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Leaf rust is a major disease of wheat crop in the world as a whole. This study was undertaken to find the genetic effects of adult plant leaf resistance in wheat (Triticum aestivum L.). Three wheat crosses were developed from three resistant and one susceptible parent. Six populations (P 1 , P 2 , F 1 , F 2 , BC 1 and BC 2 ) of each cross were grown under field conditions and were artificially inoculated with isolates of mixture of leaf rust prevalent races. Leaf rust intensity and reaction type were observed and the coefficient of infection was computed. Generation means and variance analyses were performed for the estimation of additive, dominance and epistatic genetic effects. Additive and dominance, as well as epistatic genetic effects, are involved in the inheritance of leaf rust resistance. However, the narrow sense heritability estimates were low, which also exhibited the presence of epistatic genetic effects. Thus, selection of resistant adult plant in later segregating generations would be useful for the development of high yielding wheat genotypes.

The newer modalities of GBM treatment on the horizon are targeted therapy utilizing precision medicine, immunotherapy, Laser interstitial thermal therapy (LITT), ChemoID, CAR-T cell therapy, etc. There is always dilemma about referring a patient to the clinical trials which restrict the patient to one therapeutic agent Vs using a multi-disciplinary approach to improve patient’s survival. We present a single- institution retrospective data of the multidisciplinary management of our high grade glioma patients and their outcome. A chart review is being performed on high grade glioma patients (GBM, Gliosarcoma, Anaplastic Astrocytomas and Anaplastic Oligodendrogliomas) who had genomic alterations identified by commercial next generation sequencing. Thus far 100 patients had molecular profiling done at our institution and precision medicine was implemented in >50 patients along with other treatments. Of 100 patients 82 were GBM and 18 were Anaplastic gliomas. There were 61 males and 39 females. MGMT methylation was seen in 36 patients and 12 patients had IDH1 mutation. The actionable mutations seen EGFR, EGFRvIII, TERT, PDGFR, CDKN2A-20, BRAF, PTEN, NF1- PD/PD-L1. The targeted therapy used were imatinib, sirolimus, afinotor, debrfenib, pembrolizumab, EGFR vIII vaccine. The chemotherapies utilized were BCNU,CCNU, CPT-11, Etoposide, carboplatin. Of 100 high grade glioma patients 8 patients underwent LITT, 24 patients received SRS, 58 patients received Avastin. All patients are being followed for overall survival (OS) and progression free survival (PFS-6) at this point. Of the 82 GBM patients 35 are still alive at a median 21 months. The median overall survival of the 47 dead GBM patients was 24 months. CONCLUSION: In high grade Glioma patients a multi-disciplinary approach may prolong the survival and the genomic analysis does impact the outcome of these patients. When we implement more than one therapy at the same time overall survival can’t be credited to one specific mode of therapy.

BACKGROUND The presence of chemotherapy-resistant cancer stem cells (CSC) leading to tumor recurrence is postulated to be one of the major factors in the poor response to the current standard of care treatments in progressive high-grade gliomas. Unfortunately, in spite of several new drug discoveries for other tumor types, not many advances have been reported for this disease and therefore recurrent and progressive high-grade glioma survival remains dismal. METHODS We have used a CLIA and CAP accredited Cancer Stem Cell Cytotoxicity Assay(ChemoID) to guide most effective chemotherapy treatments from a panel of FDA approved drugs or their combinations for 12 recurrent glioblastoma (GBM) patients and 2 progressive anaplastic gliomas, all eligible to receive a stereotactic biopsy. Patients were evaluated by MRI scans and response was assessed according to RANO criteria. RESULTS The median age of our patient cohort was 49 years (21–63), with 11 males (79%) and 3 females (21%). We observed 6 complete responses (CR) 43%, 6 partial responses (PR) 43%, and 2 progressive diseases (PD) 14%. Of note, the two PD were observed in patients that could not be treated with assay recommended therapy due to their health status. Patients treated with ChemoID assay-directed therapy had a longer median overall survival (OS) of 13.3 months (5.4-NA) compared to the historical median OS of 9.0 months (8.0–10.8 months) previously reported (1). Notably, our recurrent and progressive high-grade glioma patient cohort treated with assay-guided therapy had a 57% probability to survive at 12 months, compared to the 27% historical probability of survival at 12 months observed in previous studies (1). CONCLUSIONS The data suggests that the ChemoID Cancer Stem Cell Cytotoxicity Assay has the potential to help guide individualized chemotherapy choices to improve recurrent and progressive high-grade glioma patient outcome. 1) Friedman, H.S. et. al. JCO2009 27:28, 4733–4740.