Prospective surveillance and targeted physiotherapy for arm morbidity after breast cancer surgery: a pilot randomized controlled trial.

OBJECTIVE: To evaluate prospective surveillance and targeted physiotherapy (PSTP) compared to education (EDU) on the prevalence of arm morbidity and describe the associated program cost. DESIGN: Pilot randomized single-blinded controlled trial. SETTING: Urban with assessments and treatment delivered in hospitals. PARTICIPANTS: Women scheduled for breast cancer surgery. INTERVENTIONS: Participants were randomly assigned (1:1) to PSTP ( n = 21) or EDU ( n = 20) and assessed presurgery and 12 months postsurgery. All participants received usual care, namely, preoperative education and provision of an education booklet with postsurgical exercises. The PSTP group was monitored for arm morbidity every three months and referred for physiotherapy if arm morbidity was identified. The EDU group received three education sessions on nutrition, stress and fatigue management. MAIN OUTCOME MEASURES: Arm morbidity was based on changes in the surgical arm(s) from presurgery in four domains: (1) shoulder range of motion, (2) strength, (3) volume, and (4) upper body function. Complex arm morbidity indicated ≥2 domains impaired. Second, the cost of the PSTP program was described. RESULTS: At 12 months, 18 (49%) participants (10 PSTP and 8 EDU) had arm morbidity, with EDU participants presenting more complex arm morbidity compared to PSTP participants. PSTP participants attended 4.4 of 5 assessments with 90% retention. The PSTP program cost was $150 covered by the Health Care Provider and the Patient Out-of-Pocket Travel cost was CAN$40. CONCLUSION: Our results suggest that PSTP is feasible among women with breast cancer for early identification of arm morbidity. A larger study is needed to determine the cost and effectiveness benefits.

A longitudinal analysis of chronic arm morbidity following breast cancer surgery.

Arm morbidity (AM) arising from breast cancer (BC) treatment can detrimentally impact quality of life; often limiting a survivor's ability to participate in valued activities. The present study explored (a) the developmental time course of AM [restricted range of motion (ROM), pain, and arm volume changes], negative affect, and perceived disability in the immediate years post-surgery, and (b) the mediating role of perceived disability on the relationship between AM and negative affect over time. In this 5-year longitudinal study, BC survivors from four Canadian oncology clinics (n = 431) completed five annual clinical assessments, where differences in ROM (shoulder abduction, external rotation) and arm volume between the affected and non-affected arm were measured. The profile of mood states (POMS), disability of arm, shoulder, hand, and McGill Pain Questionnaire-Short form were completed. Results from general linear modeling showed that AM, negative affect, and perceived disability were greatest 1-year post-surgery, declined, and with the exception of arm volume changes, were significantly lower 5 years later. Negative affect was significantly associated with restrictions in shoulder abduction and external rotation (average r = -0.15; p < 0.05) and present arm pain (average r = 0.28, p < 0.01) at most assessments. The mediating role of perceived disability on the relationship between AM and negative affect was statistically significant in a majority of assessments. Perceived disability is the underlying factor driving the relationship between AM and mood disturbance over time. Rehabilitative therapy to improve survivors' functional well-being might mitigate the negative impacts of AM on emotional health.

Radiotherapy and Conservative Surgery in the Locoregional Management of Merkel Cell Carcinoma: The British Columbia Cancer Agency Experience.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon aggressive skin malignancy. Published series mainly focus on wide excision, which can be difficult at some sites (e.g., face) and in patients with comorbidities. In British Columbia, an approach of conservative surgery followed by radiotherapy is common. MATERIALS AND METHODS: This is a retrospective review of 179 patients treated for MCC with curative intent in British Columbia. RESULTS: Totals of 68, 63, and 37 patients underwent narrow excision of primary, attempted wide excision, and biopsy only, respectively. Adjuvant radiotherapy reduced local recurrence after narrow excision (<10 mm margin) from 25 to 4.9 % (p = .03) and was effective in the presence of microscopic positive margins. Local recurrence rate was 7.1 % if the margin was >10 mm irrespective of radiation use. Local RFS was improved by adjuvant radiation therapy (RT) (p = 0.04), and there was a trend to reduced nodal relapse after elective nodal RT (p = .07). Irradiation of macroscopic tumor at 37 primary and 33 nodal sites provided 5-year local and nodal RFS of 90 and 75 %, respectively. The 5-year cancer specific survival was 77 % and was not improved by the use of adjuvant radiotherapy. CONCLUSIONS: Local excision plus adjuvant RT is an effective treatment for MCC. Adjuvant radiation should be considered when the excision margin is <1 cm.

