Bulletin du cancer最新文献

Introduction: Immune checkpoint inhibition has revolutionized the management of metastatic melanoma, including in the final stages of disease progression: because it is well tolerated, some teams do not discontinue it in hopes of slowing disease progression. The risks are that treatment may be continued unnecessarily, causing side effects, and reduce access to specialist palliative care, in addition to increasing the cost of treatment.

Method: We explored the experiences of 10 patients in a university hospital with metastatic melanoma under continued immune checkpoint inhibitors combined with specialist palliative care. Our goal was to gain a better understanding of the advantages and disadvantages perceived by patients. The comprehensive interviews were analysed using a method inspired by grounded theory that met the COREQ international recommendation criteria.

Results: Receiving the information of disease progression, continued treatment and onset of palliative care impacts patients' lives: from this point onwards, death becomes a reality and takes on the image of a sword of Damocles. The experience is anxiety-provoking because of the uncertainty of tomorrow, and painful because of the physical suffering and successive bereavements. However, far from causing depression and despair, joint oncology-palliative management is well accepted and helps to improve patients' daily lives and well-being.

Conclusion: Our findings highlight patients' ambivalence. On the one hand, they recount their experiences of suffering in connection with the disease and the confrontation with death, and on the other hand, their need to continue to live and to hope. Joint care provided by oncology and palliative care teams, symbolically representing hope and death, may mirror patients' psychological mindset and provide just the support they need.

Background: Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer. Pyroptosis is a programmatic cell death linked to inflammation.

Methods: The data information of 541 LUAD samples and 59 normal samples were obtained from TCGA database. The analysis of differentially expressed genes (DEGs) was carried out on LUAD patients. The intersection of integrated PRGs and IRGs with DEGs yielded IPRGs. We utilized univariate Cox regression to determine IPRGs linked to overall survival (OS). Based on their expression levels, unsupervised clustering of LUAD was conducted. Patients were divided into two clusters. Analyses of immunity and drugs were performed in two clusters.

Results: One hundred and thirty-two IPRGs were linked with OS. Cluster 1 had a longer OS. Two thousand two hundred and fifty-six DEGs were detected in various subtypes. The results of immune analysis showed that most of the immune cells in cluster 2, which had a worse prognosis, had a low degree of infiltration. High Th2 cell infiltration may be related to poor prognosis in LUAD patients. Higher tumor immune dysfunction and exclusion (TIDE) and immunophenotypic scores in Cluster 1 indicated that these patients may have a better response to immunotherapy. There were significant differences in human leukocyte antigen (HLA), immune checkpoints, immunophenoscore (IPS), and TIDE scores in the two subtypes. The mutation frequencies of the top 10 genes in cluster 2 were higher than those in cluster 1. Different subtypes also had distinct sensitivities to different drugs.

Conclusion: IPRGs can be utilized for LUAD subtyping. Different subtypes have varied immune landscapes and immunotherapy responses.

The nutritional status after bone marrow transplant plays an important role in the outcome of patients. Post-allograft dietary instructions are therefore essential to ensure quality nutrition while minimizing the risk of infection. For patients, this is one of their main concerns on discharge from hospital. With the aim of harmonizing post-allograft dietary instructions, a multidisciplinary working group has been set up within a number of French centers performing hematopoietic stem cell allogenic transplantation. The dietary guidelines have been updated by this working group, through videoconference meetings, an online questionnaire, a review of the literature and deliberations at harmonization days. These instructions will be incorporated into the next update of the adult and pediatric post-transplant follow-up booklet.

Changing practices and the limited use of cord blood units as a source of cells for allogeneic hematopoietic stem cell transplants (HSC) led us to reconsider the recommendations established in 2011 and 2012, and to propose an update incorporating recent bibliographic data. If HLA compatibility was until now established at low resolution for HLA-A and B loci, and at high resolution for HLA-DRB1, the recent papers are converging towards an increase in the level of resolution, making way for a compatibility now defined in high resolution for all the considered loci, and the inclusion of the HLA-C locus, in order to establish a level of HLA compatibility on 8 alleles (HLA-A, B, C and DRB1). The CD34+ dose is a determining factor in hematopoietic reconstitution but it is not correlated with the total nucleated cells content. This is why we recommend taking these two data into account when choosing a cord blood unit. The recommendations established by our group are presented as a flow chart taking into account the characteristics of the underlying pathology (malignant or non-malignant), the cell dose and the HLA compatibility criteria, as well as criteria linked to the banks in which units are stored.

