Faculty Bibliography

BACKGROUND:Patients with head and neck cancer (HNC) who are not candidates for definitive treatment represent an increasing challenge, with limited data to guide management. Conventional local therapies such as surgery and chemoradiation can significantly impact quality of life (QoL). There has been limited data published using stereotactic body radiotherapy (SBRT) as primary treatment in previously unirradiated patients. We hypothesize that SBRT provides high rates of control while limiting toxicity. METHODS:A total of 66 medically unfit previously unirradiated patients with HNC were treated with SBRT, consisting of 35-40 Gy to gross tumor volume and 30 Gy to clinical target volume in five fractions. RESULTS:Median age was 80 years. Local control (LC) and overall survival (OS) at 1 year were 73% and 64%. Two patients experienced grade 3 toxicity. CONCLUSION/CONCLUSIONS:SBRT shows acceptable outcomes with relatively low toxicity in previously unirradiated patients with HNC who are medically unfit for conventional treatment. SBRT may provide an aggressive local therapy with high rates of LC and OS while maintaining QoL.

The positive predictive value (PPV) of 12-week post-therapy FDG-PET/CT is low in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) after treatment with definitive chemoradiation (CRT). Moreover, the diagnostic performance of post-CRT fine needle aspiration (FNA) in detecting persistent disease is unknown in this population. Given these important shortcomings in post-CRT treatment assessment, head and neck oncologists are limited in appropriately selecting patients for consolidative neck dissection, which results in over-treatment of a favorable risk population. Using the PubMed database, we performed a literature review of published series in HPV-associated OPSCC to investigate potential strategies for improvement of post-CRT neck assessment. Several different approaches were found, including continued surveillance with PET/CT, delayed timing of restaging PET/CT, initial response evaluation with multimodality or alternative imaging, and detection of circulating HPV DNA. At present, the optimal approach to post-CRT treatment assessment is unclear; further investigation and incorporation of new technologies and surveillance protocols will be highly beneficial for patients with HPV-associated OPSCC.

INTRODUCTION/BACKGROUND:Lorlatinib is an oral anaplastic lymphoma kinase (ALK) and C-ros oncogene (ROS1) tyrosine kinase inhibitor with excellent central nervous system (CNS) penetrability. It is currently approved for use as second line therapy for those with ALK positive non-small cell lung cancer (NSCLC). Given its CNS penetrating effects, lorlatinib has shown to cause CNS adverse events such as seizures, hallucinations, and changes in cognitive function. To our knowledge proteinuria has not been previously described with this medication. CASE REPORT/METHODS:The patient's dose was reduced from 100 mg to 75 mg and further down to to 50 mg daily. At that point the proteinuria improved. Other adverse events attributable to the medication, specifically hallucinations and peripheral neuropathy also improved. DISCUSSION/CONCLUSIONS:Our case demonstrates objective evidence for proteinuria induced by lorlatinib, which may also be dose dependent.

Immune-checkpoint inhibitors (ICI), specifically inhibitors of programmed death ligand-1 (PD-L1) and receptor (PD-1) are the new standard of care for the treatment of patients with advanced non-small cell lung cancer (NSCLC) in front line setting as monotherapy or along with chemotherapy. Many of these agents are also approved for use in subsequent lines of treatment on progression on platinum doublet chemotherapy. Nivolumab, pembrolizumab and atezolizumab are currently approved ICI for advanced NSCLC. To date, no study has reported efficacy and safety of alternate PD-1/PD-L1 inhibitors in patients with NSCLC who have progressed on one ICI. Here, we report a case of a patient with advanced NSCLC who had a complete response to atezolizumab, following progression of disease on platinum doublet chemotherapy and then, nivolumab monotherapy.

Aim/UNASSIGNED: hybridization (ISH) to p16 IHC. Methods/UNASSIGNED:Fifty patients with OPSCC were analyzed. Concordance between HPV-DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. Results/UNASSIGNED:p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA-ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA-ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA-ISH and p16 IHC is fair (Gwet's AC1 = 0.318). Conclusion/UNASSIGNED:The agreement between p16 IHC and HPV-DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC.

Background/UNASSIGNED:Checkpoint inhibitors are integral to non-small-cell lung cancer treatment. Existing data suggests that nutritional status may play a role in antitumor immunity. Materials & methods/UNASSIGNED:This retrospective study of 106 non-small-cell lung cancer patients who started checkpoint inhibitors between 2014 and 2017 at our institution assessed relationship of nutritional parameters to overall survival (OS) and progression-free survival. Results/UNASSIGNED:Mean age was 68.7 ± 9.2 years and 59.4% patients were male. On multivariate analysis for OS, hypoalbuminemia and significant weight loss were prognostic at p-values of 0.0005 and 0.0052, respectively. We noted a parabolic association between age and OS (p = 0.026, 0.0025). Conclusion/UNASSIGNED:In our study, some malnutrition parameters were associated with decreased OS. U-shape relationship between age and OS noted here warrants further evaluation.