[Secondary tumors following radiation therapy and chemotherapy : Incidence of cavernous hemangiomas]. / Zweittumoren nach Bestrahlung und Chemotherapie : Auftreten von Kavernomen.

PROBLEM: There is a risk of developing secondary central nervous system (CNS) tumors after cranial radiation therapy. Meningiomas and pituitary tumors are also increasingly treated with radiation therapy, which means that the risk of secondary tumors from radiation in children and adults must be communicated. METHODS: Studies in children show that radiation causes a 7- to 10-fold increase in subsequent CNS tumors with a cumulative incidence over 20 years ranging from 1.03 to 28.9. The latency period for the occurrence of secondary tumors ranged from 5.5 to 30 years, with gliomas developing after 5-10 years and meningiomas around 15 years after irradiation. The latency period for secondary CNS tumors in adults ranged from 5 to 34 years. CONCLUSION: After radiation treatment, tumors can rarely occur as secondary sequelae, mostly meningiomas and gliomas, but also cavernomas. The treatment and long-term results of radiation-induced CNS tumors showed no worse results than primary CNS tumors over the course of time.

Is there a role for adjuvant therapy in radiation-induced angiosarcoma of the breast? A case report and review of the literature.

BACKGROUND: Angiosarcoma (AS) of the breast is very rare, accounting for 1% of all soft tissue breast tumors. AS may present as primary tumors of the breast or as secondary lesions usually associated with previous radiotherapy. Commonly, secondary AS affects older women (median age 67-71 years) with a clinical history of breast cancer. The preferred site of onset of RIAS is the edge of radiation fields, where radiation doses and tumor necrosis may be heterogeneous, resulting in a DNA damage and instability. Radical surgery is the treatment of choice, but no clear consensus exists on surgical management of breast AS. CASE REPORT: We describe an atypical case of relapsed RIAS after radical mastectomy, treated with new surgery and, considering the higher risk of recurrence, subsequent adjuvant chemotherapy with weekly paclitaxel. CONCLUSIONS: The frequency of radiation-induced angiosarcomas (RIAS) after breast-conserving surgery and radiotherapy has been increased to 0.14-0.5% among long survivors. Nevertheless, even if RIAS continues to be prognostically an extremely unfavorable cancer due to a high rate of recurrence, distant spread, and median overall survival (OS) of about 60 months, the benefits of loco-regional breast radiotherapy are clearly higher than the risk in developing angiosarcoma.

Contemporary diagnostic approach to atypical vascular lesion and angiosarcoma.

Vascular neoplasms account for a substantial fraction of cutaneous mesenchymal tumors, spanning from clinically indolent benign lesions to highly aggressive malignancies. These neoplasms present a distinctive challenge in terms of their diagnostic histopathology, both because of the breadth of their morphological manifestations and because of the significant histological overlap between different entities, even benign and malignant ones. The post-radiotherapy setting is particularly problematic diagnostically, insofar as radiation exposure predisposes not only to secondary angiosarcoma, but also to atypical vascular lesion, a largely benign proliferation of cutaneous blood vessels typically affecting the breast. To address these challenges, we explore the clinical, histological, and molecular features of malignant vascular neoplasia, including primary and secondary subtypes, through the comparative lens of atypical vascular lesion. In addition to highlighting the key morphological indicators of malignancy in superficial vasoformative tumors, we offer an approach that integrates clinical characteristics and molecular genetic profiling to facilitate accurate classification. With this current knowledge as our foundation, we also look ahead in an effort to frame some of the key unanswered questions regarding superficial vascular malignancies and their natural history, clinical management, and molecular underpinnings.

[Prevention of iodine deficiency diseases: focus on regional targeted programs].

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than the established norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

Long-Term Risks of Hemorrhage and Adverse Radiation Effects of Stereotactic Radiosurgery for Brain Arteriovenous Malformations.

