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Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival

Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated... Background: Preoperative radiotherapy is often used to facilitate excision of soft-tissue sarcomas. We aimed define factors that affect local tumour control and patient survival. Methods: A single institution registry study of 89 patients with non-metastatic soft-tissue sarcomas having preop- erative radiotherapy between 1994 and 2014. Radiologic (presence of peritumoural oedema and volume change following radiotherapy) and histopathologic (tumour volume, grade and surgical margin) parameters were recorded. Outcomes were the events of local recurrence, amputation, metastasis and death. Results: Local recurrence rate was low (12%) and marginal excision gave equal local control to wide excision. Pelvic localization was associated with a higher risk for amputation. The absence of peritumoural oedema on MRI defined a subgroup of tumours with more favourable oncologic outcome. Reduction of tumour volume following radiotherapy was also associated with better patient survival. Both these radiologic parameters were associated with lower tumour grade. Tumour necrosis was not significant for patient survival. The local complication rate, mainly wound healing problems and infection, was high (40%), but did not lead to any amputation. Conclusion: Preoperative radiotherapy of high-risk soft-tissue sarcomas allows for good local control rate at the expense of local wound complications, which are however manageable. Marginal excision is sufficient for local con- trol. Absence of peritumoural oedema on MRI, as well as tumour size reduction following radiotherapy are associated to superior patient survival and can be used ass early prognostic factors. Background is thus individualized, taking into consideration the local- Treatment of soft-tissue sarcomas is mainly surgical. ization and size of the tumour, its relationship to impor- Radiotherapy is indicated as an adjuvant treatment in all tant anatomical structures, the expected radiotherapy deep-seated tumours and in superficial tumours when a response and size of the radiotherapy field. wide surgical margin is not achieved [1, 2]. It is usually There is limited amount of data regarding the outcome given post-operatively, but may be given prior to surgery of surgery preceded by radiotherapy for soft-tissue sar- in order to facilitate tumour resection, allowing for limb- comas, and there is still a debate on the factors that may sparing surgery. Furthermore, the up-front use of radio- determine patient prognosis. Tumour necrosis may be therapy reduces the volume of irradiated tissue, and is an objective measure of the effect of preoperative radio - thought to result in a better functional outcome, but on therapy but there is no proof of its validity as a prognostic the other hand carries a higher risk for wound complica- factor [4]. The use of radiologic measures is also ques - tions [3]. The decision to give preoperative radiotherapy tionable [5–7]. We set out to investigate the outcome of patients with soft-tissue sarcomas who were treated with radiother- *Correspondence: panagiotis.tsagkozis@sll.se 1 apy prior to surgery, and define clinical, histologic and Department of Orthopaedic Surgery, Karolinska University Hospital, Solna, Sweden Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 2 of 7 radiologic prognostic factors associated with survival and radiosensitivity and the expected morbidity related to local control of the disease in a large retrospective series. radiotherapy and surgery. These criteria remained con - stant throughout the study period. Standard radiology Patients and methods was magnetic resonance imaging (MRI) prior to radio- Description of the cohort therapy with another examination after given radiother- This is a single-institution registry study. Inclusion cri - apy but prior to excision of the tumour, and a complete teria for participation were the diagnosis of a soft-tissue data set with comparable sequences prior and post radi- sarcoma of the trunk or the extremities, the administra- otherapy was available for 76 patients. All MRIs were tion of radiotherapy treatment prior to surgery and the reviewed by a radiologist with many years of experience absence of metastases at diagnosis. Exclusion criteria in musculoskeletal tumor imaging. Tumour dimensions were chemotherapy given in a neo-adjuvant setting and (maximum dimensions in 3 axes) were measured in cm a follow-up of less than 2  years for living patients. The and tumour response was evaluated either as a change in study confirmed to Institutional Review Board require - tumour volume, calculated by multiplication of the maxi- ments. The prospective database of our department was mum dimension in 3 axes, or according to the RECIST reviewed and 121 consecutive patients with a diagnosis criteria using the change in the maximum diameter of of soft-tissue sarcoma who had preoperative radiotherapy the tumour, where partial response was any reduction in treatment between 1994 and 2014 were identified, out of tumour volume ≥ 30% but with measurable tumour left, 1005 patients who had surgery for a soft-tissue sarcoma progressive disease any increase ≥ 20%, and anything else in the same time period (12%). Of these, 89 did not have was stable disease. The degree of peritumoural oedema any preoperative chemotherapy (usually given in the con- was subjectively evaluated in 3-grade scale (absent, mod- text of the SSG-XX protocol) and were finally included erate or heavy) using STIR and/or T2-sequences. Chest in this study. Patient demographics and characteristics X-ray or computed tomography was used for the detec- of the cohort are presented in Table 1. Median follow-up tion of lung metastases. Fine-needle aspiration cytology was 5 years. was done for diagnosis. Radiotherapy was given as external beam photon treat- Diagnosis, treatment and surveillance ment. The most common mode of radiotherapy, given Diagnosis was set in a multidisciplinary team meeting in 81% of the patients, was 50  Gy given in 25 sessions with the participation of orthopaedic surgeons, muscu- of 2  Gy (5  weeks of treatment). 13% of the patients had loskeletal radiologists, pathologists and oncologists. The less than 50 Gy (36–46 Gy), as a rule given in an intensity decision to give preoperative radiotherapy was taken in modulated treatment and 7% were treated with a dose the same meeting, with an indication to facilitate surgi- exceeding 50 Gy (52–70 Gy). Operations were performed cal resection of the tumour with an adequate surgical by consultant grade surgeons. Median time between margin, taking into consideration the size and anatomical radiotherapy and surgery was 6 weeks (range 2–28). location of the tumour and its relationship to important Surgical specimens were reviewed by a dedicated mus- structures such as the neurovascular bundle, its expected culoskeletal pathologist. The median tumour size, as measured in the excision specimen, was 11  cm. 57% of the tumours were undifferentiated pleomorfic sarcomas, 25% liposarcomas, 8% malignant peripheral nerve sheath Table 1 Patient demographics tumours, 7% synovial sarcomas and 3% other sarcomas. Age Median: 67 years Postoperative surveillance was according to the ESMO Range: 20–95 years guidelines [8], with clinical examination and chest X-ray Gender 51 male every 3 months for the first 2 years, every 6 months up to 38 female the 5th year after surgery, and then annually for another Location 60% lower extremity 5 years. 