25 maart 2009: Bron: ASCO 2008 en te publiceren dit jaar in Clinical Oncology

Hyperthermie met laag frequente electro-statische velden (in studieabstract afgekort als OT) zoals gebruikt in Duitsland bij o.a. dr. Gorter in Keulen en in hyperthermie centrum van Bochum  verlengt hoog significant levensduur van kankerpatienten met hersentumoren graad III en IV naast standaard behandelingen als bestraling en chemo in de vorm van Temodal - . We mogen het volledige studieverslag nog niet publiceren omdat deze wordt gepubliceerd op ASCO 2009 en daarna in Clinical Oncology maar hieronder enkele stukken uit het in ons bezit zijnde volledige studieverslag met werkwijze, patientengegevens, tabellen, statistieken enz.  Voor OPS donateurs hebben we het studieverslag beschikbaar mits aangevraagd samen met behandelend arts.

Afgelopen anderhalf jaar heb ik een Nederlandse man gefilmd met een inoperabele Glioblastoom Multiforme graad IV. November 2007 maakte ik de eerste opnames van hem toen hij van oncologen uit het Erasmus Medisch Centrum Rotterdam te horen had gekregen  dat er niets meer voor hem gedaan kon worden. Slechts een palliatieve bestraling aangevuld met Temodal zou zijn leven nog wat kunnen verlengen. Deze man begint bij dr. Robert Gorter in het Medisch Centrum Keulen met hyperthermie in combinatie met dendritische cletherapie november 2007 en aanvullend ook nog bepaalde vitamine infusen. Vorig jaar zomer 2008 stopte hij met de Temodal en dexametason en vorige week mocht ik de uitslag filmen van de laatst gemaakte scan d.d. 17 maart 2009 in het Erasmus Medisch centrum Rotterdam . Er was geen tumor noch oedeem meer op de scan te ontdekken. Over ca. drie weken zullen we zijn verhaal met verloop van zijn ziekte en behandelingen bij dr. Robert Gorter in het Medisch Centrum Keulen op video op onze site publiceren. Voor andere videoverhalen van kankerpatienten die alsnog genezing vonden voor hun ongeneesljke vorm van kanker klik op videoknop op startpagina.

Opmerkelijk detail: Teun van Vliet ook genezen van inoperabele Glioblastoom Multiforme door hyperthermie plus dendritische celtherapie tipte deze man om het nog te proberen in Keulen. Nu zijn beiden klinisch kankervrij. Zeer verheugend nieuws dus naast deze studie die bewijst dat met name electro-hyperthermie (in Nederland wordt andere vorm van hyperthermie uitgevoerd ) het leven van met name kankerpatienten met hersentumoren graad III en IV, deze zijn uit regulier oogpunt nooit meer te genezen, een hoog significant beter resutlaat laat zine op overlevingstijd en overall overleving. Ik kan nog verklappen dat 11% de 5-jaars overleving haalde met hyperthermie tegenover 0% zoals statistisch mocht worden verwacht zonder hyperthermie.

 

Retrospective clinical study for advanced brain-gliomas by adjuvant
electro-hyperthermia treatment
 
Sahinbas Hüseyin, Grönemeyer Dietrich HW, Böcher Eckhard*,
University Witten-Herdecke, Institute of Microtherapy, Universitätstrasse 142, 44799-Bochum, Germany;
(*) Clinic “Closter Paradise”, Im Stiftsfeld 1, 59494-Soest, Germany;

 

Abstract
Gliomas are one of the most common primary brain-tumors. Despite surgery and radiotherapy (RT) with or without adjuvant chemotherapy, malignant glioma remains an almost uniformly fatal disease characterized by a rapid and devastating clinical course. Oncologic hyperthermia (oncothermia or electro-hyperthermia = OT) applied either alone or in combination with chemo- and/or radio-therapy is a new modality of brain-glioma (BG) treatments. We present a retrospective study of 140 patients, which were treated/followed from January 2000 to February 2005. The endpoint was the overall survival and the survival from the 1st oncothermia treatment (survival from the relapse untreatable by other methods). The median/mean survival times were 19.8/31.7 and 6.7/10.0 months from 1st diagnosis and from 1st oncothermia, respectively. Results support the feasibility of oncothermia for advanced brain-glioma patients.

 

Table 4. The main statistical characters by the RTOG division
 
The results could be well compared to the available SEER data. Comparison of the OST of our retrospective 140 patients and SEER retrospective 28.970 patients, as well as by grade categories, shown in Table 5. The gain of the MST OST in various categories is 38,6 %, 146% and 57.0 % for DA, AA and GBM patients, respectively.
Table 5. Comparison of the data of SEER and our present study.
 
