|
1
|
Steffens JM, Budny T, Gosheger G, De Vaal M, Rachbauer AM, Laufer A, Engel NM, Deventer N. The Impact of Resection Margins in Primary Resection of High-Grade Soft Tissue Sarcomas: How Far Is Far Enough? Biomedicines 2025; 13:1011. [PMID: 40426841 PMCID: PMC12109439 DOI: 10.3390/biomedicines13051011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/14/2025] [Accepted: 04/15/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: The World Health Organization's (WHO) classification of tumors contains around 80 entities of soft tissue sarcomas (STSs). Currently, surgery is the standard treatment for patients with localized STS, but the adequacy of resection margins in soft tissue sarcomas (STSs) remains a topic of intense discussion. Methods: This single-center study retrospectively reviewed 203 patients with primary high-grade soft tissue sarcoma, including a follow-up period of at least 24 months. Patients with prior resection, secondary STS, metastasis at presentation, or those who required amputational surgery were excluded from the study. Patients were categorized based on their margin thickness: positive (n = 13, 6.4%), 0-1 mm (n = 67, 33.0%), 1-5 mm (n = 70, 34.5%), and >5 mm (n = 27, 13.3%). Results: A total of 64 out of 203 (31.5%) patients developed a local recurrence. The estimated 5-year local-recurrence-free survival (LRFS) was 11.5% (CI 4-25%) for positive margins, 58% (CI 51-64%) for margins 0-1 mm, 76% (CI 70-81%) for margins > 1-5 mm, and 93% (CI 88-98%) for margins > 5 mm. No local recurrences occurred in patients with margins > 5 mm and adjuvant radiotherapy. Margin status significantly influenced the development of distant metastasis and overall survival. Adjuvant radiotherapy improved both local control and overall survival. Conclusions: To minimize the risk of local recurrence (LR), a resection margin greater than 5 mm should be attained. When adjuvant radiotherapy is applied, the likelihood of LR decreases even more. In scenarios where preserving critical structures is essential, a resection margin of less than 5 mm can be acceptable for ensuring local control.
Collapse
Affiliation(s)
- Julian Miles Steffens
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| | - Tymoteusz Budny
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| | - Georg Gosheger
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| | - Marieke De Vaal
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| | - Anna Maria Rachbauer
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| | - Andrea Laufer
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| | - Nina Myline Engel
- Department of Orthopedics and Trauma, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany
| | - Niklas Deventer
- Department of Orthopedics and Tumororthopedics, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany; (J.M.S.); (T.B.); (G.G.); (M.D.V.); (A.M.R.); (A.L.)
| |
Collapse
|
|
2
|
Wisdom AJ, Raut CP, Haddox CL, Hornick JL, Jagannathan JP, Painter CA, Baldini EH. Clinician's primer for soft tissue sarcomas: Nuances of histologic subtypes. Cancer 2025; 131:e35772. [PMID: 39980372 DOI: 10.1002/cncr.35772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 01/10/2025] [Accepted: 01/22/2025] [Indexed: 02/22/2025]
Abstract
Soft tissue sarcomas are a rare group of mesenchymal malignancies, with greater than 100 histologic subtypes. Advancements in understanding these subtypes has enabled histology-tailored management. This primer describes the workup and management of generalized soft tissue sarcomas of the extremity, trunk, and retroperitoneum while also highlighting the unique attributes of many subtypes. The subtypes chosen for review include those that are most common as well as those demonstrating unique behaviors or targets for management. The focus is on initial management of localized disease; however, for situations in which novel systemic agents have been discovered, the treatment of metastatic disease is discussed. This report is a reference to be used in addition to other comprehensive reviews, such as guidelines from the National Comprehensive Cancer Network, the European Society for Medical Oncology, and the American Society for Radiation Oncology. It is not a substitute for referral to an expert sarcoma center for critical pathology review and management by an experienced team. Importantly, patients who are treated at expert sarcoma centers have better outcomes than those who are not.
Collapse
Affiliation(s)
- Amy J Wisdom
- Harvard Radiation Oncology Program, Boston, Massachusetts, USA
| | - Chandrajit P Raut
- Department of Surgery, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Candace L Haddox
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medical Oncology, Sarcoma Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Jason L Hornick
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jyothi P Jagannathan
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| | - Corrie A Painter
- Count Me In, Broad Institute of Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Elizabeth H Baldini
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA
| |
Collapse
|
|
3
|
Shimatani A, Katagiri H, Murata H, Wasa J, Miyagi M, Honda Y, Takahashi M, Harada H, Asakura H, Onoe T. Significance of radiation therapy in the myxoid round-cell liposarcoma treatment regimen. Int J Clin Oncol 2024; 29:1044-1051. [PMID: 38656356 DOI: 10.1007/s10147-024-02534-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 04/10/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND AND PURPOSE Because myxoid liposarcomas are more radiosensitive than other soft tissue sarcomas, there have been several reports of 50 Gy preoperative radiation therapy combined with surgery, but the wound complication rate is reportedly high. We have performed preoperative irradiation at a reduced dose of 40 Gy and definitive radiation therapy for unresectable cases. This study aimed to report the tumor reduction rate and oncological results with a reduced dose of preoperative irradiation and the outcome of definitive irradiation for unresectable cases. MATERIALS AND METHODS Forty-one patients with myxoid liposarcoma treated in our institution between 2002 and 2021 were included. We examined the tumor volume shrinkage rate with preoperative radiation, compared complications and oncological outcomes between preoperative radiation and surgery-only cases, and investigated the prognosis and tumor shrinkage of definitive radiation cases. RESULTS The total dose irradiated was 40 Gy except in two cases. The mean tumor volume reduction rate was 52.0%. A decreased dose of preoperative radiation did not worsen clinical outcomes with fewer complications. The total dose of definitive radiation was approximately 60 Gy. The mean tumor volume reduction rate was 55.0%. The tumor shrinkage maintenance rate was 100% in a median follow-up period of 50.5 months. CONCLUSION Preoperative radiation therapy for myxoid liposarcoma near vital organs is a good approach because even with a reduced dose of 40 Gy, significant tumor reduction and excellent results were achieved. Definitive radiation therapy is the recommended treatment for older patients with serious comorbidities or inoperable patients.
Collapse
Affiliation(s)
- Akiyoshi Shimatani
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
- Department of Orthopedic Surgery, Osaka Saiseikai Nakatsu Hospital, 2-10-39, Shibata, Kita-ku, Osaka-shi, Osaka, 530-0012, Japan.
| | - Hirohisa Katagiri
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Hideki Murata
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Junji Wasa
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Michihito Miyagi
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Yosuke Honda
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Mitsuru Takahashi
- Division of Orthopedic Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Hiroyuki Harada
- Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Hirofumi Asakura
- Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Tsuyoshi Onoe
- Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| |
Collapse
|
|
4
|
Chmiel P, Rutkowski P, Spałek M, Szumera-Ciećkiewicz A, Czarnecka AM. What is the Optimal Treatment Strategy after Sarcoma R2 Surgery? Curr Treat Options Oncol 2024; 25:798-812. [PMID: 38809411 PMCID: PMC11222198 DOI: 10.1007/s11864-024-01218-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/14/2024] [Indexed: 05/30/2024]
Abstract
OPINION STATEMENT Soft tissue sarcomas (STS) are rare tumours of mesenchymal origin, most commonly occurring in the extremity but also in the retroperitoneum. The curative treatment for STS is radical surgery with wide margins, in some cases in combination with perioperative radiotherapy and chemotherapy. Nonradical resection (R2) of STS has been an emerging issue in recent decades, as optimal subsequent management remains debatable. Similarly, there is still no consensus on optimal surgical margins. Combining multiple treatment modalities in adjuvant therapy can achieve local and distant control in patients following surgery with positive margins. Patients who have undergone nonradical resection therefore require additional surgical interventions, and adjuvant radiotherapy resulting in a better prognosis but a higher number of complications. Following non-radical treatment, patients with limb and trunk wall sarcomas and retroperitoneal sarcomas should also undergo increased oncological surveillance. Given the potential issues that may emerge in such clinical situations, it is crucial to up-date the current guidelines to enhance the long-term prognosis of these patients.
Collapse
Affiliation(s)
- Paulina Chmiel
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
- Faculty of Medicine, Medical University of Warsaw, 02-091, Warsaw, Poland
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
| | - Mateusz Spałek
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
- Department of Radiotherapy I, Maria Sklodowska-Curie National Research Institute of Oncology, 02-718, Warsaw, Poland
| | - Anna Szumera-Ciećkiewicz
- Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
- Biobank Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
| | - Anna M Czarnecka
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland.
- Department of Experimental Pharmacology, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106, Warsaw, Poland.
| |
Collapse
|
|
5
|
Lebas A, Le Fevre C, Waissi W, Chambrelant I, Brinkert D, Noel G. Factors Influencing Long-Term Local Recurrence, Distant Metastasis, and Survival in Patients with Soft Tissue Sarcoma of the Extremities Treated with Radiotherapy. Cancers (Basel) 2024; 16:1789. [PMID: 38791868 PMCID: PMC11119935 DOI: 10.3390/cancers16101789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/04/2024] [Accepted: 05/05/2024] [Indexed: 05/26/2024] Open
Abstract
INTRODUCTION The prognostic factors for extremity soft-tissue sarcomas (ESTSs) treated with multimodal surgery and radiotherapy (RT) remain a subject of debate across diverse and heterogeneous studies. METHODS We retrospectively analyzed nonmetastatic ESTS patients treated with RT between 2007 and 2020 in Strasbourg, France. We assessed local control (LC), distant control (DC), overall survival (OS), and complications. RESULTS A total of 169 patients diagnosed with localized ESTS were included. The median age was 64 years (range 21-94 years). ESTS primarily occurred proximally (74.6%) and in the lower limbs (71%). Most tumors were grade 2-3 (71.1%), deep-seated (86.4%), and had R0 margins (63.9%). Most patients were treated with helical tomotherapy (79.3%). The median biologically effective dose (BED) prescribed was 75 BEDGy4 (range 45.0-109.9). The median follow-up was 5.5 years. The 5- and 10-year LC, DC, and OS rates were 91.7%, 76.8%, and 83.8% and 84.2%, 74.1%, and 77.6%, respectively. According to the univariate analysis, LC was worse for patients who received less than 75 BEDGy4 (p = 0.015). Deep tumors were associated with worse OS (p < 0.05), and grade 2-3 and undifferentiated pleomorphic sarcoma (UPS) were linked to both shorter DC and shorter OS (p < 0.05). IMRT was associated with longer LC than 3DRT (p = 0.018). Multivariate analysis revealed that patients with liposarcoma had better OS (p < 0.05) and that patients with distant relapse had shorter OS (p < 0.0001). CONCLUSION RT associated with surgical resection was well tolerated and was associated with excellent long-term rates of LC, DC, and OS. Compared with 3DRT, IMRT improved local control. Liposarcoma was a favorable prognostic factor for OS. Intermediate- and high-grade tumors and deep tumors were associated with lower DC and OS.
Collapse
Affiliation(s)
- Arthur Lebas
- Radiotherapy Department, Institut de Cancérologie Strasbourg Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033 Strasbourg, France; (A.L.); (C.L.F.); (I.C.)
| | - Clara Le Fevre
- Radiotherapy Department, Institut de Cancérologie Strasbourg Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033 Strasbourg, France; (A.L.); (C.L.F.); (I.C.)
| | - Waisse Waissi
- Radiotherapy Department, Léon Bérard Center, 28 Rue Laennec, 69008 Lyon, France;
| | - Isabelle Chambrelant
- Radiotherapy Department, Institut de Cancérologie Strasbourg Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033 Strasbourg, France; (A.L.); (C.L.F.); (I.C.)
| | - David Brinkert
- Orthopedic Surgery Department, University Hospital of Hautepierre, 1 Rue Molière, 67200 Strasbourg, France;
| | - Georges Noel
- Radiotherapy Department, Institut de Cancérologie Strasbourg Europe (ICANS), 17 Rue Albert Calmette, BP 23025, 67033 Strasbourg, France; (A.L.); (C.L.F.); (I.C.)
- Faculty of Medicine, University of Strasbourg, 4 Rue Kirschleger, 67000 Strasbourg, France
- Radiobiology Laboratory, Centre Paul Strauss, IIMIS—Imagerie Multimodale Integrative en Santé, ICube, Strasbourg University, 67081 Strasbourg, France
| |
Collapse
|
|
6
|
Dunlop HM, Atchison TJ, Zeh R, Konieczkowski DJ, Kim A, Grignol VP, Contreras CM, Obeng-Gyasi S, Pawlik TM, Pollock RE, Beane JD. Preoperative radiation therapy increases adherence in patients with high-risk extremity soft tissue sarcoma. Surgery 2024; 175:756-764. [PMID: 37996341 DOI: 10.1016/j.surg.2023.10.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Revised: 09/26/2023] [Accepted: 10/24/2023] [Indexed: 11/25/2023]
Abstract
BACKGROUND Surgery and radiation therapy remain the standard of care for patients with high-grade extremity soft tissue sarcoma that are >5 cm. Radiation therapy is time and labor-intensive for patients, and social determinants of health may affect adherence. The aim of this study was to define demographic, clinical, and treatment factors associated with the completion of radiation therapy and determine if preoperative radiation therapy improved adherence compared to postoperative radiation therapy. METHODS The cohort included patients in the National Cancer Database with high-grade extremity soft tissue sarcoma >5 cm without nodal or distant metastases who received limb-sparing surgery and radiation therapy with microscopically negative R0 margins. Multivariable logistic regression analyses identified factors associated with radiation therapy sequencing and adherence (defined as completion of 50 Gy preoperative radiation therapy or at least 60 Gy postoperative radiation therapy). A multivariable Cox Proportional Hazards model assessed overall survival. RESULTS Among 2,145 patients, 47.1% received preoperative radiation therapy (n = 1,010), and 52.9% (n = 1135) received postoperative radiation therapy. A greater proportion of patients treated with preoperative (77.2%) versus postoperative radiation therapy (64.9%, P < .0001) received the recommended dose. More patients with private insurance (49.8% vs 35.3% Medicaid vs 44.9% Medicare, P = .011) and patients treated at an academic medical center (52.6% vs 47.4%, P < .001) received preoperative radiation therapy. Patients who received preoperative radiation therapy had lower odds of receiving insufficient doses of radiation therapy (odds ratio 0.34 [95% CI 0.27-0.47]). Neither radiation therapy adherence nor sequencing were independent predictors of overall survival. CONCLUSIONS Patients who received preoperative radiation therapy were more likely to complete therapy and receive an optimal dose than patients treated with postoperative radiation therapy. Preoperative radiation therapy improves adherence and should be widely considered in patients with high-grade extremity soft tissue sarcoma, particularly in patients at risk for not completing therapy.
