Visceral fat and clinical outcome in patients receiving first-line chemotherapy with bevacizumab for metastatic colorectal cancer.

BACKGROUND: Visceral fat produces angiogenic factors such as vascular endothelial growth factor that promote tumoral growth. However, its influence on outcome for patients with advanced cancer treated with anti-angiogenic agents is controversial. AIMS: The aim of this study was to determine whether visceral fat volume, visceral fat area and body mass index are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic colorectal cancer. METHODS: This multicenter prospective study included 103 patients with metastatic colorectal cancer who received first-line bevacizumab-based chemotherapy. Computed tomography was used to measure visceral fat volume and visceral fat area. Endpoints were tumoral response at 2 months, progression free survival and overall survival. RESULTS: Visceral fat volume and visceral fat area, but not body mass index, were significantly associated with better outcome. Using sex-specific median values progression free survival was significantly longer in patients with high visceral fat volume (13.2 versus 9.4 months; p = 0.0043). In the same way, high visceral fat volume and visceral fat area were associated with a significantly better overall survival: 31.3 versus 20.5 months (p = 0.0072) and 29.3 versus 20.5 months (p = 0.0078), respectively. By multivariate analysis, visceral fat volume was associated with longer progression free survival and overall survival. CONCLUSION: This study demonstrates that a high visceral fat volume is associated with better outcome in patients receiving first-line bevacizumab-based chemotherapy for metastatic colorectal cancer.

Non-metastatic colon cancer: French Intergroup Clinical Practice Guidelines for diagnosis, treatments, and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, AFEF, and SFR).

INTRODUCTION: This article is a summary of the French intergroup guidelines regarding the management of non-metastatic colon cancer (CC), revised in November 2022. METHODS: These guidelines represent collaborative work of all French medical and surgical societies involved in the management of CC. Recommendations were graded in three categories (A, B, and C) according to the level of evidence found in the literature published up to November 2022. RESULTS: Initial evaluation of CC is based on clinical examination, colonoscopy, chest-abdomen-pelvis computed tomography (CT) scan, and carcinoembryonic antigen (CEA) assay. CC is usually managed by surgery and adjuvant treatment depending on the pathological findings. The use of adjuvant therapy remains a challenging question in stage II disease. For high-risk stage II CC, adjuvant chemotherapy must be discussed and fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy proposed according to the type and number of poor prognostic features. Oxaliplatin-based chemotherapy (FOLFOX or CAPOX) is the current standard for adjuvant therapy of patients with stage III CC. However, these regimens are associated with significant oxaliplatin-induced neurotoxicity. The results of the recent IDEA study provide evidence that 3 months of treatment with CAPOX is as effective as 6 months of oxaliplatin-based therapy in patients with low-risk stage III CC (T1-3 and N1). A 6-month oxaliplatin-based therapy remains the standard of care for high-risk stage III CC (T4 and/or N2). For patients unfit for oxaliplatin, fluoropyrimidine monotherapy is recommended. CONCLUSION: French guidelines for non-metastatic CC management help to offer the best personalized therapeutic strategy in daily clinical practice. Each individual case must be discussed within a multidisciplinary tumor board and then the treatment option decided with the patient.

Intraoperative appearance of radiation enteritis: What should be resected?

Radiation enteritis can appear up to 30 years after radiotherapy. Outside acute complications, it usually manifests itself as chronic intestinal obstruction. If medical treatment (corticosteroid therapy) fails, surgical treatment is indicated, namely resection of the affected bowel, with removal of the ileo-caecal valve.

Cardiac adipose tissue volume assessed by computed tomography is a specific and independent predictor of early mortality and critical illness in COVID-19 in type 2-diabetic patients.

