Summary Background We previously found that dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumour growth in patient-derived xenografts of HER2 -amplified metastatic colorectal ...cancer. In this study, we aimed to assess the antitumour activity of trastuzumab and lapatinib in patients with HER2-positive colorectal cancer. Methods HERACLES was a proof-of-concept, multicentre, open-label, phase 2 trial done at four Italian academic cancer centres. We enrolled adult patients with KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer refractory to standard of care (including cetuximab or panitumumab), an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion. We defined HER2 positivity in tumour samples by use of immunohistochemistry and fluorescence in-situ hybridisation in accordance with our previously validated colorectal cancer-specific diagnostic criteria. Eligible patients received intravenous trastuzumab at 4 mg/kg loading dose followed by 2 mg/kg once per week, and oral lapatinib at 1000 mg per day until evidence of disease progression. The primary endpoint was the proportion of patients achieving an objective response (defined as complete response or partial response), which was assessed by independent central review in the intention-to-treat population. This trial is registered with EudraCT, number 2012-002128-33. Findings Between Aug 27, 2012, and May 15, 2015, we screened 914 patients with KRAS exon 2 (codons 12 and 13) wild-type metastatic colorectal cancer and identified 48 (5%) patients with HER2-positive tumours, although two died before enrolment. Of these patients, 27 were eligible for the trial. All were evaluable for response. At the time of data cutoff on Oct 15, 2015, with a median follow-up of 94 weeks (IQR 51–127), eight (30%, 95% CI 14–50) of 27 patients had achieved an objective response, with one patient (4%, 95% CI −3 to 11) achieving a complete response, and seven (26%, 95% CI 9–43) achieving partial responses; 12 (44%, 95% CI 25–63) patients had stable disease. Six (22%) of 27 patients had grade 3 adverse events, which consisted of fatigue in four patients, skin rash in one patient, and increased bilirubin concentration in one patient. No grade 4 or 5 adverse events were reported. We detected no drug-related serious adverse events. Interpretation The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer. Funding Associazione Italiana Ricerca Cancro (AIRC), Fondazione Oncologia Niguarda Onlus, and Roche.
Summary Background Radiofrequency ablation is an accepted treatment for non-surgical patients with liver cancer. The purpose of this study was to identify the feasibility, safety, and effectiveness ...of percutaneous radiofrequency ablation of malignant lung tumours. Methods Between July 1, 2001, and Dec 10, 2005, a series of 106 patients with 183 lung tumours that were 3·5 cm in diameter or smaller (mean 1·7 cm SD 1·3) were enrolled in a prospective, intention-to-treat, single-arm, multicentre clinical trial from seven centres in Europe, the USA, and Australia. Proof of malignancy was obtained by biopsy in all patients. Diagnoses included non-small-cell lung cancer (NSCLC) in 33 patients, metastasis from colorectal carcinoma in 53 patients, and metastasis from other primary malignancies in 20 patients. All patients were considered by the treating physician to be unsuitable for surgery and unfit for radiotherapy or chemotherapy. Patients underwent radiofrequency ablation in accordance with standard rules for CT-guided lung biopsy and were then followed for up to 2 years. Primary endpoints were technical success (defined as correct placement of the ablation device into all tumour targets with completion of the planned ablation protocol), safety (including identification of treatment-related complications and changes in pulmonary function), and confirmed complete response of tumours (according to modified Response Evaluation Criteria in Solid Tumors). Secondary endpoints were overall survival, cancer-specific survival, and quality of life. This trial is registered with ClinicalTrials.gov , number NCT00690703. Findings Correct placement of the ablation device into the target tumour with completion of the planned treatment protocol was feasible in 105 (99%) of 106 patients. The technical failure in one patient was caused by the inability to place the device inside a small tumour. No procedure-related deaths occurred in any of the 137 ablation procedures. Major complications consisted of pneumothorax (n=27) or pleural effusion (n=4), which needed drainage. No significant worsening of pulmonary function was noted. A confirmed complete response of target tumours lasting at least 1 year was shown in 75 (88%) of 85 assessable patients. No differences in response were noted between patients with NSCLC or lung metastases. Overall survival was 70% (95% CI 51–83%) at 1 year and 48% (30–65%) at 2 years in patients with NSCLC, 89% (76–95%) at 1 year and 66% (53–79%) at 2 years in patients with colorectal metastases, and 92% (65–99%) at 1 year and 64% (43–82%) at 2 years in patients with other metastases. Cancer-specific survival was 92% (78–98%) at 1 year and 73% (54–86%) at 2 years in patients with NSCLC, 91% (78–96%) at 1 year and 68% (54–80%) at 2 years in patients with colorectal metastases, and 93% (67–99%) at 1 year and 67% (48–84%) at 2 years in patients with other metastases. Patients with stage I NSCLC (n=13) had a 2-year overall survival of 75% (45–92%) and a 2-year cancer-specific survival of 92% (66–99%). Interpretation Percutaneous radiofrequency ablation yields high proportions of sustained complete responses in properly selected patients with pulmonary malignancies, and is associated with acceptable morbidity. Randomised controlled trials comparing radiofrequency ablation with standard non-surgical treatment options are warranted. Funding Angiodynamics (Queensbury, NY, USA).
