Macroscopic Hematuria After Conventional or Hypofractionated Radiation Therapy: Results From a Prospective Phase 3 Study.

PURPOSE: To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. METHODS AND MATERIALS: Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). RESULTS: Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P=.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P=.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer-related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P=.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. CONCLUSIONS: MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

Relationships between rectal wall dose-volume constraints and radiobiologic indices of toxicity for patients with prostate cancer.

PURPOSE: The purpose of this article was to investigate how exceeding specified rectal wall dose-volume constraints impacts on the risk of late rectal bleeding by using radiobiologic calculations. METHODS AND MATERIALS: Dose-volume histograms (DVH) of the rectal wall of 250 patients with prostate cancer were analyzed. All patients were treated by three-dimensional conformal radiation therapy, receiving mean target doses of 80 Gy. To study the main features of the patient population, the average and the standard deviation of the distribution of DVHs were generated. The mean dose , generalized equivalent uniform dose formulation (gEUD), modified equivalent uniform dose formulation (mEUD)(0), and normal tissue complication probability (NTCP) distributions were also produced. The DVHs set was then binned into eight classes on the basis of the exceeding or the fulfilling of three dose-volume constraints: V(40) = 60%, V(50) = 50%, and V(70) = 25%. Comparisons were made between them by , gEUD, mEUD(0), and NTCP. RESULTS: The radiobiologic calculations suggest that late rectal toxicity is mostly influenced by V(70). The gEUD and mEUD(0) are risk factors of toxicity always concordant with NTCP, inside each DVH class. The mean dose, although a reliable index, may be misleading in critical situations. CONCLUSIONS: Both in three-dimensional conformal radiation therapy and particularly in intensity-modulated radiation therapy, it should be known what the relative importance of each specified dose-volume constraint is for each organ at risk. This requires a greater awareness of radiobiologic properties of tissues and radiobiologic indices may help to gradually become aware of this issue.

A study of the effect of setup errors and organ motion on prostate cancer treatment with IMRT.

PURPOSE: To assess the influence of setup errors and organ motion in terms of the probability of tumor control and normal-tissue complications by tumor control probability and normal-tissue complication probability. METHODS AND MATERIALS: Twelve patients were treated for prostate cancer with intensity-modulated radiation therapy. Two orthogonal portal images were taken daily. All patients underwent three computed tomography scans during the 8-week treatment time (i.e., baseline, intermediate, and final). The original treatment plans were re-evaluated, taking into account setup errors and organ motion. RESULTS: The mean shifts +/- standard deviation of the whole patient population in the lateral, anterior-posterior, and craniocaudal direction were 1.0 +/- 1.5 mm, 0.9 +/- 2.1 mm, and 1.9 +/- 2.1 mm, respectively. In most of the recalculated dose-volume histograms, the coverage of clinical target volume was granted despite organ motion, whereas the rectal wall histograms were often very different from the planned ones. CONCLUSION: We have studied the impact of prostate and rectum motion, as well as setup errors, on dose-volume histograms. The estimate of these effects may have implications for predictive indications when planning intensity-modulated radiation therapy treatments on prostate.

Conservative treatment of invasive bladder carcinoma by transurethral resection, protracted intravenous infusion chemotherapy, and hyperfractionated radiotherapy: long term results.

BACKGROUND: Organ preservation has been investigated in patients with muscle-invasive bladder carcinoma over the past decades as an alternative to radical cystectomy. The majority of studies reported that trimodal schedules, including transurethral resection of bladder tumor (TURB), radiotherapy (RT), and chemotherapy, are a feasible and safe organ-sparing approach without deferring the survival probability. However, to the authors' knowledge the best combination of RT and chemotherapy has yet to be well defined. The current study evaluated the long-term results of a schedule of concurrent cisplatin and 5-fluorouracil (5-FU) administered as protracted intravenous infusions (PVI) during hyperfractionated radiotherapy (HFRT) with organ-sparing intent in patients with infiltrating transitional cell carcinoma of the bladder (TCCB). METHODS: Seventy-seven patients with a classification of T2-T4aN0M0 TCCB were enrolled in the current study. After a complete TURB and bladder mapping, 42 of 77 patients underwent 2 cycles of induction chemotherapy. All 77 patients underwent HFRT and a schedule of cisplatin (4-6 mg/m(2) per day) and 5-FU (180-220 mg/m(2) per day) as concomitant PVI (radiochemotherapy [RCT]). Six to 8 weeks after RCT, patient response was evaluated by computed tomography scan, urine cytology, and TURB. Patients who achieved a complete response (CR) were followed at regular intervals. For patients with residual or recurrent invasive tumor, salvage cystectomy was recommended. RESULTS: Seventy-two patients were evaluable for response: 65 achieved a CR (90.3%) and 7 (9.7%) achieved a partial response. No significant difference was observed for the different prognostic factors with the exception of stage of disease (T2 [95.7%] vs. T3-T4a [80.0%]; P = 0.04). The observed toxicity, mainly hematologic, was higher among the patients who received induction chemotherapy compared with the patients who did not receive induction chemotherapy, even though the difference was not statistically significant. After a median follow-up of 82.2 months (range, 30-138 months), 44 of 65 (57.1%) patients who achieved a CR were alive. Of these 44 patients, 33 had tumor-free bladders. The 5-year overall, bladder-intact, tumor-specific, disease-free, and cystectomy-free survival rates for all 77 patients were 58.5%, 46.6%, 75.0%, 53.5%, and 76.1%, respectively. No associations were observed in overall and tumor-specific survival with different prognostic factors. CONCLUSIONS: Combined treatment appeared to provide high response rates and can be offered as an alternative option to radical cystectomy in selected patients who refuse or are unsuitable for surgery.