Determination of biomarkers associated with neoadjuvant treatment response focusing on colibactin-producing Escherichia coli in patients with mid or low rectal cancer: a prospective clinical study protocol (MICARE).

INTRODUCTION: The management of mid and low rectal cancer is based on neoadjuvant chemoradiotherapy (CRT) followed by standardised surgery. There is no biomarker in rectal cancer to aid clinicians in foreseeing treatment response. The determination of factors associated with treatment response might allow the identification of patients who require tailored strategies (eg, therapeutic de-escalation or intensification). Colibactin-producing Escherichia coli (CoPEC) has been associated with aggressive colorectal cancer and could be a poor prognostic factor. Currently, no study has evaluated the potential association between intestinal microbiota composition and tumour response to CRT in mid and low rectal cancer. The aim of this study is to assess the association between response to neoadjuvant CRT and faecal intestinal microbiota composition and/or CoPEC prevalence in patients with mid or low rectal cancer. METHODS AND ANALYSIS: This is a non-randomised bicentric prospective clinical study with a recruitment capacity of 200 patients. Three stool samples will be collected from participants with histological-proven adenocarcinome of mid or low rectum who meet eligibility criteria of the study protocol: one before neoadjuvant treatment start, one in the period between CRT end and surgery and one the day before surgery. In each sample, CoPEC will be detected by culture in special media and molecular (PCR) approaches. The global microbiota composition will be also assessed by the bacterial 16S rRNA gene sequencing. Neoadjuvant CRT response and tumour regression grade will be described using the Dworak system at pathological examination. Clinical data and survival outcomes will also be collected and investigated. ETHICS AND DISSEMINATION: MICARE was approved by the local ethics committee (Comité de Protection des Personnes Sud-Est II, 18 December 2019. Reference number 2019-A02493-54 and the institutional review board. Patients will be required to provide written informed consent. Results will be published in a peer reviewed journal. TRIAL REGISTRATION NUMBER: NCT04103567.

Feasibility and Safety of Single-Probe Cryoablation with Liquid Nitrogen: An Initial Experience in 24 Various Tumor Lesions.

BACKGROUND: Percutaneous cryoablation with liquid nitrogen is a new technique being used in the treatment of some malignant tumors. Our objective was to assess its feasibility in the ablation of tumor lesions of various sizes and locations. METHODS: This retrospective, monocentric study included all consecutive patients who underwent percutaneous cryoablation with liquid nitrogen between December 2019 and March 2021. Cryoablation was performed using 10G or 13G cryoprobes. The ablation volume was measured on post-treatment CT or MRI. RESULTS: 22 patients (24 lesions) were included, 16 of whom were men (73%), while median age was 66 years. The lesions were located in the bone (42%), kidney (29%), soft tissue (17%), lung (8%), or liver (4%). It was feasible in all tumor locations and produced median ablation zones 25 mm in width and 35 mm in length, with a 23 min median freezing time. Freezing duration was correlated with the ice volume (p Spearman = 0.02), but not with the ablation volume (p = 0.11). The average difference between the ablation zone and ice ball sizes were -6.4 mm in width and -7.7 mm in length. Both ice and ablation volumes were larger when using the 10G probe as compared to when the 13G was used. No complications were reported. DISCUSSION: We showed that this technique was safe and feasible in all organs tested. The freezing duration was correlated with the ice ball size, but not with the ablation zone.

Feasibility of Neovessel Embolization in a Large Animal Model of Tendinopathy: Safety and Efficacy of Various Embolization Agents.

Targeting neovessels in chronic tendinopathies has emerged as a new therapeutic approach and several embolization agents have been reported. The aim of this study was to investigate the feasibility of embolization with different agents in a porcine model of patellar tendinopathy and evaluate their safety and efficacy. Eight 3-month-old male piglets underwent percutaneous injection of collagenase type I to induce patellar tendinopathies (n = 16 tendons). They were divided into four groups (2 piglets, 4 tendons/group): the control group, 50-100 µm microspheres group, 100-300 µm microspheres group, and the Imipenem/Cilastatin (IMP/CS) group. Angiography and embolization were performed for each patellar tendon on day 7 (D7). The neovessels were evaluated visually with an angiography on day 14. The pathological analysis assessed the efficacy (Bonar score, number of neovessels/mm2) and safety (off-target persistent cutaneous ischemic modifications and presence of off-target embolization agents). The technical success was 92%, with a failed embolization for one tendon due to an arterial dissection. Neoangiogenesis was significantly less important in the embolized groups compared to the control group angiographies (p = 0.04) but not with respect to histology (Bonar score p = 0.15, neovessels p = 0.07). Off-target cutaneous embolization was more frequently depicted in the histology of the 50-100 µm microspheres group (p = 0.02). Embolization of this animal model with induced patellar tendinopathy was technically feasible with different agents and allowed assessing the safety and efficacy of neovessel destruction. Particles smaller than 100 µm seemed to be associated with more complications.

