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Purpose: To investigate the utility of endorectal coil magenetic resonance imaging (eMRI) in predicting biochemical relapse in prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy., Methods and Materials: Between 2000 and 2008, 279 men with intermediate- or high-risk prostate cancer underwent eMRI of their prostate before receiving brachytherapy and supplemental intensity-modulated radiotherapy. Endorectal coil MRI was performed before treatment and retrospectively reviewed by two radiologists experienced in genitourinary MRI. Image-based variables, including tumor diameter, location, number of sextants involved, and the presence of extracapsular extension (ECE), were incorporated with other established clinical variables to predict biochemical control outcomes. The median follow-up was 49 months (range, 1-13 years)., Results: The 5-year biochemical relapse-free survival for the cohort was 92%. Clinical findings predicting recurrence on univariate analysis included Gleason score (hazard ratio [HR] 3.6, p = 0.001), PSA (HR 1.04, p = 0.005), and National Comprehensive Cancer Network risk group (HR 4.1, p = 0.002). Clinical T stage and the use of androgen deprivation therapy were not correlated with biochemical failure. Imaging findings on univariate analysis associated with relapse included ECE on MRI (HR 3.79, p = 0.003), tumor size (HR 2.58, p = 0.04), and T stage (HR 1.71, p = 0.004). On multivariate analysis incorporating both clinical and imaging findings, only ECE on MRI and Gleason score were independent predictors of recurrence., Conclusions: Pretreatment eMRI findings predict for biochemical recurrence in intermediate- and high-risk prostate cancer patients treated with combination brachytherapy and external-beam radiotherapy. Gleason score and the presence of ECE on MRI were the only significant predictors of biochemical relapse in this group of patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To compare toxicity profiles and biochemical tumor control outcomes between patients treated with high-dose image-guided radiotherapy (IGRT) and high-dose intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer., Materials and Methods: Between 2008 and 2009, 186 patients with prostate cancer were treated with IGRT to a dose of 86.4 Gy with daily correction of the target position based on kilovoltage imaging of implanted prostatic fiducial markers. This group of patients was retrospectively compared with a similar cohort of 190 patients who were treated between 2006 and 2007 with IMRT to the same prescription dose without, however, implanted fiducial markers in place (non-IGRT). The median follow-up time was 2.8 years (range, 2-6 years)., Results: A significant reduction in late urinary toxicity was observed for IGRT patients compared with the non-IGRT patients. The 3-year likelihood of grade 2 and higher urinary toxicity for the IGRT and non-IGRT cohorts were 10.4% and 20.0%, respectively (p = 0.02). Multivariate analysis identifying predictors for grade 2 or higher late urinary toxicity demonstrated that, in addition to the baseline Internatinoal Prostate Symptom Score, IGRT was associated with significantly less late urinary toxicity compared with non-IGRT. The incidence of grade 2 and higher rectal toxicity was low for both treatment groups (1.0% and 1.6%, respectively; p = 0.81). No differences in prostate-specific antigen relapse-free survival outcomes were observed for low- and intermediate-risk patients when treated with IGRT and non-IGRT. For high-risk patients, a significant improvement was observed at 3 years for patients treated with IGRT compared with non-IGRT., Conclusions: IGRT is associated with an improvement in biochemical tumor control among high-risk patients and a lower rate of late urinary toxicity compared with high-dose IMRT. These data suggest that, for definitive radiotherapy, the placement of fiducial markers and daily tracking of target positioning may represent the preferred mode of external-beam radiotherapy delivery for the treatment of prostate cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To review the impact of high-dose radiotherapy (RT) in the postprostatectomy salvage setting on long-term biochemical control and distant metastases-free survival, and to identify clinical and pathologic predictors of outcomes., Methods and Materials: During 1988-2007, 285 consecutive patients were treated with salvage RT (SRT) after radical prostatectomy. All patients were treated with either three-dimensional conformal RT or intensity-modulated RT. Two hundred seventy patients (95%) were treated to a dose ≥66 Gy, of whom 205 (72%) received doses ≥70 Gy. Eighty-seven patients (31%) received androgen-deprivation therapy as a component of their salvage treatment. All clinical and pathologic records were reviewed to identify treatment risk factors and response., Results: The median follow-up time after SRT was 60 months. Seven-year actuarial prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival were 37% and 77%, respectively. Independent predictors of biochemical recurrence were vascular invasion (p < 0.01), negative surgical margins (p < 0.01), presalvage PSA level >0.4 ng/mL (p < 0.01), androgen-deprivation therapy (p = 0.03), Gleason score ≥7 (p = 0.02), and seminal vesicle involvement (p = 0.05). Salvage RT dose ≥70 Gy was not associated with improvement in biochemical control. A doubling time <3 months was the only independent predictor of metastatic disease (p < 0.01). There was a trend suggesting benefit of SRT dose ≥70 Gy in preventing clinical local failure in patients with radiographically visible local disease at time of SRT (7 years: 90% vs. 79.1%, p = 0.07)., Conclusion: Salvage RT provides effective long-term biochemical control and freedom from metastasis in selected patients presenting with detectable PSA after prostatectomy. Androgen-deprivation therapy was associated with improvement in biochemical progression-free survival. Clinical local failures were rare but occurred most commonly in patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses ≥70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer., Methods and Materials: Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data., Results: The 10-year likelihood of SM development was 25% after EBRT and 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population., Conclusions: Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased, number of skin cancers in the EBRT patients compared with that of the general population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To compare biochemical outcomes and morbidity associated with iodine-125 ((125)I) and palladium-103 ((103)Pd) brachytherapy as part of combined modality therapy for clinically localized prostate cancer., Methods and Materials: Between October 2002 and December 2008, 259 patients underwent prostate brachytherapy ((125)I prescription dose, 110Gy: n=199; (103)Pd prescription dose, 100Gy: n=60) followed by external beam radiotherapy (median dose, 50.4Gy). Eighty-seven patients also received neoadjuvant androgen deprivation therapy. Toxicities were recorded with CTCAE v 3.0, International Prostate Symptoms Score (IPSS), and International Index of Erectile Function questionnaires., Results: Overall, acute Grade ≥2 genitourinary toxicity occurred in 21% and 30% of patients treated with (125)I and (103)Pd, respectively (p=0.16). There were no significant differences in IPSS change or urinary quality-of-life scores between the isotopes at 4, 6, or 12 months (p=0.20, 0.21, and 1.0, respectively). IPSS resolution occurred at a median of 11 and 6 months for (125)I and (103)Pd patients, respectively (p=0.03). On multivariate analysis, only the use of neoadjuvant androgen deprivation therapy was predictive of time to IPSS resolution (p=0.046). Late Grade ≥2 gastrointestinal toxicity occurred in 7% of (125)I patients and 6% of patients treated with (103)Pd. Of 129 potent patients at baseline, there was better erectile function in patients who received (103)Pd (p=0.02); however, the followup was shorter for these patients. The 5-year prostate-specific antigen relapse-free survival for (125)I and (103)Pd patients was 95.2% and 98.2% (p=0.73), respectively., Conclusion: There were no differences in acute or long-term genitourinary or gastrointestinal toxicity between (125)I and (103)Pd in combined modality therapy for prostate cancer. There may be less erectile toxicity with the use of (103)Pd; however, additional followup of these patients is needed. There was no significant difference in 5-year prostate-specific antigen relapse-free survival between (103)Pd and (125)I., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify predictors of biochemical tumor control and present an updated prognostic nomogram for patients with clinically localized prostate cancer treated with brachytherapy., Methods and Materials: One thousand four hundred sixty-six patients with clinically localized prostate cancer were treated with brachytherapy alone or along with supplemental conformal radiotherapy. Nine hundred one patients (61%) were treated with Iodine-125 ((125)I) monotherapy to a prescribed dose of 144Gy, and 41 (4.5%) were treated with Palladium-103 ((103)Pd) monotherapy to a prescribed dose of 125Gy. In patients with higher risk features (n=715), a combined modality approach was used, which comprised (125)I or (103)Pd seed implantation or Iridium-192 high-dose rate brachytherapy followed 1-2 months later by supplemental intensity-modulated image-guided radiotherapy to the prostate., Results: The 5-year prostate-specific antigen relapse-free survival (PSA-RFS) outcomes for favorable-, intermediate-, and high-risk patients were 98%, 95%, and 80%, respectively (p<0.001). Multivariate Cox regression analysis identified Gleason score (p<0.001) and pretreatment PSA (p=0.04) as predictors for PSA tumor control. In this cohort of patients, the use of neoadjuvant and concurrent androgen deprivation therapy did not influence biochemical tumor control outcomes. In the subset of patients treated with (125)I monotherapy, D(90)>140Gy compared with lower doses was associated with improved PSA-RFS. A nomogram predicting PSA-RFS was developed based on these predictors and had a concordance index of 0.70., Conclusions: Results with brachytherapy for all treatment groups were excellent. D(90) higher than 140Gy was associated with improved biochemical tumor control compared with lower doses. Androgen deprivation therapy use did not impact on tumor control outcomes in these patients., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Context: High-risk prostate cancer (PCa) is a potentially lethal disease. It is clinically important to identify patients with high-risk PCa early on because they stand to benefit the most from curative therapy. Because of recent advances in PCa management, a multimodal approach may be advantageous., Objective: Define high-risk PCa, and identify the best diagnostic and treatment patterns for patients with clinically localized and locally advanced disease. A critical analysis of published results following monomodal and/or multimodal therapy for high-risk PCa patients was also performed., Evidence Acquisition: A review of the literature was performed using the Medline, Embase, Scopus, and Web of Science databases as well as the Cochrane Database of Systematic Reviews., Evidence Synthesis: High-risk PCa accounts for ≤ 15% of all new diagnoses. Compared with patients with low- and intermediate-risk PCa, patients with high-risk PCa are at increased risk of treatment failure. Unfortunately, no contemporary randomized controlled trials comparing different treatment modalities exist. Evaluation of the results published to date shows that no single treatment can be universally recommended. Most often, a multimodal approach is warranted to optimize patient outcomes., Conclusions: A significant minority of patients continue to present with high-risk PCa, which remains lethal in some cases. Outcomes following treatment of men with high-risk tumors have not substantially improved over time. However, not all high-risk patients are at the same risk of PCa progression and death. At present, a multimodal approach seems the best way to achieve acceptable outcomes for high-risk PCa patients., (Copyright © 2012. Published by Elsevier B.V.)

