Surveillance, Epidemiology, and End Results (SEER) Program ( SEER*Stat version (downloaded 3/23/2017)
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1 APPENDIX I. SEER Search criteria and exclusion criteria. Surveillance, Epidemiology, and End Results (SEER) Program ( SEER*Stat version (downloaded 3/23/2017) SEER*Stat Database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub ( varying) - Linked To County Attributes - Total U.S., Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2016, based on the November 2015 submission. Search criteria: (({Site and Morphology.ICD-O-3 Hist/behav} = '8800/3: Sarcoma, NOS','8801/3: Spindle cell sarcoma','8802/3: Giant cell sarcoma','8803/3: Small cell sarcoma','8804/3: Epithelioid sarcoma','8805/3: Undifferentiated sarcoma','8806/3: Desmoplastic small round cell tumor','8810/3: Fibrosarcoma, NOS','8811/3: Fibromyxosarcoma','8813/3: Fascial fibrosarcoma','8815/3: Solitary fibrous tumor, malignant',,'8821/1: Aggressive fibromatosis','8821/3: Aggressive fibromatosis, malignant','8823/3: Desmoplastic fibrosarcoma','8824/3: Myofibroma, malignant','8825/3: Myofibroblastoma, malignant','8830/3: Malignant fibrous histiocytoma','8831/3: Histiocytoma, NOS, malignant','8840/3: Myxosarcoma','8850/1: Atypical lipoma','8850/3: Liposarcoma, NOS','8851/3: Liposarcoma, well differentiated','8852/3: Myxoid liposarcoma','8853/3: Round cell liposarcoma','8854/3: Pleomorphic liposarcoma','8855/3: Mixed liposarcoma', '8857/3: Fibroblastic liposarcoma','8858/3: Dedifferentiated liposarcoma','8890/3: Leiomyosarcoma, NOS','8891/3: Epithelioid leiomyosarcoma','8893/3: Bizarre leiomyosarcoma',,'8894/3: Angiomyosarcoma','8895/3: Myosarcoma','8896/3: Myxoid leiomyosarcoma','8897/3: Malignant tumor of smooth muscle','8900/3: Rhabdomyosarcoma, NOS','8901/3: Pleomorphic rhabdomyosarcoma, adult type','8902/3: Mixed type rhabdomyosarcoma','8910/3: Embryonal rhabdomyosarcoma, NOS','8912/3: Spindle cell rhabdomyosarcoma','8920/3: Alveolar rhabdomyosarcoma','8921/3: Rhabdomyosarcoma with ganglionic differentiation', '8936/2: Gastrointestinal stromal tumor, NOS, in situ','8936/3: Gastrointestinal stromal sarcoma','8963/3: Malignant rhabdoid tumor', '8982/3: Malignant myoepithelioma','9040/3: Synovial sarcoma, NOS','9041/3: Synovial sarcoma, spindle cell','9042/3: Synovial sarcoma, epithelioid cell','9043/3: Synovial sarcoma, biphasic','9044/3: Clear cell sarcoma, NOS (except of kidney M- 8964/3)','9120/3: Hemangiosarcoma', '9125/3: Epithelioid hemangiosarcoma','9130/3: Hemangioendothelioma, malignant','9133/1: Epithelioid hemangioendothelioma, NOS','9133/3: Epithelioid hemangioendothelioma, malignant','9150/3: Hemangiopericytoma, malignant','9170/3: Lymphangiosarcoma','9220/3: Chondrosarcoma, NOS','9231/3: Myxoid chondrosarcoma','9240/3: Mesenchymal chondrosarcoma','9251/3: Malignant giant cell tumor of soft parts', '9260/3: Ewing sarcoma','9364/3: Peripheral neuroectodermal tumor','9365/3: Askin tumor','9540/3: Malignant peripheral nerve sheath tumor','9550/3: Plexiform neurofibrosarcma','9560/3: Neurilemoma, malignant (OBS)','9561/3: MPNST with rhabdomyoblastic differentiation', '9580/3: Granular cell tumor, malignant','9581/3: Alveolar soft part sarcoma') 1