Impact of Prostate Cancer Treatment on the Sexual Quality of Life for Men-Who-Have-Sex-with-Men.

INTRODUCTION: With earlier prostate cancer (PCa) diagnosis and an increased focus on survivorship, post-treatment sexual quality of life (QoL) has become increasingly important. Research and validated instruments for sexual QoL assessment based on heterosexual samples have limited applicability for men-who-have-sex-with-men (MSM). AIM: We aimed to create a validated instrument for assessing sexual needs and concerns of MSM post-PCa treatment. Here we explore post-PCa treatment sexual concerns for a sample of MSM, as the first part of this multi-phase project. METHODS: Individual semi-structured interviews were conducted with 16 MSM face-to-face or via Internet-based video conferencing. Participants were asked open-ended questions about their experiences of sexual QoL following PCa. Interviews were recorded, transcribed verbatim, uploaded to NVivo 8(TM) , and analyzed using qualitative methodology. MAIN OUTCOME MEASURE: We have conducted semi-structure qualitative interviews on 16 MSM who were treated for PCa. Focus was on post-treatment sexual concerns. RESULTS: The following themes were inductively derived: (i) erectile, urinary, ejaculation, and orgasmic dysfunctions; (ii) challenges to intimate relationships; and (iii) lack of MSM-specific oncological and psychosocial support for PCa survivorship. Sexual practices pre-treatment ranked in order of frequency were masturbation, oral sex, and anal sex, an ordering that prevailed post-treatment. Sexual QoL decreased with erectile, urinary, and ejaculation dysfunctions. Post-treatment orgasms were compromised. Some single men and men in non-monogamous relationships reported a loss of confidence or difficulty meeting other men post-treatment. Limited access to targeted oncological and psychosocial supports posed difficulties in coping with PCa for MSM. CONCLUSIONS: The negative impact on sexual QoL can be severe for MSM and requires targeted attention. Penile-vaginal intercourse and erectile function have been the primary focus of sexual research and rehabilitation for men with PCa, and do not adequately reflect the sexual practices of MSM. Our findings suggest that future research dedicated to MSM with PCa is needed to incorporate their sexual practices and preferences specifically into treatment decisions, and that targeted oncological and psychosocial support services are also warranted.

Loss, adaptation and new directions: The impact of arm morbidity on leisure activities following breast cancer.

The impact of arm morbidity on leisure and quality of life is an understudied area in cancer survivorship. The purpose of this study was to qualitatively describe the impact of breast cancer-related arm morbidity on leisure participation in Canadian women. A grounded theory approach was used to generate thematic categories and a model. Drawing on participants from a larger cohort study (n = 740), 40 women with arm morbidity symptoms were purposively sampled and interviewed. Three themes emerged: a sense of loss, adapting participation, and new directions. Women with arm morbidity may experience an abrupt loss of previously enjoyed leisure activities and engage in a process of adapting to discover new meanings and directions. Comprehensive, person-centred cancer survivorship programs may assist with adaptation to arm morbidity.

Outcomes of Merkel cell carcinoma treated with radiotherapy without radical surgical excision.

BACKGROUND: Achieving clear surgical margins in Merkel cell carcinoma (MCC) can be difficult due to tumor location or patient comorbidity. Clinical impression suggests that radiation treatment achieves good control of macroscopic disease. METHODS: A retrospective chart review was undertaken of all patients with pathological evidence of MCC and treated with curative intent at the BC Cancer Agency between 1979 and 2007. This is a report on the outcomes of those with gross disease treated with radiotherapy, without radical surgery. RESULTS: Fifty-seven patients received definitive radiotherapy to the primary and/or nodal disease. Median age was 75 years and median follow-up was 34 months (84.5 months for those alive at last follow-up). American Joint Committee on Cancer (AJCC) stage distribution was 23, 19, and 58 % for stages I, II, and III, respectively. Tumor control at sites treated for macroscopic disease was 88 % at 12 months and 82 % at 2 years, and 5-year local relapse-free survival (RFS) was 90 %. Five-year RFS, cancer-specific survival (CSS), and overall survival were 57, 68, and 39 %, respectively. On univariate and multivariate analyses, only male sex was associated with a worse RFS, and a radiotherapy dose >50 Gy was associated with a better CSS. LIMITATIONS: The retrospective nature of the study and small sample size limit the strength of the conclusions. CONCLUSIONS: Radical radiotherapy is effective in the curative treatment of MCC, especially in patients who would tolerate wide surgical excision poorly, or where it would cause significant cosmetic or functional deficits.

