Faculty Bibliography

PURPOSE/OBJECTIVE:External beam radiotherapy (EBRT) plays a controversial role in the management of nonanaplastic thyroid cancer. We reviewed our institution's outcomes in patients treated with EBRT for advanced or recurrent nonanaplastic thyroid cancer. METHODS AND MATERIALS/METHODS:Between April 1989 and April 2006, 76 patients with nonanaplastic thyroid cancer were treated with EBRT. The median follow-up for the surviving patients was 35.3 months (range, 4.2-178.4). The lesions were primarily advanced and included Stage T2 in 5 (7%), T3 in 5 (7%), and T4 in 64 (84%) patients. Stage N1 disease was present in 60 patients (79%). Distant metastases before EBRT were identified in 27 patients (36%). The median total EBRT dose delivered was 6,300 cGy. The histologic features examined included medullary in 12 patients (16%) and nonmedullary in 64 (84%). Of the 76 patients, 71 (93%) had undergone surgery before RT, and radioactive iodine treatment was used in 56 patients (74%). RESULTS:The 2- and 4-year overall locoregional control rate for all histologic types was 86% and 72%, respectively, and the 2- and 4-year overall survival rate for all patients was 74% and 55%, respectively. No significant differences were found in locoregional control, overall survival, or distant metastases-free survival for patients with complete resection, microscopic residual disease, or gross residual disease. Grade 3 acute mucositis and dysphagia occurred in 14 (18%) and 24 (32%) patients, respectively. Late adverse toxicity was notable for percutaneous endoscopic gastrostomy tube use in 4 patients (5%). CONCLUSION/CONCLUSIONS:The results of our study have shown that EBRT is effective for locoregional control of selected locally advanced or recurrent nonanaplastic thyroid malignancies, with acceptable acute toxicity.

PURPOSE/OBJECTIVE:To investigate the biochemical control rates and survival for Gleason score 7-10 prostate cancer patients undergoing permanent prostate brachytherapy as a function of the biologic effective dose (BED). METHODS AND MATERIALS/METHODS:Six centers provided data on 5,889 permanent prostate brachytherapy patients, of whom 1,078 had Gleason score 7 (n = 845) or Gleason score 8-10 (n = 233) prostate cancer and postimplant dosimetry results available. The median prostate-specific antigen level was 7.5 ng/mL (range, 0.4-300). The median follow-up for censored patients was 46 months (range, 5-130). Short-term hormonal therapy (median duration, 3.9 months) was used in 666 patients (61.8%) and supplemental external beam radiotherapy (EBRT) in 620 (57.5%). The patients were stratified into three BED groups: <200 Gy (n = 645), 200-220 Gy (n = 199), and >220 Gy (n = 234). Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. RESULTS:The 5-year bFFF rate was 80%. The bFFF rate stratified by the three BED groups was 76.4%, 83.5%, and 88.3% (p < 0.001), respectively. Cox regression analysis revealed Gleason score, prostate-specific antigen level, use of hormonal therapy, EBRT, and BED were associated with bFFF (p < 0.001). Freedom from metastasis improved from 92% to 99% with the greatest doses. The overall survival rate at 5 years for the three BED groups for Gleason score 8-10 cancer was 86.6%, 89.4%, and 94.6%, respectively (p = 0.048). CONCLUSION/CONCLUSIONS:These data suggest that permanent prostate brachytherapy combined with EBRT and hormonal therapy yields excellent bFFF and survival results in Gleason score 7-10 patients when the delivered BEDs are >220 Gy. These doses can be achieved by a combination of 45-Gy EBRT with a minimal dose received by 90% of the target volume of 120 Gy of (103)Pd or 130 Gy of (125)I.

BACKGROUND:A multicenter phase 2 trial was conducted to evaluate the safety and feasibility of radiotherapy after paclitaxel, estramustine phosphate, and carboplatin (TEC) plus androgen deprivation therapy in previously untreated unfavorable-risk localized prostate cancer patients. METHODS:Patients with localized high-risk prostate cancer were treated with 4 cycles (16 weeks) of continuous weekly paclitaxel at 80 mg/m(2) intravenously with estramustine at 280 mg orally 3 times a day for 5 days a week and carboplatin (area under the curve of 6) on Day 1 of every cycle followed by 3-dimensional conformal or intensity-modulated radiotherapy (total dose of 77.4 gray [Gy] in 1.8-Gy fractions). All patients received androgen deprivation therapy with either goserelin acetate at 3.6 mg subcutaneously or leuprolide acetate at 7.5 mg intramuscularly monthly for 6 months starting at Day 1 of therapy. Patients were evaluated for acute and late toxicities along with progression-free survival and time to prostate-specific antigen (PSA) failure associated with the multimodality therapy. RESULTS:Twenty-seven of 34 patients completed therapy and were evaluable for safety and feasibility. There was 1 patient with grade 3 nausea during chemotherapy. No other grade 3 or 4 gastrointestinal, cardiovascular, or genitourinary acute or late toxicities were reported. The most common grade 1 to 2 late toxicities were proctitis (11%), dysuria (11%), and urinary frequency/urgency (33%). Two deaths due to prostate cancer were observed. Median follow-up was 38 months among 24 surviving patients; median PSA progression-free survival was 12.1 months (95% confidence interval, 13.3-25.9). CONCLUSIONS:Neoadjuvant chemohormonal therapy with TEC followed by high-dose radiation therapy is safe and feasible in a multicenter setting.