Allogeneic transplantation of haematopoietic stem cells is still the only curative treatment for certain haematological malignancies. This treatment can be responsible for a number of side-effects, leading to multiple and interdependent physical and psychological deficiencies that affect patients' quality of life and social participation, and can be experienced as a handicap, sometimes for several years after the transplant. For several years now, the integration of post-transplant rehabilitation pathways has been becoming more widespread, and initiatives to provide multidisciplinary care at an increasingly early stage are being studied. The aim of this early management is to improve the patient's overall functional state before, during and after the transplant, in order to limit the impact of the treatment and ensure the quickest possible return to a life that is as satisfying as possible. The international literature and the experiments carried out throughout the French-speaking world describe heterogeneous practices. Based on this literature and experience, the aim of this study is to issue homogenous recommendations for good clinical practice and to identify areas for further research into pre-transplant, per-transplant and post-transplant rehabilitation of haematopoietic stem cells.

Treatment of pediatric high-risk acute myeloid leukemia (AML), defined either on molecular or cytogenetic features, relies on bone marrow transplant after cytologic remission. However, relapse remains the first post-transplant cause of mortality. In this 13^th session of practice harmonization of the francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), our group worked on recommendations regarding the management of post-transplant relapse in AML pediatric patients based on international literature, national survey and expert opinion. Overall, immunomodulation strategy relying on both measurable residual disease (MRD) and chimerism evaluation should be used for high-risk AML. In very high-risk (VHR) AML with a 5-year overall survival ≤30 %, a post-transplant maintenance should be proposed using either hypomethylating agents, combined with DLI whenever possible, or FLT3 tyrosine kinase inhibitors if this target is present on leukemia cells. In the pre-emptive or early relapse settings (< 6 months post-transplant), treatments combining DLI, Azacytidine and Venetoclax should be considered. Access to phase I/II trails for targeted therapies (menin, IDH or JAK inhibitors) should be discussed in each patient according to the underlying molecular abnormalities of the disease.

Triple negative breast cancer (TNBC) is defined by the absence of expression of estrogen and progesterone receptors, as well as the absence of overexpression of HER2. Accounting for 10 to 15% of breast cancers, it remains characterized by an aggressive phenotype with an increased risk of early recurrence and overall survival less favorable compared to other subtypes. The challenges in management and therapeutic evolution are likely related to the demonstrated high biological heterogeneity of this subtype. Regarding therapeutic management, chemotherapy remains the cornerstone of TNBC treatment. In the early stage, the neoadjuvant strategy is the standard, allowing adaptation of the adjuvant sequence depending on whether a complete histological response is achieved or not. Dose-dense chemotherapy regimens and the addition of carboplatin have been associated with an improvement in these response rates. Furthermore, immunotherapy, particularly pembrolizumab, has shown significant benefits in terms of recurrence-free survival. In the metastatic setting, the role of theranostic markers is now established, allowing access to immunotherapy (pembrolizumab if CPS PD-L1>10%) or PARP inhibitors (in case of constitutional BRCA mutation). Antibody-drug conjugates are gradually moving up the lines, offering promising prospects in these complex situations. In conclusion, despite recent progress, TNBC remains a major clinical challenge. A better understanding of its biology and a personalized therapeutic approach are essential to improve clinical outcomes for patients with this aggressive form of breast cancer.

Nowadays, haploidentical hematopoietic cell transplantation (haplo-HCT) has been routinely used worldwide. However, this procedure is still rarely proposed in low- or middle-income countries. During the 13th annual harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a designated working group has proposed recommendations on how to set up such a transplantation in these countries. This was based on a review of the literature and expert-opinion as well as the previously published workshop on haplo-HCT of SFGM-TC (2016). Haploidentical donors appear to be a first alternative to HLA-matched siblings since the access to unrelated donor international registries are limited for several countries. While the procedure has the advantage of immediate access to several potential donors and of low cost, Haplo-HCT should be performed only in centers with a good experience of HLA-matched related transplantation (>10/year). In the absence of an HLA-matched related donor, haplo-HCT should be offered to all patients who are candidate for allo-HCT. Transplantation modalities should follow the conventional procedures with post-transplant cyclophosphamide as GVHD prophylaxis. Conditioning can be myeloablative or not according to each case. Our recommendations are intended to be general in scope and applicable to the majority of allo-HCT centers in these countries. An evaluation at regular basis is needed to assess the feasibility and to improve results.