Cultural Adaptation and Validation of the Punjabi Version of EPIC.

BACKGROUND: With earlier prostate cancer (PCa) diagnosis and increased survivorship, post-treatment quality of life (QoL) has become increasingly important. The Expanded Prostate Cancer Index Composite (EPIC) is a widely adopted QoL instrument for PCa. We aimed to create a Punjabi version of EPIC to further research in the Punjabi-speaking population. METHODS: A prototype of the Punjabi version of EPIC was created by forward-backward translations and revision. After concluding the cultural adaptation phase by interviewing 15 participants, a pilot version was created. Validation of the pilot version was performed by having 72 participants complete the Punjabi EPIC and another commonly used QoL instrument, the EORTC QLQ-c30, twice within a 4-week period. Test retest reliability (Pearson's correlations and difference distribution) and internal consistency (Cronbach's alpha) were measured using SAS version 9.4. RESULTS: Modifications were needed for the prototype Punjabi version after forward-backward translations. Cultural adaptation has highlighted a few issues including syntax and terminology.  Test-retest reliability of the Urinary, Bowel, Sexual and Hormone domains were 0.88, 0.91, 0.91, and 0.95, respectively, and subscale correlations ranged from 0.75 to 0.93. Internal consistency for domains and subscales was good except for Sexual Domain. Performance of EPIC is comparable, and in some cases, slightly better than validated Punjabi version of EORTC QLQ-C30. CONCLUSIONS: The EPIC questionnaire was successfully translated into Punjabi and was culturally adapted.  The resultant Punjabi version has high reliability and validity and will be an important tool for QoL research in the Punjabi population. EPIC was successfully translated, culturally adapted, and validated with high reliability and validity into Punjabi. It will be a valuable QoL tool for physicians in clinical and research settings, and for patients in decision-making.

Late Toxicity of Prostate Ultrahypofractionated Radiation Therapy Compared With Moderate Hypofractionation in a Randomized Trial.

PURPOSE: We report late toxicity, quality of life (QOL), and urinary symptom score with prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation and ultrahypofrationation. METHODS AND MATERIALS: Patients with intermediate and high-risk prostate cancer were randomized to either Arm 1 (70 Gy/28 fractions) or Arm 2 (36.25 Gy/5 weekly fractions). Late toxicity was evaluated using the Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytical scales. QOL was assessed with the Expanded Prostate Inventory Composite-26 Short Form and urinary function with the International Prostate Symptom Score. RESULTS: Eighty participants were randomized. Two from Arm 1 withdrew, leaving 36 patients in Arm 1 and 42 in Arm 2. There were no significant differences in baseline characteristics, except for worse International Prostate Symptom Score in Arm 2. No difference was observed in freedom from grade 3 or worse toxicity between treatments (P = .921), with only a single grade 3 event in each arm. There was no significant difference in freedom from grade 2 or worse toxicity (P = .280). No difference was observed in freedom from grade 2 or worse genitorurinary toxicity, with cumulative probabilities of 69.0% and 87.0% at 5 years for Arms 1 and 2, respectively (0.132). No difference was observed in freedom from grade 2 or worse gastrointestinal toxicity, with cumulative probabilities of 74.0% in Arm 1 and 80.0% in Arm 2 (P = .430). There were no significant differences in Expanded Prostate Inventory Composite-26 Short Form QOL between arms. CONCLUSIONS: Ultrahypofrationation, delivered weekly, is well tolerated with no significant differences in freedom from late toxicity compared with moderate hypofractionation.

Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer.