18% upper extremity 12% trunk Statistical methods 10% pelvis Statistics were done in the SPSS software (version 20, Stage (Enneking) 51% stage IIB SPSS Inc, Chicago, IL) and the STATA (version 13). 31% stage IIA Survival analyses and comparisons were done using the 10% stage IB Kaplan–Meier method and comparisons were done 8% stage IA using log-rank test. Hazard ratios between groups were Local invasion 96% deep-seated (subfacial) calculated using a Cox regression analysis (proportional 4% superficial (subcutaneous) hazards model), where possible prognostic factors were Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 3 of 7 age (dichotomized around the median), gender, tumour presence or absence of peritumoural oedema prior to grade (high or low), tumour volume (dichotomized or after radiotherapy did not significantly correlate with around the median), surgical margin (wide/marginal vs the degree of tissue necrosis (p = 0.365 and p = 0.098 intralesional), tumour necrosis (0–50%: poor response, respectively). 51–90% average response, 91–99% good response and 100% complete necrosis), and radiotherapy dose (dichot- omized around the median). Competitive risk analysis Local control rate, surgical complications and limb survival was done using the method of Pepe and Mori. Chi square R0 surgical margins were achieved in 89% of the patients tests (χ ) were used for comparisons between groups. (wide in 49% and marginal in 40%, as per Enneking), All tests were double-sided, and a p value of ≤ 0.05 was whereas R1 (intralesional) margins were noted in 11%. considered significant. 95% confidence intervals are No patients had R2 margins (intralesional with macro- presented in brackets. The core facility of the Statistics scopic tumour left). Local recurrence was noted in 12% of Department of the Karolinska Institute was consulted for the patients. A R0 surgical margin (p = 0.014) was impor- the analysis of the data. tant for local control (Fig. 1), but there was no difference between a wide and a marginal margin. The association between clear margins and superior local control rate did Results not reach statistical significance during separate analy - Radiologic and histologic evaluation of the effect sis of local recurrence with death as a competing factor of radiotherapy (Additional file 1: Figure S1). We first analyzed the effect that radiotherapy had on Complications were noted in 40% of the cases, with tumour volume, measured on MRI prior to radiother- infections and/or wound healing problems in 36%. There apy as well as after radiotherapy (prior to surgical exci- were 6 grade I, 9 grade II, 19 grade III and 2 grade V com- sion). We found that the tumour volume decreased after plications according to the Clavien–Dindo classification. radiotherapy in 51% of the cases, increased in 40% and The time span between radiotherapy and surgery had no remained stable in 9%. Using RECIST criteria, stable effect on local recurrence rate (p = 0.214) or the rate of disease was noted in 67% of cases, progressive disease wound complications. Radiotherapy dose was not asso- in 18% and partial regression in 15%. Another radio- ciated to the rate of wound complications (p = 0.313) or logic parameter that could be evaluated with accuracy local control rate (p = 0.605). was the presence of peritumoural oedema. We observed that prior to radiotherapy 77% of the tumours had peri- tumoural oedema (67% moderate and 10% heavy), whilst after radiotherapy 82% of the tumours had peritumoural oedema (58% moderate and 24% heavy). The absence of peritumoural oedema, both prior to as well as after radio- therapy, was associated with reduction of tumour volume as evaluated by MRI (p = 0.005). However, there was no association of peritumoural oedema with partial regres- sion according to RECIST criteria (not shown). Further- more, tumour grade (p = 0.001), but not tumour volume (p = 0.897) was inversely correlated to the degree of peri- tumoural oedema. Likewise, tumour grade (p = 0.016), but not tumour volume (p = 0.089) was also inversely cor- related to reduction in tumour volume after given radio- therapy. There was no correlation between the degree of volume change and the time period between given radio- therapy and the last MRI (data not shown). Next, the degree of tumour necrosis was quanti- fied, based on microscopic findings after excision of the tumour, since we found post-radiotherapy MRI too unreliable regarding an accurate interpretation of tissue Fig. 1 Kaplan-Meier curve of local control rate depending on the necrosis. In 27% of the specimens necrosis was poor, in surgical margin, of patients with non-metastatic soft-tissue sarcoma of the trunk and extremities, treated with preoperative radiotherapy. 33% average, in 24% good and in 16% complete. Excision with clear margin provides superior local control (p = 0.014), Additionally, we found that the change in tumour vol- but there is no difference between wide excisions and marginal ones ume had no correlation to tissue necrosis (p = 0.638). The Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 4 of 7 There were 9 amputations (in 5 patients the tumour Table 2 Overall survival excision was converted to amputation during their pri- Hazard ratio (95% CI) p mary operation due to technical difficulty in achiev - Age 1.295–3.821 0.003 ing an adequate surgical margin, and 4 had secondary Gender 0.556–1.570 0.798 amputation due to local recurrence). The 5 patients who Volume 1.292–3.989 0.003 underwent a primary amputation had comparable over- Grade 1.488–15.300 0.004 all survival to the rest of the patients (p = 0.099). There Surgical margin 0.442–2.788 0.823 were no amputations due to wound healing problems Radiotherapy dose 0.543–2.303 0.762 and infection. Limb salvage rate was 84% at 5  years and Tumour necrosis 0.715–1.184 0.517 10 years for upper extremity tumours and 89% at 5 years and 82% at 10  years for lower extremity tumours. Pelvic Effect of possible prognostic factors on the local recurrence rate as well as overall survival of patients with soft-tissue sarcomas of the trunk and the location was associated with a higher risk for amputation extremities that were treated with radiotherapy prior to surgery. Results gives as (Fig. 2). hazard rated with 95% confidence intervals and significance values (p) Oncologic outcome and prognostic factors OS. Tumour size (p = 0.002), grade (p = 0.028) and age Metastases were noted in 38% of the cases. The lungs (p = 0.023) retained their significance on multivariate were the most common localization for primary meta- analysis. A graphical presentation of the effect of grade static disease, as documented in 22% of the patients, and size on OS is given in Fig. 3. whilst other atypical locations for primary metastastic We finally tested the radiologic parameters regard - disease (lymph node, skeletal and soft-tissue metastases) ing their prognostic significance (Table  2). Reduction of were relatively common in this series, as they were doc- tumour volume,in response to radiotherapy, evaluated in umented in 16% of the cases. Of the 89 patients, 31 are absolute value, was associated with a superior