Objectives/hypothesis: To develop and validate a simple prognostic tool that would help predict larynx preservation outcome., Study Design: A retrospective review of 3 prospective studies., Methods: We reviewed consecutive chemotherapy/radiation protocols for patients (n = 170) with advanced, resectable, squamous cell, larynx, or pharynx cancer treated at Memorial Sloan-Kettering Cancer Center from 1988 to 1995 with larynx preservation intent. The outcome was successful larynx preservation. Model validation used data from U. S. Department of Veterans Affairs larynx preservation study., Results: The developed model added one point for each poor prognostic covariate present (show in parentheses) and was given the acronym TALK: T stage (T4), albumin (<4 g/dL), maximum alcohol/liquor use (≥6 drinks/day or heavy drinking), and Karnofsky performance status (<80%). The 3-year larynx preservation rates by TALK score were 65% (0), 41% (1-2), and 6% (3-4), P < .0001; on validation, the TALK 3-4 group was particularly well demarcated., Conclusions: The TALK score is an easily applied and valid tool that should assist treatment selection., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Unlabelled: Study Type--Therapy (practice patterns). Level of Evidence 2b. What's known on the subject? And what does the study add? The treatment of locally advanced prostate cancer varies widely even though there is level one evidence supporting the use of multimodality therapy as compared with monotherapy. This study defines treatment patterns of locally advanced prostate cancer within the United States and identifies predicators of who receives multimodality therapy rather than monotherapy., Objective: • To identify treatment patterns and predictors of receiving multimodality therapy in patients with locally advanced prostate cancer (LAPC)., Patients and Methods: • The cohort comprised patients ≥66 years with clinical stage T3 or T4 non-metastatic prostate cancer diagnosed between 1998 and 2005 identified from the Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims. • Treatments were classified as radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) received within 6 and 24 months of diagnosis. • We assessed trends over time and used multivariable logistic regression to identify predictors of multimodality treatment., Results: • Within the first 6 months of diagnosis, 1060 of 3095 patients (34%) were treated with a combination of RT and ADT, 1486 (48%) received monotherapy (RT alone, ADT alone or RP alone), and 461 (15%) received no active treatment. • The proportion of patients who received RP increased, exceeding 10% in 2005. • Use of combined RT and ADT and use of ADT alone fluctuated throughout the study period. • In all 6% of patients received RT alone in 2005. • Multimodality therapy was less common in patients who were older, African American, unmarried, who lived in the south, and who had co-morbidities or stage T4 disease., Conclusions: • Treatment of LAPC varies widely, and treatment patterns shifted during the study period. • The slightly increased use of multimodality therapy since 2003 is encouraging, but further work is needed to increase combination therapy in appropriate patients and to define the role of RP., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors., Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48)., Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a high single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008)., Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To analyze the effect of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) on treatment outcomes in patients treated with definitive intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC)., Methods and Materials: Between September 1998 and April 2009, a total of 442 patients with squamous cell carcinoma of the oropharynx were treated with IMRT with curative intent at our center. Thirty patients treated postoperatively and 2 additional patients who started treatment more than 6 months after diagnosis were excluded. A total of 340 patients with restorable treatment plans were included in this present study. The majority of the patients underwent concurrent platinum-based chemotherapy. The pGTV and nGTV were calculated using the original clinical treatment plans. Cox proportional hazards models and log-rank tests were used to evaluate the correlation between tumor volumes and overall survival (OS), and competing risks analysis tools were used to evaluate the correlation between local failure (LF), regional failure (RF), distant metastatic failure (DMF) vs. tumor volumes with death as a competing risk., Results: Median follow-up among surviving patients was 34 months (range, 5-67). The 2-year cumulative incidence of LF, RF and DF in this cohort of patients was 6.1%, 5.2%, and 12.2%, respectively. The 2-year OS rate was 88.6%. Univariate analysis determined pGTV and T-stage correlated with LF (p < 0.0001 and p = 0.004, respectively), whereas nGTV was not associated with RF. On multivariate analysis, pGTV and N-stage were independent risk factors for overall survival (p = 0.0003 and p = 0.0073, respectively) and distant control (p = 0.0008 and p = 0.002, respectively)., Conclusions: In this cohort of patients with OPC treated with IMRT, pGTV was found to be associated with overall survival, local failure, and distant metastatic failure., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB)., Methods and Materials: The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS., Results: Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography-based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography-magnetic resonance image fusion is viewed as useful, but not mandatory., Conclusions: Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians., (Copyright © 2012. Published by Elsevier Inc.)

