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[PMID]: 29362889 [Au] Autor: Gaudio F; Tamma R; Ingravallo G; Perrone T; Laddaga FE; De Candia M; Maiorano E; Ribatti D; Specchia G [Ad] Endereço: Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, Bari, Italy. fragaudio@alice.it. [Ti] Título: Computer-driven quantitative image analysis in the assessment of tumor cell and T cell features in diffuse large B cell lymphomas. [So] Source: Ann Hematol;97(4):663-668, 2018 Apr. [Is] ISSN: 1432-0584 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: Diffuse large B cell lymphoma (DLBCL) is recognized as the most common non-Hodgkin lymphoma subtype. Advanced high-resolution digital scans of pathology slides have enabled the development of computer-based image analysis algorithms that may assist pathologists in quantifying immunohistochemical stains. In this retrospective study, we reviewed data from 29 patients affected by DLBCL. In order to evaluate the number of tumor cells and microenvironment T cells, we performed an analysis of CD20, Ki67, and CD3 counts, assessed with the Positive Pixel Count algorithm embedded in the Aperio ImageScope software. A lower tumor cell count was observed in patients with a non-germinal center immunophenotype, high LDH, splenomegaly and an IPI ≥ 3. A lower number of CD3 was observed in patients with bulky disease, an IPI ≥ 3 and disease stage 3-4. Overall, these data confirm that quantitative analysis of the tumor cells and of the tumor microenvironment by means of computer-driven quantitative image analysis may add new information in DLBCL diagnosis. [Mh] Termos MeSH primário: Linfócitos B/patologia Interpretação de Imagem Assistida por Computador Linfonodos/diagnóstico por imagem Linfoma Difuso de Grandes Células B/diagnóstico por imagem Linfócitos T/patologia [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Algoritmos Antígenos CD20/metabolismo Linfócitos B/imunologia Linfócitos B/metabolismo Complexo CD3/metabolismo Feminino Centro Germinativo/imunologia Centro Germinativo/metabolismo Centro Germinativo/patologia Seres Humanos Imuno-Histoquímica Antígeno Ki-67/metabolismo Linfonodos/imunologia Linfonodos/metabolismo Linfonodos/patologia Linfoma Difuso de Grandes Células B/imunologia Linfoma Difuso de Grandes Células B/metabolismo Linfoma Difuso de Grandes Células B/patologia Masculino Meia-Idade Estadiamento de Neoplasias Prognóstico Estudos Retrospectivos Linfócitos T/imunologia Linfócitos T/metabolismo Microambiente Tumoral [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antigens, CD20); 0 (CD3 Complex); 0 (Ki-67 Antigen) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180309 [Lr] Data última revisão: 180309 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180125 [St] Status: MEDLINE [do] DOI: 10.1007/s00277-017-3212-6

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[PMID]: 28745824 [Au] Autor: Ma D; Wang J; Hao X; Wang Y; Hu X; Xing P; Li J [Ad] Endereço: Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [Ti] Título: Gemcitabine combined with cisplatin as adjuvant chemotherapy for non-small cell lung cancer: A retrospective analysis. [So] Source: Thorac Cancer;8(5):482-488, 2017 Sep. [Is] ISSN: 1759-7714 [Cp] País de publicação: Singapore [La] Idioma: eng [Ab] Resumo: BACKGROUND: This study was conducted to evaluate the value of gemcitabine combined with cisplatin as adjuvant chemotherapy for radical resection of non-small cell lung cancer. METHODS: Data of 100 patients who had undergone radical resection of non-small cell lung cancer and were treated with cisplatin/gemcitabine as adjuvant chemotherapy between June 2007 and December 2010 at the Chinese Academy of Medical Sciences were reviewed. RESULTS: The median age was 59 years (range 36-73); 82% of the patients were male. Forty-two percent had adenocarcinoma and 55% had squamous cell carcinoma. Most patients had pathologic IIB (29%) and IIIA (44%) stage disease. Eighty-five percent