oncologic still alive (one with persisting tumour, the rest not hav- outcome (Fig. 4a). In contrast, tumour response using the ing evidence of disease). Overall survival (OS) was 55% at RECIST criteria was not prognostic for overall survival 5 years and 44% at 10 years. (p = 0.626). Furthermore, the absence of peritumoural As presented in Table  2, tumour necrosis, loca- oedema, best evaluated at post-radiotherapy MRI, was tion and surgical margin had no effect on OS. Tumour also a favourable prognostic factor (Fig. 4b). grade, tumour size and patient age were important for Discussion The decision to give preoperative radiotherapy is mainly based on the intention to downsize the tumour and make it more easily resectable. Volume reduction may result in less morbidity by sparing important anatomical struc- tures, whereas limb-sparing surgery in cases of close proximity of the tumour to the neurovascular bundle may sometimes be feasible only when preoperative radio- therapy is successful. Our results support the notion that preoperative radi- otherapy is a successful strategy in cases of high-risk tumours, such as large-volume ones and those in close proximity to the neurovascular bundle. In our cohort, average tumour size was larger than in published cohorts [1, 9], indicating that the case mix was in favour of large, high-risk tumours. R0 (wide/marginal) surgical margins were nonetheless achieved in a percentage comparable to routine sarcoma surgery [10]. Irradiated sarcomas often displayed clear anatomical margins during excision and were easy to dissect from nearby structures. This dem - Fig. 2 Kaplan-Meier curve of limb salvage rate regarding the upper onstrates the value of preoperative radiotherapy which and lower extremity, of patients with non-metastatic soft-tissue sarcoma of the extremities, treated with preoperative radiotherapy. is in accordance to an observed higher rate of resections Pelvic localization is associated with a higher risk for amputation with clear surgical margins in this setting [11]. The limb (p = 0.029) salvage rate was also good, although patients should be Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 5 of 7 Fig. 4 Kaplan-Meier curve of overall survival depending on the Fig. 3 Kaplan-Meier curve of overall survival depending on tumour presence or absence of peri-tumoural oedema on MRI (a), as well size (a) and grade (b), of patients with non-metastatic soft-tissue as on the reduction or not of tumour size (b), of patients with sarcoma of the extremities, treated with preoperative radiotherapy. non-metastatic soft-tissue sarcoma of the extremities, treated with Patients with large tumours (dichotomized around the median preoperative radiotherapy. Absence of peri-tumoural oedema after volume) have inferior survival to the ones having smaller tumours radiotherapy (p = 0.040) and reduction of tumour volume (p = 0.015) (p = 0.003). Higher grade is also correlated to inferior overall survival are associated with superior overall survival (p = 0.004) aware that in some cases the surgeon has to convert a Whereas there is no consensus regarding how radical an planned limb-sparing surgery to an amputation. Pelvic excision of a soft-tissue sarcoma should be [13, 14], with localization is also an important risk factor for amputa- conflicting evidence [1, 15, 16], it appears that in the case tion. Importantly, there was no need to strive after wide of pre-irradiated sarcomas a close R0 surgical margin is surgical margins, since close marginal excision of the safe. tumour gave equal local control to wide surgical exci- We identified two radiologic prognostic factors that are sion, which is in agreement with one previous study [12]. associated with a favourable oncologic outcome, namely Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 6 of 7 the absence of peritumoural oedema and the reduction of rate, which however does not pose a threat to limb sur- tumour volume following radiotherapy. We believe that vival. Simple marginal excision is safe and mutilating they represent independent phenomena: The absence surgery to achieve a wide margin thus unnecessary. The of oedema probably marks a more indolent biological absence of peritumoural oedema on MRI as well as vol- behaviour, since there was an inverse correlation between ume reduction of the tumour after radiotherapy defines a tumour grade and the absence of oedema. Since tumour subgroup of patients with favourable prognosis. grade is, as a rule, determined with sufficient accu - racy only after examination of the resection specimen, absence of peritumoural oedema can be used as an early Additional file marker to predict the oncologic outcome. Reduction of tumour volume on the other hand obviously reflects the Additional file 1: Figure S1. Local relapse rate depending on the quality of surgical margins (clear or intralesional) of patients with non-metastatic response to treatment, although intratumoural bleeding soft-tissue sarcoma of the extremities, treated with preoperative radio- may contribute to a stable or increasing volume and MRI therapy, calculated in a competitive risk model with death as a competing sequences specific for the detection of tissue haemor - factor. Clear surgical margins are not associated to local control rate in a competitive risk model (p = 0.173). rhage may be useful in this setting. Two previous stud- ies failed to show any significance of tumour volume increase on survival [5, 6], and tumour volume reduction Authors’ contributions Study conception and data retrieval: OB, PT, MS. Data analysis: PT, MS. Manu- may be a more accurate marker. Tumour response using script preparation: PT, MS. All authors read and approved the final manuscript. the RECIST criteraia was not prognostic, most probably because they are more blunt and minor volume changes Author details Department of Orthopaedic Surgery, Karolinska University Hospital, Solna, are not recorded as a response. Notably, the degree of Sweden. Department of Molecular Medicine and Surgery, Karolinska necrosis at histologic examination, another parameter 3 Institutet, Stockholm, Sweden. Department of Neuroradiology, Karolinska which may reflect response to radiotherapy, did not cor - University Hospital, Solna, Sweden. relate to the oncologic outcome, corroborating recent Acknowledgements findings [4]. This is probably because tumour necrosis is None. a more complex phenomenon, which depends both on Competing interests the biological aggressiveness of the neoplasm (the more The authors declare that they have no competing interests. aggressive and fast growing, the more necrotic) and response to treatment. Availability of data and materials Data are available upon request by the corresponding author. Preoperative radiotherapy was accompanied by a very high risk for local complications, often wound infections, Consent healing problems and dehiscence, which does not depend Data are presented at a cohort level and no patients can be identified. on the time to surgery or dose. This is in line with previ - Ethics approval and consent to participate ous publications [17–20] and should be communicated to This is a retrospective study which complies to Institutional Guidelines. the patient during the process of shared decision-making. Funding The use of modern radiotherapy techniques may lower No funding was received for this study. the risk of local complications [21–23]. Yet, complica- tions were manageable and did not lead to amputations Publisher’s Note of the extremity. Springer Nature remains neutral with regard to jurisdictional claims in pub- We recognize the retrospective nature of this study as lished maps and institutional affiliations. its main limitation. However, since our aim was not a Received: 9 May 2018 Accepted: 10 August 2018 comparison of preoperative with postoperative radio- therapy, a question which has been addressed in other studies [3, 24, 25], we consider that our study provides valuable new findings regarding preoperative radiother - References apy treatment of soft-tissue sarcomas, and encourage fur- 1. Jebsen NL, Trovik CS, Bauer HCF, Rydholm A, Monge OR, Hall KS, et al. Radiotherapy to improve local control regardless of surgical margin ther research in this direction so that they are validated and malignancy grade in extremity and trunk wall soft tissue sarcoma: in separate large cohorts. a Scandinavian sarcoma group study. Int J Radiat Oncol Biol Phys. 2008;71(4):1196–203. 