Table 3.
Results summary: overview of selected quantitative comparative risks (expressed as HR, RR, RTR, OR) reported by identified studies.
| CATEGORY | LATE EFFECTS | RISK FACTOR | TREATMENT CLASS | COMPARISON | DETAILS | REPORTED INCREASE IN RISKS Expressed as HR, RR, RTR, OR (95% CI) |
|---|---|---|---|---|---|---|
| Cardiac toxicity | Cardiac toxicity (including heart failure, myocardial infarction, pericardial disease, valvular abnormalities, abnormal echocardiogram) |
Dose [27] |
ATC | Heart failure in exposed cancer survivors | DAU ≤ 300 mg/m2-<400 mg/m2 DRN ≤ 300 mg/m2-<400 mg/m2 |
HR 4.33 (1.73 to 10.84) HR 13.19 (9.04 to 19.25) |
| Primary cancer diagnosis [32] |
ATC | Myocardial infarction in exposed Hodgkin’s Lymphoma survivors vs. other tumors | Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma |
HR 12.2 (5.2 to 28.2) p < .001 HR 2.9 (0.9 to 9.6) p = .085 |
||
| Age at treatment start [23] |
ATC | Abnormal echocardiogram in younger vs. older exposed cancer survivors | Aged 1–4 years | HR 1.89 (1.08 to 3.31) | ||
| CV risk factors [24] |
ATC | Exposed cancer survivors with vs. without CV risk factors (diabetes, hypertension, dyslipidemia, obesity) | Hypertension Hypertension + dyslipidemia Hypertension + diabetes Hypertension + obesity |
RTR 12.4 (7.6 to 20.1) p < .001 RTR 11.3 (4.6 to 27.5) p < .001 RTR 16.9 (5.1 to 55.7) p < .001 RTR 6.5 (2.5 to 16.5) p < .001 |
||
| Homozygous for the CBR3 V244M G allele | ATC | Exposed cancer survivors homozygous for G allele in CBR3 vs. unexposed patients with at least one copy of variant A allele in CBR3 | 1–100mg/m2
301 + mg/m2 |
OR 2.16 (0.47 to 10.05) OR 27.71 (7.42 to 103.44) |
||
| Hormone deficiencies, infertility |
Diminished ovarian reserve (AMH level) | Dose [46] |
ALK | Exposed vs. unexposed cancer survivors | CPS > 7.5 g/m2 | OR: 12.0 (1.3 to 107.4) p = .03 |
| Acute ovarian failure/Early menopause | Drug exposure/age [38] |
ALK | Exposed younger vs. unexposed older cancer survivors | Aged 21–25 yrs, ALK + RTb | RR: 27.39 (12.42 to 60.35) p ≤ .01 | |
| Age at diagnosis [39] |
ALK | Older vs. younger exposed cancer survivors | 13–20 years (vs. 0–12) | OR 1.8 (1.4 to 2.4) p < .0001 | ||
| Primary cancer diagnosis [39] |
ALK | Hodgkin’s and non-Hodgkin’s Lymphoma survivors vs. other tumors | Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma |
OR 3.8 (2.7 to 5.4) p < .001 OR 3.2 (1.8 to 5.3) p < .001 |
||
| Risk of pregnancy | Drug exposure [42,43] |
ALK | Exposed cancer survivors vs. unexposed same sex siblings | Female Male |
RR 0.81 (0.73 to 0.90) p < .001 RR 0.56 (0.49 to 0.63) p < .001 |
|
| Secondary leukemia | t-MDS/AML | Dose [52] |
ALK | High dose vs. low dose treatment | DRN 450mg/m2 + CPS 17.6g/m2 + IFO 140g/m2 | RR 15.91 (3.84 to 65.82) |
| Dose [51] |
ALK ATC |
High dose vs. low dose treatment | ALK ≥ 10g/m2 ATC ≥ 0.2g/m2 |
RR 6.2 (2.4 to 16.1) p = .00001 RR 1.6 (0.7 to 4.0) p = .103 |
||
| Primary cancer diagnosis [51] |
ALK ATC |
Exposed Hodgkin’s Lymphoma survivors vs. other tumors | Hodgkin’s Lymphoma | OR 2.0 (0.6 to 6.6) p = .525 | ||
| Primary cancer diagnosis [56] |
ALK ATC |
Exposed Hodgkin’s Lymphoma survivors vs. other tumors | Hodgkin’s Lymphoma | RR 6.4 (1.6 to 24) p = .004 | ||
| Osteonecrosis | Osteonecrosis | Drug exposure [60] |
CTS ± RT/SG | Exposed cancer survivors vs. unexposed siblings | Chemotherapy including CTS ± RT/SG | RTR 6.2 (2.3 to 17.2) |
| Drug exposure [60] |
CTS | Exposed cancer survivors vs. unexposed siblings | DEX ± PRN | RTR 4.0 (1.8 to 8.9) p < .001 | ||
| Age at diagnosis [59] |
CTS | Older vs. younger exposed cancer survivors | Aged ≥ 10 years | OR 5.52 (4.7 to 6.5) p < .0001 | ||
| Sex [63] |
CTS | Female vs. male exposed cancer survivors | Females | OR 2.23 (1.04 to 4.81) p = .04 | ||
| Primary cancer diagnosis [60] |
CTS | Exposed Hodgkin’s and Non-Hodgkin’s lymphoma survivors vs. unexposed siblings | Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma |
RTR 6.7 (2.0 to 22.2) p = .002 RTR 6.7 (1.8 to 25.1) p = .005 |
||
| Urotoxicity, bladder malignancy | Bladder cancer | Dose [67] |
ALK | Exposed vs. unexposed cancer survivors | CPS 20‒49 g CPS ≥ 50 g |
MRR 6.3 (1.3 to 2.9) MRR 14.5 (2.3 to 94) |
| Duration of exposure [67] |
ALK | Exposed vs. unexposed cancer survivors | CPS 1–2 years CPS ≥ 2 years |
MRR 3.7 (0.6 to 22) MRR 11.88 (2.3 to 61) |
ATC: anthracycline; ALK: alkylating agents; AMH: Anti‐Müllerian hormone; CI: confidence intervals; CTS: corticosteroids; CV: cardiovascular; CPS: cyclophosphamide; DAU: daunorubicin; DEX: dexamethasone; DRN: doxorubicin; HR: hazard ratio; IFO: ifosfamide; MRR: matched relative risk; OR: odds ratio; PRN: prednisone; RR: relative risk; RTb: radiation below the diaphragm; RTR: rate ratio; SG: surgery; vs.: versus.