Collapse
Affiliation(s)
| | - T J Atchison
- The Ohio State University College of Medicine, Columbus, OH
| | - Ryan Zeh
- The University of Pittsburgh, Department of Surgery, Pittsburgh, PA
| | - David J Konieczkowski
- The Ohio State University Wexner Medical Center, Department of Radiation Oncology, Columbus, OH
| | - Alex Kim
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH
| | - Valerie P Grignol
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH
| | - Carlo M Contreras
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH
| | - Samilia Obeng-Gyasi
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH
| | - Timothy M Pawlik
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH
| | - Raphael E Pollock
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH
| | - Joal D Beane
- The Ohio State University Wexner Medical Center, Department of Surgical Oncology, Columbus, OH.
| |
Collapse
|
|
7
|
Annicchiarico A, Montali F, Baldinu M, Casali L, Virgilio E, Costi R. Leiomyosarcoma of the rectum: A systematic review of recent literature. J Surg Oncol 2024; 129:365-380. [PMID: 37814590 DOI: 10.1002/jso.27481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 09/19/2023] [Accepted: 09/28/2023] [Indexed: 10/11/2023]
Abstract
Leiomyosarcomas (LMSs) are rare tumors originating from the muscular layer. We performed a literature review of cases of confirmed rectal leiomyosarcomas (rLMSs) to clarify the history of such an infrequent tumor arising at such an uncommon location. In this research local recurrence was related to poorly differentiated rLMS and no other association between recurrence and any criteria was found. Concerning overall survival (OS), rLMS patients developing recurrence presented shorter longevity compared with the group without.
Collapse
Affiliation(s)
- Alfredo Annicchiarico
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of General Surgery, Vaio Hospital, Fidenza, Italy
| | - Filippo Montali
- Department of General Surgery, Vaio Hospital, Fidenza, Italy
| | - Manuel Baldinu
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Lorenzo Casali
- Department of General Surgery, Vaio Hospital, Fidenza, Italy
| | - Edoardo Virgilio
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of General Surgery, Vaio Hospital, Fidenza, Italy
| | - Renato Costi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Department of General Surgery, Vaio Hospital, Fidenza, Italy
| |
Collapse
|
|
8
|
Ishida H, Funaki S, Taniguchi S, Morii E, Shintani Y. Familial multiple endocrine neoplasia type 1 with intrathoracic low-grade fibromyxoid sarcoma. Surg Case Rep 2024; 10:16. [PMID: 38200366 PMCID: PMC10781903 DOI: 10.1186/s40792-024-01809-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 01/03/2024] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by endocrine tumors with mainly a parathyroid, pancreatic, or anterior pituitary origin. Low-grade fibromyxoid sarcoma (LGFMS) is a rare low-grade soft tissue tumor. There is one known report of a patient with MEN1 complicated by LGFMS, which is very rare. Our report represents the second documented case, providing valuable insights. CASE PRESENTATION A 31-year-old man with the chief complaint of a cough underwent chest contrast-enhanced computed tomography, which revealed a giant hypoabsorptive tumor with a maximum diameter of 23 cm in the left thoracic cavity. The patient was diagnosed with MEN1, as he also possessed a pancreatic neuroendocrine tumor and parathyroid tumor, and because his father had been found to have MEN1. To control hypercalcemia, surgery for the parathyroid tumor was initially performed, followed by surgical resection of the giant thoracic tumor for diagnosis and treatment. Histopathological examination findings of the tumor resulted in a diagnosis of LGFMS. CONCLUSION We experienced a very rare MEN1 with LGFMS. Although endocrine tumors generally occur more frequently in MEN1, non-endocrine tumors such as the present case should also be noted, reinforcing the importance of systemic imaging scrutiny in addition to early diagnosis and long-term follow-up of MEN1 patients.
Collapse
Affiliation(s)
- Hiroto Ishida
- Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-City, Osaka, 565-0871, Japan
| | - Soichiro Funaki
- Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-City, Osaka, 565-0871, Japan.
| | - Seiji Taniguchi
- Department of Thoracic Surgery, Osaka Habikino Medical Center, 3-7-1, Habikino, Habikino-City, Osaka, 583-8588, Japan
| | - Eiichi Morii
- Department of Pathology, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-City, Osaka, 565-0871, Japan
| | - Yasushi Shintani
- Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-City, Osaka, 565-0871, Japan
| |
Collapse
|
|
9
|
Qi W, Ren Y, Wang H, Wan Y, Wang D, Yao J, Pan H. Establishment and validation of nomogram models for overall survival and cancer-specific survival in spindle cell sarcoma patients. Sci Rep 2023; 13:23018. [PMID: 38155261 PMCID: PMC10754933 DOI: 10.1038/s41598-023-50401-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 12/19/2023] [Indexed: 12/30/2023] Open
Abstract
Spindle cell sarcoma (SCS) is rare in clinical practice. The objective of this study was to establish nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. The data of patients with SCS between 2004 and 2020 were extracted from the SEER database and randomly allocated to a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to screen for independent risk factors for both overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate Cox analysis. Then, we validated the nomograms by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, Kaplan‒Meier curves and log-rank tests were applied to compare patients with SCS at three different levels and in different treatment groups. A total of 1369 patients with SCS were included and randomly allocated to a training cohort (n = 1008, 70%) and a validation cohort (n = 430, 30%). Age, stage, grade, tumour location, surgery, radiation and diagnosis year were found to be independent prognostic factors for OS by Cox regression analysis, while age, stage, grade, tumour location and surgery were found to be independent prognostic factors for CSS. The nomogram models were established based on the results of multivariate Cox analysis for both OS and CSS. The C-indices of the OS model were 0.76 and 0.77 in the training and validation groups, respectively, while they were 0.76 and 0.78 for CSS, respectively. For OS, the 3- and 5-year AUCs were 0.801 and 0.798, respectively, in the training cohort and 0.827 and 0.799, respectively, in the validation cohort; for CSS, they were 0.809 and 0.786, respectively, in the training cohort and 0.831 and 0.801, respectively, in the validation cohort. Calibration curves revealed high consistency in both OS and CSS between the observed survival and the predicted survival. In addition, DCA was used to analyse the clinical practicality of the OS and CSS nomogram models and revealed that they had good net benefits. Surgery remains the main treatment method for SCS patients. The two nomograms we established are expected to accurately predict the personalized prognosis of SCS patients and may be useful for clinical decision-making.
Collapse
Affiliation(s)
- Weihui Qi
- Department of Orthopaedics, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People's Republic of China
- Department of Orthopaedics, Hangzhou Ding Qiao Hospital, Hangzhou, China
| | - Yanyun Ren
- Department of Stomatology, No. 903 Hospital of PLA, Hangzhou, China
| | - Huang Wang
- Department of Orthopaedics, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People's Republic of China
- Department of Orthopaedics, Hangzhou Ding Qiao Hospital, Hangzhou, China
| | - Yue Wan
- Department of Stomatology, No. 903 Hospital of PLA, Hangzhou, China
| | - Dong Wang
- Department of Orthopaedics, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People's Republic of China
- Department of Orthopaedics, Hangzhou Ding Qiao Hospital, Hangzhou, China
| | - Jun Yao
- Department of Orthopaedics, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People's Republic of China.
- Department of Orthopaedics, Hangzhou Ding Qiao Hospital, Hangzhou, China.
| | - Hao Pan
- Department of Orthopaedics, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, People's Republic of China.
- Department of Orthopaedics, Hangzhou Ding Qiao Hospital, Hangzhou, China.
| |
Collapse
|
|
10
|
Jiang L, Gong Y, Jiang J, Zhao D. Construction of novel predictive tools for post-surgical cancer-specific survival probability in patients with primary chondrosarcoma and external validation in Chinese cohorts: a large population-based retrospective study. J Cancer Res Clin Oncol 2023; 149:13027-13042. [PMID: 37466790 DOI: 10.1007/s00432-023-05186-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023]
Abstract
BACKGROUND Surgery is the predominant treatment modality for chondrosarcoma. This study aims to construct a novel clinic predictive tool that accurately predicts the 3-, 5-, and 8-year probability of cancer-specific survival (CSS) for primary chondrosarcoma patients who have undergone surgical treatment. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 982 primary chondrosarcoma patients after surgery, who were randomly divided into two sets: training set (60%) and internal validation set (40%). Cox proportional regression analyses were used to screen post-surgical independent prognostic variables in primary chondrosarcoma patients. These identified variables were used to construct a nomogram to predict the probability of post-surgical CSS of primary chondrosarcoma patients. The k-fold cross-validation method (k = 10), Harrell's concordance index (C-index), receiver operating characteristic curve (ROC) and area under curve (AUC) were used to assess the predictive accuracy of the nomogram. Calibration curve and decision curve analysis (DCA) were used to validate the clinical application of the nomogram. RESULTS Age, tumor size, disease stage and histological type were finally identified post-surgical independent prognostic variables. Based the above variables, a nomogram was constructed to predict the 3-, 5- and 8-year probability of post-surgical CSS in primary chondrosarcoma patients. The results of the C-index showed excellent predictive performance of the nomogram (training set: 0.837, 95% CI: 0.766-0.908; internal validation set: 0.835, 95% CI: 0.733-0.937; external validation set: 0.869, 95% CI: 0.740-0.998). The AUCs of ROC were all greater than 0.830 which again indicated that the nomogram had excellent predictive performance. The results of calibration curve and DCA indicated that the clinical applicability of this nomogram was outstanding. Finally, the risk classification system and online access version of the nomogram was developed. CONCLUSION We constructed the first nomogram to accurately predict the 3-, 5- and 8-year probability of post-surgical CSS in primary chondrosarcoma patients. This nomogram would assist surgeons to provide individualized post-surgical survival predictions and clinical strategies for primary chondrosarcoma patients.
Collapse
Affiliation(s)
- Liming Jiang
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China
| | - Yan Gong
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China
| | - Jiajia Jiang
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China
| | - Dongxu Zhao
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun, 130033, Jilin, People's Republic of China.
| |
Collapse
|
|
11
|
Sargos P, Stoeckle E, Ducassou A, Giraud A, Mervoyer A, Italiano A, Albert S, Ferron G, Bellera C, Kantor G. High dose (54 Gy) pre-operative helical tomotherapy for retroperitoneal liposarcoma: Results of a phase II multicenter study. Radiother Oncol 2023; 186:109791. [PMID: 37437608 DOI: 10.1016/j.radonc.2023.109791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 06/19/2023] [Accepted: 07/01/2023] [Indexed: 07/14/2023]
Abstract
PURPOSE To evaluate efficacy and feasibility of high-dose intensity-modulated radiotherapy (RT) with pre-operative helical tomotherapy, delivering 54 Gy/30 fractions in patients with retroperitoneal liposarcomas (RPLS). MATERIALS AND METHODS Patients with operable, biopsy-proven, RPLS were included in this phase II multicenter study (ClinicalTrials.gov: NCT01841047). The primary objectives were to analyze loco-regional relapse free survival (LRFS), overall survival (OS) and toxicities, graded according to CTCAE V3.0. RESULTS From April 2009 to September 2013, 48 patients were included. Histological types were: 20 well differentiated and 28 dedifferentiated liposarcomas. Median clinical target volume (CTV) was 2570 cc (range, 230-8734 cc). The radio-surgical schedule was completed as planned in all patients apart from one. A monobloc wide excision was achieved for all patients. Surgical margins were R0 (16; 34%), R1 (28; 60%), R2 (2; 4%) or missing (1, 2%).With a median follow-up of 5.5 years, 3-year LRFS rate was 74.2% (95%CI: [59.1%; 84.5%]). At 5 years, cumulative incidence of loco-regional relapse for well differentiated and dedifferentiated RPLS was 10% and 18%, respectively. The 5-year OS was 73.9% [95%CI: 58.7-84.3%]. During RT, the most common grade 3-4 adverse events were hematological (N = 20; 41.6%). After surgery and during follow-up, 17 patients (35.4%) presented a grade 3-4 toxicity. Two patients (4.1%) died due to a duodenal toxicity. Nine second cancers were observed. CONCLUSION From this phase II trial of preoperative RT in RPLS patients, the dose level proposed cannot be considered safe, leading to non-negligible toxicity and second cancers rates. Our results, combined with STRASS-1 study, suggest that the ideal indication of RT for patients with RPLS still remains to be determined.
