Access the full text.
Sign up today, get DeepDyve free for 14 days.
Loading next page...
/lp/springer-journals/toxicity-risk-of-non-target-organs-at-risk-receiving-low-dose-kieq0gi9w0
- Publisher
- Springer Journals
- Copyright
- Copyright © 2009 by Shueng et al; licensee BioMed Central Ltd.
- Subject
- Medicine & Public Health; Oncology; Radiotherapy
- eISSN
- 1748-717X
- DOI
- 10.1186/1748-717X-4-71
- pmid
- 20043839
- Publisher site
- See Article on Publisher Site
Abstract
The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8- T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off- targets and abscopal effects even with highly conformal radiotherapy. Background neously. The encouraging and safety results of patients Intensity-modulated radiotherapy (IMRT) is a powerful with various sites of malignancies in the thoracic region tool which enabled us to achieve desired dose to tumor treated by IMRT have been reported recently [1]. In addi- and reducing radiation doses to critical structures simulta- tion, Gong et al. reported conventionally-fractionated Page 1 of 5 (page number not for citation purposes) Radiation Oncology 2009, 4:71 http://www.ro-journal.com/content/4/1/71 image-guided intensity modulated radiotherapy (IG- ray revealed an osteolytic lesion in the convex posterior IMRT) is a safe and effective treatment for cancer spinal border of the L3 vertebra. Magnetic resonance imaging metastasis [2]. (MRI) of the spine demonstrated a pathologic compres- sion fracture with spinal canal stenosis of the thoracic (T) Helical tomotherapy (HT) is a new CT-based rotational 9 and L3 vertebrae. Abdominal ultrasound and abdomi- intensity modulated radiotherapy that can deliver highly nal computed tomography (CT) scan both revealed a conformal dose distributions with an ability to spare crit- tumor in the left lobe of the liver. A complete blood ical organs from radiation exposure [3]. HT is also effec- workup showed an elevated carcinoembryonic antigen tive and feasible for patients with multiple metastatic (CEA) level (33.9 ng/dl). An echo-guided biopsy of the diseases [4]. liver tumor was performed. Histopathologic examination of the biopsy specimen showed adenocarcinoma with Radiation recall phenomenon is characterized by an positive CK7 and CEA, findings compatible with primary inflammatory reaction within the previously treated radi- cholangiocarcinoma. The patient underwent a left lateral ation field during chemotherapy treatment [5]. In sectionectomy. The pathologic diagnosis was moderately humans, longer-range effects of radiotherapy occurring differentiated cholangiocarcinoma. Two weeks after the within or between tissues are referred to as abscopal, out- operation, HT with 30 Gy/10 fractions was delivered to of-field, or distant bystander responses [6]. T8-T10 for symptom relief [9]. The vertebral bodies of T8- T10 were delineated as the clinical target volume (CTV). A combination of gemcitabine, 5-fluorouracil (5-FU), and The planning target volume (PTV) was defined as the CTV leucovorin (LV) is effective in patients with unresectable plus a 3-mm margin for tumor motion and setup uncer- or metastatic biliary tract or gallbladder adenocarcinoma tainty. The contoured organs at risk (OARs), dose con- [7]. Gemcitabine chemotherapy, however, can cause radi- straints/penalty functions and planning parameters are ation recall followed by standard radiation therapy [8]. listed in Tables 1. The field width, pitch, and modulation factor (MF) used were 2.5 cm, 0.32, and 3.0, respectively. Herein, we present a case of radiation recall pneumonitis Two weeks after the radiotherapy had been completed, with simultaneous abscopal effects following highly con- the first course of gemcitabine, fluorouracil, and leucov- formal HT and gencitabine-based chemotherapy for met- orin was delivered. After two weeks of chemotherapy, astatic spine lesion in a patient with metastatic however, the patient