RESUMO
BACKGROUND: This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by chemotherapy and cetuximab. METHODS: In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D0) D7, and D21 of treatment for CTC detection by CellSearch®, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan-Meier method and compared with the log-rank test (P < 0.05). RESULTS: At D0, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D0, D7, and D21, respectively. Median PFS time was significantly lower in (a) patients with increasing or stable CTC counts (36/54) from D0 to D7 with EPISPOTEGFR (3.9 vs 6.2 months; 95% CI, 5.0-6.9; P = 0.0103) and (b) patients with ≥1 CTC detected with EPISPOT or CellSearch® (37/51) (P = 0.0311), EPISPOT or FCM (38/54) (P = 0.0480), and CellSearch or FCM (11/51) (P = 0.0005) at D7. CONCLUSIONS: CTCs can be detected before and during chemotherapy in patients with rHNSCC. D0-D7 CTC kinetics evaluated with EPISPOTEGFR are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC. CLINICALTRIALSGOV IDENTIFIER: NCT02119559.
Assuntos
Neoplasias de Cabeça e Pescoço/sangue , Células Neoplásicas Circulantes/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Contagem de Células , Intervalo Livre de Doença , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundárioRESUMO
AIMS: Cetuximab associated with cisplatin and 5-fluorouracil is used to treat patients with inoperable or metastatic head and neck squamous cell carcinomas (HNSCC) up until disease progression or unacceptable toxicities. To date, no biomarkers of efficacy are available to select patients who will benefit from treatment. METHODS: An ancillary pharmacokinetics (PK) exploration was performed in the context of a prospective study investigating circulating-tumour cells vs progression-free survival (PFS). Cetuximab plasma concentrations were analysed according to a population PK model. Individual exposure parameters were confronted with soluble epidermal growth factor receptor (sEGFR) concentrations, tumour response and PFS. RESULTS: PK data (28 patients, 203 observations) were best described by a two-compartment model with linear elimination. Performance status (PS) significantly correlated to both cetuximab clearance and central volume of distribution with both parameters increasing by 33.3% (95% CI 1-65.6) for each 1-point increase of PS compared to PS = 0. Univariate analysis showed that patients with higher trough cetuximab concentrations at Day 7 (Cmin,D7 ) had better tumour response (P = 0.03) and longer PFS (P = 0.035). However, multivariate analysis revealed that only PS and tumour size at baseline remained significantly associated with PFS. Levels of sEGFR increased during cetuximab treatment but were not associated with PFS in the multivariate analysis. CONCLUSIONS: Our study prospectively indicates that PS is likely a confounding factor in the relationship between cetuximab PK and PFS, patients with a poor PS having lower cetuximab plasma exposure and lower PFS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Cetuximab/farmacocinética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Modelos Biológicos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/sangue , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/sangue , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacocinética , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes/efeitos dos fármacos , Células Neoplásicas Circulantes/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Adulto JovemRESUMO
BACKGROUND: Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database. METHODS: Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions. RESULTS: A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis. CONCLUSION: Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.