Efficacy and safety of prostate artery embolization for patients with lower urinary tract symptoms and indwelling urinary catheter: A retrospective multicenter study.

PURPOSE: The purpose of this multicenter study was to evaluate the clinical success at three months of prostate artery embolization (PAE), assess PAE safety in centers with various experiences and identify factors associated with PAE success. PATIENTS AND METHODS: This multicenter, retrospective study included patients who underwent PAE for lower urinary tract symptoms (LUTS) including those with indwelling urinary catheter. PAE clinical success was defined as either 25% improvement of the International Prostate Symptom Score (IPSS) or 1-point improvement of quality of life (QoL) score, or catheter removal at three months. Multivariable analyses were performed using a logistic regression adjusted on patient variables, technical parameters and center experience in PAE. RESULTS: A total of 383 men (mean age, 68.4 ± 9.7 [standard deviation] years; range: 46-94) with LUTS, including 99 (25.8%) patients with indwelling urinary catheter, were included in seven centers from January 2017 to March 2019. Five patients reported major complications (1.3%), three (0.8%) penile ulceration, three (0.8%) acute urinary retention, one (0.3%) prostatic abscess, and 56 (14.6%) minor complications. Follow up data were available for 271 patients (center 1: n = 159; other centers: n = 112). Clinical success was reported in 232 patients (85.6%). In multivariable analyses, presence of cardiovascular comorbidities (diabetes, stroke history, myocardial infarction and lower limb artery disease) was the single independent variable inversely associated with PAE clinical success (odds ratio = 0.396; 95% confidence interval: 0.17-0.91; P = 0.029). There was no center effect. CONCLUSION: Our results show that PAE is safe and effective in centers with various PAE experiences. Cardiovascular comorbidity is the single independent variable associated with PAE failure.

Early results of ultra-low-dose CT-scan for extremity traumas in emergency room.

Background: Ultra-low dose computed tomography (ULD-CT) was shown to be a good alternative to digital radiographs in various locations. This study aimed to assess the diagnostic sensitivity and specificity of ULD-CT versus digital radiographs in patients consulting for extremity traumas in emergency room. Methods: Digital radiography and ULD-CT scan were performed in patients consulting at the emergency department (February-August 2018) for extremity traumas. Fracture detection was evaluated retrospectively by two blinded independent radiologists. Sensitivity and specificity were evaluated using best value comparator (BVC) and a Bayesian latent class model (LCM) approaches and clinical follow-up. Image quality, quality diagnostic and diagnostic confidence level were evaluated (Likert scale). The effective dose received was calculated. Results: Seventy-six consecutive patients (41 men, mean age: 35.2±13.2 years), with 31 wrists/hands and 45 ankles/feet traumas were managed by emergency physicians. According to clinical data, radiography had 3 false positive and 10 false negative examinations, and ULD-CT, 2 of each. Radiography and ULD-CT specificities were similar; sensitivities were lower for radiography, with BVC and Bayesian. With Bayesian, ULD-CT and radiography sensitivities were 90% (95% CI: 87-93%) and 76% (95% CI: 71-81%, P<0.0001) and specificities 96% (95% CI: 93-98%) and 93% (95% CI: 87-97%, P=0.84). The inter-observer agreement was higher for ULD-CT for all subjective indexes. The effective dose for ULD-CT and radiography was 0.84±0.14 and 0.58±0.27 µSv (P=0.002) for hand/wrist, and 1.50±0.32 and 1.44±0.78 µSv (P=NS) for foot/ankle. Conclusions: With an effective dose level close to radiography, ULD-CT showed better detection of extremities fractures in the emergency room and may allow treatment adaptation. Further studies need to be performed to assess impact of such examination in everyday practice. Trial Registration: ClinicalTrials.gov Identifier: NCT04832490.

Microwave Ablation of Liver, Kidney and Lung Lesions: One-Month Response and Manufacturer's Charts' Reliability in Clinical Practice.

