Radiation-induced Complications Research Articles

Use of cetuximab in combination with pulsed reduced dose-rate radiotherapy in a patient with recurrence of nasopharyngeal carcinoma in the neck

Reirradiation is a major therapeutic modality for patients with locally recurrent head and neck carcinoma. Due to normal tissue tolerances, reirradiation using conventional techniques has a narrow therapeutic ratio in the regional recurrence of nasopharyngeal carcinoma (NPC). Pulsed reduced dose-rate radiotherapy (PRDR), which delivers a series of 0.2 Gy pulses separated by 3 min intervals, is a new reirradiation technique. Head and neck carcinoma cells have high levels of epidermal growth factor receptor expression and cetuximab shows a clear benefit to locally advanced head and neck carcinoma. We report a 56-year-old male with a recurrent lesion of NPC in the neck following initial radical radiochemotherapy. The patient was retreated with PRDR and concurrent cetuximab. The total dose of PRDR was 70 Gy, using 35 daily fractions of 2.0 Gy. The recurrent lesion of this patient had a complete response with no apparent radiation-induced normal tissue complications. This is the first study concerning PRDR combined with cetuximab for the treatment of recurrent head and neck carcinoma following radiotherapy. The outcome of this patient reveals that treatment with PRDR and concurrent cetuximab is a promising therapeutic option for patients with recurrent head and neck carcinoma following radiotherapy.

Fat Grafting and Breast Reconstruction with Implant

In postmastectomy radiated patients, autologous tissue reconstruction is preferred over implant reconstruction, because the latter is associated with a higher rate of postoperative complications. Autologous tissue reconstruction, however, is not always feasible and is sometimes refused by the patient. A challenge also arises in breast-conserving surgery patients seeking breast augmentation with an implant. In this article, the authors present a further reconstructive option for irradiated breast cancer patients consisting of fat grafting followed by implant placement. The authors retrospectively reviewed 16 cases of irradiated breasts treated with fat grafting and subsequent alloplastic reconstruction/breast augmentation. The evaluation methods were clinical and photography-based assessments. The BREAST-Q was used to quantify patient satisfaction. Sixteen patients, with a pretreatment Late Effects on Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) score of 1 or 2, underwent two to three fat grafts to achieve a LENT-SOMA score of 0. The placement of the breast implant had been performed in a separate stage at least 3 months after the last grafting session. The average follow-up was 15 months. Reconstructive outcomes were graded from excellent to good in 93.7 percent of patients. Patient satisfaction was marked as high to very high. There were no short-term complications. A Baker grade 1 capsule contracture was found in all patients. The authors' experience shows that breast fat grafting followed by implant placement may represent a feasible reconstructive option in highly selected patients with irradiated breasts. Fat grafting seems to reduce radiation-induced complications in implants. Larger studies with a longer follow-up are needed. Therapeutic, V.

Magnetic resonance imaging in pediatric status epilepticus: not a routine, but a more focused indication

