Table 2.
Linear Regression of the Association Between Residual Platinum Values as a Continuous Variable and Phenotypes Relevant to Cisplatin-Based Chemotherapy.
| Linear Regression | Linear Regression with Age at Diagnosis | |||||
|---|---|---|---|---|---|---|
| Variable Type | n | β (95% CI) | p-value | β (95% CI) | p-value | |
| Risk Factors/Comorbidities | ||||||
| Age at Diagnosis | continuous | 1,010 | 0.01 (8.68×10−3, 0.02) | 3.13×10−9 | N/A | N/A |
| Creatinine clearancea | continuous | 769 | −2.67×10−3 (−3.89×10−3, −1.45×10−3) | 1.99×10−5 | −1.95×10−3 (−3.20×10−3, −7.09×10−4) | 2.13×10−3 |
| LDL (mg/dL) | continuous | 580 | 9.12×10−3(−3.61×10−4, 2.18×10−3) | 0.16 | 7.52×10−4 (−5.00×10−4, 2.00×10−3) | 0.24 |
| LH (mg/dL) | continuous | 437 | 0.01 (3.7×10−3, 0.02) | 6.07×10−3 | 0.01 (2.91×10-3, 0.02) | 6.58×10−3 |
| Hypogonadismb,c | categorical | 428 | 0.07 (−0.04, 0.19) | 0.22 | 0.02 (−0.10, 0.13) | 0.75 |
| Testosterone (ng/mL) | continuous | 441 | −2.28×10−3(−7.66×10−3, 3.10×10−3) | 0.41 | −1.68×10−3 (−6.97×10−3, 3.60×10−3) | 0.53 |
| Cisplatin-Induced Toxicities | ||||||
| CBM score for cisplatin-induced toxicitiesd | categorical | 1003 | 0.04 (8.80×10−3, 0.08) | 0.01 | 0.02 (−0.02, 0.05) | 0.28 |
| Peripheral sensory neuropathye | categorical | 999 | 0.08 (0.02, 0.14) | 7.52×10−3 | 0.04 (−0.02, 0.10) | 0.18 |
| Raynaud phenomenone | categorical | 994 | 0.07 (0.02, 0.12) | 9.84×10−3 | 0.05 (4.53×10-3, 0.10) | 0.03 |
| Hearing Loss (rnGM412)f | continuous | 751 | 0.03 (−0.02, 0.08) | 0.21 | −0.05 (−0.11, 6.78×10−5) | 0.05 |
| Tinnitus | categorical | 957 | 0.07 (5.44×10-3, 0.15) | 0.07 | 0.07 (−7.19×10−3, 0.15) | 0.07 |
Abbreviations: CBM: cumulative burden of morbidity; LDL: low-density lipoprotein cholesterol; LH: luteinizing hormone
For the linear regression model, the continuous version of residual platinum values was the dependent variable. The other phenotypes were classified as independent variables, and age at diagnosis was included as a covariate where indicated. Bold indicates p ≤ 0.05; italics indicates 0.05 < p < 0.10.
Was calculated by using the following formula: creatinine clearance = (140- age at clinical examination)*weight (kg) /(72* serum creatinine (mg/dL).
Excluded 54 patients who had measured LH values, but received testosterone therapy.
Defined as testosterone levels ≤ 3 ng/mL based on crude measurement or whether the patient was on testosterone therapy. All patients who had testosterone levels > 3 ng/mL and were not on testosterone therapy were labeled as normal or high, and were grouped together as controls for the linear regression analysis, as in Abu Zaid et al (30).
Calculated by using selected adverse health outcomes previously related to cisplatin exposure (i.e., peripheral sensory neuropathy, hearing damage, tinnitus, and kidney disease), using a modified version of Kerns et al. (23) by removing autonomic neuropathy.
Following conversion of the Likert scale: “none, a little, quite a bit, very much” to a 0-3 numeric scale, each individual was attributed a summary statistic for the sensory subscale (Cronbach α = 0.88) and the motor subscale (α = 0.78) by taking the mean of the response in the subscale: none (mean = 0), mild (0 < mean ≤ 1), severe (mean > 1), as in Dolan et al (9).
Defined by the rank normalized geometric mean of air conduction thresholds measured at 4, 6, 8, 10, and 12 kHz, as in Frisina et al (7).