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Outcomes for patients with metastatic colorectal cancer (mCRC) have been improved by the identification of biomarkers predictive and prognostic of clinical outcome. The present retrospective analysis was undertaken to assess the utility of key biomarkers and clinical parameters in predicting outcomes in Spanish patients with mCRC. We retrospectively analyzed tumor samples from a series of patients aged > 18 years with mCRC who were treated at the Hospital General Universitario Gregorio Maranon Spain. Real-time polymerase chain reaction was used to detect KRAS, NRAS, BRAF, and PIK3CA mutations. The key outcome of interest was overall survival (OS). Survival curves were estimated using the Kaplan–Meier method and stratified by the variables of greatest clinical interest. Differences were tested using the log-rank test. Median OS in the overall population was 24.4 months. Triple WT patients (WT KRAS, NRAS, and BRAF) and quadruple WT patients (WT KRAS, NRAS, BRAF, and PIK3CA) had significantly better OS than those who did not have triple or quadruple WT tumors. OS was significantly better in patients with left- vs. right-sided tumors, patients with resected primary tumors and metastases vs. those without resection, and patients with isolated hepatic and isolated pulmonary metastases. This retrospective, observational study has confirmed the prognostic value of the location and resection status of the primary tumor and metastases in Spanish patients with mCRC. Triple WT status, in particular, was prognostic in this patient population, with PIK3CA adding to the prognostic value in the quadruple WT population.

Background: In patients with advanced high-grade serous ovarian cancer (HGSOC) and prostate adenocarcinoma, the identification of somatic/germline BRCA1/2 mutations allows new therapeutic opportunities. To estimate the prevalence of somatic and germline BRCA1/2 mutations in non-mucinous high grade ovarian/fallopian tube/peritoneal extraovarian cancer (NMHGOC) and prostate adenocarcinoma. Methods: Prevalence was established by analyzing patients with NMHGOC or prostate adenocarcinoma, with a BRCA1/2 study in the tumor between 2017 and 2018. Whether a germline study had been carried out was subsequently reviewed. Results: 10 patients out of 43 (23.3%) with NMHGOC had a BRCA1/2 mutation in the tumor. 9 patients (20.9%) presented a BRCA1/2 mutation in the germline setting (2 without tumor result due to limited tissue sample). 3 patients (6.9%) had only somatic mutations. 30% of the mutations in the tumor were, therefore, somatic mutations. Of the 9 patients with prostate adenocarcinoma, 2 (22.2%) had a BRCA2 mutation in the tumor. While 1 (11.1%) had the mutation in the germline setting, 1 patient (11.1%) had only somatic mutations. Conclusion: In our series, the prevalence of somatic and germline BRCA1/2 mutations in NMHGOC is similar to that reported in the literature. Whereas somatic mutations are only present at the neoplastic tissue, the rate of mutations in the tumor is higher than in the germline setting. A more effective diagnostic and predictive strategy could be achieved with tumor BRCA analysis as the first attempt. Initial results in prostate adenocarcinoma point to the same conclusion for this tumor.

Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ−5D−3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively, mean difference: −12.4, p &lt, 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically.

Although there is published research on the impact of venous thromboembolism (VTE) on quality of life (QoL), this issue has not been thoroughly investigated in patients with cancer&mdash, particularly using specific questionnaires. We aimed to examine the impact of acute symptomatic VTE on QoL of patients with malignancies. This was a multicenter, prospective, case-control study conducted in patients with cancer either with (cases) or without (controls) acute symptomatic VTE. Participants completed the EORTC QLQ-C30, EQ-5D-3L, PEmb-QoL, and VEINES-QOL/Sym questionnaires. Statistically significant and clinically relevant differences in terms of global health status were examined. Between 2015 and 2018, we enrolled 425 patients (128 cases and 297 controls, mean age: 60.2 &plusmn, 18.4 years). The most common malignancies were gastrointestinal (23.5%) and lung (19.8%) tumors. We found minimally important differences in global health status on the EQ-5D-3L (cases versus controls: 0.55 versus 0.77, mean difference: &minus, 0.22) and EORTC QLQ-C30 (47.7 versus 58.4, 10.3) questionnaires. There were minimally important differences on the PEmb-QoL questionnaire (44.4 versus 23, 21.4) and a significantly worse QoL on the VEINES-QOL/Sym questionnaire (42.7 versus 51.7, 9). In conclusion, we showed that acute symptomatic VTE adversely affects the QoL of patients with malignancies.

