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Title: Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy

Abstract

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently, proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6,more » pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [6];  [3];  [4];  [3];  [4];  [3];  [4];  [2];  [2];  [2];  [3];  [4]
  1. Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki (Japan) and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki (Japan). E-mail: mhata@syd.odn.ne.jp
  2. Department of Urology, University of Tsukuba, Tsukuba, Ibaraki (Japan)
  3. Proton Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki (Japan)
  4. (Japan)
  5. Department of Radiology, University of Tsukuba, Tsukuba, Ibaraki (Japan)
  6. Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki (Japan)
Publication Date:
OSTI Identifier:
20793421
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2005.10.023; PII: S0360-3016(05)02942-1; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOPSY; BLADDER; CARCINOMAS; CHEMOTHERAPY; EVALUATION; IRRADIATION; METASTASES; METHOTREXATE; PATIENTS; PRESERVATION; PROTON BEAMS; RADIOTHERAPY; THROMBOSIS; TOXICITY; X RADIATION

Citation Formats

Hata, Masaharu, Miyanaga, Naoto, Tokuuye, Koichi, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Saida, Yukihisa, Ohara, Kiyoshi, Sugahara, Shinji, Kagei, Kenji, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Igaki, Hiroshi, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Hashimoto, Takayuki, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Hattori, Kazunori, Shimazui, Toru, Akaza, Hideyuki, Akine, Yasuyuki, and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki. Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Hata, Masaharu, Miyanaga, Naoto, Tokuuye, Koichi, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Saida, Yukihisa, Ohara, Kiyoshi, Sugahara, Shinji, Kagei, Kenji, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Igaki, Hiroshi, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Hashimoto, Takayuki, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Hattori, Kazunori, Shimazui, Toru, Akaza, Hideyuki, Akine, Yasuyuki, & Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki. Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy. United States. doi:10.1016/J.IJROBP.2005.1.
Hata, Masaharu, Miyanaga, Naoto, Tokuuye, Koichi, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Saida, Yukihisa, Ohara, Kiyoshi, Sugahara, Shinji, Kagei, Kenji, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Igaki, Hiroshi, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Hashimoto, Takayuki, Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki, Hattori, Kazunori, Shimazui, Toru, Akaza, Hideyuki, Akine, Yasuyuki, and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki. Sat . "Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793421,
title = {Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy},
author = {Hata, Masaharu and Miyanaga, Naoto and Tokuuye, Koichi and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki and Saida, Yukihisa and Ohara, Kiyoshi and Sugahara, Shinji and Kagei, Kenji and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki and Igaki, Hiroshi and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki and Hashimoto, Takayuki and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki and Hattori, Kazunori and Shimazui, Toru and Akaza, Hideyuki and Akine, Yasuyuki and Department of Radiation Oncology, University of Tsukuba, Tsukuba, Ibaraki},
abstractNote = {Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently, proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 64,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 2006},
month = {Sat Apr 01 00:00:00 EST 2006}
}
  • Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3more » weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31) in groups A and B, respectively. During the intra-arterial chemotherapy cycle, although more than 50 % patients experienced some toxicities, most were minor and reversible [grade 1-2 (46.7 %) vs. grade 1-2 (6.9 %)]. Conclusion: These findings suggest that combining intra-arterial chemotherapy with intravesical chemotherapy could delay tumour recurrence and progression compared with intravesical chemotherapy alone and this type treatment is relatively safe.« less
  • Purpose: To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy). Patients and Methods: A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose ofmore » at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method. Results: Among the 119 eligible patients, 101 (85%) achieved T0, and 18 (15%) achieved Ta or Tis after induction chemo-RT and proceeded to consolidation. After a median follow-up of 5.9 years, 36 of 101 T0 patients (36%) versus 5 of 18 Ta or Tis patients (28%) experienced bladder recurrence (P=.52). Thirteen patients among complete responders eventually required late salvage cystectomy for tumor recurrence, compared with 1 patient among near-complete responders (P=.63). Disease-specific, bladder-intact, and overall survivals were not significantly different between T0 and Ta/Tis cases. Conclusions: The bladder recurrence and salvage cystectomy rates of the complete and the near-complete responders were similar. Therefore it is reasonable to recommend that patients with Ta or Tis after induction chemo-RT continue with bladder-sparing therapy with consolidation chemo-RT to full dose (60-64 Gy).« less
  • Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction fillingmore » and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be evaluated in a randomized trial.« less
  • Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patientsmore » with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.« less
  • Purpose: To evaluate the role of chemotherapy combined with curative radiotherapy in breast cancer patients who presented with recurrent ipsilateral supraclavicular lymph node metastases (ISLM) without 'nonregional disease,' we designed an observational study performed prospectively. Patients and Methods: Forty-four consecutive patients with ISLM from breast cancer as part of recurrent regional disease without distant metastases were included in this study. All patients received chemotherapy with doxorubicin-based schema or paclitaxel for six courses and curative radiotherapy (60 Gy/30 fractions of 2 Gy/5 days a week). An 'involved field' radiation was delivered during the interval between the third and fourth chemotherapy course;more » hormonal therapy was given based on receptor status. Results: The rate of overall clinical response after chemotherapy and radiotherapy was 94.9%. Median time to progression and overall survival were 28 and 40 months, respectively; the 5-year actuarial overall survival and disease-free survival rates were 35% (95% confidence interval, 19-51) and 20% (95% confidence interval, 6-34), respectively. Conclusion: A curative course of intravenous chemotherapy and radical irradiation is feasible in patients with ISLM. All patients presenting recurrence in supraclavicular nodes should be treated with definitive locoregional treatments and systemic therapy because the outcomes are better than might be historically assumed.« less