2. Albertsmeier M, Rauch A, Roeder F, Hasenhütl S, Pratschke S, Kirsch- Conclusions neck M, et al. External beam radiation therapy for resectable soft tissue Preoperative radiotherapy allows for good local control of sarcoma: a systematic review and meta-analysis. Ann Surg Oncol. high-risk tumours and excellent limb salvage rates. This 2018;25:754–67. is at the expense of a considerable wound complication Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 7 of 7 3. Al-Absi E, Farrokhyar F, Sharma R, Whelan K, Corbett T, Patel M, et al. A sys- be close as long as the resected tumor has no ink on it. Oncologist. tematic review and meta-analysis of oncologic outcomes of pre- versus 2017;22(11):1400–10. postoperative radiation in localized resectable soft-tissue sarcoma. Ann 16. Gundle KR, Kafchinski L, Gupta S, Griffin AM, Dickson BC, Chung PW, Surg Oncol. 2010;17(5):1367–74. et al. Analysis of margin classification systems for assessing the risk 4. Schaefer I-M, Hornick JL, Barysauskas CM, Raut CP, Patel SA, Royce TJ, of local recurrence after soft tissue sarcoma resection. J Clin Oncol. et al. Histologic appearance after preoperative radiation therapy for soft 2018;JCO2017746941. tissue sarcoma: assessment of the European Organization for Research 17. Griffin AM, Dickie CI, Catton CN, Chung PWM, Ferguson PC, Wunder JS, and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response et al. The influence of time interval between preoperative radiation and Score. Int J Radiat Oncol Biol Phys. 2017;98(2):375–83. surgical resection on the development of wound healing complications 5. Delisca GO, Alamanda VK, Archer KR, Song Y, Schwartz HS, Holt GE. Tumor in extremity soft tissue sarcoma. Ann Surg Oncol. 2015;22(9):2824–30. size increase following preoperative radiation of soft tissue sarcomas 18. Baldini EH, Lapidus MR, Wang Q, Manola J, Orgill DP, Pomahac B, et al. does not affect prognosis. J Surg Oncol. 2013;107(7):723–7. Predictors for major wound complications following preoperative 6. Miki Y, Ngan S, Clark JCM, Akiyama T, Choong PFM. The significance of radiotherapy and surgery for soft-tissue sarcoma of the extremities and size change of soft tissue sarcoma during preoperative radiotherapy. Eur trunk: importance of tumor proximity to skin surface. Ann Surg Oncol. J Surg Oncol. 2010;36(7):678–83. 2013;20(5):1494–9. 7. Einarsdottir H, Wejde J, Bauer HC. Pre-operative radiotherapy in soft tissue 19. Rosenberg LA, Esther RJ, Erfanian K, Green R, Kim HJ, Sweeting R, et al. tumors. Assessment of response by static post-contrast MR imaging Wound complications in preoperatively irradiated soft-tissue sarcomas of compared to histopathology. Acta Radiol. 2001;42(1):1–5. the extremities. Int J Radiat Oncol Biol Phys. 2013;85(2):432–7. 8. ESMO/European Sarcoma Network Working Group. Soft tissue and vis- 20. Tseng JF, Ballo MT, Langstein HN, Wayne JD, Cormier JN, Hunt KK, et al. ceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment The effect of preoperative radiotherapy and reconstructive surgery on and follow-up. Ann Oncol. 2014;25(Suppl 3):102–12. wound complications after resection of extremity soft-tissue sarcomas. 9. Coindre JM, Terrier P, Bui NB, Bonichon F, Collin F, Le Doussal V, et al. Prog- Ann Surg Oncol. 2006;13(9):1209–15. nostic factors in adult patients with locally controlled soft tissue sarcoma. 21. Shah C, Verma V, Takiar R, Vajapey R, Amarnath S, Murphy E, et al. A study of 546 patients from the French Federation of Cancer Centers Radiation therapy in the management of soft tissue sarcoma: a Sarcoma Group. J Clin Oncol. 1996;14(3):869–77. Clinician’s guide to timing, techniques, and targets. Am J Clin Oncol. 10. Strander H, Turesson I, Cavallin-Ståhl E. A systematic overview of radiation 2016;39(6):630–5. therapy effects in soft tissue sarcomas. Acta Oncol. 2003;42(5–6):516–31. 22. Haas RLM, Miah AB, LePechoux C, DeLaney TF, Baldini EH, Alektiar K, et al. 11. Gingrich AA, Bateni SB, Monjazeb AM, Darrow MA, Thorpe SW, Kirane Preoperative radiotherapy for extremity soft tissue sarcoma; past, present AR, et al. Neoadjuvant radiotherapy is associated with R0 resection and and future perspectives on dose fractionation regimens and combined improved survival for patients with extremity soft tissue sarcoma under- modality strategies. Radiother Oncol J. 2016;119(1):14–21. going surgery: a National Cancer Database Analysis. Ann Surg Oncol. 23. Kubicek GJ, LaCouture T, Kaden M, Kim TW, Lerman N, Khrizman P, et al. 2017;24(11):3252–63. Preoperative radiosurgery for soft tissue sarcoma. Am J Clin Oncol. 12. Dagan R, Indelicato DJ, McGee L, Morris CG, Kirwan JM, Knapik J, et al. The 2018;41(1):86–9. significance of a marginal excision after preoperative radiation therapy 24. Sampath S, Schultheiss TE, Hitchcock YJ, Randall RL, Shrieve DC, Wong for soft tissue sarcoma of the extremity. Cancer. 2012;118(12):3199–207. JYC. Preoperative versus postoperative radiotherapy in soft-tissue sar- 13. Hoefkens F, Dehandschutter C, Somville J, Meijnders P, Van Gestel D. Soft coma: multi-institutional analysis of 821 patients. Int J Radiat Oncol Biol tissue sarcoma of the extremities: pending questions on surgery and Phys. 2011;81(2):498–505. radiotherapy. Radiat Oncol. 2016;11(1):136. 25. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preop- 14. Kandel R, Coakley N, Werier J, Engel J, Ghert M, Verma S, et al. Surgical erative versus postoperative radiotherapy in soft-tissue sarcoma of the margins and handling of soft-tissue sarcoma in extremities: a clinical limbs: a randomised trial. Lancet. 2002;359(9325):2235–41. practice guideline. Curr Oncol. 2013;20(3):e247–54. 15. Harati K, Goertz O, Pieper A, Daigeler A, Joneidi-Jafari H, Niggemann H, et al. Soft tissue sarcomas of the extremities: surgical margins can Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Sarcoma Research Springer Journals

Preoperative radiotherapy of soft-tissue sarcomas: surgical and radiologic parameters associated with local control and survival

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Copyright © 2018 by The Author(s)
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Biomedicine; Cancer Research; Oncology; Surgical Oncology
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Abstract

