RESUMO
BACKGROUND: Molecular targeted drugs having angiogenesis-inhibiting properties allow the induction of necrosis inside tumors. We retrospectively investigated the relationship between changes on imaging associated with regorafenib (REGO) and treatment outcomes using real-world data. PATIENTS AND METHODS: The eligibility criteria included an ECOG PS of 0-1, a starting dose of 120 or 160 mg/day of REGO, and a duration of treatment of at least 35 days. Regarding changes on imaging, cavitation in lung lesions (CLL), morphologic response of liver lesions (MRL), and change of liver metastasis density (CLD) were evaluated. RESULTS: We finally screened 671 cases, and 226 cases were eligible. In total, 172 and 145 patients had lung and liver metastases, respectively. Among the patients with lung metastasis, CLL was found in 69 patients (40.0%). The median progression-free survival (PFS) of the patients with and those without CLL was 3.2 and 2.4 months, respectively (hazard ratio [HR] = 0.758; 95% confidence interval [CI]: 0.529-1.087), and the median overall survival (OS) of these groups was 10.5 and 8.9 months, respectively (HR = 0.862; 95% CI: 0.579-1.285). MRL and CLD of liver metastasis were analyzed in 145 and 90 patients, respectively. The median OS with and without MRL was 8.9 and 8.2 months, respectively, whereas the median OS with and without CLD was 11.6 and 7.7 months, respectively (HR = 0.523; 95% CI: 0.275-0.992). CONCLUSION: CLL may predict PFS but not OS among patients with lung metastasis. CLD was predictive of favorable outcomes for REGO in patients with liver metastasis.
Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND: There are several methods for analyzing computed tomography (CT) images to evaluate chemotherapy efficacy in clinical studies. However, the optimal analysis method for each drug is still under debate. We conducted a pooled analysis using data from six phase II studies to evaluate four analysis methods in colorectal cancers (CRCs): morphological responses (MRs), early tumor shrinkage (ETS), depth of response (DpR), and response evaluation criteria in solid tumors (RECIST) ver.1.1. METHODS: We included 249 patients in this analysis. Pretreatments and findings of subsequent CT imaging were analyzed based on the MR, ETS, DpR, and RECIST ver.1.1. Differences in overall survival (OS) between the responders and non-responders according to each method were evaluated using survival analysis. RESULTS: The responders had significantly better hazard ratios (HRs) for OS, in terms of DpR (≥ median), ETS, objective response rate (ORR) [complete response (CR) + partial response (PR)], and disease control rate [CR + PR + stable disease (SD)]. Patients with right-sided colon cancers showed better HRs for DpR, but not for ETS and ORR. Contrastingly, patients with left-sided CRCs had better HRs for ETS, DpR, and ORR. MR was not associated with outcomes in this study, even in cases where bevacizumab was used. In patients with liver metastasis, ETS, DpR, and ORR showed better HRs, but not in those with lung metastasis. CONCLUSION: Early tumor shrinkage and DpR might be predictive markers only in left-sided CRCs with liver metastasis. Each imaging analysis has a different value based on the primary and metastatic sites.
Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Bevacizumab/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Análise de SobrevidaRESUMO
BACKGROUND: Regorafenib is a multi-kinase inhibitor, which was shown to be effective for patients with metastatic colorectal cancer refractory to standard therapies. However, its patterns of response has not yet been fully understood. METHODS: Clinical records of 10 patients who received regorafenib for evaluable colorectal liver metastases were reviewed. Response to chemotherapy was evaluated with the RECIST and morphologic response criteria, and its clinical relevance was analyzed. RESULTS: All patients received multiple lines of fluorouracil-based chemotherapy before regorafenib. The median follow-up duration after introduction of regorafenib was 4.9 months (range, 2 to 12.5 months). Median number of chemotherapy cycles was 2 (range, 1 to 15). In size-based response evaluation, 4 patients presented SD and 6 patients showed PD according to the RECIST. In non-size-based response evaluation, 3 patients were classified as optimal morphologic response and 7 patients were categorized as suboptimal morphologic response. Patients who presented optimal morphologic response showed significantly longer progression-free survival compared with those presented suboptimal response (median, 4.9 months vs. 0.7 months; P = 0.028), while size-based response evaluation could not well stratify patient prognosis. CONCLUSION: Non-size-based CT morphologic response could be a potential alternative response marker for patients treated with regorafenib.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Projetos Piloto , Prognóstico , Piridinas/administração & dosagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. PATIENTS AND METHODS: Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. RESULTS: In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. CONCLUSION: Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Prognóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Recidiva , Estudos RetrospectivosRESUMO
The increasing indications of cytostatic biotherapies and the improvement in metastatic surgery have profoundly changed the management of metastatic colorectal cancer (mCRC) patients. Then the development of prognostic and predictive scores would be useful to stratify the treatments. Tumor radiological measurement is crucial to estimate treatment efficacy, and to predict pathological response and survival, and this parameter is included when a prognostic score is developed. But the standard size-based radiologic criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), was designed ten years ago to assess tumor volume reduction after cytotoxic chemotherapy only. Nowadays, this method may be insufficient for mCRC patients. The aim of this review is to describe the different radiological assessments evaluated in mCRC, and to underline their correlations with patient's survival and pathologic response. A better knowledge of these radiological measurements would help to better integrate them in prospective trials, and in the prognostic and predictive scores. The choice of radiological measurement could be discussed regarding patient's situation, combining different approaches, and assessing tumoral mass quantification.
Assuntos
Neoplasias Colorretais , Critérios de Avaliação de Resposta em Tumores Sólidos , Carga Tumoral , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Humanos , Imunoterapia , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND/AIM: Anti-EGFR antibodies or bevacizumab comprise first-line treatment for patients with RAS wild-type colorectal liver metastases (CLM). Which marker better predicts efficacy, early tumor shrinkage or morphologic response, still remains unclear. PATIENTS AND METHODS: We retrospectively evaluated 155 patients with KRAS exon 2 wild-type CLM treated with bevacizumab (BEV group) or anti-EGFR antibodies (EGFR group). Three radiologists independently assessed early tumor shrinkage (ETS) and early optimal morphologic response (EOMR) from baseline and first follow-up CT scan. RESULTS: Patients with ETS had longer progression-free survival (PFS) than those without ETS [hazard ratio (HR)=0.69] and ETS tended to be observed in the EGFR group, while patients with EOMR had longer PFS than those without EOMR (HR=0.64) and EOMR tended to be observed in the BEV group. CONCLUSION: Among patients with KRAS exon 2 wild-type CLM, EOMR and ETS may predict better PFS, especially in patients treated with bevacizumab and anti-EGFR antibodies, respectively.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Éxons , Feminino , Humanos , Neoplasias Hepáticas/genética , Masculino , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The computed tomography (CT) morphologic response of colorectal liver metastases (CLM) after chemotherapy is reportedly correlated with pathologic response and survival outcomes of patients undergoing surgery. However, they are rather subjective criteria and not evaluable without adequate quality of contrast-enhanced CT images. This study sought the potential use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) as an objective substitute for predicting pathological viability of CLM after chemotherapy. METHODS: Predictive ability of tumor viability of ≤10% was compared between FDG-PET/CT and contrast-enhanced CT in 34 patients who underwent curative surgical resection for CLM after chemotherapy. The CT morphology and response were defined according to the reported criteria (Chun YS, JAMA 2009). RESULTS: The mean standard uptake value (SUV-mean) in CLM was significantly lower in patients with group 1 and group 2 CT morphology (median, 2.53 and 3.00, respectively) than in group 3 (median, 3.32). The tumor SUV-mean showed moderate correlation with the tumor pathologic viability (r = 0.660, P < 0.0001). A receiver operating characteristic curve analysis revealed that both the tumor SUV-mean (area under the curve [AUC], 0.916; the cut-off value, 3.00) and the CT morphology (AUC, 0.882) have excellent predictive power for ≤10% of tumor viability, while degree of tumor shrinkage showed lower predictive power (AUC, 0.692). CONCLUSIONS: FDG-PET shows significant correlation with pathologic viability of CLM after chemotherapy and may offer additional objective information for estimating tumor viability when the CT morphologic response is not evaluable.