The combination of oxaliplatin, irinotecan, fluorouracil (5-FU), and leucovorin (FOLFOXIRI) results in improved outcomes compared with standard chemotherapy when used in frontline to treat patients with metastatic colorectal cancer (mCRC). FOLFOXIRI has been recently combined with biologic agents aiming further improvement in outcomes.This manuscript provides a comprehensive review of the results achieved by the FOLFOXIRI+biologic combination when used as first-line treatment in patients with mCRC. The search retrieved 19 clinical trial reports and 7 ongoing trials. The results are discussed focusing on secondary resection of metastatic disease, impact of sidedness (right-left primary tumor site), and impact of biomarkers.Panitumumab is the only biologic that has proved its value when added to FOLFOXIRI in a randomized clinical trial. FOLFOXIRI-bevacizumab has the widest data from two large randomized phase III trials, being an option to be used in both the palliative and the conversion-therapy settings. However, the true benefit from adding bevacizumab remains to be established as it has not been evaluated in a randomized setting yet. Data on response rates and secondary resection rates are promising with the FOLFOXIRI-anti-EGFR combinations and may constitute a valuable option. Results of ongoing head-to-head studies will shed additional light on this issue.

4041 Background: Approximately 25% of patients with colorectal cancer (CRC) debut with metastatic disease. In addition, 25-35% of patients with localized disease at diagnosis develop metastatic lesions during the evolution of their disease. Consequently, approximately 50-60% of patients with CRC will present metastatic lesions at some point in their lives. Metastasis resection has improved the prognosis of these patients, achieving overall survival (OS) that exceed 40 months. However, there are doubts about the benefit of this approach in patients with mutations in oncogene BRAF or tumors located on the right-side, due their poor prognosis. The aim of the study is to analyze the impact of metastases resection on OS of these populations. Methods: We conducted a retrospective analysis of patients with mCRC attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Spain) between January 2010 and 2018. Results: 487 patients were identified and included in the analysis. Median age was 71 years (62-81). Most patients were males (62.4%). 55.2% had metastatic lesions at diagnosis. Most patients had ECOG 0-1 at diagnosis of metastatic disease (91.0%). 8.9% of patients had BRAF mutations (n = 21) and 31.8% of patients had primary tumors located on the right-side (n = 152). 474 patients received first-line chemotherapy (97.3%). OS of the entire cohort was 29.67 months; 30.69 months in BRAF mutated patients vs 35.89 in wild-type patients (p = 0.161); 25.29 months in right-side tumors vs 31.02 in left-side tumors (p = 0.044). 306 patients (62.8%) underwent metastases resection. Most common location was liver (51.4%). 147 patients (30.2%) underwent a second metastases resection. Mean number of metastases surgeries was 1.35 (+/-1.40). OS since metastases resection was 24.83 months in BRAF mutated patients vs 41.55 months in wild-type patients (p = 0.020). According to location, it was 35.49 months in right-side tumors vs 43.78 months in left-side tumors (p = 0.106). In BRAF mutated patients, OS was 38.19 months in patients underwent metastases resection vs 18.52 months in non-surgical patients (p = 0.043); 41.51 months vs 16.18 months respectively in patients with tumors located on the right-side (p < 0.001). Conclusions: Metastases resection has a positive impact on overall survival of patients with mutations in oncogene BRAF or right-side tumors, even though their prognosis is still poor compared to patients without these alterations.

