Samir Abdallah Hanna

Intensity-modulated radiation therapy for head and neck cancer: systematic review and meta-analysis.

BACKGROUND AND PURPOSE Intensity-modulated radiation therapy (IMRT) provides the possibility of dose-escalation with better normal tissue sparing. This study was performed to assess whether IMRT can improve clinical outcomes when compared with two-dimensional (2D-RT) or three-dimensional conformal radiation therapy (3D-CRT) in patients with head and neck cancer. METHODS AND MATERIALS Only prospective phase III randomized trials comparing IMRT with 2D-RT or 3D-CRT were eligible. Combined surgery and/or chemotherapy were allowed. Two authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS Five studies were selected. A total of 871 patients were randomly assigned for 2D-RT or 3D-CRT (437), versus IMRT (434). Most patients presented with nasopharyngeal cancers (82%), and stages III/IV (62.1%). Three studies were classified as having unclear risk and two as high risk of bias. A significant overall benefit in favor of IMRT was found (hazard ratio - HR=0.76; 95% CI: 0.66, 0.87; p<0.0001) regarding xerostomia scores grade 2-4, with similar loco-regional control and overall survival. CONCLUSIONS IMRT reduces the incidence of grade 2-4 xerostomia in patients with head and neck cancers without compromising loco-regional control and overall survival.

Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials

BACKGROUND AND PURPOSE Accelerated partial breast irradiation (APBI) is the strategy that allows adjuvant treatment delivery in a shorter period of time in smaller volumes. This study was undertaken to assess the effectiveness and outcomes of APBI in breast cancer compared with whole-breast irradiation (WBI). MATERIAL AND METHODS Systematic review and meta-analysis of randomized controlled trials of WBI versus APBI. Two authors independently selected and assessed the studies regarding eligibility criteria. RESULTS Eight studies were selected. A total of 8653 patients were randomly assigned for WBI versus APBI. Six studies reported local recurrence outcomes. Two studies were matched in 5 years and only one study for different time of follow-up. Meta-analysis of two trials assessing 1407 participants showed significant difference in the WBI versus APBI group regarding the 5-year local recurrence rate (HR=4.54, 95% CI: 1.78-11.61, p=0.002). Significant difference in favor of WBI for different follow-up times was also found. No differences in nodal recurrence, systemic recurrence, overall survival and mortality rates were observed. CONCLUSIONS APBI is associated with higher local recurrence compared to WBI without compromising other clinical outcomes.

The role of radiotherapy in urinary bladder cancer: current status.

The role of radiotherapy (RT) in the treatment of urinary bladder cancer has undergone several modifications along the last decades. In the beginning, definitive RT was used as treatment in an attempt to preserve the urinary bladder; however, the results were poor compared to those of radical surgery. Recently, many protocols have been developed supporting the use of multi-modality therapy, and the concept of organ preservation began to be reconsidered. Although phase III randomized clinical studies comparing radical cystectomy with bladder preservation therapies do not exist, the conservative treatment may present low toxicity and high indexes of complete response for selected patients. The aim of this study was to review the literature on the subject in order to situate RT in the current treatment of urinary bladder cancer.

Brazil's Challenges and Opportunities

*Department of Radiation Oncology/Oncology Center, Hospital Sı́rio-Libanês, São Paulo, Brazil; yDepartment of Radiology and Oncology, Instituto do Cancêr do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; zDepartment of Radiation Oncology, Hospital Beneficiência Portuguesa, São Paulo, Brazil; xDepartment of Radiology and Oncology, Instituto de Radiologia do Hospital das Clı́nicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

