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Radiation Therapy for Palliation of Sarcoma Metastases: A Unique and Uniform Hypofractionation Experience

Radiation Therapy for Palliation of Sarcoma Metastases: A Unique and Uniform Hypofractionation... Hindawi Publishing Corporation Sarcoma Volume 2010, Article ID 927972, 4 pages doi:10.1155/2010/927972 Clinical Study Radiation Therapy for Palliation of Sarcoma Metastases: A Unique and Uniform Hypofractionation Experience 1, 2 1, 2 2, 3 1, 2 Viacheslav Soyfer, Benjamin W. Corn, Yehuda Kollender, Haim Tempelhoff, 2, 3 2, 4 Isaac Meller, and Ofer Merimsky Division of Oncology, Institute of Radiation Therapy, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel National Unit of Orthopedic Oncology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel Correspondence should be addressed to Viacheslav Soyfer, slavas2506@yahoo.com Received 13 October 2009; Revised 18 January 2010; Accepted 10 February 2010 Academic Editor: Martin Robinson Copyright © 2010 Viacheslav Soyfer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma 1. Introduction Locally recurrent or metastatic disease may be palliated by systemic chemotherapy, surgery, and RT. Amputation has Soft tissue sarcomas (STS) of the extremities in young or been advocated as a palliative procedure for symptomatic good-performance-status patients are currently approached locally advanced disease that has already failed to respond by limb sparing surgery (LSS) followed by radiation therapy to radiation therapy, chemotherapy, and limited surgery [7]. (RT) [1]. We have previously reported a series of 133 adult RT is our preferred modality for local palliation of metastatic patients with intermediate or high-grade limb STS who were disease, irrespective of whether systemic chemotherapy is approached by LSS + RT [2]. Alongwithothers,wehave employed. While a protracted course of RT may be given previously demonstrated that a schedule of 1.8 Gy/fraction, as postoperative adjuvant treatment, a short and intense 5 fractions per week to a midplane dose of 63 Gy, or 70 Gy course of RT is usually needed for rapid palliation and in the setting of marginal excision or involved margins, was local control of metastatic disease. Our impression was that feasible, tolerable and efficient [2]. Locally advanced cases, the commonly applied RT doses for palliation of other involving the neurovascular bundle or the underlying bone, malignancies were not adequate for palliation of sarcoma may be treated with surgery following induction chemother- metastases. Many patients required reirradiation of lesions apy [3] or isolated limb perfusion with tumor-necrosis- (unpublished data). In this paper we report a feasibility study factor-α [4], or by definitive RT [5]orbyamputation[6]. of 39 Gy administered in 13 fractions of 3 Gy each, over 13 2 Sarcoma Kaplan-Meier PL survivorship function working days (five days per week), in a group of patients with metastatic sarcoma. 0.75 2. Materials and Methods 0.5 2.1. Patients. Seventeen patients, 8 women and 9 men, at a median age of 61 years (range 53–95 years) had symptomatic 0.25 metastatic sarcoma, and required rapid palliation. The types of sarcoma included liposarcoma (5 patients), pleomorphic sarcoma (3), chondrosarcoma (2), synovial sarcoma (1), 0 bone sarcoma (1 Ewing sarcoma of pelvis, 1 leiomyosarcoma 0 200 400 600 800 of bone), leiomyosarcoma (2), and unclassified sarcoma (2). Survival time In total there were 20 sites of involvement by metastatic Time variable: survival Event variable: status disease: trunk (chest wall, groin, axilla)—13 cases, limb- 7 cases. The symptoms related to the metastases were either Figure 1 pain or discomfort in all the patients. In 15 cases the RT was the only modality for local palliation and in 5 cases RT was given following metastasectomy with close or involved other cases within a period of two to nine months. Among margins. the 5 lesions which were irradiated post-metastasectomy, no local recurrence was observed. 