Purpose: To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC)., Methods and Materials: Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%. The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based., Results: Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia ≥Grade 2 was 11% and 29%, respectively., Conclusions: Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: With salvage radiation therapy (SRT) in the postprostatectomy setting, the need to deliver sufficient radiation doses to achieve a high probability of tumor control is balanced with the risk of increased toxicity. Intensity-modulated radiation therapy (IMRT) in the postprostatectomy salvage setting is gaining interest as a treatment strategy., Objective: Compare acute and late toxicities in patients treated with IMRT and three-dimensional conformal radiation therapy (3D-CRT) in the postprostatectomy salvage setting., Design, Setting, and Participants: A total of 285 patients who were treated at our institution between 1988 and 2007 with SRT after radical prostatectomy for biochemical recurrence were identified. All medical records were reviewed and toxicity recorded. Median follow-up was 60 mo., Intervention: All patients were treated with SRT with either 3D-CRT (n=109) or IMRT (n=176). A total of 205 patients (72%) were treated with doses ≥70Gy., Measurements: Late gastrointestinal (GI) and genitourinary (GU) toxicities were recorded using the Common Terminology Criteria for Adverse Events v. 3.0 definition., Results and Limitations: The 5-yr actuarial rates of late grade ≥2 GI and GU toxicity were 5.2% and 17.0%, respectively. IMRT was independently associated with a reduction in grade ≥2 GI toxicity compared with 3D-CRT (5-yr IMRT, 1.9%; 5-yr 3D-CRT, 10.2%; p=0.02). IMRT was not associated with a reduction in risk of grade ≥2 GU toxicity (5-yr IMRT, 16.8%; 5-yr 3D-CRT, 15.8%; p=0.86), urinary incontinence (5-yr IMRT, 13.6%; 5-yr 3D-CRT, 7.9%; p=0.25), or grade 3 erectile dysfunction (5-yr IMRT, 26%; 5-yr 3D-CRT, 30%; p=0.82). Of patients who developed late grade ≥2 GI or GU toxicity, 38% and 44%, respectively, experienced resolution of their symptoms prior to the last follow-up., Conclusions: Our experience with high-dose IMRT in the postprostatectomy salvage setting demonstrates that the treatment can be delivered safely with an associated reduction in late GI toxicity., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients., Objective: Identify predictors of biochemical tumor control and distant metastases-free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT., Design, Setting, and Participants: This retrospective analysis comprised 2551 patients with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr., Intervention: Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo., Measurements: A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed., Results and Limitations: Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2-79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes., Conclusions: Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Osteoradionecrosis (ORN) is a known complication of radiation therapy to the head and neck. However, the incidence of this complication with intensity-modulated radiation therapy (IMRT) and dental sequelae with this technique have not been fully elucidated., Methods and Materials: From December 2000 to July 2007, 168 patients from our institution have been previously reported for IMRT of the oral cavity, nasopharynx, larynx/hypopharynx, sinus, and oropharynx. All patients underwent pretreatment dental evaluation, including panoramic radiographs, an aggressive fluoride regimen, and a mouthguard when indicated. The median maximum mandibular dose was 6,798 cGy, and the median mean mandibular dose was 3,845 cGy. Patient visits were retrospectively reviewed for the incidence of ORN, and dental records were reviewed for the development of dental events. Univariate analysis was then used to assess the effect of mandibular and parotid gland dosimetric parameters on dental endpoints., Results: With a median clinic follow-up of 37.4 months (range, 0.8-89.6 months), 2 patients, both with oral cavity primaries, experienced ORN. Neither patient had preradiation dental extractions. The maximum mandibular dose and mean mandibular dose of the 2 patients were 7,183 and 6,828 cGy and 5812 and 5335 cGy, respectively. In all, 17% of the patients (n = 29) experienced a dental event. A mean parotid dose of >26 Gy was predictive of a subsequent dental caries, whereas a maximum mandibular dose >70 Gy and a mean mandibular dose >40 Gy were correlated with dental extractions after IMRT., Conclusions: ORN is rare after head-and-neck IMRT, but is more common with oral cavity primaries. Our results suggest different mechanisms for radiation-induced caries versus extractions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The objective of this review is to present an overview of each modality and delineate how to best select patients who are optimal candidates for these treatment approaches. Prostate brachytherapy as a curative modality for clinically localized prostate cancer has become increasingly utilized over the past decade; 25% of all early cancers are now treated this way in the United States (1). The popularity of this treatment strategy lies in the highly conformal nature of radiation dose, low morbidity, patient convenience, and high efficacy rates. Prostate brachytherapy can be delivered by either a permanent interstitial radioactive seed implantation (low dose rate [LDR]) or a temporary interstitial insertion of iridium-192 (Ir192) afterloading catheters. The objective of both of these techniques is to deliver a high dose of radiation to the prostate gland while exposing normal surrounding tissues to minimal radiation dose. Brachytherapy techniques are ideal to achieve this goal given the close proximity of the radiation source to tumor and sharp fall off of the radiation dose cloud proximate to the source. Brachytherapy provides a powerful means of delivering dose escalation above and beyond that achievable with intensity-modulated external beam radiotherapy alone. Careful selection of appropriate patients for these therapies, however, is critical for optimizing both disease-related outcomes and treatment-related toxicity.

