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The management of anal squamous cell carcinoma (ASCC) has yet to experience the transformative impact of precision medicine. Conducting genomic analyses may uncover novel prognostic biomarkers and offer potential directions for the development of targeted therapies. To that end, we assessed the prognostic and theragnostic implications of pathogenic variants identified in 571 cancer-related genes from surgical samples collected from a homogeneous, multicentric French cohort of 158 ASCC patients who underwent abdominoperineal resection treatment. Alterations in PI3K/AKT/mTOR, chromatin remodeling, and Notch pathways were frequent in HPV-positive tumors, while HPV-negative tumors often harbored variants in cell cycle regulation and genome integrity maintenance genes (e.g., frequent TP53 and TERT promoter mutations). In patients with HPV-positive tumors, KMT2C and PIK3CA exon 9/20 pathogenic variants were associated with worse overall survival in multivariate analysis (Hazard ratio (HR)KMT2C = 2.54, 95%CI = [1.25,5.17], P value = .010; HRPIK3CA = 2.43, 95%CI = [1.3,4.56], P value = .006). Alterations with theragnostic value in another cancer type was detected in 43% of patients. These results suggest that PIK3CA and KMT2C pathogenic variants are independent prognostic factors in patients with ASCC with HPV-positive tumors treated by abdominoperineal resection. And, importantly, the high prevalence of alterations bearing potential theragnostic value strongly supports the use of genomic profiling to allow patient enrollment in precision medicine clinical trials.
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Neoplasias do Ânus , Carcinoma de Células Escamosas , Protectomia , Humanos , Neoplasias do Ânus/genética , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Mutação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Fosfatidilinositol 3-Quinases/genética , PrognósticoRESUMO
PURPOSE: Onco-nephrology is an emerging subspecialty aiming to better understand and prevent renal events in cancer patients. We assessed patients' knowledge about (1) oncological/hematological treatments induced renal toxicity and (2) kidney protective measures. METHODS: Adult patients receiving systemic anti-tumor treatments in multiple day hospital units in France answered a self-administered questionnaire about their knowledge and expectations related to treatment-associated renal toxicity. RESULTS: In total, 621 questionnaires were collected in 8 units from November 2021 to January 2022. Among respondents, 84.5% were treated for a solid tumor. Overall, 34.3% (n = 208) patients reported they had some knowledge about potential renal adverse events related to their anticancer treatment, and 38.5% (n = 234) about kidney protection measures. Their referring oncologist or hematologist represented the commonest source of knowledge (67.8%). Sufficient hydration was cited as a kidney protection measure by 93.2% (n = 218) of patients declaring some knowledge about renal toxicity; prevention of nausea/vomiting by 52.6% (n = 123). Consumption of still and alkaline water was chosen by respectively 64.4% (n = 400) and 16.8% (n = 104) of participants to correct dehydration. A majority of patients expressed strong interest for receiving more information about renal toxicity and prevention: median Likert scale score was 10/10 (Q1-Q3, 5-10), with online resources mentioned as the most desired source of information. CONCLUSION: One-third of patients declared they had some knowledge about potential renal toxicity of their oncologic treatment and the ways to prevent them, especially regarding hydration. However, a majority expressed interest for dedicated information, which conducted to the elaboration of free online educational sheets for patients.