BACKGROUND: The information about long-term risks of hemorrhage and late adverse radiation effects (AREs) after stereotactic radiosurgery for brain arteriovenous malformations (AVMs) is lacking. OBJECTIVE: To evaluate the long-term risks of hemorrhage and late ARE rates in patients with AVM treated with Gamma Knife surgery (GKS). METHODS: We examined 1249 patients with AVM treated with GKS. The Spetzler-Martin grade was I in 313 patients (25%), II in 394 (32%), III in 458 (37%), and IV/V in 84 (7%). The median treatment volume was 2.5 cm3, and the median marginal dose was 20 Gy. RESULTS: The median follow-up period was 61 months. The 5- and 10-year nidus obliteration rates were 63% and 82%, respectively. The 5- and 10-year cumulative hemorrhage rates were 7% and 10%, respectively. The annual hemorrhage rate was 1.5% for the first 5 years post-GKS, which decreased to 0.5% thereafter. During the follow-up period, 42 symptomatic cyst formations/chronic encapsulated hematomas ([CFs/CEHs], 3%) and 3 radiation-induced tumors (0.2%) were observed. The 10- and 15-year cumulative CF/CEH rates were 3.7% and 9.4%, respectively. CONCLUSION: GKS is associated with reduced hemorrhage risk and high nidus obliteration rates in patients with AVM. The incidence of late AREs tended to increase over time. The most common ARE was CF/CEH, which can be safely removed; however, careful attention should be paid to the long-term development of fatal radiation-induced tumors.

Exercise Improves Cancer-free Survival and Health Span in a Model of Radiation-induced Cancer.

INTRODUCTION: Radiation therapy increases the risk of secondary malignancy and morbidity in cancer survivors. The role of obesity and exercise training in modulating this risk is not well understood. As such, we used a preclinical model of radiation-induced malignancy to investigate whether diet-induced obesity and/or endurance exercise training altered lifelong survival, cancer incidence, and morbidity. METHODS: Male CBA mice were randomly divided into control diet/sedentary group (CTRL/SED), high-fat diet (45% fat)/sedentary group (HFD/SED), control diet/exercise group (2-3 d·wk-1; CTRL/EX), or high-fat diet/exercise group (HFD/EX) groups then exposed to whole-body radiation (3 Gy). End point monitoring and pathology determined mortality and cancer incidence, respectively. Health span index, a measure of morbidity, was determined by a composite measure of 10 anthropometric, metabolic, performance, and behavioral measures. RESULTS: Overall survival was higher in HFD/SED compared with CTRL/SED (P < 0.05). The risk of cancer-related mortality by 18 months postradiation was 1.99 and 1.63 in HFD/SED compared with CTRL/EX (RR = 1.99, 95% confidence interval = 1.20-3.31, P = 0.0081) and CTRL/SED (RR = 1.63, 95% confidence interval = 1.06-2.49, P = 0.0250), respectively. The number of mice at end point with cancer was higher in HFD/SED compared with CTRL/EX and CTRL/SED (P < 0.05). Health span index was highest in CTRL/EX (score = +2.5), followed by HFD/EX (score = +1), and HFD/SED (score = -1) relative to CTRL/SED. CONCLUSION: This work provides the basis for future preclinical studies investigating the dose-response relationship between exercise training and late effects of radiation therapy as well as the mechanisms responsible for these effects.

Canyons and Volcanoes: The Effects of Radiation on the Chest Wall.

Tumors involving the sternum often require complete removal of the bony structure to achieve cure and prevent recurrence. The type and extent of reconstruction must be carefully selected. Full-thickness sternal defects often necessitate semirigid or rigid biocompatible prostheses and carefully transposed myocutaneous flaps. Superimposed infection on radiation-induced cancer or osteoradionecrosis involving the sternum is also observed, and optimal treatment relies on an experienced multidisciplinary team. This report describes the successful management of 2 cases of sternal involvement after radiation: a canyonlike lesion and a volcanolike lesion.

Radiation-induced sarcoma presenting as a gluteal abscess: a diagnostic and therapeutic challenge.

