TIAGO BIACHI DE CASTRIA
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- Induction Chemotherapy for Locally Advanced Esophageal Cancer(2020) HARADA, Guilherme; BONADIO, Renata Rodrigues da Cunha Colombo; ARAUJO, Frederico Cantarino Cordeiro de; VICTOR, Carolina Ribeiro; SALLUM, Rubens Antonio Aissar; RIBEIRO JUNIOR, Ulysses; CECCONELLO, Ivan; TAKEDA, Flavio Roberto; CASTRIA, Tiago Biachi deBackground Concurrent chemoradiotherapy followed by surgery is the standard treatment for locally advanced esophageal cancer (EC), and the role of induction chemotherapy (IC) remains unclear. We aimed to study if the addition of IC to standard treatment increases the rate of pathologic complete response (pCR). Methods We assembled a retrospective analysis of patients (pts) diagnosed with locally advanced EC and treated with preoperative chemoradiotherapy followed by esophagectomy (CRT+S), preceded or not by IC, between 2009 and 2017. Patients' characteristics, tumor variables, and treatment outcomes were evaluated. The Kaplan-Meier method was used to estimate overall survival and the Cox proportional hazard model to evaluate prognostic factors. Results One hundred and three patients were studied, with a median age of 62 years (range 37-84). Seventy-five patients (73%) were male, 67 (65%) had squamous cell carcinoma, and 31 (30%) had adenocarcinoma. Forty-three patients (41.7%) received IC followed by CRT+S (IC+CRT+S). The most frequent IC consisted of paclitaxel and platinum chemotherapy (90%), and the median number of cycles was 2. All patients received CRT+S. Concurrent chemotherapy was a combination of paclitaxel and platinum in 94 patients (91%). There was no statistically significant difference in pCR between the IC group and the standard CRT+S group. The pCR was 41.9% and 46.7% in the IC+CRT+S and CRT+S groups (p = 0.628), respectively. In the multivariate analysis, pCR was an independent prognostic factor for time to treatment failure (TTF) (HR 0.35, p = 0.021), but not for overall survival (OS) (p = 0.863). The factor that significantly affected OS in the multivariate analysis was positive lymph node (HR 5.9, 95%, p = 0.026). Conclusions Our data suggest that the addition of IC to standard CRT + S does not increase the pCR rate in locally advanced EC. No difference in OS was observed between pts. that received or not IC. Regardless of the treatment received, pts. achieving a pCR presented improved TTF.
- Schistosomiasis Misleading Gastric Cancer Treatment(2020) RAMOS, Marcus Fernando Kodama Pertille; DUARTE, Vinicius Campos; PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi de; SCHMERLING, Claudia Kliemann; ZILBERSTEIN, Bruno; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan
conferenceObject Immunohistochemical Scores for Programmed Death Ligand-1 (PD-L1) Expression and Prognostic in Patients with Gastric Cancer(2020) PEREIRA, Marina A.; RAMOS, Marcus Fernando Kodama P.; RIBEIRO, Renan Ribeiro e; DIAS, Andre R.; RIBEIRO JR., Ulysses; ZILBERSTEIN, Bruno; CECCONELLO, Ivan; MELLO, Evandro Sobroza; CASTRIA, Tiago B.- Impact of neoadjuvant chemotherapy on surgical and pathological results of gastric cancer patients: A case-control study(2020) CHARRUF, Amir Zeide; RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; CASTRIA, Tiago Biachi de; ZILBERSTEIN, Bruno; CECCONELO, Ivan; RIBEIRO, UlyssesBackground and Objective Neoadjuvant chemotherapy (NACT) followed by radical surgery represents a treatment option for patients with advanced gastric cancer (GC). This case-control study aimed to evaluate the clinicopathological characteristics and surgical outcomes of GC patients who received NACT, and its impact on survival. Methods We retrospectively reviewed all patients with GC who underwent gastrectomy. A total of 45 cases with NACT were matched with consecutive 45 patients who underwent upfront gastrectomy for the following characteristics: gender, age, gastrectomy type, lymphadenectomy extent, American Society of Anesthesiologists class, histological type, cT and cN. Results NACT group had smaller tumors (4.9 vs 6.8 cm P = .006), lower lymphatic invasion rate (40% vs 73.3%, P = .001), lower venous invasion rate (18% vs 46.7%, P = .003) and lower perineural invasion rate (35% vs 77.8%, P < .0001). The ypTNM stage was lower in patients treated with NACT (P < .001). The major postoperative complication (POC) rate was lower in NACT patients (6.7% vs 24.4%, P = .02), as was hospital length of stay (10.8 vs 17 days, P = .005). Conclusions NACT allowed nodal and tumor downstaging. In addition, patients who underwent NACT had fewer POC and shorter length of hospital stay.
