Genitourinary Cancer

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SU_20_2208 - A Phase I Trial of Dose-Escalated Image-Guided, Intensity Modulated Radiation Therapy in Combination With Concurrent Gemcitabine Chemotherapy for Node-Negative, Muscle-Invasive Bladder Cancer (MIBC)

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

A Phase I Trial of Dose-Escalated Image-Guided, Intensity Modulated Radiation Therapy in Combination With Concurrent Gemcitabine Chemotherapy for Node-Negative, Muscle-Invasive Bladder Cancer (MIBC)
M. A. Kollmeier, M. J. Zelefsky, S. McBride, D. Debonis, S. Lochansingh, M. Varghese, B. Bochner, J. Rosenberg, and D. Bajorin; Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): To examine the safety of dose-escalated, image-guided intensity modulated radiotherapy (IG-IMRT) and concurrent biweekly gemcitabine as part of a multimodality bladder-sparing approach.

Materials/Methods: Patients underwent a maximal transurethral resection and placement of 4 fiducials at the periphery of the tumor bed. All patients received induction with 45Gy in 1.8Gy fractions to the bilateral pelvic lymphatics (internal, external and common iliac nodes) and whole bladder with concurrent low dose gemcitabine delivered twice weekly. Restaging cystoscopy after induction in surgery-eligible patients. Patients with ≤pT1 at restaging cystoscopy or surgery-ineligible patients went on to consolidation phase. Three dose cohorts for consolidation were 1) 23.4Gy in 13 fractions (total 68.4Gy) 2) 27Gy in 15 fractions (total 72Gy) 3) 30.6Gy in 17 fractions (total 75.6Gy). Daily/weekly organ motion monitoring using kv imaging and CBCT was performed throughout treatment. Dose-limiting toxicities were assessed using CTCAE v 4.0. Cystoscopic and radiographic followup was performed every 3m post-treatment.

Results: A total of 18 patients were enrolled (17 males; 1 female). 3 patients (1 in each dose cohort) did not complete the consolidation phase due to >pT1 disease on restaging cystoscopy. 2 patients (1 in cohort 2 and 1 in cohort 3) elected to discontinue therapy prior to consolidation phase. 2 patients (1 in cohort 2 and 1 in cohort 3) developed grade 3 toxicity (hyponatremia, cystitis) prior to consolidation phase. 11 patients completed protocol therapy and were evaluable. Acute grade 2 urinary toxicity occurred in 2 patients in cohort 1, 3 in cohort 2 and 2 in cohort 3. One grade 3 urinary toxicity occurred in 1 patient from cohort 1 during the induction phase. This resolved and treatment continued dose escalation without further toxicity. The most frequent urinary toxicities were urgency/frequency and dysuria. Acute grade 2 diarrhea occurred in 2 patients in cohort 1, 3 in cohort 2 and 2 in cohort 3. No late (>90days) grade 2 or 3 toxicities were noted. In cohort 1, 2 of 3 patients had in-bladder recurrence at site of original disease. One patient underwent salvage cystectomy with pT2Nx disease with distant metastases at 15m and died 21m post-chemoradiation. One patient declined salvage cystectomy, developed distant metastases at 26m and died at 28m post-chemoradiation. One patient is NED at 60m. In cohort 2, 2 of 5 patients had disease recurrence at 4m (1 in-bladder and 1 distant). 3 patients are NED at 36, 37, 52m. 1 patient with in-bladder recurrence underwent chemotherapy, salvage cystectomy with M1 disease (para-aortic n+) and is NED on immunotherapy at 50m. In cohort 3, 3 of 3 patients have no disease recurrence at 12, 20, and 21m.

Conclusion: Dose escalated IG-IMRT with gemcitabine appears to be well tolerated. Fewer recurrences were noted in the dose escalated cohorts (72Gy and 75.6Gy). Dose escalation may be essential for improved disease control and requires additional prospective study.

Author Disclosure: M.A. Kollmeier: None. M.J. Zelefsky: Consultant; Consultant. S. McBride: None. M. Varghese: None. J. Rosenberg: None.

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SU_20_2208 - A Phase I Trial of Dose-Escalated Image-Guided, Intensity Modulated Radiation Therapy in Combination With Concurrent Gemcitabine Chemotherapy for Node-Negative, Muscle-Invasive Bladder Cancer (MIBC)



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