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BACKGROUND: Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC. METHODS: Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6-10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis. RESULTS: Fourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270-0.754), 0.371 (95 % CI: 0.149-0.926), and 0.508 (95 % CI: 0.255-1.004), respectively. CONCLUSIONS: ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP.
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Albúminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Fluorouracilo , Gemcitabina , Irinotecán , Leucovorina , Oxaliplatino , Paclitaxel , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Irinotecán/uso terapéutico , Irinotecán/administración & dosificación , Anciano , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Albúminas/administración & dosificación , Albúminas/uso terapéutico , Pronóstico , Adulto , Resultado del TratamientoRESUMEN
BACKGROUND: Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC). METHODS: Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival. RESULTS: This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients. CONCLUSIONS: Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Bevacizumab/efectos adversos , Cetuximab/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Camptotecina/efectos adversos , Fluorouracilo/efectos adversos , Neoplasias del Colon/etiología , Neoplasias del Recto/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucovorina/efectos adversosRESUMEN
Purpose: The purpose of this prospective observational study was to investigate the relationship between pretreatment neutrophil-to-lymphocyte ratio (NLR) and posttreatment early tumor shrinkage (ETS), and clinical outcomes in patients with unresectable hepatocellular carcinoma (uHCC) who received lenvatinib, programmed death-1 inhibitors plus transcatheter arterial chemoembolization. Patients and Methods: A total of 63 uHCC patients were treated with this triple combination. Multivariate analyses to determine the independent factors associated with overall survival (OS) were employed. The link between NLR and clinical results was further analyzed. Furthermore, the predictive value of combining NLR with ETS should be investigated to stratify patients receiving treatment for survival benefits. Results: Progression-free survival and OS were 9.8 and 23.0 months, respectively, with a median follow-up of 20.8 months. On a multivariate analysis of OS, NLR was the only independent prognostic factor. Patients with NLR low (NLR < 3.2) had longer progression-free survival (19.3 vs 7.3 months, P < 0.001) and OS (28.9 vs 16.9 months, P < 0.001), higher objective response rate (86.7% vs 39.4%, P < 0.001), and a higher chance of achieving ETS ≥ 10% (ETS high) (73.3% vs 21.1%, P < 0.001) compared with patients with NLR high (NLR ≥ 3.2). The Spearman correlation analysis also showed the strong consistency between NLR and ETS (R2 = 0.6751). In the subgroup analysis, greater OS benefit was found in the NLR low/ETS high group than the NLR high/ETS low group (χ2 = 31.258, P < 0.001), while there was no survival difference for patients in the NLR low/ETS low group compared with in the NLR high/ETS high group (χ2 = 0.046, P = 0.830). Conclusion: NLR has the potential to identify which patients would benefit from this triple therapy, and when combined with ETS, it has the potential to provide greater predictive power in selecting the appropriate candidates for this combination treatment.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neutrófilos/patología , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Pronóstico , Quimioembolización Terapéutica/métodos , Linfocitos/patología , BiomarcadoresRESUMEN
Introduction: In recent years, programmed cell death-ligand 1 (PD-L1) inhibitor plus platinum-etoposide chemotherapy was found to have favorable clinical outcomes in patients with extensive-stage SCLC (ES-SCLC). The usefulness of early tumor shrinkage (ETS) has been reported in various types of cancers. Nevertheless, there have been few reports evaluating ETS in ES-SCLC. Therefore, this study aimed to evaluate the role of ETS in the clinical outcomes of patients with ES-SCLC receiving chemoimmunotherapy. Methods: We prospectively identified 46 patients with ES-SCLC who received PD-L1 inhibitor plus platinum-etoposide chemotherapy at 10 institutions in Japan between September 2019 and October 2021. Of them, 35 patients were selected for analyses. Results: The responders (progression-free survival [PFS] ≥ 6.0 mo) had significantly greater tumor shrinkage at the first evaluation than the nonresponders (PFS < 6.0 mo) (65.0% versus 53.7%, p = 0.03). We defined the cutoff value for ETS as a 57% change from the baseline on the basis of the receiver operating characteristic results to determine the optimal tumor shrinkage rate at the first evaluation for identifying responders. The patients with ES-SCLC who achieved ETS had longer PFS and overall survival than those who did not achieve ETS (5.6 versus 4.0 mo, log-rank test p = 0.001 and 15.0 versus 8.3 mo, log-rank test p = 0.02). In the multivariate analyses, ETS was significantly associated with PFS and overall survival (hazard ratio = 0.27, 95% confidence interval: 0.12-0.63, p = 0.002 and hazard ratio = 0.34, 95% confidence interval: 0.13-0.85, p = 0.02). Conclusions: Our prospective observational study indicated that ETS was related to favorable clinical outcomes for patients with ES-SCLC receiving PD-L1 inhibitor plus platinum-etoposide chemotherapy.
