Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme

Leonard Farber, MD and Kenneth Blank, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

Authors: Sneed PK, Stauffer PR, McDermott MW, et. al.
Source: International Journal of Radiation Oncology, Biology and Physics, 15 January 1998, Volume 40 number 2 p287

Glioblastomas are among the most aggressive of human cancers. These tumors of the brain have a median survival of approximately one year despite the best treatment. Current standard treatment of glioblastomas includes surgery, radiation and chemotherapy. One strategy that has been extensively studied at the University of California San Francisco (UCSF) is the addition of a brachytherapy boost to conventional radiotherapy. Brachytherapy involves the placement of radioactive seeds into the tumor bed at the time of surgery. This treatment allows a high dose of radiation to be given to the tumor bed but spares the surrounding brain tissue.

Another treatment method under study is hyperthermia which involves elevating tissue temperature above 41 degrees Celsius. Hyperthermia not only kills tumor cells directly but may also make cells more sensitive to radiation by inducing re-oxygenation. Several non-randomized studies which demonstrated a benefit to treating glioblastomas with hyperthermia led the Brain Tumor Research Group to conduct a randomized prospective trial which is reported in the January 15, 1998 issue of the International Journal of Radiation Oncology, Biology and Physics.

From 1990 to 1995 112 patients were enrolled on this trial. All patients received surgery and external beam radiotherapy. Patients who were eligible for a brachytherapy boost were randomized to receive 30 minutes of hyperthermia before and after the boost or no hyperthermia. Thirty-three of the 112 patients were not randomized, most commonly because of tumor progression, leaving forty patents who received hyperthermia and thirty-nine who did not. Those patients who underwent hyperthermia had significantly longer survival times and time before progression. Two year survivor rates were 31% in the hyperthermia arm versus 15% in the no hyperthermia group.

This is the first North American trial showing a benefit to hyperthermia. Further studies are warranted before a change in the standard of care of glioblastomas will include hyperthermia, but the results reported here are very encouraging.