非腫瘤和腫瘤全身熱療和一種新的免疫途徑來攻擊癌症?

Non-oncological & oncological whole-body hyperthermia and a new immunological road to attack cancer? -some treatment procedures

There is an increasing number of publication-based non-oncological indications in which the application of modern whole-body hyperthermia (WBH) can bring about an alleviation for the patients. Some of these indications are arterial hypertension, chronic back pain, fibromyalgia syndrome, psoriatic arthritis, ankylosing spondylitis, systemic scleroderma and major depressive disorder. This presentation wants to inform about the procedure in the mentioned indications. In a first Table 1 “Publication-Based Treatment Procedures for WBH for some Non-Oncological Indications” are the main parameters for the WBH procedure given with some remarks and together with the publications behind the procedure.
Furthermore, the application of WBH adjuvant to the conventional methods for the treatment of cancer patients – surgery, radiotherapy and chemotherapy – could be helpful. By WBH before operation, which increases the microcirculation and activates the immune system, the risk of wound infection after surgery is reduced. WBH increases with its intensified perfusion the oxygen partial pressure in tumors for higher x-ray sensitivity. WBH combined with chemotherapy for the treatment of cancer patients in a therapy resistant, metastatic or advanced stage of solid malignancies can improve the response rate and increases the quality of life.
Last but not least a view onto the immune system. It is still not proved by (published) clinical trials with cancer patients but there is a good probability that WBH with temperatures until fever-range supports the efficacy of checkpoint inhibitors. Also, not proved by clinical trials is the proposal of Hatfield & Sitkovsky to activate the cytotoxic T-cells to kill cancer cells by increasing the Oxygen partial pressure in the tumor, followed by a reduced adenosine concentration in the tumor microenvironment, and in connection with an adoptive immunotherapy. Fever-range WBH could support this process by increasing the killing efficiency of the cytotoxic T-cells. In a second Table 2 “For Discussion: Treatment Procedures regarding Adjuvant Treatment of Cancer Patients with WBH” is given a proposal of the main parameters for the WBH procedure with the rationale of the procedure and remarks together with the associated publications.
For all the mentioned indications and procedures are currently two leading devices used, realizing body-core temperatures from mild until extreme WBH

Table 1 Publication-Based Treatment Procedures of Whole-Body Hyperthermia for some Non-Oncological Indications

Indication Target-Temperature

T (rectal) °C

Heating-Up

Phase min

Plateau Phase;

(Retention) min

Resting Phase

min

Number of

Sessions

Monitoring
Arterial Hypertension 38,3 30 0 30 8 (2 x /week) or

8 (every 2days)

T(axillary),

Pulse

Chronic Back Pain 38.5 45 15 30 7 (1 x /week) T(rect), T(axill),

Pulse

Fibromyalgia Syndrome 38.1 40 15 30 6 (2 x /week), or

6 (every 2 days)

or 6 consecutive

days

T(axill), Pulse

 

Based Treatment Procedures of Whole-Body Hyperthermia for some Non-Oncological

Indications
Remark ↓ systolic by 22 mmHg, ↓ diastolic by 12 mmHg, 10% non-responder

Literature • Mischke M. Wirkungen einer einmaligen bzw. seriellen Infrarot-A-Hyperthermie bei Patienten mit arterieller Hypertonie der

WHO-Stadien I und II. Diss. Humboldt-Universität Berlin 18.07.1991

  • MeffertH, Scherf HP, Meffert B. Milde Infrarot-A-Hyperthermie: Auswirkungen von Serienbestrahlungen mit

wassergefilterter Infrarotstrahlung auf Gesunde und Kranke mit arterieller Hypertonie bzw. systemischer Sklerodermie. Akt

Dermatol, 1993;19:142-148

Remark prä/post 1 year: analgetics consumption < 10%

Literature  Weller E, Ullrich D. Infrarot-A-Hyperthermie-Anwendung bei Patienten mit Analgesic-Abusus wegen chronischer

Rückenschmerzen. Vortrag auf dem 95. Kongreß der Gesellschaft für Phys Med und Rehab 5.10.1990

Remark prä/post 6 month 20% below basic pain acc. to “Fibromyalgia Impact Questionnaire”/FIQ

Literature • Brockow T, Wagner A, Franke A, Offenbächer M, Resch KL. A Randomized Controlled Trial on the Effectiveness of Mild Water-filtered

Near Infrared Whole-body Hyperthermia as an Adjunct to a Standard Multimodal Rehabilitation in the treatment of Fibromyalgia. Clin J

Pain 2007;1:67-75 • Walz J, Hinzmann J, Haase I, Witte T. Ganzkörperhyperthermie in der Schmerztherapie – eine kontrollierte Studie

an Patient. mit Fibromyalgiesyndrom. Schmerz 2013;1:38-45 • Romeyke T, Stummer H. Multi-modal pain therapy of fibromyalgia

syndrome with integration of systemic whole-body hyperthermia – effects on pain intensity and mental state: A non-randomised

controlled study. J Musculoskel Pain 2014;4:341-55

 