Collapse
Affiliation(s)
- Paul Sargos
- Department of Radiotherapy, Institut Bergonie, 229 cours de l'Argonne, 33076 Bordeaux, France.
| | - Eberhard Stoeckle
- Department of Surgery, Institut Bergonie, 229 cours de l'Argonne, 33076 Bordeaux, France
| | - Anne Ducassou
- Department of Radiotherapy, Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Antoine Giraud
- Clinical and Epidemiological Research Unit, INSERM CIC1401, Institut Bergonié, Comprehensive Cancer Center, F-33000 Bordeaux, France
| | - Augustin Mervoyer
- Department of Radiotherapy, Institut de Cancerologie de l'Ouest, Nantes, France
| | - Antoine Italiano
- Department of Medical Oncology, Institut Bergonie, 229 cours de l'Argonne, 33076 Bordeaux, France
| | - Sabrina Albert
- Clinical and Epidemiological Research Unit, INSERM CIC1401, Institut Bergonié, Comprehensive Cancer Center, F-33000 Bordeaux, France
| | - Gwenael Ferron
- Department of Surgical Oncology, INSERM CRCT19 (Oncogenesis of Sarcoma), Institut Claudius Regaud- Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
| | - Carine Bellera
- Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Epicene team, UMR 1219, F-33000 Bordeaux, France; Inserm CIC1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, F-33000 Bordeaux, France.
| | - Guy Kantor
- Department of Radiotherapy, Institut Bergonie, 229 cours de l'Argonne, 33076 Bordeaux, France
| |
Collapse
|
|
12
|
Simões R, Augustin Y, Gulliford S, Dehbi HM, Hoskin P, Miles E, Harrington K, Miah AB. Toxicity, normal tissue and dose-volume planning parameters for radiotherapy in soft tissue sarcoma of the extremities: A systematic review of the literature. Radiother Oncol 2023; 186:109739. [PMID: 37315584 DOI: 10.1016/j.radonc.2023.109739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 05/25/2023] [Accepted: 06/07/2023] [Indexed: 06/16/2023]
Abstract
BACKGROUND Patients with soft tissue sarcoma of the extremities (STSE) are left with high incidence of toxicities after Radiotherapy (RT). Understanding the normal tissue dose relationship with the development of long-term toxicities may enable better RT planning in order to reduce treatment toxicities for STSE. This systematic review of the literature aims at reporting the incidence of acute and late toxicities and identifying RT delineation guidance the normal tissues structures and dose-volume parameters for STSE. METHODS A literature search of PUBMED-MEDLINE for studies that reported data on RT toxicity outcomes, delineation guidelines and dose-volume parameters for STSE from 2000 to 2022. Data has been tabulated and reported. RESULTS Thirty of 586 papers were selected after exclusion criteria. External beam RT prescriptions ranged from 30 to 72 Gy. The majority of studies reported the use of Intensity Modulated RT (IMRT) (27%). Neo-adjuvant RT was used in 40%. The highest long-term toxicities were subcutaneous and lymphoedema, reported when delivering 3DCRT. IMRT had a lower incidence of toxicities. Normal tissue outlining such as weight-bearing bones, skin and subcutaneous tissue, corridor and neurovascular bundle was recommended in 6 studies. Nine studies recommended the use of dose-volume constraints, but only one recommended evidence-based dose-volume constraints. CONCLUSION Although the literature is replete with toxicity reports, there is a lack of evidence-based guidance on normal tissue and dose-volume parameters and strategies to reduce the normal tissues irradiation when optimising RT plans for STSE are poor compared to other tumour sites.
Collapse
Affiliation(s)
- Rita Simões
- The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK; Radiotherapy Trials Quality Assurance (RTTQA) group, Mount Vernon Hospital, Northwood, UK; University College London Hospital NHS Foundation Trust, London, UK.
| | | | - Sarah Gulliford
- University College London Hospital NHS Foundation Trust, London, UK; University College London, London, UK.
| | | | - Peter Hoskin
- Radiotherapy Trials Quality Assurance (RTTQA) group, Mount Vernon Hospital, Northwood, UK; University of Manchester, Manchester, UK.
| | - Elizabeth Miles
- Radiotherapy Trials Quality Assurance (RTTQA) group, Mount Vernon Hospital, Northwood, UK.
| | - Kevin Harrington
- The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
| | - Aisha B Miah
- The Institute of Cancer Research, London, UK; The Royal Marsden Hospital, London, UK.
| |
Collapse
|
|
13
|
Sacchetti F, Alsina AC, Muratori F, Scoccianti G, Neri E, Kaya H, Sabah D, Capanna R, Campanacci DA. Tumor size and surgical margins are important prognostic factors of synovial sarcoma - A retrospective study. J Orthop 2023; 42:74-79. [PMID: 37533628 PMCID: PMC10391603 DOI: 10.1016/j.jor.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 06/28/2023] [Accepted: 07/06/2023] [Indexed: 08/04/2023] Open
Abstract
Background Synovial Sarcoma (SS) is a rare soft tissue sarcoma. Mean time to get a SS diagnosis from the onset of symptoms is 10 years, furthermore, SS is associated with late metastasis. Surgery is the main treatment option, whose quality deeply affects SS outcomes, and it can be associated to preoperative or post-operative radiotherapy. Chemotherapy is considered very effective in Children, while in adults its efficacy is still under debate. The aim of this study was to investigate the oncologic results in SS treatment and to identify the risk factors for local and systemic control of the disease. Methods From 1994 to 2018, 211 patients affected by SS were treated in 3 Referral Centres of Orthopaedic Oncology. One hundred seventy-seven patients were included in the study, the median follow-up length was 96 months (5-374). Results Overall Survival on the Kaplan Meier Analyses was 80%, 70% and 56% at 5, 10 and 20 years. In multivariate analyses, OS correlated with tumour size and negative surgical margins. Chemotherapy use wasn't associated with better survival although patients who underwent CT had bigger and more aggressive tumours. Conclusions Our findings suggests that surgery with negative margins is the most important factor in Synovial Sarcoma. Adjuvant treatments as chemotherapy and radiation therapy didn't change the disease's course.
Collapse
Affiliation(s)
| | - Andac Celasun Alsina
- Ege University, Faculty of Medicine, Department of Orthopedics and Traumatology, Turkey
| | | | | | | | - Huseyin Kaya
- Ege University, Faculty of Medicine, Department of Orthopedics and Traumatology, Turkey
| | - Dundar Sabah
- Ege University, Faculty of Medicine, Department of Orthopedics and Traumatology, Turkey
| | | | | |
Collapse
|
|
14
|
Koeksal M, van der Hoek M, Scafa D, Koch D, Leitzen C, Schmeel LC, Feldmann G, Strauss A, Koob S, Giordano FA. Low rate of function-limiting side effects with high-dose adjuvant radiotherapy in high-grade soft tissue extremity sarcomas: a retrospective single-center analysis over 10 years. J Cancer Res Clin Oncol 2023; 149:4877-4888. [PMID: 36287264 PMCID: PMC9607852 DOI: 10.1007/s00432-022-04423-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Over the years, radiotherapy has been established as a tool to improve local control for high-grade sarcomas. Although the European Society for Medical Oncology guidelines has taken notice of a shift toward a neoadjuvant radiotherapy approach, the American Society for Radiation Oncology guidelines clearly favor a neoadjuvant approach, citing debilitating long-term adverse effects when radiotherapy is applied postoperatively. In this study, we examined these irradiation-associated adverse events for adjuvant radiotherapy and focused on the prognostic factors for disease outcome, including local control. METHODS In this retrospective study, data for 106 patients with extremity soft-tissue sarcomas diagnosed between 1997 and 2021, of which 40 received adjuvant radiotherapy, were collected from the clinical and radiological information systems of a high-volume sarcoma treatment center. These data were then analyzed for radiation-associated side effects as well as predictive factors for overall survival, disease-free survival, local control, and surgical complications. RESULTS Radiotherapy was beneficial to patients improving local control, especially for high-grade sarcomas, even when those were resected with negative margins. Side effects due to radiotherapy occurred in 87.5% of the patients, and these effects primarily included radiation dermatitis in 67.5%; however, only 40.0% had any adverse event of ≥ grade 2 according to Common Terminology Criteria for Adverse Events. Long-term function-limiting side effects occurred in 45.0% of the patients; 10% exhibited ≥ grade 2 function-limiting adverse events. Greater time between surgery and adjuvant radiotherapy was beneficial for the patients, whereas joint infiltrating sarcomas were associated with more severe long term, function-limiting adverse events. 28.3% of the patients experienced a recurrence at any location (median time 18.35 months) and in 16% the recurrence was local (median time 16.11 months), resulting in 1, 3, and 5 year disease-free survival rates of 74.1, 58.9, and 38.5% and local control rates of 78.7, 61.6, and 42.8% were observed, respectively. CONCLUSION Recurrences may be avoided with high-dose radiation, especially for high-grade G2 and G3 sarcomas, even after complete R0 resection. This resulted in a low rate of severe long-term function-limiting adverse events. Thus, adjuvant radiotherapy should be seriously considered when planning patient treatment, especially when treating patients that present with high-grade sarcomas.
Collapse
Affiliation(s)
- Muemtaz Koeksal
- Department of Radiation Oncology, University Medical Center, Bonn, Germany.
| | - Maike van der Hoek
- Department of Radiation Oncology, University Medical Center, Bonn, Germany
| | - Davide Scafa
- Department of Radiation Oncology, University Medical Center, Bonn, Germany
| | - David Koch
- Department of Radiation Oncology, University Medical Center, Bonn, Germany
| | - Christina Leitzen
- Department of Radiation Oncology, University Medical Center, Bonn, Germany
| | - Leonard C Schmeel
- Department of Radiation Oncology, University Medical Center, Bonn, Germany
| | - Georg Feldmann
- Internal Medicine Oncology, Hematology and Rheumatology, University Medical Center, Bonn, Germany
| | - Andreas Strauss
- Orthopaedics and Trauma Surgery, University Medical Center, Bonn, Germany
| | - Sebastian Koob
- Orthopaedics and Trauma Surgery, University Medical Center, Bonn, Germany
| | - Frank A Giordano
- Department of Radiation Oncology, University Medical Center, Bonn, Germany
- Department of Radiation Oncology, University Medical Center, Mannheim, Germany
| |
Collapse
|
|
15
|
Laskar S, Manjali JJ, Chargari C, Chard J. Brachytherapy for Organ and Function Preservation in Soft-Tissue Sarcomas in Adult and Paediatric Patients. Clin Oncol (R Coll Radiol) 2023:S0936-6555(23)00218-2. [PMID: 37344243 DOI: 10.1016/j.clon.2023.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 05/31/2023] [Accepted: 06/06/2023] [Indexed: 06/23/2023]
Abstract
Adjuvant radiotherapy is an integral component in the management of soft-tissue sarcomas. Brachytherapy is a very convenient and conformal way of delivering adjuvant radiotherapy in such tumours, which spares the surrounding normal tissue. Randomised studies have established the efficacy of brachytherapy in the adjuvant setting, with a 5-year local control of 80-85%. High dose rate, low dose rate and pulsed dose rate have shown equivalent local control, but high dose rate has gained popularity owing to patient convenience, radiation safety and flexibility in dose optimisation. Freehand insertion perioperative brachytherapy (intraoperative placement and postoperative treatment) is the most commonly used technique in soft-tissue sarcomas, with intraoperative radiotherapy and radioactive seed placement being the less commonly used techniques. Brachytherapy can be used as monotherapy or in combination with external beam radiotherapy, such as in cases of close/positive margins for safe dose escalation. Although the quantum of side-effects with external beam radiotherapy has considerably reduced with the evolution of technology and the introduction of intensity modulation (intensity-modulated radiotherapy), brachytherapy still scores better in terms of dose conformality, especially in recurrent tumours (previously irradiated) and when used to treat paediatric and geriatric patients.
Collapse
Affiliation(s)
- S Laskar
- Department of Radiation Oncology, Tata Memorial Centre (TMC), Mumbai, India; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, India.
| | - J J Manjali
- Department of Radiation Oncology, Tata Memorial Centre (TMC), Mumbai, India; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, India
| | - C Chargari
- Department of Radiation Oncology, Institute Gustave Roussy, France
| | - J Chard
- Department of Radiation Oncology, Westmead Hospital, Sydney, Australia
| |
Collapse
|
|
16
|
Dammerer D, Neugebauer J, Braito M, Wagner M, Neubauer M, Moser L, Süß M, Liebensteiner M, Putzer D. Midterm Results of High-Dose-Rate Intraoperative Brachytherapy in the Treatment of Soft Tissue Sarcomas. Cancers (Basel) 2023; 15:2854. [PMID: 37345191 DOI: 10.3390/cancers15102854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/27/2023] [Accepted: 05/15/2023] [Indexed: 06/23/2023] Open
Abstract
INTRODUCTION According to the literature only sparse data are available on the use of high-dose-rate intraoperative brachytherapy (IOHDR-BT) as a boost to external-beam irradiation (EBRT) in combination with a wide resection in patients with high-grade soft tissue sarcomas (STS). MATERIALS AND METHODS Applying a retrospective study design, we investigated all patients who between 2010 and 2016 underwent marginal resection of a high-grade STS and intraoperative radiotherapy, followed by EBRT. We included only patients with a traceable follow-up time of at least two years. Of 89 patients, 35 met our inclusion criteria and showed an average follow-up of four years. RESULTS We found an overall 2-year local control rate of 94.3%. The local recurrence rate for R0 resections was 6%, whereas recurrences occurred in 13% of R1 resections and in 100% of R2 resections. One affected patient received only intraoperative radiotherapy. The recurrence rate by tumour entity was 36% for LPS, 11% for myxofibrosarcoma and 17% for undifferentiated pleomorphic sarcoma. CONCLUSION The treatment regimen consisting of limb-preserving surgery, IORT and pre- or postoperative radiotherapy consistently shows excellent local control rates.
