Faculty Bibliography

PURPOSE:To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)-directed dose escalation to intraprostatic regions. METHODS AND MATERIALS:Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry. RESULTS:The median prostate D90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3-136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0-251.9%). Median urethra D30 and rectal D30 values were 142.2% (137.5-168.2%) and 56.1% (40.1-63.4%), respectively. Median followup was 86.4 months (IQR, 49.8-117.6). The 10-year actuarial prostate-specific antigen relapse-free survival was 98% (95% confidence interval, 93-100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra. CONCLUSIONS:Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture.

PURPOSE/OBJECTIVE:We provide a comprehensive analysis of anatomical patterns of recurrence following external beam radiotherapy in patients with localized prostate cancer. MATERIALS AND METHODS/METHODS:This retrospective analysis included 2,694 patients with localized prostate cancer who received definitive, dose escalated external beam radiotherapy from 1991 to 2008. First recurrence sites were defined as initial sites of clinically detected recurrence and any subsequent clinically detected recurrence within 3 months. Anatomical recurrence patterns were classified as local (prostate/seminal vesicles only), lymphotropic (lymph nodes only) and osteotropic (bones only) in patients with disease confined only to these respective sites for at least 2 years from the initial clinically detected recurrence. RESULTS:Prostate was the most common first recurrence site in the low, intermediate and high risk groups with an 8-year cumulative incidence of 3.5%, 9.8% and 14.6%, respectively. The 8-year risk of isolated pelvic lymph node relapse as the first recurrence site was 0%, 1.0% and 3.3%, respectively. In the 474 patients with clinically detected recurrence the most common first recurrence site was local in 55.3%, bone in 33.5%, pelvic lymph nodes in 21.3% and abdominal lymph nodes in 9.1%. Patients showed unique relapse distributions, including a pattern that was local in 41.6%, lymphotropic in 9.7%, osteotropic in 20.3% and multiorgan/visceral in 28.5%. Anatomical recurrence pattern was the strongest predictor of prostate cancer specific mortality on multivariate analysis of patients with clinically detected recurrence. CONCLUSIONS:The most common first recurrence site after dose escalated external beam radiotherapy for prostate cancer is in the prostate and seminal vesicles in all risk groups. In contrast, patients treated without elective pelvic lymph node irradiation are at relatively low risk for isolated pelvic lymph node relapse. Recurrence patterns revealed a tropism for specific anatomical distributions with divergent prognoses, suggesting underlying biological differences among tumors.

OBJECTIVE:To evaluate whether a history of smoking or smoking during therapy after external beam radiotherapy (EBRT) for clinically localised prostate cancer is associated with increased treatment-related toxicity or disease progression. PATIENTS AND METHODS/METHODS:Of 2358 patients receiving EBRT for prostate cancer between 1988 and 2005, 2156 had chart-recorded smoking histories. Patients were classified as 'never smokers', 'current smokers', 'former smokers', and 'current smoking unknown'. Variables considered included quantity of tobacco use in pack-years, duration of smoking, and, for former smokers, how long before initiation of RT the patient quit smoking, when available. The median EBRT dose was 8100 Gy and the median follow-up was 95 months. Toxicity was graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. RESULTS:Current smoking significantly increased the risks of both prostate-specific antigen relapse [hazard ratio (HR) 1.4, P = 0.02] and distant metastases (HR 2.37, P < 0.001), as well as prostate cancer-specific death (HR 2.25, P < 0.001). Multivariate analysis showed that smoking was also associated with increased risk of EBRT-related genitourinary toxicities (current smoker, HR 1.8, P = 0.02; former smoker, HR 1.45, P = 0.01). Smoking did not increase gastrointestinal toxicity. CONCLUSIONS:Current smokers with prostate cancer are at increased risk of biochemical recurrence, distant metastasis, and prostate cancer-related mortality after definitive RT to the prostate. Current and former smokers, regardless of duration and quantity of exposure, are at an increased risk of long-term genitourinary toxicity after EBRT. Oncologists should encourage patients to participate in smoking-cessation programmes before therapy to potentially lower their risk of relapsing disease and post-treatment toxicities.

PURPOSE/OBJECTIVE:To investigate the effects of androgen-deprivation therapy (ADT) on MRI parameters and evaluate their associations with treatment response measures. MATERIALS AND METHODS/METHODS:The study included 30 men with histopathologically confirmed prostate cancer who underwent MRI before and after initiation of ADT. Thirty-four tumours were volumetrically assessed on DW-MRI (n = 32) and DCE-MRI (n = 18), along with regions of interest in benign prostatic tissue, to calculate apparent diffusion coefficient (ADC) and transfer constant (K(trans)) values. Changes in MRI parameters and correlations with clinical parameters (change in prostate-specific antigen [PSA], treatment duration, PSA nadir) were assessed. RESULTS:Prostate volume and PSA values decreased significantly with therapy (p < 0.001). ADC values increased significantly in tumours and decreased in benign prostatic tissue (p < 0.05). Relative changes in ADC and absolute post-therapeutic ADC values differed significantly between tumour and benign tissue (p < 0.001). K(trans) decreased significantly only in tumours (p < 0.001); relative K(trans) changes and post-therapeutic values were not significantly different between tumour and benign tissue. The relative change in tumour ADC correlated significantly with PSA decrease. No changes were associated with treatment duration or PSA nadir. CONCLUSIONS:Multi-parametric MRI shows significant measurable changes in tumour and benign prostate caused by ADT and may help in monitoring treatment response. KEY POINTS/CONCLUSIONS:• Androgen-deprivation therapy caused changes of ADC, K (trans) in tumour and benign prostate. • Prostate volume and PSA values decreased significantly with therapy. • ADC values may be helpful for monitoring treatment response.

