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Background: The authors characterized the genetic landscape of chemoradiation-treated urothelial carcinoma of the bladder (UCB) with the objective of identifying potential correlates of response., Methods: Primary tumors with (n = 8) or without (n = 40) matched recurrent tumors from 48 patients who had non-metastatic, high-grade UCB and received treatment primarily with chemoradiation were analyzed using a next-generation sequencing assay enriched for cancer-related and canonical DNA damage response (DDR) genes. Protein expression of meiotic recombination 11 homolog (MRE11), a previously suggested biomarker, was assessed in 44 patients. Recurrent tumors were compared with primary tumors, and the clinical impact of likely deleterious DDR gene alterations was evaluated., Results: The profile of alterations approximated that of prior UCB cohorts. Within 5 pairs of matched primary-recurrent tumors, a median of 92% of somatic mutations were shared. A median 33% of mutations were shared between 3 matched bladder-metastasis pairs. Of 26 patients (54%) who had DDR gene alterations, 12 (25%) harbored likely deleterious alterations. In multivariable analysis, these patients displayed a trend toward reduced bladder recurrence (hazard ratio, 0.32; P = .070) or any recurrence (hazard ratio, 0.37; P = .070). The most common of these alterations, ERCC2 (excision repair cross-complementation group 2) mutations, were associated with significantly lower 2-year metastatic recurrence (0% vs 43%; log-rank P = .044). No impact of MRE11 protein expression on outcome was detected., Conclusions: A similar mutation profile between primary and recurrent tumors suggests that pre-existing, resistant clonal populations represent the primary mechanism of chemoradiation treatment failure. Deleterious DDR genetic alterations, particularly recurrent alterations in ERCC2, may be associated with improved chemoradiation outcomes in patients with UCB. A small sample size necessitates independent validation of these observations. Cancer 2016;122:3715-23. © 2016 American Cancer Society., Competing Interests: The authors declare no applicable conflicts of interest., (© 2016 American Cancer Society.)

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.)

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.

Background: The posttreatment prostate-specific antigen (PSA) bounce phenomenon has been recognized in at least 20% of all patients treated with radiation. The purpose of the current report was to determine if there was a difference in biochemical and clinical control between the bounce and nonbounce (NB) patients using pooled data on 4839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions between 1986 and 1995., Methods: The median follow-up was 6.3 years. A posttreatment PSA bounce was defined by a minimal rise of 0.4 ng/mL over a 6-month follow-up period, followed by a drop in PSA level of any magnitude. Endpoints included no biochemical evidence of disease (bNED) failure (BF) (ASTRO definition), distant failure (DF), cause-specific failure (CSF), and overall survival (OS). Patients were stratified by pretreatment PSA, Gleason score, T stage, age, dose, and risk group., Results: In all, 978 (20%) patients experienced at least 1 posttreatment PSA bounce. Within 3 subgroups (risk group, pretreatment PSA, and age), statistically significant differences of remaining bounce-free were observed on univariate analysis. Patients < 70 years had a 72% chance of remaining bounce-free at 5 years compared with 75% for older patients (P = .04). The NB patients had 72% bNED control at 10 years compared with 58% for the bounce patients. The effect of a bounce remained statistically significant on multivariate analysis (P < .0001). No statistically significant difference in DF, CSF, or OS was observed., Conclusions: Patients treated with external beam radiation therapy alone who experience a posttreatment PSA bounce have increased risk of BF. However, this did not translate into a difference in clinical failure with the available follow-up in the current study., ((c) 2006 American Cancer Society.)

Background: The objective of the current study was to provide descriptive information on a representative national sample of patients with prostate carcinoma who were treated with prostate brachytherapy (PB) in calendar year 1999., Methods: A random survey was conducted by the Patterns of Care Study in radiation oncology of 59 facilities (1 facility had no eligible patients) that treated patients with prostate carcinoma in 1999 in the United States. A weighted sample size of 36,496 patients with prostate cancer was included in the 1999 survey (unweighted sample size, 554 patients). The main measures were the clinical characteristics of men prior to treatment and the technical characteristics of PB. Patients were classified into three prognostic groups according to T stage, pretreatment prostate specific antigen (PSA) level, and Gleason score., Results: A weighted sample size of 13,293 patients (36%; unweighted sample size, 162 patients) was treated with PB. Compared with a weighted sample size of 23,203 patients (64%; unweighted sample size, 392 patients) was treated with external beam radiotherapy (EB), patients who received PB were significantly younger (mean age: PB group, 67.7 years; EB group, 70.8 years; P = 0.0006). The mean pretreatment PSA level for the PB group was lower compared with the EB group (9.9 ng/mL vs. 13.33 ng/mL; P = 0.0015). The prognostic groupings were more favorable for patients in the PB group compared with patients in EB group (P = 0.0365). The utilization of androgen deprivation therapy (ADT) in the PB group was similar to the utilization of ADT in the EB group (40.4% vs. 51.3%; P = 0.2282). The vast majority of men who were treated with PB received low-dose-rate, permanent sources (89%). Fifty-four percent of men received PB monotherapy (PBM), and the remaining 46% were treated with EB in addition to PB (EBPB). The prognostic groupings were more favorable for patients in the PBM group compared with patients in the EBPB group (P = 0.0037). Of the men who were treated with low-dose-rate PB, 59% were treated with iodine-125 (I-125), and 41% were treated with palladium-103 (Pd-103). I-125 was used more frequently in men who were treated with PBM, and Pd-103 was used more frequently in men who were treated with EBPB. Postimplantation dosimetry was documented in 61.0% of men who were treated with low-dose-rate PB. Computed tomography imaging was used for 46.5% of men., Conclusions: PB was used in 36% of men who were treated with radiotherapy nationally. The mean age of men who were treated with PB was younger than the population of men who were treated with EB alone. Nearly 50% of men who received PB also received EB. EB was used more frequently in men with higher-risk disease. ADT was used in 40% of patients in the PB group. Techniques and prescription doses were consistent with published guidelines., (Copyright 2003 American Cancer Society.)

