ONC - Artigos publicados em revistas não indexadas
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- Sarcomas de tecidos moles: a propósito de 6 casos de leiomiossarcomaPublication . Sargento, I; Almeida, M; Nogueira, M; Carvalho, C; Silva, S; Dutschmann, L
- Granulomatose de WegenerPublication . João, C; Santos, E; Leite, A; Miranda, C; Serra, I; Revés, L; Brandão, T; Martins, F; Freitas, PT; Dutschmann, LA granulomatose de Wegener corresponde a uma vasculite sistémica com atingimento das artérias de pequeno e médio calibre, em particular das vias aéreas superiores e inferiores e do rim, incluindo-se no diagnóstico diferencial das síndromas pulmão-rim. Os AA apresentam o caso clínico de uma senhora de 59 anos, internada na Unidade de Cuidados Intensivos Polivalente (UCIP) do Hospital Fernando da Fonseca com um quadro de insuficiência respiratória, hemoptises e insuficiência renal. Descreve-se o estudo etiológico desta situação, concluindo tratar-se de um caso de granulomatose de Wegener. A propósito deste caso são discutidos aspectos relevantes do diagnóstico, terapêutica e seguimento destes doentes.
- Linfoma primário do testículo: a propósito de um caso raro e revisão da literaturaPublication . Graça, B; Manso, RT; Gomes, F; Cuesta, L; Carrasquinho, J; Lourenço, M; Coelho, M; Ribeiro, FO linfoma primário do testículo é a neoplasia testicular mais frequente do idoso correspondendo no entanto a apenas1%de todos os Linfomas Não Hodgkin. A evolução natural é geralmente agressiva com metastização mesmo nos casos de doença aparentemente limitada ao testículo. Estudos retrospectivos evidenciam mau prognóstico, independentemente do estadio inicial. A taxa de recidiva é alta (50-80%) com cerca de um terço das recidivas ao nível do SNC e testículo contralateral. Discutimos o caso clínico de um doente jovem com linfoma primário de testículo. Efectuou-se uma revisão da literatura recente com ênfase no diagnóstico e novas atitudes terapêuticas.
- Phase III trial comparing 4-day chronomodulated therapy delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy GroupPublication . Giacchetti, S; Bjarnason, G; Garufi, C; Genet, D; Iacobelli, S; Tampellini, M; Smaaland, R; Focan, C; Coudert, B; Humblet, Y; Canon, J; Adenis, A; Lo Re, G; Carvalho, C; Schueller, J; Anciaux, N; Lentz, MA; Baron, B; Gorlia, T; Lévi, FPurpose: In two previous randomized trials, the adjustment of chemotherapy delivery to circadian rhythms improved tolerability and anticancer activity compared with constant-rate infusion during 5 days in patients with metastatic colorectal cancer. Patients and Methods: For this multicenter randomized trial, it was hypothesized that a chronomodulated infusion of fluorouracil, leucovorin, and oxaliplatin for 4 days (chronoFLO4) would improve survival by 10% compared with conventional 2-day delivery of the same drugs (FOLFOX2). Patients were treated every 2 weeks with intrapatient dose escalation. Results: Baseline characteristics were similar in both arms for the 564 patients (36 institutions, 10 countries). Median survival was 19.6 months (95% confidence limit [CL] 18.2, 21.2) with chronoFLO4 and 18.7 months with FOLFOX2 (95% CL 17.7, 21.0; P .55). The main dose-limiting toxicities were diarrhea for chronoFLO4 and neutropenia for FOLFOX2. The analysis of survival predictors showed that sex was the single most important factor (P .001). In women, the risk of an earlier death with chronoFLO4 was increased by 38% compared with FOLFOX2, with median survival times of 16.3 and 19.1 months (P .03), respectively. In men, the risk of death was decreased by 25% with chronoFLO4 compared with FOLFOX2, with median survival times of 21.4 and 18.3 months (P=.02), respectively. Conclusion: Both regimens achieved similar median survival times more than 18 months with an acceptable toxicity. The chronomodulated schedule produced a survival advantage over FOLFOX in men. The strong sex dependency of optimal scheduling of fluorouracil, leucovorin, and oxaliplatin calls for translational investigations of determinants related to the patient’s molecular clock.
- Coriocarcinoma não gestacional. Origem extragonadal? Caso clínicoPublication . Carvalho, R; Gomes, F; Gonçalves, L; Miranda, S; Branquinho, F; Dutschmann, LOs germinomas têm habitual localização gonadal, raramente ocorrendo de forma isolada em locais extragonadais da linha média e cujo comportamento biológico é similar aos primeiros, apesar do prognóstico ser mais desfavorável. O diagnóstico de coriocarcinoma não gestacional extragonadal é uma entidade rara, só podendo ser definido após a exclusão de patologia gonadal. Os autores descrevem o caso de um homem de 31 anos, com manifestação adenopática abdominal e lesões ocupando espaço no fígado. A biopsia cirúrgica revelou tratar-se de um coriocarcinoma puro e cujo inventário de extensão de doença revelou ser TxN3M1bS2. A urgência da situação implicou tratamento imediato com esquema de quimioterapia BEP (bleomicina, etoposido e cisplatina), com resposta completa clínico-laboratorial. Posteriormente, procedeu-se a orquidectomia radical à esquerda, orientada por alterações ecográficas, cuja avaliação anátomopatológica não identificou tecido neoplásico viável. O doente encontra-se em remissão completa com um follow-up de 24 meses pós-terapêutica.
