[RADIATION-INDUCED TUMOR DEVELOPING AFTER RADIOSURGERY: WHAT ARE THE ODDS?]

INTRODUCTION: Stereotactic radiosurgery is a disruptive therapeutic technique that has transformed neurosurgery and the treatment of intracranial tumors in the last few decades. Achieving tumor control rates over 90%, it is performed mostly in a single session, as an outpatient procedure involving no skin cuts, head shaving, or anesthesia, Radiosurgery stands out as a treatment modality with few and mostly transient side effects. Even though ionizing radiation (the energy used in radiosurgery) is known to be cancerogenic, radiosurgery-induced tumors have been exceedingly rare. In this issue of Harefuah, the Hadassah group reports a case of glioblastoma multiforme originating in the radio surgically treated site of an intracerebral arterio-venous malformation. We discuss what we can learn from this dire occurrence.

The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is associated with many different cancers, including early onset breast cancer. Due to an increased risk of radiation-induced malignancy, radiation therapy is often avoided in this patient population. This case study evaluates a 38-year-old female with a history of juvenile granulosa cell tumor of the ovary and malignant phyllodes tumor of right breast, who subsequently developed bilateral invasive ductal carcinoma and was treated with bilateral mastectomies. Studies show that in a high-risk patient, post-mastectomy radiation therapy (PMRT) should not be ruled out due to a history of LFS, as the benefit of PMRT may outweigh the risk of a radiation-induced malignancy.

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.

Microsurgical Resection of Radiation-Induced Cervical Spinal Intradural Extramedullary Meningioma: Dural Splitting Resection.

Spinal meningiomas constitute 10% of all meningiomas. They most commonly rise in the thoracic spine and are most common in middle aged women; symptoms include progressive myelopathy.1,2 Radiation induced/radiotherapy-associated cranial meningiomas are well described with aggressive behavior; however, radiation-induced spinal meningiomas are extremely rare in the literature.3-7 Our patient had a history of Hodgkin lymphoma treated with neck radiation, and thyroid cancer treated with radioactive iodine/thyroidectomy. He presented with neck pain and myelopathy from a large intradural, extramedullary tumor compressing the spinal cord (C3-C5). He had a prevertebral phlegmon that was resolved with antibiotics prior to surgery. Intraoperative neurophysiological electrodes were placed for somatosensory-evoked potential and motor-evoked potential monitoring. C3-C5 bilateral laminectomies were performed (Video 1); dura was incised over the tumor. Tumor attachments to the dura were coagulated and divided. The tumor was dissected microsurgically from the spinal cord and nerve roots. The dural layer involved by the tumor was split and resected from the uninvolved dura, achieving tumor resection. Postoperatively, the patient's myelopathy resolved. He has been followed for a 1 year now with mangetic resonance imaging scans of the cervical spine ± contrast every 6 months. To our knowledge, this is the first operative video describing resection of a spinal meningioma, which happens to be radiation-induced, using a dural splitting technique to achieve better resection and prevent tumor recurrence. The alternative treatment would be to leaving the inner layer of dura, coagulation, or excising both layers and performing duraplasty. Both alternative options, however, would increase the risk of recurrence and spinal fluid leak. Cervical spine meningiomas with spinal cord compression and myelopathy should be resected to prevent further neurological decline. Dural splitting can be utilized to achieve "radical" tumor resection to prevent recurrence, which is particularly important if the tumor is aggressive and recurrent, as is the case in radiation-induced/radiotherapy-associated meningiomas. Upon dural closure, we applied autologous fat tissue along with fibrin glue to avoid spinal fluid leak as we published earlier.8 The patient consented to the procedure and publication of his image.

Aggressive Radiation-Induced Cavernous Sinus Meningioma: 2-Dimensional Operative Video.

Radiation-induced meningiomas are the most common radiation-induced neoplasms. They exhibit a distinct aggressive clinical behavior as rapid growth, recurrences, multiplicity, and malignant progression are common features.1-4 Atypical histological findings and aberrant cytogenetics are increasingly identified.5-7 Radical resection of aggressive radiation-induced meningiomas is the best treatment option and would offer the best chance for control of the disease. Wide bone and dural margins should be pursued in the resection. Parasellar extension creates significant surgical challenges. Cavernous sinus exploration through the multidirectional axis provided by the cranioorbital zygomatic approach allows radical resection of the tumor, cranial nerve decompression, and carotid artery preservation and control.8-11 This article describes a cavernous sinus radiation-induced meningioma after radiation for Cushing disease. It demonstrates the details of the extra- and intradural exploration and dissection of the neurovascular structures in the cavernous sinus, with proximal and distal control of the carotid artery. However, even after radical resection, recurrence is a common finding in this malignant behavioral radiation-induced tumor. Patient consented for surgery. Image at 9:41 comes from the Science Museum Group, United Kingdom. Refer to the Wellcome blog post (archive). This image is licensed under the CC-BY 4.0 International license.

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.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years.

PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.

Radiation-induced glioblastoma of the conus medullaris from radiation treatment of cervical cancer.

Radiation-induced spinal glioblastoma is an extremely rare disease with only four previously published reports in the literature. We report the fifth case, a 69-year-old woman who previously underwent treatment with brachytherapy for cervical cancer, and thereafter presented with neurologic deficits from a conus medullaris tumour. Biopsy and histopathology confirm glioblastoma, not otherwise specified. Treatment of spinal glioblastoma consists of surgery, either biopsy or excision and chemoradiation. However, results are still unsatisfactory and prognosis remains poor.

Radiation-induced meningiomas.