Status epilepticus in children is one of the most common life-threatening emergencies in pediatric neurology. It is associated with significant mortality and also morbidity that may impact on daily activities and health-related quality of life. Severe sequelae of status epilepticus include recurrent epileptic seizures, impairment of cognitive function, behavioral problems, and focal neurological deficits. Etiology and prior neurological abnormalities are predictors of mortality; whereas young age, etiology, and long duration are predictors of morbidity in pediatric status epilepticus.1 The outcome is better in children with either febrile or idiopathic status epilepticus, rather than symptomatic status epilepticus. Therefore, the diagnosis of the underlying etiology plays a key role for the evaluation of prognosis in pediatric status epilepticus. Several articles and textbooks proposing diagnostic guidelines for pediatric status epilepticus are available in the literature and usually include laboratory studies, electroencephalography, and neuroimaging.2,3 The recommendations of the American Academy of Neurology (AAN) mention that neuroimaging may be considered for the evaluation of children with status epilepticus if there are clinical indications or the etiology is unknown.2 The evidence of this recommendation is, however, low and indicates the need for new prospective studies. Additionally, the AAN report notes there is insufficient evidence to support or refute recommending routine neuroimaging.2 Yoong et al.4 focus on the role of magnetic resonance imaging (MRI) and aim to identify clinical predictors of abnormal imaging. To achieve this goal, they aimed to prospectively collect a population-based sample of children within 1 to 13 weeks after status epilepticus. Unfortunately, they could only include 80 children (36%) over a collecting period of 3 years due to well-known recruitment difficulties, and of course the high number of patients not enrolled may bias the results. The prospective study design and the systematic approach are, however, innovative for this study population. The authors found abnormal MRI findings including sequelae after hypoxic-ischemic injuries or meningitis, cortical malformations, stigmata of tuberous sclerosis, mesial temporal sclerosis, and features suggesting a neurometabolic disorder in about 30% of the patients.4 This result matches the higher range of previous studies. An abnormal neurological examination after status epilepticus, seizures not due to prolonged febrile status epilepticus, and continuous status epilepticus were identified as specific predictive factors for abnormal MRI findings.4 These results suggest that routine neuroimaging in pediatric status epilepticus is not necessary, but a more focused approach only on children with risk factors for abnormal MR could be justified. The article by Yoong et al. cannot give a definitive answer to the insufficient evidence question and further prospective studies with larger cohorts of patients are needed. Nonetheless, the results of this study are important for the clinicians who treat children with status epilepticus and advance our knowledge about the role of neuroimaging in pediatric status epilepticus. Even if the authors do not discuss the role of head computed tomography in the emergency department, about half of the patients received head computed tomography during their acute admission. Children are at a greater risk than adults to suffer from radiation-induced side effects both because they are inherently more radiosensitive and because they have more years of life remaining during which a radiation-induced complication might develop.5 Additionally, the impact of ionizing radiation on the developing brain and radiosensitive structures like the eye lens should not be underestimated. In the study by Yoong et al., only seven of 30 patients had an abnormal acute computed tomography and none of these children required emergency neurosurgery. Additionally, the authors showed that a normal computed tomography in the acute setting does not offer complete reassurance of a normal MRI. Thus, we emphasize that every effort should be made to limit the use of computed tomography to patients who may need emergency neurosurgery based on their clinical history (e.g. history of trauma, signs of increased intracranial pressure). MRI should be the imaging method of choice in most other circumstances.

Serious Adverse Effects of Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy

Gamma knife radiosurgery (GKRS) for mesial temporal lobe epilepsy (MTLE) has been proposed as an alternative to surgical resection. We report serious adverse effects of the treatment after follow-up periods over 9 years in 11 patients treated with GKRS between 1997 and 2000. The target volume of the entorhinoamygdalohippocampectomy area was 4.8-17.1 ml. Marginal dose of 20-25 Gy to the 50% isodose was delivered. One patient was drowned after suffering seizure 7 months after GKRS. Two patients did not show any reduction in seizure frequency over 9 and 18 months. Both patients requested open surgery and became seizure-free postoperatively. Four of the other eight patients were classified as Engel's class I within 4 years after GKRS. One of the four patients experienced symptomatic radiation-induced cerebral edema transiently, one developed radiation necrosis and required surgery 5 years after GKRS, and one developed cognitive impairment with hemiparesis 10 years after GKRS. Magnetic resonance (MR) imaging showed a large cyst in the irradiated temporal lobe. This patient recovered fully after the cyst excision. Only one patient became seizure-free and antiepileptic drug-free without symptomatic radiation-induced complications. However, MR imaging revealed abnormal enhancement, cyst formation, and diffuse white matter change in the irradiated temporal lobe 9 years after GKRS. GKRS for MTLE causes adverse effects of delayed seizure remission and symptomatic radiation-induced complications. Therefore, GKRS cannot be considered as an ideal alternative to surgery for MTLE. Long-term follow-up studies including MR imaging with contrast medium are required for the patients even after successful control of seizures.

Gamma Knife® radiosurgery for trigeminal neuralgia

Trigeminal neuralgia is characterized by a temporary paroxysmal lancinating facial pain in the trigeminal nerve distribution. The prevalence is four to five per 100,000. Local pressure on nerve fibers from vascular loops results in painful afferent discharge from an injured segment of the fifth cranial nerve. Microvascular decompression addresses the underlying pathophysiology of the disease, making this treatment the gold standard for medically refractory trigeminal neuralgia. In patients who cannot tolerate a surgical procedure, those in whom a vascular etiology cannot be identified, or those unwilling to undergo an open surgery, stereotactic radiosurgery is an appropriate alternative. The majority of patients with typical facial pain will achieve relief following radiosurgical treatment. Long-term follow-up for recurrence as well as for radiation-induced complications is required in all patients undergoing stereotactic radiosurgery for trigeminal neuralgia.