Assuntos
Adenocarcinoma , Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Melanoma , Neoplasias dos Seios Paranasais , Neoplasias das Glândulas Salivares , Humanos , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias das Glândulas Salivares/patologia , Carcinoma Adenoide Cístico/patologia , Neoplasias dos Seios Paranasais/patologiaRESUMO
BACKGROUND: At present, there is no established standard treatment for frail older patients with recurrent or metastatic head and neck squamous cell carcinoma. We aimed to compare the efficacy and safety of cetuximab to those of methotrexate (the reference regimen) in this population. METHODS: This randomised, open-label, phase 3 trial was done at 20 hospitals in France. Patients aged 70 years or older, assessed as frail by the ELAN Geriatric Evaluation, with recurrent or metastatic head and neck squamous cell carcinoma in the first-line setting and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were eligible for inclusion. Patients were randomly assigned (1:1) to receive cetuximab 500 mg/m2 intravenously every 2 weeks or methotrexate 40 mg/m2 intravenously every week, with minimisation by ECOG performance status, type of disease evolution, Charlson Comorbidity Index score, serum albumin concentration, and geriatrician consultation. To avoid deterministic minimisation and assure allocation concealment, patients were allocated with a probability of 0·80 to the treatment that most reduced the imbalance. Treatment was continued until disease progression or unacceptable toxicity, whichever occurred first. The primary endpoint was failure-free survival (defined as the time from randomisation to disease progression, death, discontinuation of treatment, or loss of 2 or more points on the Activities in Daily Living scale, whichever occurred first) and was analysed in the intention-to-treat population. 151 failures expected out of 164 patients were required to detect a hazard ratio (HR) of 0·625 with 0·05 alpha error, with 80% power. A futility interim analysis was planned when approximately 80 failures were observed, based on failure-free survival. Safety analyses included all patients who received at least one dose of the study drug. This study is registered on ClinicalTrials.gov (NCT01884623) and was stopped for futility after the interim analysis. FINDINGS: Between Nov 7, 2013, and April 23, 2018, 82 patients were enrolled (41 to the cetuximab group and 41 to the methotrexate group); 60 (73%) were male, 37 (45%) were aged 80 years or older, 35 (43%) had an ECOG performance status of 2, and 36 (44%) had metastatic disease. Enrolment was stopped for futility at the interim analysis. At the final analysis, median follow-up was 43·3 months (IQR 30·8-52·1). At data cutoff, all 82 patients had failure; failure-free survival did not differ significantly between the groups (median 1·4 months [95% CI 1·0-2·1] in the cetuximab group vs 1·9 months [1·1-2·6] in the methotrexate group; adjusted HR 1·03 [95% CI 0·66-1·61], p=0·89). The frequency of patients who had grade 3 or worse adverse events was 63% (26 of 41) in the cetuximab group and 73% (30 of 41) in the methotrexate group. The most common grade 3-4 adverse events in the cetuximab group were fatigue (four [10%] of 41 patients), lung infection (four [10%]), and rash acneiform (four [10%]), and those in the methotrexate group were fatigue (nine [22%] of 41), increased gamma-glutamyltransferase (seven [17%]), natraemia disorder (four [10%]), anaemia (four [10%]), leukopenia (four [10%]), and neutropenia (four [10%]). The frequency of patients who had serious adverse events was 44% (18 of 41) in the cetuximab group and 39% (16 of 41) in the methotrexate group. Four patients presented with a fatal adverse event in the cetuximab group (sepsis, decreased level of consciousness, pulmonary oedema, and death of unknown cause) as did two patients in the methotrexate group (dyspnoea and death of unknown cause). INTERPRETATION: The study showed no improvement in failure-free survival with cetuximab versus methotrexate. Patients with an ECOG performance status of 2 did not benefit from these systemic therapies. New treatment options including immunotherapy should be explored in frail older patients with recurrent or metastatic head and neck squamous cell carcinoma, after an initial geriatric evaluation, such as the ELAN Geriatric Evaluation. FUNDING: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC and the Ligue Contre le Cancer), GEMLUC, GEFLUC, and Merck Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Assuntos
Neoplasias de Cabeça e Pescoço , Metotrexato , Humanos , Masculino , Idoso , Feminino , Metotrexato/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Cetuximab/efeitos adversos , Idoso Fragilizado , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Progressão da Doença , FadigaRESUMO
Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology as well as their anatomical location when arising from the paranasal sinuses, salivary glands and ear. The management of these heterogeneous rare diseases of complex treatment has considerably been structured over the last 15 years, in particular via the French ENT Cancer Expertise Network (REFCOR) and international networks and registries (EURACAN, etc.). Structuration also favors research with identification of new entities and setting up of specific therapeutic trials. A first article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the REFCOR concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. This second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Melanoma , Neoplasias Bucais , Sarcoma , Humanos , Carcinoma de Células Escamosas/patologia , Melanoma/patologia , Pescoço , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapiaRESUMO
Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology, which determines their local invasiveness, and their hematogenous/nodal spread. Their diagnosis can be difficult and often requires comprehensive immunohistochemistry and genomic techniques. Expert pathology review is recommended in the cases of undifferentiated tumors, sarcomas and at the slightest diagnostic doubt. These rare cancers can also be rare by their anatomical location when arising from the paranasal sinuses, salivary glands and ear. Their location requires knowledge of their specific extension routes, and may call for a specific surgical technique (skull base endoscopic sinus surgery, extended total parotidectomy, etc.) and adapted radiotherapy to spare healthy organs surrounding the tumor. This article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the French ENT Cancer Expertise Network (REFCOR) concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. A second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.
Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Doenças Raras , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias dos Seios Paranasais/patologia , HumanosRESUMO
OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive disease requiring multimodal treatment, and multiple new entities once included in the spectrum of SNUC, such as SWI/SNF-deficient carcinomas, are emerging. We aimed to provide new data regarding the role of chemotherapy and surgery and the prognostic factors of disease-free survival. METHODS: This study was based on data from the REFCOR database and included patients with SNUC treated with curative intent from 2007 to 2021 across 22 centres in France. RESULTS: A total of 80 patients were included in the analysis. Among the entire cohort, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58% and 63%, respectively. Of 100% of the patients treated with irradiation, 29% underwent surgery, 56% neoadjuvant chemotherapy (82% had either a partial or a complete response) and 76% chemoradiotherapy. No treatment modality was associated with a better OS or DFS, including surgery (p = 0.34). There was a trend for a better DFS for the patients treated with chemotherapy (neoadjuvant or concomitant, p = 0.062). Overall survival at 3 years was 58% for SWI/SNF deficient group and 86% for non deficient group (p = 0.14). The locoregional relapse rate without distant metastases was 21% in the exclusive radiotherapy group and 26% in the surgery group. Grade 3 or higher toxicities concerned 9%, 32% and 29% of patients for surgery, radiotherapy and chemotherapy respectively. CONCLUSION: In the management of localised SNUC among all patients treated with irradiation, surgery yielded no benefit, whereas the addition of chemotherapy tended to improve disease-free survival.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias do Seio Maxilar , Humanos , Recidiva Local de Neoplasia/terapia , Neoplasias do Seio Maxilar/terapia , Terapia Combinada , Estudos RetrospectivosRESUMO
BACKGROUND: Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. PATIENTS AND METHODS: Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. RESULTS: A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3-T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). CONCLUSIONS: These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3-T4 status and/or intermediate/high histological grade.
Assuntos
Carcinoma de Células Acinares , Neoplasias das Glândulas Salivares , Humanos , Masculino , Prognóstico , Radioterapia Adjuvante , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia , Carcinoma de Células Acinares/radioterapia , Carcinoma de Células Acinares/cirurgia , Carcinoma de Células Acinares/patologia , Esvaziamento Cervical , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Supporting a cancer patient up until the end of life and then mourning the loss represents a long, and emotionally marking period that is potentially problematic for health professionals. In addition to individual and environmental characteristics-and related to death or to the relationship prior to death-the communication established between the doctor, patient, family members and other health professionals in the team, seems to determine how an individual experiences the loss and mourning process. Acknowledging the suffering of the bereavement without always being able to respond is neither easy nor trivial, requiring modified/appropriate knowledge and skills. The opportunity to share their experiences within a healthcare team and with external health care professionals guarantees an ethical approach, professional enrichment and limits the risk of burnouts. In order to offer guidance and potential solutions, the references specific to cancerology are regularly updated in France by the AFSOS ("French Association of Supportive Cancer Care"). This multidisciplinary effort, including professionals from different professional societies (AFSOS, SFFPO, SFAP) and coordinated by the cancerology network of Nouvelle Aquitaine (Onco-Nouvelle-Aquitaine), has resulted in the recent publication of two complementary resources that address bereavement. The first report provides theoretical guidelines, while the second proposes a more clinical approach on how to support a mourning individual. Thus, with regards to the clinical situation and contextualization of the aforementioned references, this article considers the dimensions of separation, bereavement, and supportive care and further discusses tools to help health professionals protect themselves when affronting these situations.