Collapse
Affiliation(s)
- Dietmar Dammerer
- Department of Orthopaedics and Traumatology, University Hospital Krems, 3500 Krems, Austria
- Department of Orthopaedics and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Karl Landsteiner Private University for Health Sciences, 3500 Krems, Austria
| | - Johannes Neugebauer
- Department of Orthopaedics and Traumatology, University Hospital Krems, 3500 Krems, Austria
- Department of Orthopaedics and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Karl Landsteiner Private University for Health Sciences, 3500 Krems, Austria
| | - Matthias Braito
- Department of Orthopaedics and Traumatology, St. Johann in Tirol Hospital, 6380 St. Johann in Tirol, Austria
| | - Moritz Wagner
- Department of Orthopaedics and Traumatology, St. Johann in Tirol Hospital, 6380 St. Johann in Tirol, Austria
| | - Markus Neubauer
- Department of Orthopaedics and Traumatology, University Hospital Krems, 3500 Krems, Austria
| | - Lukas Moser
- Department of Orthopaedics and Traumatology, University Hospital Krems, 3500 Krems, Austria
| | - Markus Süß
- Department of Orthopaedics and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Michael Liebensteiner
- Department of Orthopaedics and Traumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - David Putzer
- Department of Experimental Orthopaedics, Medical University of Innsbruck, 6020 Innsbruck, Austria
| |
Collapse
|
|
17
|
Lu YJ, Chen CC, Chen SH, Lin CH, Lin YT, Lin CH, Hsu CC. Incidence and Risk Factors for Extremity Osteoradionecrosis after Limb-Sparing Surgery and Adjuvant Radiotherapy. Cancers (Basel) 2023; 15:cancers15082339. [PMID: 37190268 DOI: 10.3390/cancers15082339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 04/05/2023] [Accepted: 04/11/2023] [Indexed: 05/17/2023] Open
Abstract
Osteoradionecrosis (ORN) is a major complication after radiotherapy. Most studies on ORN have focused on patients with mandibular lesions, with few studies including patients with extremity soft tissue sarcoma (STS). We included 198 patients with extremity STS who underwent limb-sparing surgery and adjuvant radiotherapy between 2004 and 2017. The incidence rate of extremity ORN was 3.5% (7/198), with most lesions (6/7) located in the lower extremities. The mean follow-up time was 62 months. Clinical presentations included chronic ulcers, soft tissue necrosis, sinus discharge, bone nonunion, and pathological fractures. Compared with the non-ORN group, the ORN group had a significantly higher total radiation dose (68 Gy vs. 64 Gy, p = 0.048) and greater use of intraoperative periosteal stripping (p = 0.008). Repeat surgeries and subsequent soft tissue reconstruction or limb amputation were performed as treatments. The risk and management of ORN in patients with extremity STS was ignored previously. Because the disease is complex and affects both clinicians and patients, careful surveillance should be undertaken.
Collapse
Affiliation(s)
- Yun-Jui Lu
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chun-Chieh Chen
- Department of Orthopedic Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Shih-Heng Chen
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Cheng-Hung Lin
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Yu-Te Lin
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chih-Hung Lin
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chung-Chen Hsu
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| |
Collapse
|
|
18
|
Raza SM, Riaz A, Mansha MA, Fasih S, Awan UK, Siddiqui K, Rafi I, Shoaib A, Abu Bakar M, Fareed MM. Radiotherapy and Limb-Sparing Surgery in the Management of Localized Soft Tissue Sarcomas: Tertiary Care Center Experience From Pakistan. JCO Glob Oncol 2023; 9:e2200047. [PMID: 36989464 PMCID: PMC10281447 DOI: 10.1200/go.22.00047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 11/06/2022] [Accepted: 02/02/2023] [Indexed: 03/31/2023] Open
Abstract
PURPOSE When combined with radiotherapy, limb salvage surgery is an alternative to amputation. This study sought to determine the limb-sparing treatment outcomes in patients diagnosed with soft tissue extremity sarcomas treated at our institution. MATERIALS AND METHODS All adult patients with extremity soft tissue sarcoma treated with the radical limb salvage strategy at Shaukat Khanum Memorial Cancer Hospital and Research Canter, Lahore, Pakistan, between January 2017 and December 2019 were retrospectively assessed. RESULTS A total of 122 patients were included in the study. The mean age was 42 years (range 19-82), and 64 (52.5%) were males. The majority of patients, 65 (53.3%), were diagnosed with stage III and grade III disease according to American Joint Committee on Cancer TNM classification (Eighth edition). The most common surgical modality was wide local excision that was performed in 106 (86.9%) patients. Adjuvant radiation treatment was given in 111 (91%) patients, whereas 11 (9%) patients received neoadjuvant radiation treatment. The mean dose was 58 Gy (range: 46-66 Gy). Eighty-two (67.2%) of the patients were disease-free on post-treatment radiologic scans with disease recurrence observed in 40 (32.8%) patients. The median disease-free survival was 8 months (95% CI, 5.45 to 10.55). Local recurrence and distant metastases developed in 16 (13%) and 24 (20%) patients, respectively. CONCLUSION About two thirds of patients with extremity soft tissue sarcoma were successfully treated with limb salvage strategy, surgery, and radiation therapy. However, high rate of relapse warrants further novel strategies in this patient population.
Collapse
Affiliation(s)
- Syed M. Raza
- Department of Clinical & Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Adeel Riaz
- Department of Clinical & Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Muhammad A. Mansha
- Department of Clinical & Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Samir Fasih
- Department of Medical Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Umme Kalsoom Awan
- Department of Medical Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Kashif Siddiqui
- Department of Medical Imaging, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Ilyas Rafi
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Ahmed Shoaib
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan
| | - Muhammad Abu Bakar
- Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital & Research Center, Lahore, Pakistan
| | - Muhammad M. Fareed
- Department of Radiation Oncology, West Virginia University School of Medicine, Morgantown, WV
| |
Collapse
|
|
19
|
A Simple-to-Use Nomogram for Predicting Postoperative Early Death Risk in Elderly Patients with Spinal Tumors: A Population-Based Study. JOURNAL OF ONCOLOGY 2023; 2023:2805786. [PMID: 36915645 PMCID: PMC10008115 DOI: 10.1155/2023/2805786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 02/13/2023] [Accepted: 02/20/2023] [Indexed: 03/07/2023]
Abstract
Background For elderly patients with primary spinal tumors, surgery is the best option for many elderly patients, in addition to palliative care. However, due to the unique physical function of elderly patients, the short-term prognosis is often unpredictable. It is therefore essential to develop a novel nomogram as a clinical aid to predict the risk of early death for elderly patients with primary spinal tumors who undergo surgery. Materials and Methods In this study, clinical data were obtained from 651 patients through the SEER database, and they were retrospectively analyzed. Logistic regression analyses were used for risk-factor screening. Predictive modeling was performed through the R language. The prediction models were calibrated as well as evaluated for accuracy in the validation cohort. The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate the functionality of the nomogram. Results We identified four separate risk factors for constructing nomograms. The area under the receiver operating characteristic curve (training set 0.815, validation set 0.815) shows that the nomogram has good discrimination ability. The decision curve analysis demonstrates the clinical use of this nomogram. The calibration curve indicates that this nomogram has high accuracy. At the same time, we have also developed a web version of the online nomogram for clinical practitioners to apply. Conclusions We have successfully developed a nomogram that can accurately predict the risk of early death of elderly patients with primary spinal tumors undergoing surgery, which can provide a reference for clinicians.
Collapse
|
|
20
|
AlDossary NM, Ostler C, Donovan-Hall M, Metcalf CD. Non-oncological outcomes following limb salvage surgery in patients with knee sarcoma: a scoping review. Disabil Rehabil 2022; 44:4531-4545. [PMID: 33756091 DOI: 10.1080/09638288.2021.1900409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 02/28/2021] [Accepted: 03/03/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE Limb salvage surgery is a surgical procedure for tumour resection in bone and soft-tissue cancers. Guidelines aim to preserve as much function and tissue of the limb as possible. Surgical outcome data is routinely available as part of surgical reporting processes. What is less known are important non-oncological outcomes throughout recovery from both clinical and patient perspectives. The objective of this review was to explore non-oncological outcomes in patients diagnosed with sarcoma around the knee following limb salvage surgery. MATERIALS AND METHODS A scoping review methodology was used, and results analysed using CASP checklists. RESULTS Thirteen studies were included and following appraisal and synthesis, three themes emerged as providing important measures intrinsic to successful patient recovery: (1) physical function, (2) quality of life and, (3) gait and knee goniometry. Specifically, patients develop range of motion complications that alter gait patterns and patients often limit their post-operative participation in sport and leisure activities. CONCLUSIONS This study has shown the importance of exploring confounding factors, adopting a holistic view of patient recovery beyond surgical outcomes, proposing evidence-based guidance to support and inform healthcare providers with clinical decision-making. This review highlights the paucity and lack of quality of research available, emphasising how under-represented this population is in the research literature.IMPLICATIONS FOR REHABILITATIONPatients having undergone LSS often have limited participation in sport and leisure activities.Patients can develop range of motion complications, such as flexion contracture or extension lag, which may affect the pattern of gait.Clinical consideration should be given to walking ability and gait patterns during the rehabilitation phase to prevent poor functional outcomes during recovery.Variation of treatment protocols, outcome measurement and rehabilitative care has been identified as important in predicting the outcomes in recovery from LSS procedures.
Collapse
Affiliation(s)
- Nafla M AlDossary
- Physical Therapy Department, King Fahad Specialist Hospital, Dammam City, Saudi Arabia
| | - Chantel Ostler
- Portsmouth Enablement Centre, Portsmouth University Hospitals NHS Trust, Portsmouth, UK
- School of Health Sciences, University of Southampton, Southampton, UK
- Exceed Research Network, Lisburn, UK
| | - Maggie Donovan-Hall
- Portsmouth Enablement Centre, Portsmouth University Hospitals NHS Trust, Portsmouth, UK
- School of Health Sciences, University of Southampton, Southampton, UK
| | - Cheryl D Metcalf
- Portsmouth Enablement Centre, Portsmouth University Hospitals NHS Trust, Portsmouth, UK
- School of Health Sciences, University of Southampton, Southampton, UK
| |
Collapse
|
|
21
|
Laughlin BS, Golafshar MA, Lin K, Goulding K, Roesler K, Vern-Gross T, Seetharam M, Zaniletti I, Ashman JB. Long-term experience with intraoperative electron radiation therapy boost in extremity sarcoma. J Surg Oncol 2022; 126:1279-1287. [PMID: 35856506 DOI: 10.1002/jso.27024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/17/2022] [Accepted: 07/12/2022] [Indexed: 11/11/2022]
Abstract
BACKGROUND In patients with extremity soft tissue sarcoma (eSTS), we describe outcomes of preoperative external beam radiation therapy (EBRT), limb-sparing surgery (LSS), and intraoperative electron radiation therapy (IOERT). METHODS One hundred and eighteen patients with eSTS treated between October 17, 2002 and July 28, 2021 were identified. EBRT was delivered preoperatively followed by LSS and IOERT. RESULTS The median follow-up was 24.9 months. The presentation was primary in 102 (94%) patients and recurrent in 6 (6%) patients. Tumor location was lower extremity in 82 (76%) patients and upper extremity in 26 (24%) patients. Stage distribution was as follows: 3 (3%) IA, 24 (22%) IB, 31 (29%) II, 24 (22%) IIIA, and 25 (23%) IIIB. Final surgical margins were negative in 96 (89%) patients. The 5-year local control, failure-free survival, and overall survival were 94%, 75%, and 64%, respectively. Univariate analysis identified age >50, lower extremity, and higher grade as significant negative prognostic factors for overall survival. Grade 3 fracture or osteoradionecrosis requiring surgical fixation, neuropathy, and lymphedema occurred in 7 (6%), 1 (1%), and 0 patients, respectively. CONCLUSIONS This study represents one of the largest series using preoperative EBRT, LSS, and IOERT for eSTS, with high local control and a low rate of late severe toxicity.
Collapse
Affiliation(s)
- Brady S Laughlin
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona, USA
| | - Michael A Golafshar
- Department of Qualitative Health Sciences, Mayo Clinic, Scottsdale, Arizona, USA
| | - Keldon Lin
- Mayo Clinic Alix School of Medicine, Scottsdale, Arizona, USA
| | - Krista Goulding
- Department of Orthopedic Surgery, Mayo Clinic, Phoenix, Arizona, USA
| | | | - Tamara Vern-Gross
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona, USA
| | - Mahesh Seetharam
- Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona, USA
| | - Isabella Zaniletti
- Department of Qualitative Health Sciences, Mayo Clinic, Scottsdale, Arizona, USA
| | - Jonathan B Ashman
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona, USA
| |
Collapse
|
|
22
|
Allignet B, Sunyach MP, Geets X, Waissi W. Is there a place for definitive radiotherapy in the treatment of unresectable soft-tissue sarcoma? A systematic review. Acta Oncol 2022; 61:720-729. [PMID: 35574815 DOI: 10.1080/0284186x.2022.2066983] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
BACKGROUND Definitive external beam radiotherapy (EBRT) is an unusual treatment of unresectable soft-tissue sarcomas (STS). Recent technical innovations and physical advantages of particle therapies may improve results of this therapeutic option. The role of this review was to report the clinical results of photon- and particle-based EBRT in unresectable STS. MATERIAL AND METHODS We performed a systematic review of the literature on Pubmed database to identify studies investigating the efficacy and safety of EBRT. The primary endpoint was local control (LC) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events in a subset of patients with gross disease STS. RESULTS We identified 29 studies involving 1409 patients (pts) evaluating photon (n = 18; 956 pts), proton (n = 1; 21 pts), carbon ion (n = 2; 152 pts), neutron (n = 7; 259 pts) or pion (n = 1; 21 pts) therapy. Definitive EBRT achieves valuable 5-year LC rates of 28-73% with photon and 52-69% with particle therapies. Most local failures (66-100%) occurred within 3 years. Long-term disease control can be achieved in a fraction of patients, with 5-year PFS and OS of 0-39% and 24.7-63%, respectively. The rate of severe adverse events was highly variable with photons, <15% in proton and carbon ion therapy, whereas 25 to 50% of patients treated with neutrons and pions presented severe AE. While a dose higher or equal 64 Gy seem to improve the prognosis, delivering a dose higher or equal 68 Gy dramatically increases severe adverse events. CONCLUSION Definitive EBRT with dose 64-66 Gy seems to be a safe and efficient treatment for unresectable STS. Future clinical trials should assess the potential of biomarkers of response, thus identifying patients that could benefit from local treatment.