Background: The authors investigated long-term tumor control and toxicity outcomes after high-dose, intensity-modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer., Methods: Between April 1996 and January 1998, 170 patients received 81 gray (Gy) using a 5-field IMRT technique. Patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse, distant metastases, and cause-specific survival outcomes were calculated. The median follow-up was 99 months., Results: The 10-year actuarial prostate-specific antigen relapse-free survival rates were 81% for the low-risk group, 78% for the intermediate-risk group, and 62% for the high-risk group; the 10-year distant metastases-free rates were 100%, 94%, and 90%, respectively; and the 10-year cause-specific mortality rates were 0%, 3%, and 14%, respectively. The 10-year likelihood of developing grade 2 and 3 late genitourinary toxicity was 11% and 5%, respectively; and the 10-year likelihood of developing grade 2 and 3 late gastrointestinal toxicity was 2% and 1%, respectively. No grade 4 toxicities were observed., Conclusions: To the authors' knowledge, this report represents the longest followed cohort of patients who received high-dose radiation levels of 81 Gy using IMRT for localized prostate cancer. The findings indicated that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized prostate cancer., (Copyright © 2010 American Cancer Society.)

Objectives: To compare the long-term, prostate-specific antigen relapse-free survival outcome and incidence of toxicity for patients with low-risk prostate cancer who underwent brachytherapy or intensity-modulated radiotherapy (RT)., Methods: A total of 729 consecutive patients underwent brachytherapy (n = 448; prescription dose 144 Gy) or intensity-modulated RT alone (n = 281; prescription dose 81 Gy). The prostate-specific antigen relapse-free survival using the nadir plus 2 ng/mL definition and late toxicity using the National Cancer Institute's Common Terminology Criteria for Adverse Events were determined., Results: The 7-year prostate-specific antigen relapse-free survival rate for the brachytherapy and intensity-modulated RT groups was 95% and 89% for low-risk patients, respectively (P = .004). Cox regression analysis demonstrated that brachytherapy was associated with improved prostate-specific antigen relapse-free survival, even after adjustment for other variables. The incidence of metastatic disease between treatment sessions was low for both treatment groups. Late grade 2 gastrointestinal toxicity was observed in 5.1% and 1.4% of the brachytherapy and intensity-modulated RT groups, respectively (P = .02). No significant differences were seen between treatment groups for late grade 3 or greater rectal complications (brachytherapy 1.1% and intensity-modulated RT 0%; P = .19). Late grade 2 urinary toxicity occurred more often in the brachytherapy group than in the intensity-modulated RT group (15.6% and 4.3%, respectively; P < .0001). No significant differences were seen between the 2 treatment groups for late grade 3 urinary toxicity (brachytherapy 2.2% and intensity-modulated RT 1.4%; P = .62)., Conclusions: Among low-risk prostate cancer patients, the 7-year biochemical tumor control was superior for intraoperatively planned brachytherapy compared with high-dose intensity-modulated RT. Although significant toxicities were minimal for both groups, modest, but significant, increases in grade 2 urinary and rectal symptoms were noted for brachytherapy compared with intensity-modulated RT., (Published by Elsevier Inc.)