- Remnant gastric cancer: a neglected group with high potential for immunotherapy(2020) RAMOS, Marcus Fernando Kodama Pertille; PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi de; RIBEIRO, Renan Ribeiro e; CARDILI, Leonardo; MELLO, Evandro Sobroza de; ZILBERSTEIN, Bruno; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, IvanPurpose The importance of targeted therapy and interest in the study of predictive markers in gastric cancer (GC) have increased in recent years with the use of anti-HER2 therapy and immunotherapy with anti-PD1/PD-L1 for microsatellite instability (MSI) and PD-L1 + tumors. However, the behavior of remnant GC (RGC) in this scenario is poorly reported. Thus, this study aims to evaluate the clinicopathological characteristics and prognosis of RGC and its association with the expression of current markers for targeted therapy. Methods All RGC resections performed in a single center from 2009 to 2019 were retrospectively reviewed. As a comparison group, 53 primary proximal GC (PGC) who underwent total D2-gastrectomy were selected. HER2, MSI status and PD-L1 expression were analyzed by immunohistochemistry. Combined Positive Score (CPS) was used to determine PD-L1 positivity. Results A total of 40 RGC were included. RGC patients were older (p = 0.001), had lower BMI (p = 0.001) and number of resected lymph nodes (p < 0.001) compared to the PGC. Regarding markers expression, MSI was higher in RGC than PGC (27.5% vs 9.4%,p = 0.022). The frequency of CPS-positive was 32.5% and 26.4% in RGC and PGC, respectively (p = 0.522). HER2 positivity was 17.5% and 22.6% for RGC and PGC, respectively (p = 0.543). In survival analysis, DFS was better for RGC CPS-positive than RGC CPS-negative (p = 0.039) patients. There was no difference in survival considering MSI status. Conclusion RGC had higher incidence of MSI than PGC, and CPS-positive RGC was associated with better survival. The immunological profile of RGC patients suggests that they would be good candidates for immunotherapy.
conferenceObject Remnant Gastric Cancer: Neglect Group with High Potential for Immunotherapy(2020) RAMOS, Marcus Fernando Kodama P.; PEREIRA, Marina Alessandra; CASTRIA, Tiago Biachi; RIBEIRO, Renan Ribeiro e; MELLO, Evandro Sobroza; DIAS, Andre Roncon; ZILBERSTEIN, Bruno; RIBEIRO JR., Ulysses; CECCONELLO, Ivan- Gastric cancer molecular classification and adjuvant therapy: Is there a different benefit according to the subtype?(2020) RAMOS, Marcus F. K. P.; PEREIRA, Marina A.; AMORIM, Larissa C.; MELLO, Evandro S. de; FARAJ, Sheila F.; JR, Ulysses Ribeiro; HOFF, Paulo M. G.; CECCONELLO, Ivan; CASTRIA, Tiago B. deBackground Gastric cancer (GC) has been defined in distinct molecular subtypes with different therapeutic implications. However, its clinical significance and prognosis regarding standard chemotherapy (CMT) remains unclear. This study aimed to analyze the impact of perioperative or adjuvant treatment among subtypes of GC. Methods We retrospectively evaluated all stage II/III patients with GC who underwent a curative gastrectomy. Based on immunohistochemistry and in situ hybridization techniques, GC was classified into five subtypes: Epstein-Barr virus (EBV) positive, microsatellite instability (MSI), e-cadherin aberrant, p53-aberrant, and p53-normal. Results Among the 178 CG included, 111 patients received CMT and 67 were treated with surgery alone. Survival analysis showed that p53-aberrant GC treated with CMT had better disease-free survival (DFS) compared with surgery alone (P = .001).There was no significant difference in DFS between patients who received CMT and those with surgery alone for EBV, MSI, E-cadherin, and p53-normal GC. An improvement in overall survival was observed only for E-cadherin (P = .001) and p53-aberrant (P < .001) patients who received CMT. Conclusions CMT showed different impact on the survival of CG according to the molecular subtype. No survival benefit was observed for EBV and MSI groups who received CMT. GC with p53-aberrant had a significant benefit in survival with standard therapy.
- Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer(2020) VASCONCELLOS, Vitor F.; MARTA, Guilherme N.; SILVA, Edina M. K. da; GOIS, Aecio F. T.; CASTRIA, Tiago B. de; RIERA, RachelBackground Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care. Objectives To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug. Search methods We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources. Selection criteria Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen. Data collection and analysis Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity. Main results In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I-2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I-2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/ m2) (HR 0.93, 95% CI 0.83 to 1.04; I-2= 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I-2= 68%;10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I-2= 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; 2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I-2= 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% C10.79 to 2.38;12 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I-2=94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured. Authors' conclusions Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.
- Return to Intended Oncologic Treatment (RIOT) in Resected Gastric Cancer Patients(2020) RAMOS, Marcus Fernando Kodama Pertille; CASTRIA, Tiago Biachi de; PEREIRA, Marina Alessandra; DIAS, Andre Roncon; ANTONACIO, Fernanda Fronzoni; ZILBERSTEIN, Bruno; HOFF, Paulo Marcelo Gehm; RIBEIRO JR., Ulysses; CECCONELLO, IvanBackground Postoperative chemotherapy (CMT) or chemoradiotherapy (CRT) is commonly recommended for gastric cancer (GC) patients in order to improve survival. However, some factors that prevent patients from return to intended oncologic treatment (RIOT) may increase the risk of recurrence and decrease the survival benefits achieved with curative resection. The aim of this study was to determine the frequency and factors associated with inability to RIOT and their impact on survival. Methods This retrospective study included stage II/III GC patients treated with potentially curative gastrectomy. Patients who could return to intended oncologic treatment (RIOT group) and those who could not (inability to RIOT group) were analyzed. Results Of the 313 eligible GC patients, 89 (28.4%) and 85 (27.2%) patients receive CRT and CMT, respectively, representing a RIOT rate of 55.6%. The main reason was attributed to general poor performance status (30.2%), followed by surgical postoperative complications (POC) (20.1%). Older age, higher ASA, D1 lymphadenectomy, and major POC were related to inability to RIOT. Older age, neutrophil-lymphocyte ratio (NLR), and major POC were independent risk factors for inability to RIOT. Five-year DFS and OS were worse for the inability to RIOT group than for the RIOT group (p = 0.008 and p = 0.004, respectively). In multivariate analyses, absence of neoadjuvant therapy, total gastrectomy, pT3/T4, pN+, and inability to RIOT were associated with worse DFS. Type of gastrectomy, lymphadenectomy, pN status, Rx resection, and RIOT group were associated with OS. Conclusion Older age, high NLR, and major POC were risk factors for inability to RIOT. RIOT was an independent predictor of survival.
- Lymph node regression after neoadjuvant chemotherapy: A predictor of survival in gastric cancer(2020) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; RIBEIRO, Renan Ribeiro e; CHARRUF, Amir Zeide; CASTRIA, Tiago Biachi de; ZILBERSTEIN, Bruno; CECONELLO, Ivan; ALVES, Venancio Avancini Ferreira; RIBEIRO JR., Ulysses; MELLO, Evandro Sobroza deBackground and Objective Neoadjuvant chemotherapy (nCMT) has been increasingly used in advanced gastric cancer (GC). However, the prognostic impact of tumor response remains unclear. This study aimed to evaluate if tumor response at the primary site and lymph nodes (LN) correlate with survival in GC patients after nCMT. Methods Patients with gastric adenocarcinoma treated with nCMT followed by gastrectomy were evaluated. Residual tumor was graded from 0% to 100%, defining two groups: poor (PR) and major response (MR). LN regression rate (LNRR) was determined based on tumor/fibrosis examination at each LN and a cutoff value established by receiver operating characteristic curve. Results Among 62 cases, 20 (32.2%) had MR and 42 (67.7%) PR. Smaller size, diffuse histology, lower ypT status and less advanced stage were associated with the MR group. Based on cutoff value of 57, 45.6% and 54.4% patients were classified as low-LNRR and high-LNRR. High-LNRR correlated with absence of venous, lymphatic and perineural invasion, and less advanced stage. Survival was equivalent between MR and PR (P = .956). High-LNRR had better disease-free survival (DFS) than low-LNRR (P < .001). In multivariate analysis, only LNRR associated with DFS. Conclusion High-LNRR associates with DFS in GC treated with nCMT. Response at the primary site does not correlate with survival.