2.2. Radiation Therapy. All patients underwent CT simu- All patients were invited back for follow-up visits to lation (Phillips Brilliance Big Bore). The positioning and the multidisciplinary sarcoma clinic on a quarterly basis immobilization of patients was individualized as a function where physical exam and review of imaging was performed of tumor location. Beams were designed to achieve coverage (including RECIST criteria) (15). By evaluating tumor of the clinical treatment volume (CTV). CTV included the response in this manner we were able to determine time to gross tumor volume (GTV), that in cases of palliation mostly local progression. included the viable and visible tumor with margins of 1.5– Fourteen patients were alive at the end of the observation 2 cm, and in cases of postmetastasectomy treatment after period (Kaplan-Meir analysis—Figure 1 ). wide or marginal resections, included the tumor in it’s location before the surgery. In those cases the CTV was 4. Discussion based on the preoperative CT scan or MRI and clips which surgeons placed at the tumor bed and its edges. Special Sarcomas are usually considered, at best, moderately radio attention in postoperative cases was devoted to the linear responsive tumors. RT doses at range of 60–70 Gy are usually borders of the fields so as to be at least 4 to 5 cm beyond needed to be delivered in order to eradicate microscopic the edges of tumor bed. Treatment planning was carried disease, while doses of 50 Gy can yield similar results for out with the XiO system (CMS Corporation: St. Louis, other malignancies such as breast or rectal cancer. One of the MO, USA) and was according to requirements of ICRU-50. biological characteristics of sarcoma cells is their relatively Before the start of treatment each patient had verification low (−0.5–5.4) α-β ratio [8]. This ratio, theoretically, may of portals (Elekta I-View GT- IVIEW02). The radiation justify the use of larger-than-standard fractionation in order was provided by ELEKTA linacs (Stockholm, Sweden) with to achieve significant cell-kill by RT. We used a popular for- energies of 6 or 18 MV. Patients were assessed for side mula for standardization of different fractionation regimens: effects and compliance with treatment on a weekly basis BED = ND × (1 +D/α-β ratio), when BED is dose equivalent during therapy, at the end of treatment, and every 3 months to standard fractionation of 1.8–2 Gy, N is the number of thereafter. All patients were treated by a short and intensive fractions, and D is the given fraction dose [8]. To achieve the course of administration; 39 Gy were given in 13 fractions dose equivalent to 60–70 Gy we decided to use 13 fractions of 3 Gy/day, 5 times a week. This fractionation regimen was of mildly elevated daily dose of 3 Gy. Assuming the alpha- selected to achieve a meaningful dose based on α-β modeling beta ratio of Sarcoma cells as 4 our calculation of BED is as (vide infra). following: 13 × 3 (1+ 3/4) = 68 Gy. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for 3. Results palliation of musculoskeletal metastases from sarcoma. The The median follow-up period was 25 weeks (range: 12– chosen fractionation regime appears to achieve adequate 89 weeks). Thirteen fractions were given over 13–16 days. local and symptom control in the majority of patients during Thetreatment waswelltolerated.Acute side effects included the short to medium term. While a protracted course of grade 1 skin reaction (faint erythema as per CTC Version RT is applied for post-operative adjuvant RT as part of LSS 2.0) (16) in all cases. No wound complications were noted. approach, a short and intense course may be needed for Durablepaincontrol wasachievedin12out 15 casestreated local control and palliation. In the presence of metastatic for gross metastases. Tumor progression was seen in the 3 disease, especially when the expected survival is limited, it Survivorship S(t) Sarcoma 3 Table 1: Patient Characteristics. Pt Age Sex Site Pathology Indication of Treatment DDD TTLP TTDP 1 53 F Chest LMC Adjuvant to surgery 13 61 2 78 F Thigh Pleomorphic Adjuvant to surgery 13 3 65 M