Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue

Valenberg, F Johannes P van; Heijden, Antoine G. van der; Lammers, Rianne J.M.; Falke, J.; Arends, T.J.H.; Oosterwijk, Egbert; Witjes, J. Alfred

doi:10.1080/02656736.2017.1406618

Cited by 19 publications

(14 citation statements)

References 25 publications

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“…Healthy urothelial mucosa has been shown to be less permeable than tumor tissue, hence we believe that intravesical chemotherapy with HT may actually result in an even greater increase of MMC absorption in patients with bladder cancer than demonstrated in our study [17]. Our findings deferred from van Valenberg et al, where they found that MMC concentration did not differ between the cold MMC group and radiofrequency induced MMC group in normal urothelial tissue [15]. This could be attributed to the usage of the Synergo system, which utilizes a 915 MHz antenna to heat the chemotherapeutic agent in the bladder, while having the drug solution constantly pumped out of the bladder and re-instilled after being cooled by the device.…”

Section: Discussioncontrasting

confidence: 56%

“…Hyperthermia therapy has been shown to improve cancer cell sensitivity to therapeutic agents, cause direct cytotoxicity, trigger anti-cancer immune responses and improve drug delivery for various chemotherapeutic agents to the bladder [12,13,15,16]. Multiple clinical trials treating patients with bladder cancer with intravesical chemotherapy and HT have shown promising results in both the adjuvant setting as well as neoadjuvant setting.…”

Section: Discussionmentioning

confidence: 99%

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Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study

Tan

Chang

Brousell

et al. 2020

International Journal of Hyperthermia

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Background: Hyperthermia (heating to 43 C) activates the innate immune system and improves bladder cancer chemosensitivity. Objective: To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) pharmacokinetics in live porcine bladder models using the Combat bladder recirculation system (BRS). Methods: Forty 60 kg-female swine were anesthetized and catheterized with a 3-way, 16 F catheter. The Combat device was used to heat the bladders to a target temperature of 43 C with recirculating intravesical MMC at doses of 40, 80, and 120 mg. Dwell-heat time varied from 30-180 min. Rapid necropsy with immediate flash freezing of tissues, blood and urine occurred. MMC concentrations were measured by liquid chromatography tandem-mass spectrometry. Results: The Combat BRS system was able to achieve target range temperature (42-44 C) in 12 mins, and this temperature was maintained as long as the device was running. Two factors increased tissue penetration of MMC in the bladder: drug concentration, and the presence of heat. In the hyperthermia arm, MMC penetration saturated at 80 mg, suggesting that with heating, drug absorption may saturate and not require higher doses to achieve the maximal biological effect. Convective hyperthermia did not increase the MMC concentration in the liver, heart, kidney, spleen, lung, and lymph node tissue even at the 120 mg dose. Conclusions: Convective bladder hyperthermia using the Combat BRS device is safe and the temperature can be maintained at 43 C. Hyperthermia therapy may increase MMC penetration into the bladder wall but does not result in an increase of MMC levels in other organs.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study

Tan

Chang

Brousell

et al. 2020

International Journal of Hyperthermia

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“…The two different technologies used in our study in combination with the bladder anatomy may explain the observed differences in heating capacity. Ultimately, the goal of hyperthermia is to have a higher treatment efficacy through an increased drug tumor tissue penetration [28]. Therefore, it would be interesting to compare the resulting efficacy of both RF-HT and C-HT in a clinical setting and correlate it to the achieved tissue-drug concentrations and temperatures.…”

Section: Discussionmentioning

confidence: 99%

Inducing intravesical hyperthermia of the ex-vivo porcine bladder wall: radiofrequency-induction versus recirculation using a custom-made device

Valenberg

Witjes

Aklan

et al. 2018

International Journal of Hyperthermia

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Introduction: Several techniques can be used to treat intravesical chemohyperthermia (ChHT). We compared radiofrequency-induced hyperthermia (RF-HT) with conductive hyperthermia (C-HT) for their ability to induce bladder wall temperatures of >40.5 C, the target temperature for ChHT. Materials and Methods: Fresh porcine bladders (n ¼ 12) were placed in a temperature-controlled saline bath to simulate body temperature and circulation. HT was induced with RF-HT (43 C) or C-HT (inflow temperature 44 and 46 C) using a custom-made device. In two additional bladders, we varied intravesical solution and volume. Temperatures were recorded with a three-way catheter containing three mucosal and two urethral thermocouples (TCs) and a 915 MHz RF antenna, and with external TCs in the bladder wall at three different levels and three different locations. Results: Target temperature (40.5 C) was reached in the submucosa at all locations by both techniques. In the detrusor, target temperature was reached by RF-HT at the bladder neck and side wall. C-HT 46 reached significantly higher submucosal temperatures at the side wall. The bladder dome seemed best heated by C-HT, although a high inflow temperature (46 vs. 44 C) was required (ns). Intravesical saline resulted in higher temperatures than sterile water for RF-HT. A volume of 100 mL resulted in higher bladder dome temperatures for RF-HT, and higher bladder neck with lower dome temperatures for C-HT. Conclusion: Our results indicate a slightly superior heating capacity for RF-HT compared to C-HT, whereas for the bladder dome, the reverse seems true. Comparative studies are warranted to evaluate whether HT efficacy differs between both techniques, with emphasis on tumor location.

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“…Additionally, HT can potentiate the effect of DOX due to increased tissue penetration and induction of an immune response. 31,32 Administration of DPPG 2 -TSL-DOX was combined with bladder HT to investigate whether this results in higher and more homogeneous distributed DOX concentration in the bladder wall, while limiting DOX concentration in essential organs, compared to conventional DOX application (ie, iv administration, intravesical instillation and CHT). Since the physiology and urinary tract anatomy of pigs closely resembles that of humans, a pig bladder model was used.…”

Section: Introductionmentioning

confidence: 99%

DPPG2-Based Thermosensitive Liposomes with Encapsulated Doxorubicin Combined with Hyperthermia Lead to Higher Doxorubicin Concentrations in the Bladder Compared to Conventional Application in Pigs: A Rationale for the Treatment of Muscle-Invasive Bladder Cancer

Valenberg¹,

Brummelhuis²,

Lindner³

et al. 2021

IJN

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Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue

Abstract: Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.

Cited by 19 publications

References 25 publications

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study

Inducing intravesical hyperthermia of the ex-vivo porcine bladder wall: radiofrequency-induction versus recirculation using a custom-made device

DPPG2-Based Thermosensitive Liposomes with Encapsulated Doxorubicin Combined with Hyperthermia Lead to Higher Doxorubicin Concentrations in the Bladder Compared to Conventional Application in Pigs: A Rationale for the Treatment of Muscle-Invasive Bladder Cancer

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