Relative dose intensity of first-line triplet chemotherapy in metastatic colorectal cancer.

PURPOSE: Relative dose intensity (RDI) is a measurement of chemotherapy (CT) dose defined as the actual dose received divided by the standard calculated dose during a set period. The study objective was to assess the impact of a RDI ≥ 80% on response and survival of patients treated in first line CT by FOLFOXIRI or FOLFIRINOX ± Bevacizumab (BV) for an unresectable metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: It was a retrospective, non-interventional, multicenter study calculating RDI from the first cycles of CT to the first CT-scan evaluation (CT-scan1). Objective response and disease control rates (ORR and DCR), progression-free survival (PFS) and overall survival (OS) were compared between patients with RDI ≥ 80% and <80% and results were adjusted for age, gender, ECOG, tumor location, number of metastatic sites, RAS and BRAF status, the CT regimen, the use of BV, the delay from C1 to CT scan1. RESULTS: Among 152 screened patients, 100 met inclusion criteria, with a mean (± standard deviation) age at 59.0 (± 10.7) years. The ECOG performance status was 0-1 in 96 (96%) patients; metastases were synchronous in 95 (95%), RAS and BRAF were mutated in 60 (60%) and 22 (22%), respectively. ORR was observed in 51 (51%) at CT-scan1 with median PFS and OS of 10.5 and 21.9 months, respectively. A RDI ≥ 80% was observed in 44 (44%) patients without impact on ORR (ORa: 1.04, 95% CI: 0.37 to 2.89, p = 0.94) but was significantly associated to improved PFS and OS with HRa 0.50 (95%CI: 0.29 to 0.87, p = 0.013) and 0.52 (95% CI: 0.29 to 0.91, p = 0.023), respectively. CONCLUSION: Our results suggest a low level of FOLFOXIRI or FOLFIRINOX +/- BV exposure in first-line mCRC is associated with a significant trend on PFS and OS.

[Contributions of molecular biology to the management of colorectal cancer]. / Apports de la biologie moléculaire dans la prise en charge du cancer colorectal.

CONTRIBUTIONS OF MOLECULAR BIOLOGY TO THE MANAGEMENT OF COLORECTAL CANCER. Colorectal cancer (CRC) is a major public health problem affecting almost 43.000 people a year and causing 17.000 deaths. Advances in molecular biology have made it possible to identify some of the mechanisms involved in colorectal carcinogenesis and tumor proliferation. Some molecular alterations are now routinely investigated to adapt follow-up and therapeutic decisions in both localized and metastatic CRC.

BIOLOGIE MOLÉCULAIRE ET PRISE EN CHARGE DU CANCER COLORECTAL. Le cancer colorectal (CCR) est un problème de santé publique majeur qui touche près de 43 000 personnes par an et cause 17 000 décès. Les progrès de la biologie moléculaire ont permis d'identifier certains des mécanismes impliqués dans la carcinogenèse colorectale et la prolifération tumorale. Certaines altérations moléculaires sont désormais recherchées en pratique courante pour adapter le suivi et la décision thérapeutique dans les CCR localisés et métastatiques.

Fusion imaging for pulmonary artery embolization: impact on fluoroscopy duration and contrast agent exposure.

OBJECTIVES: To assess the impact of fusion imaging guidance on fluoroscopy duration and volume of contrast agent used for pulmonary artery embolization. METHODS: Thirty-four consecutive patients who underwent pulmonary artery embolization for pulmonary arterio-venous malformation (n = 28) or hemoptysis (n = 6) were retrospectively included. In the experimental group (n = 15), patients were treated using fusion imaging with 2D/3D registration. In the control group (n = 19), no fusion imaging has been used. Fluoroscopy duration and amount of contrast used were measured and intergroup comparison was performed. RESULTS: The average volume of contrast agent used for embolization in the fusion group (118.3 ml) was significantly lower than in the control group (285.3 ml) (p < 0.002). The mean fluoroscopy duration was not significantly different between both groups (19.5 min in the fusion group vs 31.4 min in the control group (p = 0.10)). No significant difference was observed regarding the average X-ray exposure (Air Kerma) (p = 0.68 in the univariate analysis). Technical success rate was 100% for both groups. CONCLUSION: Fusion imaging significantly reduces contrast medium volumes needed to perform pulmonary artery embolization. The fluoroscopy duration and the X-ray exposure did not vary significantly. ADVANCES IN KNOWLEDGE: CTA-based fusion imaging using 2D-3D registration is a valuable tool for performing pulmonary artery embolization, helpful for planning and guiding catheterization.Compared to the traditional imaging guidance, fusion imaging reduces the volume of contrast agent used.

