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J Gastrointest Cancer ; 49(4): 470-475, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28884286


PURPOSE: Our objective was to evaluate the benefit of re-exposing patients with refractory metastatic colorectal cancer (mCRC) to a combination of oxaliplatin, irinotecan and 5-fluorouracil treatment. METHODS: We retrospectively analysed patients with mCRC who received a combination of oxaliplatin, irinotecan and fluorouracil as a rechallenge regimen after progressing on the same drugs. Both FOLFOXIRI and FOLFIRINOX were used. Toxicity was evaluated for each treatment cycle, and survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 21 patients who were treated between January 2011 and December 2013 were selected for this study. Most of the patients (95.2%) had an ECOG status of 0-1. The median age at diagnosis was 52.1 years (range 36-77 years), and 14 (66.6%) patients had wild-type KRAS. Thirteen patients received FOLFIRINOX, and eight received FOLFOXIRI. Most patients had previously received at least three regimens, with 80% receiving anti-VEGF and 66% anti-EGFR antibodies. The response rate was 38%, and 24% patients had stable disease. The median time to disease progression was 4.0 months (range 1.0-9.1 months), and the median overall survival duration was 8.6 months (range 6.3-11.5 months). Most patients required dose adjustment and treatment delays. One patient experienced grade 5 neutropenic sepsis. CONCLUSIONS: Both FOLFIRINOX and FOLFOXIRI are active and potentially feasible rechallenge treatment options for heavily pretreated patients with good performance status. With dose reduction and close monitoring for toxicity, the risk of serious adverse events can be minimised.

Ecancermedicalscience ; 11: 767, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28955403


BACKGROUND: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities. MATERIALS AND METHODS: This is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy. Paraffin-embedded tumour samples were reviewed by a single pathologist and tested for immunohistochemistry (IHC) expression of Ki-67, ERCC1, Bcl-2, and Lin28a. All images were evaluated by the same radiologist and RR was determined by RECIST 1.1. RESULTS: From July, 2006 to July, 2014, 142 patients were identified, being 82 (57.7%) SCLC and 60 (42.3%) EPNEC. Clinical characteristics and median Ki-67 (SCLC: 60%; EPNEC: 50%; p = 0.86) were similar between the groups. RR was higher for SCLC patients (86.8% versus 44.6%; p<0.001), but median OS was similar (10.3 months in SCLC and 11.1 months in EPNEC; HR 0.69, p = 0.07). Bcl-2 expression was higher in SCLC patients (46.3% versus 28.3%, p = 0.03) and was associated with worse prognosis in EPNEC (median OS 8.0 months versus 14.7 months; HR 0.47, p = 0.02). CONCLUSION: EPNEC patients presented inferior RR to platinum-based chemotherapy than SCLC but tended to live longer. Neither ERCC1, Lin28, or Ki-67 were prognostic or predictive for RR in EPNEC or SCLC. High Bcl-2 expression was associated with poor prognosis in EPNEC patients.

J Nucl Med ; 55(10): 1598-604, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25168627


UNLABELLED: There are different metabolic imaging methods, various tracers, and emerging anatomic modalities to stage neuroendocrine tumor (NET). We aimed to compare NET lesion detectability among (99m)Tc-hydrazinonicotinamide (HYNIC)-octreotide (somatostatin receptor scintigraphy [SSRS]) SPECT/CT, (68)Ga-DOTATATE PET/CT, and whole-body diffusion-weighted MR imaging (WB DWI). METHODS: Nineteen consecutive patients (34-77 y old; mean, 54.3 ± 10.4 y old; 10 men and 9 women) underwent SSRS SPECT/CT, (68)Ga-DOTATATE PET/CT, and WB DWI. Images were acquired with a maximum interval of 3 mo between them and were analyzed with masking by separate teams. Planar whole-body imaging and SPECT/CT were performed from thorax to pelvis using a double-head 16-slice SPECT/CT scanner 4 h after injection of 111-185 MBq of (99m)Tc-HYNIC-octreotide. (68)Ga-DOTATATE PET/CT was performed from head to feet using a 16-slice PET/CT scanner 45 min after injection of 185 MBq of tracer. WB DWI was performed in the coronal plane using a 1.5-T scanner and a body coil. The standard method of reference for evaluation of image performance was undertaken: consensus among investigators at the end of the study, clinical and imaging follow-up, and biopsy of suggestive lesions. RESULTS: McNemar testing was applied to evaluate the detectability of lesions using (68)Ga-DOTATATE PET/CT in comparison to SSRS SPECT/CT and WB DWI: a significant difference in detectability was noted for pancreas (P = 0.0455 and P = 0.0455, respectively), gastrointestinal tract (P = 0.0455 and P = 0.0455), and bones (P = 0.0082 and P = 0.0082). Two unknown primary lesions were identified solely by (68)Ga-DOTATATE PET/CT. (68)Ga-DOTATATE PET/CT, SSRS SPECT/CT, and WB DWI demonstrated, respectively, sensitivities of 0.96, 0.60, and 0.72; specificities of 0.97, 0.99, and 1.00; positive predictive values of 0.94, 0.96, and 1.00; negative predictive values of 0.98, 0.83, and 0.88; and accuracies of 0.97, 0.86, and 0.91. CONCLUSION: (68)Ga PET/CT seems to be more sensitive for detection of well-differentiated NET lesions, especially for bone and unknown primary lesions. NET can be staged with (68)Ga-DOTATATE PET/CT. WB DWI is an efficient new method with high accuracy and without ionizing radiation exposure. SSRS SPECT/CT should be used only when (68)Ga-DOTATATE PET/CT and WB DWI are not available.

Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos , Imagem Corporal Total/métodos , Adulto , Idoso , Algoritmos , Biópsia , Feminino , Humanos , Hidrazinas , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Ácidos Nicotínicos , Octreotida , Compostos Organometálicos , Estudos Prospectivos , Tecnécio , Tomografia Computadorizada de Emissão de Fóton Único/métodos