Elena Mata

Circulating tumor DNA (ctDNA) has emerged as a promising non-invasive source to characterize genetic alterations related to the tumor. Upper gastrointestinal cancers, including gastroesophageal adenocarcinoma (GEC), biliary tract cancer (BTC) and pancreatic ductal adenocarcinoma (PADC) are poor prognostic malignancies, usually diagnosed at advanced stages when no longer amenable to surgical resection and show a poor prognosis even for resected patients. In this sense, ctDNA has emerged as a promising non-invasive tool with different applications, from early diagnosis to molecular characterization and follow-up of tumor genomic evolution. In this manuscript, novel advances in the field of ctDNA analysis in upper gastrointestinal tumors are presented and discussed. Overall, ctDNA analyses can help in early diagnosis, outperforming current diagnostic approaches. Detection of ctDNA prior to surgery or active treatment is also a prognostic marker that associates with worse survival, while ctDNA detection after surgery is indicative of minimal residual disease, anticipating in some cases the imaging-based detection of progression. In the advanced setting, ctDNA analyses characterize the genetic landscape of the tumor and identify patients for targeted-therapy approaches, and studies show variable concordance levels with tissue-based genetic testing. In this line, several studies also show that ctDNA serves to follow responses to active therapy, especially in targeted approaches, where it can detect multiple resistance mechanisms. Unfortunately, current studies are still limited and observational. Future prospective multi-center and interventional studies, carefully designed to assess the value of ctDNA to help clinical decision-making, will shed light on the real applicability of ctDNA in upper gastrointestinal tumor management. This manuscript presents a review of the evidence available in this field up to date.

Purpose To determine the efficacy and safety data of aflibercept + FOLFIRI in wt RAS mCRC patients after progression to standard chemotherapy + anti-EGFR treatment. Methods Retrospective, observational study in real life conducted in wt RAS mCRC patients treated with FOLFIRI-aflibercept after progression to standard first line chemotherapy + anti-EGFR treatment. Results A total of 120 patients from 12 Spanish hospitals were enrolled. Median age is 60 years (62.5%/37.5%male/female). Primary tumor site is 24.1%/75.9% right/left-side colon, and 40.8% of patients had a prior resection. All patients had wild-type RAS tumors including 5% of patients with BRAF mutations and received anti-EGFR treatment. At the time aflibercept was initiated, ECOG PS is 0/1 in 96% of patients. Median number of FOLFIRI-aflibercept cycles is 12. Efficacy results: Overall response rate is 33%; progression-free survival (PFS) is 6.9 months (95%CI: 6.1–7.8). Primary tumor resection was the only significant variable related to PFS in the multivariate analysis. Median overall survival (OS) is 14.5 months (95%CI: 9.7–19.3). ECOG and number of metastatic sites were related to OS in multivariate analysis. About 54.1% of patients received a third-line therapy including TAS-102 (23%), regorafenib (18.5%), and capecitabine (9.2%). Toxicity: Grade 3–4 toxicities were observed in 37.5% of the patients (hematologic 16.6%, hypertension 7.5%, asthenia 5.9%, and perforation 2.5%). Aflibercept dose was reduced in 18.3% of patients. Conclusions The results show that patients with wt RAS mCRC who received an anti-EGFR as part of the first-line treatment achieved similar RR, PFS, OS, and toxicities to those reported in VELOUR trial. These results suggest that FOLFIRI-aflibercept after first-line treatment with anti-EGFR is an appropriated option for RAS wt mCRC.

Background Patients with resected colorectal cancer liver metastases display heterogeneous clinical behavior. The identification of new prognostic factors would help in making more accurate decisions.