Groin HGSTS Palliation 13 4 71 M Pelvis Myxoid Chondrosarcoma Palliation 13 266 5 86 F Calf Chondrosarcoma Palliation 13 6 68 F Pelvis MFH Palliation 13 413 7 41 M Chest and thigh SS Palliation 13 196 247 8 59 F Thigh Bone LMS Palliation 16 56 9 44 M Chest HGSTS Palliation 13 180 10 49 M Thigh MFH Adjuvant to surgery 15 48 11 51 F Foot HGSTS Palliation 14 12 50 M Pelvis LMS Palliation 13 13 60 M Groin LMS Adjuvant to surgery 13 90 14 27 M Pelvis Ewing Palliation 13 5 15 51 F Chest LMS Palliation 13 12 12 16 80 F Calf, groin, axilla HGSTS Palliation 13 17 95 M Thigh LMS Adjuvant to surgery 13 270 Key:Pt: Patient; F: Female; M: Male; LMS: Leiomyosarcoma; HGSTS: High Grade Soft Tissue Sarcoma; MFH: Malignant Fibro Hystiocytoma; SS: Synovial Sarcoma; DDD: Duration of dose delivery; TTLP: time to local progression; TTDM: time to distant progression (the latter 3 parameters all measured in days). is important to deliver the RT over a short period, and was 50% (one complete response) with minimal side effects. avoid the inconvenience associated with a multifractionated The median time to progression was 155 days and the median regimen of radiotherapy. This issue may be particularly true survival time was 309 days [13]. for elderly and debilitated patients, in whom a short course A potential use of hypofractionated RT is in elderly or of RT may be the only practical option for a local palliation. debilitated population with STS. Patients with sarcoma of the All the patients received the RT during an acceptable period extremity who have a good performance status may easily of time, and well tolerated the therapy. tolerate a protracted course of adjuvant RT following LSS, Hypofractionation as a part of neoadjuvant chemo- even if induction chemotherapy or tumor-necrosis factor radiotherapy for STS was popularized by Eilber et al. [3], via isolated limb perfusion had been primarily administered who applied a regimen of 10 fractions of 3.5 Gy each. [2]. However, patients with low-performance status or with The rationale was based on the observation that irradiated multiple comorbidities and mobility difficulties may be melanoma cell lines had a large initial shoulder on their deemed medically unfit for the regimen proposed herein. survival curve. The potential radio resistance of melanoma While advanced age in the presence of a good performance and, by extension, sarcoma, was attributed to tumor cell status is not a limiting factor in the treatment strategy for STS capacity for sublethal damage repair, as implied by this (LSS and RT) [2], or in other diseases (e.g., non-Hodgkin’s shoulder [9]. lymphoma [2] and lung cancer [14]), a patient with sarcoma The histological response of dose intense chemotherapy and poor performance status or severe co-morbidities, might with preoperative hypofractionated radiotherapy in patients not be able to attend a long course of RT (5 times a week with STS was further investigated by Ryan et al. [10]. for a total of 6–8 weeks), and might even initially give They reported ahighrateofpathologicaltumor necrosis up the important postoperative treatment. Furthermore, a (95%) following an aggressive chemoradiotherapy regimen prolonged hospitalization for RT may result in unnecessary of 28 Gy administration in 8 fractions [10]. Other authors hospital-acquired infections and social problems due to a also justified an aggressive approach to palliate distant change in the patient’s close surroundings. Omitting RT in an metastases; a wide local resection of the disseminated disease LSS-approached patient increases the risk of local recurrence foci followed by adjuvant radiation therapy [11, 12]. Kepka [1]. As an alternative to LSS without RT, amputation surgery et al. [5] described the results of radiation therapy as a sole may be suggested, hampering the quality of life even more, treatment of gross disease in 112 patients [5]. Patients who and rendering the patient bed-ridden for the rest of his life. A received more than 63 Gy in standard fractionation of 1.8– short and intense course of RT may be a logical and adequate 