RESUMO
INTRODUCTION: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. METHODS: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). RESULTS: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). CONCLUSION: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Turquia , Idoso , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/patologia , Imunoterapia/métodos , Doenças Raras/tratamento farmacológico , Doenças Raras/patologia , Doenças Raras/mortalidade , Adulto Jovem , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Only a few large-scale studies have focused on large cell neuroendocrine carcinoma, a rare type of pulmonary malignancy, and uniform diagnostic criteria and standardized treatments are lacking. This study aimed to assess the treatment outcomes and factors influencing patients' prognosis with large cell neuroendocrine carcinoma. METHODS: The data of 55 patients with pathologically confirmed large cell neuroendocrine carcinoma, treated at our hospital from January 2013 to January 2018, were collected. Relationships between clinical characteristics, diagnoses, treatment outcomes, and prognoses were retrospectively analyzed. RESULTS: Patients were followed for a median of 18.5 (0.5-41.0) months. Thirty-four patients died before the final follow-up, resulting in a median overall survival of 17.9 (0.5-36.0) months, with 1-, 2-, and 3-year survival rates of 69.1%, 23.6%, and 1.8%, respectively. Single-factor analysis identified gender (P=0.036), smoking history (P=0.008), obstructive atelectasis (P=0.032), regional lymph node metastasis (P=0.020), and treatment selection (P=0.000) as factors influencing overall survival. Multifactor analysis identified treatment selection as an independent survival prognostic factor. Particularly, significant differences were observed between the combination therapies (surgery+chemotherapy, surgery+radiotherapy, surgery+radiotherapy+chemotherapy, and concurrent chemoradiotherapy) and single-therapy approaches (chemotherapy or radiotherapy alone; P<0.001), but not among the combination therapies (P=0.216). DISCUSSION: Male patients with large cell neuroendocrine carcinoma with a history of smoking, obstructive atelectasis, and regional lymph node metastasis have a particularly poor prognosis. Our observation of the treatment approach as an independent survival prognostic factor suggests that combination therapies may yield survival benefits to patients.
Assuntos
Carcinoma de Células Grandes/mortalidade , Carcinoma Neuroendócrino/mortalidade , Neoplasias Pulmonares/mortalidade , Doenças Raras/mortalidade , Carcinoma de Células Grandes/terapia , Carcinoma Neuroendócrino/terapia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Atelectasia Pulmonar/complicações , Doenças Raras/terapia , Estudos Retrospectivos , Fatores Sexuais , Fumar/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Pediatric very rare tumors (VRTs) represent a heterogeneous subset of childhood cancers, with reliable survival estimates depending dramatically on each (un)registered case. The current study aimed to evaluate the number of VRTs among Lithuanian children, to assess the impact of the registration status on survival rates and to track changes in treatment outcomes over the 16-year study period. We performed a population-based retrospective study across children below 18 years old diagnosed with VRTs in Lithuania between the years 2000 and 2015. The identified cases were cross-checked with the Lithuanian Cancer Registry-a population-based epidemiology cancer registry-for the fact of registration and survival status. The overall survival was calculated in relation to the registration status and treatment period. Thirty-seven children with VRTs were identified within the defined time frame. Six of them (16.2%) were not reported to the Lithuanian Cancer Registry at diagnosis. The probability of overall survival at 5 years (OS5y) differed significantly between the registered (n = 31) and unregistered (n = 6) cohorts: 51.6% versus 100%, respectively (p = 0.049). A 5-year survival estimate for children diagnosed with a VRT at the age of 0-14 years differed by 10 percentage points according to the registration completeness: 52.1% calculated for the entire cohort versus 42.1% for registered patients only. The OS5y has not improved over the analyzed period: 61.1% in 2000-2007 versus 57.9% in 2008-2015 (p = 0.805). The survival continued to decline beyond 5 years post-diagnosis due to late cancer-related adverse events: 59.5% of patients were alive at 5 years as compared to 44.3% at 10 years. The OS5y of children affected by VRT was lower than in more common childhood cancers. The survival rate of the unregistered patients may lead to misinterpretation of treatment outcomes. Meticulous registration of VRTs is crucial for correct evaluation of treatment outcomes, especially across small countries with few cases.
