Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer : a phase II trial

Background: Neo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with >= pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free-and overall survival as loco-regional recurrence is linked to the development of distant metastasis. Methods: We plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with >= 1 of the following characteristics: - Pathological (p) T3 stage + presence of lymphovascular invasion on pathological examination - pT4 stage - < 10 lymph nodes removed - positive lymph nodes - positive surgical margins Patients will have a F-18-FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET-CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute >= Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints. Discussion: This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC

Adenoid Cystic Carcinoma of External Auditory Canal

Adenoid cystic carcinoma is extremely rare tumour that accounts for approximately 5% of primary malignancy of external auditory canal. These tumours are related with a high risk of recurrences and significant morbidities from surgical management and adjuvant radiotherapy. Despite the aggressive management for these tumours, many patients succumb to distant metastasis, making overall prognosis of these tumours poor. Although ACC of EAC has been reported in 5th decade, but its occurrence in young patient is very rare. We report a rare case of ACC in a young 22 years old female, who presented with ear canal mass and ear pain. Biopsy suggested mass to be ACC. Patient underwent wide local excision followed by adjuvant radiotherapy

Adjuvant radiotherapy after salvage surgery for melanoma recurrence in a node field following a previous lymph node dissection

Background and Objectives: Adjuvant radiotherapy (RT) can be given to melanoma patients following salvage surgery for node field recurrence after a previous regional node dissection, but the value of this treatment strategy is poorly documented. This study evaluated long-term node field control and survival of patients treated in this way in an era before effective adjuvant systemic therapy became available. Methods: Data for 76 patients treated between 1990 and 2011 were extracted from an institutional database. Baseline patient characteristics, treatment details and oncological outcomes were analysed. Results: Adjuvant RT with conventional fractionation (median dose 48 Gy in 20 fractions) was given to 43 patients (57%) and hypofractionated RT (median dose 33 Gy in 6 fractions) to 33 patients (43%). The 5-year node field control rate was 70%, 5-year recurrence-free survival 17%, 5-year melanoma-specific survival 26% and 5-year overall survival 25%. Conclusions: Salvage surgery with adjuvant RT achieved node field control in 70% of melanoma patients with node field recurrence following a prior node dissection. However, disease progression at distant sites was common and survival outcomes were poor. Prospective data will be required to assess outcomes for contemporary combinations of surgery, adjuvant RT and systemic therapy.</p

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

Background: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. / Methods: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7–10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. / Findings: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60–68). Median follow-up was 4·9 years (IQR 3·0–6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81–1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58–1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3–4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). / Interpretation: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. / Funding: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society

Task Force 7: Training Guidelines for Research in Pediatric Cardiology

Aim of the study. The aim of the study was to analyze the benefit from adjuvant radiotherapy in patients with vulvar cancer and a single positive node without extra capsular spread. Materials and methods. The Study population comprised data of 75 patients with vulvar cancer and one lymph node metastasis. The patients were treated in three different university centers in Amsterdam, Groningen and Rotterdam between 1984 and 2005. Results. Out of 75 patients, 31 (41%) were treated with adjuvant radiotherapy. Both disease-free survival (DFS) and disease-specific survival (DSS) were comparable between the groups who did and who did not receive adjuvant radiotherapy (HR 0.98, 95% CI 0.45-2.14, p=0.97 and HR = 1.02, 95% CI 0.42-2.47, p = 0.96). Conclusion. We could not demonstrate any beneficial effect of adjuvant radiotherapy in the group Of patients with one intra capsular metastasis. (C) 2009 Elsevier Inc. All rights reserved

Patient preferences for adjuvant radiotherapy in early breast cancer are strongly influenced by treatment received through random assignment

Objective: TARGIT‐A randomised women with early breast cancer to receive external beam radiotherapy (EBRT) or intraoperative radiotherapy (TARGIT‐IORT). This study aimed to identify what extra risk of recurrence patients would accept for per‐ ceived benefits and risks of different radiotherapy treatments. Methods: Patient preferences were determined by self‐rated trade‐off question‐ naires in two studies: Stage (1) 209 TARGIT‐A participants (TARGIT‐IORT n = 108, EBRT n = 101); Stage (2) 123 non‐trial patients yet to receive radiotherapy (pre‐treat‐ ment group), with 85 also surveyed post‐radiotherapy. Patients traded‐off risks of local recurrence in preference selection between TARGIT‐IORT and EBRT. Results: TARGIT‐IORT patients were more accepting of IORT than EBRT patients with 60% accepting the highest increased risk presented (4%–6%) compared to 12% of EBRT patients, and 2% not accepting IORT at all compared to 43% of EBRT pa‐ tients. Pre‐treatment patients were more accepting of IORT than post‐treatment pa‐ tients with 23% accepting the highest increased risk presented compared to 15% of post‐treatment patients, and 15% not accepting IORT at all compared to 41% of pre‐ treatment patients. Conclusions: Breast cancer patients yet to receive radiotherapy accept a higher recurrence risk than the actual risk found in TARGIT‐A. Measured patient preferences are highly influenced by experience of treatment received. This finding challenges the validity of post‐treatment preference studies

Adjuvant vs. salvage radiation therapy in men with high-risk features after radical prostatectomy: Survey of North American genitourinary expert radiation oncologists

INTRODUCTION: The management of patients with high-risk features after radical prostatectomy (RP) is controversial. Level 1 evidence demonstrates that adjuvant radiation therapy (RT) improves survival compared to no treatment; however, it may overtreat up to 30% of patients, as randomized clinical trials (RCTs) using salvage RT on observation arms failed to reveal a survival advantage of adjuvant RT. We, therefore, sought to determine the current view of adjuvant vs. salvage RT among North American genitourinary (GU) radiation oncology experts. METHODS: A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding adjuvant vs. salvage RT for this patient population. Treatment recommendations were correlated with practice patterns using Fisher's exact test. RESULTS: Forty-two of 88 radiation oncologists completed the survey; 23 (54.8%) recommended adjuvant RT and 19 (45.2%) recommended salvage RT. Recommendation of active surveillance for Gleason 3+4 disease was a significant predictor of salvage RT recommendation (p=0.034), and monthly patient volume approached significance for recommendation of adjuvant over salvage RT; those seeing <15 patients/month trended towards recommending adjuvant over salvage RT (p=0.062). No other demographic factors approached significance. CONCLUSIONS: There is dramatic polarization among North American GU experts regarding optimal management of patients with high-risk features after RP. Ongoing RCTs will determine whether adjuvant RT improves survival over salvage RT. Until then, the almost 50/50 division seen from this analysis should encourage practicing clinicians to discuss the ambiguity with their patients