Sarcomas are a rare and fatal treatment complication following radiotherapy. Radiation-induced sarcomas (RISs) presenting as a gluteal abscess is a rarity, accounting for its varied presentation. We present a case of a middle-aged woman, post-chemo-radiation for carcinoma cervix 5 years ago, who presented with gluteal abscess. Achieving haemostasis post incision and drainage under anaesthesia was a challenge. On further evaluation, she was diagnosed with radiation-induced gluteal soft tissue sarcoma. Haemostasis was achieved after radiation following failed attempts of surgical and radiological interventions. She is currently planned for chemotherapy. Cancer survivors have an increased risk of developing a second malignancy following radiation treatment. RISs are highly aggressive, exhibit a varied clinical presentation and pose a challenge in early diagnosis; thus, have a poor outcome. RISs pose a diagnostic challenge; any dubious lesion in the previously irradiated field should raise suspicion and prompt aggressive management.

Modifying Effect of Chronic Atrophic Gastritis on Radiation Risk for Noncardia Gastric Cancer According to Histological Type.

The findings from previously published studies have suggested that radiation exposure is associated with increased mortality and incidence of gastric cancer. However, few cohort studies have incorporated risk factors such as Helicobacter pylori (H. pylori) infection or chronic atrophic gastritis (CAG). The current study is aimed at evaluating the modifying effect of CAG on radiation risk of noncardia gastric cancer by histological type, by reanalyzing data from a nested case-control study conducted within the longitudinal clinical cohort of atomic bomb survivors. The analysis was restricted to 297 intestinal- or diffuse-type noncardia cases and 873 controls rematched to the cases on gender, age, city, and time and type of serum storage, and countermatched on radiation dose. Multivariable-adjusted relative risks [95% confidence interval (CI)] of noncardia gastric cancer were 3.9 (2.1-7.2) for H. pylori IgG seropositivity with cytotoxin-associated gene A (CagA) IgG low titer, 2.6 (1.9-3.6) for CAG, 1.9 (1.3-2.8) for current smoking, and 1.4 (1.1-1.9) for 1 Gy irradiation. Among subjects without CAG, the relative risk (95% CI) of noncardia gastric cancer at 1 Gy was 2.3 (1.4-3.7), whereas relative risk (95% CI) at 1 Gy was 1.1 (0.8-1.5) among subjects with CAG (for the overall interaction, P = 0.012). By histological type, the risk at 1 Gy was high for diffuse type without CAG, with adjusted relative risk (95% CI) of 3.8 (2.0-7.6), but was not high for diffuse type with CAG or for intestinal-type irrespective of CAG status. The results indicate that radiation exposure is associated with increased risk of diffuse-type noncardia gastric cancer without CAG, and this association exists despite adjustment for H. pylori infection and smoking habit.

Supracerebellar Transtentorial Approach for Occipital Meningioma to Maximize Visual Preservation: Technical Note.

BACKGROUND AND IMPORTANCE: Surgery for resection of tentorial meningiomas compressing primary visual cortex carries a significant risk of worsening vision. This concern is especially acute in patients with a preexisting visual deficit. Approaches that involve mechanical retraction of the occipital lobe further threaten visual function. The supracerebellar transtentorial (SCTT) approach, which does not carry a risk of occipital retraction injury, should be considered for patients with occipital tentorial meningiomas to maximize functional visual outcomes. CLINICAL PRESENTATION: A 54-yr-old woman underwent 2 resections and radiation therapy for a right occipital oligodendroglioma as a teenager. She was left with a complete left homonymous hemianopsia. The patient now presented with progressive vision loss in her remaining right visual field. Imaging revealed a left occipital superiorly projecting tentorial meningioma. To preserve her remaining visual function the SCTT approach was chosen for resection. A Simpson grade 1 removal was achieved without disrupting the occipital lobe pia or requiring mechanical cerebellar retraction. A diagnosis of a WHO grade II meningioma (presumably radiation induced) was made. The patient's vision returned to premorbid baseline 1 wk after surgery. CONCLUSION: The SCTT approach should be considered for the surgical management of patients with occipital tentorial meningiomas when visual preservation is at risk. This approach avoids transgression of visual cortex and minimizes the risk of venous infarction or contusions from retraction injury.

