M. Duclos

Duration of Androgen Suppression Before Radiotherapy for Localized Prostate Cancer: Radiation Therapy Oncology Group Randomized Clinical Trial 9910

PURPOSEnTo determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer.nnnPATIENTS AND METHODSnOne thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up.nnnRESULTSnThere were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively.nnnCONCLUSIONnExtending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

The authors analyzed a preliminary report of patient‐reported outcomes (PROs) among men who received high‐dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose‐escalation trial) with either 3‐dimensional conformal RT (3D‐CRT) or intensity‐modulated RT (IMRT).

Silver Clear Nylon Dressing is Effective in Preventing Radiation-Induced Dermatitis in Patients With Lower Gastrointestinal Cancer: Results From a Phase III Study

PURPOSEnFor patients with anal canal and advanced rectal cancer, chemoradiation therapy is a curative modality or an important adjunct to surgery. Nearly all patients treated with chemoradiation experience some degree of radiation-induced dermatitis (RID). Prevention and effective treatment of RID, therefore, is of considerable clinical relevance. The present phase III randomized trial compared the efficacy of silver clear nylon dressing (SCND) with that of standard skin care for these patients.nnnMETHODS AND MATERIALSnA total of 42 rectal or anal canal cancer patients were randomized to either a SCND or standard skin care group. SCND was applied from Day 1 of radiation therapy (RT) until 2 weeks after treatment completion. In the control arm, sulfadiazine cream was applied at the time of skin dermatitis. Printed digital photographs taken 2 weeks prior to, on the last day, and two weeks after the treatment completion were scored by 10 blinded readers, who used the common toxicity scoring system for skin dermatitis.nnnRESULTSnThe radiation dose ranged from 50.4 to 59.4 Gy, and there were no differences between the 2 groups. On the last day of RT, when the most severe RID occurs, the mean dermatitis score was 2.53 (standard deviation [SD], 1.17) for the standard and 1.67 (SD, 1.2; P=.01) for the SCND arm. At 2 weeks after RT, the difference was 0.39 points in favor of SCND (P=.39). There was considerable intraclass correlation among the 10 observers.nnnCONCLUSIONSnSilver clear nylon dressing is effective in reducing RID in patients with lower gastrointestinal cancer treated with combined chemotherapy and radiation treatment.

Phase II Multicenter Trial with Carboplatin and Gemcitabine Induction Chemotherapy Followed by Radiotherapy Concomitantly with Low-Dose Paclitaxel and Gemcitabine for Stage IIIA and IIIB Non-small Cell Lung Cancer

Introduction: The optimal combination of concomitant radiotherapy (RT) and chemotherapy in stage III unresectable non-small cell lung cancer (NSCLC) remains unclear. The role of induction chemotherapy with carboplatin/gemcitabine regimen has not been established in stage III NSCLC. Methods: Forty-two stage III NSCLC patients, 41 assessable, with a median age of 60 years and good performance status, entered this trial between January 2003 and November 2004. They received carboplatin area under the curve 5 on day 1 and gemcitabine 1000 mg/m2 on days 1 + 8 every 3 weeks for two cycles, followed on day 50 by RT 60 Gy, concomitantly with paclitaxel 50 mg/m2 and gemcitabine 100 mg/m2 on days 1 + 8 every 3 weeks for two cycles. Results: After induction, the partial response (PR) was 73.1% and stable disease was 24.4%. Disease progressed in one patient. After RT and paclitaxel/gemcitabine, 22% achieved a complete response and 73% a PR, and 5% had disease progression. The median survival was 25 months, the 1-year survival rate was 73.2%, and the 2-year survival rate was 50.5%. During concomitant RT and chemotherapy, grade 3 neutropenia, thrombocytopenia, and anemia occurred in eight, three, and three patients, respectively, and grade 4 neutropenia and thrombocytopenia in one patient each. One patient developed an esophageal fistula and died shortly after, which was considered a grade 5 toxicity; one patient developed grade 4 interstitial pneumonitis, and three patients developed grade 3 esophagitis. Conclusion: This regimen appears to be effective and was well tolerated. Further studies using this approach are warranted in patients with stage III NSCLC.

Contemporary outcome and management of patients who had an aborted cystectomy due to unresectable bladder cancer

OBJECTIVESnAborted cystectomy due to unresectable disease is not uncommon in patients with bladder cancer. Our aim was to review the outcome of these patients and evaluate various prognostic variables.nnnMATERIALS AND METHODSnThirty-one bladder cancer patients who underwent aborted radical cystectomy due to unresectable disease from 1993 to 2007, and form the basis of this report. Survival was estimated by the Kaplan and Meier method, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied.nnnRESULTSnMean age of patients was 66 years with median follow-up of patients alive 10 months. The 2- and 5-year overall survival (OS) was 41% and 0%, respectively. Twenty patients had a pelvic lymph node dissection (PLND) and 11 patients did not. Twenty-three patients received postoperative therapy, of whom 8 received chemotherapy with the intent of surgical consolidation (only 2 were rendered resectable thereafter), and 15 received combined chemoradiation. OS was not significantly associated with hydronephrosis, concomitant CIS, performance status, history of superficial tumors, postoperative therapy, and salvage cystectomy. Patients with pN2-3 had similar overall survival compared with those with pT4b (13 vs. 17 months, P=0.59). However, patients who underwent PLND trended towards improved OS compared with those who did not (24 vs. 10 months, P=0.09).nnnCONCLUSIONSnOutcome of patients with unresectable disease is dismal. Patients who had an aborted cystectomy due to unresectable disease may benefit from PLND. Further refinements of clinical staging to better identify these patients preoperatively and offer them upfront chemotherapy are needed.

