Radiation necrosis

from Wikipedia, the free encyclopedia
Classification according to ICD-10
T66 Radiation Damage
Unspecified Radionecrosis Not Elsewhere Classified
ICD-10 online (WHO version 2019)
(A) Benign, progressively growing, calcified , subcutaneous, pseudotumoröse radionecrosis of the right breast, in a 65 year old female patient, 23 years after radiotherapy with 60 Gray 60 Co .
(B) The same patient after surgical removal of radionecrosis
Histological preparation from the surgically removed radionecrosis: extensive and largely scarred radionecrosis with fibrosis in muscle and fat tissue, as well as in the bones. The advanced dystrophic calcifications are the result of radiation-induced vasculopathy .

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

Removal of a radionecrosis in the area of ​​the right breast of a 65-year-old patient (see above)
(A) The surgical site. (B) Installation of two chest tubes after surgical removal of the radionecrosis. (C) and (D) reconstruction of the thoracic wall with a double-layer polypropylene mesh . (E) Mobilization and repositioning of an endogenous skin muscle flap (autologous transplantation of M. latissimus dorsi ) on the chest wall. (F) wound closure.

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

Individual evidence

  1. ↑ a b c d H. J. Schmoll, K. Höffken, K. Possinger: Compendium of internal oncology. 4th edition. Springer, 2006, ISBN 3-540-20657-4 , p. 570. ( limited preview in Google book search)
  2. ↑ J. Debus, A. Pirzkall et al .: Stereotactic one-time irradiation (radiosurgery). In: Strahlenther Onkol . Volume 175, 1999, pp. 47-56.
  3. ↑ a b c d e f P. Berlit: Radiation myelopathy. In: P. Berlit (Ed.): Clinical Neurology. 2nd Edition. Springer, 2006, ISBN 3-540-01982-0 , pp. 564-566. ( limited preview in Google Book search)
  4. ^ PJ Fitzgerald, RJ Koch: Delayed radionecrosis of the larynx. In: American journal of otolaryngology. Volume 20, No. 4, 1999 Jul-Aug, pp. 245-249, ISSN  0196-0709 . PMID 10442778 . (Review).
  5. ^ F. Bayrakli, A. Dinçer et al .: Late brain stem radionecrosis seventeen years after fractionated radiotherapy. In: Turkish neurosurgery. Volume 19, No. 2, April 2009, pp. 182-185, ISSN  1019-5149 . PMID 19431132 .
  6. ^ HP Schmitt: General pathology of the nervous system (APNS). ( Memento from December 17, 2012 in the web archive archive.today ) Ruprecht-Karls-Universität, Heidelberg, accessed on February 1, 2012.
  7. ^ W. Paulus, M. Hasselblatt: Tumors. In: G. Klöppel, HH Kreipe, W. Remmele (Ed.): Pathology: Neuropathology. 3rd edition. Springer, 2011, ISBN 978-3-642-02323-1 , p. 541. ( limited preview in Google book search)
  8. ↑ a b c d e f J. Linn, M. Wiesmann, H. Brückmann: Atlas Clinical Neuroradiology. Springer, 2011, ISBN 978-3-540-89568-8 , pp. 447-448. ( limited preview in Google Book search)
  9. ↑ A. Ziegler: Radiation accident. In: Emergency Medicine - Guide for Emergency Physicians. 3. Edition. 1998/99, ISBN 3-85175-734-3 .
  10. ↑ U. Weickhardt, J. Meier: The radiation accident - information sheet for the treatment of radiation injuries.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 1.2 MB) Status: July 2001, p. 10.@1@ 2Template: Dead Link / www.sapros.ch  
  11. ^ 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 .
  12. ↑ JL Daigle, JH Hong et al: The role of tumor necrosis factor signaling pathways in the response of murine brain to irradiation. In: Cancer Research . Volume 61, No. 24, December 2001, pp. 8859-8865, ISSN  0008-5472 . PMID 11751409 .
  13. ↑ a b J. C. Flickinger, MC Schell, DA Larson: Estimation of complications for linear accelerator radiosurgery with the integrated logistic formula. In: International journal of radiation oncology, biology, physics. Volume 19, No. 1, July 1990, pp. 143-148, ISSN  0360-3016 . PMID 2199419 .
  14. ↑ 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.
  15. ↑ BJ Blonigen, RD Steinmetz et al: Irradiated volume as a predictor of brain radionecrosis after linear accelerator stereotactic radiosurgery. In: International journal of radiation oncology, biology, physics. Volume 77, No. 4, July 2010, pp. 996-1001, ISSN  1879-355X . doi: 10.1016 / j.ijrobp.2009.06.006 . PMID 19783374 .
  16. ↑ 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.
  17. ^ G. Di Chiro, E. Oldfield et al.: Cerebral necrosis after radiotherapy and / or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies. In: American Journal of Roentgenology . Volume 150, No. 1, January 1988, pp. 189-197, ISSN  0361-803X . PMID 3257119 .
  18. ↑ U. Roelcke, KL Leenders: PET in clinical neuro-oncology. Oncologist. Volume 4, No. 7, 1998, pp. 595-598. doi: 10.1007 / s007610050242
  19. ^ A b M. J. Glantz, JM Hoffman et al.: Identification of early recurrence of primary central nervous system tumors by [18F] fluorodeoxyglucose positron emission tomography. In: Annals of Neurology . Vol. 29, No. 4, April 1991, pp. 347-355, ISSN  0364-5134 . doi: 10.1002 / ana.410290403 . PMID 1929205 .
  20. ^ A b G. Koch: Image morphological parameters of preoperative MR tomograms and survival time of patients with malignant gliomas. Dissertation, FU Berlin, 2007, p. 16.
  21. ^ A b D. Kahn, KA Follett, DL Bushnell, MA Nathan, JG Piper, M. Madsen, PT Kirchner: Diagnosis of recurrent brain tumor: value of 201Tl SPECT vs 18F-fluorodeoxyglucose PET. In: AJR. Volume 163, No. 6, December 1994, pp. 1459-1465, ISSN  0361-803X . PMID 7992747 .
  22. ↑ 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 .
  23. ↑ 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 .
  24. ^ 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 .
  25. ^ 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 .
  26. ↑ 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 .
  27. ^ 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).

Web links

Commons : Radionecrosis  - collection of images, videos and audio files