Re: Cases That Respond to Oncothermia Monotherapy

[문형철]

beyond reason

Abstract

There is a long history of hyperthermia in oncology, but its wide range acceptance and application are missing even today. A new approach of oncological hyperthermia, oncothermia, looks promising modality of the complementary treatment of advanced malignant cases. Our present paper is targeting this method, trying to answer the question of its feasibility to treat various advanced cases in monotherapy process, as well as its applicability for a long, large number of treatment sessions protocols.

1. Background

Although the hyperthermia was among the very first medical treatments in human medicine, this approach has ambivalent eval‎uation as a therapy. Hyperthermia is one of the most common therapies in “house” applications, a part of the “popular wisdom” of the traditional medicine. Heat is applied according to unwritten traditions in every culture. Heat treatment has high popularity in Korea for various preventive or curative intentions. It is applied for simple prevention or “cure” of common cold, applied to still various pains (joints, muscle spasms, various orthopedic problems, etc.). Heat is applied for better overall conditions and for simple relaxing or sometimes for spiritual reasons. The various heat therapies are commonly used complementarily with natural drugs (tees, herbs, oils, aromas, etc.) or with natural radiations (sunshine, red-hot iron radiation, etc.) This popular medicine is sometimes connected with ritual, cultural, and social events (ritual hot bath cultures) or to long-time continued chronic cures (like special spa treatments, hot-spring natural drinks, etc.).

These popular treatment applications of heating are types of “kitchen medicine”: the old recipes are “sure,” the patient takes it, and cured when it is done according to the auricular traditional regulations. This “for sure” is the disadvantage of the popular wisdom. It interprets this heating method as a simple causal process, “do it, get it.” However, the hyperthermia is not as simple as the traditions interpret it.

Internal source of heat is the fever as a reaction to infections [1] or pyrogens [2] or malignant hyperthermia [3] as well. The natural fever is induced by the living system [4]. The situation is quite different, when the heating is forced from outside of the body, and it is intended to be applied as therapy. The forced heating works against the homeostasis, and the body tries to keep the temperature normal, irrespective that the heating is local, regional, or systemic. The interpretation of hyperthermia as therapy has various stumbling blocks, because the effect caused by the absorbed heat is too complex: the applied, absorbed energy is usually depleted nonhomogeneously, and the intricacy of the living processes modifies the intended motive of application. Further complication is in the heating process itself: the efficacy certainly differs by heat sources and by the properties of the target volume and its physiological effects as well.

A frustration in understanding of the differences between the natural and constrained heat therapies and their consequent reactions characterizes the complete history of hyperthermia in medicine and explains in majority why hyperthermia has no well-deserved place in the professional medical armory to treat various diseases.

Hyperthermia as a treatment modality is battling for the step from the biomedical experiment status to a clinically proven one [5, 6].

The central problem of the forced heating in a local/regional volume is the physiological feedback reaction acting to compensate the compulsory temperature elevation. The main physiological feedback mechanism is the active blood flow in the heat-targeted volume [7–9]. The intensified blood flow is excellent heat exchanger, cooling down the heated volume and effectively increasing the temperature in the surroundings of the target. The high blood flow delivers extra nutrients (mainly glucose) supplying the tumor as well as increases the risk of dissemination of malignant cells by the blood stream. Both effects are contrary to our direct aim to destroy the cancer. The situation is a competition now between the cellular distortion by direct heat and the supply of the growth of the tumor together with its increasing dissemination ability. This is the origine of the contradictiog results and the missing satisfactory control on the oncological heat treatments.

Technically, a huge variety of heating could be applied by heat therapies [10]. Its energy production, its selectivity, locality, kind of energy delivery, locality invasivity control, and applied frequency of the electromagnetic waves, as well as their medical applications and combination with other methods make the heat therapies different.

Oncothermia is a special heating, targeting the membrane of the malignant cells [11]. This nanorange heating makes it possible to destroy the malignant cells by extreme temperature gradient on their membranes individually [12], without exciting of the physiological feedback mechanisms, without considerable blood flow increase.

Our objective in this paper is to show actual cases of how oncothermia works. The main addressed questions are as follows.(1)Which adverse effects does oncothermia have by dose escalation (extended treatment duration)?(2)How is the long treatment effective in various cases of the disease?(3)Can we apply oncothermia as monotherapy for a long time?(4)Are we able to handle the fatal cancer cases as chronic disease in the style of dialysis?

2. Method

There were chosen numerous cases, having complications with the gold-standard therapies, in high-line treatments. Oncothermia was applied or complementary to chemo- and/or radiotherapy or it was applied as monotherapy in the cases when the combination was not feasible. The study started in December 2011 and summarized the results until September 2012.

Patients were the intention-to-treat (ITT) population; no cohort was formed, a retrospective data-collection is the basis of the eval‎uation. The study was performed in single-institute basis, and the patients were rigorously diagnosed, checked, and followed up during the trial. All together 216 patients were treated in this time with 4263 sessions cumulatively. From this, we had chosen 16 cases characteristically showing the results.

We used the EHY2000+ device (Oncotherm GmbH, Germany), applying the 20 and 30 cm diameter electrodes in step-up heating protocol. The maximal energy was 150 W; duration of a session was 60 min each, 2~3 times/week, and 12 times in one cycle. The average number of the treatments was 33 sessions or 4 cycles; the duration of the time of the full cycles was over 6 months.

3. Case Reports3.1. Rectosigmoid Cancer with Liver Metastasis

A 43-year-old Asian man was diagnosed with Rectosigmoid cancer with metastasis of liver in March 10, 2012. And T-loop End Colostomy was performed on May 7, 2012. Avastin-FOLFOX chemotherapy was given 3 times after operation and the second-line FOLFIRI chemotherapy was given 3 times. He received radiotherapy to liver delivering 18 Gy in 10 fractions for 2 weeks from August 13, 2012 to August 27, 2012 and concurrent 37 times oncothermia from July 20, 2012 to November 21, 2012 (see Figure 1).

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Figure 1 

(a) Before oncothermia. (b) After 12 times of oncothermia. (c) After 31 times of OncoTx.

Tumor mass in liver regressed, and liver parenchyma increased gradually with concurrent small dose of radiation and oncothermia. No adverse effect that originated from oncothermia was observed. This result gives the large possibilities of combined treatment of oncothermia with low dose of radiation for far advanced cancer for palliative treatment.

3.2. Hepatocellular Carcinoma

A 61-year-old Asian man was diagnosed with hepatocellular carcinoma. TACE was given on February 17, 2011. He suffered from type B virus hepatitis from 1992 and liver cirrhosis from 2001. TACE could not be given anymore after one time even though HCC was aggravated with elevation of alpha-fetoprotein level in serum. Regrowing cancer and rapid rising of alphafeto-protein (20.48 to 448.90) appeared in November 2011.

Twenty four times of oncothermia were given from November 21, 2011 to February 27, 2012 (see Figure 2).

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