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BACKGROUND: We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer. METHODS: ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates. RESULTS: Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14-0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11-0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20-0.72) than those with ETS < 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08-0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07-0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15-0.58) than those with DpR < 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS. CONCLUSIONS: ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF.
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Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Cisplatino/uso terapéutico , Docetaxel/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Estimación de Kaplan-Meier , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
PURPOSE: Although early tumor shrinkage (ETS) is a predictor of improved overall survival (OS), the association between ETS and health-related quality of life (HRQOL) remains unclear for patients with metastatic colorectal cancer (mCRC) treated with first-line cetuximab plus chemotherapy. METHODS: The data were collected from a prospective trial that assessed HRQOL using the EORTC QLQ-C30. The impact of ETS on HRQOL was estimated using a linear mixed-effects model for repeated measures. RESULTS: ETS was achieved in 82 (64.1%) of 128 mCRC patients treated with first-line cetuximab plus chemotherapy, and these patients had a significantly longer OS than those without ETS (HR, 0.38; 95% CI, 0.20-0.72; P = .002). Asymptomatic patients with ETS had a favorable OS, while symptomatic patients without ETS had a worse OS (2-year OS rates, 77.8% vs. 42.5%). Symptomatic patients with ETS had similar outcomes as asymptomatic patients without ETS (2-year OS rates, 64.1% vs. 67.0%). For symptomatic patients, ETS was associated with improved HRQOL scores between baseline and 8 weeks: the mean changes for patients with and without ETS were 5.86 and -4.94 for global health status (GHS)/QOL, 26.73 and 3.79 for physical functioning, and 13.58 and -3.10 for social functioning, respectively. The improved HRQOL was comparable to that of asymptomatic patients without ETS. For asymptomatic patients, ETS showed a decreased deterioration in HRQOL. CONCLUSION: Our findings highlight the importance of ETS for HRQOL and prognostic estimates, and assessing ETS may provide clinically useful information for physicians and patients to make more informed decisions.
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Cetuximab , Neoplasias Colorrectales , Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Estudios ProspectivosRESUMEN
INTRODUCTION: Early tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial. METHODS: DpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex. RESULTS: In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS/BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p < 0.001; OS: p = 0.012) and molecular subgroup (PFS: p < 0.001; OS: p < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p < 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965). CONCLUSIONS: Initial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.
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BACKGROUND: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. METHODS: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. RESULTS: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. CONCLUSION: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Sorafenib/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. METHODS: This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled. RESULTS: Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively). CONCLUSIONS: The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. TRIAL REGISTRATION: UMIN Clinical Trials Registry ( UMIN000006706 ). Date of registration: NOV/11/2011. URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Bevacizumab/administración & dosificación , Cetuximab/administración & dosificación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Pronóstico , Tasa de Supervivencia , Tegafur/administración & dosificaciónRESUMEN
PURPOSES: Owing to recent advances in induction chemo(radio)therapy, patients with unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) are sometimes indicated for conversion surgery (CS). However, the predictors for proceeding to CS are unclear. We investigated the predictive factors for CS, especially at the early stage of induction therapy, and evaluated the impact of CS on the survival. METHODS: We analyzed 49 UR-LA PDAC patients retrospectively and investigated the predictive factors for proceeding to CS, including early tumor shrinkage (ETS). ETS in this study was defined as shrinkage of tumors by ≥ 15% at 8-12 weeks after the induction of treatment. RESULTS: CS was performed in 21 patients (43%). In a multivariate logistic regression analysis, ETS was an independent predictive factor for successfully proceeding to CS (P = 0.046). The median overall survival (OS) was not reached in the CS group but was 17.2 months in the non-CS group (P < 0.0001). A multivariate analysis by the Cox proportional hazard model identified CS as the only significant independent determinant of the OS (hazard ratio: 0.26, 95% confidence interval: 0.07-0.94, P = 0.004). CONCLUSIONS: ETS by induction therapy is a significant predictor of proceeding to CS among patients with UR-LA PDAC. CS was the only independent prognostic factor for this population.
