Image-guided cancer therapy is becoming an important new development in patient care, linking traditional methods with innovative techniques to detect and treat many forms of cancer. Advances in minimally invasive cancer treatments include ablation devices such as radiofrequency, microwave, laser, focused ultrasound and cryoablation, which not only help improve patient care, but also offer the potential to reduce overall healthcare costs.
Professor Damian Dupuy, Rhode Island Hospital, Rhode Island, presented a talk at the recent World Congress of Interventional Oncology (WCIO) meeting in Washington, DC, entitled, 'New/novel applications with radiofrequency and microwave energy'. The aim of his lecture was to discuss innovative technologies such as multi-probe heat-based ablation devices and novel imaging technologies, and also to discuss synergistic roles of chemo/XRT and ablation.
New developments in extreme hyperthermia
According to Dupuy, there have been three significant developments in extreme hyperthermia for cancer indications. These include:
Multi-probe ablation devices (radiofrequency and microwave)
Combination therapies
Guidance and imaging
Multi-probe radiofrequency (RF) ablation devices (eg. Valleylab, Celon) increase the opportunity to ablate larger tumours, or up to three separate lesions at a time, usually under ultrasound (US) and computerised tomography (CT) guidance. This technology can also ablate multiple small tumours and tumours close to vessels, without harming non-target areas, explained Dupuy. Microwave ablation uses high frequency electromagnetic waves and oscillation of polar molecules produces frictional heating. Dupuy mentioned that no electrical current is required to operate this device, therefore no grounding.
Multiple applicators enable a highly efficient method of ablating tumours over 3cm, multiple small tumours, tumours close to vessels (heat sink) and procedure time is normally reduced.
Combination approaches
Currently, there are three major heat ablation combination approaches for treatment of tumours. These include combining heat ablation with: radiation, chemotherapy and biologicals.
As Dupuy explained, combining RF ablation with radiation has the ability to ablate hypoxic tumour, reduce number of clonogens, alter cell cycle kinetics and can also alter the microenvironment inhibiting proliferation and survival in tumour cells.
Radiofrequency combined with brachytherapy is another combination therapy particularly useful for treatment of smaller tumours, <3cm. Typically, a 6F brachytherapy catheter is used and single fraction of 18 gray with high dose rate Iridium-19. Dupuy explained that this combination treatment capitalises on 'classic' hyperthermia effects.
He then briefly discussed the combination of RF ablation with chemotherapy eg. Doxil for large (eg. 8cm) hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC), followed by transarterial chemoembolisation (TACE) combined with microwave ablation, also for treatment of HCC. Both methods have shown high local tumour control rates in medically inoperable patients. Sorafenib (Bayer) is a biological agent that has displayed positive outcomes when combined with RF, said Dupuy. Sorafenib has received FDA approval (2005) and EU marketing authorisation (2006) for the treatment of advanced renal cell carcinoma and has also received 'Fast Track' designation by the FDA for the treatment of advanced HCC. In a recent article published in the New England Journal of Medicine ('sorafenib in advanced clear-cell renal-cell carcinoma') in January 2007, Dr B Escudier et al., France, conducted a Phase III, randomised, double-blind, placebo controlled trial of sorafenib in patients with advanced clear-cell renal cell carcinoma in whom previous therapy had failed.
From November 2003 to March 2005, 903 patients randomly received either continuous treatment with oral sorafenib or placebo (451 patients received sorafenib, 452 received placebo). At the first interim analysis of overall survival in May 2005, the results showed that sorafenib reduced the risk of death, as compared with placebo, although, according to the authors, this benefit was not statistically significant due to the O'Brien-Fleming threshold. Partial responses were reported as the best response in 10% of patients receiving sorafenib and in 2% of those receiving placebo, Escudier reported.
In summary, the authors showed that, "as compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma, however, treatment is associated with increased toxic effects [eg. hand-foot skin reactions, diarrhoea, rash and fatigue]."
Imaging
Dupuy concluded his lecture by emphasising the importance of imaging. Imaging allows for:
Guidance - safe and accurate
Monitoring - treatment of target area
Follow-up - to ensure the target area is dead
According to Dupuy, electromagnetic (EM) navigation (eg. Veran Medical) is a novel technology that increases precision of therapy deliver, reduces radiation exposure and time, increases safety, improves accuracy, provides assistance to less experienced operators and allows for standardisation or therapy delivery and patient care.
Conclusions
In conclusion, Dupuy stated that, "RF ablation and microwave applicator technologies are clearly improving cancer therapy in many patients. Combining them with other cancer therapies appears very promising. Integrating high-end imaging and guidance algorithms should further improve outcomes."
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