Consolidating Risk Estimates for Radiation-Induced Complications in Individual Patient: Late Rectal Toxicity

To test the feasibility of a new approach to synthesize published normal tissue complication data using late rectal toxicity in prostate cancer as an example. A data survey was performed to identify the published reports on the dose-response relationships for late rectal toxicity. The risk estimates for Grade 1 or greater, Grade 2 or greater, and Grade 3 or greater toxicity were obtained for a test cohort of patients treated at our institution. The influence of the potential factors that might have affected the reported toxicity levels was investigated. The studies that did not conform to the general data trends were excluded, and single, combined risk estimates were derived for each patient and toxicity level. A total of 21 studies of nonoverlapping patient populations were identified. Three studies provided dose-response models for more than one level of toxicity. Of these 21 studies, 6, 14, and 5 were used to derive the initial risk estimates for Grade 1, 2, and 3 or greater toxicity, respectively. A comparison of risk estimates between the studies reporting rectal bleeding and rectal toxicity (bleeding plus other symptoms) or between studies with follow-up <36 months and ≥36 months did not reveal significant differences (p ≥ .29 for all comparisons). After excluding three reports that did not conform to the general data trends, the combined risk estimates were derived from 5 reports (647 patients), 11 reports (3,369 patients), and 5 reports (1,330 patients) for Grade 1, 2, and 3 or greater toxicity, respectively. The proposed approach is feasible and allows for more systematic use of published dose-response data to estimate the complication risks for the individual patient.

A retrospective study of surgical treatment of chronic radiation enteritis

We assessed the role of surgery in the management of patients with intestinal obstruction or enterocutaneous fistula after chronic radiation enteritis (CRE) referred to our department, a specialist gastrointestinal surgical center, and analysis was made for the success of surgery. A retrospective analysis was made of 156 patients receiving radiation therapy for malignancy from Jan 2000 to Nov 2010, among which 134 received surgery for intestinal or urinary complications. The demographic data, nutritional status, previous surgery, disease location and clinical manifestations, concomitant urinary complications, and surgical procedures were analyzed. Although malnutrition was prevalent (84/156, 53.9%) in this group of patients, the majority of them (101/134, 75.4%) recovered uneventfully after surgery following nutrition therapy, and resection and anastomosis (102/134) was the predominant surgical procedure for radiation injury to the ileocecal region. Sixteen patients received surgery for radiation-induced urinary complications. There were 36 postoperative morbidities (26.87%), mainly wound complications (21/134), intestinal obstruction (5/134), and anastomotic dehiscence (3/134). Surgery is justified for patients with bowel obstruction or fistula after CRE. A comprehensive perioperative management, especially perioperative nutrition therapy was important for the success of the surgery.

Toxicité cardiaque de la radiothérapie

The radiotherapy of thoracic cancers exposes the heart to late radiation-induced complications. The physiopathological and clinical consequences of heart irradiation have been mostly studied in patients with Hodgkin lymphoma and breast cancer. The main cause of cardiac morbidity is radiation-induced coronaropathy with a relative risk estimated between 2 and 3 in earlier studies. Preexisting factors of cardiovascular risk, including chemotherapy, potentalize the cardiotoxicity of radiotherapy. Conformational radiotherapy, adapting the ballistics and the energy to the delineated volumes while carefully evaluating the dose–volume distribution in the organs at risk, allowed a drastic reduction in cardiac mortality. This toxicity no longer seems to be significant if the cardiac volume has received less than 30 Gy. Nevertheless, the prolonged life expectancy of cancer patients and the expanding use of new cardiotoxic anticancer drugs underline the persistent need to further reduce the dose delivered to the heart. Indeed, 1 Gy added to the mean heart dose would increase the cardiotoxic risk by 4% (IC 95%: 2–6%, P = 0.0002). A strengthened collaboration between the radiation oncologist and the cardiologist aims at detecting and treating long-term complications after thoracic radiotherapy.