Purpose: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites., Methods and Materials: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007., Results: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy), intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses (≤22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003)., Conclusion: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer., Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years., Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p=0.002). In a multivariate analysis, statin use (hazard ratio [HR] 0.69, p=0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p=0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p=0.51). On multivariate analysis, lower NCCN risk group (p=0.01) and ADT use (p=0.005) predicted improved DMFS., Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine if the location and number of positive surgical margins (PSMs) after radical prostatectomy (RP) are associated with recurrence after salvage external beam radiation therapy (sEBRT)., Patients and Methods: We retrospectively reviewed the medical records of 60 patients with PSMs who underwent three-dimensional conformal sEBRT for biochemical recurrence (BCR) or clinically detected local recurrence after RP between 1996 and 2007. PSMs were categorized as present or absent at three locations, and patients were classified as having either one or more than one PSM. BCR after RP was defined as a prostate-specific antigen (PSA) level of ≥ 0.1 ng/mL. BCR after sEBRT was defined as a serum PSA level of ≥ 0.1 ng/mL above the PSA nadir after sEBRT., Results: In all, 24 (40%) patients had more than one PSM. Overall, the most common location of a PSM was the posterior prostate with 40 (66%) patients having a positive posterior margin. The location of PSMs was not significantly associated with secondary BCR (global P= 0.8). There was a borderline result between the number of PSMs and BCR: men with more than one PSM were less likely to recur compared with those with only one PSM (hazard ratio 0.42; P= 0.067)., Conclusions: This is the first study to specifically analyse location and number of PSMs as prognostic factors for men who undergo sEBRT. There was no evidence to suggest that the location of a PSM predicted secondary BCR. Further research is needed to determine whether the number of PSMs is an important predictor of BCR after sEBRT., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objectives: To evaluate the use of real-time kilovoltage cone-beam computed tomography (CBCT) during prostate brachytherapy for intraoperative dosimetric assessment and correcting deficient dose regions., Methods: A total of 20 patients were evaluated intraoperatively with a mobile CBCT unit immediately after implantation while still anesthetized. The source detector system was enclosed in a circular CT-like geometry with a bore that accommodates patients in the lithotomy position. After seed deposition, the CBCT scans were obtained. The dosimetry was evaluated and compared with the standard postimplantation CT-based assessment. In 8 patients, the deposited seeds were localized in the intraoperative CBCT frame of reference and registered to the intraoperative transrectal ultrasound images. With this information, a second intraoperative plan was generated to ascertain whether additional seeds were needed to achieve the planned prescription dose. The final dosimetry was compared with the postimplantation scan assessment., Results: The mean differences between the dosimetric parameters from the intraoperative CBCT and postimplant CT scans were < .5% for percentage of volume receiving 100% of the prescription dose, minimal dose received by 90% of the prostate, and percentage of volume receiving 150% of the prescription dose. The minimal dose received by 5% (maximal dose) of the urethra differed by 8% on average and for the rectum an average difference of approximately 18% was observed. After fusion of the implanted seed coordinates from the intraoperative CBCT scans to the intraoperative transrectal ultrasound images, the dosimetric outcomes were not significantly different from the postimplantation CT dosimetric results., Conclusions: Intraoperative CT-based dosimetric evaluation of prostate permanent seed implantation before anesthesia reversal is feasible and might avert misadministration of dose delivery. The dosimetric measurements using the intraoperative CBCT scans were dependable and correlated well with the postimplant diagnostic CT findings., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: We report on a retrospective comparison of biochemical outcomes using an ultra-high dose of conventionally fractionated intensity-modulated radiation therapy (IMRT) vs. a lower dose of IMRT combined with high-dose-rate (HDR) brachytherapy to increase the biologically effective dose of IMRT., Methods: Patients received IMRT of 86.4Gy (n=470) or HDR brachytherapy (21Gy in three fractions) followed by IMRT of 50.4Gy (n=160). Prostate-specific antigen (PSA) relapse was defined as PSA nadir+2. Median followup was 53 months for IMRT alone and 47 months for HDR., Results: The 5-year actuarial PSA relapse-free survival (PRFS) for HDR plus IMRT vs. ultra-high-dose IMRT were 100% vs. 98%, 98% vs. 84%, and 93% vs. 71%, for National Comprehensive Cancer Network low- (p=0.71), intermediate- (p<0.001), and high-risk (p=0.23) groups, respectively. Treatment (p=0.0006), T stage (p<0.0001), Gleason score (p<0.0001), pretreatment PSA (p=0.0037), risk group (p<0.0001), and lack of androgen-deprivation therapy (p=0.0005) were significantly associated with improved PRFS on univariate analysis. HDR plus IMRT vs. ultra-high-dose IMRT (p=0.0012, hazard ratio [HR]=0.184); age (p=0.0222, HR=0.965); and risk group (p<0.0001, HR=2.683) were associated with improved PRFS on multivariate analysis., Conclusion: Dose escalation of IMRT by adding HDR brachytherapy provided improved PRFS in the treatment of prostate cancer compared with ultra-high-dose IMRT, independent of risk group on multivariate analysis, with the most significant benefit for intermediate-risk patients., (Copyright © 2010 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To present our single-institution experience with postoperative radiotherapy for mucosal melanoma of the head and neck., Methods: Between 1992 and 2007, 27 patients with mucosal melanoma of the head and neck underwent surgical resection followed by postoperative radiotherapy. Median age was 68 years (range: 45-89 years). Sites included were sinonasal in 24 patients, oral cavity in 2, and oropharynx in 1. All but 2 patients had stage I disease. Twenty-two patients received hypofractionated radiation. Radiation techniques were intensity-modulated radiation therapy in 13, 3-dimensional conformal in 4, and conventional in 10., Results: The median follow-up for living patients was 45 months (range: 24-122 months). The 3- and 5-year estimates of local progression-free, loco-regional progression-free, distant metastasis-free, and overall survival were: 47% and 35%; 34% and 22%; 30% and 24%; and 40% and 33%, respectively. Median time to local failure and distant metastasis was 32 and 14 months, respectively. Acute toxicities included 19% with grade 2 or higher mucositis. No late complications related to the optic structures were seen., Conclusions: Modern radiotherapeutic techniques including intensity-modulated radiation therapy appear feasible and well-tolerated in the postoperative treatment of head and neck mucosal melanoma. Unusual or serious late complications have not been observed despite extensive use of hypofractionated regimens. However, rates of local and distant failure remain high.