Background: The 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial carcinoma defined Stage IB as disease with invasion of less than one-half of the myometrium, although most of the data on prognostic factors are based on invasion of the inner one-third, middle one-third, or outer one-third of the myometrium. The objective of this study was to determine whether the depth of myometrial invasion is correlated with outcome in patients with Stage IB endometrial carcinoma., Methods: Between November, 1987 and June, 1998, 251 patients with Stage IB endometrioid adenocarcinoma of the uterus underwent simple hysterectomy followed by intravaginal brachytherapy. The depth of myometrial invasion was less than or equal to one-third (Group I) in 191 of 251 patients (79%) and greater than one-third to less than one-half (Group II) in 52 of 251 patients (21%). Comprehensive surgical staging (CSS) was done in 12% of patients. The two groups were balanced with regard to age (< 60 years vs. > or = 60 years), FIGO grade, lower uterine segment involvement (LUSI), CSS, and the use of postoperative external-beam radiation. The rate of capillary-like space invasion (CLSI), however, was 9% in Group I compared with 25% in Group II (P = 0.002). The median follow-up was 58 months., Results: The overall 5-year actuarial local-regional control (LRC), disease free (DFS) survival, and overall survival (OS) rates were 95%, 92%, and 92%, respectively. These end points, however, did not vary significantly between the two groups. The 5-year LRC, DFS, and OS rates in Groups I and II were 96% versus 95%, respectively (P = 0.9); 92% versus 94%, respectively (P = 0.7); and 92% versus 90%, respectively (P = 0.5). On multivariate analysis, the influence on outcome of age, grade, amount of myometrial invasion, LUSI, and CLSI was evaluated. Only age > or = 60 years and FIGO Grade 3 were correlated with poor DFS (P = 0.02 and P = 0.03, respectively) and OS (P = 0.001 and P = 0.01, respectively)., Conclusions: Based on this study, in patients with Stage IB endometrial carcinoma, the amount of myometrial invasion, defined as invasion less than or equal to one-third of the myometrium versus invasion greater than one-third and less than one-half of the myometrium, did not appear to influence outcome. Age > or = 60 years and FIGO Grade 3, however, emerged as independent prognostic factors for poor DFS and OS., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10660)

Background: The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT)., Methods: A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale., Results: Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction., Conclusions: The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.

Background: The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center., Methods: Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%)., Results: The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions., Conclusions: The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.

The authors retrospectively reviewed 50 episodes of spinal epidural tumor that occurred in 42 patients with metastatic prostate cancer and were treated with external-beam radiation. Treatment response was evaluated in terms of symptoms, neurologic status, and, in most cases, reduction of tumor on repeat myelography. At the completion of therapy, 92% of treated patients experienced pain relief and 67% had significant to complete improvement on neurologic examination. Thirty days after treatment, repeat myelography was performed in 40 of the 50 cases; compared with the initial findings immediately preceding radiation therapy (RT), the results of 58% of these studies had normalized completely, results were improved in 25%, and the results had not changed in 18%. The presence of a high-grade compression fracture of the vertebral body was an indicator of poor prognosis for tumor response on repeat myelography. The ability of a patient to walk before treatment and tumor response on repeat myelography were associated significantly with improved outcome of RT and with survival. The authors conclude that RT can effectively palliate epidural lesions from metastatic prostate cancer. The prognosis for the long-term response to therapy may be indicated by pretreatment ambulatory status and posttreatment imaging of the epidural space.

To define the indications for elective neck treatment, the cases of 474 previously untreated patients were reviewed who had locally confined major salivary gland cancers treated between 1939 and 1982. Clinically positive nodes were present in 14% (67 of 474). Overall, clinically occult, pathologically positive nodes occurred in 12% (47 of 407). By univariate analysis, several factors appeared to predict the risk of occult metastases; however, multivariate analysis revealed that only size and grade were significant risk factors. Tumors 4 cm or more in size had a 20% (32 of 164) risk of occult metastases compared with a 4% (nine of 220) risk for smaller tumors (P less than 0.00001). High-grade tumors (regardless of histologic type) had a 49% (29 of 59) risk of occult metastases compared with a 7% (15 of 221) risk for intermediate-grade or low-grade tumors (P less than 0.00001). In view of the low frequency of occult metastases in the entire group, routine elective treatment of the neck is not recommended. High-grade tumors and larger tumors have a high rate of occult neck metastases, and treatment should be considered in this group.

Thirty-eight histologically confirmed desmoid tumors were treated with conservative surgical resection and interstitial iridium 192. Patients included in this series constituted a poor prognostic group. Seventy five percent (75%) had previous recurrences of their disease and 50% had tumors 8 cm or greater in size. In addition, 16% of the patients had gross residual disease after surgical excision and 79% had positive or close margins of resection. With a median follow-up of 5.5 years, the 5-year actuarial in-field local control rate was 75% and the overall local control rate was 66%. Four of the 12 local recurrences developed at the periphery of the implant volume and four patients failed at least 3 cm or more beyond the treated volume. After salvage therapy, the 5-year actuarial local control rate was 95%. Two patients required amputation for recurrent disease. Thirty of 34 patients remain free of disease with an excellent functional result achieved. The authors conclude that surgical resection and postoperative interstitial iridium 192 is effective therapy for patients with desmoid tumors. Despite the fact that most patients in this series had bulky, recurrent tumors, excellent long-term local control and limb function were achieved.