Thursday, December 11, 2008

Hyperthermia in the Netherlands

Dr. Maarten Paulides from Erasmus in the Netherlands - an engineer associated with their Hyperthermia project - spoke about their current clinical efforts.

Background
12- year update of the netherlands deep ht trail
114 pts with locally advanced cervical cancer
1990-1996
ebrt + brachytherapy in all patients to 68-70Gy to point A
randomized to ht once weekly with heating goal of 42 degrees C for 60 minutes
local control 37% rt vs 56% rtht (p=0.001)
overall survival 20% rt vs 37% rtht (p=0.03)
actuarial > grade ii late toxicity was no different between arms

This is one of the strongest trials supporting a clinical benefit to hyperthermia with radiation therapy in the curative settting.  The primary weakness is that this trial occurred prior to the NCI alert in 1999 supporting the use of concurrent cisplatin based chemotherapy.

This weakness is addressed in an ongoing multi-institutional trial, currently open at Duke, exploring radiation therapy with concurrent cddp based chemo, plus or minus hyperthermia.

Current HT Clinic load at Erasmus:
deep ht - ~100 patients/year - 1.5 hour treatment time (0.5 hours of this is warm up), treated once weekly.
superficial ht - ~60 patients/year - 1 hour treatment times (0.25 hours for warmup), treated once weekly.

Ongoing ht trials at erasmus:
phase iii cervix trial (noted above)
recurrent rectal cancer: capcetabine + HT in previously irradiated patients
developing head and neck applicator

Head and Neck

Dr. Paulides referenced the below as backgound.
small randomized trial of RT +/- HT in locally advanced head and neck cancers
in 44 nodes (41 patients) the response rate was 41% rt vs 83% rtht
this trial also reported improve nodal control and overall survival at 5 years, though one must take the number of patients into account.

With this backdrop, the physicists and engineers at Erasmus have been developing a head and neck collar applicator for hyperthermia delivery, which has now been used for treating patients.  Monitoring is a bit of a problem as many of these sites are not accessible or amenable to invasive thermometry.  Addtitionally cooling from vasculature and respiration may confound attempts for homogeneous heating of the target.  However, he was able to show that this could be done, and I for one was quite surprised that they were implementing this in patients already, including a nasopharyngeal patient which he showed the thermometry for.  

Link to an Abstract describing the applicator (the Hypercollar): http://www.esho.info/esho2007/pdf/paulides1_esho2007.pdf

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