Microwave ablation systems allow for performing tumoral destruction in oncology. The objective of this study was to assess the early response and reliability of the microwave ablation zone size at one month for liver, kidney and lung lesions, as compared to the manufacturer's charts. Patients who underwent microwave ablation with the EmprintTM ablation system for liver, kidney and lung lesions between June 2016 and June 2018 were retrospectively reviewed. Local response and ablation zone size (major, L, and minor, l, axes) were evaluated on the one-month follow-up imaging. Results were compared to the manufacturers' charts using the Bland-Altman analysis. Fifty-five patients (mean age 68 ± 11 years; 95 lesions) were included. The one-month complete response was 94%. Liver ablations showed a good agreement with subtle, smaller ablation zones (L: -2 ± 5.7 mm; l: -5.2 ± 5.6 mm). Kidney ablations showed a moderate agreement with larger ablations for L (L: 8.69 ± 7.94 mm; l: 0.36 ± 4.77 mm). Lung ablations showed a moderate agreement, with smaller ablations for l (L: -5.45 ± 4.5 mm; l: -9.32 ± 4.72 mm). With 94% of early complete responses, the system showed reliable ablations for liver lesions, but larger ablations for kidney lesions, and smaller for lung lesions.

A national dose analysis of guided tumor destruction: influence of sex, age, localization and destruction technique used.

Background: Percutaneous destructions of tumor lesions by ablation (microwave, radiofrequency or cryoablation) under computed tomography (CT) guidance allow high efficiency with minimally-invasive techniques, and acute needle placement and follow-up during procedure. This study investigated the impact of patient and technique parameters on the dose delivered during these procedures under CT guidance. Methods: Data were extracted from a previous nationwide retrospective study. Patients who underwent percutaneous destruction of bone lesions, abdominal and lung tumors were included. Univariate and multivariate linear regression of the dose length product (DLP) log were performed, according to patient's gender, age, lesion location, destruction technique, adjusted to the participating center. Results: A total of 822 patients (556 men), of mean age 62±14 years, were included: 150 patients had bone lesions, 463 abdominal and 209 thoracic tumors. The mean DLP was 991.6±979.0 mGy·cm for patients with bone lesions, 2,130.7±2,051.8 mGy∙cm for abdominal tumors and 825.2±545.4 mGy·cm for lung tumors. In multivariate analysis, the age was significantly associated with higher DLP for bone (P=0.0082) but not for abdominal and thoracic lesions; the DLP was significantly higher in men for abdominal tumors (P<0.0001) while sex had no impact on the dose for bone and thoracic lesions. The dose depended on the lesion location only for bone (P<0.0001) percutaneous destructions. The technique was not correlated to DLP for all lesions. Conclusions: Patient and tumor characteristics such as sex, age and lesion location impacted on the dose delivered during percutaneous destructions of bone, abdominal and thoracic lesions, but not the destruction technique used. Further studies are needed to propose sharper reference dose levels.

'Bad news consultations' with oncology nurses: Impact on perceived stress and patient experience.

PURPOSE: 'Bad News Consultations' (BNC), conducted by nurses who are specialists in cancer, have been institutionally implemented in all French anti-cancer centres, to support the patient facing announcement-related stress. This study aimed to 1/describe the impact of the BNC on the patient's perceived stress and 2/determine the patient's benefits from the BNC. METHOD: This monocentric study, cross-sectional evaluation, used a mixed method, both quantitative and qualitative. During 8 months, 336 eligible participants who underwent a BNC were recruited by nurses. Perceived stress was self-assessed with a validated Visual Analogic Scale (VAS), at the beginning and at the end of the BNC. Stress resilience was self-assessed once using the CD-RISC2. Qualitative experiences were explored after the BNC, using a 25-item questionnaire. Multivariate analyses were conducted on perceived stress measures (on the VAS) to test mixed-effects models, including initial predispositions (e.g., stress resilience) and organisational constraints (e.g, interval between the medical consultation and the BNC). RESULTS: Analyses on the perceived stress measures revealed a significant and negative effect of Time (B = -1.91; p < .001), Gender (B = 0.72; p = .03), and Resilience score (B = -0.43; p < .001), without any significant effect of the other incorporated random effects (i.e., Type of cancer/treatment) nor fixed effects (i.e., Age, Organisational constraints). Patients mostly reported having received necessary information, having their addressed emotions with empathetic responses and respect, perceived benefits in the healthcare pathway, and heard of some supportive cares. CONCLUSION: Perceived stress was reduced after BNCs. According to the patients, the BNCs allowed a better patient-centered communication and a better care pathway.