2 OR {Site and Morphology.AYA site recode/who 2008} = '5 Soft Tissue Sarcomas',' 5.1 Fibromatous neoplasms',' 5.2 Rhabdomyosarcoma',' 5.3 Other soft tissue sarcoma',' Specified soft tissue sarcoma',' Specified (excluding Kaposi sarcoma)',' Unspecified soft tissue sarcoma' OR {Site and Morphology.Histology recode - broad groupings} = ' : soft tissue tumors and sarcomas, NOS',' : fibromatous neoplasms',' : myxomatous neoplasms',' : lipomatous neoplasms',' : myomatous neoplasms',' : blood vessel tumors',' : lymphatic vessel tumors',' : nerve sheath tumors' OR {Site and Morphology.Histology recode - broad groupings} = ' : soft tissue tumors and sarcomas, NOS',' : fibromatous neoplasms',' : myxomatous neoplasms',' : lipomatous neoplasms',' : myomatous neoplasms',' : fibroepithelial neoplasms',' : synovial-like neoplasms',' : blood vessel tumors',' : lymphatic vessel tumors',' : giant cell tumors',' : miscellaneous tumors',' : nerve sheath tumors',' : granular cell tumors & alveolar soft part sarcoma' OR {Site and Morphology.ICCC site rec extended ICD-O-3/WHO 2008} = ' XII(a.1) Gastrointestinal stromal tumor','iv Neuroblastoma and other peripheral nervous cell tumors',' IV(a) Neuroblastoma and ganglioneuroblastoma',' IV(b) Other peripheral nervous cell tumors',' VI(a.3) Kidney sarcomas',' VI(c) Unspecified malignant renal tumors',' VII(c) Unspecified malignant hepatic tumors','ix Soft tissue and other extraosseous sarcomas',' IX(a) Rhabdomyosarcomas',' IX(b) Fibrosarcomas, peripheral nerve & other fibrous',' IX(b.1) Fibroblastic and myofibroblastic tumors',' IX(b.2) Nerve sheath tumors',' IX(b.3) Other fibromatous neoplasms',' IX(c) Kaposi sarcoma',' IX(d) Other specified soft tissue sarcomas',' IX(d.1) Ewing tumor and Askin tumor of soft tissue',' IX(d.2) ppnet of soft tissue',' IX(d.3) Extrarenal rhabdoid tumor',' IX(d.4) Liposarcomas',' IX(d.5) Fibrohistiocytic tumors',' IX(d.6) Leiomyosarcomas',' IX(d.7) Synovial sarcomas',' IX(d.8) Blood vessel tumors',' IX(d.9) Osseous & chondromatous neoplasms of soft tissue',' IX(d.10) Alveolar soft parts sarcoma',' IX(d.11) Miscellaneous soft tissue sarcomas',' IX(e) Unspecified soft tissue sarcomas','xii Other and unspecified malignant neoplasms',' XII(a) Other specified malignant tumors',' XII(a.1) Gastrointestinal stromal tumor',' XII(a.6) Other specified malignant tumors',' XII(b) Other unspecified malignant tumors') 2
3 II. Diagnostic categories were grouped as follows: Undifferentiated pleomorphic sarcoma Malignant fibrous histiocytoma Undifferentiated sarcoma Histiocytoma, NOS, malignant Giant cell sarcoma Malignant tumor, giant cell type Leiomyosarcoma Leiomyosarcoma, NOS Myxoid leiomyosarcoma Epithelioid leiomyosarcoma Malignant tumor of smooth muscle Bizarre leiomyosarcoma Liposarcoma, well differentiated Dedifferentiated liposarcoma Myxoid liposarcoma Round cell liposarcoma Pleomorphic liposarcoma Mixed liposarcoma Liposarcoma, NOS MPNST Malignant peripheral nerve sheath tumor Neurilemoma, malignant MPNST with rhabdomyoblastic differentiation Plexiform neurofibrosarcoma Angiosarcoma Hemangiosarcoma Lymphangiosarcoma Epithelioid hemangiosarcoma Malignant hemangioendothelioma Malignant epithelioid hemangioendothelioma Epithelioid hemangioendothelioma Myxofibrosarcoma Fibromyxosarcoma Myxosarcoma Fibrosarcoma Fibrosarcoma, NOS Fascial fibrosarcoma Desmoplastic fibrosarcoma Synovial sarcoma Synovial sarcoma, NOS Synovial sarcoma, spindle cell Synovial sarcoma, biphasic Synovial sarcoma, epithelioid cell Embryonal rhabdomyosarcoma Spindle cell rhabdomyosarcoma 3
