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EDITORIAL
Year : 2018  |  Volume : 9  |  Issue : 3  |  Page : 107-108

Reimagining hyperthermia in oncology


Department of Radiation Oncology, Nanavati Super Speciality Hospital, Mumbai, Maharashtra, India

Date of Web Publication27-Sep-2018

Correspondence Address:
Dr. Nagraj Huilgol
Department of Radiation Oncology, Nanavati Super Speciality Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_18_18

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How to cite this article:
Huilgol N. Reimagining hyperthermia in oncology. J Radiat Cancer Res 2018;9:107-8

How to cite this URL:
Huilgol N. Reimagining hyperthermia in oncology. J Radiat Cancer Res [serial online] 2018 [cited 2018 Dec 14];9:107-8. Available from: http://www.journalrcr.org/text.asp?2018/9/3/107/242368



The galloping progress in technology has not ensured further improvements in survival patterns in most cancers. Chemoradiation comes with a considerable toxicity while targeted therapies have not turned out to be miracle drugs that one thought they would be. We are at the crossroad, though the horizon is resplendent modalities, for instance, like heating is a prudent step forward.

Heat as a treatment option has an ancient history in epics such as Ramayan, Egyptian Papyrus, and the Greeks. However, it is in the last few decades that a better understanding of thermal biology and improved technology has ensured that hyperthermia (HT) became a part of mainstream medicine. It was decided in Kadota Fund International Forum 2004 that elevation of the tumor temperature to 39°C–45°C should be termed as “hyperthermia” while any further elevation of temperature as thermal ablation.[1] The biological basis for HT has been elucidated over a period of last few decades. It stands to reason that all the cellular chemical processes are temperature dependent. HT alone can be cytocidal or may sensitize radiation therapy. It can also modulate kinetics of drug delivery by altering perfusion and cell membrane integrity.

HT works by influencing cellular targets which are distinctly different than that for radiation therapy. Hypoxic cells steeped in acidic, or those cells in S-phase are more sensitive to HT, while being resistant to radiation therapy. HT has the potential to alter perfusion and vascular permeability. There is a biphasic response to HT. Lower temperature induces increased perfusion, while heating at 44°C–45°C for over 30 min may have a contrary effect. Fluidity of cell membrane increases following HT. This influences permeability of cell membrane. The change in fluidity also impacts trafficking of membrane-bound proteins. HT may also inhibit DNA repair. Local HT may help in activating immune systems and cause direct effects on the tumor. Expression of heat shock proteins (HSPs) such as HSP90 confers transient thermal tolerance. However, HSPs may be crucial in eliciting local immunity.

Clinicians have been quick on integrating HT in clinical oncology. The euphoria of 80s quickly turned into despondence. Zee et al.'s seminal publication of lancet in the year 2000 gave a fresh impetus to clinical trials.[2] Many more randomized trials in various anatomical sites such as head and neck, breast, bladder, soft-tissue sarcoma, and cervix and superficial tumors have shown an improved survival advantage[3] Huilgol et al. demonstrated the benefit of adding HT to radiation therapy in head-and-neck cancer.[4] Similarly, a retrospective analysis of chemoradiation with HT in head-and-neck cancer has shown a spectacularly better survival.[4]

Datta et al. compiled randomized trials published in the English literature.[5] Most of the trials are underpowered. Yet, there is a strong trend toward beneficial effects of HT in conjunction with radiation therapy. HT with chemotherapy alone or in conjunction with chemoradiation may have additive effects. However, no major randomized HT has been conducted barring that by Issels in soft-tissue sarcoma.[6] Interaction of chemotherapy is more complicated than that with ionizing radiation. Drugs such as doxorubicin, cyclophosphamide, and gemcitabine interest directly with HT while taxanes, methotrexate and fluorouracil, may act by virtue of increased perfusion following HT. Cisplatin, carboplatinum, and bleomycin in conjunction with HT can sensitize hypoxic core to radiation therapy. Encapsulation of cytotoxic drugs in heat-sensitive liposomes is another area which needs greater investigation. HT may also elicit immune response leading to immunogenic cancer cell death. It may act synergistically with radiation to induce local and abscopal response. The technology of HT has evolved, yet deep heating is always a formidable challenge. Pretreatment planning and online thermometry may help optimizing delivery of heat. The existing technology of HT is capital intensive. Besides, technology is not easily available in India and the neighboring countries. The need for further improvement in survival should alert us to earlier therapeutic modalities which have shown adequate promise but not perused. The hype over targeted therapy has receded. It is time for reimagining HT as a part of multimodality treatment.

 
  References Top

1.
van der Zee J, Vujaskovic Z, Kondo M, Sugahara T. The kadota fund international forum 2004 – Clinical group consensus. Int J Hyperthermia 2008;24:111-22.  Back to cited text no. 1
    
2.
van der Zee J, González González D, van Rhoon GC, van Dijk JD, van Putten WL, Hart AA, et al. Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: A prospective, randomised, multicentre trial. Dutch deep hyperthermia group. Lancet 2000;355:1119-25.  Back to cited text no. 2
    
3.
Datta NR, Ordóñez SG, Gaipl US, Paulides MM, Crezee H, Gellermann J, et al. Local hyperthermia combined with radiotherapy and-/or chemotherapy: Recent advances and promises for the future. Cancer Treat Rev 2015;41:742-53.  Back to cited text no. 3
    
4.
Huilgol NG, Gupta S, Sridhar CR. Hyperthermia with radiation in the treatment of locally advanced head and neck cancer: A report of randomized trial. J Cancer Res Ther 2010;6:492-6.  Back to cited text no. 4
    
5.
Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, et al. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: A randomised phase 3 multicentre study. Lancet Oncol 2010;11:561-70.  Back to cited text no. 5
    
6.
Huilgol NG, Gupta S, Dixit R. Chemoradiation with hyperthermia in the treatment of head and neck cancer. Int J Hyperthermia 2010;26:21-5.  Back to cited text no. 6
    




 

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