Purpose: To use radiation exposure rate measurements to determine patient-specific radiation safety instructions with the aim of reducing unnecessary precaution times and to evaluate potential doses to members of the public., Methods and Materials: Radiation exposure rate measurements were obtained from 1279 patients with Stage T1-2 prostate cancer who underwent transperineal (125)I or (103)Pd seed implantation from January 1995 through July 2008. An algorithm was developed from these measurements to determine the required precaution times to maintain public effective doses below 50% of the limits for specific exposure situations., Results: The median air kerma rates at 30 cm from the anterior skin surface were 4.9 microGy/h (range: 0.1-31.5) for (125)I and 1.5 microGy/h (range: 0.02-14.9) for (103)Pd. The derived algorithms depended primarily on the half-life T(p), the measured exposure rate at 30 cm, and specific exposure situation factors. For the typical (103)Pd patient, no radiation safety precautions are required. For the typical (125)I patient, no precautions are required for coworkers, nonpregnant adults who do not sleep with the patient, or nonpregnant adults who sleep with the patient. Typical (125)I patients should only avoid sleeping in the "spoon" position (i.e., in contact) with pregnant adults and avoid holding a child for long periods of time in the lap for about 2 months., Conclusions: The large number of cases available for this study permitted the development of an algorithm to simply determine patient-specific radiation safety instructions. The resulting precaution times are significantly less restrictive than those generally prescribed currently., ((c) 2010 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We assessed the effect of radical prostatectomy (RP) and external beam radiotherapy (EBRT) on distant metastases (DM) rates in patients with localized prostate cancer treated with RP or EBRT at a single specialized cancer center., Patients and Methods: Patients with clinical stages T1c-T3b prostate cancer were treated with intensity-modulated EBRT (> or = 81 Gy) or RP. Both cohorts included patients treated with salvage radiotherapy or androgen-deprivation therapy for biochemical failure. Salvage therapy for patients with RP was delivered a median of 13 months after biochemical failure compared with 69 months for EBRT patients. DM was compared controlling for patient age, clinical stage, serum prostate-specific antigen level, biopsy Gleason score, and year of treatment., Results: The 8-year probability of freedom from metastatic progression was 97% for RP patients and 93% for EBRT patients. After adjustment for case mix, surgery was associated with a reduced risk of metastasis (hazard ratio, 0.35; 95% CI, 0.19 to 0.65; P < .001). Results were similar for prostate cancer-specific mortality (hazard ratio, 0.32; 95% CI, 0.13 to 0.80; P = .015). Rates of metastatic progression were similar for favorable-risk disease (1.9% difference in 8-year metastasis-free survival), somewhat reduced for intermediate-risk disease (3.3%), and more substantially reduced in unfavorable-risk disease (7.8% in 8-year metastatic progression)., Conclusion: Metastatic progression is infrequent in men with low-risk prostate cancer treated with either RP or EBRT. RP patients with higher-risk disease treated had a lower risk of metastatic progression and prostate cancer-specific death than EBRT patients. These results may be confounded by differences in the use and timing of salvage therapy.

Purpose: To report the use of high-dose-rate intraoperative radiation therapy (HDR-IORT) for recurrent head-and-neck cancer (HNC) at a single institution., Methods and Materials: Between July 1998 and February 2007, 34 patients with recurrent HNC received 38 HDR-IORT treatments using a Harrison-Anderson-Mick applicator with Iridium-192. A single fraction (median, 15 Gy; range, 10-20 Gy) was delivered intraoperatively after surgical resection to the region considered at risk for close or positive margins. In all patients, the target region was previously treated with external beam radiation therapy (median dose, 63 Gy; range, 24-74 Gy). The 1- and 2-year estimates for in-field local progression-free survival (LPFS), locoregional progression-free survival (LRPFS), distant metastases-free survival (DMFS), and overall survival (OS) were calculated., Results: With a median follow-up for surviving patients of 23 months (range, 6-54 months), 8 patients (24%) are alive and without evidence of disease. The 1- and 2-year LPFS rates are 66% and 56%, respectively, with 13 (34%) in-field recurrences. The 1- and 2-year DMFS rates are 81% and 62%, respectively, with 10 patients (29%) developing distant failure. The 1- and 2-year OS rates are 73% and 55%, respectively, with a median time to OS of 24 months. Severe complications included cellulitis (5 patients), fistula or wound complications (3 patients), osteoradionecrosis (1 patient), and radiation-induced trigeminal neuralgia (1 patient)., Conclusions: HDR-IORT has shown encouraging local control outcomes in patients with recurrent HNC with acceptable rates of treatment-related morbidity. Longer follow-up with a larger cohort of patients is needed to fully assess the benefit of this procedure., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence., Methods and Materials: Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an alpha/beta of 2., Results: The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73-81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710., Conclusion: A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The 2 primary therapeutic interventions for localized prostate cancer are delivered by different types of physicians, urologists, and radiation oncologists. We evaluated how visits to specialists and primary care physicians (PCPs) by men with localized prostate cancer are related to treatment choice., Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified 85 088 men with clinically localized prostate cancer diagnosed at age 65 years or older, between 1994 and 2002. Men were categorized by primary treatment received within 9 months of diagnosis: radical prostatectomy (n = 18 201 [21%]), radiotherapy (n = 35 925 [42%]), androgen deprivation (n = 14 021 [17%]), or expectant management (n = 16 941 [20%]). Visits to specialists and PCPs were analyzed by patient characteristics and primary therapies received and were identified using Medicare claims and the American Medical Association Physician Masterfile., Results: Overall, 42 309 men (50%) were seen exclusively by urologists, 37 540 (44%) by urologists and radiation oncologists, 2329 (3%) by urologists and medical oncologists, and 2910 (3%) by all 3 specialists. There was a strong association between the type of specialist seen and primary therapy received. Visits to PCPs were infrequent between diagnosis and receipt of therapy (22% of patients visited any PCP and 17% visited an established PCP) and were not associated with a greater likelihood of specialist visits. Irrespective of age, comorbidity status, or specialist visits, men seen by PCPs were more likely to be treated expectantly., Conclusions: Specialist visits relate strongly to prostate cancer treatment choices. In light of these findings, prior evidence that specialists prefer the modality they themselves deliver and the lack of conclusive comparative studies demonstrating superiority of one modality over another, it is essential to ensure that men have access to balanced information before choosing a particular therapy for prostate cancer.

