Radiation necrosis
Classification according to ICD-10 | |
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T66 | Radiation Damage Unspecified Radionecrosis Not Elsewhere Classified |
ICD-10 online (WHO version 2019) |
As Strahlennekrose also radionecrosis called, refers to the by the action of ionizing radiation -induced death of cells of an organism. Radionecrosis is the most important and most serious complication of radiosurgical treatments, which usually does not become clinically noticeable until months or years after radiation.
Osteoradionecrosis is a special form . This form of bone necrosis can also occur after radiation therapy and is dealt with in a separate article.
Description and clinical picture
Radiation necrosis can develop in healthy tissue after local exposure to ionizing radiation. In the vast majority of cases, radiation is targeted and dose-controlled, for example as part of radiation therapy . In radio- oncology , radiation necrosis of the tumor or its metastases , tumor necrosis, is the primary target of radiation. Therefore, not every radiation necrosis is a complication. In general, the term radiation necrosis is only used for radiation-induced necrosis in healthy tissue.
Radiation necrosis occurs as iatrogenic tissue damage, especially after radiation therapy for cerebral tumors ( brain tumors ). The average latency period here is 14 months after irradiation. In addition, cases are known in which more than 25 years passed between the radiation therapy and the symptoms of the resulting radiation necrosis. The space-occupying, circumscribed radiation necrosis of the white matter ( substantia alba ) leads to focal neurological deficits , epileptic seizures and pathologically increased intracranial pressure . The radiation necrosis produces a perifocal edema . Macrophages , which in principle are able to break down necrosis, cannot immigrate. The microglial cells present at the site of the necrosis , which are also able to phagocytize cell remains of dead cells , were killed by the irradiation. Hydrolytic enzymes were deactivated by the irradiation . They have a comparatively large " effective cross-section ". In the necrotic area there are sometimes strongly dilated blood vessels that cause stasis hyperemia and can lead to erythrodiapedesis (discharge of erythrocytes from blood vessels into the extravasation ).
From a pathological point of view, radiation necrosis is coagulation necrosis .
Radionecrosis can also occur after the treatment of arteriovenous malformations (AVM). Radiation necrosis can also be caused by radiation accidents.
The exact pathological processes that lead to radiation necrosis and especially to the sometimes very long latency periods are still largely unclear. Molecular and cellular mechanisms are responsible for its development. Cytokines , such as tumor necrosis factor , and inflammatory gene products play an essential role in this.
Incidence
The exact frequency of radiation necrosis is not known because - especially in the case of cerebral tumors - the majority of patients die of cancer before radiation necrosis can develop. In the case of cerebral tumors, an incidence of about 5% is assumed if the patients have received a dose of 45 Gray or more.
The risk of radiation necrosis increases with the dose and the size of the irradiated tissue volume, but it can be reduced by fractionation , i.e. spreading the total radiation dose over several sessions. The risk of radionecrosis can be estimated using a formula. With the significant advances in the advancement of radiation therapy, the incidence has decreased significantly compared to the early days of radiotherapy. Modern radiation techniques protect the healthy tissue as much as possible. Basically, however, there is a dilemma between sparing healthy tissue in order to avoid radiation necrosis and irradiating the area around the tumor as large as possible in order to avoid a relapse.
In the case of cerebral tumors or bone metastases , the risk of radionecrosis is consciously taken due to the usually very poor prognosis . The lesions mentioned are mostly inoperable (not to be operated on), so that radiation therapy is the last resort . In benign diseases, such as arteriovenous malformations, the risk-benefit ratio is significantly less favorable.
diagnosis
In clinical practice, it is difficult to distinguish between recurrent tumor, i.e. the recurrence of the tumor disease (usually caused by incomplete removal of the tumor), and radiation necrosis. Both diseases occur at the same expected location, i.e. in the area of the previously removed tumor and its immediate surroundings. Relapse and radiation necrosis are both characterized by masses and the latency periods after tumor removal and radiation are very similar.
