Which α/ß ratio and half-time of repair are useful for predicting outcomes in prostate cancer?

PURPOSE: To calculate the α/ß of prostate adenocarcinoma. MATERIALS AND METHODS: From January 1997 to December 2005, 328 patients were treated consecutively with external beam radiotherapy and brachytherapy boost. The patients with at least one of the following adverse prognostic factors were included: PSA>10 ng/ml, Gleason score ≥7, T≥2B. A total EQD2 of 80 Gy was delivered uniformly within the same timeframe. Prior to August 2002, the patients were treated to low-dose-rate brachytherapy using (192)Ir (n=201), and those treated thereafter received a high-dose-rate brachytherapy boost (n=127). The equivalency of dose was established using the incomplete repair model, with generally accepted α/ß ratio of 3 Gy, and half-time for repair of sublethal damage (HTR) of 1.5h. RESULTS: In a Cox proportional hazards model, the two groups displayed no difference (HR: 0.99, 95% CI: 0.87-1.1, p=0.98) in biochemical control. Analyzing using the linear quadratic model, the data fit well an α/ß ratio of 3.41 Gy (95% CI: 2.56-4.26) and the recently published HTR of 1.9 h (95% CI: 1.4-2.4), but also an α/ß of 5.87 Gy (95% CI: 4.67-7.07) and the more widely established HTR of 1.5 h. CONCLUSIONS: Unlike the previously published data, calculation of the α/ß ratio from consecutive patients and using a uniform treatment duration points to higher values than 2.5 Gy.

Adjuvant stereotactic permanent seed breast implant: a boost series in view of partial breast irradiation.

PURPOSE: The aim of this study was to use permanent seed implants in the breast and describe our experience with 15 cases, using iodine seed implants as a tumor bed boost. METHODS AND MATERIALS: Breasts were fixed with a thermoplastic sheet, a template bridge applied, the thorax scanned and the images rotated to be perpendicular to the implant axis. Skin, heart, and lung were delineated. A preplan was made, prescribing 50 Gy to the clinical target volume (CTV), consisting in this boost series of nearly a quadrant. Iodine (125) seeds were stereotactically implanted through the template, and results were checked with a postplan computed tomographic (CT) scan. RESULTS: The breast was immobilized reproducibly. Simulation, scanning, and implant were performed without difficulties. Preplan CTV D90% (the dose delivered to 90% of the CTV) was 66 Gy, and postoperative fluoroscopic or CT scan checks were satisfactory. Pre- and postplan dose-volume histogram showed good organ sparing: mean postplan skin, heart, and lung V30 Gy (the organ volume receiving a dose of 30 Gy) of 2 +/- 2.2 mL, 0.24 +/- 0.34 mL, and 3.5 +/- 5 mL, respectively. No short-term toxicity above Grade 1 was noted, except for transient Grade 3 neuropathy in 1 patient. CONCLUSIONS: Seeds remained in the right place, as assessed by fluoroscopy, absence of significant pre- to postplan dose-volume histogram change for critical organs, and total irradiated breast volume. The method could be proposed as a boost when high dosimetric selectivity is required (young patients after cardiotoxic chemotherapy for left-sided cancer). This boost series was a preliminary step before testing partial breast irradiation by permanent seed implant in a prospective trial.

Long-term follow-up reveals low toxicity of radiosurgery for vestibular schwannoma.

AIM: The long-term effects of radiosurgery of vestibular schwannomas were investigated in a group of consecutively treated patients. METHODS AND MATERIALS: Between 1995 and 2001, 26 patients (median age: 67, range: 30-82) with a vestibular schwannoma were treated by Linac-based stereotactic radiosurgery (SRS). The median follow-up was 49 months (16-85 months). Only progressive tumours were treated. The median size of tumours was 18 mm (range 9-30 mm). Before SRS, 11 patients had a useful hearing (Gardner-Robertson classes 1 and 2). Single doses of 10-14 Gy were prescribed at the 80% isodose at the tumour margin. The follow-up consisted of regular imaging with MRI the first 3-6 months after the intervention, followed by additional yearly MRIs, a hearing test and a neurological examination. RESULT: The 5-year-probability of tumour control (defined as stabilization or decrease in size) was 95%. Five-year-probability of preservation of hearing and facial nerve function was 96% and 100%, respectively. Hearing was preserved in 10 out of 11 patients who had a normal or useful hearing at the time of treatment. Mild and transient trigeminal toxicity occurred in 2 (8%) patients. It appeared to be significantly correlated to the dose used (p=0.044). However, only a tendency to significance could be demonstrated in the relationship between the two factors when using the Cox analysis (hazard ratio=1.7; 95% CI: 0.7-3.9; p=0.23). CONCLUSIONS: With the doses used, our study demonstrates that SRS provides an equivalent tumour control rate when compared to surgery, as well as on a long-term basis, an excellent preservation of the facial and the acoustic nerves. Although no permanent trigeminal toxicity was observed, our data confirm that doses below 14 Gy can avoid transient dysesthesias.