Assuntos
Neoplasias/mortalidade , Doenças Raras/epidemiologia , Doenças Raras/mortalidade , Adolescente , Fatores Etários , Idade de Início , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Lactente , Recém-Nascido , Lituânia/epidemiologia , Masculino , Neoplasias/epidemiologia , Neoplasias/terapia , Avaliação de Resultados em Cuidados de Saúde , Vigilância em Saúde Pública , Sistema de Registros/normas , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Melanoma is derived from melanocytes located in multiple regions of the body. Cutaneous melanoma (CM) represents the major subgroup, but less-common subtypes including uveal melanoma (UM), mucosal melanoma (MM), and acral melanoma (AM) arise that have distinct genetic profiles. Treatments effective for CM are ineffective in UM, AM, and MM, and patient survival remains poor. As reprogrammed cancer metabolism is associated with tumorigenesis, the underlying mechanisms are well studied and provide therapeutic opportunities in many cancers; however, metabolism is less well studied in rarer melanoma subtypes. We summarize current knowledge of the metabolic alterations in rare melanoma and potential applications of targeting cancer metabolism to improve the therapeutic options available to UM, AM, and MM patients.
Assuntos
Melanoma/metabolismo , Redes e Vias Metabólicas/genética , Mucosa/patologia , Doenças Raras/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Uveais/metabolismo , Carcinogênese/genética , Carcinogênese/metabolismo , Progressão da Doença , Humanos , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Mutação , Doenças Raras/genética , Doenças Raras/mortalidade , Doenças Raras/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Neoplasias Uveais/genética , Neoplasias Uveais/mortalidade , Neoplasias Uveais/patologiaRESUMO
BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibodies are a standard treatment for metastatic melanoma patients. However, the understanding of the efficacy of anti-PD-1 for acral melanoma (AM) and mucosal melanoma (MM) is limited as these subtypes are relatively rare compared to cutaneous melanoma (CM). METHODS: This single institution, retrospective cohort study included patients with advanced AM and MM who underwent anti-PD-1 therapy for metastatic melanoma between 2012 and 2018. Objective responses were determined using the investigator-assessed Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method. A Cox regression analysis was performed to identify the factors associated with survival outcomes. RESULTS: Ninety-seven patients were identified, 38 (39%) with AM and 59 (61%) with MM. The objective response rates (ORRs) were 21.0% and 15.2% in patients with AM and MM, respectively. The median PFS and OS were 3.6 and 25.7 months for AM patients, and 3.0 and 20.1 months for MM patients, respectively. Elevated serum lactate dehydrogenase (LDH) (AM: hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.06-0.87; p = 0.03, MM: HR, 0.20; 95% CI, 0.08-0.53; p = 0.001) was significantly associated with shorter OS for both subtypes. CONCLUSIONS: The ORR, PFS, and OS with anti-PD-1 therapy were poor in patients with AM and MM compared to those previously reported clinical trials for nonacral CM. High serum LDH was associated with significantly shorter OS.
Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Doenças Raras/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Intervalos de Confiança , Feminino , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/sangue , Masculino , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Doenças Raras/genética , Doenças Raras/mortalidade , Doenças Raras/patologia , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.
Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Hemangiossarcoma/etiologia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/mortalidade , Feminino , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/mortalidade , Hemangiossarcoma/cirurgia , Humanos , Incidência , Estimativa de Kaplan-Meier , Mastectomia , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/mortalidade , Neoplasias Induzidas por Radiação/cirurgia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/cirurgia , Doenças Raras/epidemiologia , Doenças Raras/etiologia , Doenças Raras/mortalidade , Doenças Raras/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Neoplasias Unilaterais da Mama/epidemiologia , Neoplasias Unilaterais da Mama/etiologia , Neoplasias Unilaterais da Mama/mortalidadeRESUMO
PURPOSE: Glassy cell carcinoma (GCC) of the uterine cervix is a rare entity. This study aims at describing the clinical characteristics and outcomes of cervical GCC patients treated in a comprehensive cancer center. MATERIAL AND METHODS: We retrospectively reported patients and tumors characteristics, therapeutic management, overall survival (OS), progression-free progression (PFS), relapse rates, and toxicities. RESULTS: Between 1994 and 2014, 55 patients were treated with curative intent. The median age at diagnosis was 41 years (range, 20-68). Among 22 patients with early stage tumors (IA2-IB1-IIA1), 17 had preoperative brachytherapy, followed by radical hysterectomy. Among 33 patients with locally advanced disease (≥IB2), 32 underwent chemoradiation±brachytherapy boost. After a median follow-up of 5.4 years (range, 0.15-21.7 years), 18/55 (33%) patients experienced tumor relapse. Local recurrence occurred in 2/22 (9%) patients with early disease (treated with upfront surgery) and in 3/32 (9%) patients with locally advanced disease. Most frequent relapses were distant, occurring in a total of 11/55 patients (20%). PFS rates at 5-year were 86.4% (95% CI: 63.4-95.4) for early stage versus 75.9% (95% CI: 55.2-89.2) for locally advanced stages, respectively (P=0.18). CONCLUSION: Large cohort data are warranted to guide the optimal management of GCC. From this retrospective analysis, a multimodal approach yielded to good disease control in early stages tumors. Given the high-risk of distant failure, consideration should be given to adjuvant chemotherapy in locally advanced disease.
