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Oncothermia as a modality treatment for lung cancer

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 Dr. Axel Weber , MD, Specialist surgeon

Director of the Clinic Marinus am Stein [Private clinic for holistic cancer therapy]

Special interest: Comprehensive naturopathic therapy program, conservative surgery, special treatment for tumour repression using buserelin, thermotherapy.

Biberstraße 30, 83098 Brannenburg, 
Germany
ph: +49 80 34 / 908 - 0
fax: +49 80 34 / 908 - 299
info@klinik-marinus.de
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Dr Dimitrios N. Gelis, MD, DDS, ORL, PhD Medical Life Coach

Special interests; Preventive Oncology, Medical Nutrition, Supplementary Medicin, Holistic Natural Treatments.

Damaskinou 46, Korinthos, Greece, Tel. 00302741026631, 00306944280764        mail: pharmage@otenet.gr www.gelis,gr  www,zinc.gr www.curcumin.gr

Lung cancer is the leading cause of cancer deaths worldwide, among both men and women and claims more lives each year than do colon, prostate, ovarian and breast cancers combined.

The pathological classification divides lung cancer into two major types, based on the appearance of lung cancer cells under the microscope. According to type of lung cancer the treatment decisions are based on which major type of lung cancer the patient suffers. The two general types of lung cancer include:

Small cell lung cancer [SCLC]. Small cell lung cancer occurs almost exclusively in heavy smokers and is less common than non-small cell lung cancer. The small cell lung cancer is considered the most aggressive type of lung cancer and have a range, 15-25%.

Non-small cell lung cancer [NSCLC]. Non-small cell lung cancer is a general term with which are described several types of lung cancers that behave in a similar way. Non-small cell lung cancers include squamous cell carcinoma, adenocarcinoma and large cell carcinoma. The majority of cases of lung cancer (range, 75% to 85%) are of the non-small-cell histology, and half of these are adenocarcinomas [1].

Unfortunately most of the NSCLCs are first diagnosed in an already advanced stage or have already become rapidly metastatic [2]. The majority of patients present with either locally advanced disease (stage III) or metastatic disease (stage IV).
The non-small cell lung carcinoma is the most usual cause of death due to cancer. Approximately 5-10% of patients present with an early stage tumor and can undergo radical surgery [3].

Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years [4].

The early diagnosis of the disease, in its localized state, has good five-year survival (52%), the regional or far distant stages have survival rates of only 25% and 4%, respectively. However, at the first diagnosis, 56% of cases already show distant metastatic lesions, while only 22% are regional and 15% are local only [4]
This is why the overall survival data demonstrates disappointing picture: relative survival rates (male/female) are 29.4%/33%, 7.8%/9.3%, and 4.9%/5.9% for one-, five-, and ten-year-survival studied in 2005 to 2009 [5].
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Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment [6].

The majority of the patients present with nonsurgically curable disease. For this reason major efforts have been made in the treatment of advanced non-small-cell lung cancer (NSCLC) with chemotherapy.

Several new agents and new combinations of chemotherapy are tested with randomized clinical trials investigating chemotherapy for advanced NSCLC in chemotherapy-naive patients, in patients who present with relapsed or progressive disease, and in elderly patients.

Also in the treatment of the disease are included therapies that incorporate new biological agents to target specific aberrations in lung cancer. In several clinical trials has been demonstrated improvement in overall survival as well as quality of life with chemotherapy treatment of advanced NSCLC. Better options are available for patients who have relapsed after first-line chemotherapy, and treatment of elderly patients with chemotherapy has demonstrated benefit in survival and quality of life.

New agents that target molecular pathways are being tested in patients with early-stage disease. Despite progress with newer agents for the treatment of advanced NSCLC, only 14% of patients with the disease are alive at 5 years after initial diagnosis. This situation demands new therapies [7].

Despite successful preclinical testing carried out through the use of subcutaneous xenografted tumors, many anti-cancer agents have gone on to fail in human trials.

