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Title: Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression

Abstract

Purpose: In many centers worldwide, radiotherapy for metastatic spinal cord compression (MSCC) is performed with 30 Gy in 10 fractions. This study investigated the potential benefit of dose escalation. Methods and Materials: Data from 922 patients with carcinomas causing MSCC were retrospectively evaluated. The outcome of 345 patients treated with 10 fractions of 3 Gy in 2 weeks was compared with the outcomes of 577 patients treated with 37.5 Gy in 15 fractions within 3 weeks or 40 Gy in 20 fractions within 4 weeks. Additionally, 10 potential prognostic factors were investigated: age, gender, performance status, tumor type, interval between cancer diagnosis and MSCC, number of involved vertebrae, other bone and visceral metastases, ambulatory status, and the interval to the development of motor deficits before radiotherapy. Results: Motor function improved in 19% of patients after 30 Gy in 10 fractions and in 22% after greater doses (p = 0.31). The local control (p = 0.28) and survival (p = 0.85) rates were not significantly different with doses >30 Gy. Better functional outcome was associated with the absence of visceral metastases, an interval between tumor diagnosis and MSCC of >12 months, ambulatory status, and an interval to the development of motormore » deficits of >7 days. Improved local control was significantly associated with no visceral metastases, improved survival with favorable histologic features (breast or prostate cancer), no visceral metastases, ambulatory status, an interval between cancer diagnosis and MSCC of >12 months, and an interval to the development of motor deficits of >7days. Conclusion: Escalation of the radiation dose to >30 Gy in 10 fractions did not improve the outcomes in terms of motor function, local control, or survival but did increase the treatment time for these frequently debilitated patients. Therefore, doses >30 Gy in 10 fractions are not recommended.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7]
  1. Department of Radiation Oncology, University Hospital Schleswig-Holstein, Luebeck (Germany) and Department of Radiation Oncology, University Hospital Hamburg-Eppendorf, Hamburg (Germany). E-mail: Rades.Dirk@gmx.net
  2. Department of Radiation Oncology, Hannover Medical School, Hannover (Germany)
  3. Mount Vernon Centre for Cancer Treatment, Northwood, Middlesex (United Kingdom)
  4. Department of Radiation Oncology, St. Josef Hospital, Ruhr University, Bochum (Germany)
  5. Department of Radiation Oncology, Dr. Bernard Verbeeten Institute, Tilburg (Netherlands)
  6. Department of Radiation Oncology, Mayo Clinic Scottsdale, Scottsdale, Arizona (United States)
  7. Department of Radiation Oncology, University Hospital Schleswig-Holstein, Luebeck (Germany)
Publication Date:
OSTI Identifier:
20944697
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2006.09.025; PII: S0360-3016(06)02994-4; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; DIAGNOSIS; MAMMARY GLANDS; METASTASES; PATIENTS; PROSTATE; RADIATION DOSES; RADIOTHERAPY; SPINAL CORD; VERTEBRAE

Citation Formats

Rades, Dirk, Karstens, Johann H., Hoskin, Peter J., Rudat, Volker, Veninga, Theo, Schild, Steven E., and Dunst, Juergen. Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.09.025.
Rades, Dirk, Karstens, Johann H., Hoskin, Peter J., Rudat, Volker, Veninga, Theo, Schild, Steven E., & Dunst, Juergen. Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression. United States. doi:10.1016/j.ijrobp.2006.09.025.
Rades, Dirk, Karstens, Johann H., Hoskin, Peter J., Rudat, Volker, Veninga, Theo, Schild, Steven E., and Dunst, Juergen. Thu . "Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression". United States. doi:10.1016/j.ijrobp.2006.09.025.