Repeat Radiosurgery for Intracranial Arteriovenous Malformations

Despite a high success rate in the stereotactic radiosurgical treatment of intracranial arteriovenous malformations (AVMs) that cannot be safely resected with microsurgery, some patients must be managed after treatment failure. To provide an update on the use of repeat linear accelerator radiosurgery as a treatment for failed AVM radiosurgery at the University of Florida. We reviewed 103 patients who underwent repeat radiosurgical treatment for residual AVM at the University of Florida between December 1991 and December 2007. Each of these patients had at least 2 radiosurgical treatments for the same AVM. Patient information, including AVM nidus volume, prescription dose, age, and sex, was collected at the time of initial treatment and again at the time of retreatment. Patients were followed up after treatment with magnetic resonance, computed tomography, and angiographic imaging at standard intervals to determine the status of their AVM. The median follow-up after retreatment was 31 months. Between the first and second treatments, the median AVM nidus volume was decreased by 69% (from a median volume of 12.7 to 4.0 cm), allowing the median prescribed dose to be increased from 1500 cGy on initial treatment to 1750 cGy on retreatment. The final obliteration rate on retreatment was 65.3%. After salvage retreatment, 5 patients (4.9%) experienced radiation-induced complications, and 6 patients (5.8%) experienced posttreatment hemorrhage. Repeat radiosurgery is a safe and effective salvage treatment for AVMs.

Protective effects of hominis placenta hydrolysates on radiation enteropathy in mice

The aim of this study was to investigate whether the hominis placenta hydrolysates (HPhs) have a protective effect against radiation-induced enteropathies. HPh (1–10 mg kg−1, i.p.) was treated to C57BL/6 mice, once daily for 5 days. Mice were irradiated (10 Gy) 1 h after the last injection. Cell damage was investigated at 24 and 72 h by haematoxylin-eosin staining, and the apoptotic index was determined at 24 h by deoxynucleotidyl transferase-mediated dUTP nick end labelling staining. The results showed that the HPh alleviated radiation-induced damage of crypts and suppressed apoptosis dose dependently. In conclusion, hominis placenta might be a beneficial agent against radiation-induced intestinal complications.

Combined endovascular embolization and stereotactic radiosurgery in the treatment of large arteriovenous malformations

Large cerebral arteriovenous malformations (AVMs) are often not amenable to direct resection or stereotactic radiosurgery (SRS) treatment. An alternative treatment strategy is staged endovascular embolization followed by SRS (Embo/SRS). The object of this study was to examine the experience at Washington University in St. Louis with Embo/SRS for large AVMs and review the results in earlier case series. Twenty-one cases involving patients with large AVMs treated with Embo/SRS between 1994 and 2006 were retrospectively evaluated. The AVM size (before and after embolization), procedural complications, radiological outcome, and neurological outcome were examined. Radiological success was defined as AVM obliteration as demonstrated by catheter angiography, CT angiography, or MR angiography. Radiological failure was defined as residual AVM as demonstrated by catheter angiography, CT angiography, or MR angiography performed at least 3 years after SRS. The maximum diameter of all AVMs in this series was > 3 cm (mean 4.2 cm); 12 (57%) were Spetzler-Martin Grade IV or V. Clinical follow-up was available in 20 of 21 cases; radiological follow-up was available in 19 of 21 cases (mean duration of follow-up 3.6 years). Forty-three embolization procedures were performed; 8 embolization-related complications occurred, leading to transient neurological deficits in 5 patients (24%), minor permanent neurological deficits in 3 patients (14%), and major permanent neurological deficits in none (0%). Twenty-one SRS procedures were performed; 1 radiation-induced complication occurred (5%), leading to a permanent minor neurological deficit. Of the 20 patients with clinical follow-up, none experienced cerebral hemorrhage. In the 19 patients with radiological follow-up, AVM obliteration was confirmed by catheter angiography in 13, MR angiography in 2, and CT angiography in 1. Residual nidus was found in 3 patients. In patients with follow-up catheter angiography, the AVM obliteration rate was 81% (13 of 16 cases). Staged endovascular embolization followed by SRS provides an effective means of treating large AVMs not amenable to standard surgical or SRS treatment. The outcomes and complication rates reported in this series compare favorably to the results of other reported therapeutic strategies for this very challenging patient population.

Side Effects of Radiation in Musculoskeletal Oncology: Clinical Evaluation of Radiation-Induced Fractures

Radiation therapy and chemotherapy, while they remain an essential part of the multidisciplinary treatment of cancers, they have led to unwanted complications. Radiation-induced complications include wound and bone, growth, nervous system, tumorigenic, lung, gastrointestinal, hepatic and other complications. In this article we review the side effects of radiation therapy in musculoskeletal oncology emphasizing on bone, present our long experience, and discuss the current literature regarding radiation-induced bone complications and their management and outcome.

A possible prevention strategy of radiation pneumonitis: Combine radiotherapy with aerosol inhalation of hydrogen-rich solution

SummaryRadiotherapy is an important modality of cancer treatment. Radiation pneumonitis is a major obstacle to increasing the radiation dose in radiotherapy, and it is important to prevent this radiation-induced complication. Recent studies show that hydrogen has a potential as an effective and safe radioprotective agent by selectively reducing hydroxyl and peroxynitrite radicals. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, we hypothesize that a treatment combining radiotherapy with aerosol inhalation of a hydrogen-rich solution may be an effective and novel prevention strategy for radiation pneumonitis (hydrogen is explosive, while a hydrogen-rich solution such as physiological saline saturated with molecular hydrogen is safer).

Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: A cross sectional, single center study

Children treated with cranial radiotherapy (CRT) for leukemia are at risk of developing central nervous system injuries. Magnetic resonance imaging (MRI) represents the examination method of choice for evaluating radiation-induced brain complications. The purpose of this report is to describe the spectrum of MRI abnormalities detected in a group of survivors of leukemia treated with cranial irradiation. In this cross-sectional, single center study, 56 patients (median age at follow-up 19 years) receiving CRT as cranial prophylaxis (CP) included in the leukemia protocol (total dose 1,800-2,400 cGy) and/or in the total body irradiation regimen (990-1,200 cGy) before hematopoietic stem cell transplant, were evaluated by MRI after a median interval of 11 years (range 2-27) following CRT. Fifty-nine MRI abnormalities (32 cavernomas, nine focal areas of gliosis, seven dystrophic mineralizations, five cerebral atrophies, four pituitary atrophies, one diffuse radiation leukoencephalopathy, and one meningioma) were found in 43 patients. The longest interval between CRT and MRI and oldest age at follow-up represented the two risk factors that were statistically associated with MRI lesions (P = 0.032 and 0.033, respectively). Cerebral cavernomas (CC) were the most frequent MRI abnormalities (57%). All patients with CC were asymptomatic at diagnosis and during follow-up, except one who had aspecific neurological manifestations and micro hemorrhages. These results confirm that total doses and modalities of fractionation dose of CRT were not significantly associated with MRI abnormalities. Moreover, in our experience none of the patients developed neurological symptoms related to MRI abnormalities, and furthermore, the CC remained substantially stable during follow-up.

Radiation-Induced Bowel Complications: Laparoscopic Versus Open Staging of Gynecologic Malignancy

To evaluate whether the type of surgical approach used to stage gynecologic malignancies influences the risk of developing nonrectal radiation-induced intestinal injury (NRRIII) in patients who subsequently receive adjuvant radiotherapy. A prospectively entered database was queried for all women with either primary or recurrent gynecologic malignancy who underwent external-beam radiation therapy±brachytherapy and who had prior abdominopelvic surgery at our institution. Univariate and multivariate analysis of variables potentially affecting the risk of developing significant bowel toxicity (defined as grade 2 or more according to Radiation Therapy Oncology Group scoring) were performed. One hundred fifty-nine patients were identified. The site of primary tumor was the cervix in 61(38%) patients and the corpus uteri in the remaining patients (98, 62%). Treatment was delivered with a combination of external-beam and intracavitary irradiation to 50 (31.4%) patients, and 109 (68.6%) patients received only external-beam irradiation. Staging procedures were performed by open surgery in 93 (58.5%) patients, whereas laparoscopy was the surgical approach of choice in 66 (41.5%) women. Fifteen patients (9.4%) developed grade 2 or greater NRRIII, at median latency of 10months (range 3-64months); six were diagnosed as grade 3 complications requiring surgery, and three developed grade 4 complication. Multiple regression revealed an independent protective effect of pretreatment laparoscopic staging against the risk of developing both grade ≥2 and grade ≥3 NRRIII. Notwithstanding potential limitations of nonrandomized study design, our findings suggest that the benefits of minimal-access surgery used to perform staging procedures may translate into long-term reduction in radiation-induced bowel injury.