2 Gy achieved best local control, disease free interval, and solution to this dilemma. overall survival rate. The results reported offer encouraging data that can An animal model of a hypofractionation regimen for be applied to patients suffering from this daunting disease. macroscopic soft tissue sarcomas was created and reported by Prospective studies could assess the role of hypofractionation Lawrence et al. [13]. Four fractions of 8 Gy were prescribed to and other palliative strategies among debilitated or elderly 16 dogs with overt masses of STS. The overall response rate patients with STS. 4 Sarcoma References [1] S. A. Rosenberg, J. Tepper, E. Glatstein, et al., “The treat- ment of soft-tissue sarcomas of the extremities. Prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy,” Annals of Surgery, vol. 196, pp. 305–315, 1982. [2] O. Merimsky, V. Soyfer, F. Kovner, et al., “Limb sparing approach: adjuvant radiation therapy in adults with interme- diate or high-grade limb soft tissue sarcoma,” Radiotherapy and Oncology, vol. 77, pp. 295–300, 2005. [3] F. C. Eilber, G. Rosen, J. Eckardt, et al., “Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high- grade extremity soft tissue sarcomas,” Journal of Clinical Oncology, vol. 19, pp. 3203–3209, 2001. [4] I. Nachmany, A. Subhi, I. Meller, et al., “Efficacy of high vs low dose TNF-isolated limb perfusion for locally advanced soft tissue sarcoma,” European Journal of Surgical Oncology, vol. 35, no. 2, pp. 209–214, 2009. [5] L.Kepka,T.F.DeLaney,H.D.Suit,and S. I. Goldberg,“Results of radiation therapy for unresected soft-tissue sarcomas,” International Journal of Radiation Oncology Biology Physics, vol. 63, pp. 852–859, 2005. [6] O. Merimsky, Y. Kollender, M. Inbar, et al., “Is forequarter amputation justified for palliation of intractable cancer symp- toms?” Oncology, vol. 60, pp. 55–59, 2001. [7] O. Merimsky, Y. Kollender, M. Inbar, et al., “Palliative major amputation and quality of life in cancer patients,” Acta Oncologica, vol. 36, pp. 151–157, 1997. [8] L. L. Gunderson and J. E. Tepper, Clinical Radiation Oncology, Churchill Livingstone, London, UK, 2007. [9] P. W. Pisters, “Preoperative multimodality treatment of localized soft tissue sarcoma: addition through subtraction?” Annals of Surgical Oncology, vol. 12, pp. 583–586, 2005. [10] C. W. Ryan, A. G. Montag, J. R. Hosenpud, et al., “Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas,” Cancer, vol. 112, pp. 2432–2439, 2008. [11] D. Lev-Chelouche, R. Nakache, D. Soffer, et al., “Metastases to the retroperitoneum in patients with extremity soft tissue sarcoma: an unusual metastatic pattern,” Cancer, vol. 88, pp. 364–368, 2000. [12] X. Shi, S. Matsumoto, J. Manbe, et al., “Long-term survival of soft tissue sarcoma patients with extrapulmonary metastasis,” Journal of Orthopaedic Science, vol. 11, pp. 92–96, 2006. [13] J. Lawrence,L.Forrest,W.Adams,etal., “Four-fraction radiation therapy for macroscopic soft tissue sarcomas in 16 dogs,” Journal of the American Animal Hospital Association, vol. 44, no. 3, pp. 100–108, 2008. [14] A. G. Pallis, A. Polyzos, I. Boukovinas, et al., “Pooled analysis of elderly patients with non-small cell lung cancer treated with front line docetaxel/gemcitabine regimen: the hellenic oncology research group experience,” Journal of Thoracic Oncology, vol. 3, pp. 505–510, 2008. 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Radiation Therapy for Palliation of Sarcoma Metastases: A Unique and Uniform Hypofractionation Experience