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Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Conversión a Cirugía Abierta , Quimioterapia de Inducción , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Adulto , Anciano , Carcinoma Ductal Pancreático/mortalidad , Femenino , Predicción , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV. PATIENTS AND METHODS: After blinded independent central review of ETS (≥20% reduction of the sum of target lesions) and DoR in patients enrolled in Valentino, the prognostic and predictive role of such parameters was investigated, along with their combination with PRESSING panel (uncommon genomic alterations associated with anti-EGFRs resistance beyond RAS and BRAF). RESULTS: One hundred and ninety-six patients were included (ETS in 132 [67.3%], median DoR: 44.1%). Both ETS and DoR ≥34% were associated with longer mPFS (p = 0.010 and p < 0.001) and mOS (p = 0.006 and p < 0.001). The PFS benefit of 5-FU/LV added to panitumumab maintenance, reported in the study, was independent from ETS and DoR status (interaction tests NS for both PFS and OS). However, outcomes were extremely poor in patients who received single-agent panitumumab and had no-ETS (mPFS and mOS: 7.7 and 18.7 months) or DoR < 34% (mPFS and mOS: 6.5 and 18 months). Combining PRESSING panel ('molecular hyperselection') and response dynamics allowed to stratify both PFS (p < 0.001 and p < 0.001 for ETS and DoR, respectively) and OS (p < 0.001 and p = 0.017 for ETS and DoR, respectively). CONCLUSIONS: ETS and DoR allow on-treatment anticipation of outcomes following an anti-EGFR-based strategy planning de-escalation, and poor radiological response may guide enrolment in crossover strategy trials. As in vivo markers of drug sensitivity, ETS and DoR may be integrated with several patient- and tumor-related factors to wisely drive decision-making on upfront treatment duration and intensity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Quimioterapia de Mantención/mortalidad , Proteínas ras/genética , Anciano , Bevacizumab/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Metástasis de la Neoplasia , Oxaliplatino/administración & dosificación , Panitumumab/administración & dosificación , Pronóstico , Tasa de SupervivenciaRESUMEN
Objective: To explore the relationship of early tumor shrinkage (ETS) and depth of response (DpR) with the prognosis and treatment effect of trastuzumab combined with chemotherapy as first-line treatment in advanced gastric cancer with epidermal growth factor receptor 2 (HER-2) positive. Methods: We retrospectively analyzed the clinical and pathological data of 23 patients with metastatic gastric adenocarcinoma diagnosed by imaging in The Second Affiliated Hospital of Zhejiang University School of Medicine from January 1st, 2008 to December 31th, 2017. Kaplan-Meier method and the log-rank test were used for the survival analysis. Cox regression was used to analyze the factors associated with prognosis. Results: The objective response rate (ORR) of the 23 patients was 43.5% and the disease control rate (DCR) was 82.6%. Univariate analysis showed the median progress-free survival (mPFS) of ETS≥20% and ETS<20% were 13.0 months and 4.5 months, respectively, with statistical significance (P<0.001). The median overall survival (mOS) of ETS≥20% and ETS<20% were 26.8 months and 10.1 months, respectively, with statistical significance (P<0.001). The median progress-free survival (mPFS) of DpR≥15% and DpR<15% were 13.0 months and 4.5 months, respectively, with statistical significance (P=0.001). The median overall survival (mOS) of DpR≥15% and DpR<15% were 26.8 months and 9.5 months, respectively, with statistical significance (P<0.001). Multivariable Cox regression analysis revealed ETS was an independent factor of PFS (P=0.030), tumor site and Eastern Cooperative Oncology Group (ECOG) score were independent factors of OS (P<0.05). Conclusion: ETS and DpR might be used to predict the treatment efficacy and prognosis of trastuzumab combined with chemotherapy as the first-line treatment of HER-2 positive gastric cancer.
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Neoplasias Gástricas , Trastuzumab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Pronóstico , Receptor ErbB-2/genética , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: To evaluate whether the depth of response (DepRe) and early tumor shrinkage (ETS) are predictive factors of clinical outcomes in HER2-positive metastatic breast cancer (mBC) patients treated with trastuzumab. METHODS: We performed a retrospective study of 100 HER2-positive mBC patients who received trastuzumab combined with chemotherapy as first-line treatment. ETS and DepRe were calculated. We employed Youden's index to determine the optimal cutoff value of ETS and DepRe for predicting progression-free survival (PFS) and overall survival (OS). We used Kaplan-Meier analysis, Log-rank tests, and Cox proportional hazards regression models to evaluate the impacts of ETS and DepRe on clinical outcomes. RESULTS: The optimal cutoff values were 30% for ETS and 40% for DepRe; ETS and DepRe were observed in 51.0% (51/100) and in 56.0% (56/100) of patients, respectively. Both ETS≥30% and DepRe≥40% were significant tumor-size metrics for predicting PFS (ETS: median 1.43 vs 0.69 years, hazard ratio [HR] = 0.384; 95% confidence interval [CI]: 0.245 to 0.601; P=0.000030; DepRe: median 1.43 vs 0.59 years, HR = 0.390; 95% CI: 0.250 to 0.609; P=0.0000034), but only DepRe≥40% was a significant predictor for OS (median 4.02 vs 3.07 years, HR = 0.484; 95% CI: 0.255 to 0.919; P = 0.027). Multivariate analyses also identified DepRe as an independent prognostic factor for PFS (HR = 0.52; 95% CI: 0.29 to 0.93; P = 0.028) and OS (HR=0.37; 95% CI:0.15 to 0.90; P = 0.029). CONCLUSION: ETS≥30% and DepRe≥40% were significant predictors of better clinical outcomes in mBC patients treated with first-line trastuzumab-based chemotherapy. Further validation in prospective trials with larger patient populations is needed.