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Antineoplásicos , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Inquéritos e Questionários , Idoso , França , Adulto , Neoplasias/tratamento farmacológico , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Qualitative research on the perceptions of healthcare professionals involved in cancer care about their respective roles in the patient care pathway is limited. Therefore, the aim of this qualitative study was to document these perceptions. METHODS: A multidisciplinary team that included patient researchers constructed a semi-structured interview guide on the perceptions of the colorectal cancer care pathway by professionals. Interviews were conducted with healthcare professionals from two French hospitals that manage patients with colorectal cancer. Then, the interviews were fully transcribed and analysed by the whole multidisciplinary team. RESULTS: Thirteen healthcare professionals were interviewed (six nurses, four physicians, one psychologist, one social worker and one secretary). They described the colorectal care pathway using a great lexical diversity and listed a significant number of professionals as taking part in this pathway. Among the people mentioned were healthcare professionals working inside and outside the hospital, family members and non-conventional medicine practitioners. However, they did not spontaneously mention the patient. Their views on the role of the referring physician, the general practitioner and the patient were further explored. The interviews highlighted the coordination difficulties among the various professionals, particularly between general practitioners and hospital teams. These data provided interesting elements for developing a tool to help coordination among professionals. CONCLUSIONS: This preliminary study, with its participatory design, brings interesting elements of reflection on the care pathway for patients with colorectal cancer. It will continue through the creation of a larger participatory project. PATIENT OR PUBLIC CONTRIBUTION: Patient partners were included in all steps of this study. This transdisciplinary project was coordinated by a group composed of three patient partners, two healthcare professionals and two humanities and social sciences researchers. Their knowledge of the patient's perspective on the care pathway enriched discussions from the study design to results analysis.
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Atitude do Pessoal de Saúde , Neoplasias Colorretais , Entrevistas como Assunto , Pesquisa Qualitativa , Humanos , Neoplasias Colorretais/psicologia , Neoplasias Colorretais/terapia , Feminino , Masculino , Procedimentos Clínicos , França , Pessoal de Saúde/psicologia , Equipe de Assistência ao Paciente , Pessoa de Meia-Idade , AdultoRESUMO
INTRODUCTION: Renal events are common in cancer patients and malignancy is a prevalent complication in both patients transplanted and under kidney replacement therapy (KRT). In recent years, onco-nephrology has been developed as a subspecialty whose scope has not been well established yet. The aim of our study was to assess resident and senior physicians' knowledge and expectations about onco-nephrology. METHODS AND MATERIALS: Two anonymous self-administered online questionnaires were developed by a multidisciplinary team and distributed to French residents and senior physicians. RESULTS: Two hundred twenty-eight physicians answered the survey, including 128 (56%) nephrologists, of which 98 (43%) were senior physicians and 130 (57%) were residents. Nephrologists rated their confidence in their ability to face onco-nephrological situation at 6/10 (interquartile range (IQR) 4.0-7.0) and oncologists at 6.0/10 (5.0-7.0). Managing cancer drugs in patients on KRT or in transplanted patients and discussion about introducing dialysis in cancer patients were designated as the most challenging topics. Asking if they had received appropriate learning, residents' median agreement was ranked at 3.0/10 (2.0-4.0). Forty-six percent of the respondents considered available resources as not appropriate. Specialized onco-nephrology consultations were accessible for 21% of the respondents. Finally, respondents thought there is a strong need for a national working group (8.3/10) with 87% of them expecting new reliable guidelines. CONCLUSION: The present survey revealed physicians' expectations about onco-nephrology implementation in France. An appropriate answer could be the creation of a national working group. Therefore, GRIFON (Groupe de Recherche Interdisciplinaire en OncoNéphrologie) has recently been created.