BACKGROUND: Patients with type 2-diabetes mellitus (T2D), are characterized by visceral and ectopic adipose tissue expansion, leading to systemic chronic low-grade inflammation. As visceral adiposity is associated with severe COVID-19 irrespective of obesity, we aimed to evaluate and compare the predictive value for early intensive care or death of three fat depots (cardiac, visceral and subcutaneous) using computed tomography (CT) at admission for COVID-19 in consecutive patients with and without T2D. METHODS: Two hundred and two patients admitted for COVID-19 were retrospectively included between February and June 2020 and distributed in two groups: T2D or non-diabetic controls. Chest CT with cardiac (CATi), visceral (VATi) and subcutaneous adipose tissue (SATi) volume measurements were performed at admission. The primary endpoint was a composite outcome criteria including death or ICU admission at day 21 after admission. Threshold values of adipose tissue components predicting adverse outcome were determined. RESULTS: One hundred and eight controls [median age: 76(IQR:59-83), 61% male, median BMI: 24(22-27)] and ninety-four T2D patients [median age: 70(IQR:61-77), 70% male, median BMI: 27(24-31)], were enrolled in this study. At day 21 after admission, 42 patients (21%) had died from COVID-19, 48 (24%) required intensive care and 112 (55%) were admitted to a conventional care unit (CMU). In T2D, CATi was associated with early death or ICU independently from age, sex, BMI, dyslipidemia, CRP and coronary calcium (CAC). (p = 0.005). Concerning T2D patients, the cut-point for CATi was > 100 mL/m2 with a sensitivity of 0.83 and a specificity of 0.50 (AUC = 0.67, p = 0.004) and an OR of 4.71 for early ICU admission or mortality (p = 0.002) in the fully adjusted model. Other adipose tissues SATi or VATi were not significantly associated with early adverse outcomes. In control patients, age and male sex (OR = 1.03, p = 0.04) were the only predictors of ICU or death. CONCLUSIONS: Cardiac adipose tissue volume measured in CT at admission was independently predictive of early intensive care or death in T2D patients with COVID-19 but not in non-diabetics. Such automated CT measurement could be used in routine in diabetic patients presenting with moderate to severe COVID-19 illness to optimize individual management and prevent critical evolution.

Abdominal Extrarenal Involvement in Erdheim-Chester Disease in a Cohort of 304 Patients.

This cohort study estimates the prevalence of nonretroperitoneal abdominal organ involvement in Erdheim-Chester disease in a large cohort of patients.

Impact of trough concentrations of regorafenib and its major metabolites M-2 and M-5 on overall survival of chemorefractory metastatic colorectal cancer patients: Results from a multicentre GERCOR TEXCAN phase II study.

PURPOSE: This prospective pharmacokinetic (PK) ancillary study of the TEXCAN phase II GERCOR trial of patients with chemorefractory metastatic colorectal cancer and treated with regorafenib (REGO) investigated correlations between overall survival (OS) and concentrations (C) of REGO and its active metabolites, M-2 and M-5. METHODS: 55 patients received REGO 160 mg/day for 21 days of a 28-day cycle (NCT02699073). REGO, M-2, M-5 were measured by liquid chromatography-mass spectrometry assay on day 15 of cycle 1 (C1) and 2 (C2). We studied the association between OS and Cmin of REGO, M-2 and M-5 at C1 and their accumulations between C1 and C2. RESULTS: Medians of C2/C1 M-2 and M-5 ratios were 0.82 (interquartile range 0.50-1.78) and 0.75 (interquartile range 0.41-1.93), respectively. Patients with C2/C1 M-2 ratio ≥ median had improved survival compared to those < median (12.6 versus 4.0 months, P = 0.023), corresponding to a 66% mortality risk reduction in multivariate analysis. The C2/C1 M-2 ratio correlated with C1 REGO+M-2+M-5 (Csum; P = 0.006). Restricted cubic spline analysis showed an increased OS benefit as the C2/C1 M-2 ratio raises and when C1 Csum ranged between 2.5 and 5.5 mg/L. Patients within the Csum range had a reduced incidence of serious adverse events and improved OS. CONCLUSIONS: We identified PK parameters associated with a survival benefit in patients with metastatic colorectal cancer treated by REGO. OS and safety were favourable when C1 REGO+M-2+M-5 Csum ranged between 2.5 and 5.5 mg/L. These results pave the way for individual REGO dose modification strategies based on PK monitoring. CLINICAL TRIAL REFERENCE: NCT02699073.