Collapse
Affiliation(s)
- Benoît Allignet
- Department of Radiation Oncology, Centre Léon Bérard, Lyon, France
| | | | - Xavier Geets
- Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgique
| | - Waisse Waissi
- Department of Radiation Oncology, Centre Léon Bérard, Lyon, France
| |
Collapse
|
|
23
|
Abstract
Radiation therapy is an integral component of local management with oncologic resection for soft tissue sarcoma. Radiotherapy is indicated in patients at an increased risk of local recurrence so that improved local control may be achieved. Sequencing of radiotherapy and resection should be determined by multidisciplinary input before treatment initiation. For most patients, preoperative delivery of radiation therapy is preferred. In patients initially thought to be at low risk for local recurrence and found to have unexpected adverse pathologic features at resection, postoperative radiation therapy is indicated. The use of radiation therapy for retroperitoneal sarcoma is controversial; when used, preoperative delivery of radiation is recommended.
Collapse
|
|
24
|
Allignet B, Waissi W, Geets X, Dufresne A, Brahmi M, Ray-Coquard I, Blay JY, Bouhamama A, Meeus P, Vaz G, Gouin F, Moncharmont C, Sunyach MP. Long-term outcomes after definitive radiotherapy with modern techniques for unresectable soft tissue sarcoma. Radiother Oncol 2022; 173:55-61. [PMID: 35640770 DOI: 10.1016/j.radonc.2022.05.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 05/24/2022] [Accepted: 05/25/2022] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The use of definitive radiotherapy (dRT) in unresectable soft-tissue sarcomas (STS) is still controversial and recent data are scarce. We report clinical results of this therapeutic option. METHODS We retrospectively included STS patients treated between 2009 and 2020, with dRT for unresectable or with a measurable residual disease after R2 surgery. Response rate, local failure (LF), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS 116 patients with localized/locally advanced STS were treated from 2009 to 2020, with a median age of 71 years (range 18-92). Most tumors were deep-seated (96.6%), grade 2-3 (85.1%), located in the trunk or extremities (74.2%). Helical tomotherapy, volumetric modulated arc therapy, or stereotactic radiotherapy was performed in 39.7%, 19% and 8.6% of patients, respectively. The median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR 52-65). At first follow-up, 66 (58.9%) and 25 (22%) patients had stable disease and partial response. After a median follow-up of 54.8 months (IQR 40.3-95.4), 3-year LF, PFS and OS were 43.2%, 16.6% and 34%, respectively. Median OS was 21.4 months (95%CI 14-26). The multivariate analysis identified grade 3 and AJCC T3-T4 stage to be associated with both shorter PFS and OS (all p<0.001). Macroscopically incomplete resection and EQD2 ≥64Gy were associated with better OS (p=0.016 and p=0.007). Acute and late severe adverse events occurred in 24 (19.7%) and 5 (4.3%) patients. CONCLUSION In unresectable STS patients, definitive modern radiotherapy is a safe and effective treatment yielding long term control in selected patients.
Collapse
Affiliation(s)
- Benoît Allignet
- Department of Radiation Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
| | - Waisse Waissi
- Department of Radiation Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Xavier Geets
- Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgique
| | - Armelle Dufresne
- Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Mehdi Brahmi
- Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Isabelle Ray-Coquard
- University Claude Bernard Lyon 1, Lyon, France; Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Jean-Yves Blay
- University Claude Bernard Lyon 1, Lyon, France; Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Amine Bouhamama
- Department of Radiology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Pierre Meeus
- Department of Surgery, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Gualter Vaz
- Department of Surgery, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Francois Gouin
- Department of Surgery, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Coralie Moncharmont
- Department of Radiation Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| | - Marie-Pierre Sunyach
- Department of Radiation Oncology, Centre Léon Bérard, 28 rue Laennec, 69673 Lyon, France
| |
Collapse
|
|
25
|
The effect of preoperative radiotherapy on surgical resectability, tumor volume and the necrosis rate of soft tissue sarcomas: A retrospective single-center analysis. Surg Oncol 2021; 39:101668. [PMID: 34653769 DOI: 10.1016/j.suronc.2021.101668] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/09/2021] [Accepted: 10/03/2021] [Indexed: 11/24/2022]
Abstract
INTRODUCTION The mainstay of soft tissue sarcoma treatment is limb preserving resection, often combined with radiotherapy, preferably preoperative radiotherapy. The goal of this study is to retrospectively assess the effect of preoperative (neoadjuvant) radiotherapy on the minimal distance to critical neurovascular structures, on tumor volume and the necrosis rate. MATERIAL AND METHODS The data of fifty-one patients treated for a localized soft tissue sarcoma (STS) of the extremity or the trunk were retrospectively reviewed. All patients were analyzed with MR imaging before and after preoperative radiotherapy to determine the impact of radiotherapy on the precise planning and execution of the surgical excision of the tumor. The volume of the tumor as well as the distance to anatomically relevant structures were measured on MRI. Tumor type, characteristics and necrosis rate were obtained from the pathology report. RESULTS At latest follow-up (median 51 months (range 6-113)) 32/51 (63%) patients were alive. The minimal distance between the myxoid liposarcomas (n = 12) and the vessels was significantly increased by preoperative radiotherapy from 1.09 mm [0-21.1] to 5.23 mm [0-32.70] (P = 0.045). High-grade tumors showed a significant increase in tumor volume after irradiation (p = 0.03) and a significantly greater necrosis rate than low-grade tumors (p < 0.001). CONCLUSION Preoperative radiotherapy significantly increases the minimal distance from myxoid liposarcomas to the vessel. In the subgroup of STS that demonstratea volume reduction the distance to nerves and vessels increases, but with the low number of cases, this increase is not statistically significant. The effect of preoperative radiotherapy on the tumor volume varies greatly, whereas the subtype of myxoid liposarcoma shows a significant volume reduction in all cases.
Collapse
|
|
26
|
Salerno KE, Alektiar KM, Baldini EH, Bedi M, Bishop AJ, Bradfield L, Chung P, DeLaney TF, Folpe A, Kane JM, Li XA, Petersen I, Powell J, Stolten M, Thorpe S, Trent JC, Voermans M, Guadagnolo BA. Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2021; 11:339-351. [PMID: 34326023 DOI: 10.1016/j.prro.2021.04.005] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/29/2021] [Accepted: 04/30/2021] [Indexed: 11/15/2022]
Abstract
PURPOSE This guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults. METHODS The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS Multidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended. CONCLUSIONS Based on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life.
Collapse
Affiliation(s)
- Kilian E Salerno
- Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland.
| | - Kaled M Alektiar
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York
| | - Elizabeth H Baldini
- Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | - Manpreet Bedi
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Andrew J Bishop
- Department of Radiation Oncology, UT-MD Anderson Cancer Center, Houston, Texas
| | - Lisa Bradfield
- American Society for Radiation Oncology, Arlington, Virginia
| | - Peter Chung
- Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Center, Toronto, Ontario, Canada
| | - Thomas F DeLaney
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts
| | - Andrew Folpe
- Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, Minnesota
| | - John M Kane
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - X Allen Li
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Ivy Petersen
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - John Powell
- Department of Radiation Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Michael Stolten
- Department of Radiation Oncology, University of Rochester Medical Center, Rochester, New York
| | - Steven Thorpe
- Department of Orthopedic Surgery, UC Davis Medical Center, Sacramento, California
| | - Jonathan C Trent
- Division of Medical Oncology, Sylvester Comprehensive Cancer Center, The University of Miami Health System, Miami, Florida
| | - Maria Voermans
- Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin
| | | |
Collapse
|
|
27
|
Zhang HX, Wang K, Hong P, Lu M, Liu Z, Liu L, Wang GL, Ma LL. Clinical experience with the treatment of retroperitoneal vascular leiomyosarcoma originating from large veins. BMC Surg 2021; 21:326. [PMID: 34392834 PMCID: PMC8364698 DOI: 10.1186/s12893-021-01322-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 08/08/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Retroperitoneal vascular leiomyosarcoma (RVLMS) is an extremely rare disease in clinical practice, and it has poor prognosis. This article is to explore the diagnosis and treatment of RVLMS and present our experience. METHODS Data of RVLMS patients were continuously collected in our hospital from August 2018 to February 2020: two males and two females with a median age of 56 (min-max = 33-61) years were included. Patients in whom paraganglioma could not be excluded were asked to take phenoxybenzamine before surgery. A multi-disciplinary team (MDT) meeting had been held and surgery was recommended. The operation procedures varied based on the tumor location, shape, and stage, and the core steps were "exposure of the retroperitoneum and tumor, identification of vital blood vessels, blocking the bloodstream, complete removal of the tumor and tumor thrombus, and release of blood flow". A Satinsky clamp was used to partially block the blood vessels. Follow-up was conveyed by revisits and phone calls. RESULTS One patient underwent open surgery, and three patients underwent laparoscopic surgery, one of whom underwent conversion to open surgery. The procedures were finished successfully, with a median operative time of 314.5 (min-max = 224-467) mins. The median amount of intraoperative bleeding was 550 (min-max = 200-1500) ml, and three patients had transfusion during the operation. The mass was irregular in shape, with a median maximum size of 7.45 (min-max = 4.2-10.7) cm, and the pathological examination confirmed RVLMS, which has spindle-shape, high mitotic activity and atypia. One week after the operation, the median serum creatinine level was 85 (min-max = 70-99) µmol/L. The median follow-up time was 16 (min-max = 13-21) months, and 1 case reported asymptomatic recurrence. CONCLUSION Uncharacteristic manifestations and imaging features contribute to the problematic diagnosis of RVLMS. Comprehensive preoperative evaluation and careful surgical planning are essential. Multicenter research is needed in the future to reach a dominant consensus.
Collapse
Affiliation(s)
- Hong-Xian Zhang
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China
| | - Kai Wang
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China
| | - Peng Hong
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China
| | - Min Lu
- Department of Pathology, Peking University Third Hospital, 100191, Beijing, People's Republic of China
| | - Zhuo Liu
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China
| | - Lei Liu
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China
| | - Guo-Liang Wang
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China.
| | - Lu-Lin Ma
- Department of Urology, Peking University Third Hospital, 100191, Beijing, People's Republic of China.
| |
Collapse
|
|
28
|
American Brachytherapy Society (ABS) consensus statement for soft-tissue sarcoma brachytherapy. Brachytherapy 2021; 20:1200-1218. [PMID: 34303600 DOI: 10.1016/j.brachy.2021.05.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/17/2021] [Accepted: 05/21/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE Growing data supports the role of radiation therapy in the treatment of soft tissue sarcoma (STS). Brachytherapy has been used for decades in the management of STS and can be utilized as monotherapy or as a boost to external beam radiation. We present updated guidelines from the American Brachytherapy Society regarding the utilization of brachytherapy in the management of STS. METHODS AND MATERIALS Members of the American Brachytherapy Society with expertise in STS and STS brachytherapy created an updated clinical practice guideline including step-by-step details for performing STS brachytherapy based on a literature review and clinical experience. RESULTS Brachytherapy monotherapy should be considered for lower-recurrence risk patients or after a local recurrence following previous external beam radiation; a brachytherapy boost can be considered in higher-risk patents meeting implant criteria. Multiple dose/fractionation regimens are available, with determination based on tumor location and treatment intent. Techniques to limit wound complications are based on the type of wound closure; wound complication can be mitigated with a delay in the start of brachytherapy with immediate wound closure or by utilizing a staged reconstruction technique, which allows an earlier treatment start with a delayed wound closure. CONCLUSIONS These updated guidelines provide clinicians with data on indications for STS brachytherapy as well as guidelines on how to perform and deliver high quality STS brachytherapy safely with minimal toxicity.
Collapse
|
|
29
|
Levy A, Honoré C, Dumont S, Bourdais R, Cavalcanti A, Faron M, Ngo C, Haddag-Miliani L, Le Cesne A, Mir O, Le Péchoux C. [Preoperative versus postoperative radiotherapy in soft tissue sarcomas: State of the art and perspectives]. Bull Cancer 2021; 108:868-876. [PMID: 34246458 DOI: 10.1016/j.bulcan.2021.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 03/03/2021] [Accepted: 03/13/2021] [Indexed: 11/26/2022]
Abstract
Radiation therapy is a standard treatment for limbs soft tissue sarcomas. Preoperative versus postoperative radiotherapy has been a controversial topic for years. With preoperative irradiation, the treatment volume is more limited, the delivered dose possibly lower and the tumor volume easier to delimit. Only one randomized trial compared these two irradiation sequences. The results in terms of local control and survival were equivalent but the risk of acute postoperative complications was higher if irradiation was administered before surgery. However, in the latest update of this trial, patients who received adjuvant irradiation exhibited more severe late toxicity than those treated preoperatively. In addition, with modern irradiation techniques such as conformal with image-guided intensity modulated radiotherapy and flap coverage techniques, the incidence of complications after preoperative irradiation were lower than historically published rates. Locally advanced proximal sarcomas and the failure of other neoadjuvant treatments are nowadays classical indications for preoperative irradiation. As with other neoadjuvant treatments, induction radiotherapy must be personalized according to the histological subtype, the tumor site and the benefit/risk ratio, which is best appreciated by a multidisciplinary surgical and oncological team in a specialized center in the management of soft-tissue sarcomas.