Most advice currently available with regard to fluoroscopic skin reactions is based on a table published in 1994. Many caveats in that report were not included in later reproductions, and subsequent research has yielded additional insights. This review is a consensus report of current scientific data. Expected skin reactions for an average patient are presented in tabular form as a function of peak skin dose and time after irradiation. The text and table indicate the variability of reactions in different patients. Images of injuries to skin and underlying tissues in patients and animals are provided and are categorized according to the National Cancer Institute skin toxicity scale, offering a basis for describing cutaneous radiation reactions in interventional fluoroscopy and quantifying their clinical severity. For a single procedure performed in most individuals, noticeable skin changes are observed approximately 1 month after a peak skin dose exceeding several grays. The degree of injury to skin and subcutaneous tissue increases with dose. Specialized wound care may be needed when irradiation exceeds 10 Gy. Residual effects from radiation therapy and from previous procedures influence the response of skin and subcutaneous tissues to subsequent procedures. Skin irradiated to a dose higher than 3-5 Gy often looks normal but reacts abnormally when irradiation is repeated. If the same area of skin is likely to be exposed to levels higher than a few grays, the effects of previous irradiation should be included when estimating the expected tissue reaction from the additional procedure., ((c) RSNA, 2010.)

Background: There has been an increase in the utilization of single-fraction stereotactic body radiation therapy (SBRT) to treat thoracic structures, but there have been few reports describing toxicity outcomes with this treatment., Methods: We evaluated 119 sites (114 patients) with no prior history of thoracic radiation were treated from 10/1/2003 to 10/27/2008 with single-fraction SBRT to thoracic structures. The median dose to the gross tumor volume was 2400 cGy (range 1800-2400 cGy), as was the median dose to the planning target volume (range 1600-2400 cGy). A detailed review of thoracic toxicities was performed to include pneumonitis or Grade 2 or higher esophageal and bronchial toxicity. In addition, we retrospectively contoured the esophagus and bronchus of 48 patients treated in 2004-2005, prior to the establishment of dose constraints to determine the range of doses that these structures received., Results: Of the contoured patients, the median dose to the hottest 1cc (D1cc) of the esophagus was 1250 cGy (range 158-2572 cGy). The median bronchial D1cc was 1101 cGy (range 260-2211 cGy). At a median follow-up of 11.6 months, there were seven Grade 2 or higher esophageal toxicities, including one Grade 3 and one Grade 4 toxicities. There were two bronchial toxicities, one Grade 2 and one Grade 3. There were no cases of pneumonitis., Conclusions: High-dose single-fraction SBRT is well tolerated to the thoracic region, with most patients tolerating high doses to central structures without significant toxicity.

Purpose: To report the influence of posttreatment prostate-specific antigen (PSA) nadir response at 2 years after external beam radiotherapy (RT) on distant metastases (DM) and cause-specific mortality (CSM)., Methods and Materials: Eight hundred forty-four patients with localized prostate cancer were treated with conformal RT. The median duration of follow-up was 9.1 years. A fixed landmark time point at 2 years was used to assess the influence of nadir PSA value as a time-dependent variable on long-term outcomes., Results: Multivariate analysis demonstrated that nadir PSA

For men diagnosed with clinically localized prostate cancer, definitive therapy with radical prostatectomy, external beam radiation therapy, or brachytherapy offers a high chance of cure. Currently, there are insufficient data to recommend 1 treatment approach over another, leaving physicians and patients to decide based on their own biases and preferences. Prediction tools, such as nomograms and probability tables, have been created as decision aids to facilitate patient counseling and decision making. Nomograms in particular can assess the therapeutic efficacy of a given therapy by providing individualized estimates of the risk of failure after treatment. The authors performed a comprehensive literature review to identify nomograms assessing the efficacy of brachytherapy in patients with clinically localized prostate cancer, and found a paucity of such models. Analysis of currently available brachytherapy nomograms reveals suboptimal predictive power compared with models based on other treatment modalities. The purpose of this review is to spur development of new and more accurate prediction tools for predicting outcomes after brachytherapy, offering physicians and patients the opportunity to equally assess the efficacy of all available treatment modalities for clinically localized prostate cancer. Cancer 2009;115(13 suppl):3121-7. (c) 2009 American Cancer Society.

Background: To the authors' knowledge, the indications for adjuvant treatment in acinic cell carcinoma (AciCC) of the parotid gland have not been elucidated to date. The aim of the current study was to determine patterns of failure and adverse prognostic features., Methods: Between March of 1989 and August of 2006, 35 patients underwent surgery at Memorial Sloan-Kettering Cancer Center for AciCC of the parotid gland and had their clinical and pathologic features retrospectively analyzed at the primary site. All cases were reviewed by 2 head and neck pathologists. Five-year estimates of survival outcomes were performed, followed by univariate analysis of potential prognostic features., Results: The T classifications were as follows: T1 in 46% of patients, T2 in 23% of patients, T3 in 18% of patients, and T4 in 9% of patients. Three patients had cervical lymph node involvement. All patients underwent surgery as their primary treatment. Approximately 63% of patients (n = 22) received radiation treatment. The median follow-up time for surviving patients was 59.9 months. Five-year estimates of disease-free survival (DFS), overall survival (OS), and local control were 85%, 90%, and 90%, respectively. Of the clinical variables tested, clinical extracapsular extension (ECE), facial nerve sacrifice, and lymph node involvement were found to be significantly associated with a detriment in DFS and OS (P < .05). Positive surgical margins, histologic ECE, >2 mitoses per 10 high-power fields (HPF), atypical mitosis, vascular invasion, perineural invasion, pleomorphism, and necrosis were associated with adverse DFS (P < .05). All of these variables except for vascular invasion (P = .377) and perineural invasion (P = .07) were associated with OS. If high-grade tumors were defined on the basis of high mitotic activity (>2 mitoses/10 HPF) and/or tumor necrosis, high-grade carcinomas had a significantly lower DFS and OS (P = .001)., Conclusions: AciCC had a low treatment failure rate, and a large number of patients could be considered candidates for surgery only. A histologic grading system was devised to help stratify patients for adjuvant treatment.