One potential factor accounting for this discrepancy may relate to the inadequacy of the commonly employed preclinical models to recapitulate the human disease, particularly when it comes to discovery of agents that are effective against advanced disease.
Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.

Current treatments of pulmonary cancer
Non-small cell lung cancer [NSCLC]. The majority of patients either presents with advanced disease requiring chemotherapy or require chemotherapy at the time of relapse after surgical resection The standard first-line strategy for the treatment of advanced stage NSCLCs is a limited number of chemotherapy cycles to achieve tumor regression or at least stabilization [8].

Patients who undergo curative surgical resection for apparent localized disease have survival rates ranging between 50% and 80%, implying the need for better systemic treatment to cure occult micrometastatic disease.

NSCLC should now be further sub-classified by histology and driver mutation if one is known or present. Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life [9].

NSCLC is relatively insensitive to chemotherapy, compared to small cell carcinoma (SCLC). When possible, they are primarily treated by surgical resection with curative intent; however, chemotherapy is increasingly being used both preoperatively (neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy).

In general, the median survival of patients with NSCLC with such chemotherapy is average 7 -12 months [10].
Exept of surgery, radiation, and platinum-based doublet chemotherapy, another promising drug family was developed connected to growth factor receptors (GFR) to treat NSCLC

In order to increase the efficacy of such growth factor receptor, tyrosine kinase inhibitors, the coinhibition of GFR signaling pathways and combination of inhibitors along with radiation or chemotherapy have been studied.
Although clinical trials about single-agent receptor tyrosine kinase inhibitors (RTKIs) or their combination strategies suggest their increase potency against cancer, they are not beyond adverse effects, and sometimes the effects are more deadly than chemotherapy [11].

Small cell lung cancer [SCLC]. The treatment protocol for the SCLC is different from that of NSCLC. Currently, the optimal treatment is platinum-etoposide chemotherapy (four cycles) applied with complementary thoracic irradiation in patients in early stages, but radiotherapy is not applied in the late stage [12].
Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. Epirubicin with paclitaxel is an active and tolerable second-line regimen in patients with SCLC. 

Treatment of any kind lung cancer with oncothermia (loco-regional hyperthermia)

Hyperthermia (HT), combined with radiotherapy and chemotherapy, seems to be a promising method for cancer treatment [14] , although many of the underlying molecular mechanisms of this combination treatment are still not clearly understood.

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Oncothermia apparatus. 1. The patient is a part of an electric circuit controlled by highly sophisticated software. The modulated radiofrequency supply pumps current through the patient.

2. The electric contacts are two conductive sheets mainly parallel arranged above and below the body. The inequalities of the body-surface are smoothed by energy-transmitting liquid boluses.

3. The current flow is personalized, depends on the patient shape and tumor stage. The current could be modified during the treatment also, to follow the tumor-destruction process.

4. The radiofrequency current works in low frequency (13.56 MHz). This frequency is about ten times lower than the broadcasting frequency (over 100 MHz) of the popular radio stations. Oncothermia is entirely harmless by its “radiation”.

5. The personal fit is supported by various sizes of the applicators.

Reference: https://db.oncotherm.org/devicedb/web/phy/Oncothermia%20Therapy.pdf

It is reminded that there is high incidence of pulmonary malignancies. The variety of primary tumors frequently metastasize to the lungs e.g.( breast cancer, colon cancer, prostate cancer, and bladder cancer).

Metastatic lung malignancies can be developed quickly in other lobs, from the primary lung lesion. After that, cancer is progressively and quickly advanced and requires a high stage of care (frequently stage IV).
For this reason always any kind of lung cancer is consider as a medical emergency, without any delay of the starting of any available treatment.

In a such cases there are not multiple effective therapies for high-line treatment (third-line or over and there are not real treatment options available. This is another cause of the high mortality rate of the lung cancer sufferers. As the quality of life of patients with lung malignancies is very poor, there is urgent need for new treatments with minimal adverse effects which also can improve the quality of life of the patients.

One of the most advanced hyperthermia (HT) promising modalities devoted to oncology is loco-regional oncothermia [15, 16, 17].


