Normal Tissue Radiation Research Articles

Optimal weekly scheduling in fractionated radiotherapy: effect of an upper bound on the dose fraction size.

This work concerns the optimization of the dose fractionation for cancer radiotherapy schedules of the kind one fraction/day, five fractions/week, assuming a fixed overall treatment time. Constraints are set to limit the radiation damages to surrounding normal tissues, as well as the daily fraction size. The response to radiation of tumour and normal tissues is represented by the classical LQ model, including the exponential repopulation term. We provide a framework to analytically determine the optimal weekly scheme of radiation doses as a function of the tumour type, the fraction upper bound and the normal tissue parameters. For a comparison with the literature, we present some numerical examples of optimal treatment schedules for specific tumour types.

Sci—Thur PM: Planning & Delivery — 04: Respiratory margin derivation and verification in partial breast irradiation

Partial breast irradiation (PBI) following breast‐conserving surgery is emerging as an effective means to achieve local control and reduce irradiated breast volume. Patients are planned on a static CT image; however, treatment is delivered while the patient is free‐breathing. Respiratory motion can degrade plan quality by reducing target coverage and/or dose homogeneity. A variety of methods can be used to determine the required margin for respiratory motion in PBI. We derive geometric and dosimetric respiratory 1D margin. We also verify the adequacy of the typical 5 mm respiratory margin in 3D by evaluating plan quality for increasing respiratory amplitudes (2–20 mm). Ten PBI plans were used for dosimetric evaluation. A database of volunteer respiratory data, with similar characteristics to breast cancer patients, was used for this study. We derived a geometric 95%‐margin of 3 mm from the population respiratory data. We derived a dosimetric 95%‐margin of 2 mm by convolving 1D dose profiles with respiratory probability density functions. The 5 mm respiratory margin is possibly too large when 1D coverage is assessed and could lead to unnecessary normal tissue irradiation. Assessing margins only for coverage may be insufficient; 3D dosimetric assessment revealed degradation in dose homogeneity is the limiting factor, not target coverage. Hotspots increased even for the smallest respiratory amplitudes, while target coverage only degraded at amplitudes greater than 10 mm. The 5 mm respiratory margin is adequate for coverage, but due to plan quality degradation, respiratory management is recommended for patients with respiratory amplitudes greater than 10 mm.

Radiation biology in the context of changing patterns of radiotherapy.

The last decade has witnessed a revolution in the clinical application of high-dose "ablative" radiation therapy. Initially this approach was limited to the treatment of brain tumors, but more recently we have seen its successful extension to tumors outside the brain, e.g., for small lung nodules. These advances have been driven largely by improvements in image-guided inverse treatment planning that allow the dose per fraction to the tumor to be increased over the conventional 2 Gy dose while keeping the late normal tissue complications at an acceptable level by dose limitation. Despite initial concerns about excessive late complications, as might be expected based on dose extrapolations using the linear-quadratic equation, these approaches have shown considerable clinical promise. Our knowledge of the biological consequences of high-doses of ionizing radiation in normal and cancerous tissues has lagged behind these clinical advances. Our intent here is to survey recent experimental findings from the perspective of better understanding the biological effects of high-dose therapy and whether they are truly different from conventional doses. We will also consider the implications of this knowledge for further refining and improving these approaches on the basis of underlying mechanisms.

Delivery systems for brachytherapy.

Brachytherapy is described as the short distance treatment of cancer with a radioactive isotope placed on, in, or near the lesions or tumor to be treated. The main advantage of brachytherapy compared with external beam radiation (EBR) is the improved localized delivery of dose to the target volume of interest, thus normal tissue irradiation is reduced. The precise and targeted nature of brachytherapy provides a number of key benefits for the effective treatment of cancer such as efficacy, minimized risk of side effects, short treatment times, and cost-effectiveness. Brachytherapy devices have yielded promising results in preclinical and clinical studies. However, brachytherapy can only be used in localized and relatively small tumors. Although the introduction of new delivery devices allows the treatment of more complex tumor sites, with wider range of dose rate for improving treatment efficacy and reduction of side effects, a better understanding about the safety, efficacy, and accuracy of these systems is required, and further development of new techniques is warranted. Therefore, this review focuses on the delivery devices for brachytherapy and their application in prostate, breast, brain, and other tumor sites.