192Ir low dose rate brachytherapy for boosting locally advanced prostate cancers after external beam radiotherapy: a phase II trial.

BACKGROUND AND PURPOSE: To evaluate on 201 locally advanced prostatic cancers prospectively treated in a phase II trial, the efficacy of a combination of external beam radiotherapy (39.6 Gy) and (192)Ir low dose rate brachytherapy (Bt) (40-45 Gy). PATIENTS AND METHODS: Sixty-four patients were included in the intermediate prognosis group with only one of the following adverse factors (PSA > 10 ng/ml, Gleason score > or = 7 or clinical stage > or =T2b) and 137 in the unfavourable group when at least two of these factors were present. RESULTS: The actuarial 4 years biochemical no evidence of disease is 82.8% for the entire population. It is, respectively, 97 and 76% in the intermediate and unfavourable prognosis groups (P < 0.0001). Grade > or =3 late urinary complications occurred in 13 patients (6.5%). Eight patients (4%) presented late grade 2 rectal complications but no grades 3-5 was observed. CONCLUSIONS: Even if an alpha/beta of 1.5-3 Gy theoretically favours the use of a high dose rate mode of irradiation, the early results presented here are as good as those reported for similar groups of patients with high dose rate treatments. Late toxicity is identical but our urinary toxicity is within the less favourable and rectal toxicity within the most favourable results. We can postulate that while inducing very high hyperdosage regions (V150) mainly focused on the peripheral zone, most of the Bt techniques consist of a more ablative treatment. Many of the radiobiological studies on Bt did not in fact take into account the heterogeneity of irradiation inside the CTV. This study highlights the need to explore pulsed dose rate therapies, permanent implant and new available radioisotopes such as (169)Ytterbium that will offer the safety of low and lower dose rates. The actual late toxicity of the different Bt techniques is not yet inexistent indeed.

Prognostic value of PSA nadir < or =4 ng/mL within 4 months of high-dose radiotherapy for locally advanced prostate cancer.

PURPOSE: To investigate early prostate-specific antigen (PSA) kinetics after high radiation doses of 85 Gy on locally advanced prostate cancer. METHODS AND MATERIALS: A total of 201 patients were prospectively and consecutively treated with external beam radiotherapy and a brachytherapy boost. Of the 201 patients, 104 received concomitant hormonal therapy on the decision of the referring urologist and were excluded, yielding a study population of 97 patients. The first posttreatment PSA analysis was performed not earlier than 1 month after treatment completion but within the first 4 months, and then every 4 months. Analysis of PSA kinetics included the PSA nadir (nPSA) at values of < or =4 ng/mL to < or =0.5 ng/mL. The nPSA at < or =4 ng/mL within 4 months (nPSA < or =4/4m) was the variable of interest. RESULTS: We established highly significant associations between an nPSA of < or =1 and < or =0.5 ng/mL and the nPSA < or =4/4m (p <0.0001). A hazard ratio of 0.33 (95% Confidence Interval (CI), 0.12-0.91) underlined the lower risk of recurrence related to nPSA < or =4/4m achievement (p = 0.033). Using time-dependent covariate models for patients who did not reach an nPSA < or =4/4m, an nPSA of < or =1 ng/mL remained without prognostic significance (p = 0.06). However, for patients who reached an nPSA < or =4/4m, an nPSA of < or =1 ng/mL did significantly improve the prognosis (p <0.001), but much later after treatment. The same analysis was repeated for nPSA < or =0.5 ng/mL with similar conclusions as when nPSA < or =4/4m was obtained (p <0.01). CONCLUSION: The nPSA < or =4/4m has been demonstrated to be a significant predictor of biochemical no evidence of disease after high radiation doses of 85 Gy. Its major advantage is that it was available earlier than the other nadirs.