BACKGROUND: The objective of this study was to report the rates of disease-free survival (DFS), cause-specific survival (CSS), and overall survival after low-dose-rate (LDR) prostate brachytherapy (PB). METHODS: Data from 1006 consecutive patients with prostate cancer who received LDR-PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low-risk (58%) or intermediate-risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty-five percent of patients received 3 months of neoadjuvant androgen-deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables. RESULTS: The median follow-up was 7.5 years. By using Fine and Gray competing risks analysis, the 5-year and 10-year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%-97.7%) and 94.1% (95% confidence interval, 92%-95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10-year CSS rate was 99.1% (95% confidence interval, 97.3%-99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%-95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%-86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis. CONCLUSIONS: In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low-risk and intermediate-risk prostate cancer, the actuarial rate of recurrent disease after LDR-PB was approximately 3% at 5 years and 6% at 10 years.

Acute Toxicity of Ultrahypofractionation Compared With Moderate Hypofractionation in Prostate Cancer Treatment: A Randomized Trial.

PURPOSE: We report on the early toxic effects and quality of life of localized prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation (MHF) with ultrahypofractionation (UHF). METHODS AND MATERIALS: We randomized patients with intermediate- to high-risk localized prostate cancer to radiation therapy with MHF (70 Gy in 28 daily fractions) or UHF (36.25 Gy in 5 weekly fractions). We analyzed early toxic effects (using Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytic scales) and patient-reported quality of life (using the Expanded Prostate Inventory Composite questionnaire) when all patients had at least 6 months of follow-up. RESULTS: We randomized 80 participants. Two patients withdrew from radiation therapy. We ran analysis on results for 78 patients. The 2 arms were balanced in key patient and disease characteristics, except for a statistically worse baseline urinary function in the UHF arm (International Prostate Symptom Score >7: 68% vs 36%, P = .004). There were no statistically significant differences between the 2 arms in grade 3 or grade 2 toxic effects: grade ≥3 MHF 8%, UHF 2% (P = .235); grade ≥2 MHF 36%, UHF 24% (P = .235). There were also no significant differences in percentages of patients with a "minimal important change" of quality of life in the Incontinence (MHF 36%, UHF 33%; P = .746), Irritative/Obstructive (MHF 56%, UHF 74%; P = .074), or Bowel domains (MHF 58%, UHF 52%; P = .508) on the Expanded Prostate Inventory Composite questionnaire. CONCLUSIONS: UHF radiation therapy for prostate cancer is well tolerated, and there were no significant differences in toxic effects and quality of life changes between UHF and MHF up to 6 months after treatment in the current trial.

Web-Based Peer Navigation for Men with Prostate Cancer and Their Family Caregivers: A Pilot Feasibility Study.

This study assessed the feasibility, acceptability and potential effects of True North Peer Navigation (PN)­a web-based peer navigation program for men with prostate cancer (PC) and their family caregivers. A one-arm, pre-post pilot feasibility study was conducted at two cancer centres in Canada. Participants were matched through a web-app with a specially trained peer navigator who assessed needs and barriers to care, provided support and encouraged a proactive approach to health for 3 months. Descriptive statistics were calculated, along with paired t-tests. True North PN was feasible, with 57.9% (84/145) recruitment, 84.5% (71/84) pre-questionnaire, 77.5% (55/71) app registration, 92.7% (51/55) match and 66.7% (34/51) post-questionnaire completion rates. Mean satisfaction with Peer Navigators was 8.4/10 (SD 2.15), mean program satisfaction was 6.8/10 (SD 2.9) and mean app usability was 60/100 (SD 14.8). At 3 months, mean ± SE patient/caregiver activation had improved by 11.5 ± 3.4 points (p = 0.002), patient quality of life by 1.1 ± 0.2 points (p < 0.0001), informational support by 0.4 ± 0.17 points (p = 0.03), practical support by 0.5 ± 0.25 points (p = 0.04) and less need for support related to fear of recurrence among patients by 0.4 ± 19 points (p = 0.03). The True North web-based peer navigation program is highly feasible and acceptable among PC patients and caregivers, and the associated improvements in patient and caregiver activation are promising. A randomized controlled trial is warranted to determine effectiveness.

A phase II trial of a soy beverage for subjects without clinical disease with rising prostate-specific antigen after radical radiation for prostate cancer.

Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.

Predictors of arm morbidity following breast cancer surgery.