developed progressive dyspnea. cholangiocarcinoma. Chest X-ray showed diffuse reticular interstitial processes in both lungs. Atypical infection was suspected. The Case presentation patient was transferred to the Medical Intensive Care Unit In August, 2008, a 55-year-old man presented to the neu- with intubation. The blood cultures, sputum cultures, and rosurgical outpatient department of with a 2-month his- fungus cultures were all negative. Bronchoscopy to inves- tory of progressive claudication. The lumbar (L) -spine X- tigate the pneumonitis was not performed at the request Table 1: The contoured organs at risk (OARs), dose constraints/penalty functions and planning parameters of plan was listed as below Tumor Importance Max Dose Max Dose DVH vol [%] DVH dose DVH dose Min Dose Constraint Penalty [Gy] [Gy] Penalty [Gy] PTV_T8- 50 30.00 800 95 30.00 30.00 100 T10_30Gy Sensitive Importance Max Dose Max Dose DVH vol [%] DVH dose DVH Point Structure Constraint Penalty [Gy] Penalty [Gy] Right lung 10 30.00 5 2 10.00 20 Left lung 10 30.00 5 1 15.00 20 Spinal cord 40 20.00 40 45 5.00 40 Heart 10 26.00 10 20 5.00 15 Spleen 5 7.00 5 10 2.00 5 Stomach 113.00 5 10 2.00 5 Ring* 1 30.00 50 3 28.00 20 Abbriviations: PTV = Planning target volume; Max = maximal; Min = minimal; DVH = dose-volume histogram; Vol = volume. *The ring was a dummy structure surrounded PTV with an outer margin 2.5 cm, and a gap of 2 mm from PTV. Page 2 of 5 (page number not for citation purposes) Radiation Oncology 2009, 4:71 http://www.ro-journal.com/content/4/1/71 of the patient's family. Follow-up chest CT revealed a dif- fuse irregular interlobular thickness and honeycombing of both lungs (Figure 1) indicative of chronic fibrotic change. The fibrotic change in both lungs in transverse view was compatible with low dose irradiation of non-tar- get OARs (Figure 2 and 3). Acute radiation pneumonitis was diagnosed. The following empirical antibiotics were administered: Pisutam (2.25 mg) (China Chemical & Pharmaceutical CO., LTD., Taiwan) 2 vial i.v.d. q8 h; Cravit (500 mg) (Sanofi-Aventis Deutschland GmbH, Germany) 750 mg i.v.d. qd; and Sevatrim (480 mg) (Swiss Pharmaceutical CO., LTD., Taiwan) 3 vial i.v.d. q12 h. Steroid therapy comprising methylprednisolone Chest computed tomogr MICU sh op ma bilatera Figure 2 acities and a rginal l lung fields ar ows interst eas, a diffuse ground-g irspia tial ce co pattern aphy (CT) post intuba nsolid lawith ati ss pattern on traction and fi , bleb forma br bronchiectasis, otion in the sis in th te ion in (40 mg), 20 mg iv. q8 h was administered for inflamma- Chest computed tomography (CT) post intubation in tory lung disease. The patient also received antioxidants the MICU shows interstitial pattern with traction and supportive treatment simultaneously. After one bronchiectasis, opacities and a diffuse ground-glass month in the intensive care unit, the patient stabilized pattern, bleb formation in marginal areas, airspace and was transferred to the hematology ward for further consolidation and fibrosis in the bilateral lung fields. care. The transverse views of chest CT. Discussion Radiation therapy (RT) is a common and safe treatment to relieve pain of symptomatic osseous metastases. In addi- astatic patients as multi-fractionated wide-field radiation tion, RT is reserved for palliation of prevention or treat- therapy (MF-WFRT) [10]. ment of spinal cord compression. Generally, RT focuses on limited area for symptom relief. However, RT also is Radiation pneumonitis in patients undergoing treatment safe and effective for multiple symptomatic osseous met- for lung cancer has been shown to be associated with a V20 > 20%, where V20 represents the percentage of lung volume receiving at least 20 Gy [11], and a mean lung dose > 13.6 Gy [12]. The V20 and mean lung dose in our patient were 1% and 2.7 Gy, respectively. Therefore, our plan was a safe protocol for palliative treatment of meta- static