which is characterised by an ...increased risk of breast and thyroid cancers. Because PHTS is rare, data regarding cancer risks and genotype-phenotype correlations are limited. The objective of this study was to better define cancer risks in this syndrome with respect to the type and location of PTEN mutations.
154 PHTS individuals with a deleterious germline PTEN mutation were recruited from the activity of the Institut Bergonié genetic laboratory. Detailed phenotypic information was obtained for 146 of them. Age and sex adjusted standardised incidence ratio (SIR) calculations, cumulative cancer risk estimations, and genotype-phenotype analyses were performed.
Elevated SIRs were found mainly for female breast cancer (39.1, 95% CI 24.8 to 58.6), thyroid cancer in women (43.2, 95% CI 19.7 to 82.1) and in men (199.5, 95% CI 106.39 to 342.03), melanoma in women (28.3, 95% CI 7.6 to 35.4) and in men (39.4, 95% CI 10.6 to 100.9), and endometrial cancer (48.7, 95% CI 9.8 to 142.3). Cumulative cancer risks at age 70 were 85% (95% CI 70% to 95%) for any cancer, 77% (95% CI 59% to 91%) for female breast cancer, and 38% (95% CI 25% to 56%) for thyroid cancer. The risk of cancer was two times greater in women with PHTS than in men with PHTS (p<0.05).
This study shows a considerably high cumulative risk of cancer for patients with PHTS, mainly in women without clear genotype-phenotype correlation for this cancer risk. New recommendations for the management of PHTS patients are proposed.
Summary
Relapse after transplantation is a major cause of treatment failure in paediatric acute lymphoblastic leukaemia (ALL). Here, we report the findings of a prospective national study designed to ...investigate the feasibility of immune intervention in children in first or subsequent remission following myeloablative conditioning. This study included 133 children who received a transplant for ALL between 2005 and 2008. Minimal Residual Disease (MRD) based on T cell receptor/immunoglobulin gene rearrangements was measured on days −30, 30, 90 and 150 post‐transplantation. Ciclosporin treatment was rapidly discontinued and donor lymphocyte infusions (DLI) were programmed for patients with a pre‐ or post‐transplant MRD status ≥10−3. Only nine patients received DLI. Pre‐ and post‐transplant MRD status, and the duration of ciclosporin were independently associated with 5‐year overall survival (OS), which was 62·07% for the whole cohort. OS was substantially higher in patients cleared of MRD than in those with persistent MRD (52·3% vs. 14·3%, respectively). Only pre‐transplant MRD status (Hazard Ratio 2·57, P = 0·04) and duration of ciclosporin treatment (P < 0·001) were independently associated with relapse. The kinetics of chimerism were not useful for predicting relapse, whereas MRD monitoring up to 90 d post‐transplantation was a valuable prognostic tool to guide therapeutic intervention.
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical ...donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.
In natural product drug discovery, several strategies have emerged to highlight specifically bioactive compound(s) within complex mixtures (fractions or crude extracts) using metabolomics tools. In ...this area, a great deal of interest has raised among the scientific community on strategies to link chemical profiles and associated biological data, leading to the new field called “biochemometrics”. This article falls into this emerging research by proposing a complete workflow, which was divided into three major steps. The first one consists in the fractionation of the same extract using four different chromatographic stationary phases and appropriated elution conditions to obtain five fractions for each column. The second step corresponds to the acquisition of chemical profiles using HPLC-HRMS analysis, and the biological evaluation of each fraction. The last step evaluates the links between the relative abundances of molecules present in fractions (peak area) and the global bioactivity level observed for each fraction. To this purpose, an original bioinformatics script (encoded with R Studio software) using the combination of four statistical models (Spearman, F-PCA, PLS, PLS-DA) was here developed leading to the generation of a “Super list” of potential bioactive compounds together with a predictive score. This strategy was validated by its application on a marine-derived Penicillium chrysogenum extract exhibiting antiproliferative activity on breast cancer cells (MCF-7 cells). After the three steps of the workflow, one main compound was highlighted as responsible for the bioactivity and identified as ergosterol. Its antiproliferative activity was confirmed with an IC50 of 0.10 μM on MCF-7 cells. The script efficiency was further demonstrated by comparing the results obtained with a different recently described approach based on NMR profiling and by virtually modifying the data to evaluate the computational tool behaviour. This approach represents a new and efficient tool to tackle some of the bottlenecks in natural product drug discovery programs.
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•Fractionation coupled to biochemometrics is an interesting strategy for drug discovery.•The workflow proposed provides a new tool for the detection of bioactive compounds.•R-FiBiCo script proved to be efficient in detecting bioactive compounds from a mixture.•Performance evaluation of the script showed its ability to detect minor compounds.•Mass spectrometry- and NMR-based biochemometrics approaches can be complementary.
Highlights • Prescriptions of 207,979 elderly people aged 75 years and older were analyzed. • PIMs were found in 32.6% of patients. • 10% of patients were exposed to a prescription with a high ...anticholinergic score. • 24% of nursing homes patients were exposed to a prescription with a high anticholinergic score.
Summary
Minimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at ...high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non‐ex vivo T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T‐cell receptor MRD 30 d before transplant could be obtained in 122 of the 133 cases of high‐risk paediatric ALL enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with MRD <10−3 and the 27 with MRD ≥10−3. Multivariate analysis identified sex match and MRD as being significantly associated with 5‐year survival. MRD ≥10−3 compromised the 5‐year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between MRD and prognosis. Thus, pre‐transplant MRD is still a major predictor of outcome for ALL. The MRD‐guided strategy resulted in survival for 72·3% of patients with MRD<10−3 and 40·4% of those with MRD ≥10−3.
Summary
Minimal residual disease (
MRD
) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (
ALL
). Haematopoietic cell transplantation is a treatment option for patients ...at high risk of relapse. Between 2005 and 2008, we conducted a prospective study evaluating the feasibility and efficacy of the reduction of immunosuppressive medication shortly after a non‐
ex vivo
T depleted myeloablative transplantation. Immunoglobulin (Ig)H/T‐cell receptor
MRD
30 d before transplant could be obtained in 122 of the 133 cases of high‐risk paediatric
ALL
enrolled. There were no significant demographic differences except remission status (first or second complete remission) between the 95 children with
MRD
<10
−3
and the 27 with
MRD
≥10
−3
. Multivariate analysis identified sex match and
MRD
as being significantly associated with 5‐year survival.
MRD
≥10
−3
compromised the 5‐year cumulative incidence of relapse (43·6 vs. 16·7%). Complete remission status and stem cell source did not modify the relationship between
MRD
and prognosis. Thus, pre‐transplant
MRD
is still a major predictor of outcome for
ALL
. The
MRD
‐guided strategy resulted in survival for 72·3% of patients with
MRD
<10
−3
and 40·4% of those with
MRD
≥10
−3
.
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