Gastroduodenal Complications After Concurrent Chemoradiation Therapy in Patients With Hepatocellular Carcinoma: Endoscopic Findings and Risk Factors

Concurrent chemoradiation therapy (CCRT) is useful in advanced hepatocellular carcinoma (HCC), but little is known about radiation-induced gastroduodenal complications following therapy. To determine risk factors, we investigated the prevalence and patterns of gastroduodenal complications following CCRT using endoscopy. Enrolled in the study were 123 patients treated with CCRT for unresectable HCC between January 1998 and December 2005. Radiation-induced gastroduodenal complications were defined as radiation gastritis/duodenitis, radiation gastric/duodenal ulcer, or other gastroduodenal toxicity associated with radiation, based on Common Terminology Criteria for Adverse Events (CTCAE 3.0). Serious gastroduodenal complications were defined as events occurring within 12 months from completion of CCRT, those requiring prompt therapeutic intervention, or symptoms equivalent to Grade 3 or 4 radiation-related gastroduodenal toxicity, including nausea or vomiting, based on CTCAE 3.0. A month after completion of CCRT, 65 (52.8%) patients displayed endoscopic evidence of radiation-induced gastroduodenal complications. Radiation gastric and duodenal ulcers were found in 32 (26.0%) and 20 (16.3%) patients, respectively; radiation gastritis and duodenitis were found in 50 (40.7%) and 42 (34.1%) patients, respectively. Radiation-related bleeding was observed in 13 patients (10.6%). Serious gastroduodenal complications occurred in 18 patients (14.6%) and were significantly more frequent in patients with liver cirrhosis than in those without cirrhosis (p=0.043). There were no radiation-related deaths. Endoscopically detectable radiation-induced gastroduodenal complications were common in HCC following CCRT. Although serious complications were uncommon, the frequency was higher in patients with liver cirrhosis; thus, these patients should be closely monitored when receiving CCRT.

Reduced versus full doses of irradiation after 3 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine in early stage Hodgkin lymphomas

The combination of 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and a tailored, extended irradiation schedule has been used to treat patients with early Hodgkin lymphoma (HL) in the authors' group since 1981. The randomized H97-E trial (1997-2004) was designed to assess the impact of a slightly reduced irradiation dose on the freedom from treatment failure (FFTF) rate. Patients with supradiaphragmatic HL at clinical stages I and II who had </=2 affected lymph node areas and a mediastinal mass ratio <0.33 were randomized into an experimental arm (EA) and a control arm (CA). Patients in the EA received 3 cycles of ABVD followed by irradiation at 36 grays (Gy) to initially involved sites and 24 Gy to adjacent sites, the upper infradiaphragmatic area, and the spleen. Patients in the CA received the same chemotherapy regimen and the same irradiation given at doses of 40 Gy and 30 Gy, respectively. Two hundred two patients who had received the CA treatment in 2 previous trials served as a historic control group (HCG). The 10-year FFTF and overall survival rates were similar for the 89 patients in the EA (88.6% and 97.8%, respectively), for the 99 patients in the CA (92.6% and 95%, respectively), and for the 202 patients in the HCG (91.9% and 92.9%, respectively). Surprisingly, the 10-year incidence of severe or fatal complications was nil in the EA but reached 15.5% in the CA (P < .003) and 11.1% in the HCG. Slightly lowering the radiation dose did not have an impact on the excellent cure rate among patients with early HL but significantly reduced the rate of long-term, radiation-induced complications.