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Copyright © 2010 Viacheslav Soyfer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Publishing Corporation Sarcoma Volume 2010, Article ID 927972, 4 pages doi:10.1155/2010/927972 Clinical Study Radiation Therapy for Palliation of Sarcoma Metastases: A Unique and Uniform Hypofractionation Experience 1, 2 1, 2 2, 3 1, 2 Viacheslav Soyfer, Benjamin W. Corn, Yehuda Kollender, Haim Tempelhoff, 2, 3 2, 4 Isaac Meller, and Ofer Merimsky Division of Oncology, Institute of Radiation Therapy, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel National Unit of Orthopedic Oncology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel-Aviv 64239, Israel Correspondence should be addressed to Viacheslav Soyfer, slavas2506@yahoo.com Received 13 October 2009; Revised 18 January 2010; Accepted 10 February 2010 Academic Editor: Martin Robinson Copyright © 2010 Viacheslav Soyfer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Radiotherapy (RT) is our preferred modality for local palliation of metastatic soft tissue sarcoma (STS). A short and intense course of RT is usually needed for rapid palliation and local control of metastatic disease. Seventeen patients at a median age of 61 had symptomatic metastatic sarcoma and required rapid palliation. The symptoms related to the metastases were either pain or discomfort. All patients were treated by a short and intensive course of administration: 39 Gy were given in 13 fractions of 3 Gy/day, 5 times a week. Median follow-up period was 25 weeks. The treatment was well tolerated. Acute side effects included grade one skin toxicity. No wound complications were noted among those undergoing surgery. Late side effects included skin pigmentation and induration of irradiated soft tissues. Durable pain control was achieved in 12 out 15 cases treated for gross metastases. Tumor progression was seen in the 3 other cases within a period of two to nine months. Among 5 lesions which were irradiated as an adjunctive treatment following resection, no local recurrence was observed. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for palliation of musculoskeletal metastases from sarcoma 1. Introduction Locally recurrent or metastatic disease may be palliated by systemic chemotherapy, surgery, and RT. Amputation has Soft tissue sarcomas (STS) of the extremities in young or been advocated as a palliative procedure for symptomatic good-performance-status patients are currently approached locally advanced disease that has already failed to respond by limb sparing surgery (LSS) followed by radiation therapy to radiation therapy, chemotherapy, and limited surgery [7]. (RT) [1]. We have previously reported a series of 133 adult RT is our preferred modality for local palliation of metastatic patients with intermediate or high-grade limb STS who were disease, irrespective of whether systemic chemotherapy is approached by LSS + RT [2]. Alongwithothers,wehave employed. While a protracted course of RT may be given previously demonstrated that a schedule of 1.8 Gy/fraction, as postoperative adjuvant treatment, a short and intense 5 fractions per week to a midplane dose of 63 Gy, or 70 Gy course of RT is usually needed for rapid palliation and in the setting of marginal excision or involved margins, was local control of metastatic disease. Our impression was that feasible, tolerable and efficient [2]. Locally advanced cases, the commonly applied RT doses for palliation of other involving the neurovascular bundle or the underlying bone, malignancies were not adequate for palliation of sarcoma may be treated with surgery following induction chemother- metastases. Many patients required reirradiation of lesions apy [3] or isolated limb perfusion with tumor-necrosis- (unpublished data). In this paper we report a feasibility study factor-α [4], or by definitive RT [5]orbyamputation[6]. of 39 Gy administered in 13 fractions of 3 Gy each, over 13 2 Sarcoma Kaplan-Meier PL survivorship function working days (five days per week), in a group of patients with metastatic sarcoma. 0.75 2. Materials and Methods 0.5 2.1. Patients. Seventeen patients, 8 women and 9 men, at a median age of 61 years (range 53–95 years) had symptomatic 0.25 metastatic sarcoma, and required rapid palliation. The types of sarcoma included liposarcoma (5 patients), pleomorphic sarcoma (3), chondrosarcoma (2), synovial sarcoma (1), 0 bone sarcoma (1 Ewing sarcoma of pelvis, 1 leiomyosarcoma 0 200 400 600 800 of bone), leiomyosarcoma (2), and unclassified sarcoma (2). Survival time In total there were 20 sites of involvement by metastatic Time variable: survival Event variable: status disease: trunk (chest wall, groin, axilla)—13 cases, limb- 7 cases. The symptoms related to the metastases were either Figure 1 pain or discomfort in all the patients. In 15 cases the RT was the only modality for local palliation and in 5 cases RT was given following metastasectomy with close or involved other cases within a period of two to nine months. Among margins. the 5 lesions which were irradiated post-metastasectomy, no local recurrence was observed. 