@article{osti_20944697,
title = {Escalation of radiation dose beyond 30 Gy in 10 fractions for metastatic spinal cord compression},
author = {Rades, Dirk and Karstens, Johann H. and Hoskin, Peter J. and Rudat, Volker and Veninga, Theo and Schild, Steven E. and Dunst, Juergen},
abstractNote = {Purpose: In many centers worldwide, radiotherapy for metastatic spinal cord compression (MSCC) is performed with 30 Gy in 10 fractions. This study investigated the potential benefit of dose escalation. Methods and Materials: Data from 922 patients with carcinomas causing MSCC were retrospectively evaluated. The outcome of 345 patients treated with 10 fractions of 3 Gy in 2 weeks was compared with the outcomes of 577 patients treated with 37.5 Gy in 15 fractions within 3 weeks or 40 Gy in 20 fractions within 4 weeks. Additionally, 10 potential prognostic factors were investigated: age, gender, performance status, tumor type, interval between cancer diagnosis and MSCC, number of involved vertebrae, other bone and visceral metastases, ambulatory status, and the interval to the development of motor deficits before radiotherapy. Results: Motor function improved in 19% of patients after 30 Gy in 10 fractions and in 22% after greater doses (p = 0.31). The local control (p = 0.28) and survival (p = 0.85) rates were not significantly different with doses >30 Gy. Better functional outcome was associated with the absence of visceral metastases, an interval between tumor diagnosis and MSCC of >12 months, ambulatory status, and an interval to the development of motor deficits of >7 days. Improved local control was significantly associated with no visceral metastases, improved survival with favorable histologic features (breast or prostate cancer), no visceral metastases, ambulatory status, an interval between cancer diagnosis and MSCC of >12 months, and an interval to the development of motor deficits of >7days. Conclusion: Escalation of the radiation dose to >30 Gy in 10 fractions did not improve the outcomes in terms of motor function, local control, or survival but did increase the treatment time for these frequently debilitated patients. Therefore, doses >30 Gy in 10 fractions are not recommended.},
doi = {10.1016/j.ijrobp.2006.09.025},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 67,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}
  • Purpose: Since life expectancy is markedly reduced in patients with metastatic spinal cord compression (MSCC), a short and effective radiation schedule is desired. This study investigates a reduction of the overall treatment time to only one day by comparing 1 x 8 Gy to the multi-fractionated 10 x 3 Gy for functional outcome. Methods and materials: Data of 204 patients, treated for MSCC with either 1 x 8 Gy (n = 96) or 10 x 3 Gy (n = 108), were analyzed retrospectively. Motor function and ambulatory status were evaluated before and up to 24 weeks after RT. A multivariatemore » analysis (nominal regression) was performed including radiation schedule, performance status, age, irradiated vertebra, and relevant prognostic factors (histology, ambulatory status, time of developing motor deficits). Improvement of motor deficits was selected as basic category and compared with no change and deterioration. Results: Univariate analysis showed no significant difference between the schedules for post-treatment motor function and ambulatory rates. Multivariate analysis demonstrated a significant effect on functional outcome for the prognostic factors, but not for the radiation schedule (p = 0.853 for no change, p = 0.237 for deterioration). Conclusions: Our data suggest the two fractionation schedules to be comparably effective for functional outcome. Thus, 1 x 8 Gy should be considered for patients with a poor survival prognosis.« less
  • Purpose: Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC) from relatively radioresistant tumors such as renal cell carcinoma, colorectal cancer, and malignant melanoma. However, the results of the 'standard' regimen 30 Gy/10 fractions need to be improved with respect to functional outcome. This study investigated whether a dose escalation beyond 30 Gy can improve treatment outcomes. Methods and Materials: A total of 91 patients receiving 30 Gy/10 fractions were retrospectively compared to 115 patients receiving higher doses (37.5 Gy/15 fractions, 40 Gy/20 fractions) for motor function and local control of MSCC. Ten further potential prognosticmore » factors were evaluated: age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, pretreatment ambulatory status, and time developing motor deficits before radiotherapy. Results: Motor function improved in 18% of patients after 30 Gy and in 22% after higher doses (p = 0.81). On multivariate analysis, functional outcome was associated with visceral metastases (p = 0.030), interval from tumor diagnosis to radiotherapy (p = 0.010), and time developing motor deficits (p < 0.001). The 1-year local control rates were 76% after 30 Gy and 80% after higher doses, respectively (p = 0.64). On multivariate analysis, local control was significantly associated with visceral metastases (p = 0.029) and number of involved vertebrae (p = 0.043). Conclusions: Given the limitations of a retrospective study, escalation of the radiation dose beyond 30 Gy/10 fractions did not significantly improve motor function and local control of MSCC in patients with relatively radioresistant tumors.« less