- ERF3A/GSPT1 12-GGC allele increases the susceptibility for breast cancer developmentPublication . Malta-Vacas, J; Chauvin, C; Gonçalves, L; Nazaré, A; Carvalho, C; Monteiro, C; Bagrel, D; Jean-Jean, O; Brito, M
- Associação entre anemia perniciosa e tumor carcinóide gástrico: a propósito de um caso clínicoPublication . Carvalho, R; Leichsenring, C; Félix, J; Gomes, F; Manso, RT; Geraldes, V; Cuña, L; Branquinho, F; Perloiro, MCOs tumores carcinóides gástricos são raros, representando ≤ 1% dos tumores gástricos e 8,7% de todos os carcinóides gastrentestinais. Os autores descrevem o caso clínico de uma mulher de 32 anos admitida por anemia macrocítica, e cuja investigação etiológica revelou tratar-se de uma anemia perniciosa (AP). Realizou uma endoscopia digestiva alta (EDA), onde se encontraram 6 nódulos bem delimitados no corpo e fundo gástricos. O resultado histopatológico foi consistente com o diagnóstico de tumor carcinóide, bem diferenciado. Após exclusão de metastização secundária (por TC e cintigrafia com octreótido), tendo em conta o envolvimento multifocal do tumor e a presença de metaplasia intestinal completa no corpo e fundo gástricos, a doente foi proposta para gastrectomia total que decorreu sem intercorrências. Iniciou terapêutica com vitamina B-12, com excelente resposta clínica e analítica. O objectivo da publicação deste caso assenta no alertar para o risco do aparecimento dos carcinóides gástricos nos doentes com AP e da necessidade de realização de EDA imediatamente após o diagnóstico da mesma. Nos carcinóides gástricos tipo I que não apresentam doença à distância, a evolução é benigna.
- Posterior reversible encephalopathy syndrome and anti-angiogenic agents: a case reportPublication . Silva, F; Pêgo, P; Vendrell, MC; Farias, MJ; Timóteo, A; Costa, MC; Cravo, I; Gomes, FPosterior reversible encephalopathy syndrome is an increasingly recognised clinico-radiological entity, associated with several medical conditions (such as systemic arterial hypertension) and characterised by seizures, altered mental status, headaches, and visual symptoms. Magnetic resonance imaging is a key component in this diagnosis, with hyperintense foci in T2-weighted images, corresponding to vasogenic oedema. The pathophysiology is not fully understood but probably involves loss of auto-regulation of cerebral vasculature or endothelial dysfunction or both. A 56-year-old male, suffering from a gastro-intestinal stromal tumour with hepatic metastasis resistant to imatinib, on therapy with sunitinib, came to the Emergency Department because of headaches, hallucinations, and loss of vision. There was no previous history of high blood pressure. A hypertensive crisis was diagnosed; ophthalmological examination on admission showed no light perception bilaterally. Brain imaging displayed bilateral parieto-occipital and frontal vasogenic oedema, consistent with the clinical diagnosis of posterior reversible encephalopathy syndrome. After treatment of hypertension and suspension of sunitinib, the patient recovered from his symptoms. Control imaging showed no oedema. Angiogenesis inhibitors, such as sunitinib and bevacizumab, can cause hypertension, one of the many medical conditions associated with the posterior reversible encephalopathy syndrome. This syndrome should be considered in cases of acute visual loss, particularly in view of its reversible nature when diagnosed and treated promptly.
- Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963)Publication . Innominato, PF; Giacchetti, S; Moreau, T; Carvalho, C, et al.Circadian clocks control cellular proliferation and drug metabolism over the 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N = 556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p < .0001), and G3-4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p = .36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR = 0.56; p = .015), and worse survival on chronoFLO4 (HR = 1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy.
- Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancerPublication . Innominato, PF; Giacchetti, S; Moreau, T; Bjarnason, GA; Smaaland, R; Focan, C; Garufi, C; Iacobelli, S; Tampellini, M; Tumolo, S; Carvalho, C; Karaboué, A; Poncet, A; Spiegel, D; Lévi, F; International Association for Research on Time in Biology and Chronotherapy (ARTBC) Chronotherapy Group.BACKGROUND:Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapy-induced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy. METHODS:Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data. Patients with metastatic colorectal cancer (n = 543) from an international phase 3 trial comparing FOLFOX2 with chronoFLO4 were categorized into 4 subgroups according to the occurrence of FWL or other clinically relevant toxicities during the initial 2 courses of chemotherapy. Multivariate Cox models were used to assess the role of toxicity on the time to progression (TTP) and overall survival (OS). RESULTS:The proportions of patients in the 4 subgroups were comparable in both treatment arms (P = .77). No toxicity was associated with TTP or OS on FOLFOX2. The median OS on FOLFOX2 ranged from 16.4 (95% confidence limits [CL], 7.2-25.6 months) to 19.8 months (95% CL, 17.7-22.0 months) according to toxicity subgroup (P = .45). Conversely, FWL, but no other toxicity, independently predicted for significantly shorter TTP (P < .0001) and OS (P = .001) on chronoFLO4. The median OS on chronoFLO4 was 13.8 months (95% CL, 10.4-17.2 months) or 21.1 months (95% CL, 19.0-23.1 months) according to presence or absence of chemotherapy-induced FWL, respectively. CONCLUSIONS: Early onset chemotherapy-induced FWL was an independent predictor of poor TTP and OS only on chronotherapy. Dynamic monitoring to detect early chemotherapy-induced circadian disruption could allow the optimization of rapid chronotherapy and concomitant improvements in safety and efficacy.
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