4 Alveolar rhabdomyosarcoma Pleomorphic rhabdomyosarcoma Mixed type rhabdomyosarcoma Rhabdomyosarcoma, NOS Rhabdomyosarcoma, NOS Rhabdomyosarcoma with ganglionic differentiation Myosarcoma Primitive neuroectodermal tumor Ewing sarcoma Peripheral neuroectodermal tumor Askin tumor Neuroepithelioma, NOS Gastrointestinal stromal tumor Myxoid chondrosarcoma Chondrosarcoma, NOS Malignant hemangiopericytoma Epithelioid sarcoma Malignant solitary fibrous tumor Malignant myoepithelioma Clear cell sarcoma Desmoplastic small round cell tumor Alveolar soft part sarcoma Extrarenal rhabdoid tumor Osteosarcoma, NOS Malignant granular cell tumor Mesenchymal chondrosarcoma Myofibroblastic sarcoma Myofibroma, malignant Myofibroblastoma, malignant Sarcoma, NOS, Spindle cell sarcoma Malignant tumor, spindle cell type III. Assignment of histologic grade Histologic grade for sarcoma cases coded by Collaborative Stage (CS) schema were extracted from the CS site-specific factor-1 variable; for non-soft tissue coded sites, grade was converted from ICD-O-3 code into low grade (well differentiated), intermediate grade (moderately differentiated) and high grade (poorly differentiated and undifferentiated). 4
5 IV. Definition of regional tumor extension Regional extension is defined by site-specific Collaborative Stage criteria as invasion of adjacent organs/structures: adrenal(s), aorta, ascending colon, bone/cartilage, descending colon, kidney(s), pancreas, vena cava, vertebra or further contiguous extension, including: extension to colon other than ascending or descending (coding details are available at URL: Similarly, regional extension is defined in EOD 10 - extent ( ) as invasion of adjacent organs/structures including bone/cartilage, pancreas, ascending colon, descending colon, kidneys, adrenal glands, vertebra, aorta, vena cava or further contiguous extension (coding details are available at URL: V. Classification of histologic subtypes of sarcoma Histologic type was classified as unfavorable or favorable based evaluation of hazard ratios from multivariable Cox proportional hazard regression (Supplementary Table 4). Histologic subtypes with hazard ratios 0.5 or statistically significantly lower than the referent category (undifferentiated pleomorphic sarcoma) were considered favorable; subtypes not meeting these criteria were considered unfavorable. Of note, some (perhaps most) cases recorded as fibrosarcoma and myxofibrosarcoma of the retroperitoneum likely represent dedifferentiated liposarcoma. 1,2 5
6 VI. Development of Vanderbilt Staging system Based on pairwise analysis of hazard ratios for AJCC 8 th edition T categories in multivariable Cox regression (Supplementary Table 5), T1 ( 5 cm) and T2 (>5 and 10 cm) size categories were not significantly different. Therefore, tumor size was recoded as: T1 T2 T3 10 cm (N=864) >10 cm and 15 cm (N=769) >15 cm (N=1,683) Lymph node status was omitted from the staging system algorithm based on low prevalence (2.2%; Supplementary Table 2) and low impact of nodal metastasis on clinical outcome (see results of multivariable Cox regression, Supplementary Table 3 and nomogram, Supplementary Figure 7). Cases were then grouped according to histologic grade, modified AJCC T category, histologic type, and presence of distant, non-nodal metastasis. Disease-specific survival was calculated for each subgroup at 1, 2, 3, 5 and 10 years (Supplementary Table 6). Kaplan-Meier plots were generated to visually identify subgroups with similar survival rates (Supplementary Figure 8). Subgroups were then categorized according to similar clinical outcomes to generate the Vanderbilt Staging System (Table 1). 6