OBJECTIVE: Arm morbidity post-breast cancer surgery is increasingly being recognized as a chronic problem for some women following breast cancer surgery. The purpose of this study was to examine demographic, disease, and treatment-related predictors of a comprehensive array of chronic arm morbidity (pain, lymphedema, functional disability, and range of motion) post-breast cancer surgery. METHODS: Women (n=316) with a non-metastatic primary diagnosis of breast cancer were accrued from cancer centers in four Canadian cities. Patients completed a clinical assessment and measures of arm morbidity at 6-12 months post-breast cancer surgery. The independent variables in the MANOVA to predict arm morbidity included: Lymph node management type, number of axillary nodes dissected, type of surgery, disease stage, presence of post-operative infection, radiation to the axilla, body mass index (BMI), assessment time post-surgery, education, and partner status. RESULTS: Pain was significantly predicted by axillary lymph node management, lack of a partner, and post-operative infection; lymphedema by axillary lymph node management, number of axillary nodes dissected, radiation to the axilla, and having a modified radical mastectomy; functional disability by post-operative infection and high BMI; and restricted external rotation by axillary lymph node management, low educational attainment, and advanced disease. CONCLUSION: Comprehensive behavioral management and rehabilitation programs are needed to treat arm morbidity following breast cancer surgery. These programs should address the full scope of symptoms and associated psychosocial and functional sequelae.

Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model.

PURPOSE/BACKGROUND: Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). MATERIAL AND METHODS: One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. RESULTS: Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44). CONCLUSIONS: Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.

Cultural adaptation and validation of the Chinese version of the expanded prostate cancer index composite.

AIM: The expanded prostate cancer index composite (EPIC) is a widely adopted instrument for the quality of life of patients with prostate cancer. We aimed to create a Chinese version of EPIC to further research in the Chinese-speaking population. METHODS: A prototype was created by forward-backward translations and revisions. During cultural adaptation, 15 participants were interviewed after they had completed the prototype. A few issues highlighted included confusion related to the question format, subject non-familiarity with the Chinese term for "hot flashes," and the use of the Chinese term for "breast" as a strictly female body part. A pilot version was created based on the cultural adaptation findings. Validation of the pilot version was performed by having 50 participants complete the Chinese EPIC and EORTC QLQ-c30 twice within a 4-week period. Test-retest reliability (Pearson's correlations and difference distribution) and internal consistency (Cronbach's α) were measured using SAS version 9.4. RESULTS: Test-retest reliability values for the urinary, bowel, sexual and hormone domains were 0.71, 0.51, 0.51 and 0.66, respectively; subscale test-retest reliability ranged between 0.29 and 0.82. Internal consistency for domains was good with Cronbach's α ranging from 0.76 to 0.78 for the initial test and 0.67 to 0.85 for the retest. The performance of this version of EPIC was comparable to the validated EORTC QLQ-C30. CONCLUSION: The EPIC questionnaire was successfully translated into Chinese and was culturally adapted. The resultant Chinese version has high reliability and validity and will be an important tool for research on quality of life in the Chinese population.

What is the optimal duration of androgen deprivation therapy in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/ml?

PURPOSE: To evaluate the optimal duration of androgen deprivation therapy (ADT) in patients with prostate cancer treated with external beam radiotherapy (EBRT), who present with PSA levels > 20 ng/mL. METHODS AND MATERIALS: A total of 307 patients presenting with a PSA > 20 ng/ml were treated with EBRT and ADT. The cohort was divided into four groups according to the duration of ADT: Group 1 received < 6 months (n = 71), group 2 received 6-12 months (n = 80), group 3 received 12-24 months (n = 72), and group 4 received > 24 months (n = 84) of ADT. The endpoints analyzed were biochemical control (bNED), overall survival (OS) and cause-specific survival (CSS). Statistical analysis was conducted using Kaplan-Meier estimates and Cox regression models. RESULTS: Compared to patients who received < 6 months of ADT, patients treated with 12-24 months or > 24 months of ADT experienced significantly improved bNED (p = 0.01 and p < 0.0001, respectively). Cause-specific survival with ADT durations 12-24 and > 24 months were significantly higher compared to < 6 months (p < 0.007 and 0.024, respectively). Overall survival with ADT durations > 24 months was also significantly higher compared to < 6 months (p = 0.0025). CONCLUSIONS: The present analysis supports the hypothesis that longer durations of ADT improves bNED, CSS and OS in patients presenting with a PSA > 20 ng/ml.

Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms.

PURPOSE: To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. METHODS AND MATERIALS: Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ2 analysis, and multivariate ordinal regression. RESULTS: Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy. CONCLUSIONS: Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

Randomized trial comparing two fractionation schedules for patients with localized prostate cancer.