ROLE OF INTRA- OR PERIPROSTATIC CALCIFICATIONS IN IMAGE-GUIDED RADIOTHERAPY FOR PROSTATE CANCER

PURPOSE Image-guided radiotherapy (IGRT) allows more precise localization of the prostate, thus minimizing errors resulting from organ motion and set-up during treatment of prostate cancer. Using megavoltage cone-beam computed tomography (MVCBCT), references such as bones, the prostate itself or implanted fiducial markers can be used as surrogates to correct patient positioning immediately before each treatment fraction. However, the use of fiducials requires an invasive procedure and may increase costs. We aimed to assess whether intra- or periprostatic calcifications (IPC) could be used as natural fiducials. METHODS AND MATERIALS Data on patients treated with IGRT for prostate cancer with clearly visible IPC and implanted fiducials in both planning CT and MVCBCT images were reviewed. IPC were classified as central when inside the prostate and peripheral when within the planning target volume. Daily deviations in lateral, longitudinal, and vertical directions from baseline positioning using fiducials and using IPC were compared. RESULTS A total of 287 MVCBCT images were obtained and analyzed from 10 patients. The mean ± standard deviation daily deviation (mm) in the lateral, longitudinal, and vertical coordinates were 0.55 ± 3.11, 0.58 ± 3.45, and -0.54 ± 4.03, respectively, for fiducials, and 0.72 ± 3.22, 0.63 ± 3.58, and -0.69 ± 4.26, for IPC. The p values for comparisons (fiducials vs. IPC) were 0.003, 0.653, and 0.078 for lateral, longitudinal, and vertical coordinates, respectively. When cases with central IPC were analyzed (n = 7), no significant difference was found in such comparisons. Central IPC and fiducials exhibited a similar pattern of displacement during treatment, with equal values for daily displacements in the three directions for more than 90% of measurements. CONCLUSIONS Our data suggest that centrally located IPC may be used as natural fiducials for treatment positioning during IGRT for prostate cancer, with potential reductions in the risks and costs associated with fiducial implantation.

Outcomes of high-dose intensity-modulated radiotherapy alone with 1 cm planning target volume posterior margin for localized prostate cancer.

BackgroundClinically localized prostate cancer may be treated by different approaches of radiation therapy. The aim of this study was to report the results of disease control and toxicity in patients with clinically localized prostate cancer treated with high dose IMRT alone with 1 cm PTV posterior margin.MethodsFrom September 2001 to April 2008, 140 patients with localized prostate cancer were treated with definitive IMRT (dose ≥ 74 Gy) without hormone therapy. Outcomes were measured from the conclusion of radiotherapy. Biochemical failure was defined as PSA nadir + 2.0 ng/dL. Toxicities were assessed using the NCI-CTCAE-version 3.0. Median follow-up was 58 months.ResultsBiochemical failure occurred in 13.6% of patients. Actuarial 5-year biochemical control rates were 91.7%, 82.5% and 85.9% for low-, intermediate-, and high-risk patients, respectively. Stage T2 patients presented a risk of biochemical failure almost three times higher than stage T1 (RR = 2.91; 95% CI: 1.04; 8.17). Distant metastases occurred in 3 (2%) patients. Five-year metastasis-free and overall survivals were 96% and 97.5%, respectively. Late grade 3 genitourinary and gastrointestinal toxicity rates were, respectively, 1.6% and 3%.ConclusionHigh-dose IMRT alone with 1 cm posterior PTV margin was effective and safe for patients with localized prostate cancer.

The value of positron-emission tomography/computed tomography for radiotherapy treatment planning: a single institutional series

BackgroundThis study aimed to compare the clinical target volumes (CTV) delineated by computed tomography (CT) and positron emission tomography (PET)/CT using fluoro-deoxy-glucose to assess the impact of using PET information for radiotherapy (RT) planning. MethodsWe retrospectively reviewed data on patients with tumors from different sites who had indications for RT and had undergone RT treatment planning with PET/CT at our institution between July 2003 and July 2009. Statistical analysis included the comparison of CTV planned for treatment only by CT (CTVCT) with that by PET/CT (CTVPET) using the Wilcoxon test for paired samples. ResultsOf 105 patients eligible for analysis, 56.2% were men. The most common diagnoses were head and neck cancer (28.6%), lung cancer (21.9%), lymphoma (11.4%), upper gastrointestinal (10.5%), and others (14.3%). Comparison of CTVCT and CTVPET revealed that RT planning has changed in 77% of cases because of PET/CT additional information, with impact on treatment volume varying according to diagnosis. Despite the absolute difference observed between median CTVs, there was no significant difference between CTVCT and CTVPET (114 vs. 90.4 ml, respectively; P=0.1266), considering all patients. Nonetheless, a significant difference between CTVs delineated by CT and PET/CT was found when only head and neck, lung and lymphoma cases – representing more than 60% of the sample – were examined (112.5 and 80.7 ml, respectively; P=0.0053). ConclusionWe have shown that PET/CT use promotes significant changes in the CTV delineated for treatment of different tumors, modifying RT planning. Our data suggest that PET/CT has a good potential for optimizing RT treatment planning, especially in head and neck, lung, and lymphoma tumors.

