RESUMO
BACKGROUND: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. METHODS: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m2) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m2) every 2 weeks followed by three cycles of intensified CMF (Control Arm A, E-T-CMF) that was previously used in BC or three cycles of epirubicin followed by three cycles of CMF followed by nine consecutive weekly cycles of docetaxel (wD) 35 mg/m2 (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m2 (Arm C, E-CMF-wT). Trastuzumab was administered for HER2-positive disease. RESULTS: At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms. CONCLUSIONS: Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000151033.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália , Quimioterapia Adjuvante , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Epirubicina/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Humanos , Paclitaxel/efeitos adversos , Trastuzumab/efeitos adversosRESUMO
Neuroendocrine neoplasms (NENs) are a group of heterogeneous malignancies, arising from the neuroendocrine system. These neoplasms are divided into two distinct groups, the low-proliferating, well-differentiated neuroendocrine tumors (NETs), and the highly-proliferating, poorly-differentiated neuroendocrine carcinomas (NECs). Recent data demonstrate that the incidence of gastroenteropancreatic (GEP) neuroendocrine neoplasms, GEP-NETs and GEP-NECs, has increased exponentially over the last three decades. Although surgical resection is considered the best treatment modality, patients with GEP-NETs often present with advanced disease at diagnosis associated with a 5-year survival rate of 57% for well-differentiated tumors, and only 5.2% for small-cell tumors. Immunotherapy is a novel treatment approach, which has demonstrated effective and promising therapeutic results against several types of cancers. In the present study, we review the current ongoing clinical trials and to evaluate the efficacy of immunotherapy in GEP-NENs. Furthermore, we analyze the importance of tumor genetic profiling and its clinical implications in immunotherapy response.
Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Imunoterapia , Neoplasias Intestinais/genética , Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológicoRESUMO
BACKGROUND: Data on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with concurrent autoimmune diseases (AID) are limited. METHODS: We performed a retrospective multicenter review of medical records of patients with cancer and underlying AID who received ICI. The primary endpoint was progression-free survival (PFS). RESULTS: Among 123 patients with pre-existing AID who received ICI, the majority had been diagnosed with non-small cell lung cancer (NSCLC, 68.3%) and melanoma (14.6%). Most patients had a rheumatologic (43.9%), or an endocrine disorder (21.1%). Overall, 74 (60.2%) patients experienced an immune-related adverse event (irAE) after ICI initiation, AID flare (25.2%), or new irAE (35%). Frequent irAEs included thyroiditis, dermatitis and colitis. ICI was permanently discontinued due to unacceptable (8.1%) or fatal (0.8%) toxicity. In patients with NSCLC, corticosteroid treatment at the initiation of immunotherapy was associated with poor PFS (HR = 2.78, 95% CI 1.40-5.50, p = 0.003). The occurrence of irAE was associated with increased PFS (HR = 0.48, 95% CI 0.25-0.92, p = 0.026). Both parameters maintained their independent prognostic significance. CONCLUSIONS: ICI in patients with cancer and pre-existing AID is associated with manageable toxicity that infrequently requires treatment discontinuation. However, since severe AID flare might occur, expected ICI efficacy and toxicity must be balanced. CLINICAL TRIAL IDENTIFIER: NCT04805099.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/mortalidade , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Stress management programs have demonstrated benefits for patients with breast cancer, but their adoption in clinical practice is limited mainly due to the absence of necessary resources. The aim of this study was to investigate the effects of an 8-week stress management program, carried out by one psychologist, in women treated for breast cancer. In this randomized controlled trial, patients were allocated to two groups (control and intervention groups) that received standard care; women in the intervention group also participated in an 8-week stress management program. Intervention included stress- and diet-related psychoeducation, diaphragmatic breathing, guided imagery, progressive muscle relaxation, and cognitive reconstruction. Anthropometric and psychological measurements were carried out in both groups, pre- and post-intervention, using a battery of questionnaires. A total of 53 patients participated in the study, of whom 27 in the intervention group. Analysis revealed statistically significant differences between the two groups post-intervention in body mass index (P = 0.040) and quality of life, including global health status (P = 0.019), emotional functioning (P = 0.024), cognitive functioning (P = 0.041), and diarrhea (P = 0.012). There was a statistically significant effect of the type of surgery (partial or total mastectomy) to role functioning (P = 0.030), with major benefits identified in the subgroup of patients that had undergone mastectomy with immediate reconstruction. This stress management program, carried out by a single health professional, significantly improved some psychosomatic health parameters of patients with breast cancer. Short interventional programs can be successfully implemented with minimal resources to deliver quality care in these women.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/cirurgia , Aconselhamento , Feminino , Humanos , Mastectomia , Qualidade de Vida , Estresse Psicológico/terapia , Inquéritos e QuestionáriosRESUMO
