Dosimetric accuracy of three dose calculation algorithms for radiation therapy of in situ non-small cell lung carcinoma

BackgroundStudy determines differences in calculated dose distributions for non-small cell lung carcinoma (NSC LC) patients. NSC LC cases were investigated, being the most common lung cancer treated by radiotherapy in our clinical practice.Materials and methodsA retrospective study of 15 NSCLC patient dose distributions originally calculated using standard superposition (SS) and recalculated using collapsed cone (CC ) and Monte Carlo (MC) based algorithm expressed as dose to medium in medium (MCD_m) and dose to water in medium (MCD_w,) was performed so that prescribed dose covers at least 99% of the gross target volume (GTV). Statistical analysis was performed for differences of conformity index (CI), heterogeneity index (HI), gradient index (GI), dose delivered to 2% of the volume (D_2%), mean dose (D_mean) and percentage of volumes covered by prescribed dose (V_70Gy). For organs at risk (OARs), D_mean and percentage of volume receiving 20 Gy and 5Gy (V_20Gy, V_5Gy) were analysed.ResultsStatistically significant difference for GTVs was observed between MCD_w and SS algorithm in mean dose only. For planning target volumes (PTVs), statistically significant differences were observed in prescribed dose coverage for CC, MCD_m and MCD_w. The differences in mean CI value for the CC algorithm and mean HI value for MCD_m and MCD_w were statistically significant. There is a statistically significant difference in the number of MUs for MCD_m and MCD_w compared to SS.ConclusionAll investigated algorithms succeed in managing the restrictive conditions of the clinical goals. This study shows the drawbacks of the CC algorithm compared to other algorithms used.     

The role of medical physics in prostate cancer radiation therapy

Medical physics, both as a scientific discipline and clinical service, hugely contributed and still contributes to the advances in the radiotherapy of prostate cancer. The traditional translational role in developing and safely implementing new technology and methods for better optimizing, delivering and monitoring the treatment is rapidly expanding to include new fields such as quantitative morphological and functional imaging and the possibility of individually predicting outcome and toxicity. The pivotal position of medical physicists in treatment personalization probably represents the main challenge of current and next years and needs a gradual change of vision and training, without losing the traditional and fundamental role of physicists to guarantee a high quality of the treatment. The current focus issue is intended to cover traditional and new fields of investigation in prostate cancer radiation therapy with the aim to provide up-to-date reference material to medical physicists daily working to cure prostate cancer patients. The papers presented in this focus issue touch upon present and upcoming challenges that need to be met in order to further advance prostate cancer radiation therapy. We suggest that there is a smart future for medical physicists willing to perform research and innovate, while they continue to provide high-quality clinical service. However, physicists are increasingly expected to actively integrate their implicitly translational, flexible and high-level skills within multi-disciplinary teams including many clinical figures (first of all radiation oncologists) as well as scientists from other disciplines.     

The role of autophagy in sensitizing malignant glioma cells to radiation therapy

Malignant gliomas represent the majority of primary brain tumors. The current standard treatments for malignant gliomas include surgical resection, radiation therapy, and chemotherapy. Radiotherapy, a standard adjuvant therapy, confers some survival advantages, but resistance of the glioma cells to the efficacy of radiation limits the success of the treatment. The mechanisms underlying glioma cell radioresistance have remained elusive. Autophagy is a protein degradation system characterized by a prominent formation of double-membrane vesicles in the cytoplasm. Recent studies suggest that autophagy may be important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer therapy. Also, autophagy is a novel response of glioma cells to ionizing radiation. Autophagic cell death is considered programmed cell death type II, whereas apoptosis is programmed cell death type I. These two types of cell death are predominantly distinctive, but many studies demonstrate a cross-talk between them. Whether autophagy in cancer cells causes death or protects cells is controversial. The regulatory pathways of autophagy share several molecules. PI3K/Akt/mTOR, DNA-PK, tumor suppressor genes, mitochondrial damage, and lysosome may play important roles in radiation-induced autophagy in glioma cells. Recently, a highly tumorigenic glioma tumor subpopulation, termed cancer stem cell or tumor-initiating cell, has been shown to promote therapeutic resistance. This review summarizes the main mediators associated with radiation-induced autophagy in malignant glioma cells and discusses the implications of the cancer stem cell hypothesis for the development of future therapies for brain tumors.     

