Long-term Side Effects Of Radiotherapy Research Articles

Caloric Restriction Diet Attenuates Systemic Bone Fragility after Radiotherapy

Bone fragility is a well-documented long-term side effect of radiotherapy, which currently has no preventative treatments. In this study, we applied a caloric restriction (CR) diet to attenuate both local and systemic bone loss after irradiation (RTx) in an established female Balb/c mouse model (4 consecutive daily doses of 5 Gy to the right hindlimb only). CR mice were tapered down to a 30% reduced calorie diet (RTx/CR) one week before irradiation, while regular diet (RD) mice received food ad libitum (RTx/RD). Unirradiated (sham) mice received either a 30% CR diet (SH/CR) or received food ad libitum (SH/RD). Irradiated, contralateral, and unirradiated hindlimbs were evaluated at 2, 4, and 8 weeks postirradiation using micro-computed tomography (μCT) to assess bone morphology and 3-point bending to quantify femur strength. Histological analysis of irradiated and unirradiated tibiae was performed to examine general bone tissue cytology and serum biomarker analysis was performed using terminal blood draw samples. After treatment, femur strength and metaphyseal bone quantity was decreased in irradiated and contralateral femora of RTx/RD mice compared to SH/RD femurs; this finding is consistent with previous studies. RTx/CR mice had positive effects when compared to RTx/RD mice, including increased strength relative to body mass in both the irradiated and contralateral limb, increased trabecular bone mass, and decreased marrow adiposity. However, a number of adverse effects were also observed, including a significant decrease in body mass and decreased cortical bone. Overall, CR shows promise as a preventative treatment for postirradiated bone fragility, yet questions remain to be addressed in future studies. Ideal diet duration, impact to normal tissue, and mechanism of action must be explored to better understand the clinical implication of a CR diet.

The patient's perspective on radiation for rectal cancer: Initial expectations versus actual experience.

The aim of this study was to compare patient perceptions of radiotherapy (RT) before and after treatment to better inform future patients and providers. Seventy-eight consecutive patients with rectal adenocarcinoma treated with neo- or adjuvant chemoradiation, surgical resection, and adjuvant chemotherapy from 2009 to 2018 and who were without recurrence were included. Patients were surveyed ≥6 months after ileostomy reversal or ≥3 months after adjuvant chemotherapy. The survey assessed patients' baseline knowledge and fears of RT, how their short- and long-term side effects compared with initial expectations, and how their experiences compared for each modality (RT, surgery, and chemotherapy). Forty patient-responses were received. Before treatment, 70% of patients indicated little to no knowledge of RT, though 43% reported hearing frightening stories about RT. The most commonly top-ranked fears included organ damage (26%), skin burns (14%), and inability to carry out normal daily activities (10%). Eighty percent reported short-term effects of RT to be less than or as expected, with urinary changes (93%), abdominal discomfort (90%), and anxiety (88%) most commonly rated as less than or as expected. 85% reported long-term effects to be less than or as expected, with pain (95%), changes to the appearance of the treated area (85%), and dissatisfaction with body image (80%) most commonly rated as less than or as expected. Surgery was most commonly rated as the most difficult treatment (50%) and most responsible for long-term effects (55%). RT was least commonly rated as the most difficult treatment (13%), and chemotherapy was least commonly rated as most responsible for long-term effects (13%). The majority of patients indicated short- and long-term side effects of RT for rectal cancer to be better than initial expectations. In the context of trimodality therapy, patients reported RT to be the least difficult of the treatments.

Incorporating economic methods into Cochrane systematic reviews: case studies in brain tumour research

BackgroundCochrane systematic reviews have established methods for identifying and critically appraising empirical evidence in health. In addition to evidence regarding the clinical effectiveness of interventions, the resource implications of such interventions can have a huge impact on a decision maker’s ability to adopt and implement them. In this paper, we present examples of the three approaches to include economic evidence in Cochrane reviews.MethodsThe Cochrane Handbook presents three different methods of integrating economic evidence into reviews: the Brief Economic Commentary (BEC), the Integrated Full Systematic Review of Economic Evaluations (IFSREE) and using an Economic Decision Model. Using the examples from three different systematic reviews in the field of brain cancer, we utilised each method to address three different research questions. A BEC was utilised in a review that evaluates the long-term side effects of radiotherapy (with or without chemotherapy). An IFSREE was utilised in a review comparing different treatment strategies for newly diagnosed glioblastoma in the elderly. Finally, an economic model was included in a review assessing diagnostic test accuracy for tests of codeletion of chromosomal arms in people with glioma.ResultsThe BEC mirrored the results of the main review and found a paucity of quality evidence with regard to the side effects of radiotherapy in those with glioma. The IFSREE identified a single economic evaluation regarding glioblastoma in the elderly, but this study had a number of methodological issues. The economic model identified a number of potentially cost-effective strategies for tests for codeletion of chromosomal arms 1p and 19q in people with glioma.ConclusionsThere are strengths and limitations of each approach for integrating economic evidence in Cochrane systematic reviews. The type of research question, resources available and study timeline should be considered when choosing which approach to use when integrating economic evidence.