Various imaging techniques can be used for differential diagnosis . With magnetic resonance spectroscopy (MRS), the reduced concentrations of N-acetyl aspartate (NAA), choline and creatine in the area of radiation necrosis and the increased choline content in the tumor (recurrent) can make it possible to differentiate.
In computed tomography (CT) and magnetic resonance tomography (MRI), radionecrosis usually appears as a ring-shaped structure surrounded by edema that absorbs any contrast agent that may be applied . With these two imaging methods, radionecrosis can hardly be distinguished from relapse.
The positron emission tomography (PET) with the radiotracer 18 F- fluorodeoxyglucose (FDG) is a widely used imaging technique for differentiating between recurrence and Strahlennekrose. Tumor cells show an increased uptake of FDG (also compared to healthy tissue), while necrotic cells no longer require FDG. However, PET with FDG has its limitation in resolution, which is in the range of several millimeters. As a result, a circumscribed relapse in an area with a relatively low metabolism (hypometabolism) cannot be reliably detected. The differential diagnosis is only unambiguous if the relapse can be demonstrated by an increased metabolism (hypermetabolism). The sensitivity (81 to 86%) of FDG-PET for the detection of tumor recurrence is therefore correspondingly high , while the specificity of 22 to 40% is comparatively low. Some forms of radionecrosis, such as non-small cell lung cancer (NSCLC), can show increased FDG uptake on FDG-PET.
Some authors recommend in brain tumors as an imaging method, the single-photon emission computed tomography (SPECT) with 201 Th thallium (I) chloride . Here, too, the radiotracer is absorbed to a greater extent by the malignant tumor.
The differences between Th-201-SPECT and FDG-PET are negligibly small in terms of specificity and sensitivity. FDG-PET has established itself as the non-invasive diagnostic method of choice in neuro-oncology to differentiate between tumor recurrence and radiation necrosis. In cerebral tumors, the two radiotracers 18 F- fluoroethyl tyrosine and 18 F- fluorocholine offer several advantages over FDG. Also, 11 C- choline appears to be a higher selectivity and sensitivity to offer compared to FDG. However, these radiotracers have so far hardly been used in clinical practice.
In addition to the statistically most likely case of a relapse, metastases and abscesses and, in the case of a medical history with cerebral tumors, multiple sclerosis must also be taken into account for the differential diagnosis . A foreign body reaction after a surgical procedure can also produce a clinical picture similar to radiation necrosis.
The greatest possible diagnostic reliability is offered by a biopsy in which histologically it is relatively easy to differentiate between benign necrotic and malignant tissue.
therapy
Space-consuming cerebral radiation necrosis can be treated well with high-dose corticosteroids such as dexamethasone . Accessible and operable radionecrosis can be surgically removed.
Course and prognosis
If left untreated, radiation necrosis develops progressively and is irreversible. In the case of radiation necrosis in the brain, the necrotic growth can be fatal for the patient due to the space it takes up. In younger patients the prognosis is worse than in older ones.
further reading
- PG Morris, PH Gutin et al .: Seizures and radionecrosis from non-small-cell lung cancer presenting as increased fluorodeoxyglucose uptake on positron emission tomography. In: Journal of clinical oncology . Volume 29, No. 12, April 2011, pp. E324-e326, ISSN 1527-7755 . doi: 10.1200 / JCO.2010.33.0837 . PMID 21263097 .
- E. Maranzano, F. Trippa, F. Loreti: Tumor relapse or radionecrosis after radiosurgery: single-photon emission computed tomography for differential diagnosis. In regard to Blonigen et al. Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. (Int J Radiat Oncol Biol Phys 2010; 77: 996-1001). In: International Journal of Radiation Oncology - Biology - Physics . Volume 78, No. 4, November 2010, p. 1279, ISSN 1879-355X . doi: 10.1016 / j.ijrobp.2010.07.026 . PMID 20970034 .
- O. Belohlávek, G. Simonová et al .: Brain metastases after stereotactic radiosurgery using the Leksell gamma knife: can FDG PET help to differentiate radionecrosis from tumor progression? In: European journal of nuclear medicine and molecular imaging. Volume 30, No. 1, January 2003, pp. 96-100, ISSN 1619-7070 . doi: 10.1007 / s00259-002-1011-2 . PMID 12483415 .
