Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy - A prospective observational study.

OBJECTIVE: With an aim to investigate the impact of Human Papilloma Virus (HPV) 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy, we undertook this prospective study. METHODS: Between May 2010 and April 2012, 150 histologically proven cervical cancer patients treated with radio (chemo) therapy were accrued. Cervical biopsies/brushings were collected at pre-treatment, end of treatment and at 3 monthly intervals up to 24months. Quantitative estimation of HPV 16/18 was done using real-time polymerase chain reaction (RT-PCR) and correlated with various clinical end-points. RESULTS: Out of 150 patients accrued, 135 patients were considered for final analysis. Pre-treatment HPV16/18 DNA was detected in 126 (93%) patients, with HPV-16 present in 91%. The mean log (±SD) HPV-16 and HPV-18 viral load at pre-treatment was 4.76 (±2.5) and 0.14 (±2.1) copies/10ng of DNA, respectively. Though significant decline in viral load was observed on follow-ups (p<0.0001); by 9-month follow-up, 89 (66%) patients had persistence of HPV infection. Patients with persistent HPV 16/18 infection had a significantly higher overall and loco-regional relapses [44/89 (49%) and 29/89 (32%)] as compared to HPV clearance by 9months [12/43 (28%) and 5/43 (11%)] with p=0.024 and p=0.02, respectively. Also, persistent HPV infection by 24-month showed a significant impact on loco-regional control (LRC) and recurrence-free survival (RFS). CONCLUSION: In locally advanced cervical cancers treated with radical radio (chemo) therapy, persistent HPV 16/18 infection is significantly high in immediate post-treatment period and correlated with higher loco-regional, overall relapses and was also associated with early relapses.

Prospective longitudinal assessment of parotid gland function using dynamic quantitative pertechnate scintigraphy and estimation of dose-response relationship of parotid-sparing radiotherapy in head-neck cancers.

PURPOSE: To estimate dose-response relationship using dynamic quantitative (99m)Tc-pertechnate scintigraphy in head-neck cancer patients treated with parotid-sparing conformal radiotherapy. METHODS: Dynamic quantitative pertechnate salivary scintigraphy was performed pre-treatment and subsequently periodically after definitive radiotherapy. Reduction in salivary function following radiotherapy was quantified by salivary excretion fraction (SEF) ratios. Dose-response curves were modeled using standardized methodology to calculate tolerance dose 50 (TD50) for parotid glands. RESULTS: Salivary gland function was significantly affected by radiotherapy with maximal decrease in SEF ratios at 3-months, with moderate functional recovery over time. There was significant inverse correlation between SEF ratios and mean parotid doses at 3-months (r = -0.589, p<0.001); 12-months (r = -0.554, p<0.001); 24-months (r = -0.371, p = 0.002); and 36-months (r=-0.350, p=0.005) respectively. Using a post-treatment SEF ratio <45% as the scintigraphic criteria to define severe salivary toxicity, the estimated TD50 value with its 95% confidence interval (95% CI) for the parotid gland was 35.1Gy (23.6-42.6Gy), 41.3Gy (34.6-48.8Gy), 55.9Gy (47.4-70.0Gy) and 64.3Gy (55.8-70.0Gy) at 3, 12, 24, and 36-months respectively. CONCLUSIONS: There is consistent decline in parotid function even after conformal radiotherapy with moderate recovery over time. Dynamic quantitative pertechnate scintigraphy is a simple, reproducible, and minimally invasive test of major salivary gland function.

Impact of comorbidity on therapeutic decision-making in head and neck cancer: audit from a comprehensive cancer center in India.

BACKGROUND: Head and neck cancer has increased incidence of comorbidity due to tobacco and alcohol use. METHODS: Two hundred consecutive patients were included in this cross-sectional study. Data on clinico-demographic characteristics and comorbidity was extracted from case records. Comorbidity was assessed with Adult Comorbidity Evaluation 27 (ACE-27) and Charlson Comorbidity Index (CCI). Change in therapeutic decision-making from institutional evidence-based guidelines was classified as low, medium, or high-impact. RESULTS: Of 200 patients, 68(34%) had comorbidity while 15 had multimorbidity. No change in therapeutic decision-making was seen in 139 patients (69.5%), 61patients (30.5%) had change from institutional evidence-based guidelines. There was strong positive correlation (Spearman's correlation coefficient = 0.80; p < .001) between ACE-27 and change in therapeutic decision-making. For CCI, there was moderate positive correlation (Spearman's correlation coefficient = 0.50; p < .001). CONCLUSION: Comorbidity in patients with head and neck cancer can influence therapeutic decision-making. Prospective longitudinal rigorous collection of comorbidity data is warranted for correlation with outcomes. ACE-27 may be a clinically more meaningful tool for comorbidity assessment.