7 Supplementary Table 1. Initial SEER cohort and exclusion criteria used. N (%) Initial SEER cohort: 379,647 Diagnostic categories excluded: 8000/3: Neoplasm, malignant 188, /3: Tumor cells, malignant 4, /3: Malignant tumor, small cell type /3: Malignant tumor, clear cell type /3: Paraganglioma, malignant /3: Gangliocytic paraganglioma, malignant /3: Glomus jugulare tumor, malignant /3: Aortic body tumor, malignant /3: Carotid body tumor, malignant /3: Extra-adrenal paraganglioma, malignant /3: Pheochromocytoma, malignant /3: Glomangiosarcoma /3: Glomus tumor, malignant /3: Small cell sarcoma /3: Epithelioid sarcoma /3: Desmoplastic small round cell tumor /3: Periosteal fibrosarcoma /3: Infantile fibrosarcoma /3: Aggressive fibromatosis, malignant /3: Abdominal fibromatosis, malignant /3: Angiomyofibroblastoma, malignant /3: Dermatofibrosarcoma, NOS 8, /3: Pigmented dermatofibrosarcoma protuberans /3: Malignant plexiform fibrohistiocytic tumor /3: Malignant angiomatoid fibrous histiocytoma /3: Angiomyxoma, malignant /3: Ossifying fibromyxoid tumor, malignant /3: Fibroblastic liposarcoma /3: Angiomyoliposarcoma /3: Angiomyosarcoma /3: Rhabdomyosarcoma, NOS /3: Rhabdomyosarcoma, mixed type /3: Rhabdomyosarcoma, embryonal /3: Rhabdomyosarcoma, spindle cell /3: Rhabdomyosarcoma, alveolar 20 7
8 Supplementary Table 1, continued. N (%) 8930/3: Endometrial stromal sarcoma, NOS 2, /3: Endometrial stromal sarcoma, low grade /3: Adenosarcoma 1, /3: Carcinofibroma /3: Gastrointestinal stromal tumor /3: Müllerian mixed tumor 7, /3: Mesodermal mixed tumor 1, /3: Extrarenal rhabdoid tumor /3: Clear cell sarcoma of kidney /3: Pancreatoblastoma /3: Pulmonary blastoma /3: Pleuropulmonary blastoma /3: Carcinosarcoma, NOS 8, /3: Carcinosarcoma, embryonal /3: Adenomyoepithelioma, malignant /3: Mesenchymoma, malignant /3: Embryonal sarcoma /3: Brenner tumor, malignant /3: Adenofibroma, malignant /3: Serous adenocarcinofibroma /3: Mucinous adenocarcinofibroma /3: Phyllodes tumor, malignant 2, /3: Clear cell sarcoma /3: Mesothelioma, malignant 10, /3: Fibrous mesothelioma, malignant 1, /3: Epithelioid mesothelioma, malignant 4, /3: Mesothelioma, biphasic, malignant /3: Adenomatoid tumor, malignant /3: Multicystic mesothelioma, malignant /3: Mesonephroma, malignant /3; 9215/3: Hemangiosarcoma /3: Kupffer cell sarcoma /3; 9133/3: Hemangioendothelioma /3: Kaposi sarcoma 23, /3: Angiofibrosarcoma /3: Hemangioblastoma, malignant /3: Chondrosarcoma, NOS 8 8
9 Supplementary Table 1, continued. N (%) 9231/3: Myxoid chondrosarcoma /3: Mesenchymal chondrosarcoma /3: Giant cell tumor of bone, malignant /3: Malignant giant cell tumor of soft parts /3: Malignant tenosynovial giant cell tumor /3, 9364/3, 9365/3: Primitive neuroectodermal tumor /3: Craniopharyngioma, malignant /3: Malignant craniopharyngioma, adamantinomatous /3: Pinealoma, malignant /3: Pineocytoma, malignant /3: Pineoblastoma /3: Melanotic neuroectodermal tumor, malignant /3: Chordoma, NOS 1, /3: Chondroid chordoma /3: Dedifferentiated chordoma /3: Ganglioneuroblastoma /3: Neuroblastoma, NOS 3, /3: Medulloepithelioma, NOS /3: Teratoid medulloepithelioma /3: Olfactory neurogenic tumor /3: Olfactory neurocytoma /3: Olfactory neuroblastoma /3: Olfactory neuroepithelioma /3: Neurothekeoma, malignant /3: Perineurioma, malignant /3: Granular cell tumor, malignant /3: Alveolar soft part sarcoma 4 9
