Alpha/beta (α/ß) ratio for prostate cancer derived from external beam radiotherapy and brachytherapy boost.

OBJECTIVE: There is disagreement regarding the value of the α/ß ratio for prostate cancer. Androgen deprivation therapy (ADT) may dominate the effects of dose fractionation on prostate-specific antigen (PSA) response and confound estimates of the α/ß ratio. We estimate this ratio from combined data on external beam radiation therapy (EBRT) and brachytherapy (BT)-treated patients, providing a range of doses per fraction, while accounting for the effects of ADT. METHODS: We analyse data on 289 patients with local prostate cancer treated with EBRT (2 Gy per fraction) or EBRT plus one or two BT boosts of 10 Gy each. The timing of ADT was heterogeneous. We develop statistical models to estimate the α/ß ratio based upon PSA measurements at 1 year as a surrogate for the surviving fraction of cancer cells as well as combined biochemical + clinical recurrence-free survival (bcRFS), controlling for ADT. RESULTS: For the PSA-based end point, the α/ß ratio estimate is 7.7 Gy [95% confidence interval (CI): 4.1 to 12.5]. Based on the bcRFS end point, the estimate is 18.0 Gy (95% CI: 8.2 to ∞). CONCLUSION: Our model-based estimates of the α/ß ratio, which account for the effects of ADT and other important confounders, are higher than some previous estimates. ADVANCES IN KNOWLEDGE: Although dose inhomogeneities and other limitations may limit the scope of our findings, the data suggest caution regarding the assumptions of the α/ß ratio for prostate cancer in some clinical environments.

Collecting (Bellini) duct carcinoma: A clinical study of a rare tumour and review of the literature.

INTRODUCTION: We report our 15-year experience of Collecting (Bellini) duct carcinoma (CDC). We retrospectively analyzed patient and tumour characteristics, clinical manifestations, surgical techniques, clinical outcomes, and salvage therapies. METHODS: From January 1999 to December 2013, 1042 patients underwent surgical resection of renal neoplasm. We examined all renal tumors and identified 10 cases (0.96%) of CDC. RESULTS: The study group included 8 men and 2 women, with a median age of 62.5 years. Of these 10 patients, 9 were symptomatic (90%). All patients were treated with open nephrectomy. The mean tumour size was 5.7 cm. The pathologic stages were distributed as follows: pT1b in 2 patients (20%); pT2a in 1 patient (10%); pT3a in 3 patients (30%); and pT3b in 4 patients (40%). Grading was assessed according to Fuhrman scale as follows: grade II in 1 patient (10%); grade III in 3 patients (30%); grade IV in 5 patients (50%); undetermined grade in 1 patient (10%). Four patients (40%) relapsed locally. The median time of local recurrence was 4.9 months. Distant metastases occurred in 9 patients (90%): 4/9 at the time of diagnosis and 5/9 after nephrectomy. The median time of distant metastases after surgery was 8.1 months. Six patients received chemotherapy (gemcitabine plus platinum salts). Radiotherapy was performed in 5 patients. One patient had surgery because of local recurrence and 2 patients were irradiated in the area of the local recurrence. The median overall survival was 7.6 months, and only 2 patients survived more than 2 years after the nephrectomy. CONCLUSIONS: CDCs of the kidney are aggressive and they have a low survival rate. All patients in our study experienced a relapse of their disease. Local recurrence preceded distant metastases. Results of salvage treatments were poor.

The effectiveness and side effects of conformal external beam radiotherapy combined with high-dose-rate brachytherapy boost compared to conformal external beam radiotherapy alone in patients with prostate cancer.

BACKGROUND: Clinical data that compare external-beam radiotherapy (EBRT) combined with high-dose-rate brachytherapy (HDR-BT) boost versus EBRT alone are scarce. The analysis of published studies suggest that biochemical relapse-free survival in combined EBRT and HDR-BT may be superior compared to EBRT alone. We retrospectively examined the effectiveness and tolerance of both schemes in a single center study. METHODS: Between March 2003 and December 2004, 229 patients were treated for localized T1-T2N0M0 prostate cancer. Median age was 66 years (range, 49 - 83 years). PSA level ranged from 0.34 to 64 ng/ml (median 12.3 ng/ml) and Gleason score ranged from 2 to 10. The analysis included 99 patients who underwent EBRT with HDR-BT (group A) and 130 patients who were treated with EBRT alone (group B). RESULTS: Median follow-up was 6 years. Biochemical relapses occurred in 34% vs. 22% (p = 0.002), local recurrences in 17% vs. 5% (p = 0.002), and distant metastases in 11% vs. 6% (p = 0.179) of patients in groups A and B, respectively. Five-year biochemical relapse-free survival was 67% vs. 81% (p = 0.005), local recurrence-free survival 95% vs. 99% (p = 0.002), metastases-free survival 95% vs. 94% (p = 0.302) for groups A and B, respectively. Five-year overall survival was 85% in both groups (p = 0.596). Grade 2/3 late GI complications appeared in 9.2% and 24.8% (p = 0.003), respectively. Grade 2/3 late GU symptoms occurred in 12% in both groups. CONCLUSIONS: Although because of the retrospective character of the study and nonrandomized selection of fractionation schedule the present conclusions had limitations EBRT alone appeared more effective than EBRT combined with HDR-BT. It was likely the result of the less frequent use of androgen deprivation therapy (ADT) for combined scheme group, too low dose in a single BT fraction or inadequate assumptions regarding fractionation sensitivity of prostate cancer.

