There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy. Our PDO test predicted response of the biopsied lesion in more than 80% of patients treated with irinotecan-based therapies without misclassifying patients who would have benefited from treatment. This correlation was specific to irinotecan-based chemotherapy, however, and the PDOs failed to predict outcome for treatment with 5-fluorouracil plus oxaliplatin. Our data suggest that PDOs could be used to prevent cancer patients from undergoing ineffective irinotecan-based chemotherapy.

PurposeTo assess safety and outcome of radiofrequency ablation (RFA) and microwave ablation (MWA) as compared to systemic chemotherapy and partial hepatectomy (PH) in the treatment of colorectal liver metastases (CRLM).MethodsMEDLINE, Embase and the Cochrane Library were searched. Randomized trials and comparative observational studies with multivariate analysis and/or matching were included. Guidelines from National Guideline Clearinghouse and Guidelines International Network were assessed using the AGREE II instrument.ResultsThe search revealed 3530 records; 328 were selected for full-text review; 48 were included: 8 systematic reviews, 2 randomized studies, 26 comparative observational studies, 2 guideline-articles and 10 case series; in addition 13 guidelines were evaluated. Literature to assess the effectiveness of ablation was limited. RFA + systemic chemotherapy was superior to chemotherapy alone. PH was superior to RFA alone but not to RFA + PH or to MWA. Compared to PH, RFA showed fewer complications, MWA did not. Outcomes were subject to residual confounding since ablation was only employed for unresectable disease.ConclusionThe results from the EORTC-CLOCC trial, the comparable survival for ablation + PH versus PH alone, the potential to induce long-term disease control and the low complication rate argue in favour of ablation over chemotherapy alone. Further randomized comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical. Hence, the highest achievable level of evidence for unresectable CRLM seems reached. The apparent selection bias from previous studies and the superior safety profile mandate the setup of randomized controlled trials comparing ablation to surgery.Electronic supplementary materialThe online version of this article (10.1007/s00270-018-1959-3) contains supplementary material, which is available to authorized users.

The procedure-specific complication rate was almost 10 per cent and it is recommended that RFA should be performed only by an experienced team comprising a hepatobiliary surgeon, gastroenterologist, hepatologist and interventional radiologist. Biliary stricture, hepatic vascular damage and hepatic abscesses were the most common major complications.

Background: Organoid technology has recently emerged as a powerful tool to assess drug sensitivity of individual patient tumors in vitro. Organoids may therefore represent a new avenue for precision medicine, as this circumvents many of the complexities associated with DNA-or transcriptional-profiling. Materials and methods: The SENSOR trial was a single-arm, single-center, prospective intervention trial to evaluate the feasibility of patient-derived organoids to allocate patients for treatment with off-label or investigational agents. The primary endpoint was an objective response rate of !20%. Patients underwent a biopsy for culture before commencing their last round standard of care. Organoids were exposed to a panel of eight drugs and patients were treated after progression on standard-of-care treatment and when a clear signal of antitumor activity was identified in vitro.Results: Sixty-one patients were included and we generated 31 organoids of 54 eligible patients. Twenty-five cultures were subjected to drug screening and 19 organoids exhibited substantial responses to one or more drugs. Three patients underwent treatment with vistusertib and three with capivasertib. Despite drug sensitivity of organoids, patients did not demonstrate objective clinical responses to the recommended treatment. Conclusions: Organoid technology had limited value as a tool for precision medicine in this patient population because a large fraction of patients could not undergo treatment or because the recommended treatment did not elicit an objective response. We identified several essential parameters, such as the culture success rate, clinical deterioration of patients during standard of care, and rational design of drug panels that need to be accounted for in organoid-guided clinical studies.