Assuntos
Carcinoma Adenoescamoso/terapia , Doenças Raras/terapia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Braquiterapia , Institutos de Câncer/estatística & dados numéricos , Carcinoma Adenoescamoso/epidemiologia , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Quimiorradioterapia/métodos , Terapia Combinada/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Doenças Raras/epidemiologia , Doenças Raras/mortalidade , Doenças Raras/patologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto JovemRESUMO
INTRODUCTION: Congenital microgastria is an extremely rare birth defect. The aim of this study was to present an overview of existing literature on the treatment of microgastria. MATERIALS AND METHODS: The term "microgastria" was used in a PubMed and Medline search. Since merely case reports were found, only a narrative synthesis with limited statistical analysis can be given. Data of different treatment modalities were collected and divided into two groups: conservative or less invasive treatment (C/LT, i.e., modified diet or a gastrostomy/jejunostomy) and extensive gastric surgery (EGS, i.e., Hunt-Lawrence pouch or total esophageal gastric dissociation). Clinical outcome parameters (nutrition, growth pattern, and mortality) were compared. RESULTS: Out of 73 articles published from 1973 to 2019, 38 articles describing 51 cases were included. In four patients, microgastria was an isolated anomaly (8%). Type of treatment was described in only 46 patients, 19 were treated by C/LT. Mortality was 9/19 (47%) in the C/LT group versus 4/27 (15%) in the EGS group (chi-square = 5.829, p = 0.016, Fisher = 0.022). There was a negative correlation between the invasiveness of the treatment and both mortality (r = -0.356, p = 0.015) and comorbidity (r = -0.506, p <0.001). Patients in the C/LT group had significantly more comorbidity than in the EGS group (mean = 4.32 vs. 2.26, p = 0.001). There was a positive correlation between comorbidity and mortality (r = 0.400, p = 0.006). Median follow-up was 42 months (range: 1-240). Type and way of nutrition were poorly described. In at least 9 of the 33 surviving patients, oral feeding was reported as normal, of whom 8 belonged to the EGS group. In all patients, growth could be acknowledged, but in comparison to peers, final body length was less. There was no difference in final body length between the two treatment groups. CONCLUSION: In patients with congenital microgastria, only minimal differences in clinical outcome in terms of type of nutrition and body growth were found when C/LT was compared with treatment by EGS. Mortality was significantly higher in the first group as well as the amount of comorbidities.