Oncothermia preserves all positive effects of conventional hyperthermia (HT) while improving on the imperfections and answering the challenges posed by conventional approaches.

Oncothermia is based on a strong synergy between the temperature and the electric field. The radio frequency [RF] current is chosen with a proper amplitude-modulated RF (13.56 MHz), which is absorbed in the nanoscopic range only by the malignant cells .
In oncothermia there is a focused and controlled heat which is directed only to the tumor [18].

Oncothermia technology heats nonequally; concentrating the absorbed energy to the intercellular electrolytes [19].

This method creates inhomogeneous heating, microscopic temperature differences far from thermal equilibrium. The definitely large temperature gradient between the intra- and extracellular liquids changes the membrane processes and ignites signal pathways for natural programmed cell-death, avoiding the toxic effects of the simple necrosis. The synergy of electric field with the thermal effects potently and selectively makes the job [20].

Oncothermia is a highly customized treatment method, because the physiological differences of the malignant cells from their healthy counterparts distinguish the malignancy, which is self-selected by additional time-fractal modulation.

Oncothermia works on conduction principle. Radiofrequency current flows through the patient from one electrode to the other one. Electrodes are flat-metals, both under water pillow: one is in the bolus; one is under the water-mattress. Water is a transmitter of the RF-current, making possible a good fit of the human body to the flat metals.
The region of the body of the patient which is affected by the tumor is positioned between two electrodes. Both electrodes are active, current flows through them in all the frequency periods. The oncothermia session usually has a 60 min duration and the temperature in the malignant tumor is 42° C to 48° C. 
The created temperature exist only in the malignant tumor and the surrounding the tumor, healthy cells, remain intact.

Oncothermia destroys blood flow in the tumor, resulting in inadequate heat dissipation, starvation of the cancer cells of oxygen, metabolic division of the cancer cells is inhibited and the repair and surviving of the malignant cells is not possible.

Oncothermia produces apoptosis of the malignant cells. The apoptotic process is not using the mitochondrial internal pathway that is used in normal hyperthermia [21].

The electric field and the concomitant heat (electrohyperthermia) can synergistically induce cell death in tumor tissue, due to elevated glycolysis, ion concentration, and permittivity in malignant compared with nonmalignant tissues [22].
Oncothermia became a widely used and popular method in over 15 countries of the world. It is not a “gold standard” yet, but it is on the way to reach its stable and important position as a “fourth column” among the main oncotherapy modalities. It has wide-range applicability for every solid.

Oncothermia is a personalized non toxic treatment. Oncothermia, in most of the cases, is applied when the conventional cancer therapies fail. When the applied

therapies need sensitizing or their substitution is necessary. Oncothermia efficacy is focused on on patient-centered values: Survival time and quality of life.

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Reference: Oncotherm: https://db.oncotherm.org/devicedb/web/phy/Oncothermia%20Therapy.pdf

Studies have demonstrated that a combination of oncothermia and radiation or chemotherapy can be highly effective, and that oncothermia strongly enhances the effects of such other treatments. Oncothermia markedly improves patients’ quality of life and their chances for a complete cure.
Oncothermia can be applied as triple- or quadruple-modality (radio-chemo-thermo-therapy) and additional to surgery (adjuvant or neo-adjuvant) as well as some supportive therapies ( (vitamins, enzymes, etc) can be given alongside [23].

Oncothermia is a feasible and successful treatment for lung cancer. Results show a remarkable survival benefit for patients, with a good quality of life. The treatment has no, or in some cases mild, side-effects and could decrease the adverse effects of the complementary treatment.
Applying oncothermia together with other treatment methods could increase the effects and result in better performance. A comparison of studies demonstrates a good correspondence in the data, which strengthens the reliability of the studies, and clearly shows the feasibility of the application of oncothermia to treating all kinds of pulmonary malignancies including non-small-cell and small-cell primary tumors, and all of the metastatic diseases of the pulmonary system [24].

References
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