18F-FDG PET/CT in the detection of a primary radiation-induced metastatic angiosarcoma / 18F-FDG PET/TC en la detección de angiosarcoma primario radioinducido metastásico

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Coexistence of Radiation-Induced Meningioma and Moyamoya Syndrome 10 Years after Irradiation against Medulloblastoma: a Case Report.

Radiotherapy is one of the standard treatments for medulloblastoma. However, therapeutic central nervous system irradiation in children may carry delayed side effects, such as radiation-induced tumor and vasculopathy. Here, we report the first case of coexisting meningioma and moyamoya syndrome, presenting 10 years after radiotherapy for medulloblastoma. A 13-year-old boy presented with an enhancing mass at the cerebral falx on magnetic resonance imaging (MRI) after surgery, radiotherapy (30.6 Gy craniospinal axis, 19.8 Gy posterior fossa) and chemotherapy against medulloblastoma 10 years ago, previously. The second tumor was meningioma. On postoperative day 5, he complained of right-sided motor weakness, motor dysphasia, dysarthria, and dysphagia. MRI revealed acute cerebral infarction in the left frontal lobe and both basal ganglia. MR and cerebral angiography confirmed underlying moyamoya syndrome. Four months after the meningioma surgery, the patient presented with headaches, dysarthria, and dizziness. Indirect bypass surgery was performed. He has been free from headaches since one month after the surgery. For patients who received radiotherapy for medulloblastoma at a young age, clinicians should consider the possibility of the coexistence of several complications. Careful follow up for development of secondary tumor and delayed vasculopathy is required.

Morbidity and Mortality Associated With Meningioma After Cranial Radiotherapy: A Report From the Childhood Cancer Survivor Study.

Purpose Little is known about neurologic morbidity attributable to cranial radiotherapy (CRT) -associated meningiomas. Materials and Methods From 4,221 survivors exposed to CRT in the Childhood Cancer Survivor Study, a diagnosis of meningioma and onset of neurologic sequelae were ascertained. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% CIs to evaluate the factors associated with neurologic sequelae after subsequent meningioma. Results One hundred ninety-nine meningiomas were identified among 169 participants. The median interval from primary cancer to meningioma diagnosis was 22 years (5 to 37 years). The cumulative incidence of a subsequent meningioma by age 40 years was 5.6% (95% CI, 4.7% to 6.7%). CRT doses of 20 to 29.9 Gy (HR, 1.6; 95% CI,1.0 to 2.6) and doses ≥ 30 Gy (HR, 2.6; 95% CI, 1.6 to 4.2) were associated with an increased risk of meningioma compared with CRT doses of 1.5 to 19.9 Gy ( P < .001). Within 6 months before or subsequent to a meningioma diagnosis, 20% (30 of 149) reported at least one new neurologic sequela, including seizures (8.3%), auditory-vestibular-visual deficits (6%), focal neurologic dysfunction (7.1%), and severe headaches (5.3%). Survivors reporting a meningioma had increased risks of neurologic sequelae > 5 years after primary cancer diagnosis, including seizures (HR, 10.0; 95% CI, 7.0 to 15.3); auditory-vestibular-visual sensory deficits (HR, 2.3; 95% CI, 1.3 to 4.0); focal neurologic dysfunction (HR, 4.9; 95% CI, 3.2 to 7.5); and severe headaches (HR, 3.2; 95% CI, 1.9 to 5.4). With a median follow-up of 72 months after meningioma diagnosis (range, 3.8 to 395 months), 22 participants (13%) were deceased, including six deaths attributed to a meningioma. Conclusion Childhood cancer survivors exposed to CRT and subsequently diagnosed with a meningioma experience significant neurologic morbidity.

A Rat Model to Study the Effects of Diet-Induced Obesity on Radiation-Induced Mammary Carcinogenesis.