Assuntos
Anormalidades do Sistema Digestório/terapia , Anormalidades Múltiplas/epidemiologia , Tratamento Conservador/mortalidade , Anormalidades do Sistema Digestório/mortalidade , Nutrição Enteral/mortalidade , Gastrostomia/mortalidade , Humanos , Jejunostomia/mortalidade , Doenças Raras/mortalidade , Doenças Raras/terapiaRESUMO
BACKGROUND: Medulloblastoma is extremely rare in adults. The role of chemotherapy for average-risk adult patients remains controversial. Surgery and radiotherapy provide a significant disease control and a good prognosis, but about 25% of average-risk patients have a relapse and die because of disease progression. No data in average-risk adult patients are available to compareradiotherapy alone and radiotherapyfollowed byadjuvant chemotherapy. METHODS: We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016. RESULTS: Median age was 29 years (range 16-61). Based on histological subtypes, 15 patients (31.3%) had classic, 15 patients (31.3%) had desmoplastic, 5 patients (10.4%) had extensive nodularity and 2 patients (4.2%) had large cells/anaplastic medulloblastoma. Twenty-four patients (50%) received adjuvant radiotherapy alone and 24 (50%) received radiotherapy and chemotherapy. After a median follow-up of 12.5 years, we found that chemotherapyincreases progression-free survival (PFS-15 82.3 ± 8.0% in patients treated with radiotherapy and chemotherapyvs. 38.5% ± 13.0% in patients treated with radiotherapy alone p = 0.05) and overall survival (OS-15 89.3% ± 7.2% vs. 52.0% ± 13.1%, p = 0.02). Among patients receiving chemotherapy, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia (6 cases of G3 neutropenia [25%] and 3 cases of G4 neutropenia [13%]), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%). CONCLUSIONS: Our study with a long follow up period suggests that adding adjuvant chemotherapy to radiotherapy might improve PFS and OS in average-risk adult medulloblastoma patients.
Assuntos
Neoplasias Cerebelares/tratamento farmacológico , Meduloblastoma/tratamento farmacológico , Doenças Raras/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/radioterapia , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/mortalidade , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Meduloblastoma/mortalidade , Meduloblastoma/radioterapia , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Radioterapia/efeitos adversos , Doenças Raras/mortalidade , Doenças Raras/radioterapia , Risco , Trombocitopenia/induzido quimicamente , Adulto JovemRESUMO
OBJECTIVE: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor. This study aims to examine the clinicopathological features and surgical treatments of SPN and compare the clinical behavior and prognosis between men and women with SPN. METHODS: We collected the population data of patients with SPN diagnosed between 2004 and 2017 from the SEER database. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-specific survival (DSS), and log-rank tests were used to evaluate the differences between subgroups. Univariate and multivariate Cox regression analyses were performed to screen out prognostic risk factors of SPN. RESULTS: A total of 378 patients with SPN were included, with 246 (65.1%) female patients. 1-, 3-, and 5-year overall survival rates were 98.9%, 95.7%, and 93.7%, respectively. Survival analysis revealed that regardless of stage, patients with SPN who underwent surgical interventions still had a significantly better prognosis than those without surgical interventions (P < .001). The patients with lymphatic dissection had a significantly better prognosis than those without lymphatic dissection (P < .001). Moreover, compared with female patients, male patients had significantly poorer OS and DSS (P < .001). Female SPN showed a bimodal age-frequency distribution with early-onset incidence at 28 years and late-onset peak incidence at 62 years, while male SPN presented a unimodal distribution with peak incidence at approximately age 64 years. In female patients, the tumor size in premenopausal females (<65 years old) was significantly larger than that in postmenopausal females (≥65 years old) (P < .001). Clinicopathological characteristic profiles were different not only between male SPN and premenopausal female SPN but also between premenopausal and postmenopausal female SPN. CONCLUSION: SPN presents indolent behavior and predominantly occurs in young women. Regardless of stage, surgical intervention is recommended. Moreover, our study is the first large enough study to demonstrate sex-related discrepancies in SPN. Thus, different treatment strategies should be designed for patients of different sexes at different ages and hormone therapy is a promising approach for SPN.