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INTRODUCTION: Chromophobe renal cell carcinoma presents in early pathological stages with a lower risk of metastasis. However, aggressive features and metastasis can occur. A rare case of rapidly progressive disease with histological changes is presented. CASE PRESENTATION: A 56-year-old woman had a right renal tumor with multiple lymph node metastases, and the pathological diagnosis of the biopsy specimens from the primary tumor was chromophobe renal cell carcinoma. After sunitinib treatment, the metastatic lymph node had decreased in size and the numbers of circulating tumor cells were decreased, consequently, cytoreductive nephrectomy was performed. However, rapid progression of lymph node metastases was observed. Histopathological examination showed that the renal tumor was diagnosed as spindle cell renal carcinoma. CONCLUSION: It appears that the primary tumor underwent epithelial-mesenchymal transition; further tissue specimen collection and analysis might be needed.
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PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Panitumumab/administración & dosificación , Resultado del Tratamiento , Proteínas ras/genéticaRESUMEN
We investigated the association between early tumor shrinkage (ETS) and treatment outcome in patients with hepatocellular carcinoma treated with lenvatinib (LEN). A retrospective analysis was performed in 104 patients. ETS was defined as tumor shrinkage at the first evaluation in the sum of target lesions' longest diameters from baseline according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 5.0 months. The receiver operating characteristic curve analysis in differentiating long-term responders (PFS ≥ 5.0 months) from short-term responders (PFS < 5.0 months) revealed an ETS cut-off value of 10%. ETS ≥ 10% was significantly correlated with better PFS and OS compared with ETS < 10%. Additionally, ETS ≥ 10% showed a better discrimination ability on prognosis compared with modified RECIST-based objective response at the first evaluation. Multivariate analysis confirmed ETS ≥ 10% as an independent predictor of better OS, as well as a Child-Pugh score of 5 and macrovascular invasion. In conclusion, ETS ≥ 10% was strongly associated with outcome in patients treated with LEN. This biomarker could allow earlier assessment of the treatment response and guide treatment decision-making for HCC.
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The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials. World Health Organization and Response Evaluation Criteria in Solid Tumors (RECIST) are anatomic response criteria developed mainly for cytotoxic chemotherapy. These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography (CT) or magnetic resonance imaging. Anatomic response criteria may not be optimal for biologic agents, some disease sites, and some regional therapies. Consequently, modifications of RECIST, Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors. Despite its limitations, RECIST v1.1 is validated in prospective studies, is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents. Finally, some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors. Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging. Some graphical methods may be useful to show longitudinal change in the tumor burden over time. Tumor tissue is a tridimensional heterogenous mass, and tumor shrinkage is not always symmetrical; thus, metabolic response assessments using positron emission tomography (PET) or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments. The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage, possibly preventing delays in drug approval. Computer-assisted automated volumetric assessments, quantitative multimodality imaging in radiology, new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.