High incidence and prognostic relevance of thromboembolic disease in patients with ALK-rearranged NSCLCs

49 Background: Elderly patients with mCRC are underrepresented in clinical trials. For this reason, the optimal treatment in this population is uncertain. The aim of this study is to compare efficacy and safety outcomes in patients with mCRC treated in our institution according to age ( [Table: see text]

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e15136 Background: A recent study has suggested that KRAS mutation could increase the risk of VTE in patients with CRC. The role of others biomarkers, such as BRAF, in this setting is unknown. The aim of this study is to analyze the incidence of cancer-associated thrombosis in a cohort of patients with CRC based on KRAS, NRAS and BRAF status. Methods: We performed a retrospective review of patients with metastatic CRC and KRAS/NRAS/BRAF status known, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Marañón (Madrid, Spain) between January 2010 and January 2018. Results: 194 patients were identified and included in the analysis. The median age was 64 years (18-86). Most were metastatic at diagnosis (58.1%). Khorana’s predictive model: low-risk 67.7%, intermediate-risk 31.0%, high-risk 2.3%. The median follow-up was 35 months (2-240). 41 patients (21.1%) experienced VTE (11 pulmonary embolism, 15 lower extremity deep-vein thrombosis, 12 visceral vein thrombosis, 2 catheter-related thrombosis, 1 unknown). Most had metastatic disease at the moment of VTE (90.2%). 40% of the events occurred at the time of diagnosis or within the first 6 months. 65% were incidental events. Khorana’s predictive model in VTE patients: low-risk 63.4%, intermediate-risk 24.5%, high-risk 7.3%. According to biomarkers, the incidence was 19.1% (13/68) in KRAS/NRAS mutated patients, 28.6% (6/21) in BRAF mutated patients and 21% (22/105) in triple-wild-type patients. 6/38 patients (15.8%) developed recurrent thrombosis. In the univariate analysis, the presence of chronic kidney disease (p = 0.022), ECOG ≥ 2 (p = 0.038) and high-risk Khorana score (p = 0.011) were significantly associated with increased risk of VTE. Metastatic disease showed a trend towards the statistical significance (p = 0.053). In the multivariate model, including this variables, age, sex and biomarkers, only ECOG ≥ 2 remained independent predictor of VTE (OR 8.73; CI 95% 1.32-57.82; p = 0.025). Conclusions: The biomarkers have not been associated with the risk of VTE. We have observed a high incidence of VTE in BRAF mutated patients that should be investigated in further studies.

690 Background: In recent years, prognostic and predictive factors in mCRC are becoming more important, outstanding the tumor and metastasic location, the primary tumor and/or metastasis resections as well as molecular biomarkers (KRAS, NRAS, BRAF and PIK3CA). Methods: We conducted a retrospective study of 334 patients with mCRC diagnosticated between January 2010 and June 2015 in the Oncology Service from HGUGM. The objective of our study was to evaluate the overall survival (OS) relating to each of these settings. We also evaluated OS considering the biological treatment received in first line. Multivariant analysis was performed with independence of tumor and metastasic location, metastasectomies, no primary tumor resection, biological treatment used in first line, age, sex and moleculars biomarkers. Results: Median OS was 24,34m. The advantageous prognostic factors which statistically significant impact on the median OS have been triple (RAS and BRAF) (n = 86) and quadruple (RAS, BRAF and PIK3CA) (n = 76) wild-type (wt 36,6m vs mut 23m, p = 0,02; wt 37,6m vs mut 23,38m, p = 0.02, respectively), left tumor location with rectum (left 25,55m vs right 19,44m, p = 0,001) and isolated hepatic and pulmonary metastasic location (30,32 vs 23 m, p = 0,03; 45,32m vs 23,38 m, p = 0,004, respectively). The main disadvantageous prognostic factor has been the no primary tumor resection (13,75m vs 31,61m, p = 0,00001) with independence of synchronous presentation of the disease as well as biomarkers mutational status. Median OS in first line was 30.13 m with bevacizumab (n = 54) vs 16,18m with antiEGFR (n = 28) (p = 0.02) in extended RAS wild-type patients (n = 101). Considering the multivariate analysis, the independent prognostic factors have been the isolated pulmonary metastasis (HR = 0,46; CI 95% 0,30-0,73;p = 0,001), quadruple wild-type (HR = 0,69;CI 95% 0,49-0,97; p = 0,031), metastasectomies (HR = 0,29; CI 95% 0,21-0,4; p = 0,000), right location (HR = 1,43; CI 95% 1,08-1,9;p = 0,014) and no primary tumor resection (HR = 2,06; CI 95% 1,49-2,86; p = 0,000). Conclusions: Isolated pulmonary metastasis, quadruple wild-type, metastasectomies, left location and primary tumor resection have independent positive prognostic value, according to our retrospective study.