Mitigation of experimental radiation nephropathy by renin-equivalent doses of angiotensin converting enzyme inhibitors

Purpose: We tested five different angiotensin converting enzyme inhibitors (ACEI) as mitigators of experimental radiation nephropathy at drug doses calibrated to the plasma renin activity (PRA). This was done to determine whether all ACEI had the same efficacy as mitigators of radiation nephropathy when used at drug doses that gave equivalent suppression of the renin angiotensin system.Method: 10 Gy total body irradiation with bone marrow transplantation was used to cause radiation nephropathy in barrier-maintained rats. Equivalent ACEI doses were determined based on their effect to inhibit angiotensin converting enzyme (ACE) and raise the PRA in unirradiated animals.Results: PRA-equivalent doses were found for captopril, lisinopril, enalapril, ramipril and fosinopril. These doses overlap the human doses of these drugs on a body surface area basis. All ACE inhibitors, except fosinopril, mitigated radiation nephropathy; captopril was a somewhat better mitigator than lisinopril, enalapril or ramipril.Conclusions: Most, but not all, ACEI mitigate radiation nephropathy at doses that overlap their clinically-used doses (on a body surface area basis). Fosinopril is known to be an ineffective mitigator of radiation pneumonitis, and it also does not mitigate radiation nephropathy. These pre-clinical data are critical in planning human studies of the mitigation of normal tissue radiation injury.

Association d’une chimiothérapie ou d’un traitement ciblé à une irradiation stéréotaxique : état des lieux et recommandations préliminaires

The clinical management of systemic treatments and irradiation has long been studied for conventional irradiation. Yet, many associations are of difficult management and some drugs are contra-indicated in the concomitant setting owing to excessive toxicities. Sequential regimens using a therapeutic window of variable duration (based on drug half-life and tissue wash out) between each modality may be preferred for easier logistics and to avoid toxicities. The use of intra- and extracranial stereotactic ablative radiation therapy (hypofractionated) is expanding rapidly. Yet, little is known regarding associations between stereotactic ablative radiation therapy and systemic treatments. The short stereotactic ablative radiation therapy course in one day to two weeks offers a theoretical advantage compared to longer conventional irradiation with respect to shorter discontinuation of therapy. This may be of particular interest in situations where cancer is addicted to systemic treatment. While it is believed that stereotactic ablative radiation therapy might be safer because of limited irradiation volumes and steep gradients sparing most organs at risk, it should be noted that irradiation of normal tissues cannot be considered null; that stereotactic ablative radiation therapy has vascular effects in addition to other cell death radiation-induced mechanisms and cancer progression with discontinuation of systemic treatment is often reversible. To date, based on several phase II studies, combined stereotactic ablative radiation therapy and cetuximab can be recommended in head and neck tumours. Other stereotactic ablative radiation therapy-based combinations require prospective phase I–II studies and sufficient therapeutic window (in the order of at least 5 half-lives) between the systemic and local modalities must be left in routine practice.

A preclinical rodent model of acute radiation-induced lung injury after ablative focal irradiation reflecting clinical stereotactic body radiotherapy.

In a previous study, we established an image-guided small-animal micro-irradiation system mimicking clinical stereotactic body radiotherapy (SBRT). The goal of this study was to develop a rodent model of acute phase lung injury after ablative irradiation. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice using a small animal stereotactic irradiator. At days 1, 3, 5, 7, 9, 11 and 14 after irradiation, the lungs were perfused with formalin for fixation and paraffin sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome. At days 7 and 14 after irradiation, micro-computed tomography (CT) images of the lung were taken and lung functional measurements were performed with a flexiVent™ system. Gross morphological injury was evident 9 days after irradiation of normal lung tissues and dynamic sequential events occurring during the acute phase were validated by histopathological analysis. CT images of the mouse lungs indicated partial obstruction located in the peripheral area of the left lung. Significant alteration in inspiratory capacity and tissue damping were detected on day 14 after irradiation. An animal model of radiation-induced lung injury (RILI) in the acute phase reflecting clinical stereotactic body radiotherapy was established and validated with histopathological and functional analysis. This model enhances our understanding of the dynamic sequential events occurring in the acute phase of radiation-induced lung injury induced by ablative dose focal volume irradiation.

Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

Development of Peptide and Protein Based Radiopharmaceuticals

Radiolabelled peptides and proteins have recently gained great interest as theranostics, due to their numerous and considerable advantages over small (organic) molecules. Developmental procedures of these radiolabelled biomolecules start with the radiolabelling process, greatly defined by the amino acid composition of the molecule and the radionuclide used. Depending on the radionuclide selection, radiolabelling starting materials are whether or not essential for efficient radiolabelling, resulting in direct or indirect radioiodination, radiometal-chelate coupling, indirect radiofluorination or (3)H/(14)C-labelling. Before preclinical investigations are performed, quality control analyses of the synthesized radiopharmaceutical are recommended to eliminate false positive or negative functionality results, e.g. changed receptor binding properties due to (radiolabelled) impurities. Therefore, radionuclidic, radiochemical and chemical purity are investigated, next to the general peptide attributes as described in the European and the United States Pharmacopeia. Moreover, in vitro and in vivo stability characteristics of the peptides and proteins also need to be explored, seen their strong sensitivity to proteinases and peptidases, together with radiolysis and trans-chelation phenomena of the radiopharmaceuticals. In vitro biomedical characterization of the radiolabelled peptides and proteins is performed by saturation, kinetic and competition binding assays, analyzing KD, Bmax, kon, koff and internalization properties, taking into account the chemical and metabolic stability and adsorption events inherent to peptides and proteins. In vivo biodistribution can be adapted by linker, chelate or radionuclide modifications, minimizing normal tissue (e.g. kidney and liver) radiation, and resulting in favorable dosimetry analyses. Finally, clinical trials are initiated, eventually leading to the marketing of radiolabelled peptides and proteins for PET/SPECT-imaging and therapy of different clinical diseases.

TH‐C‐12A‐09: Planning and Delivery of the Fully Dynamic Trajectory Modulated Arc Therapy: Application to Accelerated Partial Breast Irradiation

Purpose:A novel trajectory modulated arc therapy (TMAT) system was developed that uses source motion trajectory involving synchronized gantry rotation with translational and rotational couch movement. MLC motion and dose rate were fully optimized for dynamic beam delivery. This work presents a platform for planning deliverable TMAT on a collision free coronal trajectory and evaluates its benefit for accelerated partial breast irradiation (APBI) in a prone position.Methods:The TMAT algorithm was built on VMAT with modifications (physical properties on couch movement were defined) and enhancements (pencil beam dose calculation engine to support extended SSDs) to make it feasible for TMAT delivery. A Matlab software environment for TMAT optimization and dose calculation was created to allow any user specified motion axis. TMAT delivery was implemented on Varian TrueBeamTM STx via XML scripts. 10 prone breast irradiation cases were evaluated in VMAT and compared with a 6‐ field non‐coplanar IMRT plan. Patient selection/exclusion criteria and structure contouring followed the guidelines of NSABP B‐39/RTOG 0413 protocol.Results:TMAT delivery time was ∼4.5 minutes. 251.5°±7.88° of non‐isocentric couch arc was achieved by the optimized trajectory with 180– 210 control points at 1°–2° couch increments. The improved dose distribution by TMAT was most clearly observed by the marked reduction in the volume of irradiated normal breast tissue in the high dose region. The ratios of the normal breast tissue volume receiving more than 50%, 80% and 100% of the prescription dose for TMAT versus IMRT were: V50%(TMAT/IMRT) = 78.38%±13.03%, V80%(TMAT/IMRT) = 44.19%±9.04% and V100% (TMAT/IMRT) = 9.96%±7.55%, all p≤0.01.Conclusion:The study is the first demonstration of planning and delivery implementation of a fully dynamic APBI TMAT system with continuous couch motion. TMAT achieved significantly improved dosimetry over noncoplanar IMRT on dose volume parameters correlated with toxicity and cosmetic outcome of APBI.This project was supported by Varian Research Grant.

SU-E-T-596: Axillary Nodes Radiotherapy Boost Field Dosimetric Impact Study: Oblique Field and Field Optimization in 3D Conventional Breast Cancer Radiation Treatment