Tolerability and toxicity of prophylactic cranial irradiation in patients with non-small cell lung cancer - Results of a phase II study (with estimation of hematological toxicity, pituitary function and magnetic resonance spectra changes).

AIM: To evaluate the tolerability and toxicity of PCI in patients with NSCLC. BACKGROUND: Prophylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment. MATERIALS AND METHODS: From 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30 Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with (1)H nuclear magnetic resonance spectra, and estimation of pituitary function. RESULTS: During follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease (p = 0.062). Visual-motor function deteriorated after treatment (p < 0.059). Performance IQ decreased (p < 0.025) and the difference between performance IQ and verbal IQ increased (p < 0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI. CONCLUSION: PCI in the current series was well tolerated and associated with a relatively low toxicity.

Early closure of phase II prospective study on acute and late tolerance of hypofractionated radiotherapy in low-risk prostate cancer patients.

AIM: To assess acute and late toxicity of hypofractionated radiotherapy, its efficacy and impact on quality of life in patients with low-risk prostate cancer. MATERIALS AND METHODS: Since August 2006 to October 2007, 15 prostate cancer patients with favorable clinical features, aged 54-74 years (mean 67 years) entered the study. Tumor stage in the majority (73%) of patients was T2a, the mean pretreatment PSA value was 7.2 ng/ml (range 5-10.9 ng/ml). The study group was treated 3 times a week with 4 Gy per fraction to the total dose of 60 Gy within 5 weeks. 3D conformal treatment planning was used with no fiducial markers. Acute and late toxicity was evaluated using modified EORTC/RTOG/LENT scoring systems. Patients regularly filled the EORTC QLQ-PR25 questionnaires. RESULTS: All patients completed radiotherapy according to the plan. During radiotherapy, 26% of patients had grade 1-2 rectal symptoms. The incidence of acute urinary toxicity score was 26%, 60%, and 14% for grade 0-1, 2 and 3, respectively. One year after RT, the incidence of grade 2 GI toxicity was 27%, which was the reason for an early closure of the accrual. Grade 2 late urinary toxicity was noted in 20% of patients. The mean PSA level was 0.61 ng/ml after 24 months and 0.47 ng/ml after 36 months (range: 0.06-1.54 ng/ml). CONCLUSIONS: Low number of patients does not allow to determine the influence of hypofractionation on unsatisfactory tolerance of this regimen. Suboptimal (from the present day's perspective) target localization (no fiducial markers) could potentially explain higher than expected late GI reactions in our series.

Salvage brachytherapy for local recurrences of prostate cancer treated previously with radiotherapy.

PURPOSE: The aim of the study was to analyze early effects and toxicity of salvage high dose rate brachytherapy for local recurrences of adenocarcinoma of the prostate after external beam radiotherapy (EBRT). MATERIAL AND METHODS: In MCS Memorial Institute of Oncology in Gliwice a research programme on salvage HDR brachytherapy for local recurrences of prostate cancer treated previously with EBRT has been ongoing since February 2008. The treatment consisted of 3 fractions of 10 Gy each given every 14 days. Maximal urethral doses were constrained to be ≤ 120% of the prescribed dose. Maximal bladder and rectum doses were constrained to be ≤ 70% of the prescribed dose. RESULTS: Fifteen eligible patients were treated and analyzed from February 2008. All patients completed the treatment without major complications. The most common early complications were: macroscopic haematuria, pain in lower part of the abdomen, and transient dysuria. During the first week after the procedure a transient increase in IPSS score was noticed. The Foley catheter was removed on day 2 to 5. No complications after spinal anaesthesia were observed. Acute toxicity according to EORTC/RTOG was low. For bladder EORTC/RTOG score ranged from 0 to 2. Only in two patients grade 1 toxicity for rectum was observed. The follow-up ranged from 3 to 9 months. In one patient grade 2 rectal toxicity was observed, and one had urethral stricture. Other patients did not have any other significant late toxicity of the treatment. Two patients developed bone metastases. CONCLUSIONS: Salvage brachytherapy for localized prostate cancer (3 × 10 Gy every 14 days) seems to be a safe and well tolerated procedure. A significant decline in prostate-specific antigen (PSA) level is seen in patients with hormone-responsive cancer. Long-term efficiency and toxicity of the procedure are yet to be established.