Retrospective analysis of clinical characteristics of mCRC patients receiving three or more lines of chemotherapy.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 682-682
Author(s):  
Pilar Garcia Alfonso ◽  
Íñigo Martínez Delfrade ◽  
Javier Soto Alsar ◽  
Marianela Bringas Beranek ◽  
Natalia Gutiérrez Alonso ◽  
...  

682 Background: Prognostic and predictive factors are becoming more important in mCRC patients, and may have an impact in overall survival and in the number of lines of chemotherapy that a patient can receive. Methods: We conducted a retrospective analysis of 334 patients with mCRC. We analyzed the clinical characteristics of 113 (33.8%) mCRC patients who received ≥3 lines of chemotherapy. We apply the statistical test Chi square in order to identify significant association. Results: Several characteristics were significantly associated with receiving ≥ 3 lines of chemotherapy (n = 113): age < 80 years (n = 93, OR = 3.07, p = 0.001), ECOG 0-1 (n = 98, OR = 3.21, p = 0.055), primary tumor resection (n = 62, OR = 2.36, p = 0.000) and resection of metastases (n = 56, OR = 2.07, p = 0.002). Partial or complete response rate in the first line of chemotherapy was also significantly associated with receiving ≥ 3 lines of treatment (n = 65, p = 0.011). Tumor mutational status was analyzed in 333 patients: KRAS mutation was detected in 163 over 333 patients genotyped (48.9%), NRAS in 25/206 (12.1%), BRAF in 15/217 (6.9%) and PI3K in 31/213 (14.5%). In the group of patients receiving ≥ 3 lines of chemotherapy (n = 113): KRAS mutation was found in 60/113 patients (53.1%), NRAS in 5/77 (6.5 %), BRAF in 5/84 (5.9%) and PI3K in 8/80 (11.1%). Tumor mutations were not significantly associated with ≥ 3 lines of chemotherapy. No significant association was found between sex, tumor location (right [n = 33, 29.2%] or left [n = 76, 73%]), liver or lung isolated metastases and 3 or later lines of chemotherapy. We also performed in our database a survival analysis in the 334 patients: those who received ≥3 lines of chemotherapy had significantly higher survival rates (median OS 18 m in the group of < 3 lines of treatment vs. 37.2 m in the group of ≥ 3 lines of chemotherapy, HR = 1,6; CI 95% 1,2-2.1; p < 0,001). Conclusions: This retrospective analysis showed that mCRC patients with < 80 years, ECOG 0-1, primary tumor and or metastases resected and those with complete or partial response in the first line of treatment have a higher probability of receiving ≥ 3 lines of chemotherapy. [Table: see text]

2020 ◽  
pp. 647-657
Author(s):  
Germán Calderillo ◽  
Matías Muñoz-Medel ◽  
Edelmira Carbajal ◽  
Miguel Córdova-Delgado ◽  
Doris Durán ◽  
...  

PURPOSE Like other malignancies, GI stromal tumors (GIST) are highly heterogeneous. This not only applies to histologic features and malignant potential, but also to geographic incidence rates. Several studies have reported GIST incidence and prevalence in Europe and North America. In contrast, GIST incidence rates in South America are largely unknown, and only a few studies have reported GIST prevalence in Latin America. PATIENTS AND METHODS Our study was part of a collaborative effort between Chile and Mexico, called Salud con Datos. We sought to determine GIST prevalence and patients’ clinical characteristics, including survival rates, through retrospective analysis. RESULTS Overall, 624 patients were included in our study. Our results found significant differences between Mexican and Chilean registries, such as stage at diagnosis, primary tumor location, CD117-positive immunohistochemistry status, mitotic index, and tumor size. Overall survival (OS) times for Chilean and Mexican patients with GIST were 134 and 156 months, respectively. No statistically significant differences in OS were detected by sex, age, stage at diagnosis, or recurrence status in both cohorts. As expected, patients categorized as being at high risk of recurrence displayed a trend toward poorer progression-free survival in both registries. CONCLUSION To the best of our knowledge, this is the largest report from Latin America assessing the prevalence, clinical characteristics, postsurgery risk of recurrence, and outcomes of patients with GIST. Our data confirm surgery as the standard treatment of localized disease and confirm a poorer prognosis in patients with regional or distant disease. Finally, observed differences between registries could be a result of registration bias.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3507-3507 ◽  
Author(s):  
Matthieu Faron ◽  
Abderrahmane Bourredjem ◽  
Jean-Pierre Pignon ◽  
Olivier Bouche ◽  
Jean-Yves Douillard ◽  
...  