Continuous and Early Progression of Carotid Intima-Media Thickness after Radiotherapy for Head and Neck Cancer: 5-Year Prospective Observational Study

Introduction: Radiation-induced carotid artery stenosis (RI-CS) is known as one of long-term side effects of radiotherapy for head and neck cancer (HNC). However, the clinical time course after irradiation has been poorly understood. We aimed to investigate the natural history of radiation-induced carotid atherosclerosis, comparing the patients who received radiotherapy for HNC with the patients who were treated without radiotherapy. Methods: The patients who received treatment of HNC at Department of Otolaryngology, Head and Neck Surgery of Kyoto University Hospital, from November 2012 to July 2015 were enrolled. The patients were assigned into the RT group and the control group, depending on whether radiotherapy was planned or not. Annual carotid ultrasound was performed from the enrollment to 5 years. The increase of mean intima-media thickness (IMT) at common carotid artery from the enrollment (Δmean IMT) was evaluated. Results: Fifty-six patients in the RT group and 25 patients in the control group were enrolled. From 5-year follow-up data, the significant higher increase of Δmean IMT was consistently observed in the RT group than in the control group after 2 years. The RT group presented a 7.8-fold increase of mean IMT compared to the control group (0.060 mm per year in the RT group and 0.008 mm per year in the control group). Cumulative incidence curves obtained from the analysis of all vessels revealed that the RT group presented higher incidence of Δmean IMT ≥0.25 mm than the control group (p < 0.01). In the RT group, the patients with mean IMT ≥1.0 mm at enrollment exhibited significantly higher incidence of Δmean IMT ≥0.25 mm than the patients with mean IMT <1.0 mm (p < 0.01). Discussion: Radiotherapy for HNC induces continuous carotid mean IMT progression. The irradiated carotid arteries with mean IMT ≥1.0 mm before radiotherapy presented earlier IMT progression than those with mean IMT <1.0 mm.

CTNI-16. NRG-RTOG 9802 OBSERVATION ARM - LONG TERM RESULT

Abstract BACKGROUND Radiation Therapy Oncology Group 9802 was a phase III trial for patients with centrally confirmed LGG (WHO grade II). Participants ³ 40 years or those with neurosurgeon defined less than gross total resection (GTR) were randomized to radiotherapy (RT) +/- PCV. In a separate cohort, adults age &amp;lt; 40 years with neurosurgeon defined GTR were observed by MRI every 6 months without adjuvant therapy. At last report, outcome for the observation cohort was immature with median follow-up of only 4.4 years. Here, we present mature outcomes for the observation arm. METHODS Eligible adults (as above) were observed by MRI every 6 months. OS and PFS were estimated by Kaplan-Meier method and estimated hazard ratios to characterize the prognostic variables. RESULTS There were 111 eligible patients (median age 30; median KPS = 100). Median follow-up was 16.1 years with 71 (64%) alive at the last follow-up. 79 patients (71%) had progressed with median PFS of 6.9 years. 5, 10, and 15 year-PFS and OS rates were 54%, 39%, 28% and 94%, 77%, and 65%. 1p19q status was codeleted in 32%, IDH1/2 mutant in 78% and MGMT promoter methylated in 39% of tested cases. Multivariate Cox analyses showed that preoperative tumor size ³ 4 cm (HR = 2.43 for PFS, p = 0.001; HR = 2.58 for death, p = 0.016) and residual disease on imaging ³ 1 cm (HR = 2.97 for PFS, P &amp;lt; 0.001; HR = 2.02 for death, p = 0.05) were associated with worse outcomes. Analyses based on molecular results will be presented. CONCLUSION A subset of low-grade gliomas can be observed after the initial resection based on younger age, smaller tumor size, and no residual disease on neuroimaging. This can likely be further refined by prognostic molecular markers. Patients with the most favorable prognostic factors can avoid or delay the acute and long-term side effects of RT and chemotherapy for several years.

Aggressive giant prolactinoma: a case report

BackgroundManaging treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited.Case presentationA 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm3) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case.ConclusionThis case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy.