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

To asses the moment of local recurrence and its influence on the appraisal of the results of neoadjuvant chemoradiotherapy (CRT). We evaluated 317 patients with a preoperative diagnosis of stage II or III rectal cancer who underwent rectal resection. Gender, age, neoadjuvant treatment, circumferencial resection margin, adjuvant treatment, pretreatment carcinoembryonic antigen level, tumor location, TNM stage, lymph node retrieval, abdominoperineal resection, and lymphatic or vascular infiltration were registered prospectively. Follow-up was performed to detect local or systemic recurrences. Timing of local recurrence (LR) in regard to analyzed variables was performed by using analysis of variance. To evaluate the influence of late local recurrence (LLR) on the results of neoadjuvant CRT, we performed a log-rank test censoring all observations at 60 and at 120 months. After a mean follow-up of 73.6 months (range, 1-171), 68 patients developed a recurrence. Twenty-three patients developed LRs (6.9%), and 5 developed LLRs. The earliest relapse was diagnosed 4 months after rectal surgery, and the latest was diagnosed 120 months after surgery. Patients who underwent neoadjuvant CRT developed LR significantly later than patients without neoadjuvant CRT (51.8 vs 13.5 months; P = 0.002). LR rates in patients who underwent preoperative CRT and those who did not were 9.2% and 3.5% (difference, 5.7%), respectively, after censoring all observations at 60 months and 9.2% and 6.1% (difference, 3.1%) after censoring all observations at 120 months. Local recurrence was diagnosed significantly later in patients treated with neoadjuvant CRT. Follow-up longer than 5 years is needed to evaluate definitive results in patients treated with neoadjuvant CRT.

The aim of this study was to evaluate the rate of complications from the primary tumour (CPT) requiring surgical or endoscopic intervention during chemotherapy treatment in patients with incurable synchronous stage IV colorectal cancer, the possibility of predicting such complications and their influence on survival. One hundred and twenty-five patients were initially treated with chemotherapy. Patients were grouped on the basis of appearance or not of CPT. We assessed the relation between age, gender, carcinoembryonic antigen (CEA) level, primary tumour location, alkaline phosphatase level, unilobar or bilobar liver involvement, presence of peritoneal carcinomatosis, the number of sites of metastatic disease, the addition of target therapies to chemotherapy, the ability to traverse the tumour with an endoscope and the appearance of complications due to the primary tumour and overall survival. Mean age was 64.9 years, and 89 patients were men. Over a mean of 234 days, 25 patients (20 %) developed a CPT. Eighteen patients required surgery, and seven were treated exclusively by an endoscopic procedure. Mean survival was 15.8 months. We found a statistically relevant correlation between the inability to traverse the tumour with an endoscope and the occurrence of a CPT. There was no statistical differences in survival between both groups, but patients receiving target therapies had better survival. Twenty percent of patients will suffer a CPT during chemotherapy treatment. The inability to pass the tumour with an endoscope can predict the CPT. Survival was only related to the addition of target therapies to chemotherapy.

To assess management patterns and outcome in patients with glioblastoma multiforme (GBM) treated during 2008–2010 in Spain. Retrospective analysis of clinical, therapeutic, and survival data collected through filled questionnaires from patients with histologically confirmed GBM diagnosed in 19 Spanish hospitals. We identified 834 patients (23% aged >70 years). Surgical resection was achieved in 66% of patients, although the extent of surgery was confirmed by postoperative MRI in only 41%. There were major postoperative complications in 14% of patients, and age was the only independent predictor (Odds ratio [OR], 1.03; 95% confidence interval [CI],1.01–1.05; P = .006). After surgery, 57% received radiotherapy (RT) with concomitant and adjuvant temozolomide, 21% received other regimens, and 22% were not further treated. In patients treated with surgical resection, RT, and chemotherapy (n = 396), initiation of RT ≤42 days was associated with longer progression-free survival (hazard ratio [HR], 0.8; 95% CI, 0.64–0.99; P = .042) but not with overall survival (HR, 0.79; 95% CI, 0.62–1.00; P = .055). Only 32% of patients older than 70 years received RT with concomitant and adjuvant temozolomide. The median survival in this group was 10.8 months (95% CI, 6.8–14.9 months), compared with 17.0 months (95% CI, 15.5–18.4 months; P = .034) among younger patients with GBM treated with the same regimen. In a community setting, 57% of all patients with GBM and only 32% of older patients received RT with concomitant and adjuvant temozolomide. In patients with surgical resection who were eligible for chemoradiation, initiation of RT ≤42 days was associated with better progression-free survival.