2.2. Radiation Therapy. All patients underwent CT simu- All patients were invited back for follow-up visits to lation (Phillips Brilliance Big Bore). The positioning and the multidisciplinary sarcoma clinic on a quarterly basis immobilization of patients was individualized as a function where physical exam and review of imaging was performed of tumor location. Beams were designed to achieve coverage (including RECIST criteria) (15). By evaluating tumor of the clinical treatment volume (CTV). CTV included the response in this manner we were able to determine time to gross tumor volume (GTV), that in cases of palliation mostly local progression. included the viable and visible tumor with margins of 1.5– Fourteen patients were alive at the end of the observation 2 cm, and in cases of postmetastasectomy treatment after period (Kaplan-Meir analysis—Figure 1 ). wide or marginal resections, included the tumor in it’s location before the surgery. In those cases the CTV was 4. Discussion based on the preoperative CT scan or MRI and clips which surgeons placed at the tumor bed and its edges. Special Sarcomas are usually considered, at best, moderately radio attention in postoperative cases was devoted to the linear responsive tumors. RT doses at range of 60–70 Gy are usually borders of the fields so as to be at least 4 to 5 cm beyond needed to be delivered in order to eradicate microscopic the edges of tumor bed. Treatment planning was carried disease, while doses of 50 Gy can yield similar results for out with the XiO system (CMS Corporation: St. Louis, other malignancies such as breast or rectal cancer. One of the MO, USA) and was according to requirements of ICRU-50. biological characteristics of sarcoma cells is their relatively Before the start of treatment each patient had verification low (−0.5–5.4) α-β ratio [8]. This ratio, theoretically, may of portals (Elekta I-View GT- IVIEW02). The radiation justify the use of larger-than-standard fractionation in order was provided by ELEKTA linacs (Stockholm, Sweden) with to achieve significant cell-kill by RT. We used a popular for- energies of 6 or 18 MV. Patients were assessed for side mula for standardization of different fractionation regimens: effects and compliance with treatment on a weekly basis BED = ND × (1 +D/α-β ratio), when BED is dose equivalent during therapy, at the end of treatment, and every 3 months to standard fractionation of 1.8–2 Gy, N is the number of thereafter. All patients were treated by a short and intensive fractions, and D is the given fraction dose [8]. To achieve the course of administration; 39 Gy were given in 13 fractions dose equivalent to 60–70 Gy we decided to use 13 fractions of 3 Gy/day, 5 times a week. This fractionation regimen was of mildly elevated daily dose of 3 Gy. Assuming the alpha- selected to achieve a meaningful dose based on α-β modeling beta ratio of Sarcoma cells as 4 our calculation of BED is as (vide infra). following: 13 × 3 (1+ 3/4) = 68 Gy. The results of this series, although limited in size, point to the safety and feasibility of hypofractionated RT for 3. Results palliation of musculoskeletal metastases from sarcoma. The The median follow-up period was 25 weeks (range: 12– chosen fractionation regime appears to achieve adequate 89 weeks). Thirteen fractions were given over 13–16 days. local and symptom control in the majority of patients during Thetreatment waswelltolerated.Acute side effects included the short to medium term. While a protracted course of grade 1 skin reaction (faint erythema as per CTC Version RT is applied for post-operative