3507 Background: In patients with colorectal cancer (CRC) and unresectable metastasis, the prognostic impact of primary tumor resection still remains a matter of debates. The goal of this study was to estimate, after adjustment for prognostic factors, the effect of primary tumor resection on survival. Methods: Individual patients’ data of the 1155 patients with metastatic CRC included in 4 first-line chemotherapy trials (FFCD 9601, FFCD 2000-05, ACCORD 13 and ML 16987) where retrieved. Patients were eligible for this study if they had synchronous metastasis judged unresectable. Primary endpoint was overall survival (OS), secondary endpoint was progression free survival (PFS). A Cox proportional hazard model stratified on the trial was used to estimate the impact on survival. Results: 810 patients beginning first-line chemotherapy with either fluoropyrimidine alone, oxaliplatin, irinotecan and/or bevacizumab were eligible. Patients with a history of resection (n = 478 (59%)), as compared to those without (n = 332 (41%)), were more likely to have colonic primary (p < 0.0001), lower carcino embryonic antigen (CEA) (p < 0.0001) or alkaline phosphatase (ALP) level (p=0.04) and normal white blood cell count (WBC) (p < 0.0001). In the univariate analysis, stratified on the trial, primary tumor resection was associated with a better OS (Hazard Ratio HR: 0.73 [0.63-0.84]; p < 0.0001) and PFS (HR : 0.73 [0.63-0.84]; p < 0.0001). Multivariate analysis, adjusted for primary tumor location, CEA, ALP and WBC levels, OMS performance status and number of metastatic sites confirmed that primary tumor resection was an independent predictor of better OS (HR : 0.63 [0.53-0.75] ; p < 0.0001), and PFS (HR : 0.82 [0.70-0.95] ; p = 0.0007). Significant interactions were found between resection and CEA level (p=0.02) and resection and primary tumor location (p=0.01) for OS (not for PFS) with a lower impact of resection with higher CEA levels or a colonic primary. Conclusions: This study confirmed the independent prognostic value on survival of primary tumor resection in patients with unresectable metastases of CRC.


2021 ◽  
Author(s):  
George Kafatos ◽  
Victoria Banks ◽  
Peter Burdon ◽  
David Neasham ◽  
Kimberly A Lowe ◽  
...  

Background: Advances in therapies for patients with metastatic colorectal cancer (mCRC) and improved understanding of prognostic and predictive factors have impacted treatment decisions. Materials & methods: This study used a large oncology database to investigate patterns of monoclonal antibody (mAb) plus chemotherapy treatment in France, Germany, Italy, Spain and the UK in mCRC patients treated in first line in 2018. Results: Anti-EGFR mAbs were most often administered to patients with RAS wild-type mCRC and those with left-sided tumors, while anti-VEGF mAbs were preferred in RAS mutant and right-sided tumors. Adopted treatment strategies differed between countries, largely due to reimbursement. Conclusion: Biomarker status and primary tumor location steered treatment decisions in first line. Adopted treatment strategies differed between participating countries.


2019 ◽  
pp. 1-14 ◽  
Author(s):  
Anna Luiza S.A. Vicente ◽  
Camila S. Crovador ◽  
Graziela Macedo ◽  
Cristovam Scapulatempo-Neto ◽  
Rui M. Reis ◽  
...  

PURPOSE Mutation testing of the key genes involved in melanoma oncogenesis is now mandatory for the application of targeted therapeutics. However, knowledge of the mutational profile of melanoma remains largely unknown in Brazil. PATIENTS AND METHODS In this study, we assessed the mutation status of melanoma driver genes BRAF, NRAS, TERT, KIT, and PDGFRA in a cohort of 459 patients attended at Barretos Cancer Hospital between 2001 and 2012. We used polymerase chain reaction followed by Sanger sequencing to analyze the hot spot mutations of BRAF exon 15 (V600E), NRAS (codons 12/13 and 61), TERT (promoter region), KIT (exons 9, 11, 13, and 17), and PDGFRA (exons 12, 14, and 18) in tumors. The mutational profile was investigated for associations with demographic, histopathologic, and clinical features of the disease. RESULTS The nodular subtype was most frequent (38.9%) followed by the superficial spreading subtype (34.4%). The most frequent tumor location was in the limbs (50.0%). The mutation rates were 34.3% for TERT and 34.1% for BRAF followed by NRAS (7.9%), KIT (6.2%), and PDGFRA (2.9%). The BRAF ( P = .014) and TERT ( P = .006) mutations were associated with younger patients and with different anatomic locations, particularly in the trunk, for the superficial spreading and nodular subtypes, respectively ( P = .0001 for both). PDGFRA mutations were associated with black skin color ( P = .023) and TERT promoter mutations with an absence of ulceration ( P = .037) and lower levels of lactate dehydrogenase. There was no association between patient survival rates and mutational status. CONCLUSION The similar mutational profile we observe in melanomas in Brazil compared with other populations will help to guide precision medicine in this country.