Purpose: To evaluate dosimetric impact of two axillary nodes (AX) boost techniques: (1) posterior-oblique optimized field boost (POB), (2) traditional posterior-anterior boost (PAB) with field optimization (O-PAB), for a postmastectomy breast patient with positive axillary lymph nodes. Methods: Five patients, 3 left and 2 right chest walls, were included in this study. All patients were simulated in 5mm CT slice thickness. Supraclavicular (SC) and level I/II/III AX were contoured based on the RTOG atlas guideline. Five treatment plans, (1) tangential chest wall, (2) oblique SC including AX, (3) PAB, O-PAB and POB, were created for each patient. Three plan sums (PS) were generated by sum one of (3) plan with plan (1) and (2). The field optimization was done through PS dose distribution, which included a field adjustment, a fractional dose, a calculation location and a gantry angle selection for POB. A dosimetric impact was evaluated by comparing a SC and AX coverage, a PS maximum dose, an irradiated area percentage volume received dose over 105% prescription dose (V105), an ipsi-laterial mean lung dose (MLD), an ipsi-laterial mean humeral head dose (MHHD), a mean heart dose (MHD) (for left case only) and their DVH amount these three technique. Results: O_PAB, POB and PAB dosimetric results showed that there was no significant different on SC and AX coverage (p>0.43) and MHD (p>0.16). The benefit of sparing lung irradiation from PAB to O-PAB to POB was significant (p<0.004). PAB showed a highest PS maximum dose (p<0.005), V105 (p<0.023) and MLD (compared with OPAB, p=0.055). MHHD showed very sensitive to the patient arm positioning and anatomy. O-PAB convinced a lower MHHD than PAB (p=0.03). Conclusion: 3D CT contouring plays main role in accuracy radiotherapy. Dosimetric advantage of POB and O-PAB was observed for a better normal tissue irradiation sparing.

MO‐D‐BRF‐01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side‐effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long‐term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose‐response data for follow‐up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose‐volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose‐volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis.This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose‐response differences between children and adults4. Methodology for literature review, data mining of outcomes databases, and NTCP or longitudinal modeling of doseresponse. 5. PENTEC goals and timetable.Learning Objectives: Understand important differences between normal tissue effects of radiation therapy in pediatric and adult patients. Be able to identify situations where there is ‘interplay’ between organ development and radiation‐induced complications. Identify methods to systematically extract quantitative dose‐volumeresponse relationships from existing outcomes databases. Provide guidance for the medical physicist to properly understand, implement, guide and control contemporary technology and applications in pediatric radiation oncology.

Intraoperative radiotherapy for breast cancer.

Intra-operative radiotherapy (IORT) as a treatment for breast cancer is a relatively new technique that is designed to be a replacement for whole breast external beam radiotherapy (EBRT) in selected women suitable for breast-conserving therapy. This article reviews twelve reasons for the use of the technique, with a particular emphasis on targeted intra-operative radiotherapy (TARGIT) which uses X-rays generated from a portable device within the operating theatre immediately after the breast tumour (and surrounding margin of healthy tissue) has been removed. The delivery of a single fraction of radiotherapy directly to the tumour bed at the time of surgery, with the capability of adding EBRT at a later date if required (risk-adaptive technique) is discussed in light of recent results from a large multinational randomised controlled trial comparing TARGIT with EBRT. The technique avoids irradiation of normal tissues such as skin, heart, lungs, ribs and spine, and has been shown to improve cosmetic outcome when compared with EBRT. Beneficial aspects to both institutional and societal economics are discussed, together with evidence demonstrating excellent patient satisfaction and quality of life. There is a discussion of the published evidence regarding the use of IORT twice in the same breast (for new primary cancers) and in patients who would never be considered for EBRT because of their special circumstances (such as the frail, the elderly, or those with collagen vascular disease). Finally, there is a discussion of the role of the TARGIT Academy in developing and sustaining high standards in the use of the technique.

Accelerated dose escalation with proton beam therapy for non-small cell lung cancer.

Local tumor control remains challenging in many cases of non-small cell lung cancer (NSCLC), particularly those that involve large or centrally located tumors. Concurrent chemotherapy and radiation can maximize tumor control and survival for patients with locally advanced disease, but a substantial proportion of such patients cannot tolerate this therapy, and sequential chemoradiation regimens or radiation given alone at conventionally fractionated doses produces suboptimal results. An alternative approach is the use of hypofractionated proton beam therapy (PBT). The energy distribution of protons can be exploited to reduce involuntary irradiation of normal tissues, particularly the low-dose irradiation problematic in intensity-modulated (photon) radiation therapy (IMRT). Here we summarize current evidence on the use of hypofractionated PBT for both early-stage and locally advanced NSCLC, and the possibility of using hypofractionated regimens for patients who are not candidates for concurrent chemotherapy.