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Neoplasias , Nefrologia , Médicos , Humanos , Nefrologia/educação , Nefrologia/métodos , Motivação , Neoplasias/terapia , Neoplasias/complicações , Diálise Renal , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Early palliative care integration into the oncologic treatment pattern is recognized and strongly recommended to anticipate end-of-life issues and avoid disproportionate care. Targeted therapies (TTs), with their very rapid onset of action and relatively good tolerance, may have an effect on cancer-related symptoms, which could be beneficial in the context of palliative care. METHODS: Data were extracted from a cohort of all patients hospitalized in an acute palliative care unit between 03.04.2019 and 07.04.2020. Data for all consecutive patients for which a decision on a TT was made during hospitalization were retrospectively analyzed. RESULTS: Forty-two patients were identified. Thirty-one patients were currently receiving TT on admission. For 19/31 (61.3%) patients, the treatment was discontinued. The remaining 12 patients had TT after discharge from the palliative care unit (continuation of the same TT or modification of the TT during the stay), with an average duration of 208 days and an average of 46 days between the last TT and death. TT was introduced or reintroduced in 7 patients of the 11 patients hospitalized without treatment at admission. In this group, the average duration of treatment was 28 days, with an average of 28 days between the last TT and death. Five of the patients who received re-challenged TT experienced a subjective improvement of their symptom. SIGNIFICANCE OF RESULTS: TT was discontinued in the majority of our patients. However, in some cases, the treatment was maintained because it was effective on cancer-related symptoms even at the end of life. However, this should not overshadow the palliative process. The continuation or introduction of a specific oncological treatment requires close cooperation between oncologists and palliative care physicians and an honest and clear explanation to patients and their families.
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INTRODUCTION: Molecular profiling has become essential in the management of patients with biliary tract cancer (BTC). The aim of this study was to evaluate the practices of French genetics platforms in the management of BTCs. METHODS: A survey was developed by a multidisciplinary group and distributed to each of the 28 French genetics platforms over a one-month period. RESULTS: Twenty-one platforms answered the survey (75%). A majority (62%) had performed more than 50 analyses for BTCs over the last two years, with an average turnaround time for results evaluated between 11 and 15 days for 62% of them. Three quarters (76%) of the platforms performed both DNA and RNA analysis, while a quarter (24%) performed RNA analysis only. A commercial panel was used by 50% of platforms for DNA analysis, and 80% for RNA. Panels included between 10 and 50 genes for 76% of platforms. All responding platforms systematically tested for IDH1 mutations, FGFR2 fusions and BRAF mutations. A majority systematically tested for HER2 amplification, MSI status and TP53 mutation (88%, 81% and 69% respectively). DISCUSSION: This national survey of French genetics platforms shows good performance and compliance with recommendations for molecular analysis. However, many medical, financial and organizational obstacles remain upstream of these platforms.
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Neoplasias do Sistema Biliar , Proteínas Proto-Oncogênicas B-raf , Humanos , França , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias do Sistema Biliar/genética , Mutação , Receptor ErbB-2/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Isocitrato Desidrogenase/genética , DNA de Neoplasias/genética , DNA de Neoplasias/análise , RNA Neoplásico/genética , RNA Neoplásico/análise , Proteína Supressora de Tumor p53/genética , Instabilidade de Microssatélites , Perfilação da Expressão Gênica/métodos , Pesquisas sobre Atenção à Saúde , Amplificação de GenesRESUMO
CONTEXT: The reform of the third cycle of medical studies in France has introduced of the "Junior Doctor" status during the concluding year of residency. We wish to evaluate its implementation for the first promotion of medical oncology residents during 2021-2022 in correlation with the published guidelines. METHOD: AERIO conducted a cross-sectional study among French medical oncology residents. The survey was released via social networks and emails. RESULTS: Twenty-eight of 47 residents responded. The typical week involved one to two half-days of consultation, one dedicated to clinical research, one multidisciplinary team meetings, with the rest of time being occupied by day care (mostly) and hospitalization. Teaching and quality management activities were infrequent (monthly or less). The Junior Doctors rated their overall satisfaction at 8/10. A large majority (92.5 %) felt equipped to handle most of the situations they encountered. Almost all residents (92.9 %) had negotiated with their placement supervisor prior to the selection procedure. In one third of the cases (35.7 %), the principle of mismatch between the number of residents and the number of training sites was not respected. Only 42.9 % received training in scientific writing and 82.2 % of the residents agreed on the relevance of the post-internship training modules developed in other specialties. CONCLUSIONS: Junior doctors in medical oncology express overall satisfaction with this reform, which aligns with the recommendations. Nevertheless, certain concerns, such as selection procedure and inadequacy, along with areas requiring improvement, such as post-internship training and scientific writing, are clearly established.