PURPOSE: The optimal radiation dose fractionation schedule for localized prostate cancer is unclear. This study was designed to compare two dose fractionation schemes (a shorter 4-week radiation schedule v a longer 6.5-week schedule). PATIENTS AND METHODS: Patients with early-stage (T1 or T2) prostate cancer were randomly assigned to 66 Gy in 33 fractions over 45 days (long arm) or 52.5 Gy in 20 fractions over 28 days (short arm). The study was designed as a noninferiority investigation with a predefined tolerance of -7.5%. The primary outcome was a composite of biochemical or clinical failure (BCF). Secondary outcomes included presence of tumor on prostate biopsy at 2 years, survival, and toxicity. RESULTS: From March 1995 to December 1998, 936 men were randomly assigned to treatment; 470 were assigned to the long arm, and 466 were assigned to the short arm. The median follow-up time was 5.7 years. At 5 years, the BCF probability was 52.95% in the long arm and 59.95% in the short arm (difference = -7.0%; 90% CI, -12.6% to -1.4%), favoring the long arm. No difference in 2-year postradiotherapy biopsy or in overall survival was detected between the arms. Acute toxicity was found to be slightly higher in the short arm (11.4%) compared with the long arm (7%; difference = -4.4%; 95% CI, -8.1% to -0.6%); however, late toxicity was similarly low in both arms (3.2%). CONCLUSION: Given the results, we cannot exclude the possibility that the chosen hypofractionated radiation regimen may be inferior to the standard regimen. Further evaluation involving higher dose hypofractionated radiation regimens in contemporary radiation settings is necessary.

Relationship between delay in radiotherapy and biochemical control in prostate cancer.

PURPOSE: The aim of this study was to investigate whether a delay in radiotherapy is associated with a poorer biochemical control for prostate cancer. METHODS: The time to treatment (TTT) from diagnosis of prostate cancer to radiotherapy was analyzed with respect to prostate-specific antigen (PSA) control in 1024 hormone-naive patients. The Kaplan-Meier PSA control curves for patients with TTT less than the median were compared with those for patients with TTT greater than the median in 3 predefined risk groups. Statistical significant differences in PSA control were further analyzed using Cox multivariate analysis with pretreatment PSA, Gleason score, T stage, and radiotherapy dose as covariates. RESULTS: The median TTT and median follow-up are 3.7 months and 49 months respectively. Patients with a longer TTT have a statistically significant better PSA control than patients with a shorter TTT if they have intermediate- or high-risk disease. However in multivariate analysis TTT was not found to be significant in predicting PSA control, with pretreatment PSA and Gleason score emerging as highly significant in predicting PSA failure in both intermediate- and high-risk disease. CONCLUSION: In this study in prostate cancer patients in British Columbia, there was no evidence that a longer time interval between diagnosis and radiotherapy was associated with poorer PSA control.

Hemoglobin levels do not predict biochemical outcome for localized prostate cancer treated with neoadjuvant androgen-suppression therapy and external-beam radiotherapy.

PURPOSE: To investigate whether hemoglobin (Hb) levels affect outcome in men with localized prostate adenocarcinoma (LPA) treated with neoadjuvant androgen-suppression therapy (NAST) and external-beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 563 men with LPA treated with NAST (median: 5.3 months) and EBRT who had Hb levels during treatment were retrospectively reviewed. Patient, tumor, and treatment variables, including the following Hb variables, were subjected to univariate and multivariable analyses to identify factors that predict biochemical control (bNED) and overall survival (OS): pre-EBRT Hb, Hb nadir during EBRT, and change in Hb from pre-EBRT to nadir during EBRT. RESULTS: Median PSA follow-up was 4.25 years. Forty-nine percent of men were anemic during EBRT, with a median Hb of 13.4 g/dL, and 68% experienced a decline in Hb from pre-EBRT to during EBRT of median 0.6 g/dL. Five-year Nadir+2 bNED and OS rates were similar for anemic and nonanemic patients during EBRT. High percent-positive biopsies, PSA and Gleason score, and use of AA monotherapy predicted worse bNED. High stage and age predicted worse OS. Hb variables were not predictive of bNED or OS. CONCLUSIONS: Anemia is a common side effect of NAST and is usually mild. Hb levels, however, do not predict biochemical control or survival.