10 Supplementary Table 1, continued. Anatomic sites excluded: N (%) Soft tissue, extremity/trunk 34,996 Gastrointestinal tract 12,993 Genitourinary tract 10,251 Soft tissue, head/neck 9,573 Bone, bone marrow, and lymph nodes 7,970 Soft tissue, pelvis 5,714 Soft tissue, abdomen 4,628 Thoracic viscera 2,175 Soft tissue, NOS 1,975 Abdominal viscera 1,039 Central nervous system 772 Mediastinum 515 Eye/orbit 328 Pleura 300 Thymus 8 Unknown primary site 1,329 No diagnostic confirmation a 839 Patient <18 years of age 37 Tumor size >60 cm b 14 Tumor size <2 cm b 44 Not resected or primary surgery could not be confirmed 1,363 No follow-up data 15 No information on distant metastasis 116 Diagnosed before Final SEER cohort for study: 3,703 Abbreviations: NOS, not otherwise specified; SEER, Surveillance, Epidemiology, and End Results. a Diagnosis not confirmed by histopathologic or cytopathologic examination. b Cases with tumor size listed as >60 cm or <2 cm were excluded based on sparsity of data in these size ranges. 10
11 Supplementary Table 2. Clinicopathologic characteristics of the Surveillance, Epidemiology, and End Results cohort of patients with sarcomas of the retroperitoneum (N=3,703). N (%) Sex Female 1,992 (53.8) Male 1,711 (46.2) Histologic type Leiomyosarcoma, NOS 1,046 (28.3) Liposarcoma, well differentiated 642 (17.3) Dedifferentiated liposarcoma 596 (16.1) Liposarcoma, NOS 316 (8.5) Undifferentiated pleomorphic sarcoma 284 (7.7) Sarcoma, NOS 247 (6.7) Myxoid liposarcoma 187 (5.1) Pleomorphic liposarcoma 88 (2.4) Mixed liposarcoma 84 (2.3) Malignant peripheral nerve sheath tumor 61 (1.7) Malignant hemangiopericytoma 44 (1.2) Fibrosarcoma 24 (0.7) Malignant solitary fibrous tumor 24 (0.7) Myxofibrosarcoma 22 (0.6) Round cell liposarcoma 16 (0.4) Synovial sarcoma 12 (0.3) Pleomorphic rhabdomyosarcoma 7 (0.2) Myofibroblastic sarcoma 3 (0.1) Histologic group a Favorable 1,600 (43.2%) Unfavorable 2,103 (56.8%) Histologic grade Grade 1 (low grade) 1,016 (27.4) Grade 2 (intermediate grade) 639 (17.3) Grade 3 (high grade) 1,432 (38.7) Missing 616 (16.7) AJCC Stage, 8 th edition Stage IA 61 (1.6) Stage IB 816 (22.0) Stage II 91 (2.5) Stage IIIA 341 (9.2) Stage IIIB 1,315 (35.5) Stage IV 351 (9.5) Missing 728 (19.7) 11
12 Supplementary Table 2, continued. N (%) Metastasis at presentation Localized 3,272 (88.4) Nodal metastasis 80 (2.2) Distant metastasis 351 (9.5) Neoadjuvant chemotherapy None 1,854 (50.1) Administered 187 (5.0) Unknown 1,662 (44.9) Adjuvant radiation therapy No radiation therapy 2,680 (72.4) Administered 946 (25.5) Unknown 77 (2.1) Regional tumor extension b Not identified 2,413 (65.2%) Present 1,290 (34.8%) Abbreviations: NOS, not otherwise specified; AJCC, American Joint Committee on Cancer. a Defined in Methods section and Appendix. b Defined in Methods section (see URL: aspx and URL: for coding details). 12
13 Supplementary Table 3. Sarcoma-specific survival analysis. a Univariable P Multivariable P hazard ratio (95% CI) hazard ratio (95% CI) Age 1.15 ( ) < ( ) < (10-year intervals) Male sex 1.11 ( ) Year of diagnosis 0.88 ( ) < ( ) (5-year intervals) Histologic grade Low grade (reference group) Intermediate grade 2.39( ) < ( ) < High grade 3.89 ( ) < ( ) < Size (cm) 1.01 ( ) ( ) < Metastasis Localized (reference group) Nodal metastasis 1.28 ( ) ( ) 0.96 Distant metastasis 3.67 ( ) < ( ) < Neoadjuvant 0.89 ( ) 0.47 chemotherapy Radiation therapy 0.90 ( ) ( ) Abbreviations: CI, confidence interval. a Multivariable survival analysis was initially performed including all variables listed in Supplementary Table 2 except AJCC stage, histologic group, and regional tumor extension; insignificant variables were removed from the model step-wise in order of increasing absolute value of Z-score. 13
