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Title: Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins

Abstract

Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p < 0.01), radiation dose >64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving >64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if {<=}64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (>50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were sitemore » (extremity vs. other), p < 0.01 and dose (>64 vs. {<=}64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. Conclusion: Local control is achieved in most PM STS patients undergoing RT. Doses >64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [4];  [4];  [7];  [3];  [4];  [8];  [8];  [3]
  1. Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States). E-mail: tdelaney@partners.org
  2. Department of Radiation Oncology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland)
  3. Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)
  4. Department of Orthopaedic Oncology, Department of Orthopaedics, Massachusetts General Hospital, Boston, MA (United States)
  5. Department of Orthopaedics, Beth Israel Deaconess Medical Center, Boston, MA (United States)
  6. Department of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Boston, MA (United States)
  7. Department of Hematology Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA (United States)
  8. Department of Pathology, Massachusetts General Hospital, Boston, MA (United States)
Publication Date:
OSTI Identifier:
20951592
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2006.11.035; PII: S0360-3016(06)03499-7; 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; FAILURES; MULTIVARIATE ANALYSIS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; REVIEWS; SARCOMAS; SURGERY

Citation Formats

DeLaney, Thomas F., Kepka, Lucyna, Goldberg, Saveli I., Hornicek, Francis J., Gebhardt, Mark C., Yoon, Sam S., Springfield, Dempsey S., Raskin, Kevin A., Harmon, David C., Kirsch, David G., Mankin, Henry J., Rosenberg, Andrew E., Nielsen, G. Petur, and Suit, Herman D.. Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.11.035.
DeLaney, Thomas F., Kepka, Lucyna, Goldberg, Saveli I., Hornicek, Francis J., Gebhardt, Mark C., Yoon, Sam S., Springfield, Dempsey S., Raskin, Kevin A., Harmon, David C., Kirsch, David G., Mankin, Henry J., Rosenberg, Andrew E., Nielsen, G. Petur, & Suit, Herman D.. Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins. United States. doi:10.1016/j.ijrobp.2006.11.035.
DeLaney, Thomas F., Kepka, Lucyna, Goldberg, Saveli I., Hornicek, Francis J., Gebhardt, Mark C., Yoon, Sam S., Springfield, Dempsey S., Raskin, Kevin A., Harmon, David C., Kirsch, David G., Mankin, Henry J., Rosenberg, Andrew E., Nielsen, G. Petur, and Suit, Herman D.. Sun . "Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins". United States. doi:10.1016/j.ijrobp.2006.11.035.
@article{osti_20951592,
title = {Radiation Therapy for Control of Soft-Tissue Sarcomas Resected With Positive Margins},
author = {DeLaney, Thomas F. and Kepka, Lucyna and Goldberg, Saveli I. and Hornicek, Francis J. and Gebhardt, Mark C. and Yoon, Sam S. and Springfield, Dempsey S. and Raskin, Kevin A. and Harmon, David C. and Kirsch, David G. and Mankin, Henry J. and Rosenberg, Andrew E. and Nielsen, G. Petur and Suit, Herman D.},
abstractNote = {Purpose: Positive margins (PM) remain after surgery in some soft-tissue sarcoma (STS) patients. We investigated the efficacy of radiation therapy (RT) in STS patients with PM. Methods and Materials: A retrospective chart review was performed on 154 patients with STS at various anatomic sites with PM, defined as tumor on ink, who underwent RT with curative intent between 1970 and 2001. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis of prognostic and treatment factors. Results: At 5 years, actuarial LC, DFS, and OS rates were: 76%, 46.7%, and 65.2%, respectively. LC was highest with extremity lesions (p < 0.01), radiation dose >64 Gy (p < 0.05), microscopically (vs. grossly visible) positive margin (p = 0.03), and superficial lesions (p = 0.05). Patients receiving >64 Gy had higher 5-year LC, DFS, and OS rates of 85%, 52.1%, and 67.8% vs. 66.1%, 41.8%, and 62.9% if {<=}64 Gy, p < 0.04. OS was worse in patients with G2/G3 tumors with local failure (LF), p < 0.001. Other known prognostic factors, including grade, stage, size, and age (>50), also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other), p < 0.01 and dose (>64 vs. {<=}64 Gy), p < 0.05; the best predictors for OS were size, p < 0.001, gross vs. microscopic PM, p < 0.05, and LF, p < 0.01. Conclusion: Local control is achieved in most PM STS patients undergoing RT. Doses >64 Gy, superficial location, and extremity site are associated with improved LC. OS is worse in patients with tumors with lesions >5 cm, grossly positive margins, and after local failure.},