[Initial staging of rectal cancer]. / Bilan initial et stadification du cancer du rectum.

Initial staging of rectal cancer. Rectal cancers are one of the most frequent digestive cancers. Most of them are diagnosed during organized cancer screening or based on evocative symptoms. After a thorough clinical examination including rectal examination, the next step is to confirm the diagnosis by colonoscopy with biopsies. Once diagnosis is confirmed, other imaging exams are necessary to assess loco-re¬gional extension and metastatic spread. Rectal magnetic resonance imaging (MRI) and thoracic-abdominal-pelvic computed tomography (CT) are the modalities of choice, respectively for loco-regional and metastatic spread. MRI protocol is standardized, and its report must provide specific information to guide surgical and non-surgical mana¬gement options (especially tumor localization, local poor prognosis factors and node involvement). Thoraco-abdominal-pelvic CT especially seeks for liver and lung metas¬tasis. Other imaging modalities (such as endoscopic ultrasound and positron emission tomography scan) are reserved for specific cases.

Bilan initial et stadification du cancer du rectum. Les cancers du rectum font partie des cancers digestifs les plus fréquents. Ils peuvent être diagnostiqués en cas de symptômes évocateurs ou dans le cadre du dépistage organisé. Après un examen clinique comportant systématiquement un toucher rectal, l'examen complémentaire de première intention est la coloscopie, avec des biopsies pour confirmer le diagnostic. Les examens d'imagerie interviennent dans un second temps, afin de préciser l'extension locorégionale et à distance de la maladie. Ce bilan comporte deux examens indispensables : l'imagerie par résonnance magnétique (IRM) rectale pour l'extension locorégionale et le scanner thoraco-abdomino-pelvien pour l'extension à distance. Le protocole d'IRM est standardisé, et son compte-rendu doit préciser un certain nombre d'éléments guidant la prise en charge, en particulier la localisation tumorale, la présence d'éléments de mauvais pronostic locaux et l'extension ganglionnaire. Le scanner thoraco- abdomino-pelvien recherche en particulier des métastases hépatiques et pulmonaires. Les autres examens d'imagerie (écho-endoscopie et tomographie par émission de positons (TEP-scan) sont en revanche réservés à certains cas particuliers.

Zonal anatomy of the prostate using magnetic resonance imaging, morphometrics, and radiomic features: impact of age-related changes.

OBJECTIVE: To evaluate the impact of age on the zonal anatomy of the prostate by MRI using morphometric and textural analysis. METHODS: A total of 154 men (mean age: 63 years) who underwent MRI due to a high prostate-specific antigen (PSA) level were included retrospectively. At each MRI examination the following variables were measured: overall dimensions of the prostate (whole gland (WG), transitional zone (TZ), and peripheral zone (PZ)), and thickness of the anterior fibromuscular stroma (AFMS) and the periprostatic venous plexus (PPVP) on T2 weighted images. Identical regions of interest (ROIs) were delineated on the apparent diffusion coefficient (ADC) map on the anterior (horn) and posterior part of the PZ. Textural (TexRAD®) parameter differences between TZ and PZ ROIs on T2 weighted images were analyzed by linear regression. Results were correlated with age (distributed into five decades from 22 to 89 years). RESULTS: Age was positively correlated with PSA level and glandular volumes (WG, TZ, and TZ/WG ratio; p < 0.0001) and was negatively correlated with AFSM and PPVP thickness (p < 0.0001). There was a positive correlation between ADC values of the PZ and age (p = 0.003) and between entropy of the TZ and PZ and age (p < 0.001). CONCLUSION: Gradual variations in morphologic and textural features of the prostate were observed with age, mainly due to the increase in TZ volume while PZ volume tended to decrease. These modifications resulted in textural changes mainly at the expense of entropy. ADVANCES IN KNOWLEDGE: Entropy could be relevant for studying the process of aging of the prostate.

Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients.

BACKGROUND: COVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission. METHODS: Eighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined. RESULTS: Of the enrolled patients (median age 66 years [IQR: 59-74]), 73% male, median body mass index (BMI) 27 kg/m2 [IQR: 24-31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2, p < 0.0001) and ICU-R (respectively OR = 3.27, p = 0.01; OR = 4.86, p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p < 0.0001). CONCLUSIONS: Cardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission, a fortiori associated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.

Quantitative and Qualitative Approach for Shear Wave Elastography in Superficial Lymph Nodes.

The diagnostic contribution of 2-D shear-wave elastography (SWE) in management of superficial lymph nodes (LNs) of any origin was evaluated in 222 patients referred for needle core biopsy. Each patient underwent conventional B-mode/Doppler ultrasound examinations (conventional ultrasound) and SWE. Quantitative SWE parameters and qualitative SWE map features were extracted. Carcinomas were found to be significantly stiffer than benign LNs (29.5 ± 32.3 kPa vs. 6.7 ± 12.3 kPa). Lymphomas exhibited intermediate stiffness (11.4 ± 5.2 kPa). Qualitative SWE analysis provided color patterns specific to histopathology (stiff rim, nodular and undetermined patterns related to malignancy and blue pattern to benignity). Adding SWE to conventional ultrasound improved the sensitivity of LN diagnosis (from 81.1% to 92.0%) but decreased its specificity (from 73.2% to 67.6%) because of the high prevalence of lymphomas compared with carcinomas. Inter-observer agreement for quantitative SWE was good (intra-class correlation coefficient = 0.82) as was inter-observer diagnostic agreement for qualitative SWE (κ = 0.65). LN location and histology type were found to influence the reported diagnostic performance of SWE.

Peritoneal or mesenteric tumours revealing histiocytosis.

OBJECTIVE: Peritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process. DESIGN: We performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes. RESULTS: Abdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease. CONCLUSION: Diagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.

Association of shear-wave elastography with clinical outcomes post-liver transplantation.

PURPOSE: Two-dimensional shear-wave elastography (2D-SWE) assessment of liver stiffness has the advantage of being obtained during conventional ultrasound. Liver-stiffness values on 2D-SWE for grafted livers are unknown, as are their potential link to post-transplantation morbidity. This study was undertaken to determine liver-stiffness values on 2D-SWE for grafted livers without complications, and examine relationships between liver-stiffness values on 2D-SWE and early post-operative arterial or biliary complications. METHODS: In our facility, all liver-transplant recipients are entered in a comprehensive surgical database, where donor, procedure and recipient characteristics are described. All patients underwent systematic 2D-SWE assessment. Potential relationships were analyzed between liver-stiffness findings and donor, procedure and recipient characteristics, and follow-up events, including death, arterial or biliary complications, graft removal and allograft-dysfunction scores. RESULTS: Liver-stiffness values on 2D-SWE of 337 ultrasound examinations from 165 liver-transplant recipients were collected retrospectively. Median time from transplantation to 2D-SWE examination was 149 days, with median follow-up at 36 months. The mean±SD stiffness value for grafts without complications was 7.3±2.3kPa; it was significantly higher during the first 90 days (8.2±2.5kPa) post-transplant than after 1year (7.0±2.4kPa) (P=0.01). Patients with biliary complications during the first-year post-transplantation had significantly higher mean liver-stiffness values on 2D-SWE than those without, respectively: 9.8±7.0 vs 7.5±1.8kPa (P=0.01). CONCLUSIONS: Post-transplantation patients without complications had stiffer livers than the general population, with higher values during the first 90 days after surgery. Liver-stiffness values on 2D-SWE were significantly higher for patients with biliary, but not arterial, complications.

Prostate cancer local staging using biparametric MRI: assessment and comparison with multiparametric MRI.