of patients completed four cycles of chemotherapy, with 76% completing the planned full dose. The main reason for a reduced gemcitabine dose in 13 patients was grade 3/4 neutropenia or thrombocytopenia. The median dose and dose intensity were 8377.1 mg/m and 708 mg/(m /week) for gemcitabine and 293.38 mg/m and 25.24 mg/(m /week) for cisplatin, respectively. During follow-up the median disease-free survival was 33.8 months (95% confidence interval [CI] 15.938-51.676). Patients with squamous cell carcinoma (hazard ratio [HR] 0.404, 95% CI 0.241-0.676; P = 0.001) and pathologic stage I (HR 4.379, 95% CI 1.721-11.142; P = 0.002) achieved better disease-free survival. The survival rates at one, two, and five years were 94%, 77%, and 55%, while the survival rates without recurrence were 64%, 53%, and 39%, respectively. CONCLUSION: As an adjuvant chemotherapy regimen, gemcitabine with cisplatin is well tolerated. Patients with squamous cell carcinomas or pathologic stage I achieve better results. [Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico Cisplatino/administração & dosagem Desoxicitidina/análogos & derivados Neoplasias Pulmonares/tratamento farmacológico [Mh] Termos MeSH secundário: Adulto Idoso Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico Carcinoma Pulmonar de Células não Pequenas/patologia Carcinoma Pulmonar de Células não Pequenas/cirurgia Quimioterapia Adjuvante Cisplatino/uso terapêutico Desoxicitidina/administração & dosagem Desoxicitidina/uso terapêutico Feminino Seres Humanos Neoplasias Pulmonares/patologia Neoplasias Pulmonares/cirurgia Masculino Meia-Idade Estadiamento de Neoplasias Estudos Retrospectivos Análise de Sobrevida Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0W860991D6 (Deoxycytidine); B76N6SBZ8R (gemcitabine); Q20Q21Q62J (Cisplatin) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180309 [Lr] Data última revisão: 180309 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170727 [St] Status: MEDLINE [do] DOI: 10.1111/1759-7714.12472

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[PMID]: 29267666 [Au] Autor: Iriya PMO; Romaniszen LW; Fernandes TMF; Poleti ML [Ad] Endereço: Universidade Estadual do Norte do Paraná - Unopar, Londrina, PR, Brazil. [Ti] Título: Health-related quality of life of patients with squamous cell carcinoma: a comparison according to tumor location. [So] Source: Braz Oral Res;31:e105, 2017 Dec 18. [Is] ISSN: 1807-3107 [Cp] País de publicação: Brazil [La] Idioma: eng [Ab] Resumo: The aim of this study was to evaluate the health-related quality of life (QOL) of patients with squamous cell carcinoma (SCC) according to tumor location. The sample consisted of 27 patients with primary SCC in the oral cavity (n = 15), pharynx (n = 7), and larynx (n = 5) who were undergoing cancer treatment at the Cancer Hospital of Londrina, regardless of age, sex, clinical stage, and type of antineoplastic treatment. Health-related QOL was evaluated using the 30-item Cancer-Quality of Life Questionnaire (QLQ-C30), the 35-item Head and Neck Cancer-Quality of Life Questionnaire (QLQ-HN35), and the University of Washington Quality of Life Questionnaire (UW-QOL). These questionnaires were administered individually to each patient before ambulatory care. Sociodemographic data (age and sex) and clinical data (T stage, tumor location, and type of antineoplastic treatment) were collected from the patients' medical records. Scores were compared according to tumor location using the chi-squared test and one-way analysis of variance (p < 0.05). No score differed significantly according to tumor location. It can be concluded that the health-related QOL of patients with SCC was not influenced by tumor location. [Mh] Termos MeSH primário: Carcinoma de Células Escamosas Neoplasias Laríngeas Neoplasias Bucais Neoplasias Faríngeas Qualidade de Vida [Mh] Termos MeSH secundário: Fatores Etários Idoso Análise de Variância Antineoplásicos/uso terapêutico Carcinoma de Células Escamosas/tratamento farmacológico Carcinoma de Células Escamosas/patologia Estudos Transversais Feminino Seres Humanos Neoplasias Laríngeas/tratamento farmacológico Neoplasias Laríngeas/patologia Masculino Meia-Idade Neoplasias Bucais/tratamento farmacológico Neoplasias Bucais/patologia Estadiamento de Neoplasias Neoplasias Faríngeas/tratamento farmacológico Neoplasias Faríngeas/patologia Fatores Sexuais Inquéritos e Questionários [Pt] Tipo de publicação: JOURNAL ARTICLE; OBSERVATIONAL STUDY [Nm] Nome de substância: 0 (Antineoplastic Agents) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: D; IM [Da] Data de entrada para processamento: 171222 [St] Status: MEDLINE

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[PMID]: 29222650 [Au] Autor: Lowe NM; Bernstein JM; Mais K; Garcez K; Lee LW; Sykes A; Thomson DJ; Homer JJ; West CM; Slevin NJ [Ad] Endereço: Translational Radiobiology Group, Division of Cancer Sciences, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester, England, M20 4BX, UK. nataliemarielowe@gmail.com. [Ti] Título: Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage IV neck node-positive head and neck cancer and a good performance status. [So] Source: J Cancer Res Clin Oncol;144(2):389-401, 2018 Feb. [Is] ISSN: 1432-1335 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: PURPOSE: The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most. METHODS: A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m IV) and cisplatin (75 mg/m IV) on day 1 plus 5-FU (750 mg/m IV) on days 2-5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor. RESULTS: Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis. CONCLUSION: With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation. [Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem Carcinoma de Células Escamosas/tratamento farmacológico Carcinoma de Células Escamosas/radioterapia Neoplasias de Cabeça e Pescoço/tratamento farmacológico Neoplasias de Cabeça e Pescoço/radioterapia [Mh] Termos MeSH secundário: Adulto Idoso Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos Carcinoma de Células Escamosas/patologia Quimiorradioterapia Cisplatino/administração & dosagem Cisplatino/efeitos adversos Esquema de Medicação Feminino Fluoruracila/administração & dosagem Fluoruracila/efeitos adversos Neoplasias de Cabeça e Pescoço/patologia Seres Humanos Quimioterapia de Indução Metástase Linfática Masculino Meia-Idade Estadiamento de Neoplasias Estudos Retrospectivos Taxoides/administração & dosagem Taxoides/efeitos adversos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Taxoids); 15H5577CQD (docetaxel); Q20Q21Q62J (Cisplatin); U3P01618RT (Fluorouracil) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171210 [St] Status: MEDLINE [do] DOI: 10.1007/s00432-017-2553-9

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[PMID]: 29203756 [Au] Autor: Kononenko M; Vynnychenko I; Moskalenko Y; Vynnychenko O [Ad] Endereço: Department Of Surgery And Oncology, Sumy State University, Sumy, Ukraine. [Ti] Título: 12 years of fighting liposarcoma: a case report. [So] Source: Wiad Lek;70(5):995-997, 2017. [Is] ISSN: 0043-5147 [Cp] País de publicação: Poland [La] Idioma: eng [Ab] Resumo: The proportion of liposarcoma in the structure of cancer incidence is from 10 to 35% of all mesenchymal tumors. This clinical observation describes an 12-year struggle with myxoid liposarcoma of the left upper arm, during which 17 surgeries were performed due to local recurrences, 17 radiation therapy courses and 5 chemotherapy courses were conducted. Clinical observation shows the whole complexity of myxoid liposarcoma treatment. The effectiveness of therapeutic management is determined by persistent surgery, and also by the lack of expression of Pgp, glutathione-S-transferase, metallothionein and mutant p53 in tumor structure. [Mh] Termos MeSH primário: Braço/patologia Lipossarcoma Mixoide/terapia Recidiva Local de Neoplasia/terapia [Mh] Termos MeSH secundário: Adulto Terapia Combinada Seres Humanos Lipossarcoma Mixoide/tratamento farmacológico Lipossarcoma Mixoide/radioterapia Lipossarcoma Mixoide/cirurgia Masculino Recidiva Local de Neoplasia/tratamento farmacológico Recidiva Local de Neoplasia/radioterapia Recidiva Local de Neoplasia/cirurgia Estadiamento de Neoplasias Resultado do Tratamento [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171206 [St] Status: MEDLINE