Interest in focal therapy for prostate cancer has recently been renewed owing to downward stage migration, improved biopsy and imaging techniques, and the prevalence of either unifocal cancer or a dominant cancer with secondary tumors of minimal malignant potential. Several techniques have potential for focal ablation of prostate cancer. Cryotherapy has been used for some time as primary therapy for complete ablation of the prostate or local recurrence after radiotherapy. Enthusiasm for cryotherapy as the primary therapy has been tempered by the uncertainty about complete ablation of the cancer, the frequent persistence of measurable prostate-specific antigen levels after the procedure, and a high rate of erectile dysfunction. Studies have reported "focal ablation" of prostate cancer with cryotherapy, targeting 1 side of the gland to eliminate a cancer confined to that side with less risk of urinary or sexual complications. Whether cryotherapy has sufficient power to eradicate focal cancer and can be targeted with sufficient accuracy to avoid damage to surrounding structures remains to be demonstrated in prospective clinical trials. High-intensity focused ultrasound (HIFU) has been used widely in Europe for complete ablation of the prostate, especially in elderly men who are unwilling or unable to undergo radical therapy. For low- or intermediate-risk cancer, the short- and intermediate-term oncologic results have been acceptable but need confirmation in prospective multicenter trials presently underway. Whole gland therapy with transrectal ultrasound guidance has been associated with a high risk of acute urinary symptoms, often requiring transurethral resection before or after HIFU. Adverse effects on erectile function seem likely after a therapy that depends on heat to eradicate the cancer, but erectile function after HIFU has not been adequately documented with patient-reported questionnaires. HIFU holds promise for focal ablation of prostate cancer. As with cryotherapy, focal HIFU should reduce the adverse sexual, urinary, and bowel effects of whole gland ablation. New techniques are being developed to allow HIFU treatment under real-time guidance using magnetic resonance imaging, which could improve the precision and reduce the adverse effects further. Another promising technique, currently in clinical trials, is vascular-targeted photodynamic therapy, which has been used for whole gland ablation of locally recurrent cancer after radiotherapy and, more recently, for focal ablation of previously untreated cancer. In combination with a new, systemically administered photodynamic agent, laser light is delivered through fibers introduced into the prostate under ultrasound guidance. This technique does not heat the prostate but destroys the endothelial cells and cancer by activating the photodynamic agent. Damage to surrounding structures appears to be limited and can be controlled by the duration and intensity of the light. We have reviewed the principles of focal therapy and these new therapeutic modalities.

Established therapeutic approaches for clinically localized prostate cancer include watchful waiting (active surveillance), radical prostatectomy, and radiotherapy. The risk of progression during surveillance is related to the initial cancer stage and grade; reasonable evidence has supported the safety and feasibility, during a period of 5-10 years, of an active surveillance regimen for men with low-risk prostate cancer. The progression rates at >10 years have not yet been studied in modern trials. Patients with low-risk tumor characteristics can be actively monitored without sacrificing the possibility of cure and without being exposed to an undue risk of disease progression, although some patients will not accept the emotional burden of living with an untreated cancer. Focal ablation might be an attractive alternative to active surveillance for some patients with low-risk cancer, if it proves to have minimal adverse effects on their quality of life. Radical prostatectomy is an effective form of therapy for patients with clinically significant prostate cancer; however, outcomes are highly sensitive to variations in surgical technique. Because of the risks of perioperative complications and urinary and sexual dysfunction, which appear to be as great with robotic-assisted prostatectomy as with any other technique, patients with low-risk cancer, especially those >60 years, might be attracted to more conservative alternatives, including active surveillance, radiotherapy, and focal ablation. External beam radiotherapy is an effective, noninvasive form of therapy, but it carries the long-term risks of troublesome bowel and sexual and urinary dysfunction. It might be too aggressive for many low-risk cancers detected in screened populations. For more aggressive cancers, local recurrence after radiotherapy carries substantial morbidity and low rates of long-term cancer control. Brachytherapy, a convenient, effective form of radiotherapy, is targeted at selected patients with clinically confined cancer and a prostate size of <60 g without evidence of extraprostatic extension on imaging. However, excellent outcomes require meticulous technique; acute urinary symptoms are frequent; and the long-term risks of proctitis and erectile dysfunction are comparable to the risks associated with external beam radiotherapy. Androgen-deprivation therapy is not recommended for men with localized prostate cancer who would otherwise be candidates for surgery or radiotherapy, because, even with short-term use, the risk of side effects, including osteopenic fracture and major cardiovascular events, serious. For locally extensive cancer, androgen-deprivation therapy should be used alone only for the relief of local symptoms in men with a life expectancy of <5 years who are not eligible for more aggressive treatment.

