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1 Supplementary Online Content Acuna SA, Fernandes KA, Daly C, et al. Cancer mortality among recipients of solidorgan transplantation in Ontario, Canada. JAMA Oncol. Published online January 7, doi: /jamaoncol efigure 1. Timing of cancer death assignment diagram etable 1. Reassignment of cancer sites for certain causes of death etable 2. Characteristics of all the included solid organ transplant recipients, recipients with any cancer death and those who died of a post-transplant de novo malignancy etable 3. Leading cause of death in Ontario Solid Organ Transplant Recipients efigure 2. Overall cancer standardized mortality ratios for all transplant recipients by age group and transplanted organ efigure 3. Cumulative incidence of cancer death for all transplant recipients by transplant period etable 4. Standardized mortality ratios (SMR) by cancer site for all cancer deaths by transplanted organ This supplementary material has been provided by the authors to give readers additional information about their work.

2 efigure 1. Timing of cancer death assignment diagram. efigure 1. Timing of cancer death assignment diagram. After verification of concordance of the ICD-9 diagnosis code for the cause of death in the OCR and in the ORGD, the cause of death was matched with a diagnosis date in the OCR and categorized as pre-transplant (up to seven days post-transplant) or post-transplant. This procedure matched most of the cancer deaths to a cancer diagnosis date (89.2%). In the remaining 65 cases, no cancer diagnosis existed in the OCR in 21 cases, and the cancer cause of death did not march any of the cancer diagnosis available in the OCR in in 44 cases. These cases were not excluded from the overall and site-specific SMR but were excluded from the post-transplant de novo SMR calculations. a Underlying cause of death ICD-9 codes Abbreviations: ICD-9, International Classification of Diseases 9 th Revision; OCR, Ontario Cancer Registry

3 etable 1. Reassignment of cancer sites for certain causes of death Cancer causes of death with unknown site Causes of death listed as benign, uncertain or unspecified behavior malignancy but site specific (e.g. neoplasm of uncertain behavior of lung were assigned to lung cancer deaths) ICD-9 codes: 215, 235.0, 235.1, 235.3, 235.7, 236.0, 236.2, 236.3, 236.7, , 238.6, 239.3, Neoplasm of uncertain behavior or unspecified nature with unknown site as well malignant neoplasms of other and ill-defined sites but known system (e.g. neoplasm of unspecified nature of digestive system). ICD-9: 159, 165, 235.2, 235.4, 235.5, 235.9, , , 239.0, 239.1, 239.2, Malignant neoplasm of other and ill-defined sites, without specification of site, and secondary malignancies (e.g. secondary malignant neoplasm of respiratory and digestive systems). ICD-9 codes: , 229, 238.9, Action Assigned to the respective cancer site (e.g. assigned to lung cancer deaths) Assigned to a cancer site if they had a cancer diagnosis corresponding to the same system, otherwise kept as unknown site (e.g. if a colorectal diagnosis code was recorded in OCR it was assigned to colorectal). Assigned to any post-transplant diagnosis if this was the only diagnosis and it was site specific, otherwise they were kept as unknown (e.g. if a post-transplant colorectal cancer diagnosis was recorded in OCR it was assigned to colorectal cancer death). Abbreviations: ICD-9, International Classification of Diseases 9 th Revision; OCR, Ontario Cancer Registry

4 etable 2. Characteristics of all the included solid organ transplant recipients, recipients with any cancer death and those who died of a post-transplant de novo malignancy. Characteristics No. (%) of Transplant Recipients No. (%) of cancer deaths From any From a post-transplant malignanc de novo malignancy y Total 11,061 (100) 603 (100) 411 (100) Patient characteristics at transplantation Age, years > 61 Sex Female Male Transplant characteristics and outcomes Transplanted organ Kidney Liver Heart Lung Pancreas/Kidney Other (incl. other comb.) Transplant period (7.3) 1,575 (14.2) 3,608 (32.6) 3,035 (27.4) 2,040 (18.4) 4,004 (36.2) 7,057 (63.8) 6,516 (58.9) 2,606 (23.6) 929 (8.4) 705 (6.4) 255 (2.3) 50 (0.5) 2,443 (22.1) 2,531 (22.9) 3,061 (27.7) 3,026 (27.4) 21 (3.5) 30 (5.0) 157 (26.0) 218 (36.2) 177 (29.4) 179 (29.7) 424 (70.3) 283 (46.9) 214 (35.5) 58 (9.6) 40 (6.6) <5 <5 218 (36.2) 157 (26.0) 155 (25.7) 73 (12.1) 13 (3.2) 22 (5.4) 107 (26.0) 142 (34.5) 127 (30.9) 129 (31.4) 282 (68.6) 245 (59.6) 93 (22.6) 48 (11.7) 20 (4.9) <5 <5 171 (41.6) 112 (27.3) 92 (22.4) 36 (8.8) Pre-transplant malignancy 1,124 (10.2) 171 (28.4) 22 (5.4) Post-transplant de novo malignancy 1,267 (11.5) 440 (73.1) 411 (100) Graft Failure 2,154 (19.5) 130 (21.6) 64 (15.6) Abbreviations: Q: quintile.