Importance of Patient Education for At-home Yoga Practice in Women With Hormonal Therapy-induced Pain During Adjuvant Breast Cancer Treatment: A Feasibility Study.

BACKGROUND: Osteo-articular pain (OAP) is experienced by approximately 50% of women under hormonal therapy (HT) for breast cancer (BC), which increases the risk for therapy discontinuation. This study was aimed to assess benefits of yoga practice combined with patient education (PE) for at-home practice by evaluating feasibility among BC patients under HT and measuring OAP, flexibility and satisfaction. METHODS: Feasibility was evaluated by patient adherence as accomplishment of at least 4 out of 6 supervised yoga-PE sessions along with 70% or more at-home yoga sessions. Intervention (12 weeks) included two 6-weeks periods: P1 comprising one 90-minutes supervised yoga-PE session/week and 15-minutes daily at-home yoga and P2, daily autonomous at-home yoga sessions. Evaluations (at inclusion and by the end of each period) consisted in assessment of OAP on Visual Analog Scale (VAS), forward flexibility (cm) and patient satisfaction on Likert (0-10 points) scale. RESULTS: Between September 2018 and May 2019 we included 24 patients of median 53 years (range 36-72). Feasibility was validated by 83% successful adherence rate. Pain was significantly reduced from median VAS of 6 [range 4-10] to 4 [range 0-7] at the end of both P1 and P2 (p < 0.01), albeit with no difference between P1 and P2. Forward flexibility improved by a median gain of 8 cm (end of P2) and median satisfaction score of 10/10 [range 8-10]. CONCLUSION: Combined physiotherapy-yoga-PE intervention is a feasible strategy to increase at-home yoga practice with potential benefit on pain, flexibility, and satisfaction, thus prompting further evaluations in larger randomized multicenter trials. CLINICALTRIALS.GOV: NCT04001751.

Changes in vitamin D and calcium metabolism markers in patients undergoing adjuvant chemotherapy for breast cancer.

BACKGROUND: Changes in calcium metabolism and calcium urinary excretion during chemotherapy have not been thoroughly assessed in patients with early breast cancer (EBC), a population who frequently present vitamin D insufficiency. As hypercalciuria is a classical contra-indication to vitamin D (VD) supplementation, this study evaluated changes in VD and calcium metabolism parameters in patients with EBC undergoing adjuvant chemotherapy (CT). METHODS: In patients with EBC who received six cycles of adjuvant CT, VD and calcium parameters were monitored at inclusion, and then every 3 weeks, at each CT cycle initiation. The primary endpoint was the percentage of patients showing hypercalciuria during adjuvant CT (between Day 1, Cycle 1 [D1C1] and Day 1, Cycle 6 [D1C6]). RESULTS: The primary endpoint could be evaluated in 82 patients. Most patients (n = 66, 80.5%) had VD insufficiency (< 30 ng/mL) at baseline. Hypercalciuria was detected in 29 patients (35.4%; 95% CI: 25.6-46.5) between D1C1 and D1C6, but was not clinically significant in any of the affected patients. The percentage of hypercalciuria events was not different between patients with sufficient and insufficient baseline VD levels (34.8% vs. 37.5%), and between patients who received or not VD supplementation (37.5% vs. 34.5%,). CONCLUSIONS: This comprehensive study on VD and calcium parameter changes in patients with EBC during adjuvant chemotherapy shows that hypercalciuria is a frequent abnormality in this setting, although asymptomatic. Therefore, it should not be considered as a limitation for high dose VD supplementation in this population. TRIAL REGISTRATION: EudraCT:2014-A01454-43 . Registered 29 august 2016.

Ultra-low-dose chest CT performance for the detection of viral pneumonia patterns during the COVID-19 outbreak period: a monocentric experience.