Rumination has been identified as a negative psychological response of women diagnosed with breast cancer. The aim of the present study was to validate the Event-Related Rumination Inventory (ERRI) in Greek women with breast cancer. Sixty female patients with newly diagnosed breast cancer were included in the study. The ERRI questionnaire was translated with the back-forward procedure. Sociodemographic, anthropometric, and medical parameters were also assessed. The principal component analysis resulted in the following two-factor solution: (1) intrusive thoughts and (2) positive outcome. All subscales showed satisfactory internal consistency and variance, relative to theoretical score ranges. Subscale scores and the total score were significantly correlated with post-traumatic growth, distress, depression, and anxiety, demonstrating good criterion validity. Associations with patients' sociodemographic and medical characteristics, such as the stage of the disease and the type of treatment, were also identified. The Greek version of the ERRI provides valid and reliable measures of rumination when administered to women with breast cancer.
Assuntos
Idioma , Transtornos Mentais , Ansiedade , Cognição , Feminino , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Psychosocial interventions in families of children with cancer are considered an effective way of empowering family members to tackle the complex hurdles they face. The ability of parents to develop adaptive coping strategies during the child's treatment is not only important to their own mental and physical health, but also to their child's well-being and long-term adjustment with the disease. METHODS: The aim of this review was to evaluate the existing literature for the period from 2009 to 2017 on psychosocial interventions targeting families of children with cancer. We searched the PubMed database using the following combination of keywords: "cancer AND children AND (intervention OR training) AND (mothers OR primary caregivers OR parents OR fathers OR siblings)." RESULTS: After careful evaluation of 995 papers, 17 full-text papers were found to match our criteria (12 randomized controlled trials and 5 quasi-experimental studies). The quality of the studies was assessed using the Delphi score questionnaire, and the score of the reviewed studies ranged from 3 to 5. The findings suggest that most interventions reduced distress and improved coping strategies among participants. Interventions, mainly cognitive behavioral therapy and problem-solving skills training targeting maternal distress, were associated with improved adjustment outcomes in mothers of children with cancer. SIGNIFICANCE OF RESULTS: Psychosocial interventions are helpful, and efforts should be made to promote them in a larger scale. Protocols should be implemented to ensure that all parents benefit. Computer-assisted methods may provide additional benefit by improving cancer-related knowledge and cancer-related communication.
Assuntos
Neoplasias , Intervenção Psicossocial , Adaptação Psicológica , Criança , Pai , Feminino , Humanos , Masculino , Mães , Neoplasias/terapiaRESUMO
BACKGROUND: Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. In the past, single-gene analysis of specific high risk genes was used for the determination of the genetic cause of cancer heritability in certain families. The application of Next Generation Sequencing (NGS) technology has facilitated multigene panel analysis and is widely used in clinical practice, for the identification of individuals with cancer predisposing gene variants. The purpose of this study was to investigate the extent and nature of variants in genes implicated in hereditary cancer predisposition in individuals referred for testing in our laboratory. METHODS: In total, 1197 individuals from Greece, Romania and Turkey were referred to our laboratory for genetic testing in the past 4 years. The majority of referrals included individuals with personal of family history of breast and/or ovarian cancer. The analysis of genes involved in hereditary cancer predisposition was performed using a NGS approach. Genomic DNA was enriched for targeted regions of 36 genes and sequencing was carried out using the Illumina NGS technology. The presence of large genomic rearrangements (LGRs) was investigated by computational analysis and Multiplex Ligation-dependent Probe Amplification (MLPA). RESULTS: A pathogenic variant was identified in 264 of 1197 individuals (22.1%) analyzed while a variant of uncertain significance (VUS) was identified in 34.8% of cases. Clinically significant variants were identified in 29 of the 36 genes analyzed. Concerning the mutation distribution among individuals with positive findings, 43.6% were located in the BRCA1/2 genes whereas 21.6, 19.9, and 15.0% in other high, moderate and low risk genes respectively. Notably, 25 of the 264 positive individuals (9.5%) carried clinically significant variants in two different genes and 6.1% had a LGR. CONCLUSIONS: In our cohort, analysis of all the genes in the panel allowed the identification of 4.3 and 8.1% additional pathogenic variants in other high or moderate/low risk genes, respectively, enabling personalized management decisions for these individuals and supporting the clinical significance of multigene panel analysis in hereditary cancer predisposition.