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Luto , Neoplasias , Comunicação , Morte , Família , Pesar , Humanos , Neoplasias/terapiaRESUMO
BACKGROUND: Pazopanib is a tyrosine kinase inhibitor given at the approved dose of 800 mg orally once daily (OD), but often requiring individual dose adjustment due to toxicity. Limited data is available to guide prescription in older patients especially the unfit according to geriatric assessment. PATIENTS AND METHODS: VOTRAGE is a 3 + 3 dose-escalation, open-label phase I trial of continuous OD oral administration of pazopanib to evaluate safety, PK and PD data in unfit older patients with advanced solid tumors. The primary objective was to determine the maximum tolerated dose (MTD). PK data were compared with those obtained in younger adult patients in a population PK analysis. RESULTS: Eighteen patients with a median age of 82.5 years (range 75-91) were included in three dosing cohorts (400, 600, and 800 mg daily). Three dose-limiting toxicities (DLT) were observed in five patients at 800 mg and one DLT at 600 mg in six evaluable patients. MTD was defined as level 2 dose (600 mg). Individual oral clearance was not correlated with age. A relationship was observed between the occurrence of DLT and pazopanib plasma exposure. Decreased oral bioavailability of pazopanib when given with proton-pump inhibitors was confirmed in this group of patients. CONCLUSION: We recommend performing geriatric assessment in patients older than 75 and starting pazopanib at 600 mg per day in unfit older patients. Therapeutic drug monitoring appears very helpful in this population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Humanos , Indazóis , Neoplasias/tratamento farmacológico , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: Due to their advanced age in average, colon cancer patients are likely to be exposed to comorbidity. However, the influence of comorbidity on patients' care trajectory and survival is largely under-explored. Hence, we investigate the effect of comorbidity on patients care trajectory and survival based on an observational study in "real-life" setting. METHODS: This prospective observational study in two French regions includes patients aged over 18 and firstly treated for a colon cancer, stage II and III, diagnosed between 1st January and 31st December 2010. We assessed the influence of comorbidity (severe vs moderate or none), using the Charlson Comorbidity Index, on overall survival and patients' management steps. RESULTS: We analyzed 762 patients. We found comorbidity to be associated with adjuvant treatment delivery with a longer delay between surgery and chemotherapy initiation among patients with severe comorbidity. Severe comorbidity had an independent detrimental effect on overall survival that is slightly downsized after adjustment for adjuvant treatment delivery. CONCLUSION: Using observational "real-life" data, we showed that comorbidity impacts the colon cancer patients' care trajectory directly but also through indirect pathways involving adjuvant chemotherapy delivery. However, further studies are needed to better understand this mechanism.
Assuntos
Neoplasias do Colo , Idoso , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/terapia , Comorbidade , Humanos , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: Multikinase inhibitor (MKI) treatments have shown efficacy in progressive radioiodine refractory thyroid cancers (RAIR-TC), but most patients experienced substantial adverse effects. This randomised multicentric study investigated intermittent versus continuous pazopanib administration. PATIENTS AND METHODS: The PAZOTHYR study included RAIR-TC patients with progressive disease in the last 12 months, who may have received one prior MKI. RAIR-TC patients received pazopanib for 6 months, and patients with stable disease or tumour response were randomly assigned (1:1) to receive continuous (CP) or intermittent (IP) pazopanib until progression. The primary end-point was time to treatment failure (TTF) defined as the time from randomisation to permanent discontinuation of pazopanib, due to any cause. One hundred randomised patients were needed to demonstrate an increase from 50% (CP) to 70% (IP) (hazard ratio (HR) 0.515, 80% power) in the rate of patients still under treatment 6 months (6m-SuT) post-randomisation. Secondary end-points included the overall response rate (ORR), progression-free survival (PFS) under pazopanib and safety. RESULTS: RAIR-TC patients (168) enrolled from June 18, 2013 to January 16, 2018, received 6-month pazopanib treatment and showed 35.6% (95% CI 28.2-43.6) best response rate and 89.4% (83.5-93.7) disease control rate. One hundred patients were randomised (IP:50; CP:50). With a median follow-up of 31.3 months, median TTF was not statistically different between arms (IP:14.7, 95% confidence interval (CI) 9.3-17.4; CP:11.9, 95% CI 7.5-15.6) months (HR 0.79, 0.49-1.27). 6m-SuT rates were similar (IP:80% 66.0-88.7%; CP:78% 63.8-87.2%). Median PFS under pazopanib were not statistically different (IP:5.7 4.8-7.8; CP: 9.2 7.3-11.1) months (HR 1.36, 0.88-2.12). Pazopanib-related adverse events grade 3-4 occurred in 36 (IP: 19, 38%; CP: 17, 34%) randomised patients. Seven pazopanib-related deaths occurred. CONCLUSIONS: Intermittent administration of pazopanib did not demonstrate significant superiority in efficacy or tolerance compared with continuous treatment. An intermittent administration scheme cannot be recommended outside clinical trials. This study was registered with ClinicalTrial.gov, number NCT01813136.
