M.L. Mierzwa

Recent Advances in Combined Modality Therapy

This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy.

Influence of human papillomavirus on the clinical presentation of oropharyngeal carcinoma in the United States

Much of what is known about the significance of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is derived from single‐institution retrospective studies, post hoc analyses of tissue specimens from clinical trials, and tissue bank studies with a small sample size. The objective of this study is to investigate the impact of HPV on the frequency and clinical presentation of oropharyngeal carcinoma in a large, national sample with information from patients who underwent HPV testing.

Sparing all salivary glands with IMRT for head and neck cancer: Longitudinal study of patient-reported xerostomia and head-and-neck quality of life

BACKGROUND AND PURPOSE While parotid-sparing intensity modulated radiotherapy (IMRT) has demonstrated superiority to conventional RT in terms of observer-rated xerostomia, patient-reported outcome measures (PROMs) have only marginally improved. We investigated how sparing all salivary glands affects PROMs. MATERIALS AND METHODS Patients treated to the bilateral neck with all-gland-sparing IMRT answered xerostomia (XQ) and head-and-neck quality of life (HNQOL) questionnaires. Longitudinal regression was used to assess the relationship between questionnaire scores and mean bilateral parotid gland (bPG), contralateral submandibular gland (cSMG), and oral cavity (OC) doses. Marginal R2 and Akaike information criterion (AIC) were used for model evaluation. RESULTS 252 patients completed approximately 600 questionnaires. On univariate analysis, bPG, cSMG, and OC doses significantly correlated with XQ-summary, XQ-eating, and HNQOL-eating scores. On multivariate analysis, bPG and OC doses significantly correlated with XQ-summary, XQ-eating, and HNQOL-eating scores; and cSMG dose with HNQOL-summary. Combining doses to all three structures yielded the highest R2 for XQ-summary, XQ-rest, XQ-eating, and HNQOL-eating. In the 147 patients who received a mean cSMG dose ≤39Gy, there were no failures in contralateral level IB. CONCLUSIONS Reducing doses to all salivary glands maximizes PROMs. A cSMG dose constraint of ≤39Gy does not increase failure risk.

Quantification of liver function by linearization of a two-compartment model of gadoxetic acid uptake using dynamic contrast-enhanced magnetic resonance imaging

Dynamic gadoxetic acid‐enhanced magnetic resonance imaging (MRI) allows the investigation of liver function through the observation of the perfusion and uptake of contrast agent in the parenchyma. Voxel‐by‐voxel quantification of the contrast uptake rate (k1) from dynamic gadoxetic acid‐enhanced MRI through the standard dual‐input, two‐compartment model could be susceptible to overfitting of variance in the data. The aim of this study was to develop a linearized, but more robust, model. To evaluate the estimated k1 values using this linearized analysis, high‐temporal‐resolution gadoxetic acid‐enhanced MRI scans were obtained in 13 examinations, and k1 maps were created using both models. Comparison of liver k1 values estimated from the two methods produced a median correlation coefficient of 0.91 across the 12 scans that could be used. Temporally sparse clinical MRI data with gadoxetic acid uptake were also employed to create k1 maps of 27 examinations using the linearized model. Of 20 scans, the created k1 maps were compared with overall liver function as measured by indocyanine green (ICG) retention, and yielded a correlation coefficient of 0.72. In the 27 k1 maps created via the linearized model, the mean liver k1 value was 3.93 ± 1.79 mL/100 mL/min, consistent with previous studies. The results indicate that the linearized model provides a simple and robust method for the assessment of the rate of contrast uptake that can be applied to both high‐temporal‐resolution dynamic contrast‐enhanced MRI and typical clinical multiphase MRI data, and that correlates well with the results of both two‐compartment analysis and independent whole liver function measurements.

Submandibular gland sparing when irradiating neck level IB in the treatment of oral squamous cell carcinoma

Patients with oral squamous cell carcinoma (OSqCCA) frequently require postoperative radiation (PORT), which may include contralateral level IB within the clinical target volume (CTV). The submandibular gland (SMG) is typically included within the level IB CTV; however, the SMG does not contain lymph nodes or lymphatic vessels. We hypothesized that level IB could be adequately irradiated while sparing the SMG to reduce xerostomia. Twelve patients with OSqCCA receiving PORT, which included the contralateral level IB within the planning target volume (PTV), were retrospectively reviewed and replanned using volumetric modulated arc therapy. CTV contouring, including contralateral level IB, was in accordance with the consensus contouring atlas but excluded the SMG. The contralateral neck PTVs were planned to 54 Gray (Gy) (PTV54). Dose requirements were per Radiation Therapy Oncology Group-1008: PTV54 D95% >54 Gy, with an allowable variation of >48.6 Gy. The dose constraint for the SMG was mean dose ≤39 Gy based on published dose-effect data for the SMGs. Mean SMG and PTV54 doses were 38.5 Gy and 56.3 Gy, respectively. Median PTV54 D95% was 53.0 Gy (range 52.5 to 54.6 Gy), with all cases meeting our allowable coverage goal. When assessing the portion of the PTV associated with level IB only (PTV_IB), mean PTV_IB dose was 54.4 Gy and median PTV_IB D95% was 43.3 Gy (range 42.5 to 52.2). Median D95% to CTV_IB was 50.2 Gy. SMG sparing resulted in 10% to 20% underdosing of the part of the PTV corresponding to level IB, as a portion of the PTV lies within the SMG. The SMG can be spared to a mean dose ≤39 Gy with slight underdosing of the surrounding PTV where the PTV overlaps with the SMG. Clinical trials evaluating SMG sparing are warranted.

Individualized survival prediction for patients with oropharyngeal cancer in the human papillomavirus era: Assessment of OPSCC Survival Calculators

Accurate, individualized prognostication in patients with oropharyngeal squamous cell carcinoma (OPSCC) is vital for patient counseling and treatment decision making. With the emergence of human papillomavirus (HPV) as an important biomarker in OPSCC, calculators incorporating this variable have been developed. However, it is critical to characterize their accuracy prior to implementation.