Postoperative circulating tumor DNA detection is associated with the risk of recurrence in patients resected for a stage II colorectal cancer.

Circulating tumor DNA (ctDNA) is reported to be promising in localized colorectal cancer (CRC). The present study aimed to retrospectively evaluate the impact of ctDNA in patients with a resected stage II CRC from the PROGIGE 13 trial with available paired tumor and blood samples. A group of recurrent patients were matched one-to-one with nonrecurrent patients according to sex, tumor location, treatment sequence, and blood collection timing. CtDNA was analyzed by digital PCR according to NGS of tumors. Disease-free survival (DFS) and overall survival (OS) were analyzed based on ctDNA, and the risks of recurrence and death were determined. A total of 134 patients were included, with 67 patients in each group. At least one alteration was identified in 115/134 tumors. Postoperative ctDNA was detected in 10/111 (9.0%) informative samples and was detected more frequently in the recurrent group (16.7% versus 1.8%; p = 0.02). The median DFS of ctDNA+ versus ctDNA- patients was 16.8 versus 54 months (p = 0.002), respectively, and the median OS was 51.3 versus 69.5 months (p = 0.03), respectively. CtDNA was associated with recurrence (ORa = 11.13, p = 0.03) and death (HRa = 3.15, p = 0.01). In conclusion, the presence of postoperative ctDNA is associated with both recurrence and survival in stage II CRC.

Evaluation of a colorectal cancer screening program composed of successive waves of different tests: The experience of the French Calvados County.

BACKGROUNDS: The value of colorectal cancer (CRC) screening program in a population with a limited participation rate is debated. This study assesses the real-life performances of different screening tests in a population benefiting from an organized program and included in a cancer registry. METHODS: Patients who participated in at least one screening campaign between 2004 and 2016 were included. Four screening procedures were used: Hemoccult II, Magstream, Hemoccult and Magstream combined, and OC Sensor. Data were crossed with the Digestive Cancer Registry of Calvados to detect CRCs diagnosed during this period. The main outcomes were CRC detection and the incidence rate of interval cancers. RESULTS: Screening consisted of 325,083 tests in 134,498 patients. Of the 2580 CRCs detected in patients aged 50-74, 534 (20.7 %) were screen-detected. OC Sensor had the highest sensitivity for CRC detection (83.7 %, 95 % CI [76.8-89.1 %]) and the lowest interval cancer rate (2.0 per 10,000 person-years, 95 % CI [1.4-2.7]) compared with other screening tests, excluding combinations. The overall participation rate was 28.9 %. CONCLUSION: Real-life differences in performance between different screening tests exist, and OC Sensor appears to be the best. The low participation rate suggests that the rate of screen-detected CRC could be higher.

Colorectal cancer chemoprevention: is aspirin still in the game?

Screening strategies have demonstrated their potential for decreasing the incidence and mortality of cancers, particularly that of colorectal cancer (CRC). Another strategy that has been developed to reduce CRC occurrence is the use of chemoprevention agents. Among them, aspirin is the most promising. Aspirin acts in colorectal tumourigenesis through several mechanisms, either directly in tumor cells or in their microenvironment, such as through its anti-inflammatory activity or its effect on the modulation of platelet function. Many retrospective studies, as well as follow-up of large cohorts from trials with primary cardiovascular end points, have shown that long-term treatment with daily low-dose aspirin decreases the incidence of adenomas and colorectal cancers. Therefore, aspirin is currently recommended by the United States Preventive Services Task Force (USPSTF) for primary prevention of CRC in all patients aged 50 to 59 with a 10-y risk of cardiovascular events greater than 10%. Furthermore, several studies have also reported that long-term aspirin treatment taking after CRC resection decreases recurrence risk and increases overall survival, especially in patients with PIK3CA-mutated tumors. This review summarizes current knowledge on the pathophysiological mechanisms of aspirin chemoprevention, discusses the primary clinical results on CRC prevention and highlights the potential biomarkers identified to predict aspirin efficacy.

[Aspirin and colorectal cancer]. / Aspirine et cancer colorectal.

Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation.