Integrating Loco-Regional Hyperthermia Into the Current Oncology Practice: SWOT and TOWS Analyses

in situ tumor vaccination” through upregulation of the release of heat shock proteins (HSPs) that act as danger signalsnHighlight:Systematic reviews (, ) and meta-analyses have reported positive outcome with HTnHighlight:overall complete response (CR) of 54.9% with HTRT vs. 39.8% with RT alonenHighlight:Heat over a temperature range of 41.5–46.5°C kills cells in a predictable, exponential mannernHighlight:Hyperthermia results in inhibitions of the DNA repair enzymesnHighlight:mitotic catastrophe, induction of senescence, apoptosis, and necrosisnHighlight:Low pH exerts a profound cytotoxic effect and enhances thermal sensitivity, especially at 41–43°CnHighlight:direct implications in hypoxic regions of tumor, which are usually radioresistant owing to low pH secondary to elevated glycolysis and lactic acid productionnHighlight:temperature-dependent effects on loco-regional vascularity, interactions at the molecular levels especially DNA repair, induction of HSPs, modification of the tumor cell phenotype, and direct thermal cytotoxicitynHighlight:Longer exposure to temperatures higher than 42.5°C could result in impairment of blood flow due to damage of the fragile and chaotic neoangiogenic tumor microcirculation. This could result in even complete shutdown of tumor blood flownHighlight:temperatures of 39°C and higher foster immune cell infiltrationnHighlight:temperatures above 41°C lead to immunogenic cancer cell deathnHighlight:These complementary effects activate the immune system at multiple levelsnHighlight:effect HT should be considered as a cumulative effect on blood flow changes and oxygenation, DNA repair inhibition, thermal sensitization, and direct thermal cytotoxicity over the temperature range of 39–45°CnHighlight:Moderate HT is one of the most potent known radiosensitizers through a combination of induced thermophysiological changes in the tumor matrix, along with sustainable interactions at the cellular and molecular levelsnHighlight:clinical hyperthermia at 39–45°C with its effects as a potent radiosensitizernHighlight:Hyperthermic radiosensitizationnHighlight:Moderate HT radiosensitizes in principle both normal and tumor tissuesnHighlight:thermal enhancement ratio (TER)nHighlight:The higher the temperature and the longer the heating period, the greater the enhancemennHighlight:When HT and RT are delivered simultaneously, the TERnHighlight:clinically, HT and RT are normally given sequentially, and a short time interval between HT and RT is considered optimalnHighlight:HT also temporarily inhibits the repair of RT-induced sublethal and potentially lethal DNA damagenHighlight:Radioresistant late “S” phase cells are heat sensitivenHighlight:HT inhibits the homologous recombination (HR) repair of DNA double-strand breaks (DSBs) by inducing degradation of BRCA2, a key protein for HR repair, with a clear dose–effect relationshipnHighlight:Physiological vasodilation following HT also contributes to radiosensitization by improving tumor perfusion and oxygenation, thereby rendering treatment-resistant hypoxic cells radiosensitivenHighlight:HT leads in part of the tumors to reperfusion and reoxygenation (, ), and this reoxygenation appears to be associated with better clinical outcomenHighlight:The enhanced oxygen levels appear to last up to 1–2 days after HT treatmentnHighlight:Hyperthermic cytotoxicity:nHighlight:Heat kills cells by various mechanisms including necrosis and apoptosisnHighlight:HT-induced cytotoxicity is primarily directed toward the chronically hypoxic cell fraction embedded in the acidic milieunHighlight:This effect is temperature dependent but independent of the time interval between HT and RTnSticky notes:HT is effective as a stand alone treatment.nHighlight:Thermotolerance is induced during an HT sessionnHighlight:transitory resistancenHighlight:The phenomenon is attributed to HSPsnHighlight:The higher the initial tumor temperature, the longer the thermotolerance persistsnHighlight:Clinically, HT is delivered once or twice a week to avoid ineffective HT sessions due to thermotolerancen]]>

About Dr. Nathan Goodyear
About Dr. Nathan Goodyear

Dr. Nathan Goodyear, a medical doctor with years of experience in the field of integrative cancer care, has announced the launch of an online training program. This program, available on his new website, will provide individuals with access to video trainings led by Dr. Goodyear himself, covering a range of topics related to integrative cancer care. These trainings will include information on the latest research and techniques in the field, as well as guidance on how to incorporate these approaches into a patient’s overall cancer treatment plan. With this online program, Dr. Goodyear hopes to make his expertise and knowledge more widely accessible, and help more people understand the benefits of integrative cancer care.

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