BACKGROUND: Ultra low dose chest computed tomography (CT) acquisitions have been used for selected emergency room patients with acute dyspnea or minor thoracic trauma. The purpose of this study was to evaluate the diagnostic performance of ultra-low-dose (ULD) chest CT for detecting viral pneumonia patterns compared to standard (STD) dose chest CT. METHODS: All consecutive adult patients with two non-enhanced chest CT acquisitions, one STD and one ULD, for suspicion of viral pneumonia between March 5th and April 2nd 2020 were included. CT results were divided into two groups: non-viral pneumonia CT or compatible with viral pneumonia CT based on viral pneumonia CT patterns: ground-glass opacity (GGO), consolidation, crazy paving, air bronchogram signs and fibrous stripes. The diagnostic performance of ULD CT for suspicion of viral pneumonia was evaluated. For CTs compatible with viral pneumonia, CT pattern detection on ULD CT was assessed and STD CT was used as a reference. RESULTS: The study included 380 patients with 97 CTs (25.5%) compatible with viral pneumonia. The mean effective doses (EDs) were 1.66 (1.29; 2.18) mSv for STD and 0.20 (0.18; 0.22) mSv for ULD CT (P<0.001). The sensitivity and specificity of ULD CT for viral pneumonia detection were 98.9% and 99.0%, respectively. GGO, consolidation and fibrous stripes were equally visible in STD and ULD in 100% (n=97), 36% (n=35) and 23% (n=22) of compatible viral pneumonia-CT patients, respectively. Air bronchogram sign detection was equivalent, concerning 23% (n=22) of patients in STD and 22% (n=21) in ULD. Crazy paving was visible in 24% (n=23) of patients in STD and only 8% (n=8) in ULD (P=0.003). CONCLUSIONS: In comparison to STD dose chest CT, ULD chest CT, with a mean reduction dose of 88.0%, has comparable diagnostic performance for detecting viral pneumonia on CT.

Impact of additional mattresses in emergency CT on the automated patient centering proposed by a 3D camera: a phantom study.

To assess the impact of the use of additional mattresses of different thicknesses on radiation dose and image noise based on the patient centering proposed by a 3D camera for CT. An anthropomorphic phantom was placed on mattresses of different thicknesses (from 3.5 to 13.5 cm) on the table of a CT scanner. The automated patient centering proposed by a 3D camera was analysed as a function of mattress thickness and corrected for table height. For this purpose, the impact on image noise in the lung tissues in the chest area and in the soft tissues in the abdomen-pelvis area, modulated mAs (mAsmod) by the tube current modulation system (TCM) and volume CT dose index (CTDIvol) was assessed slice-by-slice along the z-axis after CT scans. With the use of a mattress, the automated centering proposed by the 3D camera resulted in placement of the phantom above the isocentre. This incorrect positioning led to a significant increase in the mAsmod along the z-axis (p < 0.05) and in the CTDIvol. Image noise was significantly higher (p < 0.05) for automated phantom centering than with manual phantom centering. Differences of image noise between acquisitions with mattresses after automatic and manual phantom centering increased with the mattress thicknesses. The use of an additional mattress placed between the patient's back and the table-top would require correcting the vertical centering proposed by the 3D camera. This manual correction is essential to avoid increased dose delivered to the patient and higher image noise.

Diagnostic performance of ultra-low dose versus standard dose CT for non-traumatic abdominal emergencies.

PURPOSE: The purpose of this study was to compare the diagnostic performance of ultra-low dose (ULD) to that of standard (STD) computed tomography (CT) for the diagnosis of non-traumatic abdominal emergencies using clinical follow-up as reference standard. MATERIALS AND METHODS: All consecutive patients requiring emergency abdomen-pelvic CT examination from March 2017 to September 2017 were prospectively included. ULD and STD CTs were acquired after intravenous administration iodinated contrast medium (portal phase). CT acquisitions were performed at 125mAs for STD and 55mAs for ULD. Diagnostic performance was retrospectively evaluated on ULD and STD CTs using clinical follow-up as a reference diagnosis. RESULTS: A total of 308 CT examinations from 308 patients (145 men; mean age 59.1±20.7 (SD) years; age range: 18-96 years) were included; among which 241/308 (78.2%) showed abnormal findings. The effective dose was significantly lower with the ULD protocol (1.55±1.03 [SD] mSv) than with the STD (3.67±2.56 [SD] mSv) (P<0.001). Sensitivity was significantly lower for the ULD protocol (85.5% [95%CI: 80.4-89.4]) than for the STD (93.4% [95%CI: 89.4-95.9], P<0.001) whereas specificities were similar (94.0% [95%CI: 85.1-98.0] vs. 95.5% [95%CI: 87.0-98.9], respectively). ULD sensitivity was equivalent to STD for bowel obstruction and colitis/diverticulitis (96.4% [95%CI: 87.0-99.6] and 86.5% [95%CI: 74.3-93.5] for ULD vs. 96.4% [95%CI: 87.0-99.6] and 88.5% [95%CI: 76.5-94.9] for STD, respectively) but lower for appendicitis, pyelonephritis, abscesses and renal colic (75.0% [95%CI: 57.6-86.9]; 77.3% [95%CI: 56.0-90.1]; 90.5% [95%CI: 69.6-98.4] and 85% [95%CI: 62.9-95.4] for ULD vs. 93.8% [95%CI: 78.6-99.2]; 95.5% [95%CI: 76.2-100.0]; 100.0% [95%CI: 81.4-100.0] and 100.0% [95%CI: 80.6-100.0] for STD, respectively). Sensitivities were significantly different between the two protocols only for appendicitis (P=0.041). CONCLUSION: In an emergency context, for patients with non-traumatic abdominal emergencies, ULD-CT showed inferior diagnostic performance compared to STD-CT for most abdominal conditions except for bowel obstruction and colitis/diverticulitis detection.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