bone disease. Although the low dose around the irradiation target is usually overlooked, such as the V5 in the plan presented here (Figure 3) which was only 20%, it can potentially induce severe radiation toxicity (Figure 2). Chest comp MICU shows opacitie m bi Figure 1 lateral l arginal areas, s and a ung fi uted tomograp interstiti el di air ds ffs us pa e gro ce c al pattern with tra o uns nd- hy (C ol gid laati ss T) post intubation o pattern, bleb formation n and ction bronch fibrosis in th in th iectasis, e e in Chest computed tomography (CT) post intubation in the MICU shows interstitial pattern with traction bronchiectasis, opacities and a diffuse ground-glass The dose therapy Figure 3 distribution of radiotherapy designed for tomo- pattern, bleb formation in marginal areas, airspace The dose distribution of radiotherapy designed for consolidation and fibrosis in the bilateral lung fields. tomotherapy. The transverse view of low dose distribution The coronal views of chest CT. is compatible with the recall radiation pneumonitis area. Page 3 of 5 (page number not for citation purposes) Radiation Oncology 2009, 4:71 http://www.ro-journal.com/content/4/1/71 Although rare, gemcitabine can induce radiation recall found to be increased, reaching a maximum by 12 to 48 h reactions [13]. The time from gemcitabine administration after irradiation, followed by a gradual decrease over the to the manifestation of recall reaction ranges from 3 days 7-day time course [18]. Biomolecules known to be to 8 months [8]. Our patient suffered from severe pulmo- involved in bystander responses include interleukin 6 (Il- nary toxicity 2 weeks after gemcitabine administration. 6), Il-8, transforming growth factor-β1 (TGF-β1), and Radiographic findings characteristic of radiation-induced tumor necrosis factor-α (TNFα), reactive oxygen species pulmonary changes include ground-glass opacities with (ROS), and reactive nitrogen species [19]. Recently, the irregular linear opacity and interstitial thickening [14]. In correlation between TGF-β1 and developing radiation our patient, the opacities with ground-glass pattern and pneumonitis has been reported [20] and the observation bleb formation in the transverse views of chest CT (Figure could also partially response to the contribution of bio- 2) confined in the previous low dose non-target OAR field molecules on bystander responses. When distant (Figure 3) indicate radiation pneumonitis recalled by bystander responses to radiotherapy occur during cancer gemcitabine. The diffuse irregular interlobular thickness treatment that the potential lung injury could be hap- and honeycombing of both lungs in the chest CT (Figure pened. If subsequent treatment is radiation recall agents 1) are compatible with radiation-induced pulmonary that it could induce nearly fatal interstitial lung disease as changes, although no radiaiton was directed to these the case we present here. fields (Figure 4). The low dose irradiation to non-target OARs noted in this Khan et al.,[15] reported that when rat lung was partially patient is not unique to tomotherapy, rather it can occur irradiated, micronucleus formation was observed in non- with any technique that creates a relatively large low dose irradiated areas of the lung, indicating DNA damage at volume such as multifield IMRT, volumetric arc therapies these non-irradiated sites. In humans, abscopal events or stereotactic radiation therapy (SRT). For example, inho- such as bilateral pneumonitis have been observed in mogeneity corrections have a large influence on the dose humans after unilateral irradiation [16]. Additionally, a delivered to the PTV and OARs for SRT of lung tumors survival benefit of local control by simultaneous thoracic [21]. SRT allows for the minimization of normal tissue radiochemotherapy in the case of improved distant con- volume exposed to high radiation dose that is to mini- trol due to chemotherapy and prophylactic