Satellite Cells are Activated in a Rat Model of Radiation-Induced Muscle Fibrosis.

Radiation-induced muscle fibrosis is a long-term side effect of radiotherapy that significantly affects the quality of life and even reduces the survival of cancer patients. We have demonstrated that radiation induces satellite cell (SC) activation at the molecular level; however, cellular evidence in a rat model of radiation-induced muscle fibrosis was lacking. In this study, we evaluated SC activation in vivo and investigated whether radiation affects the proliferation and differentiation potential of SCs in vitro. For in vivo studies, Sprague-Dawley rats were randomly divided into six groups (n = 6 per group): non-irradiated controls, 90 Gy/1 week-, 90 Gy/2 weeks-, 90 Gy/4 weeks-, 90 Gy/12 weeks- and 90 Gy/24 weeks-postirradiation groups. Rats received a single dose of radiation in the left groin area and rectus femoris tissues were collected in the indicated weeks. Fibrosis, apoptosis, and autophagy were evaluated by Masson's trichrome staining, TUNEL staining, and electron microscopy, respectively. SC activation and central nuclear muscle fibers were evaluated by immunofluorescence staining and hematoxylin and eosin staining. IL-1β concentrations in serum and irradiated muscle tissue samples were determined by ELISA. For in vitro studies, SCs were isolated from rats with radiation-induced muscle fibrosis and their proliferation and differentiation were evaluated by immunofluorescence staining. In vivo, fibrosis increased over time postirradiation. Apoptosis and autophagy levels, IL-1β concentrations in serum and irradiated skin tissues, and the numbers of SCs and central nuclear muscle fibers were increased in the irradiated groups when compared with the control group. In vitro, cultured SCs from irradiated muscle were positive for the proliferation marker Pax7, and differentiated SCs were positive for the myogenic differentiation marker MyHC. This study provided cellular evidence of SC activation and proliferation in rats with radiation-induced muscle fibrosis.

Stroke rate after external fractionated radiotherapy for benign meningioma.

Patients with a benign meningioma often have a long survival following the treatment of their meningioma. Since radiotherapy is frequently part of the treatment, long-term side effects are of considerable concern. A controversial long-term side effect of radiotherapy is stroke. Due to its severity, it is important to know the frequency of this side effect. The aim of this study was to assess the stroke incidence and risk factors among patients receiving radiotherapy for their benign meningioma. We performed a retrospective database study of patients who underwent primary or adjuvant radiotherapy for their benign meningioma at University Hospitals Leuven from January 2003 to December 2017. We included 169 patients with a median age of 51years (range 22-84). Every patient received fractionated radiotherapy using photons with a median dose of 56Gy (range 54-56) in fractions of 2Gy (range 1.8-2). The median follow-up was 5.3years (range 0.1-14). The cumulative stroke incidence function showed an incidence of 11.6% after 9years of follow-up, translating to a stroke incidence per year of 1.29%. We found two significant risk factors for stroke: medically treated arterial hypertension (p = 0.005) and history of previous stroke or transient ischemic attack (p < 0.001). 5-year local control and overall survival rates were respectively 97.4% and 91.2%. Other late grade III/IV toxicities occurred in 16.0% (27/169) of patients. Our study shows a higher incidence of stroke in patients who received radiotherapy for their benign meningioma compared to the general population.

Current treatment of pediatric bladder and prostate rhabdomyosarcoma (bladder preserving vs. radical cystectomy).

To discuss alternative strategies for multimodal treatments of nonmetastatic bladder-prostate rhabdomyosarcoma performed with the aim of preserving organ function. Bladder-prostate rhabdomyosarcomas are seldom fully resectable at presentation or after induction chemotherapy, and extensive resection might not improve survival. When an organ-sparing approach is pursued, radiotherapy might be unavoidable to achieve reliable local control of the disease. Benefits of preoperative vs. postoperative radiotherapy have yet to be investigated. Multimodal treatments may often result in bladder function impairment and erectile dysfunction. To reduce long-term side effects of radiotherapy, irradiation modalities allowing for more targeted treatment should be favoured. For this purpose, external beam proton therapy or nonradical surgery associated with brachytherapy may be viable options. Nevertheless, experience with these treatments is still limited. Advancements in lower urinary tract reconstruction make preservation of volitional voiding and erectile function possible after cystoprostatectomy. But in the context of multimodal treatment, cystoprostatectomy is reserved to patients who respond poorly to other treatments. For the vast majority of bladder-prostate rhabdomyosarcoma, we believe that reliable local control of disease can only be achieved with the use of radiotherapy. Efforts should be made to find the best modality for targeted radiotherapy. Further studies are required to compare preoperative vs. postoperative radiotherapy and the best dose to be administered in order to reduce long-term side effects. If creation of an orthotopic continent diversion is deemed appropriate in patients undergoing cystoprostatectomy, it should be performed concurrently with extirpative surgery.