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Internato e Residência , Oncologistas , Humanos , Estudos Transversais , Inquéritos e Questionários , Corpo Clínico HospitalarRESUMO
OBJECTIVES: The perception of oncologists could impact the attractiveness of the specialty and dialogue between oncologists and other physicians. The aim of the study was to describe and understand the stereotypes and social representation (SR) associated with oncologists among medical students, residents and physicians in France. METHODS: This nationwide web-based survey conducted in 2021 was based on hierarchical evocation methods. Qualitative analyses were based on the Reinert method with factorial analyses. Each respondent's SR was graded from 1 to 5 (from 1: very positive SR to 5: very negative SR). RESULTS: Oncologists suffer from a rather negative SR. The negative representation was mostly related to difficulties in practising and the proximity with death and end of life. Oncologists were also associated with more positive notions like interdisciplinarity or intellectual complexity. Attendance to an oncology course was associated with a better SR of oncology (p=0.036), whereas having someone in the family practising oncology had a negative impact (p=0.028). CONCLUSIONS: SR of oncologists is rather contrasted. It was positively influenced by attendance to an oncology course, which could be an option to correct stereotypes and update on this rapidly evolving specialty.
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Atitude do Pessoal de Saúde , Oncologistas , Estereotipagem , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Estudos Transversais , Masculino , Feminino , França , Oncologistas/psicologia , Adulto , Médicos/psicologia , Internato e Residência , Oncologia/educação , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
CONTEXT: Obesity prevalence is persistently increasing worldwide. Among surgical therapeutic procedures, bypass surgery and sleeve gastrectomy have shown the best results regarding weight loss, prevention, and treatment of secondary complications. However, these surgeries are associated with an increased risk of malabsorption and metabolic changes that could further affect the pharmacokinetics of drugs. On the other hand, patients with a history of such surgeries are more likely to experience pain and request analgesic initiation or adaptation. The question of how to manage pain medication in these patients is challenging due to their narrow therapeutic indexes. OBJECTIVES: To summarize the current literature on the impact of bariatric surgery on the subsequent pharmacokinetics of analgesics and propose a multidisciplinary therapeutic attitude to optimize pain management in these patients. METHODS: We conducted a systematic review that included all pharmacological studies published after 2000. RESULTS: Unexpectedly, these surgeries seem to increase the bioavailability of drugs by long-term improvement of hepatic function. Yet, the medical community drastically lacks robust guidelines for pain management in those patients. This systematic review aims to bring together pharmacological studies related to the use of pain treatments in patients who underwent bypass surgery or sleeve gastrectomy. CONCLUSIONS: Caution should be exercised regarding the risk of overdose in every circumstance: treatment initiation, change of doses, or change of molecule. More prospective trials comparing the pharmacokinetics of medications in obese patients with and without prior bariatric surgery are needed.
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Analgésicos , Cirurgia Bariátrica , Manejo da Dor , Humanos , Analgésicos/uso terapêutico , Analgésicos/farmacocinética , Manejo da Dor/métodos , Obesidade/cirurgia , Obesidade/complicações , Dor/tratamento farmacológicoRESUMO
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with significant public health concerns. This review examines the landscape of KRAS inhibition in colorectal cancer (CRC), focusing on recent advances in therapeutic strategies targeting this oncogene. Historically deemed undruggable due to its complex structure and essential role in tumorigenesis, KRAS mutations are prevalent in CRC and are associated with poor prognosis. However, breakthroughs in drug development have led to the emergence of KRAS inhibitors as promising treatment options. This review discusses various classes of KRAS inhibitors, including covalent and non-covalent inhibitors, as well as combination therapies aimed at enhancing efficacy and overcoming resistance mechanisms. It highlights recent clinical trials evaluating the efficacy of KRAS inhibitors either as monotherapy or in combination with other agents, such as anti-EGFR antibodies. Despite challenges such as resistance mechanisms and tumor heterogeneity, the development of KRAS inhibitors represents a significant advance in CRC treatment and holds promise for improving patient outcomes in the future.