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[PMID]: 29185092 [Au] Autor: Ma M; Dai J; Xu T; Yu S; Yu H; Tang H; Yan J; Wu X; Yu J; Chi Z; Si L; Cui C; Sheng X; Kong Y; Guo J [Ad] Endereço: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Beijing, 100142, China. [Ti] Título: Analysis of TSC1 mutation spectrum in mucosal melanoma. [So] Source: J Cancer Res Clin Oncol;144(2):257-267, 2018 Feb. [Is] ISSN: 1432-1335 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: PURPOSE: Mucosal melanoma is a relatively rare subtype of melanoma for which no clearly established therapeutic strategy exists. The genes of the mTOR signalling pathway have drawn great attention as key targets for cancer treatment, including melanoma. In this study, we aimed to investigate the mutation status of the upstream mTOR regulator TSC1 and evaluated its correlation with the clinicopathological features of mucosal melanoma. METHODS: We collected 91 mucosal melanoma samples for detecting TSC1 mutations. All the coding exons of TSC1 were amplified by PCR and subjected to Sanger sequencing. Expression level of TSC1 encoding protein (hamartin) was detected by immunohistochemistry. The activation of mTOR pathway was determined by evaluating the phosphorylation status of S6RP and 4E-BP1. RESULTS: The overall mutation frequency of TSC1 was found to be 17.6% (16/91 patients). TSC1 mutations were more inclined to occur in advanced mucosal melanoma (stages III and IV). In the 16 patients with TSC1 mutations, 14 different mutations were detected, affecting 11 different exons. TSC1 mutations were correlated with upregulation of S6RP phosphorylation but were unrelated to 4E-BP1 phosphorylation or hamartin expression. Mucosal melanoma patients with TSC1 mutations had a worse outcome than patients without TSC1 mutations (24.0 versus 34.0 months, P = 0.007). CONCLUSIONS: Our findings suggest that TSC1 mutations are frequent in mucosal melanoma. TSC1 mutations can activate the mTOR pathway through phospho-S6RP and might be a poor prognostic predictor of mucosal melanoma. Our data implicate the potential significance of TSC1 mutations for effective and specific drug therapy for mucosal melanoma. [Mh] Termos MeSH primário: Melanoma/genética Mutação Proteínas Supressoras de Tumor/genética [Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo Análise Mutacional de DNA Feminino Seres Humanos Masculino Melanoma/metabolismo Melanoma/patologia Meia-Idade Membrana Mucosa/patologia Estadiamento de Neoplasias Fosfoproteínas/metabolismo Prognóstico Proteína S6 Ribossômica/metabolismo Serina-Treonina Quinases TOR/metabolismo Proteínas Supressoras de Tumor/biossíntese [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Adaptor Proteins, Signal Transducing); 0 (EIF4EBP1 protein, human); 0 (Phosphoproteins); 0 (Ribosomal Protein S6); 0 (Tumor Suppressor Proteins); 0 (tuberous sclerosis complex 1 protein); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171130 [St] Status: MEDLINE [do] DOI: 10.1007/s00432-017-2550-z

