Browsing by Author "Longo, Thomas A"

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    ItemOpen Access
    Bone scan positivity in non-metastatic, castrate-resistant prostate cancer: external validation study.
    (International braz j urol : official journal of the Brazilian Society of Urology, 2020-01) Johnston, Ashley W; Longo, Thomas A; Davis, Leah Gerber; Zapata, Daniel; Freedland, Stephen J; Routh, Jonathan C

    Introduction

    Tables predicting the probability of a positive bone scan in men with non-metastatic, castrate-resistant prostate cancer have recently been reported. We performed an external validation study of these bone scan positivity tables.

    Materials and methods

    We performed a retrospective cohort study of patients seen at a tertiary care medical center (1996-2012) to select patients with non-metastatic, castrate-resistant prostate cancer. Abstracted data included demographic, anthropometric, and disease-specific data such as patient race, BMI, PSA kinetics, and primary treatment. Primary outcome was metastasis on bone scan. Multivariable logistic regression was performed using generalized estimating equations to adjust for repeated measures. Risk table performance was assessed using ROC curves.

    Results

    We identified 6.509 patients with prostate cancer who had received hormonal therapy with a post-hormonal therapy PSA ≥2ng/mL, 363 of whom had non-metastatic, castrate-resistant prostate cancer. Of these, 187 patients (356 bone scans) had calculable PSA kinetics and ≥1 bone scan. Median follow-up after castrate-resistant prostate cancer diagnosis was 32 months (IQR: 19-48). There were 227 (64%) negative and 129 (36%) positive bone scans. On multivariable analysis, higher PSA at castrate-resistant prostate cancer (4.67 vs. 4.4ng/mL, OR=0.57, P=0.02), shorter time from castrate-resistant prostate cancer to scan (7.9 vs. 14.6 months, OR=0.97, P=0.006) and higher PSA at scan (OR=2.91, P<0.0001) were significantly predictive of bone scan positivity. The AUC of the previously published risk tables for predicting scan positivity was 0.72.

    Conclusion

    Previously published risk tables predicted bone scan positivity in men with non-metastatic, castrate-resistant prostate cancer with reasonable accuracy.
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    Heated Intravesical Chemotherapy: Biology and Clinical Utility.
    (The Urologic clinics of North America, 2020-02) Tan, Wei Phin; Longo, Thomas A; Inman, Brant A
    Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.
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    Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.
    (International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, 2020-01) Tan, Wei Phin; Chang, Andrew; Brousell, Steven C; Grimberg, Dominic C; Fantony, Joseph J; Longo, Thomas A; Etienne, Wiguins; Spasojevic, Ivan; Maccarini, Paolo; Inman, Brant A

    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.