cranial irradi- mize toxicity while maximizing tumor control [22]. How- ation has been reported [17]. These long-range bystander ever, even in SRT, the large amount of low dose irradiation responses have also been studied in a lung reconstruction to non-target OARs, the incidence of lung toxicity can model in which levels of the phosphorylated histone var- become high has been reported by Yamashita et al. [23] iant γH2AX, a marker of double-strand break (DSBs), were Oncologists should be alert to the potential risk of low dose irradiation of non-target OARs when reviewing plans in the lung. It is important to review the low dose volumes and include the low dose volumes in the dose distribu- tion, especially if there is a plan to give chemotherapy. Also, in cases in which there is a chance of recall within the thorax, a static field Posterior-Anterior (PA) or AP/PA, or a three-dimensional conformal radiation therapy (3DCRT) approach with fewer beams and smaller irradi- ated volume may be preferred for palliative (or radical treatment) to avoid this problem. In addition, even with volumetric or helical arc therapy, strong penalty functions on the lung could reduce the volume of the lung receiving even low doses. Conclusion Non-target OARs can be impacted by arc therapy because of the low dose bath phenomenon. These effects can be magnified by agents known or unknown to be associated with recall effects. Optimization of planning should be considered in these situations. The th Figure 4 erapy dose distribution of radiotherapy designed for tomo- The dose distribution of radiotherapy designed for Consent tomotherapy. The coronal views of dose distribution. Written informed consent was obtained from the patient for publication of this case report and any accompanying Page 4 of 5 (page number not for citation purposes) Radiation Oncology 2009, 4:71 http://www.ro-journal.com/content/4/1/71 13. Friedlander PA, Bansal R, Schwartz L, Wagman R, Posner J, Kemeny images. A copy of the written consent is available for N: Gemcitabine-related radiation recall preferentially review by the Editor-in-Chief of this journal. involves internal tissue and organs. Cancer 2004, 100:1793-9. 14. Choi YW, Munden RF, Erasmus JJ, Park KJ, Chung WK, Jeon SC, Park CK: Effects of radiation therapy on the lung: radiologic Competing interests appearances and differential diagnosis. Radiographics 2004, The authors declare that they have no competing interests. 24:985-97. discussion 98 15. Khan MA, Hill RP, Van Dyk J: Partial volume rat lung irradiation: an evaluation of early DNA damage. Int J Radiat Oncol Biol Phys Authors' contributions 1998, 40:467-76. CH Hsieh and PW Shueng carried out all CT evaluations, 16. Morgan GW, Breit SN: Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. Int J Radiat study design, target delineations and interpretation of the Oncol Biol Phys 1995, 31:361-9. study. CH Hsieh drafted the manuscript. SC Lin and HT 17. Eckert F, Muller AC: SCLC extensive disease--treatment guid- Chang took care of patient. NS Chong participated in data ance by extent or/and biology of response? Radiat Oncol 2008, 3:33. of planning preparation. YJ Chen participated in manu- 18. Sedelnikova OA, Nakamura A, Kovalchuk O, Koturbash I, Mitchell script preparation. LY Wang and YP Hsieh gave advice on SA, Marino SA, Brenner DJ, Bonner WM: DNA double-strand breaks form in bystander cells after microbeam irradiation the work. All authors read and approved the final manu- of three-dimensional human tissue models. Cancer Res 2007, script. 67:4295-302. 19. Prise KM, O'Sullivan JM: Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 2009, 9:351-60. Acknowledgements 20. Kim JY, Kim YS, Kim YK, Park HJ, Kim SJ, Kang JH, Wang YP, Jang HS, The authors thank Hsing-Yi Lee M.S. for her assistance with radiation plan- Lee SN, Yoon SC: The TGF-beta1 dynamics during radiation ning and management of images. This study was supported by grants of Far therapy and its correlation to symptomatic radiation pneu- Eastern Memorial Hospital (FEMH-97-C-045), Taiwan. monitis in lung cancer patients. Radiat Oncol 2009, 4:59. 