Using CAF profiling, we identified two mRCC patient groups, a candidate plasma signature for predicting PFS benefit, and distinct marker changes occurring with each treatment. This platform may provide valuable insights into renal cell carcinoma biology and the molecular consequences of targeted therapies.

We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III-IV organ damage, engraftment failure or death within 30 days. 'Response' was engraftment and remission (CR) on day þ 30. We sought to determine the GO dose (2, 4 or 6 mg m À2 ) giving the best tradeoff between toxicity and response. All patients were not candidates for myeloablative regimens. Treatment plan: GO (day À12), fludarabine 30 mg m À2 (days À5 to À2), melphalan 140 mg m À2 (day À2) and HSCT (day 0). GVHD prophylaxis was tacrolimus and mini-methotrexate. Diagnoses were AML (n ¼ 47), MDS (n ¼ 4) or CML (n ¼ 1). Median age was 53 years (range, 13-72). All but three patients were not in CR. Donors were related (n ¼ 33) or unrelated (n ¼ 19). Toxicity and response rates at 4 mg m À2 were 50% (n ¼ 4) and 50% (n ¼ 4). GO dose was de-escalated to 2 mg m À2 : 18% had toxicity (n ¼ 8) and 82% responded (n ¼ 36). 100-day TRM was 15%; one patient had reversible hepatic VOD. Median follow-up was 37 months. Median event-free and overall survival was 6 and 11 months. GO 2 mg m À2 can be safely added to fludarabine/melphalan, and this regimen merits further evaluation.

No abstract

No abstract

Background Most current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables. Methods A prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort. Results A total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases. Conclusion The contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.