Gustavo Nader Marta

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.

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.

The Rationale for Targeted Therapies and Stereotactic Radiosurgery in the Treatment of Brain Metastases

UNLABELLED Brain metastases are the most common intracranial malignancy. Many approaches, including radiation therapy, surgery, and cytotoxic chemotherapy, have been used to treat patients with brain metastases depending on the patients disease burden and symptoms. However, stereotactic surgery (SRS) has revolutionized local treatment of brain metastases. Likewise, targeted therapies, including small-molecule inhibitors and monoclonal antibodies that target cancer cell metabolism or angiogenesis, have transformed managing systemic disease. Prospective data on combining these treatments for synergistic effect are limited, but early data show favorable safety and efficacy profiles. The combination of SRS and targeted therapy will further individualize treatment, potentially obviating the need for cytotoxic chemotherapy or whole-brain radiation. There is a great need to pursue research into these exciting modalities and novel combinations to further improve the treatment of patients with brain metastases. This article discusses reported and ongoing clinical trials assessing the safety and efficacy of targeted therapy during SRS. IMPLICATIONS FOR PRACTICE Treatment of patients with brain metastases requires a multidisciplinary approach. Stereotactic radiosurgery is increasingly used in the upfront setting to treat new brain metastasis. Targeted therapies have revolutionized systemic treatment of many malignancies and may sometimes be used as initial treatment in metastatic patients. There is sparse literature regarding safety and efficacy of combining these two treatment modalities. This article summarizes the supporting literature and highlights ongoing clinical trials in combining radiosurgery with targeted therapy.

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.

MicroRNAs, cancer and ionizing radiation: Where are we?

The aim of this study is to describe the biogenesis of microRNA, its relations with carcinogenesis, and the correlation between microRNA and ionizing radiation (IR), focusing on radioresponsiveness. It is known that microRNA biogenesis is well established and involves different enzymatic cleavages, resulting in the production of mature microRNA. MicroRNAs are involved in carcinogenesis. Their interaction is related to the genetic and epigenetic changes associated with activation of proto-oncogenes or inactivation of tumor suppressor genes. Several studies have shown that the levels of expression of some microRNAs vary significantly after irradiation. There are evidences that microRNAs can influence cellular response after IR. In addition, microRNAs are related to modulation of the expression of several post-transcriptional targets in DNA damage response pathways, and to the DNA damage repair regulation mechanism. Future studies can clarify a possible clinical use of microRNAs as a new class of radiosensitive agents.

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.

Early stage breast cancer and radiotherapy: update

Breast cancer (BC) is the most common malignancy among women. Therapeutic options are based on disease staging, histopathological characteristics, age, and others. The objective of the present study is to carry out an update of the concepts and definitions of radiotherapy (RT) in conservative treatment of early-stage breast cancer, with emphasis on indications, contraindications, RT dose fractionation schedules (classic, hypofractionated and partial breast irradiation), adjuvant RT in ductal carcinoma in situ (DCIS) and molecular predictors of recurrence. MEDLINE, SciELO and Cochrane databases were used for article selection. Adjuvant RT is indicated for patients with BC who underwent conservative breast surgery. In selected patients, hypofractionated or partial breast irradiation can be used. Adjuvant RT should be provided for all patients with DCIS. The correlation of RT and molecular predictors of local and systemic recurrence are not yet well-known.

Câncer de mama estádio inicial e radioterapia: atualização

O câncer de mama e a neoplasia maligna mais frequente entre as mulheres. A escolha terapeutica depende do estadio clinico da doenca, das caracteristicas anatomopatologicas, idade, entre outros. O objetivo do presente estudo e apresentar uma atualizacao dos conceitos e definicoes da radioterapia (RT) no tratamento conservador do câncer de mama estadio inicial, enfatizando as indicacoes, contraindicacoes, dose e fracionamento da RT (esquema classico, hipofracionado e irradiacao parcial da mama), RT adjuvante no carcinoma ductal in situ (CDIS), irradiacao das cadeias linfonodais e relacao da RT com preditores moleculares de recorrencia. Foram utilizadas as bases de dados MEDLINE, SciELO e Cochrane para a selecao dos principais artigos disponiveis sobre a tematica proposta. A RT adjuvante tem um papel definido na abordagem das pacientes com câncer da mama submetidas a terapia cirurgica conservadora. Em pacientes selecionadas, podem-se empregar esquemas de RT hipofracionada ou irradiacao parcial das mamas. Todas as pacientes com CDIS devem receber RT adjuvante. Nao se sabe a correlacao do papel da RT com preditores moleculares de recorrencia local e sistemica.

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.

O médico frente a novidades no tratamento do câncer: quando parar?

The issue of life-ending has been a source of considerations since the dawn of civilization, and calls for great circumspection when one attempts to fit it socially throughout the history of human thinking. The development and improvement of Medicine might modify, in most cases, the natural history of disease. We have managed to prolong life and the process of dying. This has created a new medical prototype that needs to care for terminally-ill patients, a situation often accompanied by severe suffering. Society attributes to the physician the role of being responsible for conquering and overcoming death. In the oncology context, these questions are well addressed, as in many situations there is no possibility to offer a curative treatment to the patients. The objective of the present study was to discuss the relations that guide the proposed theme, based on a medical literature review. Therefore, a perspective is sought as an argumentative alternative that brings evidence to the proposed debate.