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.
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.
摘要
介绍。VELOUR 研究对二线治疗中采用 FOLFIRI(氟尿嘧啶、甲酰四氢叶酸、伊立替康)联合阿帕西普治疗转移性结直肠癌 (mCRC) 的疗效和安全性进行了评估。然而，无法用列线图表示根据预后情况对患者进行的分层，且在临床实践中实际使用改良给药方案的频率和效果尚不可知。
方法。样本包括 2013 年 1 月至 2015 年 9 月期间，在西班牙 9 家学术中心接受阿帕西普和基于伊立替康化疗的 250 名mCRC患者。利用 Cox 比例风险回归模型得出的总生存期 (OS) 结果(根据临床实践中可用的协变量进行校正)可用列线图和基于网络的计算器表示。同时，利用 Harrell 的 C 指数来评估区分度。
结果。关于OS的预后列线图中包含六个变量:美国东部肿瘤协作组的体力状态、肿瘤位置、转移部位的数量、突变状态、对先前治疗的较好反应率及癌胚抗原。模型经过准确校准，具有合格的鉴别能力 乐观校正 C 指数为 0.723；95% 置信区间(CI)，0.666–0.778。高风险、中度风险及低风险组的中位OS分别为 6.1 个月(95% CI，5.1–8.8)、12.4 个月(95% CI，9.36–14.8)及 22.9 个月(95% CI，16.6–未达到)。年龄、合并症或使用改良的 FOLFIRI 方案对本组预后无影响。在使用经改良的给药方案后，3‐4 级不良事件较为罕见。在 65 岁(含)以上的患者中，因毒性反应而入院的比率更高(9.7% vs. 19.6%；比值比，2.26；p = 0.029)。
结论。我们开发了一个预后模型并进行了内部验证，此模型可针对启用 FOLFIRI 联合阿帕西普治疗的结直肠癌患者预测其OS及实际改良传统治疗方案对药物疗效和安全性的影响。这有助于制定医疗决策和设计未来的试验。《肿瘤学家》
实践意义:在本研究中，作者编制了一份预后列线图并进行了内部验证，以便能够基于生存概率对符合 FOLFIRI 联合阿帕西普二线治疗的患者进行分层。此模型由 9 家西班牙医院利用多中心样本进行开发。此外，为提高本研究的有效性，我们研究了在此种情况下使用阿帕西普的实际情况，包括剂量或务实性改良。结果表明，经改良的给药方案常用于基于日常临床实践的患者群体中，与较少的严重毒性反应相关，但不会明显损害生存终点。我们认为，这些数据补充了 VELOUR 试验所提供的信息，有助于肿瘤学家研究结肠癌的二线治疗。
This article reports on a prognostic model for use in patients with colorectal cancer initiating therapy with FOLFIRI/aflibercept to predict overall survival and aid in decision making, with the goal of optimizing treatment results in actual patient populations.
Lung carcinosarcoma is a neoplasm of high grade composed of epithelial and mesenchymal cells. It is exceptional; and usually affects men who are smokers, between the fifth and eighth decades of life. ...Medical treatment, chemotherapy and radiotherapy are not active in this kind of tumour, so surgery is the treatment of choice. Prognosis is poor with survival rates at 6 months around 27%. We describe the diagnostic process and the clinical outcome of a patient with lung carcinosarcoma with several paraneoplastic syndromes.
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 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.
Objetivos: Describir el perfil del paciente oncológico atendido en el servicio de urgencias
de un hospital terciario, los motivos de consulta y su manejo clínico.
Método: Desde octubre de 2007 a ...marzo de 2008, se recogieron las características de
estos pacientes junto con los motivos de consulta y el manejo clínico de los pacientes
oncológicos en el servicio de urgencias.
Resultados: Se atendieron un total de 251 pacientes (12 pacientes/semana): 65 pacientes
padecían cáncer de pulmón (25,9%), 47 padecían cáncer colorrectal (18,7%), y
32 cáncer de mama (12,7%). De todos ellos, 185 tenían enfermedad metastásica
(73,7%) y 133 recibían tratamiento quimioterápico (52,9%). Los motivos de consulta
más frecuentes fueron fiebre en 46 casos (18,3%), dolor relacionado con el tumor en
39 casos (15,5%), disnea en 36 casos (14,3%) y náuseas-vómitos en 28 casos (11,2%).
Tras la atención urgente, 121 pacientes precisaron ingreso hospitalario (48,2%).
Conclusiones: Los pacientes metastáticos y aquellos que están en tratamiento activo
son los pacientes oncológicos que más demandan atención urgente y casi la mitad precisan
ingreso hospitalario.
PDF