adjuvant RT as part of LSS 2.0) (16) in all cases. No wound complications were noted. approach, a short and intense course may be needed for Durablepaincontrol wasachievedin12out 15 casestreated local control and palliation. In the presence of metastatic for gross metastases. Tumor progression was seen in the 3 disease, especially when the expected survival is limited, it Survivorship S(t) Sarcoma 3 Table 1: Patient Characteristics. Pt Age Sex Site Pathology Indication of Treatment DDD TTLP TTDP 1 53 F Chest LMC Adjuvant to surgery 13 61 2 78 F Thigh Pleomorphic Adjuvant to surgery 13 3 65 M Groin HGSTS Palliation 13 4 71 M Pelvis Myxoid Chondrosarcoma Palliation 13 266 5 86 F Calf Chondrosarcoma Palliation 13 6 68 F Pelvis MFH Palliation 13 413 7 41 M Chest and thigh SS Palliation 13 196 247 8 59 F Thigh Bone LMS Palliation 16 56 9 44 M Chest HGSTS Palliation 13 180 10 49 M Thigh MFH Adjuvant to surgery 15 48 11 51 F Foot HGSTS Palliation 14 12 50 M Pelvis LMS Palliation 13 13 60 M Groin LMS Adjuvant to surgery 13 90 14 27 M Pelvis Ewing Palliation 13 5 15 51 F Chest LMS Palliation 13 12 12 16 80 F Calf, groin, axilla HGSTS Palliation 13 17 95 M Thigh LMS Adjuvant to surgery 13 270 Key:Pt: Patient; F: Female; M: Male; LMS: Leiomyosarcoma; HGSTS: High Grade Soft Tissue Sarcoma; MFH: Malignant Fibro Hystiocytoma; SS: Synovial Sarcoma; DDD: Duration of dose delivery; TTLP: time to local progression; TTDM: time to distant progression (the latter 3 parameters all measured in days). is important to deliver the RT over a short period, and was 50% (one complete response) with minimal side effects. avoid the inconvenience associated with a multifractionated The median time to progression was 155 days and the median regimen of radiotherapy. This issue may be particularly true survival time was 309 days [13]. for elderly and debilitated patients, in whom a short course A potential use of hypofractionated RT is in elderly or of RT may be the only practical option for a local palliation. debilitated population with STS. Patients with sarcoma of the All the patients received the RT during an acceptable period extremity who have a good performance status may easily of time, and well tolerated the therapy. tolerate a protracted course of adjuvant RT following LSS, Hypofractionation as a part of neoadjuvant chemo- even if induction chemotherapy or tumor-necrosis factor radiotherapy for STS was popularized by Eilber et al. [3], via isolated limb perfusion had been primarily administered who applied a regimen of 10 fractions of 3.5 Gy each. [2]. However, patients with low-performance status or with The rationale was based on the observation that irradiated multiple comorbidities and mobility difficulties may be melanoma cell lines had a large initial shoulder on their deemed medically unfit for the regimen proposed herein. survival curve. The potential radio resistance of melanoma While advanced age in the presence of a good performance and, by extension, sarcoma, was attributed to tumor cell status is not a limiting factor in the treatment strategy for STS capacity for sublethal damage repair, as implied by this (LSS and RT) [2], or in other diseases (e.g., non-Hodgkin’s shoulder [9]. lymphoma [2] and lung cancer [14]), a patient with sarcoma The histological response of dose intense chemotherapy and poor performance status or severe co-morbidities, might with preoperative hypofractionated radiotherapy in patients not be able to attend a long course of RT (5 times a week with STS was further investigated by Ryan et al. [10]. for a total of 6–8 weeks), and might even initially give They reported ahighrateofpathologicaltumor necrosis up the important postoperative treatment. Furthermore, a (95%) following an aggressive chemoradiotherapy regimen prolonged hospitalization for RT may result in unnecessary of 28 Gy administration in 8 fractions [10]. Other authors hospital-acquired infections and social problems due to a also justified an aggressive approach to palliate distant change in the patient’s close surroundings. Omitting RT in an metastases; a