2019 ◽  
Vol 15 (27) ◽  
pp. 3149-3157
Author(s):  
Juan M O´Connor ◽  
Fernando Sanchez Loria ◽  
Victoria Ardiles ◽  
Jorge Grondona ◽  
Pablo Sanchez ◽  
...  

Aim: To determine the impact of KRAS mutation status on survival in patients undergoing surgery for colorectal liver metastases (CLM). Patients & methods: Patients with resected CLM and KRAS mutations. Survival was compared between mt-KRAS and wt-KRAS. Results: Of 662 patients, 174 (26.3%) were mt-KRAS and 488 (73.7%) wt-KRAS. mt-KRAS patients had significantly lower recurrence-free survival (HR: 1.42; 95% CI: 1.10–1.84). There were no differences between the groups for sidedness. Poorer survival was associated with mt-KRAS with positive lymph nodes, >1 metastases, tumors >5 cm, synchronous tumors and R1–R2. Conclusion: KRAS mutation status can help predict recurrence-free survival. Primary tumor location was not a prognostic factor after resection. KRAS mutation status can help design a multidisciplinary approach after curative resection of CLM.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1514 ◽  
Author(s):  
Ghimessy ◽  
Gellert ◽  
Schlegl ◽  
Hegedus ◽  
Raso ◽  
...  

Bevacizumab, combined with platinum-based chemotherapy, has been widely used in the treatment of advanced-stage lung adenocarcinoma (LADC). Although KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutation is the most common genetic alteration in human LADC and its role in promoting angiogenesis has been well established, its prognostic and predictive role in the above setting remains unclear. The association between KRAS exon 2 mutational status and clinicopathological variables including progression-free survival and overall survival (PFS and OS, respectively) was retrospectively analyzed in 501 Caucasian stage IIIB-IV LADC patients receiving first-line platinum-based chemotherapy (CHT) with or without bevacizumab (BEV). EGFR (epidermal growth factor receptor)-mutant cases were excluded. Of 247 BEV/CHT and 254 CHT patients, 95 (38.5%) and 75 (29.5%) had mutations in KRAS, respectively. KRAS mutation was associated with smoking (p = 0.008) and female gender (p = 0.002) in the BEV/CHT group. We found no difference in OS between patients with KRAS-mutant versus KRAS wild-type tumors in the CHT-alone group (p = 0.6771). Notably, patients with KRAS-mutant tumors demonstrated significantly shorter PFS (p = 0.0255) and OS (p = 0.0186) in response to BEV/CHT compared to KRAS wild-type patients. KRAS mutation was an independent predictor of shorter PFS (hazard ratio, 0.597; p = 0.011) and OS (hazard ratio, 0.645; p = 0.012) in the BEV/CHT group. G12D KRAS-mutant patients receiving BEV/CHT showed significantly shorter PFS (3.7 months versus 8.27 months in the G12/13x group; p = 0.0032) and OS (7.2 months versus 16.1 months in the G12/13x group; p = 0.0144). In this single-center, retrospective study, KRAS-mutant LADC patients receiving BEV/CHT treatment exhibited inferior PFS and OS compared to those with KRAS wild-type advanced LADC. G12D mutations may define a subset of KRAS-mutant LADC patients unsuitable for antiangiogenic therapy with BEV.


2017 ◽  
Vol 28 ◽  
pp. iii118-iii119
Author(s):  
Gonçalo Atalaia ◽  
Marta Vaz Baptista ◽  
Tiago Tomás ◽  
Susana Almeida ◽  
Inês Eiriz ◽  
...  

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