PURPOSE: The value of adding dynamic contrast-enhanced (DCE) imaging to T2-weighted (T2W) magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) to improve the detection and staging of prostate cancer (PCa) is unclear. The aim of this retrospective study was to compare the diagnostic performance of non-contrast biparametric MRI (bpMRI) with multiparametric MRI (mpMRI), for local staging of PCa. METHODS: Ninety-two patients who underwent prostate MRI on a 3-Tesla MRI system before radical prostatectomy for PCa were included retrospectively. Four readers independently assigned a Likert score (ranging from 1 to 5) for predicting extra-prostatic extension (EPE) on T2W + DWI (bpMRI) and then on T2W + DWI + DCE imaging (mpMRI). MRI-based staging results were compared with radical prostatectomy histology. A prediction of EPE generalized linear mixed model was used to assess the added-value of DCE and discriminative power of staging accuracy by area under the receiver-operating curve (AUC ROC). RESULTS: AUC was not significantly improved by DCE (mpMRI, AUC = 0.73 [95%CI: 0.655‒0.827] vs. bpMRI, AUC = 0.76 [95%CI: 0.681‒0.846]). After applying a selection procedure, only MRI criteria were retained in a multivariate model. The following criteria were significantly associated with local extension: localization in the peripheral zone (p < 0.001), maximal diameter of the lesion (<0.0001), curvilinear capsular contact on T2W (p < 0.0001), capsular irregularity on T2W (p < 0.0001), bulging on T2W (p < 0.001) and seminal vesicle hypo-signal (p < 0.001). CONCLUSION: Use of bpMRI did not result in a decrease in local staging accuracy.

Monitoring Dual VEGF Inhibition in Human Pancreatic Tumor Xenografts With Dynamic Contrast-Enhanced Ultrasound.

BACKGROUND: Association of drugs acting against different antiangiogenic mechanisms may increase therapeutic effect and reduce resistance. Noninvasive monitoring of changes in the antiangiogenic response of individual tumors could guide selection and administration of drug combinations. Noninvasive detection of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway was investigated in an ectopic subcutaneous xenograft model for human pancreatic tumor. METHODS: Dynamic contrast-enhanced ultrasound 12 MHz was used to monitor tumor-bearing Naval Medical Research Institute mice beginning 15 days after tumor implantation. Mice received therapy from 15 to 29 days with sorafenib (N = 9), ziv-aflibercept (N = 11), combined antiangiogenic agents (N = 11), and placebo control (N = 14). Sorafenib (BAY 43-9006; Nexavar), a multikinase inhibitor acting on Raf kinase and receptor tyrosine kinases-including vascular endothelial growth factor receptors 2 and 3-was administered daily (60 mg/kg, per os). Ziv-aflibercept (ZALTRAP), a high-affinity ligand trap blocking the activity of vascular endothelial growth factor A, vascular endothelial growth factor B, and placental growth factor was administered twice per week (40 mg/kg, intraperitoneally). RESULTS: Functional evaluation with dynamic contrast-enhanced ultrasound indicated stable tumor vascularization for the control group while revealing significant and sustained reduction after 1 day of therapy in the combined group (P = .007). There was no survival benefit or penalty due to drug combination. The functional progression-free survival assessed with dynamic contrast-enhanced ultrasound was significantly higher for the 3 treated groups; whereas, the progression-free survival based on tumor size did not discriminate therapeutic effect. CONCLUSIONS: Dynamic contrast-enhanced ultrasound, therefore, presents strong potential to monitor microvascular modifications during antiangiogenic therapy, a key role to monitoring antiangiogenic combining therapy to adapt dose range drug.

RECIST and CHOI criteria in the evaluation of tumor response in patients with metastatic colorectal cancer treated with regorafenib, a prospective multicenter study.

