Electric Field Therapy and Photodynamic Therapy
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Electric Field Therapy and Photodynamic Therapy

by Stephen Western
Astrocytoma Options.com

Tumor Treating Fields

NovoTTF (Tumor Treating Fields) is an innovative glioma therapy developed by Novocure Ltd. based in Israel. The system consists of "a portable device delivering low intensity, intermediate frequency, alternating electric fields using non-invasive, disposable transducer arrays" worn on the patient's shaved head for 22 hours per day (breaks allowed for showers). Four weeks is considered to be the minimum interval to reverse tumour growth. The electric fields interfere with active cell division, leading to disruption of chromosome segregation and eventually to cell death.

A recent phase III trial led by Roger Stupp compared NovoTTF alone to physician's choice chemotherapy in recurrent glioblastomas (1). Significantly, 6 month progression-free survival and response rate favored NovoTTF. As well, there was less toxicity and improved quality of life in the NovoTTF group compared to the chemotherapy group. Skin rash beneath the transducer array was the most noted side-effect for NovoTTF treatment. Patients in this trial underwent a median of four cycles (of four weeks per cycle) with the NovoTTF device.

It is expected that adding NovoTTF to conventional chemotherapy will significantly increase median survival for glioblastoma, and there is currently a phase III trial underway to test NovoTTF plus temozolomide for newly diagnosed glioblastoma, with an estimated study completion date of April 2015.

A news article appearing on Bloomberg.com in 2010 reveals that use of the device costs $10,000 to $15,000 per month (2).

Photodynamic Therapy

The first glioma treatment with photodynamic therapy happened in 1980. Since then, thousands of glioma patients have been treated with this modality at the time of first surgery or repeat surgery. Photodynamic therapy consists of two phases. First, hours prior to surgery, a photosensitizing agent (often porphyrin based) is intravenously injected into the patient and tumour cells selectively take up this agent. Secondly, after surgical resection of the tumour, laser light is applied to the resection cavity. The tumour cells are primarily killed off during this treatment with singlet oxygen, which is a result of the interaction between the photosensitizer and the laser light (3).

An impressive retrospective study of 136 anaplastic astrocytoma and glioblastoma patients (both newly diagnosed and recurrent) treated in Melbourne, Australia between 1986 and 2000 has been published (4).

Most impressively, 29 recurrent anaplastic astrocytoma patients (median age 35) had a median survival of 66.6 months from the time of repeat surgery. By Kaplan Meier estimate, 35% of these patients survived to 15 years beyond repeat surgery. For recurrent anaplastic astrocytomas, this is by far the longest median survival statistic from the time of recurrence that I've encountered in the literature for any therapy.

Another retrospective study which included 96 primary glioma patients (grades III and IV) treated with photodynamic therapy at St. Michael's Hospital in Toronto, showed much less impressive results (5). In this study, 24 anaplastic astrocytoma patients (median age 44, both newly diagnosed and recurrent) had a median survival of 50 weeks (11.5 months). This is roughly 6-fold shorter median survival than the patients in the previously mentioned study.

If we look at the details of these two studies for comparison, two outstanding differences were the dosage of photosensitizer applied, and the intensity of light used. In the Australian study, patients received 5 mg haematoporphyrin derivative per kg body weight. In the Canadian study, patients received only 2 mg of Photofrin (similar to haematophorphyrin derivative) per kg body weight. An even larger difference occurred in the intensity of light applied. The Australian study used a median dose of 230 Joules of laser light per square centimeter, with only 11% of patients receiving less than 150 Joules. The Canadian study used a median of only 58 Joules per square centimeter, with the highest dose being 150 Joules. This striking difference in laser intensity perhaps explains the equally striking difference in survival outcomes observed between these two retrospective studies.

References

  1. Novo TTF-100A versus physican’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Stupp et al. 2012.
    READ SOURCE DOCUMENT

  2. Electric helmet slows brain tumors without chemotherapy’s side effects. Tom Randall. 2010.
    READ SOURCE DOCUMENT

  3. Photodynamic therapy of cerebral glioma - a review. Part II - clinical studies. Stylli et al. 2006.
    READ SOURCE DOCUMENT (abstract only)

  4. Photodynamic therapy of high grade glioma - long term survival. Stylli et al. 2005.
    READ SOURCE DOCUMENT (PDF)

  5. Photodynamic therapy of brain tumors - a work in progress. Muller et al. 2006.
    READ SOURCE DOCUMENT (abstract only)


This page was created on 12/15/2013 and last updated on 12/15/2013



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