IMMUNE MODULATORY EFFECT OF HYPERTHERMIA DURING TREATMENT OF RECURRENT, METASTATIC OR LOCALLY ADVANCED SOLID ORGAN MALIGNANCIES Background: The use of hyperthermia as an adjunct to improve conventional therapies in multimodal cancer treatment is supported by an increasing body of research. The underlying biological contribution of hyperthermia in modulating the cells of the immune system has been a growing area of interest. This study aims to evaluate the immune modulatory effect of locoregional hyperthermia given with standard of care treatment for patients with recurrent or metastatic solid malignancies. Secondary endpoints were tolerability, change in pain score and quality of life, and tumour control rate. Methods: A single-centre prospective study, conducted from December 2019 to December 2021 at the University of Malaya Medical Centre, recruited 30 patients with solid organ malignancy at baseline. Alongside standard cancer treatment, patients also received hyperthermia treatment for 2 hours, two or three times a week for up to 16-weeks using REMISSION1ºC hyperthermia-induction device. Flow cytometry for lymphocyte enumeration and immunophenotyping was done on blood samples collected from patients at 4 different time points (Baseline, week 1 post hyperthermia, week 1 post standard therapy, week 4. Results: In the analysis of lymphocyte subsets, an increase in CD8+ central memory T cells between baseline and week 1 post hyperthermia (Mean: Baseline 3.854, Week 1A 5.818; P = 0.013) was noted. An increase of CD4+ effector memory T cells between baseline and week 4 post hyperthermia in conjunction with standard therapy (Mean: Baseline 33.60, Week 4 39.34; P = 0.022) was recorded. There was also a marked increase in the percentage of CD8+ T cell expressing checkpoint inhibitory marker PD-1 post week 1 hyperthermia treatment (Mean: Baseline 7.439, week 1A 9.757; P = 0.048) as well as post standard treatment (Mean: Baseline 7.439, Week 1B 9.222; P = 0.033) from baseline. Conclusion: Hyperthermia produced significant effects on the immune cell profiles of cancer patients on treatment. The subset of CD4 effector memory T cells increased significantly, although there was also sign of increased T cells exhaustion. These findings serve as a stepping stone for further research in exploring the mechanisms of hyperthermia in immune modulation and also its translation into clinical practice.

Background: The incidence of colorectal cancer (CRC) is rapidly rising in several Asian countries, including Malaysia, but there is little data on health care provider costs in this region. The aim of this study was to estimate the cost of CRC management from the perspective of the health care provider, based on standard operating procedures. Methods: A combination of top-down approach and activity-based costing was applied. The standard operating procedure (SOP) for CRC was developed for each stage according to national data and guidelines at the University of Malaya Medical Centre (UMMC). The unit cost was calculated and incorporated into the treatment pathway in order to obtain the total cost of managing a single CRC patient according to the stage of illness. The cost data were represented by means and standard deviation and the results were demonstrated by tabulation. All cost data are presented in Malaysian Ringgit (RM). The cost difference between early stage (Stage I) and late stage (Stage II–IV) was analysed using independent t-test. Results: The cost per patient increased with stage of CRC, from RM13,672 (USD4,410.30) for stage I, to RM27,972 (USD9,023.20) for Stage IV. The early stage had statistically significant lower cost compared to late stage t(2) = −4.729, P = 0.042. The highest fraction of the cost was related to surgery for Stage I, but was superseded by oncology day care treatment for Stages II–IV. CRC is a costly illness. From a provider perspective, the highest cost was found in Stages III and IV. The early stages conserved more resources than did the advanced stages of cancer. Conclusion: Early diagnosis and management of CRC, therefore, not only affects oncologic prognosis, but has implications for health care costs. This adds further justification to develop and implement CRC screening programmes in Malaysia.