BACKGROUND: To evaluate the objective response rate (ORR) at 2 months of treatment with regorafenib according to RECIST 1.1, Choi, and modified Choi (mChoi) criteria in patients with metastatic colorectal cancer (mCRC). METHODS: Baseline and 2-month contrast-enhanced computed-tomography (CECT) scans of 55 patients with mCRC, prospectively enrolled in phase II TEXCAN trial, were centrally assessed. The primary endpoint was 2-month ORR by RECIST 1.1, Choi, and mChoi criteria. Final outcome was overall survival (OS). RESULTS: Of 55 patients included in this study (Intention-to-treat [ITT1] population), 35 had CECT at 2 months (ITT2 population). According to RECIST 1.1 criteria, 20 (57%) patients were SD and 15 were PD (43%) in the ITT2 population. According to Choi criteria, 18 (51%) patients were responders and 17 (48%) were non-responders. Median OS was 5.3 months (95% CI 3.7-8.6) in the ITT1 population and 8.9 months (95% CI 5.1-12.6) in the ITT2 population. In the ITT2 population, median OS was 16 months (95% CI 6.6-17.5) in SD patients (n = 20) and 4.6 months (95% CI 3.3-5.8) in PD patients (n = 15), according to RECIST 1.1 criteria (HR = 6.48). Median OS was 7.9 months (95% CI 4.2-17.5) in responders (n = 18) and 9.9 months (95% CI 3.7-NA) in non-responders (n = 17) according to Choi criteria (HR = 1.06). All patients except one were classified as non-responders with mChoi criteria. CONCLUSION: At 2 months, unlike RECIST 1.1, Choi and mChoi criteria could not identify mCRC patients with regorafenib survival benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02699073.Registered March 4, 2016, Retrospectively registered.

Tumor-size responses to first-line is a predictor of overall survival in metastatic colorectal cancer.

OBJECTIVES: Early tumor shrinkage (ETS) has been reported to be associated with survival of metastatic colorectal cancer (mCRC) patients. Our aim was to analyze long-term tumor-size evolution, according to early mCRC best responses during the first-line therapy, to evaluate first best response-survival links. METHODS: Sixty-five patients with unresectable mCRCs, treated between 2010 and 2015, were included retrospectively in this descriptive monocenter study and grouped according to their RECIST 1.1 first-line best responses: progressive disease (PDfl), stable disease with tumor-size evolution between 0 and + 19% (SDfl+) or 0 and - 29% (SDfl-), and partial responders (PRs), who were classed PR with ETS (ETSfl) or without (PRfl). Tumor-size evolution and best tumor responses to each chemotherapy line were analyzed. RESULTS: Tumor loads of ETSfl or PRfl mCRCs tended to remain inferior to their initial values: 60% of patients died with target lesion sums below baseline. For first-line SDfl+ or PDfl mCRCs, rapid tumor load increases continued during successive lines: > 80% died with target lesion sums above baseline. ETSfl mCRCs responded better to subsequent lines (37.5% second-line PR), whereas PDfl mCRCs remained refractory to other therapies (0% second- and third-line PR). Overall survival rates were significantly (p = 0.03) longer for the ETSfl group (29.9 [95% CI: 12.6-47.1] months) and shorter for the PDfl group (17.1 [95% CI: 1.5-37.5] months). CONCLUSION: Tumors responding to first-line chemotherapy also responded better to subsequent lines, whereas PDfl mCRCs remained refractory, which may explain the better survival associated with ETSfl. KEY POINTS: • Early shrinking tumors under first-line chemotherapy responded better to subsequent lines, maintaining low tumor loads, potentially explaining the link between early tumor shrinkage and overall survival of metastatic colorectal cancer (mCRC) patients. • mCRCs progressing under first-line chemotherapy remained refractory to other therapies and their tumor loads increased rapidly. • Even outside a clinical trial, an early first CT scan reevaluation with RECIST criteria 8 weeks after starting first-line therapy is crucial to determine long-term mCRC evolution.

LCR1 and LCR2, two multi-analyte blood tests to assess liver cancer risk in patients without or with cirrhosis.

