Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. In these advanced cases, chemotherapy and radiation have shown limited tumor control, and PC continues to be refractory to treatment and results in a poor survival outcome. In recent years, there has been intensive research on checkpoint inhibitor immunotherapy for PC, however, PC is characterized with dense stromal tissue and a tumor microenvironment (TME) that is highly immunosuppressive, which makes immunotherapy less effective. Interestingly, when immunotherapy is combined with radiation therapy (RT) and loco-regional hyperthermia (HT), it has demonstrated enhanced tumor responses. HT improves tumor killing via a variety of mechanisms, targeting both the tumor and the TME. Targeted HT raises the temperature of the tumor and surrounding tissues to 42–43 °C and makes the tumor more immunoresponsive. HT can also modulate the immune system of the TME by inducing and synthesizing heat shock proteins (HSP), which also activate an anti-tumor response. It is well known that HT can enhance RT-induced DNA damage in cancer cells and simultaneously help to oxygenate hypoxic regions. Thus, it is envisaged that combined HT and RT might have immunomodulatory effects in the PC-TME, making PC more responsive to immunotherapies. Moreover, the combined tripartite approach of immunotherapy, RT, and HT could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the immunotherapeutic effect of overall individual therapies to treat local and metastatic PC. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than monotherapy or dual therapy to treat and increase the survival of the PC patients.

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Prostate cancer is the second most frequent cancer among males worldwide. 1,2 Most cases are locoregional disease, with excellent prognosis; 5-, 10-, and 15 year relative survival rates are 99%, 98%, and 96%, respectively. Among patients treated for locoregional disease, approximately one-third receive some form of radiation therapy (RT). 3 Given the high rates of long-term survival of these patients, increased interest has focused on long-term post-RT toxicities, which include radiation-induced erectile dysfunction (RiED), bowel dysfunction, and urinary dysfunction. 4 Mounting evidence from clinical studies, including the Prostate Cancer Outcomes Study 4 and the recently matured multi institutional Phase III randomized ProtecT trial, 5 indicates that patients with posttreatment side-effects consistently experience moderate-to-severe loss of quality of life (QoL).Approaches to mitigate post-RT toxicity are based on: (a) dosimetric avoidance of critical structures through more frequent image guidance, RT plan optimization, and in-room real-time motion monitoring, as well as realtime adaptive dose delivery 6 ; (b) phosphodiesterase Type

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