Assuntos
Carcinoma Papilar , Neoplasias Pancreáticas , Fatores Sexuais , Adulto , Idade de Início , Idoso , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Doenças Raras/mortalidade , Doenças Raras/patologia , Doenças Raras/cirurgia , Análise de Regressão , Taxa de Sobrevida , Carga TumoralRESUMO
BACKGROUND: Trichilemmal carcinoma (TC) is an extremely rare hair follicle tumor. We aimed to explore the genetic abnormalities involved in TC to gain insight into its molecular pathogenesis. METHODS: Data from patients diagnosed with TC within a 12-year period were retrospectively reviewed. Genomic DNA isolated from a formalin-fixed paraffin-embedded (FFPE) tumor tissue block was sequenced and explored for a panel of cancer genes. RESULTS: DNA was extracted from the FFPE tissue of four patients (50% female; mean age, 51.5 years) diagnosed with TC for analysis. The tumor was located in the head and neck of three patients and in the shoulder of one patient. TP53 mutations (p.Arg213*, p.Arg249Trp, and p.Arg248Gln) were found in three patients. Fusions previously identified in melanoma were detected in two patients (TACC3-FGFR3 and ROS1-GOPC fusions). Other mutations found included NF1-truncating mutation (Arg1362*), NRAS mutation (p.Gln61Lys), TOP1 amplification, and PTEN deletion. Overall, genetic changes found in TC resemble that of other skin cancers, suggesting similar pathogenesis. All patients with TP53 mutations had aggressive clinical course, two who died (OS 93 and 36 months), and one who experienced recurrent relapse. CONCLUSIONS: We reported the genomic variations found in TC, which may give insight into the molecular pathogenesis. Overall, genetic changes found in TC resembled that of other skin cancers, suggesting similar pathogenesis. TP53 mutations was were identified in patients who had an aggressive clinical course. Genetic alterations identified may further suggest the potential treatment options of TC.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Folículo Piloso/patologia , Doenças Raras/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , DNA Topoisomerases Tipo I/genética , Intervalo Livre de Doença , Evolução Fatal , Feminino , GTP Fosfo-Hidrolases/genética , Doenças do Cabelo/genética , Doenças do Cabelo/patologia , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Neurofibromina 1/genética , Proteínas de Fusão Oncogênica/genética , PTEN Fosfo-Hidrolase/genética , Doenças Raras/mortalidade , Doenças Raras/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/genéticaRESUMO
Introduction: Studies on the epidemiology of primary sclerosing cholangitis (PSC) are mainly based on tertiary referral centers; and are retrospective case series susceptible to selection bias. The aim of this study was to estimate incidence; survival and cause of mortality of PSC in Italy; using population-based data. Methods: Data collected from the National Rare Diseases Registry (RNMR) and the National Mortality Database (NMD) were integrated and analyzed. Results: We identified 502 PSC incident cases. The crude incidence rate between 2012 and 2014 was 0.10 per 100,000 individuals. Sixty percent were male; mean age at disease onset and at diagnosis were 33 and 37 years; respectively; highlighting a mean diagnostic delay of 4 years. The rate of interregional mobility was 12%. Ten-year survival was 92%. In 32% of cases the cause of death was biliary-related; 12% died of biliary or gallbladder cancer. Conclusions: For rare diseases such as PSC; population-based cohort's studies are of paramount importance. Incidence rates of PSC in Italy are markedly lower and survival much longer than the ones reported from tertiary; single-centre series. Moreover; the diagnostic delay and the patient interregional mobility highlights the need for increasing awareness on the disease and for resource reallocation among Italian regions within the National Health Service.
Assuntos
Colangite Esclerosante , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/mortalidade , Efeitos Psicossociais da Doença , Diagnóstico Tardio , Feminino , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Raras/epidemiologia , Doenças Raras/mortalidade , Sistema de Registros , Estudos Retrospectivos , Medicina Estatal , Adulto JovemRESUMO
PURPOSE: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx). METHODS AND MATERIALS: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis. RESULTS: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively. CONCLUSIONS: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia/métodos , Radiação Cranioespinal/métodos , Germinoma/tratamento farmacológico , Germinoma/radioterapia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Quimiorradioterapia/efeitos adversos , Criança , Pré-Escolar , Gonadotropina Coriônica Humana Subunidade beta/sangue , Gonadotropina Coriônica Humana Subunidade beta/líquido cefalorraquidiano , Radiação Cranioespinal/tendências , Craniotomia/métodos , Craniotomia/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Seguimentos , Germinoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Induzidas por Radiação/etiologia , Radioterapia/métodos , Radioterapia/tendências , Dosagem Radioterapêutica , Doenças Raras/tratamento farmacológico , Doenças Raras/mortalidade , Doenças Raras/radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Falha de Tratamento , Adulto JovemRESUMO
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
Tumor profiling has been shown to benefit patients with rare or refractory metastatic cancer, but several limitations hamper its use in daily clinical practice. We aim to assess the added benefit of a comprehensive tumor profiling, including factors predictive of response to targeted and cytotoxic therapy, in the treatment of refractory or rare solid tumors outside of a formal clinical trial. Patients were included between 2013 and 2017. Multiplatform comprehensive tumor profiling (CTP) was performed on FFPE specimens. Tumor response was evaluated by imaging using the RECIST criteria version 1.1. The PFS ratio was defined as PFS under CTP-guided therapy (PFS2)/PFS under previous standard therapy (PFS1). A clinical benefit was identified if the PFS ratio exceeded the 1.3 threshold value. In total, 184 patients were enrolled among whom 104 were evaluable for the PFS ratio. Objective response rates (ORR) were equal to 25% (CI95: 16.6-33.4%) and 36.5% (CI95: 27.2-45.8%) on the last therapy before CTP and on the CTP-guided therapy respectively (P-value=0.058 on paired proportion comparison test). The proportion of patients achieving a PFS2/PFS1 ratio≥1.3 was equal to 50%. The median PFS1 was statistically lower than PFS2 (120 days compared to 184 days respectively, P-value log rank 0.01). These results confirm the feasibility and the added benefit of a CTP in patients with refractory tumors in daily clinical practice especially in patients not able to enter a clinical trial.
Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular/métodos , Proteínas de Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Doenças Raras/tratamento farmacológico , Doenças Raras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/antagonistas & inibidores , Tomada de Decisão Clínica , Estudos de Viabilidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização In Situ/métodos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/mortalidade , Probabilidade , Intervalo Livre de Progressão , Análise Serial de Proteínas/métodos , Doenças Raras/mortalidade , Critérios de Avaliação de Resposta em Tumores Sólidos , Taxa de Sobrevida , Adulto JovemRESUMO
For rare cancers, challenges in establishing standard therapies are greater than those for major cancers, and effective methods are needed. MASTER KEY Project is a multicenter study based in Japan, with two main parts: prospective registry study and multiple clinical trials. Advanced rare cancers, cancers of unknown primary origin, and those with rare tissue subtypes of common cancers are targeted. The registry study accumulates highly reliable consecutive data that can be used for future drug development. The multiple trials are conducted simultaneously, targeting either a specific biomarker or a rare tumor type of interest. The first interim data set from the registry part presented here shows the prevalence of genetic abnormalities, response rates, survival rates, and clinical trial enrollment rates. From May 2017 to April 2019, 560 patients (mean age = 53) were enrolled in the project. Frequent cancer types included soft tissue sarcomas, neuroendocrine tumors, and central nervous system tumors. Among the 528 patients with assessable data, 69% (364/528) had next-generation sequencing tests, with 48% (176/364) harboring an "actionable" alteration. Seventy-one (13%) patients have been enrolled in one of the clinical trials, with an accrual rate of 3.94 patients/month. A descriptive analysis of biomarker-directed or non-biomarker-directed treatment survival was performed. This project is expected to accelerate development of treatments for rare cancers and show that comprehensive platform trials are an advantageous strategy.
Assuntos
Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Neoplasias/tratamento farmacológico , Doenças Raras/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Tomada de Decisão Clínica , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Terapia de Alvo Molecular , Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Seleção de Pacientes , Medicina de Precisão , Valor Preditivo dos Testes , Estudos Prospectivos , Doenças Raras/genética , Doenças Raras/mortalidade , Doenças Raras/patologia , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Nonimmune hydrops fetalis (NIHF) historically has been considered a lethal fetal condition. Understanding NIHF to be a symptom or an end-stage status of a variety of fetal conditions, along with improved fetal diagnostics and interventions, has changed the landscape for at least some fetuses. Understanding the pathophysiologic mechanisms has led to the development of diagnostic algorithms, improved understanding of cause, and therefore fetal or neonatal treatments. Multidisciplinary counseling and shared decision making are critical to supporting families through pregnancy decisions, potential fetal therapeutic interventions, neonatal management decisions, and at times accepting or transitioning to palliative care.