Background: Preoperative radiotherapy is often used to facilitate excision of soft-tissue sarcomas. We aimed define factors that affect local tumour control and patient survival. Methods: A single institution registry study of 89 patients with non-metastatic soft-tissue sarcomas having preop- erative radiotherapy between 1994 and 2014. Radiologic (presence of peritumoural oedema and volume change following radiotherapy) and histopathologic (tumour volume, grade and surgical margin) parameters were recorded. Outcomes were the events of local recurrence, amputation, metastasis and death. Results: Local recurrence rate was low (12%) and marginal excision gave equal local control to wide excision. Pelvic localization was associated with a higher risk for amputation. The absence of peritumoural oedema on MRI defined a subgroup of tumours with more favourable oncologic outcome. Reduction of tumour volume following radiotherapy was also associated with better patient survival. Both these radiologic parameters were associated with lower tumour grade. Tumour necrosis was not significant for patient survival. The local complication rate, mainly wound healing problems and infection, was high (40%), but did not lead to any amputation. Conclusion: Preoperative radiotherapy of high-risk soft-tissue sarcomas allows for good local control rate at the expense of local wound complications, which are however manageable. Marginal excision is sufficient for local con- trol. Absence of peritumoural oedema on MRI, as well as tumour size reduction following radiotherapy are associated to superior patient survival and can be used ass early prognostic factors. Background is thus individualized, taking into consideration the local- Treatment of soft-tissue sarcomas is mainly surgical. ization and size of the tumour, its relationship to impor- Radiotherapy is indicated as an adjuvant treatment in all tant anatomical structures, the expected radiotherapy deep-seated tumours and in superficial tumours when a response and size of the radiotherapy field. wide surgical margin is not achieved [1, 2]. It is usually There is limited amount of data regarding the outcome given post-operatively, but may be given prior to surgery of surgery preceded by radiotherapy for soft-tissue sar- in order to facilitate tumour resection, allowing for limb- comas, and there is still a debate on the factors that may sparing surgery. Furthermore, the up-front use of radio- determine patient prognosis. Tumour necrosis may be therapy reduces the volume of irradiated tissue, and is an objective measure of the effect of preoperative radio - thought to result in a better functional outcome, but on therapy but there is no proof of its validity as a prognostic the other hand carries a higher risk for wound complica- factor [4]. The use of radiologic measures is also ques - tions [3]. The decision to give preoperative radiotherapy tionable [5–7]. We set out to investigate the outcome of patients with soft-tissue sarcomas who were treated with radiother- *Correspondence: panagiotis.tsagkozis@sll.se 1 apy prior to surgery, and define clinical, histologic and Department of Orthopaedic Surgery, Karolinska University Hospital, Solna, Sweden Full list of author information is available at the end of the article © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 2 of 7 radiologic prognostic factors associated with survival and radiosensitivity and the expected morbidity related to local control of the disease in a large retrospective series. radiotherapy and surgery. These criteria remained con - stant throughout the study period. Standard radiology Patients and methods was magnetic resonance imaging (MRI) prior to radio- Description of the cohort therapy with another examination after given radiother- This is a single-institution registry study. Inclusion cri - apy but prior to excision of the tumour, and a complete teria for participation were the diagnosis of a soft-tissue data set with comparable sequences prior and post radi- sarcoma of the trunk or the extremities, the administra- otherapy was available for 76 patients. All MRIs were tion of radiotherapy treatment prior to surgery and the reviewed by a radiologist with many years of experience absence of metastases at diagnosis. Exclusion criteria in musculoskeletal tumor imaging. Tumour dimensions were chemotherapy given in a neo-adjuvant setting and (maximum dimensions in 3 axes) were measured in cm a follow-up of less than 2  years for living patients. The and tumour response was evaluated either as a change in study confirmed to Institutional Review Board require - tumour volume, calculated by multiplication of the maxi- ments. The prospective database of our department was mum dimension in 3 axes, or according to the RECIST reviewed and 121 consecutive patients with a diagnosis criteria using the change in the maximum diameter of of soft-tissue sarcoma who had preoperative radiotherapy the tumour, where partial response was any reduction in treatment between 1994 and 2014 were identified, out of tumour volume ≥ 30% but with measurable tumour left, 1005 patients who had surgery for a soft-tissue sarcoma progressive disease any increase ≥ 20%, and anything else in the same time period (12%). Of these, 89 did not have was stable disease. The degree of peritumoural oedema any preoperative chemotherapy (usually given in the con- was subjectively evaluated in 3-grade scale (absent, mod- text of the SSG-XX protocol) and were finally included erate or heavy) using STIR and/or T2-sequences. Chest in this study. Patient demographics and characteristics X-ray or computed tomography was used for the detec- of the cohort are presented in Table 1. Median follow-up tion of lung metastases. Fine-needle aspiration cytology was 5 years. was done for diagnosis. Radiotherapy was given as external beam photon treat- Diagnosis, treatment and surveillance ment. The most common mode of radiotherapy, given Diagnosis was set in a multidisciplinary team meeting in 81% of the patients, was 50  Gy given in 25 sessions with the participation of orthopaedic surgeons, muscu- of 2  Gy (5  weeks of treatment). 13% of the patients had loskeletal radiologists, pathologists and oncologists. The less than 50 Gy (36–46 Gy), as a rule given in an intensity decision to give preoperative radiotherapy was taken in modulated treatment and 7% were treated with a dose the same meeting, with an indication to facilitate surgi- exceeding 50 Gy (52–70 Gy). Operations were performed cal resection of the tumour with an adequate surgical by consultant grade surgeons. Median time between margin, taking into consideration the size and anatomical radiotherapy and surgery was 6 weeks (range 2–28). location of the tumour and its relationship to important Surgical specimens were reviewed by a dedicated mus- structures such as the neurovascular bundle, its expected culoskeletal pathologist. The median tumour size, as measured in the excision specimen, was 11  cm. 57% of the tumours were undifferentiated pleomorfic sarcomas, 25% liposarcomas, 8% malignant peripheral nerve sheath Table 1 Patient demographics tumours, 7% synovial sarcomas and 3% other sarcomas. Age Median: 67 years Postoperative surveillance was according to the ESMO Range: 20–95 years guidelines [8], with clinical examination and chest X-ray Gender 51 male every 3 months for the first 2 years, every 6 months up to 38 female the 5th year after surgery, and then annually for another Location 60% lower extremity 5 years. 