Nonisocentric Treatment Strategy for Breast Radiation Therapy: A Proof of Concept Study

To propose a nonisocentric treatment strategy as a special form of station parameter optimized radiation therapy, to improve sparing of critical structures while preserving target coverage in breast radiation therapy. To minimize the volume of exposed lung and heart in breast irradiation, we propose a novel nonisocentric treatment scheme by strategically placing nonconverging beams with multiple isocenters. As its name suggests, the central axes of these beams do not intersect at a single isocenter as in conventional breast treatment planning. Rather, the isocenter locations and beam directions are carefully selected, in that each beam is only responsible for a certain subvolume of the target, so as to minimize the volume of irradiated normal tissue. When put together, the beams will provide an adequate coverage of the target and expose only a minimal amount of normal tissue to radiation. We apply the nonisocentric planning technique to 2 previously treated clinical cases (breast and chest wall). The proposed nonisocentric technique substantially improved sparing of the ipsilateral lung. Compared with conventional isocentric plans using 2 tangential beams, the mean lung dose was reduced by 38% and 50% using the proposed technique, and the volume of the ipsilateral lung receiving ≥ 20 Gy was reduced by a factor of approximately 2 and 3 for the breast and chest wall cases, respectively. The improvement in lung sparing is even greater compared with volumetric modulated arc therapy. A nonisocentric implementation of station parameter optimized radiation therapy has been proposed for breast radiation therapy. The new treatment scheme overcomes the limitations of existing approaches and affords a useful tool for conformal breast radiation therapy, especially in cases with extreme chest wall curvature.

Dosimetric advantages of O‐ring design radiotherapy system for skull‐base tumors

The purpose of this study was to investigate whether a new O‐ring design radiotherapy delivery system has advantages in radiotherapy planning for skull‐base tumors. Twenty‐five patients with skull‐base tumors were included in this study. Two plans were made using conventional (Plan A) or new (Plan B) techniques. Plan A consisted of four dynamic conformal arcs (DCAs): two were horizontal, and the other two were from cranial directions. Plan B was created by converting horizontal arcs to those from caudal directions making use of the O‐ring design radiotherapy system. The micromultileaf collimators were fitted to cover at least 99% of the planning target volume with prescribed doses, 90% of the dose at the isocenter. The two plans were compared in terms of target homogeneity, conformity, and irradiated volume of normal tissues, using a two‐sided paired t‐test. For evaluation regarding target coverage, the homogeneity indices defined by the International Commission on Radiation Units and Measurements 83 were 0.099±0.010 (mean ± standard deviation) and 0.092±0.010, the conformity indices defined by the Radiation Therapy Oncology Group were 1.720±0.249 and 1.675±0.239, and the Paddick's conformity indices were 0.585±0.078 and 0.602±0.080, in Plans A and B, respectively. For evaluation of irradiated normal tissue, the Paddick's gradient indices were 3.118±0.283 and 2.938±0.263 in Plans A and B, respectively. All of these differences were statistically significant (p‐values <0.05). The mean doses of optic nerves, eyes, brainstem, and hippocampi were also significantly lower in Plan B. The DCA technique from caudal directions using the new O‐ring design radiotherapy system can improve target homogeneity and conformity compared with conventional DCA techniques, and can also decrease the volume of surrounding normal tissues that receives moderate doses.PACS numbers: 87.55.‐x, 87.55.D‐, 87.55.dk

Radioprotective Intraoral Appliance as Sole Radiotherapy For Carcinoma of Lip: Case Report

Radioprotective oral appliances can be used during radiotherapy (RT) to prevent radiation-induced oral complications. Three women and 2 men with squamous cell carcinoma (SCC) of the lip (T1-T2N0M0), age 46 to 72 years, were eligible for curative RT with electron beam (60 to 66 Gy) and the use of personalized radioprotective oral appliances. Patients were evaluated before, during, and after RT for xerostomia and mucositis with scales (Eisbruch et al and World Health Organization). One patient complained of mild oral dryness that did not interfere with function; the others showed no xerostomia. Except for the tumor margins, protected areas of the oral mucosa showed no radiation mucositis, nor did patients experience taste alterations. The oral appliances prevented unnecessary irradiation of normal tissues, thus reducing the risk of morbidity in the form of mucositis and osteoradionecrosis. Treated patients had no signs of recurrence. Acknowledgment: FAPEMIG.

Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

Evils of radiotherapy

Radiotherapy, alone or associated with surgery or chemotherapy, has produced a significant increase in cure rates for many malignancies of the head and neck region. However, high doses of radiation in large areas, including the oral mucosa, skin, maxilla, mandible and salivary glands may result in several undesired reactions that manifest during or after the completion of therapy. This damage is caused by the ionizing radiation in normal tissues located in the radiation field.

EP-1591: Normal tissue irradiation during micro-MLC based SRT or SRS: impact of the prescription isodose

EP-1591: Normal tissue irradiation during micro-MLC based SRT or SRS: impact of the prescription isodose