In one of a recent publication, the 1 and 2 year survivals with TMZ shows 58% and 31%, respectively. Compare these results with ours, the gain is also remarkable. 71.7 % (66/92) and 30.4 % (28/92) for 1 and 2 years survival, respectively. (The two-year survival for GBM by RTOG study (no TMZ application) is only 17%, [22].) The most recent TMZ randomized clinical trial for GBM, summarizing the results of 573 patients from 85 cooperating centers shows a gain of MST from 12.1 m (without TMZ) to 14.6 m (with TMZ). A former TMZ results were similar, having MST in only RT group (n=24) 11.2 m, RT+CT (not TMZ) group (n=32) 12.7 m and for RT+TMZ group (n=23) 14.9 m. The two-year survival in the new study [25] increased form 10.4% (without TMZ) to 26.5% (with TMZ). Our present results were even better than the presently published best TMZ applications.
The long term survival of GBM is very rare, about over three years is only 1.8% is a 279 patients trial. In our case from 92 GBM patient 13 (14.1 %) had longer OST than 3 years, which is a remarkable gain.
Studying the MRI images we have some indicative hints to suppose an extended apoptosis initialized by the oncothermia. This could be in good correspondence with some theoretical considerations as well as with some experimental facts. More considerable investigations on this line are in progress.
The presented results are well comparable with the oncothermia results published earlier on smaller groups (n=35) [13], and (n=17) of patient by another research group.
Conclusions
The results are well indicating the feasibility and the benefit of the oncothermia treatment by numerous reasons:
1.      Oncothermia was applied for brain tumors, showing a valid treatment potential and safe application.
2.      Transcranially applied non-invasive electric field is able to perform the treatment.
3.      No safety or mentionable toxicity problem was occur. The oedema development, which was the general block of hyperthermia applications in the past, is not the case with oncothermia. Was no any eye-damage and/or vision-complication which was also a risk in the radiative hyperthermia methods. The treatment is safe and convenient to use.
4.      The survival time, as one of the most important parameters, was increased for the patients having no other treatment possibilities.
5.      The quality of life of anyone of the oncothermia treated patients were not worsen, even according to their subjective reports, the quality of life was considerable increasing in most of the cases. (No objective evaluation was done yet.)
According to our present retrospective study on a relatively large number (n=140) of brain-glioma patients, the electro-hyperthermia is feasible to treat anaplastic astrocytoma and glioblastoma multiforme. Electro-hyperthermia is a potential way to escape from the present impasse situation to treat successfully brain gilomas. Comparison of the presently indicated data to the expected historical ones given from the large databases, shows a remarkable increase of the overall survival. As well as the method is safe and stable; it is easy to use and well tolerated by the patients.

Our present data are only retrospective indications of the efficacy of Electro-hyperthermia method. Prospective, randomized, controlled double-arm clinical study is necessary for the evidence-based evaluation. The study is in progress.