A detailed understanding of the relationship between radiation-induced breast cancer and obesity is needed for appropriate risk management and to prevent the development of a secondary cancer in patients who have been treated with radiation. Our goal was to develop an animal model to study the relationship by combining two existing Sprague-Dawley rat models of radiation-induced mammary carcinogenesis and diet-induced obesity. Female rats were fed a high-fat diet for 4 weeks and categorized as obesity prone or obesity resistant based on their body weight at 7 weeks of age, at which time the rats were irradiated with 4 Gy. Control rats were fed a standard diet and irradiated at the same time and in the same manner. All rats were maintained on their initial diets and assessed for palpable mammary cancers once a week for the next 30 weeks. The obesity-prone rats were heavier than those in the other groups. The obesity-prone rats were also younger than the other animals at the first detection of mammary carcinomas and their carcinoma weights were greater. A tendency toward higher insulin and leptin blood levels were observed in the obesity-prone rats compared to the other two groups. Blood angiotensin II levels were elevated in the obesity-prone and obesity-resistant rats. Genes related to translation and oxidative phosphorylation were upregulated in the carcinomas of obesity-prone rats. Expression profiles from human breast cancers were used to validate this animal model. As angiotensin is potentially an important factor in obesity-related morbidities and breast cancer, a second set of rats was fed in a similar manner, irradiated and then treated with an angiotensin-receptor blocker, losartan and candesartan. Neither blocker altered mammary carcinogenesis; analyses of losartan-treated animals indicated that expression of renin in the renal cortex and of Agtr1a (angiotensin II receptor, type 1) in cancer tissue was significantly upregulated, suggesting the presence of compensating mechanisms for blocking angiotensin-receptor signaling. Thus, obesity-related elevation of insulin and leptin blood levels and an increase in available energy may facilitate sustained protein synthesis in cancer cells, which is required for rapid cancer development.

Subsequent Cancer Risk of Women Receiving Hysterosalpingography: A Nationwide Population-Based Retrospective Cohort Study.

The objective of this study was to estimate the subsequent cancer risk of women after receiving hysterosalpingography (HSG) by conducting a nationwide retrospective cohort study. We identified a study cohort of 4,371 patients who had had a HSG examination and a comparison cohort of 17,484 women without HSG examination between 1998 and 2005. Both cohorts were followed up with until the end of 2010 to measure the incidence of cancer. The risk of developing cancer for patients with HSG was assessed using the Cox proportional hazard model. In the multivariate analyses, the HSG cohort did not have a significantly greater risk of cancer (Hazard Ratio [HR] = 1.02, 95% CI = 0.79-1.31) than the non-HSG cohort. The HR was highest for genital cancer (HR = 1.32, 95% CI = 0.77-2.25), followed by urinary system cancer (HR = 1.11, 95% CI = 0.23-5.40), and abdominal cancer not involving the GU system (HR = 1.04, 95% CI = 0.53-2.03), all of which were non-significant elevations. The cancer incidence rates, especially that for urinary system cancer, were increased in the HSG cohort, but the increase in cancer incidence was small and not statistically significant.

Sunlight, vitamin D and malignant melanoma: an update.

Solar radiation represents an essential requirement for life, not only by spending the thermal energy for photosynthesis in plants, which provides our atmosphere with oxygen, but also by facilitating the cutaneous synthesis of vitamin D in vertebrates and many other organisms. It is well known that humans and most vertebrates have to obtain an adequate source of vitamin D, in order to develop and maintain a healthy mineralized skeleton and in order to be protected against cancer and a broad variety of other diseases. On the other hand, solar UV radiation can be assumed to be the most relevant environmental carcinogen causing melanoma and nonmelanoma skin cancer with increasing incidences. During the last decades, epidemiological studies and experimental animal models, including genetically engineered mice, the Xiphophorus hybrid fish, the south american oppossum and human skin xenografts, have further elucidated the multi-step process of UV-induced melanomagenesis. It has to be emphasized that, in contrast to intermittent, short-term high-dose solar UV-exposure, more chronic less intense exposure (which is recommended by many experts in the field to obtain a sufficient vitamin D status) has not been found to be a risk factor for the development of melanoma and in fact has been found in several studies to be protective. Interestingly, several independent lines of investigation have demonstrated convincing evidence that vitamin D and/or analogs may be effective in the prevention and treatment of melanoma. This essay summarizes our present understanding about the pathogenic role of UV radiation and of vitamin D for malignant melanoma.