A dosimetric comparison of two high-dose-rate brachytherapy planning systems in cervix cancer: Standardized template planning vs. computerized treatment planning

PURPOSEnHigh-dose-rate brachytherapy is an important component of the curative treatment for cervical cancer. Some institutions use standardized template planning (STP), based on a precalculated table of dose rates, instead of computerized treatment planning (CTP), based on digitized orthogonal X-ray films. STP can be used as a backup check in case of computer hardware malfunction, and/or as a way to minimize treatment planning time. We performed a dosimetric comparison of STP and CTP to determine dose differences at point A and the International Commission on Radiation Units and Measurements Report 38 bladder and rectal reference points.nnnMETHODS AND MATERIALSnWe retrospectively reviewed the treatment plans of 62 patients (135 applications) treated with a tandem and two ovoids using the CTP method. For each of these plans, we calculated the dwell times required to deliver the same prescription dose had STP been used. We also used the planning computer to vary tandem and ovoid geometry and develop a table of dose rates based on geometric parameters.nnnRESULTSnThe mean dose at point A was 7.6 Gy using CTP, increasing to 8.4 Gy when the STP approach was used (p<0.05). The mean doses at the International Commission on Radiation Units and Measurements Report 38 bladder and rectal points were both 4.5 Gy with CTP and increased to 4.9 and 5.0 Gy, respectively using STP (p<0.05). Our table of dose rates showed significant dose rate dependency on the applicators geometry.nnnCONCLUSIONSnOur study shows that if the STP approach had been used, a significantly higher dose would have been delivered, and that STP tables accounting for differences in implant geometry should be carefully considered.

Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial

Importance Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences. Objective To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer. Design, Setting, and Participants The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008. Men with stage cT1b to T2b, Gleason score 2 to 6, and prostate-specific antigen (PSA) level of 10 or greater and less than 20 or Gleason score of 7 and PSA less than 15 received 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions. Main Outcomes and Measures Time to OS measured from randomization to death due to any cause. American Society for Therapeutic Radiology and Oncology (ASTRO)/Phoenix definitions were used for biochemical failure. Acute (⩽90 days of treatment start) and late radiation therapy toxic effects (>90 days) were graded using the National Cancer Institute Common Toxicity Criteria, version 2.0, and the RTOG/European Organisation for the Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme, respectively. Results With a median follow-up of 8.4 (range, 0.02-13.0) years in 1499 patients (median [range] age, 71 [33-87] years; 70% had PSA <10 ng/mL, 84% Gleason score of 7, 57% T1 disease), there was no difference in OS between the 751 men in the 79.2-Gy arm and the 748 men in the 70.2-Gy arm. The 8-year rates of OS were 76% with 79.2 Gy and 75% with 70.2 Gy (hazard ratio [HR], 1.00; 95% CI, 0.83-1.20; Pu2009=u2009.98). The 8-year cumulative rates of distant metastases were 4% for the 79.2-Gy arm and 6% for the 70.2-Gy arm (HR, 0.65; 95% CI, 0.42-1.01; Pu2009=u2009.05). The ASTRO and Phoenix biochemical failure rates at 5 and 8 years were 31% and 20% with 79.2 Gy and 47% and 35% with 70.2 Gy, respectively (both Pu2009<u2009.001; ASTRO: HR, 0.59; 95% CI, 0.50-0.70; Phoenix: HR, 0.54; 95% CI, 0.44-0.65). The high-dose arm had a lower rate of salvage therapy use. The 5-year rates of late grade 2 or greater gastrointestinal and/or genitourinary toxic effects were 21% and 12% with 79.2 Gy and 15% and 7% with 70.2 Gy (Pu2009=u2009.006 [HR, 1.39; 95% CI, 1.10-1.77] and Pu2009=u2009.003 [HR, 1.59; 95% CI, 1.17-2.16], respectively). Conclusions and Relevance Despite improvements in biochemical failure and distant metastases, dose escalation did not improve OS. High doses caused more late toxic effects but lower rates of salvage therapy. Trial Registration clinicaltrials.gov Identifier: NCT00033631

Tratamento do câncer de pequenas células de pulmão: doença limitada: resultados de uma única instituição

OBJECTIVE: To report the results of the treatment of patients with small-cell lung cancer with limited disease (SCLC-LD) in a single institution during a 10-year period, for quality assurance and comparison with data from the literature. MATERIALS AND METHODS: Between January 1992 and December 2002, 101 patients with SCLC-LD completed treatment at our institution. The outcomes were reviewed and included chemotherapy, radiotherapy, the sequence of the two treatments, and the use of prophylactic cranial irradiation. Radiation was delivered with a median dose of 45 Gy in 1.8 to 2 Gy per fraction. The median dose of the prophylactic cranial irradiation was 25 Gy in 10 fractions. RESULTS: Average follow-up was of 50.6 months and the average age of the patients was 63 years. There were 85 confirmed deaths, 5 patients were lost to follow up and 11 patients were alive. The median survival time was 11 months, the overall survival at 2 and 5 years was 25.5% and 10% respectively. There were no significant difference in overall survival at 2 or 5 years according to the age and sex of the patients. In addition, there were no statistical difference in overall survival among patients who had prophylactic cranial irradiation or not, or who were treated in two different periods (1997-2002 vs. 1992-1996). CONCLUSION: The results of the treatment of SCLC-LD patients in our institution reflect the constant changes in the management of SCLC. The 2-years 25.5% overall survival seen in our institution is similar to reports published from other single institution, but lower than the 47% to 54% recently published results from cooperative groups.