Assuntos
Neoplasias da Mama/genética , Neoplasias Colorretais/genética , Testes Genéticos/métodos , Mutação , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Variação Genética , Grécia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , Romênia , Turquia , Adulto JovemRESUMO
BACKGROUND: Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers. METHODS: Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. -Results: Seventy-nine patients with gastroenteropancreatic (grades 1-2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6-55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6-14.2) and 102.9 months (43.3-162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1-0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11-4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3-4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months). CONCLUSIONS: CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Capecitabina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Análise de Sobrevida , Temozolomida/administração & dosagem , Resultado do TratamentoRESUMO
The majority of neuroendocrine tumours (NETs) are well-differentiated tumours that follow an indolent course, in contrast to a minority of poorly differentiated neuroendocrine carcinomas (NECs) which exhibit an aggressive course and assocaited with an overall short survival. Although surgery is the only curative treatment for NETs it is not always feasible,necessitating the application of other therapies including chemotherapy. Streptozotocin (STZ)-based regimens have long been used for advanced or metastatic well-to-moderately differentiated (G1-G2) NETs, especially those originating from the pancreas (pNETs). In poorly differentiated grade 3 (G3) tumours, platinum-based chemotherapy is recommended as first-line therapy, albeit without durable responses. Although data for temozolomide (TMZ)-based chemotherapy are still evolving, this treatment may replace STZ-based regimens in pNETs due to its better tolerability and side effect profile. In addition, there is evidence that TMZ could also be used in the subgroup of well-differentiated G3 NETs. There is less clear-cut evidence of a benefit for chemotherapy in intestinal NETs, but still evolving data suggest that TMZ may be efficacious in particular patients. In lung and thymic carcinoids, chemotherapy is reserved for patients with progressive metastatic disease in whom other treatment options are unavailable. Overall, chemotherapy is indicated in patients who have progressed on first-line treatment with somatostatin analogues, have extensive tumour load or exhibit rapid growth following a period of follow-up, and/or have a high proliferative rate; it may occasionally can be used in a neo-adjuvant setting. Prospective randomised studies are awaited to substantiate the role of chemotherapy in the therapeutic algorithm of NETs along with other evolving treatments.
Assuntos
Antineoplásicos/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , HumanosRESUMO
BACKGROUND: Many cancer patients use a wide variety of techniques to improve their physical and mental well-being, including relaxation therapy and, specifically, Progressive Muscle Relaxation (PMR). However, there is no strong evidence that supports the efficacy of this technique. OBJECTIVE: Our aim was to review the evidence regarding the use of PMR as a supportive intervention for cancer patients undergoing chemotherapeutic treatment. METHOD: Six databases were electronically searched: AMED, the Cochrane Library, MEDLINE, PsychINFO, Scopus, and the Web of Science. After removing duplicates, 700 publications were screened and 57 identified as potentially relevant. The flow of information from record identification to study inclusion was conducted in accordance with the PRISMA statement. Original articles published in peer-reviewed journals that studied the use of PMR as an intervention, were randomized or included a matched control group, and that included patients receiving chemotherapy were included. Studies that combined PMR with other interventions were excluded. The methodological quality of included trials was assessed using the Jadad Scale and the CONSORT guidelines. RESULTS: A total of 5 of the 57 papers fulfilled the preset criteria and were included in our systematic review. Our findings indicate that PMR might improve comfort and reduce the anxiety levels and side effects caused by chemotherapy, with the exception of vomiting. Nonetheless, the quality of all the included studies was extremely low. SIGNIFICANCE OF RESULTS: There is evidence that PMR might have a few benefits for patients undergoing chemotherapy. Still, the small number of studies included and their poor quality limit the significance of our results. Despite the fact that pharmaceutical approaches for controlling side effects might be reaching their full potential and that there might be further usefulness for such integrative treatments as PMR, the need to run more high-quality trials testing the efficacy of this technique is warranted before suggesting its adoption as part of standard cancer care.