21. Schuring D, Hurkmans CW: Developing and evaluating stereo- tactic lung RT trials: what we should know about the influ- References ence of inhomogeneity corrections on dose. Radiat Oncol 2008, 1. Kataria T, Rawat S, Sinha SN, Garg C, Bhalla NK, Negi PS: Dose 3:21. reduction to normal tissues as compared to the gross tumor 22. Milano MT, Constine LS, Okunieff P: Normal tissue toxicity after by using intensity modulated radiotherapy in thoracic malig- small field hypofractionated stereotactic body radiation. nancies. Radiat Oncol 2006, 1:31. Radiat Oncol 2008, 3:36. 2. Gong Y, Wang J, Bai S, Jiang X, Xu F: Conventionally-fractionated 23. Yamashita H, Nakagawa K, Nakamura N, Koyanagi H, Tago M, Igaki image-guided intensity modulated radiotherapy (IG-IMRT): H, Shiraishi K, Sasano N, Ohtomo K: Exceptionally high incidence a safe and effective treatment for cancer spinal metastasis. of symptomatic grade 2-5 radiation pneumonitis after stere- Radiat Oncol 2008, 3:11. otactic radiation therapy for lung tumors. Radiat Oncol 2007, 3. Shueng PW, Lin SC, Chong NS, Lee HY, Tien HJ, Wu LJ, Chen CA, 2:21. Lee JJ, Hsieh CH: Total marrow irradiation with helical tomo- therapy for bone marrow transplantation of multiple mye- loma: first experience in Asia. Technol Cancer Res Treat 2009, 8:29-38. 4. Lee IJ, Seong J, Lee CG, Kim YB, Keum KC, Suh CO, Kim GE, Cho J: Early clinical experience and outcome of helical tomother- apy for multiple metastatic lesions. Int J Radiat Oncol Biol Phys 2009, 73:1517-24. 5. Schwarte S, Wagner K, Karstens JH, Bremer M: Radiation recall pneumonitis induced by gemcitabine. Strahlenther Onkol 2007, 183:215-7. 6. Kaminski JM, Shinohara E, Summers JB, Niermann KJ, Morimoto A, Brousal J: The controversial abscopal effect. Cancer Treat Rev 2005, 31:159-72. 7. Alberts SR, Al-Khatib H, Mahoney MR, Burgart L, Cera PJ, Flynn PJ, Finch TR, Levitt R, Windschitl HE, Knost JA, Tschetter LK: Gemcit- abine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treat- ment Group phase II trial. Cancer 2005, 103:111-8. 8. Jeter MD, Janne PA, Brooks S, Burstein HJ, Wen P, Fuchs CS, Loeffler JS, Devlin PM, Salgia R: Gemcitabine-induced radiation recall. Int J Radiat Oncol Biol Phys 2002, 53:394-400. Publish with Bio Med Central and every 9. Ben-Josef E, Shamsa F, Williams AO, Porter AT: Radiotherapeutic scientist can read your work free of charge management of osseous metastases: a survey of current pat- terns of care. Int J Radiat Oncol Biol Phys 1998, 40:915-21. "BioMed Central will be the most significant development for 10. Hayashi S, Hoshi H, Iida T, Kajiura Y: Multi-fractionated wide-field disseminating the results of biomedical researc h in our lifetime." radiation therapy for palliation of multiple symptomatic Sir Paul Nurse, Cancer Research UK bone metastases from solid tumors. Radiat Med 1999, 17:411-6. 11. Tsujino K, Hirota S, Endo M, Obayashi K, Kotani Y, Satouchi M, Kado Your research papers will be: T, Takada Y: Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after con- available free of charge to the entire biomedical community current chemoradiation for lung cancer. Int J Radiat Oncol Biol peer reviewed and published immediately upon acceptance Phys 2003, 55:110-5. 12. Belderbos JS, Heemsbergen WD, De Jaeger K, Baas P, Lebesque JV: cited in PubMed and archived on PubMed Central Final results of a Phase I/II dose escalation trial in non-small- yours — you keep the copyright cell lung cancer using three-dimensional conformal radio- therapy. Int J Radiat Oncol Biol Phys 2006, 66:126-34. BioMedcentral Submit your manuscript here: http://www.biomedcentral.com/info/publishing_adv.asp Page 5 of 5 (page number not for citation purposes)
Journal
Radiation Oncology – Springer Journals
Published: Dec 31, 2009