Can intensity-modulated radiation therapy of the paraaortic region overcome the problems of critical organ tolerance?

BACKGROUND AND PURPOSE: The recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy's (IMRT) possibilites of either increasing, in a safe way, the dose to 50-60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting. MATERIAL AND METHODS: The dosimetric charts of 14 patients irradiated to the PO region at the Department of Radiation Oncology, University Hospital of Liege, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radiotherapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were planned to theoretically deliver 60 Gy to the PO region in the safest way possible. Dose-volume histograms (DVHs) were calculated for clinical target volume (CTV), planning target volume (PTV), and OR. Student's t-test was used to compare the paired DVH data issued from CEBR and IMRT planning. RESULTS: The IMRT approach allowed to cover the PTV at a higher level as compared to CEBR. Using IMRT, the maximal dose to the spinal cord was reduced from 42.5 Gy to 26.2 Gy in comparison with CEBR (p < 0.00001). Doses to the kidneys were significantly reduced, with < 20% receiving >or= 20 Gy in the IMRT approach (p < 0.00001). Irradiation of digestive structures was not different, with < 25% receiving 35 Gy. Doses to the liver remained low regardless of the method used. CONCLUSION: At 60 Gy, IMRT is largely sparing the spinal cord and kidneys as compared to CEBR and represents an interesting approach not only for dose escalation up to 50-60 Gy (probably facilitating the radiochemotherapy approaches) but also in an adjuvant setting at lower doses. The dosimetric data of this study are in the same range as those published recently with a dynamic arc conformal approach.

Does inverse planning applied to Iridium192 high dose rate prostate brachytherapy improve the optimization of the dose afforded by the Paris system?

BACKGROUND AND PURPOSE: The purpose of the work is to analyse for 192Ir prostate brachytherapy (BT) some of the different steps in optimizing the dose delivered to the CTV, urethra and rectum. MATERIALS AND METHODS: Between 07/1998 and 12/2001, 166 patients were treated with 192Ir wires providing a low dose rate, according to the Paris system philosophy and with the 2D version of the treatment planning IsisR. 40-45 Gy were delivered after an external beam radiotherapy of 40 Gy. The maximum tolerable doses for BT were 25 Gy to the anterior third of the rectum on the whole length of the implant (R dose) and 52 Gy to the urethra on a 1cm length (Umax). A Umax/CTV dose ratio >1.3 represented a pejorative value as the planned dose of 40-45 Gy could not be achieved. On the other side a ratio 1.25 decreased significantly with optimization required on CTV contours and additional constraints on urethra while the R/CTV ratio was maintained under 0.55. For initial Umax/CTV >1.3 or >1.25 but

Increased IL-6 and TGF-beta1 concentrations in bronchoalveolar lavage fluid associated with thoracic radiotherapy.

PURPOSE: To assess, in lung cancer patients, the effects of thoracic radiotherapy (RT) on the concentrations of transforming growth factor-beta(1) (TGF-beta(1)) and interleukin-6 (IL-6) in the bronchoalveolar lavage (BAL) fluid. METHODS AND MATERIALS: Eleven patients with lung cancer requiring RT as part of their treatment were studied. BAL was performed bilaterally before, during, and 1, 3, and 6 months after RT. Before each BAL session, the patient's status was assessed clinically using pulmonary function tests and an adapted late effects on normal tissue-subjective, objective, management, analytic (LENT-SOMA) scale, including subjective and objective alterations. The National Cancer Institute Common Toxicity Criteria were used to grade pneumonitis. The TGF-beta(1) and IL-6 levels in the BAL fluid were determined using the Easia kit. RESULTS: The TGF-beta(1) and IL-6 concentrations in the BAL fluid recovered from the irradiated areas were significantly increased by thoracic RT. The increase in TGF-beta(1) levels tended to be greater in the group of patients who developed severe pneumonitis. In the BAL fluid from the nonirradiated areas, the TGF-beta(1) and IL-6 concentrations remained unchanged. CONCLUSION: The observed increase in TGF-beta(1) and IL-6 concentrations in the BAL fluid recovered from the irradiated lung areas demonstrated that these cytokines may contribute to the process leading to a radiation response in human lung tissue.