Purpose: To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade., Methods and Materials: The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model., Results: For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score >/=4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reach a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes., Conclusions: In patients with biopsy Gleason score >/=4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.

Purpose: 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: 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: 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.

Objectives: 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.

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.

Purpose: To evaluate long-term outcomes and toxicity in patients with unresectable paranasal sinus carcinoma treated with radiotherapy, with or without chemotherapy., Methods and Materials: 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.

Objectives: To examine the long-term neck failure outcome in patients with advanced head and neck cancer treated on larynx/organ preservation protocols at Memorial Sloan-Kettering Cancer Center., Materials and Methods: Two hundred thirteen patients were enrolled from 1983 through 1995 on larynx/organ preservation protocols receiving induction chemotherapy followed by radiotherapy alone or with concomitant chemotherapy. Eighty-six patients with node-positive disease received definitive chemoradiotherapy at Memorial Sloan-Kettering Cancer Center. A median dose of 70 Gy was delivered. The median follow-up of the surviving patients was 9 years., Results: Sixty-five patients with node-positive disease achieved a clinical complete response and were observed after chemoradiation without immediate neck dissection. The crude rate of subsequent neck failure among those patients according to initial nodal classification was: N1 14% (3 of 21), N2: 15% (6 of 40), N3: 0% (0 of 4). The median overall survival of these patients was: N1: 12.2 years; N2: 6.5 years; N3: 0.8 years. Patients who experienced a complete response to induction chemotherapy in the neck had improved overall survival (53% vs. 29%; P = 0.005) and a lower incidence of neck failure (10% vs. 24%; P = 0.14) when compared with those patients who had less than a complete response., Conclusions: Our data suggests that in patients with advanced neck disease who have a clinical complete response in the neck to chemoradiation long-term neck control is 85% or greater without neck dissection. Whether functional imaging or treatment response to induction chemotherapy would provide better discrimination of the 10% to 15% who may experience neck relapse is an important question for future research initiatives.

Purpose: To report prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival (DMFS) outcomes for patients with clinically localized prostate cancer treated with high-dose conformal radiotherapy., Methods and Materials: Between 1988 and 2004, a total of 2,047 patients with clinically localized prostate cancer were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Prescribed dose levels ranged from 66-86.4 Gy. Median follow-up was 6.6 years (range, 3-18 years)., Results: Although no differences were noted among low-risk patients for the various dose groups, significant improvements were observed with higher doses for patients with intermediate- and high-risk features. In patients with intermediate-risk features, multivariate analysis showed that radiation dose was an important predictor for improved PSA relapse-free survival (p < 0.0001) and improved DMFS (p = 0.04). In patients with high-risk features, multivariate analysis showed that the following variables predict for improved PSA relapse-free survival: dose (p < 0.0001); age (p = 0.0005), and neoadjuvant-concurrent androgen deprivation therapy (ADT; p = 0.01). In this risk group, only higher radiation dose was an important predictor for improved DMFS (p = 0.04)., Conclusions: High radiation dose levels were associated with improved biochemical tumor control and decreased risk of distant metastases. For high-risk patients, despite the delivery of high radiation dose levels, the use of ADT conferred an additional benefit for improved tumor control outcomes. We observed a benefit for ADT in high-risk patients who received higher doses.

Background: Our aim was to review Memorial Sloan-Kettering Cancer Center's experience with postoperative intensity-modulated radiotherapy (IMRT) for paranasal sinus, nasal cavity, and lacrimal gland cancer and report dosimetric measures, toxicity, and outcomes., Methods: Between September 2000 and June 2006, 37 patients with paranasal sinus, nasal cavity, or lacrimal gland cancer underwent postoperative IMRT. Median values were as follows: prescription dose, 60 Gy (range, 50-70); PTV(D95), 99% (range, 79-101%); optic nerve Dmax, 53 Gy (range, 2-54); optic chiasm Dmax, 51Gy (range, 2-55). Acute and late toxicities were scored by Radiation Therapy Oncology Group morbidity criteria., Results: Median follow-up was 28 months. Two-year local progression-free and overall survivals were 75% and 80%. No early- or late-grade 3/4 radiation-induced ophthalmologic toxicity occurred., Conclusions: Preliminary results show that adjuvant IMRT in these patients is feasible, allowed for excellent planning target volume (PTV) coverage, and minimized dose delivered to optic structures. Longer follow-up is warranted to assess the extent of late effects and outcomes.

Purpose: To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT., Methods and Materials: A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging., Results: The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed., Conclusion: High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

Purpose: To report toxicity and preliminary biochemical outcomes with high-dose intensity-modulated radiation therapy (IMRT) to a dose of 86.4 Gy for localized prostate cancer., Methods and Materials: Between August 1997 and March 2004, 478 patients were treated with 86.4 Gy using a 5- to 7-field IMRT technique. To adhere to normal tissue constraints, the mean D95 and V100 for the planning target volume were 83 Gy and 87%, respectively. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse was calculated. The median follow-up was 53 months., Results: Thirty-seven patients (8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. There was no acute Grade 3 or 4 GI toxicity. One hundred and five patients (22%) experienced acute Grade 2 genitourinary (GU) toxicity and three patients (0.6%) had Grade 3 GU toxicity. There was no acute Grade 4 GU toxicity. Sixteen patients (3%) developed late Grade 2 GI toxicity and two patients (<1%) developed late Grade 3 GI toxicity. Sixty patients (13%) had late Grade 2 GU toxicity and 12 (<3%) experienced late Grade 3 GU toxicity. The 5-year actuarial PSA relapse-free survival according to the nadir plus 2 ng/mL definition was 98%, 85% and 70% for the low, intermediate, and high risk NCCN prognostic groups., Conclusion: This report represents the largest data set of patients treated to ultra-high radiation dose levels of 86.4 Gy using IMRT for localized prostate cancer. Our findings indicate that this treatment is well tolerated and the early excellent biochemical control rates are encouraging.