Browsing by Author "Grimberg, Dominic C"

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    Assessments of frailty in bladder cancer.
    (Urologic oncology, 2020-05-22) Grimberg, Dominic C; Shah, Ankeet; Molinger, Jeroen; Whittle, John; Gupta, Rajan T; Wischmeyer, Paul E; McDonald, Shelley R; Inman, Brant A
    BACKGROUND AND AIMS:The incidence of frailty is increasing as the population ages, which has important clinical implications given the associations between frailty and poor outcomes in the bladder cancer population. Due to a multi-organ system decline and decreased physiologic reserve, frail patients are vulnerable to stressors of disease and have poorer mortality and morbidity rates than their nonfrail peers. The association between frailty and poor outcomes has been documented across multiple populations, including radical cystectomy, creating a need for frailty assessments to be used preoperatively for risk stratification. We aim to provide a review of the common frailty assessments and their relevance to radical cystectomy patients. FINDINGS:A variety of assessments for frailty exist, from short screening items to comprehensive geriatric assessments. The syndrome spans multiple organ systems, as do the potential diagnostic instruments. Some instruments are less practical for use in clinical practice by urologists, such as the Canadian Study of Health and Aging Frailty Index and Comprehensive Geriatric Assessment. The tool most studied in radical cystectomy is the modified Frailty Index, associated with high grade complications and 30-days mortality. Frailty often coexists with malnutrition and sarcopenia, stressing the importance of screening for and addressing these syndromes to improve patient's perioperative outcomes. CONCLUSIONS:There is no universally agreed upon frailty assessment, but the most studied in radical cystectomy is the modified Frailty Index, providing valuable data with which to counsel patients preoperatively. Alterations in immune phenotypes provide potential future diagnostic biomarkers for frailty.
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    Clinical trial of high dose hyperthermic intravesical mitomycin C for intermediate and high-risk non-muscle invasive bladder cancer during BCG shortage.
    (Urologic oncology, 2021-08) Grimberg, Dominic C; Dudinec, John; Shah, Ankeet; Inman, Brant A

    Purpose

    Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), but availability is limited by global shortages. We present the first North American clinical experience using intravesical hyperthermia (HIVEC) with high-dose mitomycin C (MMC) during BCG shortage.

    Materials and methods

    Single arm intermediate size expanded access protocol for high dose HIVEC MMC in patients with intermediate and high-risk NMIBC during BCG shortage. Patients received 120 mg intravesical MMC using the Combat BRS to achieve 43°C HIVEC. Primary outcome was a safety assessment of adverse events, with recurrence-free survival and a descriptive analysis of hematologic impacts as secondary outcomes.

    Results

    Fourteen patients were treated from May 2019 to June 2020, 4 (29%) intermediate and 10 (71%) high risk. The cohort is heavily pretreated, only 2 (14%) BCG naïve and median 6 BCG instillations (IQR 5.25, 8.25), with median 3.5 recurrences per patient (IQR 1.00, 5.25) 67% with >1 per year. Patients underwent a median 6 instillations (IQR 3.25, 9.25) which were well tolerated in 11/14 (79%). Seven patients (50%) experienced 10 adverse events, all grades 1 or 2. Most common was MMC allergy (4/14, 29%), followed by bladder spasm (3/14, 21%). Two had recurrences at median 11 months follow up, but both discontinued HIVEC after only 2 treatments.

    Conclusions

    High dose MMC HIVEC is a safe and well-tolerated substitute for BCG during global shortages. The higher rate of systemic effects implies increased drug delivery, which may improve efficacy.
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    En Bloc Resection of Bladder Tumors: Style or Substance?
    (European Urology, 2020-06) Grimberg, Dominic C; Shah, Ankeet; Inman, Brant A
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    From Dog's Breakfast to Michelin Guide: Post-bacillus Calmette-Guérin Trials in Non-muscle-invasive Bladder Cancer.
    (European urology, 2020-04-14) Shah, Ankeet; Grimberg, Dominic C; Inman, Brant A
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    Genomic Scores are Independent of Disease Volume in Men with Favorable Risk Prostate Cancer: Implications for Choosing Men for Active Surveillance
    (The Journal of Urology, 2017-09) Nyame, Yaw A; Grimberg, Dominic C; Greene, Daniel J; Gupta, Karishma; Kartha, Ganesh K; Berglund, Ryan; Gong, Michael; Stephenson, Andrew J; Magi-Galluzzi, Cristina; Klein, Eric A
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    Overview of Taris GemRIS, a Novel Drug Delivery System for Bladder Cancer.
    (European urology focus, 2019-09-24) Grimberg, Dominic C; Shah, Ankeet; Inman, Brant A
    GemRIS, an implantable drug delivery system from Taris Biomedical that delivers continuous intravesical gemcitabine, shows potential for use in multiple bladder cancer settings. Ongoing and recently completed phase 1 trials in non-muscle-invasive as well as muscle-invasive bladder cancer are yielding promising preliminary results.
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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.
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    Successful Diagnosis and Treatment of Occult Prostate Cancer Despite Multiple Negative Prostate Biopsies and Negative Prostate MRIs.
    (Oncology (Williston Park, N.Y.), 2022-03) Morris, Kostantinos E; Grimberg, Dominic C; Gupta, Rajan T; Pendse, Avani A; Moul, Judd W
    Prostate-specific antigen (PSA) values above 100 ng/mL often suggest metastatic prostate cancer. We present the case of a patient with a PSA of 110 ng/mL, 4 negative prostate biopsies, and 4 negative prostate MRIs. After his fifth MRI revealed a PI-RADS 5 lesion, he underwent his fifth transrectal biopsy; this revealed Gleason 3 + 4 = 7. He was found to have organ-confined pT2 disease on subsequent radical prostatectomy pathology. This case highlights that there may be no PSA for which one can assume metastatic disease with certainty. Depending on life expectancy, patients with extremely elevated PSA may still warrant a full staging workup.