To assess long-term clinical outcome of percutaneous vertebroplasty (PV).
PV was performed in 1,634 patients (1,387 women; median age 73 years ± 9.3) with painful osteoporotic vertebral compression ...fractures (VCFs). All patients had back pain that persisted for ≥ 2 months with a concordant magnetic resonance imaging study. After PV, medical therapy for osteoporosis was continued, and patients were prospectively evaluated (follow-up 11.8-44.9 months, mean 25.0 months). Visual analog scale (VAS), Oswestry Disability Index (ODI), analgesic drug use, and use of external brace support were recorded at baseline and during follow-up. New occurrences of symptomatic vertebral fractures were recorded.
The mean VAS score of 7.94 significantly improved to 1.12 at the primary endpoint (P < .001). Differences in patterns of analgesic usage compared with baseline values were highly statistically significant (marginal homogeneity test, P < .001). Median ODI values of 82% before treatment significantly decreased to 6% (P < .001). Before intervention, 1,279 patients wore a brace; 1,167 (91.2%) patients did not wear a brace after PV (χ(2) = 31.005, P < .0001). A new painful fracture with a significant higher proportion of contiguous vertebrae (63.6%) occurred in 214 (13.1%) patients (z = 7.59, P = .025).
PV can provide durable pain relief and improvement in ambulation in patients with VCFs.
Chemotherapy could induce benign liver alterations presenting as diffuse or focal lesions mimicking metastases. Oxaliplatin-induced vascular liver injury is described in literature, but the ...association with FNH-like lesions has been reported in a limited number of cases. We herewith describe the case of a 67-year-old male, who had laparoscopic right-sided hemicolectomy, 8 years ago, because of colonic adenocarcinoma (pT3N0M0) and subsequent adjuvant chemotherapy (capecitabine + oxaliplatin), who referred to the ultrasound service of our Radiology Unit because of abdominal pain. Five-years follow-up was negative for metastases. Ultrasound examination showed 2 small hypoechoic hepatic nodules, in segment VIII and VII, confirmed at CT, suspected for metastases. FDG-PET was negative, and blood tumor markers were within normal ranges. For further evaluation we performed gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI that showed hyperintensity of the nodules in the hepatobiliary phase with central small hypointensity due to a central scar. Considering the previous oxaliplatin-based chemotherapy the findings were compatible with FNHlike lesions and the diagnostic suspicion was confirmed at ultrasound-guided core needle biopsy. Knowledge of the possible occurrence of FNH-like lesions in oncologic setting, along with the detection of typical MRI appearance, is important for appropriate management and may avoid unnecessary biopsy or surgery and reduce patients’ anxiety.
A case of a 75-year-old patient with a painful pathologic humeral shaft fracture, with unacceptably high surgical risk and unsatisfactory analgesia is reported. In this case, impaired arm function ...and persistent pain with conservative management resulted in a poor quality of life. Palliation with image-guided percutaneous osteoplasty was considered. Because of potential cement leakage, inadequate fracture reduction, the site of the fracture, and the mobility of the joints in that area, image-guided percutaneous delivery of metallic bone marrow nails implanted together with polymethyl methacrylate (PMMA) osteoplasty was performed. This procedure achieved humeral shaft stabilization, bone fragment alignment, fracture reduction, and pain relief.
Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and ...interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points.
Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method.
Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified.
This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.
•Across European cancer centres, imaging protocols show considerable heterogeneity.•This European collaboration conducted a consensus finding survey on mCRC imaging.•An imaging protocol scorecard is provided to facilitate implementation in trials.
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