Utility of treatment planning for thermochemotherapy treatment of nonmuscle invasive bladder carcinoma.

PURPOSE A recently completed Phase I clinical trial combined concurrent Mitomycin-C chemotherapy with deep regional heating using BSD-2000 Sigma-Ellipse applicator (BSD Corporation, Salt Lake City, UT, U.S.A.) for the treatment of nonmuscle invasive bladder cancer. This work presents a new treatment planning approach, and demonstrates potential impact of this approach on improvement of treatment quality. METHODS This study retrospectively analyzes a subset of five patients on the trial. For each treatment, expert operators selected "clinical-optimal" settings based on simple model calculation on the BSD-2000 control console. Computed tomography (CT) scans acquired prior to treatment were segmented to create finite element patient models for retrospective simulations with Sigma-HyperPlan (Dr. Sennewald Medizintechnik GmbH, Munchen, Germany). Since Sigma-HyperPlan does not account for the convective nature of heat transfer within a fluid filled bladder, an effective thermal conductivity for bladder was introduced. This effective thermal conductivity value was determined by comparing simulation results with clinical measurements of bladder and rectum temperatures. Regions of predicted high temperature in normal tissues were compared with patient complaints during treatment. Treatment results using "computed-optimal" settings from the planning system were compared with clinical results using clinical-optimal settings to evaluate potential of treatment improvement by reducing hot spot volume. RESULTS For all five patients, retrospective treatment planning indicated improved matches between simulated and measured bladder temperatures with increasing effective thermal conductivity. The differences were mostly within 1.3 °C when using an effective thermal conductivity value above 10 W/K/m. Changes in effective bladder thermal conductivity affected surrounding normal tissues within a distance of ∼1.5 cm from the bladder wall. Rectal temperature differences between simulation and measurement were large due to sensitivity to the sampling locations in rectum. The predicted bladder T90 correlated well with single-point bladder temperature measurement. Hot spot locations predicted by the simulation agreed qualitatively with patient complaints during treatment. Furthermore, comparison between the temperature distributions with clinical and computed-optimal settings demonstrated that the computed-optimal settings resulted in substantially reduced hot spot volumes. CONCLUSIONS Determination of an effective thermal conductivity value for fluid filled bladder was essential for matching simulation and treatment temperatures. Prospectively planning patients using the effective thermal conductivity determined in this work can potentially improve treatment efficacy (compared to manual operator adjustments) by potentially lower discomfort from reduced hot spots in normal tissue.

[1]  H P Kok,et al.  Optimization in hyperthermia treatment planning: the impact of tissue perfusion uncertainty. , 2010, Medical physics.

[2]  H. H. Pennes Analysis of tissue and arterial blood temperatures in the resting human forearm. 1948. , 1948, Journal of applied physiology.

[3]  J. Lagendijk,et al.  Towards patient specific thermal modelling of the prostate , 2006, Physics in Medicine and Biology.

[4]  P. Rigatti,et al.  Neoadjuvant combined microwave induced local hyperthermia and topical chemotherapy versus chemotherapy alone for superficial bladder cancer. , 1996, The Journal of urology.

[5]  J Crezee,et al.  The theoretical and experimental evaluation of the heat balance in perfused tissue. , 1994, Physics in medicine and biology.

[6]  M. Desai,et al.  Phase I Trial of Intravesical Docetaxel in the Management of Superficial Bladder Cancer Refractory to Standard Intravesical Therapy , 2006 .

[7]  S. Weinbaum,et al.  A new simplified bioheat equation for the effect of blood flow on local average tissue temperature. , 1985, Journal of biomechanical engineering.

[8]  C Gabriel,et al.  The dielectric properties of biological tissues: I. Literature survey. , 1996, Physics in medicine and biology.

[9]  [Study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrences of superficial tumors of the bladder]. , 1999, Progres en urologie : journal de l'Association francaise d'urologie et de la Societe francaise d'urologie.

[10]  J. van der Zee,et al.  Steering in locoregional deep hyperthermia: Evaluation of common practice with 3D-planning , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[11]  Kenneth R. Holmes,et al.  MICROVASCULAR CONTRIBUTIONS IN TISSUE HEAT TRANSFER , 1980, Annals of the New York Academy of Sciences.

[12]  R L Levin,et al.  An evaluation of the Weinbaum-Jiji bioheat equation for normal and hyperthermic conditions. , 1990, Journal of biomechanical engineering.

[13]  L. Blank,et al.  Results of deep body hyperthermia with large waveguide radiators. , 1990, Advances in experimental medicine and biology.

[14]  M. Seebass,et al.  Impact of nonlinear heat transfer on temperature control in regional hyperthermia , 1999, IEEE Transactions on Biomedical Engineering.

[15]  F. Longo,et al.  Interaction of ultrasonic hyperthermia with two alkylating agents in a murine bladder tumor. , 1983, Cancer research.

[16]  O. Nativ,et al.  Thermo-chemotherapy for intermediate or high-risk recurrent superficial bladder cancer patients. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  K R Foster,et al.  Heat transport mechanisms in vascular tissues: a model comparison. , 1986, Journal of biomechanical engineering.

[18]  Peter Schlag,et al.  Clinical use of the hyperthermia treatment planning system HyperPlan to predict effectiveness and toxicity. , 2003, International journal of radiation oncology, biology, physics.

[19]  R. Hall,et al.  Effects of Hyperthermia on Bladder Cancer , 1974, British medical journal.

[20]  J. Mooibroek,et al.  Hyperthermia treatment planning. , 1986 .

[21]  Olaf Minet,et al.  Specific heat capacities of human and animal tissues , 1996, European Conference on Biomedical Optics.

[22]  R. W. Lau,et al.  The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues. , 1996, Physics in medicine and biology.

[23]  R. Rietbroek,et al.  Feasibility, toxicity, and preliminary results of weekly loco-regional hyperthermia and cisplatin in patients with previously irradiated recurrent cervical carcinoma or locally advanced bladder cancer. , 1996, International journal of radiation oncology, biology, physics.

[24]  P. Rigatti,et al.  A new approach using local combined microwave hyperthermia and chemotherapy in superficial transitional bladder carcinoma treatment. , 1995, The Journal of urology.

[25]  Paolo F Maccarini,et al.  Improved hyperthermia treatment control using SAR/temperature simulation and PRFS magnetic resonance thermal imaging , 2011, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[26]  R. W. Lau,et al.  The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. , 1996, Physics in medicine and biology.

[27]  K R Foster,et al.  Perfused phantom models of microwave irradiated tissue. , 1986, Journal of biomechanical engineering.

[28]  P. Deuflhard,et al.  Clinical evaluation and verification of the hyperthermia treatment planning system hyperplan. , 2000, International journal of radiation oncology, biology, physics.

[29]  J. Witjes,et al.  Combined local bladder hyperthermia and intravesical chemotherapy for the treatment of high-grade superficial bladder cancer. , 2004, Urology.

[30]  Jeffery H. Wootton,et al.  Optimisation-based thermal treatment planning for catheter-based ultrasound hyperthermia , 2010, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[31]  J Crezee,et al.  Dose uniformity in MECS interstitial hyperthermia: the impact of longitudinal control in model anatomies. , 1996, Physics in medicine and biology.

[32]  T. Kenner,et al.  The measurement of blood density and its meaning , 1989, Basic Research in Cardiology.