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BACKGROUND AND AIMS: To gather real-life data on biliary tract cancer (BTC) in France, an ambispective ACABi GERCOR Pronobil cohort was initiated. This nested study, Amber, utilized data from this cohort to document clinical practices in this setting. METHODS: Inclusion criteria encompassed patients with locally advanced/metastatic BTC managed between 2019 and 2021 in nine French referral hospitals. Objectives included describing demographic and clinical data, treatments outcomes (safety and efficacy), and overall survival. RESULTS: Of the 138 patients (median age 65 years, a balanced sex ratio) included, most displayed ECOG 0-1 (83 %), at least one comorbidity (79 %), and had intrahepatic (56 %) and metastatic (82 %) BTC. Among surgically-resected patients, 60 % received adjuvant chemotherapy, mainly capecitabine (67 %). CisGem, the primary first-line palliative chemotherapy (69 %), showed a 23 % objective response rate, a median progression-free survival of 5.3 months, and a median overall survival of 13.4 months. Second-, third-, and fourth-line were given to 75 % (FOLFOX: 35 %, targeted therapy: 14 %), 32 %, and 13 % of patients. In total, 67 % of patients had a molecular profile (IDH1 mutations and FGFR2 fusions: accounting for 21 % each in intrahepatic cholangiocarcinoma). CONCLUSION: BTC patients were predominantly treated according to international recommendations. The obtained demographic, tumor, and molecular data were consistent with existing literature.
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Immune checkpoint inhibitors (ICI) have deeply changed the therapeutic management of a broad spectrum of solid tumors. Recent observations showed that obese patients receiving ICIs might have better outcomes than those with normal weight, while obesity was historically associated with a worse prognosis in cancer patients. Of note, obesity is associated with alterations in the gut microbiome profile, which interacts with immune and inflammatory pathways, both at the systemic and intratumoral levels. As the influence of the gut microbiota on the response to ICI has been repeatedly reported, a specific gut microbiome profile in obese cancer patients may be involved in their better response to ICI. This review summarizes recent data on the interactions between obesity, gut microbiota, and ICIs. In addition, we highlight possible pathophysiological mechanisms supporting the hypothesis that gut microbiota could be one of the links between obesity and poor response to ICIs.
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Microbioma Gastrointestinal , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Obesidade/tratamento farmacológicoRESUMO
The objective of this study was to determine the proportion of phase 3 clinical trials investigating a systemic therapy for patients with prostate, breast, lung, or colorectal cancer that excluded patients with Chronic Kidney Disease (CKD) and the exclusion criteria chosen, if any. A search was conducted using the ClinicalTrials.gov database to identify eligible studies. Of the 268 included trials, 185 (69%) had at least one renal exclusion criteria. Of these 185 trials, 116 (63%) had an undefined exclusion criterion. Only disease site was associated with exclusion of patients with CKD in the univariate analysis, but no factors in the multivariate analysis. There are several potential barriers to including patients with CKD in clinical trials. Nevertheless, solutions can be proposed to allow the inclusion of these patients. This would allow them to access to innovative therapeutic strategies, but also allow a better applicability of trial results to this patient population.