5 etable 3. Leading cause of death in Ontario Solid Organ Transplant Recipients Causes of death by diagnostic group No. (%) of all recipients No. (%) of recipients by transplanted organ Kidney Liver Heart Lung Total (100) (100) 825 (100) 332 (100) 332 (100) Circulatory System 737 (24.0) 440 (28.5) 80 (9.7) 189 (56.7) 24 (7.2) Neoplasms 603 (19.7) 283 (18.3) 215 (26.1) 59 (17.8) 40 (12.0) Neoplasms (Non-Indication a ) 499 (16.3) 126 (15.3) 25 (7.5) Endocrine, Metabolic, and Immunity 350 (11.4) 221 (14.3) 38 (4.6) 7 (2.1) 73 (22.0) Genitourinary System 303 (9.9) 258 (16.7) 27 (3.3) 8 (2.4) 6 (1.8) Infectious and Parasitic Diseases 296 (9.6) 74 (4.8) 187 (22.7) 11 (3.3) 22 (6.6) Digestive System 283 (9.2) 67 (4.3) 202 (24.5) 6 (1.8) 5 (1.5) Respiratory System 239 (7.8) 59 (3.8) 21 (2.5) 20 (6.0) 138 (41.6) External Causes of Injury and Poisoning 74 (2.4) 44 (2.9) 18 b(2.2) 8 (2.4) <5 Congenital abnormalities 65 (2.1) 33 (2.1) 10 (1.2) 17 (5.1) <5 Musculoskeletal and Connective Tissue 37 (1.2) 18 (1.2) 7 (0.8) <5 9 (2.7) Other 81 (2.6) 46 (3.0) 20 (2.4) 5 (1.5) 8 (2.4) a Does not include deaths secondary to malignancies that were the indication for transplantation.

6 efigure 2. Overall cancer standardized mortality ratios for all transplant recipients by age group and transplanted organ. efigure 2. Overall cancer standardized mortality ratios for all transplant recipients by age group and transplanted organ. Overall cancer standardized mortality ratios for all transplant recipients by (A) age group and (B) transplanted organ. Cancer mortality from recurrent and post transplant de novo malignancies shown in black; cancer mortality associated only with post transplant de novo malignancies shown in blue. SMR are presented in a log scale. Recipients who underwent combined organ transplantation were allocated in the following way: any combination including a lung transplant were allocated to lung, combinations of heart transplant (but not lung) were allocated to heart, liver and kidney transplants were allocated to liver. Abbreviations: SMR, standardized mortality ratio; CI, confidence interval.

7 efigure 3. Cumulative incidence of cancer death for all transplant recipients by transplant period. efigure 2. Cumulative incidence of cancer death for all transplant recipients by transplant period. Non-cancer deaths were considered competing events for this calculation (not shown). The cumulative incidence functions were compared using the Gray s test (p=0.16).

8 etable 4. Standardized mortality ratios (SMR) by cancer site for all cancer deaths by transplanted organ Cancer site SMR Kidney Liver Heart Lung Lowe Uppe Lowe Uppe Lowe Upper Lowe r 95% r 95% SMR r 95% r 95% SMR r 95% 95% SMR r 95% CI CI CI CI CI CI CI Upper 95% CI Lung Lung (exc. cancer ind.) Liver/biliary Liver/biliary (exc. cancer ind.) NHL Leukemia Colorectal Melanoma Pancreas NMSC Esophagus Stomach OCP Prostate Kidney Bladder Breast Gynecologi c Other Unknown Abbreviations: SMR, Standardized Mortality Ratio; CI, Confidence Interval; NHL, Non-Hodgkin Lymphoma; NMSC, Non-Melanoma Skin Cancer; OCP, Oral Cavity and Pharynx