Hypothyroidism post-chemoradiation on outcomes in head-and-neck cancer

Background: Hypothyroidism is a known side effect of head-and-neck cancer treatment and might improve outcomes. However, whether the development of hypothyroidism or maintaining a hypothyroid state remains a factor is unclear. Methods: Once-a-week versus once-every-3-weeks cisplatin chemoradiation in locally advanced head and neck cancer was a Phase III open-label, noninferiority randomized study conducted by our group in the Medical Oncology Department of Tata Memorial Hospital, Mumbai, India. The database of this study was assessed for this analysis. Hypothyroidism was defined as a serum thyroid-stimulating hormone (TSH) level of above 5 uIU/ml. Duration of hypothyroidism was defined as cumulative duration in days postrandomization that the patient spent in hypothyroid state before progression. The relationship between duration of hypothyroidism (continuous variable) and peak TSH values and outcomes (locoregional failure [LRF] rate, progression-free survival [PFS], and overall survival [OS]) were analyzed. Results: Higher duration of time spent in a hypothyroid state had a favorable impact on PFS (HR: 0.996, 95% CI: 0.994–0.999, P = 0.007), and OS (HR: 0.995, 95% CI: 0.991–0.999, P = 0.016). This favorable impact on LRF (HR: 0.963, 95% CI: 0.929–0.997, P = 0.034), PFS (HR: 0.996, 95% CI: 0.993–0.999, P = 0.005), and OS (HR: 0.993, 95% CI: 0.987–0.999, P = 0.022) was confirmed on multivariate analysis too. Peak TSH value between 30 and 40 uIU/ml provided the maximum benefit for LRF with HR of 4.76 (standard error (SE) of HR as 0.627, P = 0.01). Conclusion: A longer duration and higher state of hypothyroidism (TSH – 30–40 Iu/ml) provided the maximum improvement in outcomes, this is an interesting hypothesis which needs to be confirmed with more studies.