BACKGROUND: No blood test has been shown to be effective in the prediction of primary liver cancer in patients without cirrhosis. AIM: To construct and internally validate two sequential tests for early prediction of liver cancer. These tests enable an algorithm which could improve the performance of the standard surveillance protocol recommended (imaging with or without AFP), limited to patients with cirrhosis. METHODS: We performed a retrospective analysis in prospectively collected specimens from an ongoing cohort. We designed an early sensitive high-risk test (LCR1) that combined (using Cox model) hepatoprotective proteins (apolipoproteinA1, haptoglobin) with known risk factors (gender, age, gammaglutamyltranspeptidase), and a marker of fibrosis (alpha2-macroglobulin). To increase the specificity, we then combined (LCR2) these components with alpha-fetoprotein. RESULTS: A total of 9892 patients, 85.9% without cirrhosis, were followed up for 5.9 years [IQR: 4.3-9.4]. LCR1 and LCR2 time-dependent AUROCs were not different in construction and validation randomised subsets. Among 2027 patients with high-LCR1 then high-LCR2, 167 cancers (113 with cirrhosis, 54 without cirrhosis) were detected, that is 12 patients needed to screen one cancer. The negative predictive value was 99.5% (95% CI 99.0-99.7) in the 2026 not screened patients (11 cancers without cirrhosis) higher than the standard surveillance, which detected 113 cancers in 755 patients screened, that is seven patients needed to screen one cancer, but with a lower negative predictive value 98.0% (97.5-98.5; Z = 4.3; P < 0.001) in 3298 not screened patients (42 cancers without cirrhosis). CONCLUSIONS: In patients with chronic liver disease the LCR1 and LCR2 tests identify those with a high risk of liver cancer, including in those without cirrhosis. NCT01927133.

Long-Term Survival in Gastroesophageal Junction Adenocarcinoma: Ramucirumab.

We report a case of long-term survival with complete response of liver metastases within RAINBOW, a randomized, controlled trial of ramucirumab 8 mg/kg intravenously (days 1, 15) versus placebo, both plus paclitaxel 80 mg/m2 intravenously (days 1, 8, 15), every 4 weeks in patients with previously treated advanced gastroesophageal junction adenocarcinoma. A 64-year-old man with gastroesophageal junction adenocarcinoma and liver metastases received first-line folinic acid, 5-fluorouracil plus oxaliplatin (FOLFOX) following jejunostomy. On liver progression, he enrolled in RAINBOW (April 2012), receiving ramucirumab. In November 2013, positron emission tomography scan was consistent with complete metabolic response, confirmed by a follow-up scan in March 2016.

Multiparametric MRI for Suspected Recurrent Prostate Cancer after HIFU:Is DCE still needed?

PURPOSE: To assess the added value of the dynamic contrast-enhanced sequence (DCE) to combination T2-weighted imaging (T2w) + diffusion-weighted imaging (DWI) in detecting prostate cancer (PCa) recurrence after HIFU (high-intensity focused ultrasound). METHODS: Forty-five males with clinical and biological suspected PCa recurrence were retrospectively selected. All underwent multi-parametric MRI (mpMRI) before biopsies. Two readers independently assigned a Likert score of cancer likelihood on T2w + DWI + DCE and T2w + DWI images. Prostatic biopsies were taken as the gold standard. RESULTS: Recurrent PCa was identified at biopsy for 37 patients (82%). Areas under the receiver-operating curve of T2w + DWI and T2w + DWI + DCE imaging were not significantly different for both readers. Using a Likert score ≥ 3 for the PCa diagnosis threshold, sensitivity at the lobe level for the (1) senior and (2) junior reader for T2w +DWI +DCE sensitivity was (1) 0.97 and (2) 0.94 vs. (1) 0.94 and (2) 0.97 for T2w + DWI. CONCLUSION: Accuracy of mpMRI was not significantly improved by adding DCE to T2w + DWI. Sensitivity was high for T2w + DWI + DCE and T2w + DWI with no significant difference for either the junior or senior reader. KEY POINTS: • MpMRI has the capability to detect PCa recurrence in post-HIFU monitoring. • The sensitivity of T2w and DWI for detecting PCa recurrence was not improved by DCE. • Readers with different degrees of experience did not improve their performance with DCE.