[[1]] Ries LAG, Eisner MP, Kosary CL, et al (eds): SEER Cancer Statistics, 1973-1998. Bethesda, MD, National Cancer Institute, 2001
[[1]] Stupp R, Dietrich PY, Kraljevic SO, et al. Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide. JCO 2002 ; 20:5: 1375-1382
[[1]] Walker MD, Alexander E Jr, Hunt WE, et al: Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: A cooperative clinical trial. J Neurosurg 1978; 49: 333-343
[[1]] Kristiansen K, Hagen S, Kollevold T, et al: Combined modality therapy of operated astrocytomas grade III and IV: Confirmation of the value of postoperative irradiation and lack of potentiation of bleomycin on survival time; A prospective multicenter trial of the Scandinavian Glioblastoma Study Group. Cancer 1981; 47: 649-652
[[1]] Sakaguchi Y, Stephens LC, Makino M, Kaneko T, Strebel FR, Danhauser LL, JenkinsGN, Bull JM: Apoptosis in tumors and normal tissues induced by whole body hyperthermia in rats. Cancer Res 57:5459-64, 1995
[[1]] Friedlander DR, Zagzag D, Shiff B et al. Migration of brain tumor cells on extracellular matrix proteins in vitro correlates with tumor type and grade and involves alphaV and beta1 integrins. Cancer Res. 56:1939-47, 1996
[[1]] Eikesdal HP, Bjorkhaug ST, Dahl O. Hyperthermia exhibits anti-vascular activity in the s.c. BT4An rat glioma: lack of interaction with the angiogenesis inhibitor batimastat. Int. J. Hyperthermia. 18(2):141-52, 2002
[[1]] Fisher PG, Buffler PA: Malignant gliomas in 2005. Where to GO from here?, Editorials, JAMA 293:615-617, 2005.
[[1]] Hermisson M, Weller M. Hyperthermia enhanced chemosensitivity of human malignant glioma cells. Anticancer Res. 20(3A):1819-23, 2000
[[1]] Ley-Valle A: .Non invasive intracranial hyperthermia with Electric Capacitive Transference -ECT- Intratumoral and cerebral thermometry results, Neurocirugia (Astur). 14(1):41-45, 2003
[[1]] Sneed PK, Stauffer PR, McDermott MW, Diederich CJ, Lamborn KR, Prados MD, Chang S, Weaver KA, Spry L, Malec MK, Lamb SA, Voss B, Davis RL, Wara WM, Larson DA, Phillips TL, Gutin PH.: Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme, Int J Radiat Oncol Biol Phys. 1998 Jan 15; 40(2):287-95
[[1]] Sahinbas H, Groenemeyer DHW. Boecher E, et al. Hyperthermia treatment of advanced relapsed glioma and astrocytoma 9th ICHO 2004.page;85
[[1]] D. Hager, H. Dziambor, E. M. App et al. The treatment of patients with high-grade malignant gliomas with RF-hyperthermia . 39th ASCO Annual Meeting. 2003 (Abstract No. 470)
[[1]] Kurzen H, Schmitt S, Naher H et al. Inhibition of angiogenesis by non-toxic doses of temozolomide. Anticancer Drugs; 14(7):515-22, 2003
[[1]] Pagani E, Falcinelli R, Repponi R et al. Combined effects of temozolamide- hyperthermia on cell growth and O6-Alkylguanine-DNA alkyltransferase (OGAT) activity of human melanoma cell lines. Antican. Resrch 1998; 18 (237):4807-5006
[[1]] D. Hager, H. Dziambor, E. M. App et al. The treatment of patients with high-grade malignant gliomas with RF-hyperthermia 39th ASCO Annual Meeting. 2003 (Abstract No. 470).
[[1]] A.Szasz, H.Sahinbas, A.Dani: Electro- hyperthermia for anaplastic astrocytoma and gliobastoma multiforme ICACT 2004, Paris, 9-12. February, 2004
[[1]] Sahinbas H, Groenemeyer DHW. Boecher E, et al. Hyperthermia treatment of advanced relapsed glioma and astrocytoma . 9th ICHO 2004.page;85.
[[1]] Davis DL, Ahlborn A, Hoel D, et al: Is brain cancer mortality increasing in industrial countries? Am.J.Ind.Med. 19:421-431, 1991
[[1]] Greig NH, Ries LG, Yancik R , et al: Increasing Annual Incidence of Primary Malignant Brain Tumors in the Elderly. Natl. Canc. Inst. 82:1621-1624, 1990
[[1]] Karatsu J, Ushio Y: Epidemiological study of primary intracranial tumours in elderly people, Journal of Neurology, Neurosurgery and Psychiatry, 63:116-118, 1977
[[1]] Scott CB, Scarantino C, Urtasun R, et al: Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: A report using RTOG 90-06. Int J Radiat Oncol Biol Phys 40:51-55, 1998
[[1]] Surveillance, Epidemiology, and End Results (SEER), National Cancer Institute, April 2000,
www-seer.cancer.gov
[[1]] Stupp R, Dietrich P-Y, Kraljevic SO, Pica A, Maillard I, Maeder P, Meuli R, Janzer R, Pizzolato G, Mirabell R, Porchet F, Regli L, deTribolet N, Miramanoff RO, Leyvraz S: Promising survival for patients with newly diagnosed clioblastoma multiforme treated with concomitant radiation plus temi=ozolomide followed by adjuvant temozolomide, J. Clin. Oncol. 20:1375-1382, 2002
[[1]] Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn, MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma, The New England J. of Med., 352:987-996, 2005
[[1]] Alba A. Brandes, Francesca Vastola, et.al.: A prospective study on glioblastoma in the elderly, Am. Cancer Society, 97:3 February 1, 2003
[[1]] Scott JN, Rewcastle NB, Brasher PMA, Fulton D, Hagen NA, MacKinnon JA, Sutherland G, Cairncross JG, Forsyth P: Long-term glioblastoma multiforme survivors: a population-based study, Can. J. Neurol. Sci. 25:197-201, 1998
[[1]] Chen JW, Lin J, Madamanchi N, Trier TT, Campbell G: Apoptosis occurs in a new model of thermal brain injury, J. Biomed. Sci. 7:459-465, 2000
[[1]] Fuse T, Yoon K-W, Kato T, Yamada K: Heat-induced apoptosis in human glioblastoma cell-line A172, Neurosurgery 42:843-849, 1998
[[1]] Andocs G, Szasz A: Preliminary results of Oncothermia induced apoptosis in nude-mouse inoculated human-glioblastoma cells, Results of hyperthermia, Seminar, St. Istvan University, Aug. 24., 2005. (in Hungarian)
[[1]] Vogel P, Dux E, Wiessner C: Evidence of apoptosis in primary neuronal cultures after heat shock, Brain Res. 764:205-213, 1997
[[1]] Dani A, Varkonyi A: Electro-hyperthermia treatment of malignant brain tumors, Results of hyperthermia, Seminar, St. Istvan University, Aug. 26-27., 2003. (in Hungarian) 

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