Phase II study evaluating the association of gemcitabine, trastuzumab and erlotinib as first-line treatment in patients with metastatic pancreatic adenocarcinoma (GATE 1).

In a previous phase II study (THERAPY), cetuximab and trastuzumab combination, as second-line after progression with gemcitabine, showed disease stabilization in 27% of 33 patients with pancreatic carcinoma. In the present phase II multicenter study, we assessed the efficacy and tolerance of gemcitabine, trastuzumab plus erlotinib as first-line treatment of metastatic pancreatic cancer. The primary endpoint was disease control rate (DCR, RECIST v.1); secondary endpoints were progression-free (PFS), overall (OS) survival and toxicity (NCI-CTCAE v3.0). Ancillary study addressed the predictive value of both EGFR/HER2 expression and KRAS mutational status. Sixty-three patients from four centers were included (62 evaluable for toxicity, 59 for efficacy), median age was 62 years (35-77), 59.7% men. The median treatment duration was 16.1 weeks (2.1-61). Eleven patients (19%) reported a partial tumor response, and 33 (56%) disease stabilization. DCR was 74.6% (95%CI: 61.8-85.0; 44/59 patients). After a median follow-up of 23.3 months (0.6-23.6), median PFS was 3.5 months (95%CI: 2.4-3.8) and median OS 7.9 months (95%CI: 5.1-10.2). PFS was significantly longer in patients with grade ≥ 2 cutaneous toxicities vs patients with grade 0-1 toxicities (HR = 0.55, 95%CI: 0.33-0.92, P = .020). Expression of EGFR and HER2 was correlated with PFS and OS in multivariate analysis; HER2 expression was correlated with the tumor response. Main severe toxicities were neutropenia (32%), cutaneous rash (37%) and thrombosis/embolisms (35.5%). This triplet combination is effective in terms of disease control, PFS and OS, and acceptable for safety. A larger study to investigate this combination compared to the standard regimen should be discussed.

Collagenase-Induced Patellar Tendinopathy with Neovascularization: First Results towards a Piglet Model of Musculoskeletal Embolization.

BACKGROUND: Therapeutic strategies targeting neovessels responsible for musculoskeletal chronic pain have emerged, including neovessels embolization. Our study aimed to develop a large animal model of patellar tendinopathy with neovascularization. METHODS: Nine 3-month-old male piglets (18 patellar tendons) received percutaneous injections of increasing doses of collagenase (0 to 50 mg) at day 0 (D0). Tendinopathy was evaluated by ultrasound (D7 and D14). Neovascularization was evaluated visually and on angiographies. Bonar score was used for histological analysis (D14). Correlations were evaluated using Spearman's rank (Rs) test. RESULTS: Research protocol was well tolerated. All tendons were enlarged with a median increase of 31.58% [25-40.28] at D7 (p = 0.244) at D7 and 57.52% [48.41-91.45] at D14 (p = 0.065). Tendons with collagenase injection had more hypoechoic changes, with one tendon rupture (p = 0.012). Neovascularization was reported above 5 mg collagenase (p < 0.01) at D7 and D14 with dose-related neovessels induction (Rs = 0.8, p < 0.001). The Bonar score increased above 5 mg collagenase, correlated with the dose (Rs = 0.666, p = 0.003). CONCLUSIONS: The study shows the feasibility, safety and reproducibility of this new large animal model of patellar tendinopathy with neovascularization after collagenase injection. It will allow studying new treatments on direct embolization of neovessels by endovascular approach.