Hierarchy of evidence referring to the central nervous system in a high-impact radiation oncology journal: a 10-year assessment. Descriptive critical appraisal study

CONTEXT AND OBJECTIVE To the best of our knowledge, there has been no systematic assessment of the classification of scientific production within the scope of radiation oncology relating to central nervous system tumors. The aim of this study was to systematically assess the status of evidence relating to the central nervous system and to evaluate the geographic origins and major content of these published data. DESIGN AND SETTING Descriptive critical appraisal study conducted at a private hospital in São Paulo, Brazil. METHODS We evaluated all of the central nervous system studies published in the journal Radiotherapy & Oncology between 2003 and 2012. The studies identified were classified according to their methodological design and level of evidence. Information regarding the geographical location of the study, the institutions and authors involved in the publication, main condition or disease investigated and time of publication was also obtained. RESULTS We identified 3,004 studies published over the 10-year period. Of these, 125 (4.2%) were considered eligible, and 66% of them were case series. Systematic reviews and randomized clinical trials accounted for approximately 10% of all the published papers. We observed an increase in high-quality evidence and a decrease in low-quality published papers over this period (P = 0.036). The inter-rater reliability demonstrated significant agreement between observers in terms of the level of evidence. CONCLUSIONS Increases in high-level evidence and in the total number of central nervous system papers were clearly demonstrated, although the overall number of such studies remained relatively small.

Self-reported Conflicts of Interest and Trial Sponsorship of Clinical Trials in Prostate Cancer Involving Radiotherapy.

Objectives: To examine the association between trial sponsorship and conflicts of interest (COI) with clinical trial conclusions for prostate cancer trials related to radiotherapy. Materials and Methods: The MEDLINE database was searched for all prostate cancer clinical trials published between 2004 and 2013 and identified 1396 studies. Two investigators independently identified trials published in the English language of ≥30 patients, and extracted relevant data. Clinical trials were classified according to trial characteristics, sponsorship source and type, COI, and study conclusion, and analyzed by univariable and multivariable logistic regression. Results: Of 240 eligible trials, 160 (67.5%) evaluated drugs without radiotherapy, 60 (25%) involved radiotherapy, and 18 (7.5%) involved procedures without radiotherapy. Of the 60 radiotherapy trials eligible for analysis, positive sponsorship and potential COI were present in 58.3% and 20% of trials, respectively. Study conclusions were positive, negative, or neutral in 78.3%, 5%, and 16.7% of trials, respectively. No association was found between positive conclusions and either industry support of potential COI. Positive conclusions were reported in 86.7% and 83.3% of trials with sponsorship and COI, respectively, as compared with 75.6% and 77.1% of those without sponsorship (P=0.37) and COI (P=0.64). Sponsorship was significantly associated with radiotherapy trials combined with drugs (odds ratio 5.5, P=0.01) and higher-risk disease (odds ratio 4.71, P=0.01). Conclusions: The presence of sponsorship was associated with radiotherapy trials involving drugs or studying higher-risk prostate cancer. However, there were no identified associations between study conclusion and sponsorship type or COI.

Biochemical control of prostate cancer with iodine-125 brachytherapy alone: experience from a single institution

AimBrachytherapy is an adequate option as monotherapy for localised prostate cancer. The objective of this study was to evaluate and compare biochemical failure free survival (BFFS) after low-dose-rate brachytherapy (LDRB) alone for patients with prostate cancer using ASTRO and Phoenix criteria, and detect prognostic factors.MethodsData on 220 patients treated between 1998 and 2002 with LDRB were retrospectively analysed. Neoadjuvant hormone therapy was used in 74 (33.6%) patients.ResultsMedian follow-up was 53.5 months (24–116). Five year BFFS was 83.0% and 83.7% using, respectively, the ASTRO and Phoenix criteria. Low -and intermediate-risk patients presented, respectively, 86.7% and 77.8% 5-year BFFS using the ASTRO definition (p=0.069), and 88.5% and 78.6% considering the Phoenix criteria (p=0.016). Bounce was observed in 66 (30%) patients. Multivariate analysis detected PSA at diagnosis <10 ng/ml and less than 50% positive biopsy fragments as favourable prognostic factors, regarding BF using both criteria. For the Phoenix criteria, also Gleason score <7 and low-risk group were identified as independent favourable prognostic factors.ConclusionsLDRB alone should be considered mostly for low-risk patients. PSA level was a strong independent prognostic factor. We support the use of the Phoenix criteria for detection of BF in patients submitted to LDRB alone.