18% upper extremity 12% trunk Statistical methods 10% pelvis Statistics were done in the SPSS software (version 20, Stage (Enneking) 51% stage IIB SPSS Inc, Chicago, IL) and the STATA (version 13). 31% stage IIA Survival analyses and comparisons were done using the 10% stage IB Kaplan–Meier method and comparisons were done 8% stage IA using log-rank test. Hazard ratios between groups were Local invasion 96% deep-seated (subfacial) calculated using a Cox regression analysis (proportional 4% superficial (subcutaneous) hazards model), where possible prognostic factors were Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 3 of 7 age (dichotomized around the median), gender, tumour presence or absence of peritumoural oedema prior to grade (high or low), tumour volume (dichotomized or after radiotherapy did not significantly correlate with around the median), surgical margin (wide/marginal vs the degree of tissue necrosis (p = 0.365 and p = 0.098 intralesional), tumour necrosis (0–50%: poor response, respectively). 51–90% average response, 91–99% good response and 100% complete necrosis), and radiotherapy dose (dichot- omized around the median). Competitive risk analysis Local control rate, surgical complications and limb survival was done using the method of Pepe and Mori. Chi square R0 surgical margins were achieved in 89% of the patients tests (χ ) were used for comparisons between groups. (wide in 49% and marginal in 40%, as per Enneking), All tests were double-sided, and a p value of ≤ 0.05 was whereas R1 (intralesional) margins were noted in 11%. considered significant. 95% confidence intervals are No patients had R2 margins (intralesional with macro- presented in brackets. The core facility of the Statistics scopic tumour left). Local recurrence was noted in 12% of Department of the Karolinska Institute was consulted for the patients. A R0 surgical margin (p = 0.014) was impor- the analysis of the data. tant for local control (Fig. 1), but there was no difference between a wide and a marginal margin. The association between clear margins and superior local control rate did Results not reach statistical significance during separate analy - Radiologic and histologic evaluation of the effect sis of local recurrence with death as a competing factor of radiotherapy (Additional file 1: Figure S1). We first analyzed the effect that radiotherapy had on Complications were noted in 40% of the cases, with tumour volume, measured on MRI prior to radiother- infections and/or wound healing problems in 36%. There apy as well as after radiotherapy (prior to surgical exci- were 6 grade I, 9 grade II, 19 grade III and 2 grade V com- sion). We found that the tumour volume decreased after plications according to the Clavien–Dindo classification. radiotherapy in 51% of the cases, increased in 40% and The time span between radiotherapy and surgery had no remained stable in 9%. Using RECIST criteria, stable effect on local recurrence rate (p = 0.214) or the rate of disease was noted in 67% of cases, progressive disease wound complications. Radiotherapy dose was not asso- in 18% and partial regression in 15%. Another radio- ciated to the rate of wound complications (p = 0.313) or logic parameter that could be evaluated with accuracy local control rate (p = 0.605). was the presence of peritumoural oedema. We observed that prior to radiotherapy 77% of the tumours had peri- tumoural oedema (67% moderate and 10% heavy), whilst after radiotherapy 82% of the tumours had peritumoural oedema (58% moderate and 24% heavy). The absence of peritumoural oedema, both prior to as well as after radio- therapy, was associated with reduction of tumour volume as evaluated by MRI (p = 0.005). However, there was no association of peritumoural oedema with partial regres- sion according to RECIST criteria (not shown). Further- more, tumour grade (p = 0.001), but not tumour volume (p = 0.897) was inversely correlated to the degree of peri- tumoural oedema. Likewise, tumour grade (p = 0.016), but not tumour volume (p = 0.089) was also inversely cor- related to reduction in tumour volume after given radio- therapy. There was no correlation between the degree of volume change and the time period between given radio- therapy and the last MRI (data not shown). Next, the degree of tumour necrosis was quanti- fied, based on microscopic findings after excision of the tumour, since we found post-radiotherapy MRI too unreliable regarding an accurate interpretation of tissue Fig. 1 Kaplan-Meier curve of local control rate depending on the necrosis. In 27% of the specimens necrosis was poor, in surgical margin, of patients with non-metastatic soft-tissue sarcoma of the trunk and extremities, treated with preoperative radiotherapy. 33% average, in 24% good and in 16% complete. Excision with clear margin provides superior local control (p = 0.014), Additionally, we found that the change in tumour vol- but there is no difference between wide excisions and marginal ones ume had no correlation to tissue necrosis (p = 0.638). The Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 4 of 7 There were 9 amputations (in 5 patients the tumour Table 2 Overall survival excision was converted to amputation during their pri- Hazard ratio (95% CI) p mary operation due to technical difficulty in achiev - Age 1.295–3.821 0.003 ing an adequate surgical margin, and 4 had secondary Gender 0.556–1.570 0.798 amputation due to local recurrence). The 5 patients who Volume 1.292–3.989 0.003 underwent a primary amputation had comparable over- Grade 1.488–15.300 0.004 all survival to the rest of the patients (p = 0.099). There Surgical margin 0.442–2.788 0.823 were no amputations due to wound healing problems Radiotherapy dose 0.543–2.303 0.762 and infection. Limb salvage rate was 84% at 5  years and Tumour necrosis 0.715–1.184 0.517 10 years for upper extremity tumours and 89% at 5 years and 82% at 10  years for lower extremity tumours. Pelvic Effect of possible prognostic factors on the local recurrence rate as well as overall survival of patients with soft-tissue sarcomas of the trunk and the location was associated with a higher risk for amputation extremities that were treated with radiotherapy prior to surgery. Results gives as (Fig. 2). hazard rated with 95% confidence intervals and significance values (p) Oncologic outcome and prognostic factors OS. Tumour size (p = 0.002), grade (p = 0.028) and age Metastases were noted in 38% of the cases. The lungs (p = 0.023) retained their significance on multivariate were the most common localization for primary meta- analysis. A graphical presentation of the effect of grade static disease, as documented in 22% of the patients, and size on OS is given in Fig. 3. whilst other atypical locations for primary metastastic We finally tested the radiologic parameters regard - disease (lymph node, skeletal and soft-tissue metastases) ing their prognostic significance (Table  2). Reduction of were relatively common in this series, as they were doc- tumour volume,in response to radiotherapy, evaluated in umented in 16% of the cases. Of the 89 patients, 31 are absolute value, was associated with a superior oncologic still alive (one with persisting tumour, the rest not hav- outcome (Fig. 4a). In contrast, tumour response using the ing evidence