wide local resection of the disseminated disease LSS-approached patient increases the risk of local recurrence foci followed by adjuvant radiation therapy [11, 12]. Kepka [1]. As an alternative to LSS without RT, amputation surgery et al. [5] described the results of radiation therapy as a sole may be suggested, hampering the quality of life even more, treatment of gross disease in 112 patients [5]. Patients who and rendering the patient bed-ridden for the rest of his life. A received more than 63 Gy in standard fractionation of 1.8– short and intense course of RT may be a logical and adequate 2 Gy achieved best local control, disease free interval, and solution to this dilemma. overall survival rate. The results reported offer encouraging data that can An animal model of a hypofractionation regimen for be applied to patients suffering from this daunting disease. macroscopic soft tissue sarcomas was created and reported by Prospective studies could assess the role of hypofractionation Lawrence et al. [13]. Four fractions of 8 Gy were prescribed to and other palliative strategies among debilitated or elderly 16 dogs with overt masses of STS. The overall response rate patients with STS. 4 Sarcoma References [1] S. A. Rosenberg, J. Tepper, E. Glatstein, et al., “The treat- ment of soft-tissue sarcomas of the extremities. Prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy,” Annals of Surgery, vol. 196, pp. 305–315, 1982. [2] O. Merimsky, V. Soyfer, F. Kovner, et al., “Limb sparing approach: adjuvant radiation therapy in adults with interme- diate or high-grade limb soft tissue sarcoma,” Radiotherapy and Oncology, vol. 77, pp. 295–300, 2005. [3] F. C. Eilber, G. Rosen, J. Eckardt, et al., “Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high- grade extremity soft tissue sarcomas,” Journal of Clinical Oncology, vol. 19, pp. 3203–3209, 2001. [4] I. Nachmany, A. Subhi, I. Meller, et al., “Efficacy of high vs low dose TNF-isolated limb perfusion for locally advanced soft tissue sarcoma,” European Journal of Surgical Oncology, vol. 35, no. 2, pp. 209–214, 2009. [5] L.Kepka,T.F.DeLaney,H.D.Suit,and S. I. Goldberg,“Results of radiation therapy for unresected soft-tissue sarcomas,” International Journal of Radiation Oncology Biology Physics, vol. 63, pp. 852–859, 2005. [6] O. Merimsky, Y. Kollender, M. Inbar, et al., “Is forequarter amputation justified for palliation of intractable cancer symp- toms?” Oncology, vol. 60, pp. 55–59, 2001. [7] O. Merimsky, Y. Kollender, M. Inbar, et al., “Palliative major amputation and quality of life in cancer patients,” Acta Oncologica, vol. 36, pp. 151–157, 1997. [8] L. L. Gunderson and J. E. Tepper, Clinical Radiation Oncology, Churchill Livingstone, London, UK, 2007. [9] P. W. Pisters, “Preoperative multimodality treatment of localized soft tissue sarcoma: addition through subtraction?” Annals of Surgical Oncology, vol. 12, pp. 583–586, 2005. [10] C. W. Ryan, A. G. Montag, J. R. Hosenpud, et al., “Histologic response of dose-intense chemotherapy with preoperative hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas,” Cancer, vol. 112, pp. 2432–2439, 2008. [11] D. Lev-Chelouche, R. Nakache, D. Soffer, et al., “Metastases to the retroperitoneum in patients with extremity soft tissue sarcoma: an unusual metastatic pattern,” Cancer, vol. 88, pp. 364–368, 2000. [12] X. Shi, S. Matsumoto, J. Manbe, et al., “Long-term survival of soft tissue sarcoma patients with extrapulmonary metastasis,” Journal of Orthopaedic Science, vol. 11, pp. 92–96, 2006. [13] J. Lawrence,L.Forrest,W.Adams,etal., “Four-fraction radiation therapy for macroscopic soft tissue sarcomas in 16 dogs,” Journal of the American Animal Hospital Association, vol. 44, no. 3, pp. 100–108, 2008. [14] A. G. Pallis, A. Polyzos, I. Boukovinas, et al., “Pooled analysis of elderly patients with non-small cell lung cancer treated with front line docetaxel/gemcitabine regimen: the hellenic oncology research group experience,” Journal of Thoracic Oncology, vol. 3, pp. 505–510, 2008. 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