- LS Chin, L. Ma, S. DiBiase: Radiation necrosis following gamma knife surgery: a case-controlled comparison of treatment parameters and long-term clinical follow up. In: Journal of Neurosurgery . Volume 94, No. 6, June 2001, pp. 899-904, ISSN 0022-3085 . doi: 10.3171 / jns.2001.94.6.0899 . PMID 11409517 .
- ST Chao, JH Suh et al .: The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery. In: International Journal of Cancer . Volume 96, No. 3, June 2001, pp. 191-197, ISSN 0020-7136 . PMID 11410888 .
- T. Tashima, T. Morioka et al .: Delayed cerebral radionecrosis with a high uptake of 11C-methionine on positron emission tomography and 201Tl-chloride on single-photon emission computed tomography. In: Neuroradiology. Volume 40, No. 7, July 1998, pp. 435-438, ISSN 0028-3940 . PMID 9730342 .
Individual evidence
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- ^ Y. Yoshii: Pathological review of late cerebral radionecrosis. In: Brain tumor pathology. Volume 25, No. 2, 2008, pp. 51-58, ISSN 1433-7398 . doi: 10.1007 / s10014-008-0233-9 . PMID 18987829 .
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- ↑ a b P. Wolf: Survival time and influencing factors on survival in patients with cerebral metastases after treatment with stereotactic radiation alone vs. Stereotactic radiation in combination with whole-brain radiation. (PDF; 1.3 MB) Dissertation, Ludwig Maximilians University Munich, 2010.
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- ↑ a b R. Engenhart, B. Wowra et al.: Stereotactic convergence irradiation : Current perspectives on the basis of clinical results. In: Strahlenther Onkol. Volume 168, 1992, pp. 245-259.
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- ↑ PG Morris, PH Gutin et al .: Seizures and radionecrosis from non-small-cell lung cancer presenting as increased fluorodeoxyglucose uptake on positron emission tomography. In: Journal of Clinical Oncology . Volume 29, No. 12, April 2011, pp. E324-e326, ISSN 1527-7755 . doi: 10.1200 / JCO.2010.33.0837 . PMID 21263097 .
- ↑ M. Stokkel, H. Stevens et al .: Differentiation between recurrent brain tumor and post-radiation necrosis: the value of 201Tl SPET versus 18F-FDG PET using a dual-headed coincidence camera - a pilot study. In: Nuclear medicine communications. Volume 20, No. 5, May 1999, pp. 411-417, ISSN 0143-3636 . PMID 10404525 .
- ^ CT Wang, YH Young: Potential usefulness of Tl-201 SPECT for differentiating radionecrosis in an irradiated nasopharyngeal carcinoma patient. In: European archives of oto-rhino-laryngology. Volume 263, No. 2, February 2006, pp. 135-138, ISSN 0937-4477 . doi: 10.1007 / s00405-005-0964-8 . PMID 16003552 .
- ^ N. Spaeth, MT Wyss et al .: Uptake of 18F-fluorocholine, 18F-fluoroethyl-L-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence. In: Journal of nuclear medicine. Volume 45, No. 11, November 2004, pp. 1931-1938, ISSN 0161-5505 . PMID 15534065 .
- ↑ H. Tan, L. Chen et al .: Comparison of MRI, F-18 FDG, and 11C-choline PET / CT for their potentials in differentiating brain tumor recurrence from brain tumor necrosis following radiotherapy. In: Clinical Nuclear Medicine. Volume 36, No. 11, November 2011, pp. 978-981, ISSN 1536-0229 . doi: 10.1097 / RLU.0b013e31822f68a6 . PMID 21975383 .
- ^ H. Gerullis, CJ Heuck, P. Schneider: Breast pseudotumoral radionecrosis as a late radiation-induced injury: a case report. In: Journal of medical case reports. Volume 3, 2009, p. 71, ISSN 1752-1947 . doi: 10.1186 / 1752-1947-3-71 . PMID 19946547 . PMC 2783070 (free full text).