Assuntos
Indazóis/administração & dosagem , Radioisótopos do Iodo/uso terapêutico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Indazóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Sulfonamidas/efeitos adversos , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/radioterapia , Falha de TratamentoRESUMO
Sinonasal carcinomas account for 3% of ENT cancers. They are subdivided into squamous cell carcinomas (50%), adenocarcinomas [20%, mostly of intestinal type (ITAC)], and more rarely, adenoid cystic carcinomas, olfactory neuroblastomas (=esthesioneuroblastomas), neuroendocrine carcinomas or undifferentiated sinonasal carcinomas (SNUC). The 5-year survival rates are, in descending order, 72% for neuroblastomas, 63% for adenocarcinomas, 50-60% for large-cell neuroendocrine carcinomas, 53% for squamous cell carcinomas, 25-50% for adenoid cystic, 35% for small-cell neuroendocrine carcinomas and 35% for SNUC and newly discovered histologies. Surgery is the main treatment; endoscopic approaches reduce the morbidity with equivalent tumour control. Intensity-modulated radiation therapy (IMRT) is almost systematic. Nodal involvement is rare in ethmoidal adenocarcinomas and adenoid cystic carcinomas; it is intermediate and may justify prophylactic radiotherapy for N0 necks in SNUC, neuroblastoma, squamous cell carcinomas and sinonasal neuroendocrine carcinomas. IMRT or proton therapy is the mainstay of treatment of unresectable disease. Radiotherapy optimization by carbon ion therapy for adenoid cystic carcinomas, or by chemotherapy for all carcinomas with IMRT or proton therapy, is investigated within clinical trials in France. Neoadjuvant chemotherapy is reserved for rapidly progressive disease or histologies with a high metastatic potential such as neuroendocrine carcinomas or SNUC. Given their histologic and molecular specificities and different relapse patterns, an expertise of the REFCOR network, with REFCORpath review, is likely to correct diagnoses, rectify treatments, with an impact on survival.
Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias dos Seios Paranasais , Doenças Raras , Adenocarcinoma/classificação , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/terapia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/terapia , Carcinoma de Células Escamosas/classificação , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Humanos , Neoplasias dos Seios Paranasais/classificação , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/terapia , Prognóstico , Doenças Raras/diagnóstico , Doenças Raras/mortalidade , Doenças Raras/terapiaRESUMO
BACKGROUND: The management of patients with locally recurrent rectal cancer (LRRC) is often complex and requires multidisciplinary input whereas only few patients are referred to a specialist centre. The aim of this study was to design a regional referral pathway for LRRC, in Nouvelle Aquitaine (South-West, France). METHODS: In 2016, we conducted with a Study Steering Committee (SC) a three phase mixed-methods study including identification of key factors, identification of key stakeholders and Delphi voting consensus. During three rounds of Delphi voting, a consensus was defined as favorable, if at least 80% of participating experts rate the factor, below or equal to 3/10 using a Likert scale, or consider it as "useful" using a binary scale (third round only). Finally, the SC drafted guidelines. RESULTS: Among the 423 physicians involved in 29 regional digestive Multi-Disciplinary Team (MDT) meeting, 59 participants (from 26 MDT meeting) completed all three rounds of Delphi voting. Thirteen out of twenty initially selected factors reached a favorable consensus. All patients with a LRRC need to be included into a referral pathway. Patients with a central pelvic recurrence offered curative treatment in their local hospital and patients with unresectable metastatic disease were excluded of the referral. Key performance indicators were also agreed including the time to referral and completion of pelvic MRI-, CT-, PET-scan prior to MDT referral. CONCLUSION: The development of this referral pathway represents an innovative health service, which will improve the management of patients with LRRC in France.
