A molecular classification of papillary renal cell carcinoma.

Despite the moderate incidence of papillary renal cell carcinoma (PRCC), there is a disproportionately limited understanding of its underlying genetic programs. There is no effective therapy for metastatic PRCC, and patients are often excluded from kidney cancer trials. A morphologic classification of PRCC into type 1 and 2 tumors has been recently proposed, but its biological relevance remains uncertain. We studied the gene expression profiles of 34 cases of PRCC using Affymetrix HGU133 Plus 2.0 arrays (54,675 probe sets) using both unsupervised and supervised analyses. Comparative genomic microarray analysis was used to infer cytogenetic aberrations, and pathways were ranked with a curated database. Expression of selected genes was validated by immunohistochemistry in 34 samples with 15 independent tumors. We identified two highly distinct molecular PRCC subclasses with morphologic correlation. The first class, with excellent survival, corresponded to three histologic subtypes: type 1, low-grade type 2, and mixed type 1/low-grade type 2 tumors. The second class, with poor survival, corresponded to high-grade type 2 tumors (n = 11). Dysregulation of G1-S and G2-M checkpoint genes were found in class 1 and 2 tumors, respectively, alongside characteristic chromosomal aberrations. We identified a seven-transcript predictor that classified samples on cross-validation with 97% accuracy. Immunohistochemistry confirmed high expression of cytokeratin 7 in class 1 tumors and of topoisomerase IIalpha in class 2 tumors. We report two molecular subclasses of PRCC, which are biologically and clinically distinct and may be readily distinguished in a clinical setting.

Hippocampal Sparing Whole Brain Radiotherapy and Integrated Simultaneous Boost vs Stereotactic Radiosurgery Boost: A Comparative Dosimetric Planning Study.

BACKGROUND: Whole brain radiotherapy (WBRT) and stereotactic radiosurgery were frequently used to palliate patients with brain metastases. It remains controversial which modality or combination of therapy is superior especially in the setting of limited number of brain metastases. The availability of newer medical therapy that improves survival highlighted the importance of reducing long term radiation toxicity associated with WBRT. In this study, we aim to demonstrate the hippocampal sparing technique with whole brain and integrated simultaneous boost Materials and Methods: Planning data from 10 patients with 1-5 brain metastases treated with SRS were identified. Based on the contouring guideline from RTOG atlas, we identified and contoured the hippocampus with 5mm isocentric expansion to form the hippocampal avoidance structure. The plan was to deliver hippocampal sparing whole brain radiotherapy (HSWBRT) of 30 Gy in 10 fractions and simultaneous boost to metastatic lesions of 30 Gy in 10 fractions each. RESULTS: The PTV, hippocampus and hippocampal avoidance volumes ranges between 1.00 - 39.00 cc., 2.50 - 5.30 cc and 26.47 - 36.30 cc respectively. The mean hippocampus dose for the HSWBRT and HSWBRT and SIB plans was 8.06 Gy and 12.47 respectively. The max dose of optic nerve, optic chiasm and brainstem were kept below acceptable range of 37.5 Gy. CONCLUSIONS: The findings from this dosimetric study demonstrated the feasibility and safety of treating limited brain metastases with HSWBRT and SIB. It is possible to achieve the best of both worlds by combining HSWBRT and SIB to achieve maximal local intracranial control while maintaining as low a dose as possible to the hippocampus thereby preserving memory and quality of life.