RESUMEN
Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan-Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.
RESUMEN
BACKGROUND: Image-guided tissue biopsies are critically important in the diagnosis and management of cancer patients. High-yield samples are also vital for biomarker and resistance mechanism discovery through molecular/genomic analyses. PATIENTS AND METHODS: All consecutive patients who underwent plugged image-guided biopsy at Royal Marsden from June 2013 until September 2016 were included in the analysis. In the next step, a second cohort of patients prospectively treated within two clinical trials (PROSPECT-C and PROSPECT-R) were assessed for the DNA yield from biopsies assessed for complex genomic analysis. RESULTS: A total of 522 plugged core biopsies were performed in 457 patients [men, 52%; median age, 63 years (range, 17-93)]. Histological diagnosis was achieved in 501 of 522 (96%) performed biopsies. Age, gender, modality, metastatic site, and seniority of the interventionist were not found to be significant factors associated with odds of failure on a logistic regression. Seventeen (3.3%) were admitted due to biopsy-related complications; nine, three, two, one, one, and one were admitted for grade I/II pain control, sepsis, vasovagal syncope, thrombosis, hematuria, and deranged liver functions, respectively; two patients with right upper quadrant pain after liver biopsy were found to have radiologically confirmed subcapsular hematoma requiring conservative treatment. One patient (0.2%) developed grade III hemorrhage following biopsy of a gastric gastrointestinal stromal tumor (GIST). Overall molecular analysis was successful in 89% (197/222 biopsies). Prospective validation in 62 biopsies gave success rates of 92.06 and 79.03% for DNA extraction of >1 µm and tmour content of >20%, respectively. CONCLUSION: The probability of diagnostic success for complex molecular analysis is increased with plugged large coaxial needle biopsy technique, which also minimizes complications and reduces hospital stay. High-yield DNA acquisition allows genomic molecular characterization for personalized medicine.
RESUMEN
The incidence of early onset colorectal cancer (EOCRC) is rapidly increasing, but there remains paucity of outcome data for young CRC patients. We reviewed the characteristics and outcomes of 241 adults, age <50, who were diagnosed with EOCRC between January 2009 and December 2014. Median age was 42, 56% were male, and 7% had hereditary etiology. Seventy percent had left-sided primaries. At diagnosis, 11%, 50%, and 39% had stage II, III, and IV CRC. Of the patients with stage II and III CRC who underwent curative surgery, 60% and 88% had adjuvant chemotherapy, with 5-year relapse free survival of 82% and 74% respectively. Of the 123 patients with metastatic (m) EOCRC, 93%, 63%, 33%, and 12% had 1st, 2nd, 3rd, and 4th line systemic anticancer therapy (SACT) respectively. For first line SACT, 99% had doublet chemotherapy, with bevacizumab or an anti-EGFR antibody in 57%. Median overall survival (mOS) of mEOCRC patients was 20.1 months (95% C.I: 15.9-23.2). Younger age and signet cells were associated with shorter mOS, whereas more lines of SACT and curative metastasectomy with longer mOS. Metastatic EOCRC patients had poorer outcomes than expected, despite optimal multimodality treatment. This suggests an aggressive disease biology that warrants further research and therapy development.