BACKGROUND:We evaluated outcomes of intraoperative radiotherapy delivered with focal high-dose-rate (HDR) brachytherapy [intraoperative radiotherapy (IORT)] in the management of locally recurrent (LR) and locally advanced (LA) primary T4 colorectal carcinoma (CRC). LR CRC or LA primary disease is a clinical challenge due to the difficulty in obtaining negative margins after radical surgery and the high risk of subsequent recurrence. Few data exist on long-term outcomes of patients treated with surgery and HDR-IORT for LR or LA primary CRC. METHODS:Three hundred CRC patients underwent HDR-IORT to the pelvis with gross surgical resection during November 1992-December 2007. Median follow-up for surviving patients was 53 (range 5-216) months. Eighty-eight patients (29 %) were treated for LA primary and 212 (71 %) LR disease. HDR-IORT was delivered using an iridium-192 remote afterloader and a Harrison-Anderson-Mick applicator. Median IORT dose was 1,500 (range 1,000-2,000) cGy. RESULTS:Five-year overall survival probability was 49 %. Positive margin status was associated with inferior overall survival and disease-free survival. Competing-risks analysis for time to local failure and distant metastases identified a 5-year cumulative incidence of local failure and distant metastases of 33 and 47 %, respectively. Five-year cumulative incidence of local failure was 22 % for the LA group and 38 % in the LR group. Five-year probability of disease-free survival was 48 and 31 % for LA and LR patients, respectively, and 5-year probability of overall survival was 56 and 45 % for LA and LR patients, respectively. CONCLUSIONS:HDR-IORT combined with resection results in encouraging local control rates with acceptable toxicity for patients with locally aggressive CRC.

BACKGROUND:Although intensity-modulated radiotherapy (IMRT) is a standard of care for many head and neck cancers, its use for carotid-sparing (CS) therapy in early-stage laryngeal carcinoma is controversial. METHODS:330 consecutive patients with early-stage laryngeal carcinoma were treated from 1/1989 to 5/2011, including 282 conventional radiotherapy (CRT) and 48 CS-IMRT patients. The median follow-up was 43 (CS-IMRT) and 66 (CRT) months. RESULTS:There was no difference in local failure rates comparing patients undergoing CS-IMRT with CRT, with 3-year local control rates of 88% vs. 89%, respectively (p=0.938). Using a 1cm circumferential margin, the average dose to the left and right carotid arteries was 48.3 and 47.9 Gy, respectively. 88% of locoregional recurrences involved the ipsilateral true vocal cord, including all local recurrences in the IMRT group. CONCLUSIONS:These results warrant further prospective evaluation of CS-IMRT for early-stage glottic larynx cancer.

BACKGROUND:The management of biochemical failure (BF) following external beam radiotherapy (EBRT) for prostate cancer is controversial, due to both the heterogeneous disease course following a BF and a lack of clinical trials in this setting. OBJECTIVE:We sought to characterize the natural history and predictors of outcome for patients experiencing BF in a large cohort of men with localized prostate cancer undergoing definitive dose-escalated EBRT. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This retrospective analysis included 2694 patients with localized prostate cancer treated with EBRT at a large academic center. Of these, 609 experienced BF, defined as prostate-specific antigen (PSA) nadir + 2 ng/ml. The median follow-up was 83 mo for all patients and 122 mo for BF patients. INTERVENTION(S)/METHODS:All patients received EBRT at doses of 75.6-86.4 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:The primary objective of this study was to determine predictors of distant progression at the time of BF. Cox proportional hazards models were used in univariate and multivariate analyses of distant metastases (DM), and a competing risks method was used to analyze prostate cancer-specific mortality (PCSM). RESULTS AND LIMITATIONS/CONCLUSIONS:From the date of BF, the median times to DM and PCSM mortality were 5.4 yr and 10.5 yr, respectively. Shorter posttreatment PSA doubling time, a higher initial clinical tumor stage, a higher pretreatment Gleason score, and a shorter interval from the end of radiotherapy to BF were independent predictors for clinical progression following BF. Patients with two of these risk factors had a significantly higher incidence of DM and PCSM following BF than those with zero or one risk factor. The main limitations of this study are its retrospective nature and heterogeneous salvage interventions. CONCLUSIONS:Clinical and pathologic factors can help identify patients at high risk of clinical progression following BF. PATIENT SUMMARY/RESULTS:In this report, we look at predictors of outcome for patients with prostate cancer recurrence, as determined by prostate-specific antigen (PSA) levels, following radiation treatment. We found that the approximate median times to distant metastasis and death from prostate cancer for patients in this situation were 5 yr and 10 yr, respectively. Furthermore, we found that patients with a rapid increase in PSA levels following treatment, a short time to PSA recurrence, invasion of extraprostatic organs, or a high Gleason score had worse outcomes.