doi = {10.1016/j.ijrobp.2006.11.035},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 67,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}
  • Purpose: To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. Methods and Materials: From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). Results: The median patient age was 67 years (range 18-87). The median planning targetmore » volume (PTV) was 455 cm{sup 3} (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm{sup 3} were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm{sup 3} were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). Conclusions: Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a longer follow-up period is needed to confirm these results.« less
  • Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with themore » largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.« less
  • Between May 1975 and April 1981, 43 adult patients with high-grade soft tissue sarcomas of the extremities were prospectively randomized to receive either amputation at or above the joint proximal to the tumor, including all involved muscle groups, or to receive a limb-sparing resection plus adjuvant radiation therapy. The limb-sparing resection group received wide local excision followed by 5000 rads to the entire anatomic area at risk for local spread and 6000 to 7000 rads to the tumor bed. Both randomization groups received postoperative chemotherapy with doxorubicin (maximum cumulative dose 550 mg/m/sup 2/), cyclophosphamide, and high-dose methotrexate. Twenty-seven patients randomizedmore » to receive limb-sparing resection and radiotherapy, and 16 received amputation (randomization was 2:1). There were four local recurrences in the limb-sparing group and none in the amputation group (p/sub 1/ = 0.06 generalized Wilcoxon test). However, there were no differences in disease-free survival rates (83% and 88% at five years; p/sub 2/ = 0.99) between the limb-sparing group and the amputation treatment groups. Multivariate analysis indicated that the only correlate of local recurrence was the final margin of resection. Patients with positive margins of resection had a higher likelihood of local recurrence compared with those with negative margins (p/sub 1/ < 0.00001) even when postoperative radiotherapy was used. A simultaneous prospective randomized study of postoperative chemotherapy in 65 patients with high-grade soft-tissue sarcomas of the extremities revealed a marked advantage in patients receiving chemotherapy compared with those without chemotherapy in three-year continuous disease-free (92% vs. 60%; p/sub 1/ = 0.00008) and overall survival (95% vs. 74%; p/sub 1/ = 0.04).« less
  • We have formulated certain techniques for soft tissue sarcomas of the extremities in adults, based on the experience of treating 75 patients at the National Cancer Institute. Attaining a high likelihood of tumor control is heavily dependent on a variety of factors. These factors include a knowledge of the biological characteristics of the tumor, of the normal tissue anatomy and its relationship to the tumor and of the surgical techniques available and the details of the surgery already performed. Obtaining good long term function in the irradiated extremity is dependent on sparing a strip of soft tissue and using sophisticatedmore » radiation therapy techniques. These techniques include casting of the extremity for immobilization, using a variety of gantry and collimator angulations, using treatment planning for determining the necessity for wedges or compensating filters in the radiation field and utilizing secondary collimation. With this highly individualized approach to treatment of patients with soft tissue sarcomas, optimal results can be obtained.« less
  • Between 1971 and 1982, 23 patients have been treated with radiation therpy at the Massachusetts General Hospital(MGH) for retroperitoneal soft tissue sarcomas. Seventeen patients were treated with curative intent and six with palliative intent. Of the patients treated with curative intent, the 5 year actuarial survivial rate was 54% and the 5 year actuarial local control rate was also 54%. With a complete surgical resection local tumor control was obtained in 5 of 7 patients (71%), 4 of 7 (57%) with incomplete resection and 1/3 (33%) with no resection having local control. The radiation dose appeared to influence tumor controlmore » with 2 of 6 patients (33%) having local control with less than 5,000 cGY compared to 0 of 5 patients with doses of 5,000 to 6,000 cGy and 5 of 6 (83%) with doses greater than 6,000 cGy. An effect of tumor grade on either local control or on rate of metastasis formation could not be demonstrated in this series. Long-term local control and survival appears to be associated with maximal surgical resection and high dose radiation therapy.« less