Factors influencing the use of adaptive radiation therapy in vulvar carcinoma

AimWe aim to evaluate the variables affecting the frequency of adaptive radiotherapy (ART) in vulvar cancer.BackgroundART may be needed throughout a definitive RT course for vulvar carcinoma due to changes in patient’s anatomy and tumor response.Materials and methodsCharts of patients charts who had been treated with definitive concurrent chemo-radiotherapy for vulvar carcinoma, between January 2015 and December 2019 were inquired. Radiation therapy was delivered using intensity modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT). ART was defined as re-simulation and re-planning based on deformation in the irradiated volume by more than 1 cm. Univariate analysis was conducted to study the impact of patient’s demographics as well as tumor characteristics on the frequency of ART.Results22 patients were eligible for analysis. Median age at diagnosis was 55 years (range 43–82). Radiotherapy dose was 60−66 Gy over 30–35 fractions (fx). Median primary tumor volume was 30cc (9–140). Median Body Mass Index (BMI) was 32 (range 21–40). Thirteen out of 22 patients (59%) required ART, with median timing at 25 fx (19–31). On univariate analysis, larger primary tumor volume (> = 30cc) was associated significantly with increased frequency of ART (p value = 0.0005). There was no significant impact of ART on the frequency with respect to patient’s age, BMI, tumor stage, grade and location.ConclusionChanges in radiation target volume are common among vulvar carcinoma patients who are treated with definitive radiotherapy, especially large primary tumors. This review highlights the importance of ART for patients with vulvar carcinoma treated with definitive radiotherapy.     

The potential for gene-targeted radiation therapy of cancers

Targeted cancer therapy is the mantra now chanted by oncologists of all types. Everyone hopes that the rapid expansion in the knowledge of cancer cell genetics, signaling, regulatory factors and other changes that underlie malignant transformation and metastasis will lead to innovative approaches for the treatment of cancers. To date, successful targeted therapies have been derived from pharmaceutical chemistry - designing chemical compounds intended to disrupt a crucial pathway for malignant cells to survive, grow and metastasize. Radiotherapy also has a goal of more-selective targeting of therapeutic radiation effects to only tumor cells. In this review, we describe our efforts to create a form of gene-targeted radiation therapy by using the unique radiation effects of radionuclides that decay by the Auger process attached to oligonucleotide carrier-molecules that are capable of forming triplex DNA structures with target sequences in the genome of the human cancer cell.     

The role of radiation-induced apoptosis as a determinant of tumor responses to radiation therapy

Ionizing radiation is an effective means of killing tumor cells. Approximately 50% of all American cancer patients are treated with radiotherapy at some time during the course of their disease, making radiation one of the most widely used cytotoxic therapies. Currently, much effort is focused on understanding the molecular pathways that regulate tumor cell survival following radiotherapy, with the long term goal of developing novel therapeutic strategies for specifically sensitizing tumors to radiation. At present, there is particular interest in the role of tumor cell apoptotic potential as a regulator of both intrinsic and extrinsic determinants of the response of tumors to radiation therapy. Here we review what is currently known about the role of apoptosis as a mechanism of tumor cell killing by ionizing radiation and the relative contribution of apoptosis to cellular radiosensitivity and the ability to control human cancers using radiotherapy. The following topics will be discussed: (1) radiation-induced apoptosis in normal and malignant cells, (2) clinical findings with respect to apoptosis in human cancers treated with radiotherapy, (3) the contribution of apoptosis to intrinsic radiosensitivity in vitro, (4) the relevance of apoptosis to treatment outcome in experimental tumor models in vivo and (5) the potential of exploiting apoptosis as a means to improve the therapeutic efficacy of radiotherapy.     

图像引导放射治疗老年非小细胞肺癌30例

目的:分析图像引导放射治疗(IGRT)对老年非小细胞肺癌患者的临床疗效.方法:30例老年非小细胞肺癌患者,全部采用医科达图像引导放射治疗系统,GTV:60Gy,参考剂量线为95%～98%,分割方式3～4Gy/次.结果:肿瘤完全缓解率为33%(10/30),部分缓解率为50%(15/30),总有效率为83%(25/30).1、2、3年生存率为85%、70%、67%.结论:图像引导放射治疗(IGRT)对老年非小细胞肺癌有较好的局部控制率,是治疗老年非小细胞肺癌患者的有效方法之一.     

The evolution of hormonal therapy for prostatic carcinoma

It is well recognized that testosterone has a number of untoward effects on prostatic carcinoma and that castration is associated with significant tumor shrinkage and resolution of symptoms of advanced prostatic carcinoma. Approaches to hormonal therapy have evolved significantly over the last several decades. Initially castration was utilized, which provided effective reduction of testicular androgens, but with adverse psychological factors. The next approach was utilization of diethylstilbestrol, but with significant cardiovascular toxicity in higher doses. The development of the luteinizing hormone-releasing hormone agonists provided an improvement in pharmacologic castration; however, they are associated with a transient testosterone surge and the potential for exacerbation of clinical manifestations of advanced prostate carcinoma (the so-called "testosterone flare"). Recently, gonadotropin-releasing hormone (GnRH) antagonists have been investigated. Abarelix is a pure GnRH antagonist that blocks the anterior pituitary receptor, resulting in prompt and significant reduction not only of luteinizing hormone but also follicle-stimulating hormone. This results in castrate levels of testosterone while avoiding the testosterone surge.