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[PMID]: 28456837 [Au] Autor: Ulaner GA; Castillo R; Wills J; Gönen M; Goldman DA [Ad] Endereço: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ulanerg@mskcc.org. [Ti] Título: F-FDG-PET/CT for systemic staging of patients with newly diagnosed ER-positive and HER2-positive breast cancer. [So] Source: Eur J Nucl Med Mol Imaging;44(9):1420-1427, 2017 Aug. [Is] ISSN: 1619-7089 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: OBJECTIVES: This study assesses F-FDG-PET/CT for patients with newly diagnosed estrogen receptor-positive/human epidermal growth factor receptor-negative (ER+/HER2-) and human epidermal growth factor receptor-positive (HER2+) breast cancer. METHODS: In this Institutional Review Board-approved retrospective study, our Healthcare Information System was screened for patients with ER+/HER2- and HER2+ breast cancer who underwent F-FDG-PET/CT prior to systemic or radiation therapy. The initial stage was determined from mammography, ultrasound, magnetic resonance imaging, and/or surgery. F-FDG-PET/CT was evaluated to identify unsuspected extra-axillary regional nodal and distant metastases. The proportion of patients upstaged overall and stratified by stage and receptor phenotypes was calculated along with confidence intervals (CI). RESULTS: A total of 238 patients with ER+/HER2- and 245 patients with HER2+ who met inclusion criteria were evaluated. For patients with ER+/HER2-breast cancer, F-FDG-PET/CT revealed unsuspected distant metastases in 3/71 (4%) initial stage IIA, 13/95 (14%) stage IIB, and 15/57 (26%) stage III. For patients with HER2+ breast cancer, F-FDG-PET/CT revealed unsuspected distant metastases in 3/72 (4%) initial stage IIA, 13/93 (14%) stage IIB, and 13/59 (22%) stage III. The overall upstaging rate for IIB was 14% (95% confidence interval (CI): 9-20%). CONCLUSIONS: F-FDG-PET/CT revealed distant metastases in 14% (95% CI: 9-20%) of patients with stage IIB ER+/HER2- and HER2+ breast cancer, which is similar to upstaging rates previously seen in patients with stage IIB triple-negative breast cancer (15%, 95% CI: 9-24%). The detection of unsuspected distant metastases in these patients alters treatment and prognosis. NCCN guidelines should consider adding patients with stage IIB breast cancer for consideration of systemic staging with F-FDG-PET/CT at the time of initial diagnosis. [Mh] Termos MeSH primário: Neoplasias da Mama/diagnóstico por imagem Neoplasias da Mama/patologia Fluordesoxiglucose F18 Tomografia Computadorizada com Tomografia por Emissão de Pósitrons Receptor ErbB-2/metabolismo Receptores Estrogênicos/metabolismo [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Neoplasias da Mama/metabolismo Feminino Seres Humanos Meia-Idade Estadiamento de Neoplasias Estudos Retrospectivos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Receptors, Estrogen); 0Z5B2CJX4D (Fluorodeoxyglucose F18); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170501 [St] Status: MEDLINE [do] DOI: 10.1007/s00259-017-3709-1

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[PMID]: 28922790 [Au] Autor: Marisa L; Svrcek M; Collura A; Becht E; Cervera P; Wanherdrick K; Buhard O; Goloudina A; Jonchère V; Selves J; Milano G; Guenot D; Cohen R; Colas C; Laurent-Puig P; Olschwang S; Lefèvre JH; Parc Y; Boige V; Lepage C; André T; Fléjou JF; Dérangère V; Ghiringhelli F; de Reynies A; Duval A [Ad] Endereço: Programme "Cartes d'Identité des Tumeurs," Ligue Nationale Contre le Cancer, Paris, France; INSERM, UMRS 938 - Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers," Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France; Sorbonne Université, UPMC U [Ti] Título: The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors. [So] Source: J Natl Cancer Inst;110(1), 2018 Jan 01. [Is] ISSN: 1460-2105 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided. Results: The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004). Conclusions: ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients. [Mh] Termos MeSH primário: Biomarcadores Tumorais/genética Biomarcadores Tumorais/imunologia Neoplasias Colorretais/genética Neoplasias Colorretais/imunologia Linfócitos do Interstício Tumoral Linfócitos T Citotóxicos [Mh] Termos MeSH secundário: Antígenos CD/genética Antígeno B7-H1/análise Antígeno B7-H1/genética Antígenos CD8/análise Antígeno CTLA-4/genética Colo/química Neoplasias Colorretais/química Neoplasias Colorretais/patologia