14 Supplementary Table 4. Hazard ratios for disease-specific survival by histologic subtype of retroperitoneal sarcoma. a Histologic subtype Hazard ratio (95% CI) P Favorable Liposarcoma, well differentiated 0.43 ( ) < Liposarcoma, NOS 0.51 ( ) < Dedifferentiated liposarcoma 0.60 ( ) < Fibrosarcoma 0.37 ( ) 0.09 Myxofibrosarcoma 0.50 ( ) 0.18 Unfavorable Malignant hemangiopericytoma 0.79 ( ) 0.61 Mixed liposarcoma 0.81 ( ) 0.36 Pleomorphic liposarcoma 0.84 ( ) 0.43 Leiomyosarcoma, NOS 0.94 ( ) 0.61 Myxoid liposarcoma 0.96 ( ) 0.82 Undifferentiated pleomorphic sarcoma 1.00 Round cell liposarcoma 1.06 ( ) 0.89 Sarcoma, NOS 1.12 ( ) 0.48 Malignant solitary fibrous tumor 1.21 ( ) 0.74 Synovial sarcoma 1.61 ( ) 0.35 Malignant peripheral nerve sheath tumor 1.66 ( ) Pleomorphic rhabdomyosarcoma 2.65 ( ) Myofibroblastic sarcoma 15.2 ( ) Abbreviations: CI, confidence interval; NOS, not otherwise specified. a Adjusted for patient age, year of diagnosis, tumor size, histologic grade, distant metastasis, and radiation therapy, (N=2,756 with 916 events). 14
15 Supplementary Table 5. Pairwise comparisons of American Joint Committee on Cancer 8 th edition T categories. a Comparison Hazard ratio P (95% CI) T2 vs. T ( ) 0.29 T3 vs. T ( ) T4 vs. T ( ) Abbreviations: CI, confidence interval; T1, tumor size 5 cm; T2, tumor size >5 and 10 cm; T3, tumor size >10 and 15 cm; T4, tumor size >15 cm. a Adjusted for patient age, year of diagnosis, histologic grade, radiation therapy, and presence of distant metastasis (N=2,756 with 916 events). 15
16 Supplementary Table 6. Histologic grade, modified AJCC 8 th edition T category, and histologic type groups used in development of the Vanderbilt Staging System for retroperitoneal sarcoma. Group Disease-specific survival (years) N % Grade 1; T1; Favorable histology % 98% 98% 97% 95% 84% Grade 1; T1; Unfavorable histology % 97% 97% 93% 88% 62% Grade 1; T2; Favorable histology % 100% 100% 100% 97% 95% Grade 1; T2; Unfavorable histology % 90% 79% 70% 55% 40% Grade 1; T3; Favorable histology % 98% 96% 94% 89% 74% Grade 1; T3; Unfavorable histology % 96% 91% 89% 78% 60% Grade 2 T1; Favorable histology % 96% 91% 91% 77% 62% Grade 2 T1; Unfavorable histology % 96% 88% 83% 71% 66% Grade 2 T2; Favorable histology % 100% 91% 85% 85% 78% Grade 2 T2; Unfavorable histology % 91% 89% 84% 72% 51% Grade 2 T3; Favorable histology % 95% 89% 83% 65% 47% Grade 2 T3; Unfavorable histology % 90% 78% 70% 54% 35% Grade 3 T1; Favorable histology % 85% 76% 74% 68% 68% Grade 3 T1; Unfavorable histology % 92% 83% 75% 62% 46% Grade 3 T2; Favorable histology % 87% 81% 72% 67% 51% Grade 3 T2; Unfavorable histology % 82% 69% 60% 54% 34% Grade 3 T3; Favorable histology % 86% 76% 68% 58% 42% Grade 3 T3; Unfavorable histology % 79% 60% 50% 40% 31% Grade 1; Tx; M % 83% 83% 71% 54% 47% Grade 2; Tx; M % 76% 58% 45% 21% 17% Grade 3; Tx; M % 60% 39% 28% 22% 15% Abbreviations: M1, distant, non-nodal metastasis present; T1, tumor size 10 cm; T2, tumor size >10 and 15 cm; T3, tumor size >15 cm; Tx, any T category. 16
17 Supplementary Table 7. Hazard ratios for disease-specific survival by American Joint Committee on Cancer, 7 th and 8 th edition staging systems for retroperitoneal sarcoma (N=2,942; 1,028 deaths). Staging system Hazard ratio (95% CI) P AJCC 8 th edition Stage IA 1.00 Stage IB 1.10 ( ) 0.79 Stage II 1.62 ( ) 0.26 Stage IIIA 2.78 ( ) Stage IIIB 3.89 ( ) <0.001 Stage IV 9.77 ( ) <0.001 AJCC 7 th edition Stage IA 1.00 Stage IB 1.10 ( ) 0.80 Stage IIA 1.62 ( ) 0.25 Stage IIB 2.70 ( ) Stage III 4.16 ( ) <0.001 Stage IV 9.80 ( ) <
