The 5-y survival for cancer patients after diagnosis and treatment is strongly dependent on tumor type. Prostate cancer patients have a >99% chance of survival past 5 y after diagnosis, and pancreatic patients have <6% chance of survival past 5 y. Because each cancer type has its own molecular signaling network, we asked if there are "signatures" embedded in these networks that inform us as to the 5-y survival. In other words, are there statistical metrics of the network that correlate with survival? Furthermore, if there are, can such signatures provide clues to selecting new therapeutic targets? From the Kyoto Encyclopedia of Genes and Genomes Cancer Pathway database we computed several conventional and some less conventional network statistics. In particular we found a correlation (R 2 = 0.7) between degree-entropy and 5-y survival based on the Surveillance Epidemiology and End Results database. This correlation suggests that cancers that have a more complex molecular pathway are more refractory than those with less complex molecular pathway. We also found potential new molecular targets for drugs by computing the betweenness-a statistical metric of the centrality of a node-for the molecular networks.network entropy | signaling pathway | degree distribution | prostate cancer | basal cell carcinoma

Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival .180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.

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Although nonoptimized KVAT dose distributions presented here were of inferior quality to VMAT plans, this work has demonstrated the feasibility of delivering low-energy kilovoltage x-rays to lesions up to 4 cm in diameter to depths of 8.1 cm while sparing surrounding tissue.

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