Feminino Expressão Gênica Receptor Celular 2 do Vírus da Hepatite A/genética Seres Humanos Proteína Coestimuladora de Linfócitos T Induzíveis/genética Masculino Instabilidade de Microssatélites Meia-Idade Estadiamento de Neoplasias Prognóstico Proteína 2 Ligante de Morte Celular Programada 1/genética Receptor de Morte Celular Programada 1/genética Estudos Retrospectivos Taxa de Sobrevida Células Th1 [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY [Nm] Nome de substância: 0 (Antigens, CD); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD223 antigen); 0 (CD274 protein, human); 0 (CD8 Antigens); 0 (CTLA-4 Antigen); 0 (HAVCR2 protein, human); 0 (Hepatitis A Virus Cellular Receptor 2); 0 (ICOS protein, human); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (PDCD1 protein, human); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Programmed Cell Death 1 Receptor) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170920 [St] Status: MEDLINE [do] DOI: 10.1093/jnci/djx136

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[PMID]: 28922786 [Au] Autor: Suciu S; Eggermont AMM; Lorigan P; Kirkwood JM; Markovic SN; Garbe C; Cameron D; Kotapati S; Chen TT; Wheatley K; Ives N; de Schaetzen G; Efendi A; Buyse M [Ad] Endereço: European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Gustave Roussy Cancer Campus Grand Paris, Villejuif, France; The Christie NHS Foundation Trust, Manchester, UK; University of Pittsburgh Cancer Institute and School of Medicine, Pittsburgh, PA; Mayo Clinic Ro [Ti] Título: Relapse-Free Survival as a Surrogate for Overall Survival in the Evaluation of Stage II-III Melanoma Adjuvant Therapy. [So] Source: J Natl Cancer Inst;110(1), 2018 Jan 01. [Is] ISSN: 1460-2105 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Background: We assessed whether relapse-free survival (RFS; time until recurrence/death) is a valid surrogate for overall survival (OS) among resected stage II-III melanoma patients through a meta-analysis of randomized controlled trials. Methods: Individual patient data (IPD) on RFS and OS were collected from 5826 patients enrolled in 11 randomized adjuvant trials comparing interferon (IFN) to observation. In addition, IPD from two studies comparing IFN and vaccination in 989 patients were included. A two-level modeling approach was used for assessing Spearman's patient-level correlation (rho) of RFS and OS and the trial-level coefficient of determination (R²) of the treatment effects on RFS and on OS. The results were validated externally in 13 adjuvant studies without available IPD. We then tested the results on the European Organisation for Research and Treatment of Cancer (EORTC) 18071 double-blind trial comparing ipilimumab 10 mg/kg with placebo, which showed a statistically significant impact of the checkpoint inhibitor on RFS and OS. All statistical tests were two-sided. Results: With a median follow-up of seven years, 12 of 13 trials showed a consistency between the IFN vs No IFN differences regarding RFS (hazard ratio [HR]RFS = 0.88) and OS (HROS = 0.91), but the small trial, Eastern Cooperative Oncology Group 2696, was an outlier (HRRFS = 0.72 vs HROS = 1.11). Therefore, even if rho was high, R² was low and could not reliably be estimated. Based on the 12 trials, rho remained high (0.89), and the hazard ratios for RFS and OS were strongly correlated (R² = 0.91). The surrogate threshold effect for RFS was estimated to be 0.77. For the EORTC 18071 trial, the hazard ratio for RFS was 0.75, predicting an effect of ipilimumab on OS. This was subsequently confirmed (HROS = 0.72, 95.1% confidence interval = 0.58 to 0.88, P = .001). Conclusions: In high-risk stage II-III melanoma, RFS appeared to be a valid surrogate end point for OS for adjuvant randomized studies assessing interferon or a checkpoint inhibitor. In future similar adjuvant studies, a hazard ratio for RFS of 0.77 or less would predict a treatment impact on