18 Supplementary Figure 1. Flowchart of case exclusions for univariable analysis of tumor size as a continuous variable. Number censored Not missing size N=2,011 No nodal or distant metastasis N=2,960 Number of deaths Initial cohort N=3,703 N=3,272 Missing size N=312 N=949 Metastasis present N=431 Excluded 18
19 Supplementary Figure 2. Flowchart of case exclusions for multivariable analysis of tumor size as a continuous variable. 19
20 Supplementary Figure 3. Flowchart of case exclusions for logistic regression analysis of tumor staging systems. Survived at least 5 years Initial cohort N=3,703 Not missing staging information for any system N=2,942 Missing staging information for 1 system Not censored before 5 years follow-up N=1,800 Censored before 5 years follow-up N=1,142 Excluded N=970 Died within 5 years N=830 N=761 20
21 Supplementary Figure 4. Flowchart of case exclusions for calculation of Gönen & Heller s K, O Quigley s ρ 2 k, Royston s R 2, and Bayesian Information Criterion. Initial cohort N=3,703 Not missing staging information for any system N=2,942 Missing staging information for 1 system N=761 Number censored N=1,914 Number of deaths N=1,028 Excluded 21
22 Supplementary Figure 5. Flowchart of case exclusions for calculation of Harrell s c and Somers D concordance indices. Survived at least 5 years Initial cohort N=3,703 Not missing staging information for any system N=2,942 Missing staging information for 1 system Not censored before 5 years follow-up N=1,800 Censored before 5 years follow-up N=1,142 Excluded N=970 Died within 5 years N=830 N=761 22
23 Supplementary Figure 6. Predicted hazard ratios for American Joint Committee on Cancer 8 th edition T classifications by histologic grade of tumor. Note the relatively weak effect of increasing tumor size in comparison to histologic grade. Separate analysis of tumor size modeled as a continuous variable showed only a 1.7% increase in risk (95% confidence interval, %) for each 1 cm increase in size (data not shown) T1 T2 T3 T4 AJCC 8 th Ed. T classification Grade 1 Grade 2 Grade 3 23
24 Supplementary Figure 7: Nomogram for predicting 5-year and 10-year disease-specific survival for patients with retroperitoneal sarcoma. * Values used for years since diagnosis were calculated using the formula, 2013 (calendar year of diagnosis). 24
25 Supplementary Figure 8: Kaplan-Meier disease-specific survival plots with cases classified by histologic grade, modified American Joint Committee on Cancer 8 th edition T category (T1, tumor size 10 cm; T2, >10 and 15 cm; T3, >15 cm), and histology (FH, favorable histology; UH, unfavorable histology). M1 denotes cases with distant, non-nodal metastasis at diagnosis. 100% Grade 1 100% Grade 2 100% Grade 3 80% 80% 80% 60% 60% 60% 40% 40% 40% 20% 20% 20% 0% 0% 0% Follow-up time (years) Follow-up time (years) Follow-up time (years) T1,FH T2,FH T3,FH M1 T1,UH T2,UH T3,UH 25
26 REFERENCES 1. Bahrami A, Folpe AL. Adult-type fibrosarcoma: a reevaluation of 163 putative cases diagnosed at a single institution over a 48-year period. Am J Surg Pathol. 2010;34: Hasegawa T, Seki K, Hasegawa F, et al. Dedifferentiated liposarcoma of retroperitoneum and mesentery: varied growth patterns and histological grades--a clinicopathologic study of 32 cases. Hum Pathol. 2000;31:
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