Prognostic Nomogram and Patterns of Use of FOLFIRI-Aflibercept in Advanced Colorectal Cancer: A Real-World Data Analysis.

INTRODUCTION: The VELOUR study evaluated the efficacy and safety of adding aflibercept to FOLFIRI (fluorouracil, leucovorin, irinotecan) in second-line therapy for metastatic colorectal cancer (mCRC). However, a nomogram that can stratify patients according to prognosis is unavailable, and the frequency and effect of the pragmatic use of modified schedules in actual practice remains unknown. METHOD: The sample consists of 250 patients with mCRC treated with aflibercept and irinotecan-based chemotherapy at nine Spanish academic centers between January 2013 and September 2015. The result of a Cox proportional hazards model regression for overall survival (OS), adjusted for covariates available in daily practice, was represented as a nomogram and web-based calculator. Harrell's c-index was used to assess discrimination. RESULTS: The prognostic nomogram for OS includes six variables: Eastern Cooperative Oncology Group performance status, tumor location, number of metastatic sites, mutational status, better response to previous treatment(s), and carcinoembryonic antigen. The model is well calibrated and has acceptable discriminatory capacity (optimism-corrected c-index, 0.723; 95% confidence interval [CI], 0.666-0.778). Median OS was 6.1 months (95% CI, 5.1-8.8), 12.4 months (95% CI, 9.36-14.8), and 22.9 months (95% CI, 16.6-not reached) for high-, intermediate-, and low-risk groups, respectively. Age, comorbidity, or use of modified FOLFIRI regimens did not affect prognosis in this series. Grade 3-4 adverse events were less common following modified schedules. The admission rate because of toxicity was higher in ≥65 years (9.7% vs. 19.6%; odds ratio, 2.26; p = .029). CONCLUSION: We have developed and internally validated a prognostic model for use in individuals with colorectal cancer initiating therapy with FOLFIRI-aflibercept to predict both OS and the effect of pragmatic modifications of the classic regime on efficacy and safety. This can aid in decision making and in designing future trials. IMPLICATIONS FOR PRACTICE: In this study, the authors developed and conducted the internal validation of a prognostic nomogram that makes it possible to stratify patients who are eligible for second-line FOLFIRI-aflibercept based on their probability of survival. This model was developed in a multicenter sample from nine Spanish hospitals. Furthermore, to increase the study's validity, the practical use of aflibercept in this setting was investigated, including doses or pragmatic modifications. The results suggest that the modified schedules often used in this daily clinical practice-based patient population are associated with less severe toxicity without apparent detriment to survival endpoints. It is believed that these data complement the information provided by the VELOUR trial and are relevant for the oncologist in treating colon cancer in the second-line setting.

Brain metastases in colorectal cancer: prognostic factors and survival analysis.

PURPOSE: Colorectal cancer (CRC) brain metastases (BM) are an uncommon and late event. We aim to investigate the impact of clinical factors, treatment modalities and RAS/BRAF status on the outcomes of CRC patients with BM. PATIENTS: We retrospectively analysed CRC patients who developed BM in our centre between January 1997 and June 2017. Clinical factors, treatment modalities, RAS/BRAF status and survival were evaluated. RESULTS: Twenty-eight patients were recorded; 82% had left-sided (LS) CRC and 71% had lung metastases. Median time to BM diagnosis was 36 months (m) and 93% of patients received local treatment of BM (43% whole brain radiotherapy, 50% surgery). Right-sided (RS) CRC showed shorter time to BM, not previously described (9.3 vs 46.6 m for RS and LS CRC, respectively; HR = 4.7, p = 0.006). Median overall survival (mOS) from BM treatment was 9.5 m, better in patients who underwent surgery than those treated with radiotherapy alone (12.1 vs 4.6 m, respectively; HR = 0.3, p = 0.019) and in those without progressive metastatic extracranial disease (7.2 vs 20.9 m, for progressive and non-progressive, respectively; HR = 0.3, p = 0.056). Patients with two or more metastatic extracranial locations showed worse prognosis (5.9 vs 16.3 m, for > 2 vs 0-1, respectively; HR = 3.7, p = 0.015). RAS/BRAF status did not showed prognostic value. CONCLUSIONS: Time to BM diagnosis is shorter in RS CRC. The presence of two or more metastatic extracranial locations and progressive metastatic extracranial disease at the time of BM diagnosis could be bad prognosis factors for CRC BM patients.

Dramatic complete response in patient with lung adenocarcinoma.

The poor prognosis of non-small-cell lung cancer (NSCLC) is changing thanks to the constant development of new treatments and the introduction of target therapies, even in stage IV disease. This patient had bone metastases when he was diagnosed. Maintenance treatment, a much discussed topic nowadays, achieved a dramatic complete response.

Skull base chondrosarcoma: a case treated by the CyberKnife system.

Skull base chondrosarcomas represent 2% of all chondrosarcomas. They usually have a low grade of malignity and a complete resection may be curative. However, often they are considered irresectable because of the difficult approach and another kind of treatment is needed. We present a 54-year-old male case who, after weeks suffering from diplopia, was diagnosed with skull base chondrosarcoma and treated with the CyberKnife system. A review of radiosurgery techniques for skull base neoplasms is carried out.