of disease). Overall survival (OS) was 55% at RECIST criteria was not prognostic for overall survival 5 years and 44% at 10 years. (p = 0.626). Furthermore, the absence of peritumoural As presented in Table  2, tumour necrosis, loca- oedema, best evaluated at post-radiotherapy MRI, was tion and surgical margin had no effect on OS. Tumour also a favourable prognostic factor (Fig. 4b). grade, tumour size and patient age were important for Discussion The decision to give preoperative radiotherapy is mainly based on the intention to downsize the tumour and make it more easily resectable. Volume reduction may result in less morbidity by sparing important anatomical struc- tures, whereas limb-sparing surgery in cases of close proximity of the tumour to the neurovascular bundle may sometimes be feasible only when preoperative radio- therapy is successful. Our results support the notion that preoperative radi- otherapy is a successful strategy in cases of high-risk tumours, such as large-volume ones and those in close proximity to the neurovascular bundle. In our cohort, average tumour size was larger than in published cohorts [1, 9], indicating that the case mix was in favour of large, high-risk tumours. R0 (wide/marginal) surgical margins were nonetheless achieved in a percentage comparable to routine sarcoma surgery [10]. Irradiated sarcomas often displayed clear anatomical margins during excision and were easy to dissect from nearby structures. This dem - Fig. 2 Kaplan-Meier curve of limb salvage rate regarding the upper onstrates the value of preoperative radiotherapy which and lower extremity, of patients with non-metastatic soft-tissue sarcoma of the extremities, treated with preoperative radiotherapy. is in accordance to an observed higher rate of resections Pelvic localization is associated with a higher risk for amputation with clear surgical margins in this setting [11]. The limb (p = 0.029) salvage rate was also good, although patients should be Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 5 of 7 Fig. 4 Kaplan-Meier curve of overall survival depending on the Fig. 3 Kaplan-Meier curve of overall survival depending on tumour presence or absence of peri-tumoural oedema on MRI (a), as well size (a) and grade (b), of patients with non-metastatic soft-tissue as on the reduction or not of tumour size (b), of patients with sarcoma of the extremities, treated with preoperative radiotherapy. non-metastatic soft-tissue sarcoma of the extremities, treated with Patients with large tumours (dichotomized around the median preoperative radiotherapy. Absence of peri-tumoural oedema after volume) have inferior survival to the ones having smaller tumours radiotherapy (p = 0.040) and reduction of tumour volume (p = 0.015) (p = 0.003). Higher grade is also correlated to inferior overall survival are associated with superior overall survival (p = 0.004) aware that in some cases the surgeon has to convert a Whereas there is no consensus regarding how radical an planned limb-sparing surgery to an amputation. Pelvic excision of a soft-tissue sarcoma should be [13, 14], with localization is also an important risk factor for amputa- conflicting evidence [1, 15, 16], it appears that in the case tion. Importantly, there was no need to strive after wide of pre-irradiated sarcomas a close R0 surgical margin is surgical margins, since close marginal excision of the safe. tumour gave equal local control to wide surgical exci- We identified two radiologic prognostic factors that are sion, which is in agreement with one previous study [12]. associated with a favourable oncologic outcome, namely Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 6 of 7 the absence of peritumoural oedema and the reduction of rate, which however does not pose a threat to limb sur- tumour volume following radiotherapy. We believe that vival. Simple marginal excision is safe and mutilating they represent independent phenomena: The absence surgery to achieve a wide margin thus unnecessary. The of oedema probably marks a more indolent biological absence of peritumoural oedema on MRI as well as vol- behaviour, since there was an inverse correlation between ume reduction of the tumour after radiotherapy defines a tumour grade and the absence of oedema. Since tumour subgroup of patients with favourable prognosis. grade is, as a rule, determined with sufficient accu - racy only after examination of the resection specimen, absence of peritumoural oedema can be used as an early Additional file marker to predict the oncologic outcome. Reduction of tumour volume on the other hand obviously reflects the Additional file 1: Figure S1. Local relapse rate depending on the quality of surgical margins (clear or intralesional) of patients with non-metastatic response to treatment, although intratumoural bleeding soft-tissue sarcoma of the extremities, treated with preoperative radio- may contribute to a stable or increasing volume and MRI therapy, calculated in a competitive risk model with death as a competing sequences specific for the detection of tissue haemor - factor. Clear surgical margins are not associated to local control rate in a competitive risk model (p = 0.173). rhage may be useful in this setting. Two previous stud- ies failed to show any significance of tumour volume increase on survival [5, 6], and tumour volume reduction Authors’ contributions Study conception and data retrieval: OB, PT, MS. Data analysis: PT, MS. Manu- may be a more accurate marker. Tumour response using script preparation: PT, MS. All authors read and approved the final manuscript. the RECIST criteraia was not prognostic, most probably because they are more blunt and minor volume changes Author details Department of Orthopaedic Surgery, Karolinska University Hospital, Solna, are not recorded as a response. Notably, the degree of Sweden. Department of Molecular Medicine and Surgery, Karolinska necrosis at histologic examination, another parameter 3 Institutet, Stockholm, Sweden. Department of Neuroradiology, Karolinska which may reflect response to radiotherapy, did not cor - University Hospital, Solna, Sweden. relate to the oncologic outcome, corroborating recent Acknowledgements findings [4]. This is probably because tumour necrosis is None. a more complex phenomenon, which depends both on Competing interests the biological aggressiveness of the neoplasm (the more The authors declare that they have no competing interests. aggressive and fast growing, the more necrotic) and response to treatment. Availability of data and materials Data are available upon request by the corresponding author. Preoperative radiotherapy was accompanied by a very high risk for local complications, often wound infections, Consent healing problems and dehiscence, which does not depend Data are presented at a cohort level and no patients can be identified. on the time to surgery or dose. This is in line with previ - Ethics approval and consent to participate ous publications [17–20] and should be communicated to This is a retrospective study which complies to Institutional Guidelines. the patient during the process of shared decision-making. Funding The use of modern radiotherapy techniques may lower No funding was received for this study. the risk of local complications [21–23]. Yet, complica- tions were manageable and did not lead to amputations Publisher’s Note of the extremity. Springer Nature remains neutral with regard to jurisdictional claims in pub- We recognize the retrospective nature of this study as lished maps and institutional affiliations. its main limitation. However, since our aim was not a Received: 9 May 2018 Accepted: 10 August 2018 comparison of preoperative with postoperative radio- therapy, a question which has been addressed in other studies [3, 24, 25], we consider that our study provides valuable new findings regarding preoperative radiother - References apy treatment of soft-tissue sarcomas, and encourage fur- 1. Jebsen NL, Trovik CS, Bauer HCF, Rydholm A, Monge OR, Hall KS, et al. Radiotherapy to improve local control regardless of surgical margin ther research in this direction so that they are validated and malignancy grade in extremity and trunk wall soft tissue sarcoma: in separate large cohorts. a Scandinavian sarcoma group study. Int J Radiat Oncol Biol Phys. 2008;71(4):1196–203. 