  • In assessing effectiveness of radiation therapy (RT) in metastatic spinal cord compression (MSCC), we performed a prospective trial in which patients with this complication were generally treated with RT plus steroids, and surgery was reserved for selected cases. Of the 209 evaluable cases, 110 were females and 99 males, and median age was 62 years. Median follow-up was 49 months (range, 13 to 88) and treatment consisted of 30 Gy RT (using two different schedules) together with steroids (standard or high doses, depending on motor deficit severity). Back pain total response rate was 82% (complete or partial response or stablemore » pain, 54, 17, or 11%, respectively). About three-fourths of the patients (76%) achieved full recovery or preservation of walking ability and 44% with sphincter dysfunction improved. Early diagnosis was the most important response predictor so that a large majority of patients able to walk and with good bladder function maintained these capacities. Duration of response was also influenced by histology. Median survival time was 6 months, with a 28% probability of survival for 1 year. Survival time was longer for patients able to walk before and/or after RT, those with favourable histologies, and females. There was agreement between patient survival and duration of response, systemic relapse of disease being generally the cause of death. Early diagnosis of MSCC was a powerful predictor of outcome. Primary tumor histology had weight only when patients were nonwalking, paraplegic, or had bladder dysfunction. The effectiveness of RT plus steroids in MSCC emerged in our trial. The most important factors positively conditioning our results were: the high rate of early diagnoses (52%) and the number of tumors with favorable histologies (124 out of 209, 63%) recruited, and the choice of best treatment based on appropriate patient selection for surgery and RT or RT alone. 30 refs., 5 figs., 7 tabs.« less
  • Purpose: This study compared single-fraction to multi-fraction short-course radiation therapy (RT) for symptomatic metastatic epidural spinal cord compression (MESCC) in patients with limited survival prognosis. Methods and Materials: A total of 121 patients who received 8 Gy × 1 fraction were matched (1:1) to 121 patients treated with 4 Gy × 5 fractions for 10 factors including age, sex, performance status, primary tumor type, number of involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, pre-RT ambulatory status, and time developing motor deficits prior to RT. Endpoints included in-field repeated RT (reRT) for MESCC, overall survival (OS), and impact of RT onmore » motor function. Univariate analyses were performed with the Kaplan-Meier method and log-rank test for in-field reRT for MESCC and OS and with the ordered-logit model for effect of RT on motor function. Results: Doses of 8 Gy × 1 fraction and 4 Gy × 5 fractions were not significantly different with respect to the need for in-field reRT for MESCC (P=.11) at 6 months (18% vs 9%, respectively) and 12 months (30% vs 22%, respectively). The RT regimen also had no significant impact on OS (P=.65) and post-RT motor function (P=.21). OS rates at 6 and 12 months were 24% and 9%, respectively, after 8 Gy × 1 fraction versus 25% and 13%, respectively, after 4 Gy × 5 fractions. Improvement of motor function was observed in 17% of patients after 8 Gy × 1 fraction and 23% after 4 Gy × 5 fractions, respectively. Conclusions: There were no significant differences with respect to need for in-field reRT for MESCC, OS, and motor function by dose fractionation regimen. Thus, 8 Gy × 1 fraction may be a reasonable option for patients with survival prognosis of a few months.« less
  • Purpose: To investigate the feasibility and effectiveness of reirradiation (re-RT) for in-field recurrence of metastatic spinal cord compression after primary RT with 1 x 8 Gy or 5 x 4 Gy. Methods and Materials: A total of 62 patients, treated with 1 x 8 Gy (n = 34) or 5 x 4 Gy (n = 28) between January 1995 and August 2003, received re-RT for in-field recurrence of metastatic spinal cord compression. The median time to recurrence was 6 months (range, 2-40 months). Re-RT was performed with 1 x 8 Gy (after 1 x 8 Gy or 5 x 4more » Gy, n = 34), 5 x 3 Gy (after 1 x 8 Gy or 5 x 4 Gy, n = 15), or 5 x 4 Gy (after 1 x 8 Gy, n = 13). The cumulative biologically effective dose (primary RT plus re-RT) was 80-100 Gy{sub 2}. The median follow-up after re-RT was 8 months (range, 2-42 months). Motor function was evaluated up to 6 months after re-RT. Results: After re-RT, 25 patients (40%) showed improvement of motor function, 28 (45%) had no change, and 9 (15%) had deterioration. Of the 16 previously nonambulatory patients, 6 (38%) regained the ability to walk. No second in-field recurrence in the same spinal region was observed after re-RT. The outcome was not significantly influenced by the radiation schedule. Radiation myelopathy was not observed. Conclusions: Spinal re-RT with 1 x 8 Gy, 5 x 3 Gy, or 5 x 4 Gy for in-field recurrence of metastatic spinal cord compression appears safe and effective. Myelopathy seems unlikely, if the cumulative biologically effective dose is {<=}100 Gy{sub 2}.« less