Collapse
Affiliation(s)
- Antonin Levy
- Gustave-Roussy, département d'oncologie radiothérapie, 94805 Villejuif, France; Université Paris-Saclay, 94270 Le-Kremlin-Bicêtre, France; Université Paris-Saclay, Inserm U1030, radiothérapie moléculaire, 94805 Villejuif, France.
| | - Charles Honoré
- Gustave-Roussy, département de chirurgie, 94805 Villejuif, France
| | - Sarah Dumont
- Gustave-Roussy, département d'oncologie médicale, 94805 Villejuif, France
| | - Rémi Bourdais
- Gustave-Roussy, département d'oncologie radiothérapie, 94805 Villejuif, France
| | | | - Matthieu Faron
- Gustave-Roussy, département de chirurgie, 94805 Villejuif, France
| | - Carine Ngo
- Gustave-Roussy, département d'anatomopathologie, 94805 Villejuif, France
| | | | - Axel Le Cesne
- Gustave-Roussy, département d'oncologie médicale, 94805 Villejuif, France
| | - Olivier Mir
- Gustave-Roussy, département d'oncologie médicale, 94805 Villejuif, France
| | - Cécile Le Péchoux
- Gustave-Roussy, département d'oncologie radiothérapie, 94805 Villejuif, France
| |
Collapse
|
|
30
|
Sacchetti F, Alsina AC, Morganti R, Innocenti M, Andreani L, Muratori F, Scoccianti G, Totti F, Campanacci DA, Capanna R. Re-excision after unplanned excision of soft tissue sarcoma: A systematic review and metanalysis. The rationale of systematic re-excision. J Orthop 2021; 25:244-251. [PMID: 34099954 PMCID: PMC8165293 DOI: 10.1016/j.jor.2021.05.022] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 05/09/2021] [Indexed: 01/14/2023] Open
Abstract
In Soft Tissue Sarcomas (STS) referral centre many patients have already had an incomplete tumour resection. In the majority of specimen, tumoral residual is detected and linked to a worsen prognosis. Systematic surgical re-resection of the scar tissue area is often performed. Some authors suggested to postpone re-resections until a clinically evident local recurrence is detected. A searching strategy was applied to Pubmed-Central and Ovid Medline. Odds ratio (OR) for local recurrence (LR), distant metastasis (MTS) or overall survival (OS) were calculated comparing patients who had tumour residual to people who hadn't. OR of local recurrences, distant metastasis and OS were calculated in planned vs unplanned-excisions groups. OR to develop a metastasis and OS after a local recurrences were calculated. Residual tumour led to an OR for LR of 3,56, OR of MTS was 3,42; OR of decreased OS was 3,42. Having a LR lead to a OR of 1,55 for MTS and to a OR of decreased OS of 2,32. Patients who underwent a re-excision compared to planned surgery did not have an increased OR of LR and had an OR to develop a MTS of 0,56. Our data confirm that there is a strong correlation between local recurrences, distant relapses and overall survival. Although there is a selection bias; this analysis highlights the optimal oncological outcome in patients who underwent re-resection. The rationale for systematic re-resection after unplanned excision of soft tissue sarcomas is very strong and this treatment remains the gold standard of care in these patients.
Collapse
Affiliation(s)
| | | | - Riccardo Morganti
- Department of Statistics for Clinical Study, University Hospital of Cisanello, Pisa, Italy
| | - Matteo Innocenti
- Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Lorenzo Andreani
- Department of Orthopaedic and Trauma Surgery, University of Pisa, Italy
| | - Francesco Muratori
- Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Guido Scoccianti
- Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Francesca Totti
- Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Domenico Andrea Campanacci
- Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
| | - Rodolfo Capanna
- Department of Orthopaedic and Trauma Surgery, University of Pisa, Italy
| |
Collapse
|
|
31
|
DeLaney T, Mullen JT, Wang D, Goldberg SI, Kirsch DG. Preoperative radiotherapy for retroperitoneal sarcoma. Lancet Oncol 2021; 22:e1. [DOI: 10.1016/s1470-2045(20)30632-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/10/2020] [Accepted: 10/12/2020] [Indexed: 10/22/2022]
|
|
32
|
He S, Yang X, Yang J, Ye C, Liu W, Wei H, Xiao J. Customized "Whole-Cervical-Vertebral-Body" Reconstruction After Modified Subtotal Spondylectomy of C2-C7 Spinal Tumor Via Piezoelectric Surgery. Oper Neurosurg (Hagerstown) 2020; 17:580-587. [PMID: 31089696 DOI: 10.1093/ons/opz077] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 12/25/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Radical resection is the first-line option in managing cervical primary chondrosarcoma. Favorable anterior reconstruction is challenging after multilevel total spondylectomy in the cervical spine. OBJECTIVE To illustrate the application of piezoelectric surgery and three-dimensional (3D) printing techniques in spine surgery. METHODS A 27-yr-old patient was referred to our center with complaints of nocturnal neck pain and right upper extremity weakness. A 2-stage radical tumor resection was conducted using piezoelectric surgery with pathologically tumor-free margins. A 3D-printed titanium microporous prosthesis (3D-PTMP) was designed to reconstruct the anterior column of the cervical spine between C1 and T1 for stability. RESULTS The whole intraoperative blood loss was 2300 mL over the 2 procedures. The patient had an uneventful recovery, regaining ambulatory status 3 wk after the 2 operations without ventilator support or other severe complications. By the final 14-mo follow-up, the patient had achieved marked pain relief and favorable neurological improvement; a postoperative computed tomography scan indicated a good position of the 3D-printed construct between the endplates with no sign of tumor recurrence or implant subsidence. CONCLUSION The applications of piezosurgery in total spondylectomy and in 3D-PTMP in reconstruction can be a favorable alternative for managing multilevel cervical spinal tumors. Further studies are warranted to validate this surgical strategy.
Collapse
Affiliation(s)
- Shaohui He
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Xinghai Yang
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jian Yang
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Chen Ye
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Weibo Liu
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Spine Surgery, Central Hospital of Qingdao, Shandong Province, China
| | - Haifeng Wei
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jianru Xiao
- Spinal Tumor Center, Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
| |
Collapse
|
|
33
|
Haas RL, Gronchi A. In response to: "Intraoperative radiation therapy (IORT) for soft tissue sarcoma - ESTRO IORT task force/ACROP recommendations". Radiother Oncol 2020; 154:170-171. [PMID: 32980381 DOI: 10.1016/j.radonc.2020.09.040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 09/12/2020] [Indexed: 11/16/2022]
Affiliation(s)
- R L Haas
- Departments of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - A Gronchi
- Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| |
Collapse
|
|
34
|
The Effect of Resection Margin on Local Recurrence and Survival in High Grade Soft Tissue Sarcoma of the Extremities: How Far Is Far Enough? Cancers (Basel) 2020; 12:cancers12092560. [PMID: 32911853 PMCID: PMC7563962 DOI: 10.3390/cancers12092560] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 08/30/2020] [Accepted: 09/05/2020] [Indexed: 12/20/2022] Open
Abstract
Simple Summary In soft tissue sarcomas the width of surgical margins after resection determines the extent of surgery and the function after resection. But how far is really necessary? 305 patients with deep-seated, G2/3 soft tissue sarcomas of the extremity, the trunk wall, or the pelvis were reviewed. The 5-year local recurrence-free survival (LRFS) was 82%. Overall survival (OS) at 5 years was 66%. Positive (contaminated) margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. In conclusion the margin should at least be free of tumor, in sound tissue. A margin of >5 mm sound tissue seems to be sufficient. Resecting more tissue does not benefit the patient. Abstract Background: The significance of surgical margins after resection of soft tissue sarcomas in respect to local-recurrence-free survival and overall survival is evaluated. Methods: A total of 305 patients with deep-seated, G2/3 soft tissue sarcomas (STS) of the extremity, the trunk wall, or the pelvis were reviewed. The margin was defined according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification system (R0-2), the Union Internationale Contre le Cancer (UICC) classification (R + 1 mm) for which a margin <1 mm is included into the R1 group, and in groups of <1 mm, 1–5 mm, >5 mm, or >10 mm. Results: Of these patients, 31 (10.2%) had a contaminated margin, 64 (21%) a margin of <1 mm, 123 (40.3%) a margin of 1–5 mm, 47 (15.4%) a margin of >5 mm, and 40 (13.1%) a margin of >10 mm. The 5-year local recurrence-free survival (LRFS) was 81.6%. Overall survival (OS) at 5 years was 65.9%. Positive margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. Conclusions: A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. This finding supports use of the UICC classification. A margin of more than 10 mm did not improve LRFS or OS.
Collapse
|
|
35
|
Fujiwara T, Stevenson J, Parry M, Tsuda Y, Kaneuchi Y, Jeys L. The adequacy of resection margin for non-infiltrative soft-tissue sarcomas. Eur J Surg Oncol 2020; 47:429-435. [PMID: 32723608 DOI: 10.1016/j.ejso.2020.06.020] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 06/04/2020] [Accepted: 06/11/2020] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES There remains no consensus on what constitutes an adequate margin of resection for non-infiltrative soft-tissue sarcomas (STSs). We aimed to investigate the role of resection margins in millimetres for non-infiltrative STSs. METHODS 502 patients who underwent surgical resection for a localized, non-infiltrative, high-grade STSs were studied. The prognostic significance of margin width was analysed and compared with the conventional R- and R+1-classification of surgical margins. RESULTS The overall local recurrence (LR) rate was 13%; 9% and 27% with negative and positive margins, respectively (p < 0.001). In patients with negative margins, the LR rates were greater than 10% in patients with margins ≤5.0 mm but reduced to less than 4% with margins >5.0 mm. When classified by the R- (or R+1)-classification, the 5-year cumulative LR incidence was 8%, 23% (16%), and 31% for R0, R1, and R2, respectively, which did not stratify the LR risk with negative margins. On the other hand, an accurate risk stratification was possible by metric distance; the 5-year cumulative incidence of LR was 29%, 10%, and 1% with 0 mm, 0.1-5.0 mm, and >5.0 mm, respectively (p < 0.001). This classification also stratified the LR risk in patients with or without adjuvant radiotherapy. CONCLUSION While a negative margin is essential to optimize local control in patients with non-infiltrative STSs, surgical margin width greater than 5 mm minimises the risk of local failure regardless of the use of adjuvant radiotherapy.
Collapse
Affiliation(s)
- Tomohiro Fujiwara
- Oncology Service, The Royal Orthopaedic Hospital, Birmingham, UK; Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
| | | | - Michael Parry
- Oncology Service, The Royal Orthopaedic Hospital, Birmingham, UK
| | - Yusuke Tsuda
- Oncology Service, The Royal Orthopaedic Hospital, Birmingham, UK
| | - Yoichi Kaneuchi
- Oncology Service, The Royal Orthopaedic Hospital, Birmingham, UK
| | - Lee Jeys
- Oncology Service, The Royal Orthopaedic Hospital, Birmingham, UK
| |
Collapse
|
|
36
|
Murray FR, Snider JW, Schneider RA, Walser M, Bolsi A, Pica A, Lomax AJ, Weber DC. Prognostic factors for spinal chordomas and chondrosarcomas treated with postoperative pencil-beam scanning proton therapy: a large, single-institution experience. J Neurosurg Spine 2020; 32:921-930. [PMID: 32005008 DOI: 10.3171/2019.11.spine1927] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 11/15/2019] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The aim of this paper was to evaluate the prognostic factors in surgical and adjuvant care for spinal chordomas and chondrosarcomas after surgery followed by high-dose pencil-beam scanning proton therapy (PBS-PT). METHODS From 1997 to 2016, 155 patients (61 female patients; median age 55 years) with spinal (cervical, n = 61; thoracic, n = 29; lumbar, n = 13; sacral, n = 46; pelvic, n = 6) classic chordomas (n = 116) and chondrosarcomas (n = 39; most were low grade) were treated with maximal safe resection followed by PBS-PT (median dose prescribed: 74 Gy [relative biological effectiveness], range 48.6-77 Gy). The majority of patients (n = 153, 98.7%) had undergone at least 1 resection prior to PBS-PT (median 1, range 0-5; biopsy only, n = 2). Fewer than half (45.1%) of the surgeries were rated as gross-total resections (GTRs) prior to PBS-PT. Surgical stabilization (SS) was present in 39% of all patients (n = 60). Ninety-one patients (59%) presented with macroscopic tumor at the start of PBS-PT. The median follow-up duration was 64.7 months (range 12.2-204.8 months). RESULTS The 5-year local tumor control, disease-free survival (DFS), and overall survival were 64.9% (95% CI 56.3%-73.5%), 59.4% (95% CI 50.6%-68.2%), and 77.9% (95% CI 70.6%-85.2%), respectively. In total, 63 patients (40.6%) experienced failure during the follow-up period: local only in 32 (20.6%), distal only in 7 (4.5%), local + distal in 19 (12.3%), surgical pathway failure (SPF) only in 2 (1.3%), local + SPF in 2 (1.3%), and distal + SPF in 1 (< 1%). Univariate analysis identified gross residual disease, the presence of SS, and treatment era prior to 2008 as highly significant for worse outcome, with all 3 remaining significant on multivariate analysis. The type of surgery (GTR or subtotal resection/biopsy) and whether GTR was achieved by en bloc or curettage did not show a significant prognostic effect. Surgical complications prior to PBS-PT were present in 42.5% of all surgically treated patients and were seen more commonly in patients with multiple surgical interventions (p = 0.005) and those operated on with the intent of en bloc resection (p = 0.006). CONCLUSIONS The extent of resection and metallic stabilization substantially influenced clinical outcomes for patients with spinal chordoma or chondrosarcoma despite high-dose adjuvant PBS-PT. Optimal upfront surgical management of these tumors continues to include GTR, as possible, with prompt adjuvant proton therapy.