Human CD34+ cells mobilized by granulocyte colony-stimulating factor ameliorate radiation-induced liver damage in mice

IntroductionOn the basis of the recently recognized potential of hematopoietic stem cells (HSCs) to give rise to hepatocytes, we have assessed the potential of granulocyte colony-stimulating factor (G-CSF)-mobilized bone marrow-derived CD34+ HSCs to contribute to faster recovery and promote regeneration process after acute liver injury by radiation.MethodsG-CSF-mobilized CD34+ HSCs (1 × 105 cells per mouse) were injected via tail vein in the irradiated femal nonobese diabetic/severe combined immunodeficient mice. Irradiated control animals received only saline infusion.ResultsThe mobilized CD34+ HSCs significantly ameliorated radiation-induced liver damage. In the liver of recipient mice killed 21 days after irradiation, human albumin+ Y-chromosome+ hepatocyte-like cells, or human cytokeratin+ Y-chromosome+ hepatocyte-like cells formed cords of hepatocytes, occupied ~30% of the 4-μm section surrounding portal tracts. Furthermore, human-specific albumin mRNA expressed in the liver and human albumin was detected in the serum only in the CD34+ HSC-treated mice.ConclusionsTreatment with G-CSF-mobilized CD34+ HSCs from bone marrow into peripheral blood could significantly promote tissue reparation after acute liver injury by radiation in mice, possibly by the ability of CD34+ HSCs to generate hepatocytes. So mobilization of CD34+ HSCs might offer a novel therapeutic approach for the treatment of radiation-induced complications after radiotherapy or other acute liver diseases in humans.

Dose de tolérance des tissus sains : le cœur

Radistion thoracic tumors may be associated with cardiac toxicity because of the central position of the heart in the thorax. The present review aims to describe the cardiotoxicity during radiotherapy of different tumor sites most associated with this complication and the risk factors of cardiotoxicity during radiation therapy. Medline literature searches were performed using the following cardiac – heart – radiotherapy – toxicity – cardiotoxicity – breast cancer – lymphoma. Cardiac toxicity after breast cancer and mediastinal lymphoma is the most reported radiation-induced complication. The most frequent clinical complications are pericarditis, congestive heart failure, and heart infarction. These events are mostly asymptomatic. Thus clinicians have to give particular attention to these complications. Anthracyclin treatment is a major risk factor for additional cardiotoxicity during radiotherapy with a synergistic effect. Correction of cardiovascular risk is an important point of the prevention of heart complications. Total dose delivered to the planned target volume (PTV), the dose per fraction and the irradiated volume were correlated to the risk of cardiotoxicity. Volume of heart receiving 35 Gy must be inferior to 30% and dose per fraction should not exceed 2 Gy when dose of prescription exceeds 30 Gy. Maximum heart distance (maximal thickness of heart irradiated) must be less than 1 cm during irradiation of breast cancer. Modern irradiation techniques seem to be associated with a limited risk of heart complication. The use of anthracycline, other cardiotoxic chemotherapies and targeted therapies should incite for great caution by performing a careful treatment planning and optimisation.

Clinical outcome after repeated radiosurgery for brain arteriovenous malformations

Introduction We assessed the clinical and radiological outcome after repeated radiosurgery for brain arteriovenous malformations (bAVMs) after failure of initial radiosurgery. Materials and methods Fifteen patients underwent repeated radiosurgery. The mean bAVM volume at first radiosurgery (S1) was 4.6 ± 4.3 ml and that at second radiosurgery (S2) was 2.1 ± 2.5 ml. The median marginal dose was 18 Gy at S1, and 21 Gy at S2. Modified Rankin Scale (MRS) score was determined in all patients at last follow-up (FU). Results Complete obliteration was reached in nine patients (60%). Median time to obliteration was 50 months after S2. An excellent outcome (no new neurologic deficiencies, complete obliteration) was reached in seven patients (47%). Eleven patients (73%) showed a MRS ⩽ 1. Radiation-induced complications occurred in 20%, of which 13% occurred after S2. Radiological complications included cyst formation ( n = 1), radiation-related edema ( n = 4), and radiation necrosis ( n = 1), resulting in an increasing mean MRS of 0.5 at S1, 0.6 at S2, to 0.8 at FU. No (re-)bleedings were encountered during 137-patient years at risk. Discussion Repeated radiosurgery is a viable option for the treatment of small remnant bAVMs. We report 20% permanent radiation-induced complications. Such complications were mainly seen in relatively large, and therefore difficult to treat, bAVMs.