Psoriatic Arthritis 38,5 45 15 30 6 (in 8 days) or 6

consecutive days

T(rect), T(axill),

Pulse

Axial Spondyloarthritis 38 30 15 120 in bed 6 (2 x /week) T(axill), Pulse
Ankylosing Spondylitis 38,5 45 15 30 6 (in 8 days) or 6

consecutive days

T(rect),

T(axill), Pulse

Systemic Scleroderma 38,3 30 0 30 15 (2 x /week) or

15 (every 2 days)

T(axill), Pulse

 

 

  • SchleenbeckerHG, Schmidt KL. Zur Wirkung einer iterativen milden Ganzkörper-hyperthermie auf den Fibromyalgieschmerz.

Phys. Rehab. Kur Med, 1998;8:113-117

Remark prä/post 6 month alleviation of pain, ↓ Disease-Activity Score (DAS 28) 3 month (DAS28 = activity and function parameter)

Literature  Lange U, Schwab F, Müller-Ladner U, Dischereit G. Wirkung iterativer Ganzkörperhyperthermie mit wassergefilterter

Infrarot-A-Strahlung bei Arthritis psoriatica – eine kontrollierte, randomisierte, prospektive Studie. Akt Rheumatol

2014;05:310-16

Remark prä/post 3 months pain reduction

Literature • Stegemann I, Hinzmann J, Haase I, Witte T. Ganzkörperhyperthermie mit wassergefilterter Infrarot-A-Strahlung bei

Patienten mit axialer Spondyloarthritis. Orthopäd. & Unfallchirurg. Praxis 2013;10:458-463

Remark ↓ disease activity index (BASDAI) 3 month, ↓ blood sedimentation rate 3 month, ↑ TLR-4, IL-10 (BASDAI = Bath AS Disease

Activity Index

Literature • Lange U, Müller-Ladner U, Dischereit G. Effectiveness of whole-body hyperthermia by mild water-filtered infrared-A

radiation in ankylosing spondylitis – a controlled, randomized, prospective study. Akt Rheumatol 2017; 2:122-128

  • ZaunerD, Quehenberger F, Hermann J, Dejaco C, Stadner MH, et al. Whole-body hyperthermia treatment increases

interleukin 10 and toll-like receptor 4 expression in patients with ankylosing

Remark in the follow-up period of two years for about 50% of the female patients the frequency and severity of Raynaud attacks were

sustained reduced

Literature • Meffert H, Scherf HP, Meffert B. Milde Infrarot-A-Hyperthermie: Auswirkungen von Serienbestrah-lungen mit

wassergefilterter Infrarotstrahlung auf Gesunde und Kranke mit arterieller Hypertonie bzw. systemischer Sklerodermie. Akt

Dermatol, 1993;19:142-148

 

Major Depressive Disorder 38.5 110 60 0 1 T(rect), T(axill), Pulse
Procedure Rationale Target-

Temperature

T(rectal) °C

Heating-Up

Phase

min

Plateau Phase;

(Retention)

min

Resting

Phase

min

Number

of

Sessions

Monitoring
Surgery

+

Whole-Body

Hyperthermia

Whole-body hyperthermia before

surgery activates the immune

system and reduces the risk of a

postoperative infection.

Hypothesis: better wound care on

the side of the body-own immune

defense

+ 0.35 30 0 0 1 x right before

surgery

T(axill)

 

 

 

  • FörsterJ, Fleischanderl S, Wittstock S, Storch A, Meffert H. Letter to the Editor: Infrared-Mediated Hyperthermia is Effective in the

Treatment of Scleroderma-Associated Raynaud’s Phenomenon. J Investig Dermatol, 2005;6:1313-16

Remark a single session of whole-body hyperthermia produced a significant antidepressant effect apparent within a week of treatment

that persisted for 6 weeks after treatment.

Literature • Janssen CW, Lowry CA, Mehl MR, Allen JJB, Kelly KL, Gartner DE, Medrano A, Begay TK, Rentscher K, White JJ, Fridman

A, Roberts LJ, Robbins ML, Hanusch KU, Cole SP, Raison CL. Whole-Body Hyperthermia for the Treatment of Major

Depressive Disorder – A Randomized Clinical Trial. JAMA Psychiatry 2016; 8:789-95

  • MeestersY, Beersma DGM, Bouhuys AL, vdHoofdakker RH. Prophylactic Treatmet of Seasonal Affective Disorder (SAD)

by Using Light Visors: Bright White or Infrared Light. Soc Biol Psychiatry 1999; 46:239-246Table 2 For Discussion: Treatment Procedures regarding Adjuvant Treatment of Cancer Patients with

Whole-Body Hyperthermia
Remark

421 patients with clean breast, varicose vein, or hernia surgery randomized in control- and treatment group. Whole-body hyperthermia

device was left in situ until just before surgery.

 

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