Assuntos
Tratamento Farmacológico/psicologia , Terapia por Exercício/normas , Relaxamento Muscular , Neoplasias/terapia , Resultado do Tratamento , Terapia por Exercício/métodos , Humanos , Neoplasias/psicologiaRESUMO
BACKGROUND: The rare incidence of neuroendocrine neoplasms (NENs) has contributed to a paucity of large epidemiologic studies of patients with this condition. We investigated the occurrence and clinicopathologic features of NENs in Greece. METHODS: Between October 2010 and November 2012 we collected data on 246 newly diagnosed patients from a broad-based multi-institutional registry that comprises eight academic and hospital sites in Greece. The WHO 2010 pathologic classification and the 7th AJCC Staging system was applied in all cases. RESULTS: Of all patients 94 % had a sporadic and 6 % a multiple endocrine neoplasia tumor; 63.4 % were gastroenteropancreatic-(GEP)-NENs, 17.9 % Head & Neck NENs, 9.8 % NENs of Unknown Primary, 6.5 % Lung NENs and 2.4 % Pheochromocytomas. Gastric and pancreatic NENs were the most common primary sites. Poorly differentiated neuroendocrine carcinomas (NEC) were 9.3 %, all sporadic. Fifteen percent of patients were asymptomatic at presentation, 24 % had a first symptom of the disease related to endocrine syndrome and 61 % had symptoms related to locally advanced or metastatic disease. Metastatic disease was established in 25 % of tumors most frequently in the GEP NEN group. Findings are presented according to Ki-67 distribution. MRI had a higher diagnostic positive yield than Octreoscan. Somatostatin analogs, lanreotide and octreotide acetate, were prescribed at 38.5 & 61.5 % of NEN patients respectively and were found to be equally effective at providing symptomatic relief. CONCLUSIONS: This is to our knowledge the first study of a Greek tumor registry and one of the few European Registries providing information regarding clinicopathologic characteristics and therapies in patients with neuroendocrine tumors of various origin sites, beyond GEP NENs.
Assuntos
Tumores Neuroendócrinos/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/patologia , Grécia/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Adulto JovemRESUMO
Alkylating agents, such as streptozocin and dacarbazine, have been reported as active in neuroendocrine neoplasms (NENs). Temozolomide (TMZ) is an oral, potentially less toxic derivative of dacarbazine, which has shown activity both as a single agent and in combination with other drugs. Nevertheless, its role in NENs has not been well defined. Several retrospective and prospective phase I-II studies have been published describing its use in a variety of NENs. In a retrospective series, the combination of capecitabine and TMZ was reported to be associated with a particularly high tumour response in pancreatic NENs as a first-line treatment. Although in NENs, determination of the O6-methylguanine-DNA methyltransferase (MGMT) status has been suggested as a predictive biomarker of response, its role still remains investigational, awaiting validation along with the establishment of the optimal detection method. Metronomic schedules have been reported to potentially overcome MGMT-related drug resistance. Toxicity is manageable if well monitored. We reviewed the literature regarding pharmacological and clinical aspects of TMZ, focusing on specific settings of NENs, different schedules, toxicity and safety profiles, and potential predictive biomarkers of response.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Tumores Neuroendócrinos/tratamento farmacológico , Antineoplásicos Alquilantes/farmacocinética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/toxicidade , Dacarbazina/farmacocinética , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Dacarbazina/toxicidade , Humanos , TemozolomidaAssuntos
Tumores Neuroendócrinos , Temozolomida , Capecitabina , Dacarbazina , Duração da Terapia , HumanosAssuntos
Infecções por Coronavirus/economia , Infecções por Coronavirus/prevenção & controle , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/cirurgia , Pandemias/economia , Pandemias/prevenção & controle , Pneumonia Viral/economia , Pneumonia Viral/prevenção & controle , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Atenção à Saúde/economia , Grécia/epidemiologia , Humanos , Controle de Infecções/economia , Controle de Infecções/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/virologia , Programas Nacionais de Saúde/economia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Procedimentos Cirúrgicos Pulmonares/economia , Procedimentos Cirúrgicos Pulmonares/métodos , SARS-CoV-2RESUMO
Paraneoplastic syndromes such as dermatomyositis, often emerge as the initial clinical manifestation across various cancer types and are characterized by the development of B-cell responses targeting cancer-cell antigens that cross-react with normal skin and muscle cells. While these syndromes may alleviate following antineoplastic intervention, their response to immunotherapy remains elusive due to the exclusion of patients with autoimmune phenomena from clinical trials. In this report, we present the case of a female patient with advanced urothelial cancer presenting with dermatomyositis, who subsequently underwent treatment with anti-PD1 immunotherapy and experienced the onset of Stevens-Johnson syndrome. We discuss these two autoimmune entities and provide a comprehensive review of the existing literature to elucidate similar associations.