OBJECTIVES/OBJECTIVE:It is unclear whether postoperative salvage radiation therapy (SRT) and early adjuvant radiotherapy (ART) after radical prostatectomy lead to equivalent long-term tumor control. We studied a group of patients undergoing ART by comparing them with a matched control group undergoing SRT after biochemical failure. METHODS:Using a multi-institutional database of 2299 patients, 449 patients with pT3-4N0 disease were eligible for inclusion, including 211 patients receiving ART and 238 patients receiving SRT. Patients were matched in a 1:1 ratio according to preoperative prostate-specific antigen Gleason score, seminal vesicle invasion, surgical margin status, and follow-up from date of surgery. RESULTS:A total of 192 patients were matched (96:96). The median follow-up was 94 months from surgery and 73 months from RT completion. There was a significant reduction in biochemical failure with ART compared with SRT. The 5-year freedom from biochemical failure (FFBF) from surgery was 75% after ART, compared with 66% for SRT (hazard ratio [HR] = 1.6, P = .049). The 5-year FFBF from the end of RT was 73% after ART, compared with 50% after SRT (HR = 2.3, log rank [LR] P = .0007). From the end of RT, SRT and Gleason score >or=8 were independent predictors of diminished FFBF. From the date of surgery, Gleason score >or=8 was a significant predictor of FFBF. CONCLUSIONS:Early ART for pT3-4N0 prostate cancer significantly reduces the risk of long-term biochemical progression after radical prostatectomy compared with SRT. Gleason score >or=8 was the only factor on multivariate analysis associated with metastasic progression.

PURPOSE/OBJECTIVE:To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy. METHODS AND MATERIALS/METHODS:Between January 1990 and December 2006, 39 patients with unresectable Stage IVB paranasal sinus carcinoma were treated definitively with chemotherapy plus radiotherapy (n = 35, 90%) or with radiotherapy alone (n = 4, 10%). Patients were treated with three-dimensional conformal radiotherapy (n = 18, 46%), intensity-modulated radiotherapy (n = 12, 31%), or conventional radiotherapy (n = 9, 23%) to a median treatment dose of 70 Gy. Most patients received concurrent platinum-based chemotherapy (n = 32, 82%) and/or concomitant boost radiotherapy (n = 29, 74%). RESULTS:With a median follow-up of 90 months, the 5-year local progression-free survival, regional progression-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 21%, 61%, 51%, 14%, and 15%, respectively. Patients primarily experienced local relapse (n = 25, 64%), mostly within the irradiated field (n = 22). Nine patients developed neck relapses; however none of the 4 patients receiving elective neck irradiation had a nodal relapse. In 13 patients acute Grade 3 mucositis developed. Severe late toxicities occurred in 2 patients with radionecrosis and 1 patient with unilateral blindness 7 years after intensity-modulated radiation therapy (77 Gy to the optic nerve). The only significant factor for improved local progression-free survival and overall survival was a biologically equivalent dose of radiation >/=65 Gy. CONCLUSIONS:Treatment outcomes for unresectable paranasal sinus carcinoma are poor, and combined-modality treatment is needed that is both more effective and associated with less morbidity. The addition of elective neck irradiation may improve regional control.

This Practice Point commentary discusses the paper by Horwitz and colleagues, which reported the long-term results of the RTOG 92-02 trial in which patients with locally advanced, node-negative prostate cancer who were treated with neoadjuvant-concurrent hormone ablation therapy and external beam radiation therapy (70 Gy) were subsequently randomized to receive either no further androgen deprivation or long-term (2-year) goserelin therapy. The results at 10 years confirm biochemical and clinical outcome benefits with the use of long-term androgen deprivation therapy for patients treated with conventional-dose radiotherapy. How these results should best be incorporated into dose-escalated radiotherapeutic approaches remains unclear, however, and this issue requires further investigation.