Assuntos
Consenso , Gerenciamento Clínico , Recidiva Local de Neoplasia/terapia , Equipe de Assistência ao Paciente/organização & administração , Encaminhamento e Consulta/organização & administração , Técnica Delphi , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico , Tomografia por Emissão de Pósitrons , Neoplasias RetaisRESUMO
BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours [1] and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic factors influencing the event-free survival (EFS) of patients with ACC. PATIENTS AND METHODS: A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software. RESULTS: Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age ≥65 years (hazard ratio [HR] = 1.67), BMI<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08). CONCLUSION: Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.
Assuntos
Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/epidemiologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/terapia , Estudos de Coortes , Progressão da Doença , Feminino , França/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Fatores de Risco , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/epidemiologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Análise de Sobrevida , Adulto JovemRESUMO
Among the 20,000 new cases of head and neck neoplasms in France each year, squamous cell carcinomas (HNSCC) represent about 90 % of the cases. Among these, variants of conventional squamous cell carcinomas represent between 5% and 10% of cases. Patient history and risk factors are often similar from those of conventional HSNCC. Variants may, however, be misdiagnosed, which can lead to therapeutic mismanagement due to confusion with sarcomas, glandular tumors or even benign tumors. Diagnostic workup needs to be more cautionary or to include additional exams not to omit their most aggressive component in the case of composite tumors or to under stage the tumor. Immunohistochemistry and specific molecular analyses may be required for proper diagnosis. Central pathological review may also be essential for some of these variants. In addition, some variants are radioresistant and, conversely, others are radiosensitive. An update of the REFCOR 2008 standards was carried out in the light of the international literature and the 2017 WHO/IARC classification for the seven main variants of HNSCC, verrucous, acantholytic (to be named adenoid carcinomas), basaloid, papillary, spindle cell (incorrectly named sarcomatoid), adenosquamous and lymphoepithelial carcinomas.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Doenças Raras , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/terapia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/patologia , Carcinoma Papilar/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma Verrucoso/diagnóstico , Carcinoma Verrucoso/patologia , Carcinoma Verrucoso/terapia , Diagnóstico Diferencial , Erros de Diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Doenças Raras/diagnóstico , Doenças Raras/patologia , Doenças Raras/terapiaRESUMO
AIM: To identify factors that may prevent or delay patients referred for consideration of phase I studies from commencing such a study. METHODS: A retrospective audit of phase I study referrals for the period 1st March to 31st August 2005 to the Drug Development Unit was performed. All reasons that led to either delay or recruitment failure were documented and analysed. RESULTS: Data from 176 patients (105M/71F) were analysed. Median age at referral was 59 years and median performance status (PS) was 1. Of these, 56 (32%) were successfully recruited in a phase I trial. The median time from trial allocation to commencement of treatment was 4.8 weeks. Poor or deteriorating PS was the reason for delay or recruitment failure in 43 (35%) of non-recruited patients. CONCLUSIONS: Poor or deteriorating PS was the most common factor limiting accrual to phase I trials. Better patients' selection on this basis might improve recruitment rates.
Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase I como Assunto/métodos , Neoplasias/tratamento farmacológico , Seleção de Pacientes , Encaminhamento e Consulta/organização & administração , Adulto , Idoso , Feminino , Hospitalização , Humanos , Londres , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Encaminhamento e Consulta/normas , Estudos Retrospectivos , Fatores de Tempo , Listas de EsperaRESUMO
BACKGROUND: Induction chemotherapy (IC) with TPF (docetaxel, cisplatin, 5FU) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is limited to fit patients. OBJECTIVE: We conducted a retrospective cohort study to assess the use of the EXTREME regimen (platinum-based therapy, 5FU, cetuximab) as IC in frail patients with LAHNSCC. PATIENTS AND METHODS: Retrospective analysis of all consecutive patients with unresectable LAHNSCC treated with the EXTREME regimen, with or without 5FU as IC, from two French centers from 2008 to 2015. We assessed the rate of completed sequence defined as at least two cycles of IC and definitive radiation therapy. RESULTS: We included 34 patients with a median age of 56 years [44-70]. The primary site of tumor development was the oropharynx (67%, n=23, all HPV negative), hypopharynx (21%, n=7) and the oral cavity (12%, n=4). At inclusion, patients presented: T4 76, 5% (n=26), N2c 41% (n=14), N3 26% (n=9), stage disease IVa 62% (n=21), IVb 38% (n=13), ECOG PS2 38% (n=13), decreased weight (10% in one month or 15% in 6 months) 74% (n=25). The sequence was achieved for 76% (n=26) of patients and 80% (n=27) presented a clinical response after the chemotherapy course with notably increased weight (40%, n=11) or general status (75%, n=26). Median PFS and OS were 5.7 and 15.5 months, respectively. Disease progression at 3 months was significantly associated with decreased median overall survival (13.6 versus 21.9 months, p=0.01). CONCLUSION: This is the first study to report the use of the EXTREME regimen as induction chemotherapy, and although this IC was used in a very frail population, the majority completed the sequence with significant clinical benefit.
Assuntos
Quimioterapia de Indução/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Idoso Fragilizado , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Malnutrition is common in oncology. However, it is often detected too late and nutritional support is sub-optimal. The patient's opinion, although often sought in therapeutic decisions in oncology, does not appear to be frequently taken into account in dietetic management. In NutriCancer2012 study, we interviewed patients, relatives and doctors about their perceptions of the impact of malnutrition and its quality of care. Of the 2209 patients questioned, majority said they were concerned about nutrition with 75% considering it essential to take appropriate nutritional care but only 19% self-reported link between malnutrition and fatigue. Physicians underestimated impact of malnutrition on patient's "quality of life". Doctors referred to the lack of human resources and knowledge in nutrition, and more than 80% wished the creation of nutrition teams. Sensitization of the general public and patients (and relatives) as soon as the cancer diagnosis could lead to better malnutrition's screening. Better nutrition training for physicians and creation of nutrition team could optimize management and improve efficacy during cancer treatments.
Assuntos
Desnutrição/psicologia , Oncologia , Neoplasias/complicações , Pacientes/psicologia , Médicos/psicologia , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Educação Médica Continuada , Fadiga/etiologia , França , Pesquisas sobre Atenção à Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Desnutrição/dietoterapia , Desnutrição/etiologia , Neoplasias/metabolismo , Ciências da Nutrição/educação , Apoio Nutricional , Relações Médico-Paciente , Qualidade de VidaRESUMO
PURPOSE: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting. PATIENTS AND METHODS: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point. Secondary end-points were progression-free survival, overall survival and safety. RESULTS: Seventy-one patients were enrolled from August 2007 to October 2009, 41 MDTC/4 MATC patients and 26 MMTC patients. Patients received a median of 8 and 9 cycles, respectively. In the MDTC/MATC group, 13% of patients and 43% of cycles and in the MMTC group, 23% of the patients and 48.8% of cycles remained at 50 mg/d, respectively. The primary end-point was reached with an objective response rate of 22% (95% CI: 10.6-37.6) in MDTC patients and in 38.5% (95% CI: 22.6-56.4) in MMTC patients. No objective response was seen in MATC patients. Median progression-free survival and overall survival were 13.1 and 26.4 months in MDTC patients, 16.5 and 29.4 months in MMTC patients. The most frequent side effects were asthenia/fatigue (27.8% ≥ grade 3), mucosal (9.9% ≥ grade 3), cutaneous toxicities, hand-foot syndrome (18.3% ≥ grade 3). Of all, 14.1% had a cardiac event. Nine unexpected side effects were reported, out of which, five induced deaths. CONCLUSION: Sunitinib is active in MDTC and MMTC patients. Side effects were more severe than with previous reports. If using sunitinib, alternative schedule/dosage should be considered.