Radiation-induced meningiomas (RIMs) became more common as the use of ionizing radiation was adopted in the treatment of medical conditions, both benign and malignant. Currently, RIMs represent the most common radiation-induced tumors. They are heterogeneous in terms of patient characteristics, radiographic appearance, genetics, pathology, symptoms, and management strategies. They tend to occur in a younger population and are generally more aggressive in nature than their spontaneous counterparts. Their characteristics also vary based on the dose of radiation received, which is most commonly separated into low dose (<10Gy) and high dose (>10Gy). The importance of the dosing classification is that it can provide insight into the nature and biologic behavior of the tumor. Given their heterogeneity, RIMs pose significant challenges in management. While surgical resection remains the preferred treatment when feasible, recent data supports stereotactic radiosurgery (SRS) as a comparable alternative. Although there is more knowledge about the molecular pathways leading to RIMs, targeted drug therapy is still limited and is the focus of current research.

Early life-threating enlargement of a vestibular schwannoma after gamma knife radiosurgery.

Stereotactic gamma knife radiosurgery (GKS) may induce a transient enlargement of vestibular schwannomas (VS). This phenomenon, known as pseudoprogression or swelling, starts at about 3 months following GKS, peaks at about 6 months, and typically subsides thereafter, usually without significant neurological deterioration. We describe a 34-year-old female who developed an aggressive enlargement of a VS 1 month after GKS. The patient was treated with an immediate external ventricular drainage and surgical resection via retrosigmoid approach for an acute neurological deterioration due to hydrocephalus and brainstem compression. Histopathological examination revealed a VS with abundant intratumoral thrombosis and necrosis, suggesting that its rapid expansion could be related to massive radiation-induced tumor necrosis. The present case indicated that rapid life-threating enlargement of a VS may occur as an early complication following GKS.

Radiotherapy-related skin ulcer communicating with a left ventricular aneurysm.

Although radiation therapy is widely used to treat breast cancer, high doses of radiation may cause various complications. We report a case of a left ventricular aneurysm complicated with an intractable skin ulcer caused by radiation therapy for breast cancer. The communication between the aneurysm and skin ulcer caused severe bleeding. An urgent left ventricular repair and chest wall reconstruction with a rectus abdominis flap were performed successfully.

Radiation-induced undifferentiated pleomorphic sarcoma of the breast.

Breast sarcoma is a rare form of malignancy that arises from connective tissue within the breast, comprising less than 5% of all sarcomas. They develop as primary tumours or as secondary following radiation therapy. Diagnosis can be challenging as breast sarcomas are often asymptomatic and resemble benign breast tissue changes. Radiation-induced breast sarcomas present in various forms with an average latency period of 10-20 years following initial radiation therapy. Angiosarcomas are the most common form, while other types such as undifferentiated pleomorphic sarcomas remain rare. Here, we report a case of radiation-induced undifferentiated pleomorphic breast sarcoma in a 75-year-old woman that developed nearly 20 years following breast conserving surgery and radiation for invasive ductal carcinoma. The patient initially noticed a mass in 2017 on self-examination. The mammogram, ultrasound and biopsy at the time showed a benign 2.2 cm nodular fasciitis without malignancy. The mass grew rapidly in the next 6 months to 5.6 cm and repeat biopsy diagnosed undifferentiated pleomorphic sarcoma. The mass abutted the pectoralis muscle but staging workup ruled out distant metastasis and the patient underwent wide local resection of the mass with clear margins. The patient subsequently underwent further postoperative radiation due to insufficient posterior margin width on wide local excision, as chest wall resection would have been required for a wider posterior margin. Prognosis for postradiation sarcomas is generally poor with 27%-36% 5-year survival, with surgical resection as the main line of treatment. The patient currently remains disease-free after 15 months of surveillance.

Postoperative radiotherapy-induced leiomyosarcoma in breast cancer: a case report and literature review.

Radiation-induced sarcoma (RIS) is a late complication of breast cancer radiotherapy, with a very low incidence, long latent period and poor prognosis. Among them, leiomyosarcoma after radiation is an extremely rare radiation-associated sarcoma. In this study, we report a case of radiation-induced leiomyosarcoma 2 years after postoperative radiotherapy for breast cancer. After the diagnosis of leiomyosarcoma, the patient received radical resection of the left chest wall leiomyosarcoma. The patient showed no relapse or progression during the follow-up time of 1 year after operation. Rare occurrence of RIS induced by postoperative radiotherapy in breast cancer and limited experience concerning its diagnosis and treatment bring obstacle to both patients and doctors. Preoperative examinations must be carefully refined. With a perfect coordination between different disciplines, RIS induced by postoperative radiotherapy in breast cancer can be ideally treated with better prognosis.

Septum Pellucidum Cavernoma: A Case Report and Anatomical Consideration of an Extremely Rare Lesion.

Cavernous angiomas (cavernomas) are vascular malformations of the brain characterized by abnormal capillaries. Ventricular cavernomas are considered rare; however, an extremely unusual topography is the septum pellucidum, with only five reported cases in the English literature. These malformations may rupture and cause very large hematomas, leading to neurological impairment. Cavernomas can be familial or sporadic; additionally, these may appear following brain radiotherapy in extremely rare cases. Herein, we present an extremely rare and unique case of a septum pellucidum cavernoma that occurred in a young male who had previously undergone brain radiotherapy in childhood due to acute lymphoid leukemia. Following presentation, he was diagnosed with generalized seizures. The cavernoma was resected via an anterior interhemispheric transcallosal approach, following which the patient remained stable without neurological sequelae. To conclude, ventricular cavernomas are rare lesions, especially when located at the septum pellucidum, thus constitute a challenging neurosurgical approach.