Dermatomyositis, an inflammatory disorder that causes a skin rash, might be the first sign that someone has cancer. But when scientists test new cancer treatments, they often don't include people with this skin problem. So, we do not know much about how safe or effective these treatments are for them. Here's a story about someone who had bladder cancer and dermatomyositis. They received a treatment called immunotherapy, but it caused a serious problem called Stevens-Johnson syndrome. We also found similar cases in medical papers.
RESUMO
Immunotherapy has revolutionised the treatment of oncological patients, but its application in various endocrine tumours is rather limited and is mainly used when conventional therapies have failed. Immune checkpoint inhibitors (ICIs) have been employed in progressive adrenocortical carcinoma, primarily utilizing the anti-PD-L1 agent pembrolizumab, obtaining overall response rates ranging between 14% and 23%. In contrast, the response rate in phaeochromocytoma/paraganglioma was substantially less at 9%, considering the small number of patients treated. Similarly, the response rate in advanced differentiated thyroid carcinomas treated with pembrolizumab was also low at 9%, although the combination of ICIs with tyrosine kinase inhibitors showed higher efficacy. Low response rates to ICIs have also been observed in progressive medullary thyroid cancer, except in tumours with a high mutation burden (TMB). Pembrolizumab or spartalizumab can be utilized in patients with high TMB anaplastic thyroid cancer, obtaining better response rates, particularly in patients with high PD-L1 expression. Immunotherapy has also been used in a few cases of parathyroid carcinoma, showing limited antitumour effect. Pituitary carcinomas may exhibit a more favourable response to ICIs compared to aggressive pituitary tumours, particularly corticotroph tumours. Patients with advanced neuroendocrine tumours achieve an overall response rate of 15%, which varies according to the primary tumour site of origin, degree of differentiation, and therapeutic regimen utilised. Future research is needed to evaluate the potential role of immunohistochemical biomarkers, such as programmed death 1/programmed death ligand 1 and TMB, as predictors for the response to immunotherapy. Furthermore, randomised prospective studies could provide more robust data on the efficacy and side effects of ICIs.
Assuntos
Neoplasias das Glândulas Suprarrenais , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Humanos , Estudos Prospectivos , Imunoterapia , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
BACKGROUND/AIM: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing. CASE REPORT: Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor's molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father's neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions. CONCLUSION: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.
Assuntos
Astrocitoma , Inibidor de Quinase Dependente de Ciclina p15 , Inibidor p16 de Quinase Dependente de Ciclina , Mutação em Linhagem Germinativa , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/genética , Astrocitoma/genética , Astrocitoma/patologia , Inibidor de Quinase Dependente de Ciclina p15/genética , Mutação em Linhagem Germinativa/genética , Sequenciamento de Nucleotídeos em Larga Escala , Predisposição Genética para Doença , Masculino , Feminino , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem , Imageamento por Ressonância Magnética , Deleção de GenesRESUMO
Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was performed on all samples using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed in the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary, molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.
RESUMO
Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.