2. Albertsmeier M, Rauch A, Roeder F, Hasenhütl S, Pratschke S, Kirsch- Conclusions neck M, et al. External beam radiation therapy for resectable soft tissue Preoperative radiotherapy allows for good local control of sarcoma: a systematic review and meta-analysis. Ann Surg Oncol. high-risk tumours and excellent limb salvage rates. This 2018;25:754–67. is at the expense of a considerable wound complication Tsagozis et al. Clin Sarcoma Res (2018) 8:19 Page 7 of 7 3. Al-Absi E, Farrokhyar F, Sharma R, Whelan K, Corbett T, Patel M, et al. A sys- be close as long as the resected tumor has no ink on it. Oncologist. tematic review and meta-analysis of oncologic outcomes of pre- versus 2017;22(11):1400–10. postoperative radiation in localized resectable soft-tissue sarcoma. Ann 16. Gundle KR, Kafchinski L, Gupta S, Griffin AM, Dickson BC, Chung PW, Surg Oncol. 2010;17(5):1367–74. et al. Analysis of margin classification systems for assessing the risk 4. Schaefer I-M, Hornick JL, Barysauskas CM, Raut CP, Patel SA, Royce TJ, of local recurrence after soft tissue sarcoma resection. J Clin Oncol. et al. Histologic appearance after preoperative radiation therapy for soft 2018;JCO2017746941. tissue sarcoma: assessment of the European Organization for Research 17. Griffin AM, Dickie CI, Catton CN, Chung PWM, Ferguson PC, Wunder JS, and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response et al. The influence of time interval between preoperative radiation and Score. Int J Radiat Oncol Biol Phys. 2017;98(2):375–83. surgical resection on the development of wound healing complications 5. Delisca GO, Alamanda VK, Archer KR, Song Y, Schwartz HS, Holt GE. Tumor in extremity soft tissue sarcoma. Ann Surg Oncol. 2015;22(9):2824–30. size increase following preoperative radiation of soft tissue sarcomas 18. Baldini EH, Lapidus MR, Wang Q, Manola J, Orgill DP, Pomahac B, et al. does not affect prognosis. J Surg Oncol. 2013;107(7):723–7. Predictors for major wound complications following preoperative 6. Miki Y, Ngan S, Clark JCM, Akiyama T, Choong PFM. The significance of radiotherapy and surgery for soft-tissue sarcoma of the extremities and size change of soft tissue sarcoma during preoperative radiotherapy. Eur trunk: importance of tumor proximity to skin surface. Ann Surg Oncol. J Surg Oncol. 2010;36(7):678–83. 2013;20(5):1494–9. 7. Einarsdottir H, Wejde J, Bauer HC. Pre-operative radiotherapy in soft tissue 19. Rosenberg LA, Esther RJ, Erfanian K, Green R, Kim HJ, Sweeting R, et al. tumors. Assessment of response by static post-contrast MR imaging Wound complications in preoperatively irradiated soft-tissue sarcomas of compared to histopathology. Acta Radiol. 2001;42(1):1–5. the extremities. Int J Radiat Oncol Biol Phys. 2013;85(2):432–7. 8. ESMO/European Sarcoma Network Working Group. Soft tissue and vis- 20. Tseng JF, Ballo MT, Langstein HN, Wayne JD, Cormier JN, Hunt KK, et al. ceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment The effect of preoperative radiotherapy and reconstructive surgery on and follow-up. Ann Oncol. 2014;25(Suppl 3):102–12. wound complications after resection of extremity soft-tissue sarcomas. 9. Coindre JM, Terrier P, Bui NB, Bonichon F, Collin F, Le Doussal V, et al. Prog- Ann Surg Oncol. 2006;13(9):1209–15. nostic factors in adult patients with locally controlled soft tissue sarcoma. 21. Shah C, Verma V, Takiar R, Vajapey R, Amarnath S, Murphy E, et al. A study of 546 patients from the French Federation of Cancer Centers Radiation therapy in the management of soft tissue sarcoma: a Sarcoma Group. J Clin Oncol. 1996;14(3):869–77. Clinician’s guide to timing, techniques, and targets. Am J Clin Oncol. 10. Strander H, Turesson I, Cavallin-Ståhl E. A systematic overview of radiation 2016;39(6):630–5. therapy effects in soft tissue sarcomas. Acta Oncol. 2003;42(5–6):516–31. 22. Haas RLM, Miah AB, LePechoux C, DeLaney TF, Baldini EH, Alektiar K, et al. 11. Gingrich AA, Bateni SB, Monjazeb AM, Darrow MA, Thorpe SW, Kirane Preoperative radiotherapy for extremity soft tissue sarcoma; past, present AR, et al. Neoadjuvant radiotherapy is associated with R0 resection and and future perspectives on dose fractionation regimens and combined improved survival for patients with extremity soft tissue sarcoma under- modality strategies. Radiother Oncol J. 2016;119(1):14–21. going surgery: a National Cancer Database Analysis. Ann Surg Oncol. 23. Kubicek GJ, LaCouture T, Kaden M, Kim TW, Lerman N, Khrizman P, et al. 2017;24(11):3252–63. Preoperative radiosurgery for soft tissue sarcoma. Am J Clin Oncol. 12. Dagan R, Indelicato DJ, McGee L, Morris CG, Kirwan JM, Knapik J, et al. The 2018;41(1):86–9. significance of a marginal excision after preoperative radiation therapy 24. Sampath S, Schultheiss TE, Hitchcock YJ, Randall RL, Shrieve DC, Wong for soft tissue sarcoma of the extremity. Cancer. 2012;118(12):3199–207. JYC. Preoperative versus postoperative radiotherapy in soft-tissue sar- 13. Hoefkens F, Dehandschutter C, Somville J, Meijnders P, Van Gestel D. Soft coma: multi-institutional analysis of 821 patients. Int J Radiat Oncol Biol tissue sarcoma of the extremities: pending questions on surgery and Phys. 2011;81(2):498–505. radiotherapy. Radiat Oncol. 2016;11(1):136. 25. O’Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, et al. Preop- 14. Kandel R, Coakley N, Werier J, Engel J, Ghert M, Verma S, et al. Surgical erative versus postoperative radiotherapy in soft-tissue sarcoma of the margins and handling of soft-tissue sarcoma in extremities: a clinical limbs: a randomised trial. Lancet. 2002;359(9325):2235–41. practice guideline. Curr Oncol. 2013;20(3):e247–54. 15. Harati K, Goertz O, Pieper A, Daigeler A, Joneidi-Jafari H, Niggemann H, et al. Soft tissue sarcomas of the extremities: surgical margins can Ready to submit your research ? Choose BMC and benefit from: fast, convenient online submission thorough peer review by experienced researchers in your field rapid publication on acceptance support for research data, including large and complex data types • gold Open Access which fosters wider collaboration and increased citations maximum visibility for your research: over 100M website views per year At BMC, research is always in progress. Learn more biomedcentral.com/submissions

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Clinical Sarcoma ResearchSpringer Journals

Published: Oct 5, 2018

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