Collapse
Affiliation(s)
- Fritz R Murray
- 1Center for Proton Therapy, Paul Scherrer Institute, Villigen
| | - James W Snider
- 2Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland
| | | | - Marc Walser
- 1Center for Proton Therapy, Paul Scherrer Institute, Villigen
| | | | - Alessia Pica
- 1Center for Proton Therapy, Paul Scherrer Institute, Villigen
| | - Antony J Lomax
- 1Center for Proton Therapy, Paul Scherrer Institute, Villigen
- 3Department of Physics, ETH, Zurich
| | - Damien C Weber
- 1Center for Proton Therapy, Paul Scherrer Institute, Villigen
- 4Radiation Oncology Department, University Hospital of Bern
- 5Radiation Oncology Department, University Hospital of Zurich, Switzerland; and
| |
Collapse
|
|
37
|
Gamboa AC, Gronchi A, Cardona K. Soft-tissue sarcoma in adults: An update on the current state of histiotype-specific management in an era of personalized medicine. CA Cancer J Clin 2020; 70:200-229. [PMID: 32275330 DOI: 10.3322/caac.21605] [Citation(s) in RCA: 336] [Impact Index Per Article: 67.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 02/11/2020] [Accepted: 02/12/2020] [Indexed: 12/13/2022] Open
Abstract
Soft-tissue sarcomas (STS) are rare tumors that account for 1% of all adult malignancies, with over 100 different histologic subtypes occurring predominately in the trunk, extremity, and retroperitoneum. This low incidence is further complicated by their variable presentation, behavior, and long-term outcomes, which emphasize the importance of centralized care in specialized centers with a multidisciplinary team approach. In the last decade, there has been an effort to improve the quality of care for patients with STS based on anatomic site and histology, and multiple ongoing clinical trials are focusing on tailoring therapy to histologic subtype. This report summarizes the latest evidence guiding the histiotype-specific management of extremity/truncal and retroperitoneal STS with regard to surgery, radiation, and chemotherapy.
Collapse
Affiliation(s)
- Adriana C Gamboa
- Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia
| | - Alessandro Gronchi
- Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Kenneth Cardona
- Division of Surgical Oncology, Winship Cancer Institute, Emory University Hospital Midtown, Atlanta, Georgia
| |
Collapse
|
|
38
|
Schwitzer D, Kim R, Williams F, Hammer D. Spindle Cell Sarcoma of the Maxilla: A Rare Entity, Case Report, and Review of the Literature. J Oral Maxillofac Surg 2020; 78:1334-1342. [PMID: 32147227 DOI: 10.1016/j.joms.2020.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/03/2020] [Accepted: 02/03/2020] [Indexed: 10/25/2022]
Abstract
Spindle cell sarcoma (SCS) is a malignancy, with the most recent Surveillance, Epidemiology, and End Results (SEER) data citing a total of 250 reported cases occurring in the head and neck. Of these cases, none originated in the maxillofacial hard tissue. To the best of our knowledge, only 2 cases of primary osseous SCS of the maxillofacial region have been reported. These cases were not accounted for in the SEER data. The diagnosis of SCS requires its differentiation from other sarcomas and spindle cell neoplasms. Therefore, a comprehensive review to reinforce its inclusion in oral and maxillofacial surgeons' differential diagnosis for osseous neoplastic pathology is desired. In the present case report, we have described a maxillary SCS in a patient with an initial diagnosis of a spindle cell lesion of uncertain biologic behavior. We reviewed the data for SCS, including the epidemiologic data, diagnostic challenges, clinical and radiographic presentations, prognostic indicators, and treatment.
Collapse
Affiliation(s)
- David Schwitzer
- Resident, Department of Oral and Maxillofacial Surgery, Parkland Memorial Hospital, UT Southwestern Medical Center, Dallas, TX.
| | - Roderick Kim
- Director of Research and Assistant Fellowship Director, Division of Maxillofacial Oncology and Reconstructive Surgery, John Peter Smith Hospital, Fort Worth, TX
| | - Fayette Williams
- Faculty, Division and Fellowship Director, Division of Maxillofacial Oncology and Reconstructive Surgery, John Peter Smith Hospital, Fort Worth, TX
| | - Daniel Hammer
- Fellow, Division of Maxillofacial Oncology and Reconstructive Surgery, John Peter Smith Hospital, Fort Worth, TX
| |
Collapse
|
|
39
|
|
|
40
|
Gao Z, Lu T, Song H, Gao Z, Ren F, Ouyang P, Wang Y, Zhu J, Zhou S, He X. Prognostic Factors and Treatment Options for Patients with High-Grade Chondrosarcoma. Med Sci Monit 2019; 25:8952-8967. [PMID: 31765367 PMCID: PMC6894367 DOI: 10.12659/msm.917959] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background The goal of this study was to determine the prognostic factors exclusive for high-grade chondrosarcoma and whether adjuvant radiotherapy could achieve better overall survival (OS) or cancer-specific survival (CSS) for patients with high-grade chondrosarcoma. Material/Methods Surveillance, Epidemiology, and End Results (SEER) cancer registry database was utilized to extract the chondrosarcoma cases diagnosed between 1973 and 2014. Among these cases, the histological grades of poorly differentiated (grade 3) and undifferentiated (grade 4) were categorized as high-grade and included in this study. Chondrosarcoma OS and CSS were the primary outcomes in the present study. The log-rank test was performed for univariate analysis, and the Cox regression model was conducted for multivariate analysis. Results A total of 743 patients with high-grade chondrosarcoma were identified in this study (430 cases were poorly differentiated tumors, and 313 cases were undifferentiated tumors). Age at diagnosis, pathological grade, histo-type, SEER stage, tumor size and surgical resection were identified as independent predictors in both OS and CSS analysis of high-grade chondrosarcoma. When stratified by histological grade, surgical resection remained the effective treatment. Strikingly, radiotherapy was determined as an independent protective factor in both OS and CSS analysis of undifferentiated (grade 4) dedifferentiated chondrosarcoma, and adjuvant radiotherapy combined surgical resection could improve both the OS and CSS of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma compared with other treatment regimens. Conclusions Our study first demonstrated that adjuvant radiotherapy combined surgery could improve the survival of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma. These results encourage the application of adjuvant radiotherapy for patients with high-grade chondrosarcoma and maximize the patients’ outcome.
Collapse
Affiliation(s)
- Zhongyang Gao
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Teng Lu
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Hui Song
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Zhengchao Gao
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Fenggang Ren
- Research Institute of Advanced Surgical Techniques and Engineering of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Pengrong Ouyang
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Yibin Wang
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Junjie Zhu
- Department of Neurobiology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Songlin Zhou
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China (mainland)
| | - Xijing He
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| |
Collapse
|
|
41
|
Wells S, Ager B, Hitchcock YJ, Poppe MM. The radiation dose-response of non-retroperitoneal soft tissue sarcoma with positive margins: An NCDB analysis. J Surg Oncol 2019; 120:1476-1485. [PMID: 31710707 DOI: 10.1002/jso.25748] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 08/07/2019] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Positive margins can increase the risk of local recurrence of soft tissue sarcomas (STS). Utilizing a national registry, we investigated patterns of care and overall survival (OS) of patients with margin-positive non-retroperitoneal STS who received preoperative radiation therapy, adjuvant radiation therapy, or both. METHODS Adult patients with non-retroperitoneal STS who underwent resection and RT from 2004 to 2015 were included. Kaplan-Meier, log-rank analysis, and Cox regression analysis were performed. RESULTS We identified 5726 patients. Most had a tumor size >5 cm (60%), grade 3 disease (67%), and microscopically positive margins (57%). Compared to ≤50.4 Gy, a dose of 66 to 69.99 Gy was associated with decreased risk of death on multivariate analysis (HR 0.69, 95%; CI, 0.50-0.94). Receipt of a boost was associated with decreased risk of death on univariate analysis (HR 0.54, 95%; CI, 0.29-0.99). In patients with grade 2 to 3 tumors without the gross disease, there was an OS benefit associated with a boost on multivariate analysis (HR 0.39, 95%; CI, 0.16-0.97). CONCLUSION This analysis appears to show an OS benefit of dose escalation to 66 to 69 Gy for margin-positive non-retroperitoneal STS. A Postoperative boost is associated with higher OS in grade 2 to 3 STS without the gross disease.
Collapse
Affiliation(s)
- Stacey Wells
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Bryan Ager
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Ying J Hitchcock
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| | - Matthew M Poppe
- Department of Radiation Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah
| |
Collapse
|
|
42
|
Zhang J, Pan Z, Zhao F, Feng X, Huang Y, Hu C, Li Y, Lyu J. Development and validation of a nomogram containing the prognostic determinants of chondrosarcoma based on the Surveillance, Epidemiology, and End Results database. Int J Clin Oncol 2019; 24:1459-1467. [PMID: 31243629 DOI: 10.1007/s10147-019-01489-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 06/07/2019] [Indexed: 12/16/2022]
Abstract
BACKGROUND We aimed to develop and validate a reliable nomogram for predicting the disease-specific survival (DSS) of chondrosarcoma patients. METHODS The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2004 to 2015 to identify cases of histologically confirmed chondrosarcoma. Multivariate Cox regression analysis was performed to identify independent prognostic factors and construct a nomogram for predicting the 3- and 5-year DSS rates. Predictive values were compared between the new model and the American Joint Committee on Cancer (AJCC) staging system using concordance indexes (C-indexes), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS Multivariate Cox regression identified 1180 patients, who were used to establish a nomogram based on a new model containing the predictive variables of age, socioeconomic status, tumor size, surgery status, chemotherapy status, and AJCC staging. In the nomogram, age at diagnosis is the factor with the highest risk, followed by AJCC stage IV and tumor size > 100 mm. Both the C-index and the calibration plots demonstrated the good performance of the nomogram. Moreover, both NRI and IDI were improved compared to the AJCC staging system, and also DCA demonstrated that the nomogram is clinically useful. CONCLUSION We have developed a reliable nomogram for determining the prognosis and treatment outcomes of chondrosarcoma patients that is superior to the traditional AJCC staging system.
Collapse
Affiliation(s)
- Jun Zhang
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
- Department of Orthopaedics, Baoji Municipal Central Hospital, Baoji, Shaanxi, China
| | - Zhenyu Pan
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
- Department of Pharmacy, The Affiliated Children Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Fanfan Zhao
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Xiaojie Feng
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Yuanchi Huang
- Department of Orthopaedics, Baoji Municipal Central Hospital, Baoji, Shaanxi, China
| | - Chuanyu Hu
- Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuanjie Li
- Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
| | - Jun Lyu
- Clinical Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
- School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
- Institute of Evidence-Based Medicine and Knowledge Translation, Henan University, Kaifeng, China.
| |
Collapse
|
|
43
|
Revisiting the Role of Radiation Therapy in Chondrosarcoma: A National Cancer Database Study. Sarcoma 2019; 2019:4878512. [PMID: 31736653 PMCID: PMC6815626 DOI: 10.1155/2019/4878512] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 07/15/2019] [Accepted: 08/19/2019] [Indexed: 11/18/2022] Open
Abstract
Background Although chondrosarcomas (CS) are mostly considered radioresistant, advancements in radiotherapy have brought attention to its use in these patients. Using the largest registry of primary bone tumors, the National Cancer Database (NCDB), we sought to better characterize the current use of radiotherapy in CS patients and identify any potential survival benefit with higher radiation doses and advanced radiation therapies. Methods We retrospectively analyzed CS patients in the NCDB from 2004 to 2015 who underwent radiotherapy. The Kaplan–Meier method with statistical comparisons was used to identify which individual variables related to dosage and delivery modality were associated with improved 5-year survival rates. Multivariate proportional hazards analyses were performed to determine independent predictors of survival. Results Of 5,427 patients with a histologic diagnosis of chondrosarcoma, 680 received a form of radiation therapy (13%). The multivariate proportional hazards analysis controlling for various patient, tumor, and treatment variables, including RT dose and modality, demonstrated that while overall radiation therapy (RT) was not associated with improved survival (HR 0.96, 95% CI 0.76–1.20), when examining just the patient cohort with positive surgical margins, RT trended towards improved survival (HR 0.81, 95% CI 0.58–1.13). When comparing advanced and conventional RT modalities, advanced RT was associated with significantly decreased mortality (HR 0.55, 95% CI 0.38–0.80). However, advanced modality and high-dose RT both trended only toward improved survival compared to patients who did not receive any RT (HR 0.74, 95% CI 0.52–1.06 and HR 0.93, 95% CI 0.71–1.21, respectively). Conclusions Despite the suggested radioresistance of CS, modern radiotherapies may present a treatment option for certain patients. Our results support a role for high-dose, advanced radiation therapies in selected high-risk CS patients with tumors in surgically challenging locations or unplanned positive margins. While there is an associated survival rate benefit, further, prospective studies are needed for validation.
Collapse
|
|
44
|
Di Brina L, Fogliata A, Navarria P, D'Agostino G, Franzese C, Franceschini D, De Rose F, Comito T, Bertuzzi A, Marrari A, Colombo P, Quagliuolo V, Santoro A, Scorsetti M. Adjuvant volumetric modulated arc therapy compared to 3D conformal radiation therapy for newly diagnosed soft tissue sarcoma of the extremities: outcome and toxicity evaluation. Br J Radiol 2019; 92:20190252. [PMID: 31322910 PMCID: PMC6774597 DOI: 10.1259/bjr.20190252] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 06/25/2019] [Accepted: 07/15/2019] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVE To assess the impact of adjuvant volumetric modulated arc therapy (VMAT) compared with three-dimensional conformal radiation therapy (3DCRT) in terms of toxicity and local control (LC) in patients with soft tissue sarcoma of the extremities. METHODS From 2004 to 2016, 109 patients were treated, initially using 3DCRT and subsequently with VMAT. Clinical outcome was evaluated by contrast-enhanced MRI, thoracic and abdominal CT 3 months after treatments and then every 6 months. Toxicity was evaluated with Common Terminology Criteria for Adverse Events scale v. 4.3. RESULTS Patients presented Stage III soft tissue sarcoma disease (77%), localized tumor (95%) at the lower extremity (87%), adipocytic histotype (46%). Surgical resection was performed in all patients, followed by adjuvant 3DCRT in 38, and VMAT in 71. The median total dose was 66 Gy/33 fractions (range 60-70 Gy;25-35 fractions). More successful bone sparing was recorded using VMAT (p < 0.001). Median follow-up was 61 months, 93 and 58 months for 3DCRT and VMAT group, respectively. The 2- and 5 year LC were 95.3±2.1%, and 87.4±3.4% for the whole cohort, 92.0±4.5%, 82.9±6.4% for 3DCRT, 97.1±2.0%, 89.6±4.1% for VMAT (p = 0.150). On univariate and multivariate analysis the factors recorded as conditioning LC were the status of the surgical resection margins (p = 0.028) and the total dose delivered (p = 0.013). CONCLUSION The availability of modern radiotherapy technique permit a better conformity on the target with maximum sparing of normal tissue and acceptable side-effects. VMAT is a safe and feasible treatment with limited rate of toxicity, compared to 3DCRT. Results on LC of VMAT are encouraging. ADVANCES IN KNOWLEDGE Soft tissue sarcoma of the extremities can benefit from the use of VMAT, with a reduction of the high dose to bones to avoid radiation osteonecrosis. An adequate total dose of at least 66 Gy and a radical surgical margin allow a good local control.