OS. [Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico Antineoplásicos/uso terapêutico Interferon-alfa/uso terapêutico Melanoma/tratamento farmacológico Melanoma/mortalidade Neoplasias Cutâneas/tratamento farmacológico Neoplasias Cutâneas/mortalidade [Mh] Termos MeSH secundário: Quimioterapia Adjuvante Intervalo Livre de Doença Seres Humanos Ipilimumab Melanoma/patologia Melanoma/cirurgia Estadiamento de Neoplasias Ensaios Clínicos Controlados Aleatórios como Assunto Neoplasias Cutâneas/patologia Neoplasias Cutâneas/cirurgia Taxa de Sobrevida [Pt] Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS; REVIEW; VALIDATION STUDIES [Nm] Nome de substância: 0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents); 0 (Interferon-alpha); 0 (Ipilimumab) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170920 [St] Status: MEDLINE [do] DOI: 10.1093/jnci/djx133

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[PMID]: 28460061 [Au] Autor: Papaleontiou M; Hughes DT; Guo C; Banerjee M; Haymart MR [Ad] Endereço: Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48106. [Ti] Título: Population-Based Assessment of Complications Following Surgery for Thyroid Cancer. [So] Source: J Clin Endocrinol Metab;102(7):2543-2551, 2017 Jul 01. [Is] ISSN: 1945-7197 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Context: As thyroid cancer incidence rises, more patients undergo thyroid surgery. Although postoperative complication rates have been reported in single institution studies, population-based data are limited. Objective: To determine thyroid cancer surgery complication rates and identify at-risk populations. Design/Setting/Patients: Using the Surveillance, Epidemiology, and End Results-Medicare database, we evaluated general complications within 30 days and thyroid surgery-specific complications within 1 year in 27,912 patients who underwent surgery for differentiated or medullary thyroid cancer between 1998 and 2011. Multivariable analyses of patient characteristics associated with postoperative complications were performed. Main Outcome Measures: General and thyroid surgery-specific complications. Results: Overall, 1820 (6.5%) patients developed general postoperative complications and 3427 (12.3%) developed thyroid surgery-specific complications. In multivariable analyses, general and thyroid surgery-specific complications were significantly higher in patients >65 years [odds ratio (OR), 2.61; 95% confidence interval (CI), 2.31 to 2.95; OR, 3.12; 95% CI, 2.85 to 3.42], those with a Charlson/Deyo comorbidity score of 1 (OR, 2.40; 95% CI, 1.66 to 3.49; OR, 1.88; 95% CI, 1.53 to 2.31) and ≥2 (OR, 7.05; 95% CI, 5.33 to 9.56; OR, 3.62; 95% CI, 3.11 to 4.25), and those with regional (OR, 1.18; 95% CI, 1.03 to 1.35; OR, 1.31; 95% CI, 1.19 to 1.45) or distant disease (OR, 2.83; 95% CI, 2.30 to 3.47; OR, 1.85; 95% CI, 1.54 to 2.21), respectively. Conclusions: The rates of thyroid cancer surgery complications are higher than predicted, and patients with older age, more comorbidities, and advanced disease are at greatest risk. Efforts to reduce complications are needed. [Mh] Termos MeSH primário: Complicações Pós-Operatórias/epidemiologia Neoplasias da Glândula Tireoide/patologia Neoplasias da Glândula Tireoide/cirurgia Tireoidectomia/efeitos adversos [Mh] Termos MeSH secundário: Adulto Idoso Intervalo Livre de Doença Feminino Seres Humanos Incidência Modelos Logísticos Masculino Medicare/estatística & dados numéricos Meia-Idade Análise Multivariada Invasividade Neoplásica/patologia Estadiamento de Neoplasias Complicações Pós-Operatórias/fisiopatologia Estudos Retrospectivos Medição de Risco Programa de SEER Análise de Sobrevida Neoplasias da Glândula Tireoide/mortalidade Tireoidectomia/métodos Estados Unidos [Pt] Tipo de publicação: EVALUATION STUDIES; JOURNAL ARTICLE [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170502 [St] Status: MEDLINE [do] DOI: 10.1210/jc.2017-00255

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