Assuntos
Hidropisia Fetal/diagnóstico , Hidropisia Fetal/terapia , Doenças Raras/diagnóstico , Doenças Raras/terapia , Aconselhamento , Tomada de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Hidropisia Fetal/mortalidade , Hidropisia Fetal/fisiopatologia , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Prognóstico , Doenças Raras/mortalidade , Doenças Raras/fisiopatologiaAssuntos
Colo Transverso/patologia , Neoplasias do Colo/patologia , Leiomiossarcoma/patologia , Doenças Raras/patologia , Idoso , Neoplasias do Colo/mortalidade , Neoplasias do Colo/terapia , Humanos , Leiomiossarcoma/mortalidade , Leiomiossarcoma/terapia , Masculino , Prognóstico , Doenças Raras/mortalidade , Doenças Raras/terapiaRESUMO
BACKGROUND: Sarcomatoid carcinoma of unknown primary (SCUP) is a rare entity of either poorly differentiated carcinoma with sarcoma-like differentiation or a true mixed lineage neoplasm. Limited data regarding clinicopathological profile and management exists. METHODS: We retrospectively reviewed the MD Anderson Cancer of Unknown Primary database and tumor registry to identify 48 SCUP patients between 2001 and 2017. Patient characteristics, pathology, molecular diagnostics, treatments, and outcomes were obtained. Kaplan-Meier method was used to estimate overall survival (OS) and compared using log rank test. RESULTS: Median age at diagnosis was 59 years (range 27-86). Majority of patients were female (58%) and presented with ≥3 metastatic sites (52%), commonly lymph node (50%), bone (42%), lung (27%), and liver (21%). First line treatment included chemotherapy (35%), surgery (27%), and radiation (24%). Gemcitabine and docetaxel (18%) was the most common chemotherapy regimen. Median OS for entire cohort was 11 months (95% CI: 5.6 to 16.4). Poor performance status (PS), > 1 metastatic site, elevated lactate dehydrogenase (LDH), and high neutrophil-to-lymphocyte ratio (NLR) were significantly associated with worse OS on univariate analyses. On multivariate analyses, poor PS (HR 8.7; 95%CI: 3.0-25.0; p < 0.001) and high NLR (HR 3.4; 95%CI: 1.3-8.8; p = 0.011) emerged as independent prognostic factors for OS. CONCLUSIONS: SCUP is a rare presentation with an aggressive clinical course and limited survival. Diagnosis is difficult to make and requires careful review and synthesis of histology, immunohistochemistry, and molecular diagnostics. Chemotherapy resistance remains a challenge. Early mutational profiling is warranted, and clinical trial participation should be encouraged for this subset.
Assuntos
Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Neoplasias Primárias Desconhecidas/mortalidade , Neoplasias Primárias Desconhecidas/patologia , Doenças Raras/mortalidade , Doenças Raras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Carcinossarcoma/imunologia , Carcinossarcoma/terapia , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Neoplasias Primárias Desconhecidas/imunologia , Neoplasias Primárias Desconhecidas/terapia , Prognóstico , Estudos Prospectivos , Doenças Raras/imunologia , Doenças Raras/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Retroperitoneal sarcomas (RPS) are rare, histologically heterogeneous, and anatomically complex tumors. National Comprehensive Cancer Network guidelines recommend evaluation and management by multidisciplinary teams with experience in sarcoma. Our aim was to determine an appropriate hospital volume threshold for the treatment of RPS. PATIENTS AND METHODS: Patients undergoing resection of RPS were identified from the National Cancer Data Base (1998-2012). Multivariable modeling with restricted cubic splines was employed to examine the association between hospital volume and survival and identify possible hospital volume threshold. RESULTS: The study included 5,340 patients who underwent surgery at 909 different hospitals. Median annual volume was two cases per year. After adjustment, hospital volume was associated with improved survival (p=0.01), without cutoff. The cohort was then grouped into: Low-volume (≤5 cases/year), intermediate-volume (6-10 cases/year), and high-volume (>10 cases/year). The majority of patients were treated in low-volume hospitals (86%), compared to 9% in intermediate- and 5% in high-volume centers; 44% of patients were treated in hospitals that performed one case per year. Compared to low-volume, high-volume hospitals more often had patients with high-grade and larger tumors. Adjusted 90-day mortality was significantly lower in high- vs. low-volume hospitals (odds ratio(OR)=0.25, p=0.02). With adjustment, treatment in high- vs. low-volume hospitals was associated with lower odds of margin positivity (OR=0.58, p=0.001), and improved overall survival (hazard ratio(HR)=0.61, p=0.002). CONCLUSION: Treatment of RPS in high-volume centers is associated with significant reduction in short-term mortality and improved long-term survival. Hospital volume may be a surrogate for the infrastructure and support necessary for the optimal management of these complex malignancies.