Collapse
Affiliation(s)
- Lucia Di Brina
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Antonella Fogliata
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Pierina Navarria
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Giuseppe D'Agostino
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Ciro Franzese
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Davide Franceschini
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Fiorenza De Rose
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Tiziana Comito
- Radiotherapy and Radiosurgery Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Alexia Bertuzzi
- Medical Oncology Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Andrea Marrari
- Medical Oncology Department, Humanitas Clinical and Research Center – IRCCS, Rozzano - Milano – Italy
| | - Piergiuseppe Colombo
- Pahtology Department, Humanitas Clinical and Research Center – IRCCS-, Rozzano - Milano – Italy
| | | | | | | |
Collapse
|
|
45
|
Bamdad K, Hudson S, Briggs T. Factors associated with functional outcome in patients having limb salvage surgery for primary malignant bone sarcoma using TESS. J Clin Orthop Trauma 2019; 10:986-990. [PMID: 31528081 PMCID: PMC6739427 DOI: 10.1016/j.jcot.2018.06.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 06/06/2018] [Accepted: 06/26/2018] [Indexed: 01/14/2023] Open
Abstract
INTRODUCTION Achieving maximum functional outcome in primary malignant bone sarcoma surgery (PMBS) patients, is challenging for both patients and clinicians. This study, aimed to evaluate different factors that affect postoperative functional outcome of the primary malignant bone sarcoma patients following upper limb (UL) and lower limb (LL) salvage surgery using Toronto Extremity Salvage Score (TESS). METHODS 136 PMBS adult patients were identified and were grouped as lower limb (LL) and upper limb (UL). Each group then sub-grouped to major and minor surgeries. Their functional outcome was compared using TESS by demographic variables(gender and age), neoadjuvant/adjuvant therapy and tumour variables (anatomical sites). In the UL groups, TESS was also compared for major and minor surgery subgroups based on their dominant or non-dominant limb. RESULTS The result of TESS has revealed that chemotherapy, radiotherapy, and gender have no effect on the functional outcome in PMBS patients. Functional outcome however was significantly affected by age in both LL and UL groups. The TESS was significantly different between major and minor subgroups in UL group with p= 0.0001. In patients with upper LSS on their dominant limb, no significant difference between major/ minor surgery subgroups was observed with p=0.077. CONCLUSION Our findings using TESS revealed that factors such as patient's age, and type of surgery (major or minor) in PMBS patients will affect the patients' functional outcome after LSS especially in those PMBS patients with upper LSS.
Collapse
Affiliation(s)
- Katayoon Bamdad
- Royal National Orthopaedic Hospital NHS Trust, Stanmore, London, England, United Kingdom
| | | | | |
Collapse
|
|
46
|
Nassif MO, Habib RA, Almarzouki LZ, Trabulsi NH. Systematic review of anorectal leiomyosarcoma: Current challenges and recent advances. World J Gastrointest Surg 2019; 11:334-341. [PMID: 31523383 PMCID: PMC6715585 DOI: 10.4240/wjgs.v11.i8.334] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 08/10/2019] [Accepted: 08/13/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The anorectal leiomyosarcoma (LMS) is an aggressive malignant neoplasm. Owing to the rarity of LMSs, an optimal treatment modality has yet to be determined.
AIM To collect all published data on anorectal LMS characteristics, explore current treatment options, and review recent cases of postradiation LMS.
METHODS A literature search of the PubMed electronic database was conducted using the MeSH terms “rectal neoplasms”, “anus neoplasms” and “gastrointestinal neoplasms” combined with “leiomyosarcoma”. The search was limited to English language and human studies. All available case reports and case series of anal or rectal LMSs that were published from the beginning of January 1996 to May 2017 were included if the diagnosis of LMS had been confirmed by histopathologic examination. Data were analyzed using simple statistics (mean, median, and standard deviation). Independent sample t-test was used to compare means for continuous variables.
RESULTS A total of 27 articles reporting on 51 cases of anorectal LMS were identified. Among these cases, 11.7% had undergone previous pelvic radiotherapy (developing LMS at 13-35 years afterwards). Anorectal LMS affected the rectum in 92.2% of the cases, and no sex-based predominance was observed. Surgical resection with negative margins remains the mainstay of treatment, which can be accomplished with wide local excision or radical resection. The local recurrence rate was higher among cases who received wide local excision (30%), as compared to radical resection (20%); however, the overall rate of metastasis was 51.61% regardless of the treatment approach. The use of neoadjuvant radiation lowers the risk of local recurrence compared to adjuvant radiotherapy, and facilitates R0 resection of the tumor. Cases treated with adjuvant chemotherapy showed better rates of distant recurrence and overall survival. Nonetheless, multidisciplinary team discussion is necessary to determine the optimal management plan whilst considering patient- and disease-related factors.
CONCLUSION A multidisciplinary team approach, considering the underlying patient- and disease- related factors, is necessary for optimal management of these complex tumors.
Collapse
Affiliation(s)
- Mohammed O Nassif
- Department of Surgery, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Razan A Habib
- Department of Surgery, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Luai Z Almarzouki
- Department of Surgery, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Nora H Trabulsi
- Department of Surgery, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| |
Collapse
|
|
47
|
van Wulfften Palthe ODR, Tromp I, Ferreira A, Fiore A, Bramer JAM, van Dijk NC, DeLaney TF, Schwab JH, Hornicek FJ. Sacral chordoma: a clinical review of 101 cases with 30-year experience in a single institution. Spine J 2019; 19:869-879. [PMID: 30445184 DOI: 10.1016/j.spinee.2018.11.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 10/31/2018] [Accepted: 11/01/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND Local recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors. High-quality studies comparing presentation and treatments for primary and first local recurrent sacral chordoma tumors are sparse. PURPOSE To determine: whether there is a difference in how primary and tumors at first recurrence present; the overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a primary tumor; overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a first local relapse; if there any differences in overall survival, local relapse-free survival, and distant relapse-free survival rates between patients presenting with a primary tumor and those with a first local relapse. STUDY DESIGN Retrospective case series. PATIENT SAMPLE One hundred one sacral chordoma cases. OUTCOME MEASURE Overall survival, local relapse-free survival, and distant relapse-free survival rates. METHODS Between 1978 and 2013, 131 patients with sacral chordoma were seen. Of them, 17 patients (13%) presented with a history of more than one local recurrence. One patient (1%) presented with multiple distant metastases. Ten patients (8%) had less than 36 months of follow-up and had no event (eg, death, local recurrence, or distant metastasis). A total of 102 patients met our inclusion criteria: patients with primary or first recurrent tumors, without metastatic disease, who underwent surgery and with at least 36 months of follow-up. One patient (1%) died intraoperatively; therefore, 101 patients were included in the present analysis. Cox proportional hazards regression analysis was performed for primary and local recurrent tumor separately and to compare primary and local recurrent tumors. RESULTS We analyzed 73 primary and 28 first time recurrent sacral chordomas. Tumor size at presentation was different for primary and recurrent tumors (primary median size: 158 cm3, interquartile range [IQR]: 46-634; recurrent median size: 39 cm3, IQR: 14-175; p=.001). Overall survival at 5 and 10years for the primary tumors was 79% and 59%, respectively. Local relapse-free survival at 5years was 86%. For primary tumors, not receiving radiation was an independent predictor for worse local relapse-free survival (hazard ratio [HR]: 0.20; 95% confidence interval [CI]: 0.0043-0.90; p=.004) and increased tumor size was an independent predictor for both worse overall survival (HR: 1.68; 95% CI: 1.38-2.42; p=.004) and worse distant relapse-free survival (HR: 2.25; 95% CI: 1.47-3.44; p<.001). For recurrent tumors, the 5- and 10-year overall survival was 65% and 40%, respectively. Local relapse-free survival at 5years was 79% for recurrent tumors. On bivariate analysis, increased tumor size was a significant predictor for worse survival (LR median: 338 mL; IQR: 218-503 mL; no LR median: 26 mL; IQR: 9-71 mL). A trend was seen toward better distant relapse survival for tumors presenting as a primary tumor (HR: 0.51; 95% CI: 0.25-1.06; p=.072). CONCLUSION Using a combination of surgical resection and adjuvant radiotherapy allowed us to obtain a good overall survival, local relapse-free survival, and distant relapse-free survival in patients presenting with either a primary tumor or with a first time local recurrent tumor.
Collapse
Affiliation(s)
- Olivier D R van Wulfften Palthe
- Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA.
| | - Isabel Tromp
- Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
| | - Al Ferreira
- Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
| | - Anne Fiore
- Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
| | - Jos A M Bramer
- Department of Orthopaedic Surgery, Amsterdam Medical Center - University Of Amsterdam, Meidreef 9, 1105 AZ, Amsterdam-Zuidoost, The Netherlands
| | - Niek C van Dijk
- Department of Orthopaedic Surgery, Amsterdam Medical Center - University Of Amsterdam, Meidreef 9, 1105 AZ, Amsterdam-Zuidoost, The Netherlands
| | - Thomas F DeLaney
- Department of Radiation Oncology, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
| | - Joseph H Schwab
- Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
| | - Francis J Hornicek
- Department of Orthopaedic Surgery, Orthopaedic Oncology Service, Massachusetts General Hospital - Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA
| |
Collapse
|
|
48
|
Long-term results of Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiation in adult patients with soft tissue sarcomas of the extremities and the superficial trunk: Final results of a prospective controlled study. Radiother Oncol 2019; 135:91-99. [PMID: 31015176 DOI: 10.1016/j.radonc.2019.02.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 02/04/2019] [Accepted: 02/13/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND To analyze toxicity, patterns of failure, and survival in 106 adult patients with soft tissue sarcomas of the extremity and the superficial trunk treated in a prospective controlled trial of combined Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiotherapy (EBRT). METHODS Patients were treated with surgical resection and 16 Gy or 24 Gy of PHDRB for negative or close/positive margins, respectively. EBRT (45 Gy) was added postoperatively. Adjuvant chemotherapy was given to selected patients with high-grade tumors. RESULTS The median follow-up was 7.1 years (range, 0.6-16.0). Grade ≥3 adverse events were observed in 22 patients (20.8%), and grade ≥4 events in 14 patients (13.2%). No grade 5 events were noted. Multivariate analysis (p = 0.003) found that Grade ≥3 toxic events increased with increasing implant volume (TV100). Local control, locoregional control, and distant control rates at 5 and 10 years were 89% and 87%, 82% and 80% and 75% and 69%, respectively. Multivariate analysis (p = 0.024) found that positive margins correlated with decreased local control. Disease-free survival and overall survival rates at 5 and 10 years were 64% and 59% and 73% and 62%, respectively. In multivariate analysis, disease-free survival rates decreased with increasing tumor size (p = 0.0001) and inadequate margins (p = 0.024), and overall survival decreased with increasing tumor size (p = 0.001) and male gender (p = 0.039). CONCLUSIONS The combination of conservative surgery, high-dose PHDRB, and EBRT produces adequate function and local control in the majority of patients with soft tissue sarcomas of the extremities and the superficial trunk, including a substantial percentage of cases with positive margins. Patients with larger tumors are at a higher risk of complications, treatment failure, and cancer-related death and require an individualized treatment approach.
Collapse
|
|
49
|
Hobusch GM, Cernakova M, Puchner SE, Kolb A, Panotopoulos J, Windhager R. Sports activity after soft tissue sarcoma of the lower extremity. Disabil Rehabil 2019; 42:14-19. [DOI: 10.1080/09638288.2018.1520929] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Gerhard M. Hobusch
- Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| | - Miroslava Cernakova
- Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| | - Stephan E. Puchner
- Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| | - Alexander Kolb
- Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| | - Joannis Panotopoulos
- Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| | - Reinhard Windhager
- Department of Orthopaedic Surgery, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| |
Collapse
|
|
50
|
Mercado CE, Holtzman AL, Rotondo R, Rutenberg MS, Mendenhall WM. Proton therapy for skull base tumors: A review of clinical outcomes for chordomas and chondrosarcomas. Head Neck 2018; 41:536-541. [PMID: 30537295 DOI: 10.1002/hed.25479] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Revised: 04/13/2018] [Accepted: 08/15/2018] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Skull base chordomas and chondrosarcomas are rare tumors traditionally treated by surgical resection and adjuvant radiation therapy (RT). We will discuss data evaluating clinical outcomes of proton therapy in the treatment of skull base chordomas and chondrosarcomas. METHODS A literature review was performed using a MEDLINE search from January 1990 to January 2017. RESULTS The published data suggest that the dose intensification allowed by proton therapy has resulted in good clinical outcomes and a tolerable toxicity profile. CONCLUSION Proton therapy is a modern RT technique that has demonstrated improved preliminary clinical outcomes in the treatment of skull base chordomas and chondrosarcomas compared to conventional radiotherapy, and comparable to other advanced photon-based RT techniques.
Collapse
Affiliation(s)
- Catherine E Mercado
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida
| | - Adam L Holtzman
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida
| | - Ronny Rotondo
- University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida
| | - Michael S Rutenberg
- Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, Florida
| | - William M Mendenhall
- University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida
| |
Collapse
|