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BACKGROUND: Cetuximab-induced skin toxicity (Cet-ST) is positively associated with outcome in metastatic colorectal cancer (mCRC). Besides its predictive relevance for targeted therapy, we investigated its prognostic impact with early tumor shrinkage (ETS) ≥20%, another on-treatment surrogate for clinical outcome in FIRE-3. PATIENTS AND METHODS: FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumors (i.e. wild-type in KRAS and NRAS exons 2-4). Retrospective data on Cet-ST that occurred during cycles 1-3 of treatment were correlated with efficacy endpoints, including ETS. To control for guarantee-time bias, only patients who had completed three or more treatment cycles were considered. RESULTS: Of 199 patients treated with FOLFIRI/Cet, 181 (91.0%) completed three or more treatment cycles. A significant survival benefit of FOLFIRI/Cet over FOLFIRI/Bev was only evident in patients developing Cet-ST grade 2-3 [41.0 versus 26.6 months; hazard ratio (HR) = 0.73; 95% confidence interval (CI): 0.61-0.87; P < 0.001] compared with Cet-ST grade 0-1 (HR = 0.90; 95% CI: 0.67-1.20; P = 0.48). Regarding prognosis, Cet-ST grade 2-3 (n = 75; 41.4%), compared with Cet-ST grade 0-1 (n = 106; 58.6%), was associated with prolonged overall survival (OS; HR = 0.62; 95% CI: 0.42-0.91; P = 0.01). In multivariate analysis, both Cet-ST (HR = 0.66; 95% CI: 0.50-0.87; P = 0.003) and ETS (HR = 0.55; 95% CI: 0.41-0.74; P < 0.0001) were independently prognostic for OS. Absence of both Cet-ST grade ≥2 and ETS identified a subgroup of patients with very poor prognosis (median OS 15.1 months). CONCLUSIONS: In FIRE-3, the addition of cetuximab to FOLFIRI was associated with superior OS compared with FOLFIRI/Bev only in patients developing Cet-ST grade ≥2. Regarding prognostic relevance, both Cet-ST and ETS were independent and early predictors of survival. The present analysis supports that a combined evaluation of on-treatment parameters such as Cet-ST and ETS may help to guide treatment of mCRC.
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Camptotecina , Neoplasias Colorrectales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Camptotecina/efectos adversos , Cetuximab/efectos adversos , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/efectos adversos , Humanos , Leucovorina/efectos adversos , Metástasis de la Neoplasia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Short treatment-duration with early restaging is crucial to avoid liver injury after preoperative chemotherapy (preopCTX) for colorectal liver metastases (CRLM). Response evaluation according to response evaluation criteria in solid tumors (RECIST) criteria implies several limitations. Early tumor shrinkage (ETS; ≥20% size reduction <6-12 weeks) or morphological criteria (MC) may better predict oncological outcome. METHODS: In patients undergoing resection after preopCTX between 2003-2017 pathological and radiological response was reassessed according to Blazer classification, ETS, MC, and RECIST within 90 days and correlated with survival. RESULTS: Seventy-two patients were included, with a median of two (1-10) liver lesions, 53% bilobar involvement, and 7% extrahepatic disease. PreopCTX was applied for 3 months in median (1-6). During restaging after a median of 62 days, presence of ETS was associated with improved median overall survival (OS; 57.1 vs 33.7 months; P = .010) and disease-free survival (16 vs 7.2 months; P = .025). MC significantly correlated with major pathological response (P = .021). When combining ETS with optimal MC, presence of one or both factors was associated with pathological response (61.5% and 92.3%; P = .044) and OS in log-rank (P = .011), and multivariable analysis (hazard ratio [HR] 0.41; 95% confidence interval [CI], 0.19-0.90 and HR 0.32; 95%CI, 0.11-0.97). CONCLUSION: Response-grading by combined ETS/MC criteria less than 90 days after preopCTX initiation predicts pathological response and postoperative survival in CRLM.
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BACKGROUND: There is no standardized assessment of symptomatic events in metastatic colorectal cancer (mCRC) despite disease symptoms that affect treatment decisions. Data from 3 first-line panitumumab in mCRC trials were retrospectively analyzed to assess whether early tumor shrinkage (ETS) and depth of response (DpR) were associated with time to occurrence of tumor-related symptoms. PATIENTS AND METHODS: Patients with RAS wild-type mCRC from PRIME, PEAK, and Study 314 were included. ETS was defined as a reduction of ≥ 30% in the sum of the longest diameters of lesions at 8 weeks. DpR was calculated as maximum percentage change in tumor size from baseline to nadir. The proportion of patients who developed symptoms (including a composite symptomatic endpoint) during study treatment was calculated. This study was registered at ClinicalTrials.gov as PRIME (NCT00364013), PEAK (NCT00819780), and Study 314 (NCT00508404). RESULTS: Overall, data of 659 patients were analyzed. Onset of symptoms was delayed in patients with ETS ≥ 30% versus ETS < 30% and in patients with greater DpR. In patients with symptoms at baseline who experienced ETS ≥ 30%, overall survival was similar to that seen for patients without symptoms at baseline. CONCLUSION: Both ETS and DpR were associated with delayed onset of symptoms in RAS wild-type mCRC patients. Treatments with high cytoreductive potential may delay symptom development.