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Neoplasias Colorretais , Insuficiência Renal Crônica , Masculino , Humanos , Próstata , Rim , PulmãoRESUMO
Pancreatic ductal adenocarcinoma is associated with a poor prognosis and there are few treatment options. The development of immunotherapy in pancreatic ductal adenocarcinoma has been difficult, and immune checkpoint inhibitors are only effective in a very small subset of patients. Most obstacles for treatment have been related to intertumoural and intratumoural heterogeneity, the composition of tumour stroma, and crosstalk with cancer cells. Improved molecular characterisation of pancreatic ductal adenocarcinoma and a better understanding of its microenvironment have paved the way for novel immunotherapy strategies, including the identification of predictive biomarkers, the development of rational combinations to optimise effectiveness, and the targeting of new mechanisms. Future immunotherapy strategies should consider individual characteristics to move beyond the traditional immune targets and circumvent the resistance to therapies that have been developed so far.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Imunoterapia , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Through a concrete case, we discuss the main published protocols to initiate methadone and illustrate the advantages and disadvantages of rapid or gradual initiation and on-demand or fixed doses with rescue doses. Daily doses can vary widely depending on the protocol chosen. An on-demand administration could lead to an overdose as illustrated in our case. A better understanding of particularities and limitations of these protocols could lead to safer methadone initiation. Systematic comparison of different protocols and calculation of the daily dose should be a standard in clinical practice.
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Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/efeitos adversos , Overdose de Drogas/tratamento farmacológico , Humanos , Metadona/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/reabilitaçãoRESUMO
Contribution of immunotherapy in the treatment of advanced biliary tract cancer Biliary tract cancers (BTC) are rare tumors with a poor prognosis. Their treatment, at an advanced stage, relies on combinations of chemotherapies, which have a limited range and duration of benefit. Immunotherapy has emerged in recent years as a new therapeutic approach for BTC. However, the benefit with currently available treatments seems more modest than in other tumor locations and the predictive markers of response to these treatments remain to be identified. This review article summarizes the rationale, current data, and prospects and challenges for the development of immunotherapy in BTC.
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Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Neoplasias do Sistema Biliar/tratamento farmacológico , ImunoterapiaRESUMO
Cytomegalovirus (CMV) reactivation is frequent after autologous stem cell transplantation (ASCT), but generalized CMV lymphadenitis is rare. We report a CMV lymphadenitis after an ASCT mimicking a relapse of a diffuse large B-cell lymphoma. After histopathological documentation, CMV lymphadenitis should be treated to avoid systemic progression.
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BACKGROUND: COVID-19 pandemic troubled hospital and university's organization. Previous study showed oncology resident's formation has been impacted by pandemic. One year later, we aimed to evaluate the state of oncology resident's formation. METHODS: We conducted a transversal study written by AERIO and SJRO, released via social networks and mail to the French oncology residents. RESULTS: One hundred and sixty-four residents answered. Sixty-four (39%) were male and 99 (60.4%) were female, mean age was 26.8 years old, mean semester was 5.7. One hundred and five (64%) were medical oncologist and 53 (32.3%) were radiation oncologist. One hundred and forty residents (85.4%) had lectures during hospital internships, mainly in cancer center (77.1%) and academic hospitals (60.7%). One hundred and twenty-one residents (73.8%) had specialized diploma lectures, in 34.7% of case monthly. Respectively 42.7% and 18.3% of residents could access to their formation's day respectively rarely and never. Strengths of oncology residency were scientific dynamism (91.9%), clinical breadth (82%) and knowledge renewal (78.9%). Attractivity's obstacles to the residency were psychological arduousness (64%), administrative burden (48.2%) and too important worktime (47%). CONCLUSION: This survey shows the state of play of French oncology residency's formation at the end of 2021.
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COVID-19 , Internato e Residência , Adulto , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Oncologia/educação , Pandemias , Inquéritos e QuestionáriosRESUMO
The prescription of chemotherapy during the last weeks of a patient's life is a recognised criterion of decreasing quality of life but also survival. Targeted therapies have a particular efficiency and tolerance profile raising the question of their use in a palliative setting. Two patients were treated for a melanoma, at terminal stage, with poor efficiency of the symptomatic treatments. We introduced targeted therapies, which was previous treatments used in both patients.The evolution and benefits of the treatment was very different in our two patients and make us discuss the interest of targeted therapies in an end-of-life context and propose criteria for their maintenance or introduction in this indication. This discussion requires close collaboration between oncologists and palliative physicians and a very clear information given to patients and their relatives.