Long-term side effects of radiotherapy, with or without chemotherapy, for glioma

Long-term side effects of radiotherapy, with or without chemotherapy, for glioma

Radiation-Induced Maxillary Osteosarcoma and Synchronous Oropharyngeal Squamous Cell Cancer: A Rare Case Report

Radiotherapy is a treatment option for nasopharyngeal cancer. However, ionizing radiation may lead to development of secondary malignancies. In this case report, we will present a case of radiation-induced osteosarcoma of the maxilla and synchronous oropharyngeal squamous cell cancer following treatment of nasopharyngeal cancer. History, latency period, physical examinations, computed tomography, magnetic resonance imaging and biopsy results are provided. Diagnosis was confirmed by excision biopsy. Radiation-induced tumors are possible long-term side effects of radiotherapy. Although rare and possible to confuse with recurrent disease, this possibility should be considered in any patient who has received radiation therapy. Diagnostic imaging plays a pivotal role in recognition of radiation induced neoplastic disease. Accurate identification and reporting of key imaging findings allows referring physicians to choose the most appropriate treatment options.

Improvement of dose homogeneity with irregular surface compensator in whole brain radiotherapy

AbstractPurposeThe aim of this study was to evaluate the dosimetric aspects of whole brain radiotherapy (WBRT) using an irregular surface compensator (ISC) in contrast to conventional radiotherapy techniques.MethodsTreatment plans were devised for 20 patients. The Eclipse treatment planning system (Varian Medical Systems) was used for dose calculation. For the ISC, a fluence editor application was used to extend the range of optimal fluence. The treatment plan with the ISC was compared with the conventional technique in terms of doses in the planning target volume (PTV), dose homogeneity index (DHI), three-dimensional (3D) maximum dose, eye and lens doses and monitor unit (MU) counts required for treatment.ResultsCompared with conventional WBRT, the ISC significantly reduced the DHI, 3D maximum dose and volumes receiving 105% of the prescription dose, in addition to reducing both eye and lens doses (p&lt;0·05 for all comparisons). In contrast, MU counts were higher for the ISC technique than for conventional WBRT (828 versus 328, p&lt;0·01).ConclusionThe ISC technique for WBRT considerably improved the dose homogeneity in the PTV. As patients who receive WBRT have improved survival, the long-term side effects of radiotherapy are highly important.

Medical marijuana use in head and neck squamous cell carcinoma patients treated with radiotherapy

The purpose of the study was to better understand why patients with history of head and neck cancer (HNC) treated with radiotherapy are using medical marijuana (MM). Established HNC quality of life questionnaires and our own MM quality of life questionnaire were sent to 15 HNC patients treated at our institution who reported using MM. Patients are clinically disease free and currently using MM to manage long-term side effects after curative HNC treatment. There was a 100% response rate. Median time from treatment was 45months (21-136months). Most patients smoked marijuana (12 patients), while others reported ingestion (4 patients), vaporizing (3 patients), and use of homemade concentrated oil (1 patient). Six patients reported prior recreational marijuana use before diagnosis. MM provided benefit in altered sense, weight maintenance, depression, pain, appetite, dysphagia, xerostomia, muscle spasm, and sticky saliva. HNC patients report MM use to help with long-term side effects of radiotherapy.

Does intensity-modulated radiotherapy reduce the risk of pelvic insufficiency fractures in gynaecological cancers?

AbstractBackgroundIncreasingly we are using a combination of surgery, chemotherapy and radiotherapy for treatment of gynaecological malignancies. Most studies in literature are concentrated on the concept of survival. There is minimal data examining the impact of these treatments on quality of life. Survival being a surrogate marker is an arbitrary end point and is of arguable significance if quality of life is not maintained. Long-term side effects of radiotherapy are debilitating and severely affect quality of life. Pelvic insufficiency fractures (PIF) are a known long-term side effect of radiotherapy. Intensity-modulated radiotherapy (IMRT) is being routinely used in the treatment of prostate and head and neck cancer. We postulated that use of IMRT in gynaecological cancers reduces the incidence of PIF.Patients and methodsWe retrospectively reviewed 10 cases of PIF treated on standard treatment. We recalculated dose volume histograms based on IMRT protocols for patients with PIF.ResultsWe found that none of the patients received any radiation at the fracture site and the total radiation received to the sacrum was lower compared with the standard treatment protocols.ConclusionsWe conclude that the feasibility of IMRT in gynaecological cancers should be further evaluated and might be an useful tool in reducing the number of PIF.

Neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer.

Chemoradiotherapy or short-course radiotherapy followed by surgery is a standard treatment for locally advanced rectal cancer. This multimodality strategy has reduced the risk of local recurrence but failed to improve survival. Moreover, mid- and long-term side effects of radiotherapy have been reported. Alternative strategies have been investigated in an attempt to minimize treatment-related toxicities and improve outcome. Neoadjuvant chemotherapy without radiotherapy is an attractive therapeutic option that yields theoretical advantages. Moreover, if carefully selected, patients may be spared the effects of radiotherapy without compromising the oncology outcome. The authors review the available evidence on neoadjuvant chemotherapy without radiotherapy in locally advanced rectal cancer and try to anticipate potential algorithms of treatment selection to implement in clinical practice in the future.

Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation

PurposeRetrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw.MethodsA total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients’ general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up.ResultsThe patients’ dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome.ConclusionThe occurrence of IORN is an important long-term side effect of radiotherapy for oral cancers. From this data we only can conclude that a poor dental status, conventional fractionation and local tumour progression may enhance the risk of IORN which is in concordance with the literature.

Effects of Late Administration of Pentoxifylline and Tocotrienols in an Image-Guided Rat Model of Localized Heart Irradiation

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.

Does Previous Head and Neck Irradiation Increase Vascular Complications in Free Autologous Reconstruction?

Sir:FigureWe read with interest the recent article “Free Flap Reconstruction in the Head and Neck Region following Radiotherapy: A Cohort Study Identifying Negative Outcome Predictors.”1 This is an important article because there are still contradicting data regarding microsurgical complications associated with previous radiotherapy. The topic is also of general interest outside the plastic surgery community because there is an increasing population of cancer survivors for whom the long-term side effects of radiotherapy have to be considered. In fact, a growing body of clinical evidence has recently shown that radiotherapy is an independent risk factor for cardiovascular disease (i.e., myocardial infarction and stroke) at previously irradiated sites. This is further supported by molecular evidence that radiotherapy clearly exerts a detrimental effect on blood vessels, especially the endothelium.2 However, in the context of microvascular surgery, we lack a more detailed description of vascular complications related to radiotherapy. A relationship between previous chest wall irradiation and different vascular complications during free flap surgery was recently clearly shown in 1026 free flaps by Fosnot et al.,3 but this finding did not affect the free flap failure rates. The association shown by Fosnot et al., between radiotherapy and perioperative vascular complications, would be interesting to study in the cohort presented by Bourget et al., where the radiotherapy dose is higher (median, 64.5). Both studies concluded that radiotherapy is not associated with increased free flap failure rates. However, this could be explained by the fact that even relatively large clinical cohorts suffer with regard to statistical power as a result of low free flap failure rates, because it is difficult to detect an association with a limited sample size. In an attempt to overcome this, we presented a review of the literature where free flap outcome had been described in relation to previous radiotherapy. No association had been found between previous radiotherapy and complete free flap failure in any of the single studies, but a significant relationship between previous radiotherapy and free flap failure was clearly seen when all of the material was analyzed together (p < 0.0019; odds ratio, 1.72; 95 percent confidence interval, 1.22 to 2.44).4 There are several studies, outside the microsurgical field, that have been able to show that radiotherapy is associated with a prothrombotic response where the radiotherapy dose seems to be of importance.1,5 Fosnot et al. described that their results may be explained by endothelial dysfunction and prothrombotic characteristics seen in irradiated recipient veins, previously presented by us and others.6 Our group has over the past few years been studying radiation-induced gene expression in head and neck recipient arteries and veins and found an inflammatory and prothrombotic response even years after radiotherapy exposure.6,7 We believe that vascular complication is a more sensitive endpoint, compared with free flap failure, when radiotherapy shall be studied as a risk factor for microvascular surgery. Clinical studies on radiotherapy-related thrombosis during microsurgery in both arteries and veins may also contribute to increased general knowledge about radiation-induced vasculopathy, an area recently pointed out as an important field for future research in cancer survivors.1 Martin Halle, M.D., Ph.D. Filip Farnebo, M.D., Ph.D. Karolinska University Hospital, Stockholm, Sweden

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399 poster Long-term side effects of radiotherapy and chemotherapy for Hodgkin's disease

399 poster Long-term side effects of radiotherapy and chemotherapy for Hodgkin's disease