Faculty Bibliography

Aim: To compare patterns and rates of recurrence in patients with oropharyngeal squamous cell carcinoma by human papilloma virus (HPV) status. Patients & methods: Retrospective chart review of 155 patients diagnosed with oropharyngeal squamous cell carcinoma between 2012 and 2014 at a single center. Results: Two-year recurrence-free survival was higher in patients with HPV-positive tumors compared with negative (85.2% [standard error = 0.03] versus 59.3% [standard error = 0.09]; p < .001) with the former proportionally less likely to have locoregional recurrence. HPV-positive patients had proportionally higher incidence of second primary malignancies outside of head, neck and lung compared with HPV-negative (74.2 vs 37.5%; p = 0.09). Conclusion: The differences in failure by HPV status indicates a need for modified surveillance guidelines. The differences in second primary malignancies patterns are interesting, warranting further evaluation in larger studies.

Background/UNASSIGNED:Histologic subtyping of lung cancer has significant implications for treatment planning. Accurate diagnosis based on cytology/small biopsy specimens is challenging and frequently determined by morphology, as material is often not sufficient for immunohistochemical studies (IHC). We investigated the concordance between the rates of diagnosis from cytology/small biopsies compared with surgical specimens in patients with squamous cell lung cancer (SCC) and the utility of IHC for diagnostic precision in lung cancer subtyping. Methods/UNASSIGNED:We conducted a 5-year retrospective analysis identifying cases of SCC diagnosed on cytology/small biopsies ± IHC and compared them with subsequent surgical specimens when available. The number of patients with SCC on surgical biopsy and the concordance between cytology ± IHC was determined. Results/UNASSIGNED:Over the 5-year period (2011-2015), 231 cases were identified. Surgery was performed on 66 cases (28.5%), of which 87.9% concurred with cytological diagnosis (95% exact binomial confidence interval [CI] = 77.5%-94.6%). There were 36 cases diagnosed in 2014 and 2015 with IHC data. Of those cytology cases with IHC (n = 12), SCC was confirmed by surgery in 91.7% (95% CI = 61.5%-99.8%). Of those without IHC (n = 24), 95.8% were confirmed SCC by surgery (95% CI = 78.9%-99.9%). These rates were not different (Fisher exact test). All cases with IHC were morphologically squamous. Conclusions/UNASSIGNED:Our data demonstrate that diagnostic precision of identifying SCC by cytology/small biopsy is comparable with or without additional IHC studies. We recommend judicious use of IHC on cytology specimens, reserving it for cases where cytomorphology is equivocal. Tissue should be preserved for molecular analysis, which may have therapeutic implications.

Mutations in the epidermal growth factor receptor (EGFR) are common amongst those with non-small cell lung cancer and represent a major factor in treatment decisions, most notably in the advanced stages. Small molecule tyrosine kinase inhibitors (TKIs) that target the EGFR, such as erlotinib, gefitinib, icotinib, afatinib, dacomitinib and osimertinib, have all shown to be effective in this setting. Osimertinib, a third-generation EGFR TKI, is a favorable option, but almost all patients develop resistance at some time point. There are no effective treatment options for patients who progress on osimertinib, but ongoing trials will hopefully address this unmet need. The aim of this review is to provide a comprehensive review of the data with EGFR TKIs, management of the toxicities and the ongoing trials with this class of agents.

Atypical pulmonary carcinoid (APC) is a lung neuroendocrine neoplasm (NEN), whose treatment draws from management of gastrointestinal NENs and small-cell lung carcinoma. We present a patient with recurrent metastatic APC and persistent mediastinal lymphadenopathy refractory to cisplatin and etoposide. After pursuing alternative treatments, he returned with significant progression, including diffuse subcutaneous nodules, weight loss and worsening cough. New biopsy analysis demonstrated APC with low mutational burden, low Ki-67 and Programmed Death-Ligand 1 (PD-L1), and without microsatellite instability. We pursued combination nivolumab and ipilimumab treatment based on success of CheckMate 032 in small-cell lung cancer. The patient's symptoms dramatically responded within a month, with almost complete resolution of lymphadenopathy following four cycles. He has been successfully maintained on nivolumab for the last 18 months. This suggests combination immunotherapy may be beneficial in the treatment of metastatic APC, and that PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors may be valuable in treating tumours lacking traditional biomarkers.

PURPOSE/OBJECTIVE:To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT). MATERIALS AND METHODS/METHODS:A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded. RESULTS:Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease. CONCLUSIONS:This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

BACKGROUND/UNASSIGNED:Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can cause intolerable adverse events in patients with non-small cell lung cancer (NSCLC) and may be prescribed at a lower dose. OBJECTIVE/UNASSIGNED:Our objective was to analyze the starting doses of oral EGFR and ALK TKIs in patients diagnosed with NSCLC at our institution. METHODS/UNASSIGNED:We conducted a retrospective chart review with patients on EGFR and ALK TKIs for NSCLC. Patients were categorized into 2 groups: patients initiated on Food and Drug Administration (FDA) standard dose (SD) and patients initiated on a reduced dose (RD). Progression-free survival (PFS), overall survival (OS) and other treatment outcomes were compared between both groups. RESULTS/UNASSIGNED:Ninety patients were included for analysis. The median time-to-progression for the SD group (n = 67) and RD group (n = 23) were 13.4 months (95% confidence interval [CI]:8.9-15.6) and 15.1 months (95%CI: 5.6-21.5), respectively. Median time-to-death was not estimable for OS. The predicted OS probability at approximately 15 months post treatment initiation for the SD group and RD group was 81.8% and 80.5%, respectively. CONCLUSION/UNASSIGNED:Patients who initiated TKI therapy at a RD did not have different PFS and 15-month survival outcomes than patients who initiated TKI therapy at the FDA SD.

Radiation recall pneumonitis (RRP) is an entity described as pneumonitis localized to a previously irradiated field after exposure to a systemic agent. It has previously been described in the literature in the context of chemotherapeutic agents as well as certain biologics. With immunotherapy taking a more prominent role in the treatment of several different malignancies and its own baseline risk of pneumonitis, it is important to explore the likelihood of RRP, specifically in those patients who have been previously treated with radiation therapy. The current literature regarding RRP with checkpoint inhibitors is reviewed in this article. Alongside this review, we report a case of RRP after pembrolizumab initiation in a patient in our practice.

Introduction/UNASSIGNED:With the advent of immunotherapy, a new subtype of side effects called IRAEs or immune related adverse effects have become more common. They may present in various organ systems as colitis, pneumonitis, hypophysitis, and thyroiditis and commonly as dermatological reactions. Case/UNASSIGNED:This is a case report of a lung cancer patient that was started on Pembrolizumab and developed shortly after what appeared to be clinically at first pustular psoriasis but on biopsy was confirmed to be lichen planus. She was discontinued on the Pembrolizumab and treated with both systemic and topical steroids and improved. Conclusion/UNASSIGNED:This case highlights a cutaneous reaction from Pembrolizumab and the subsequent management that helped resolve her condition but also weighing the benefits against the risk of treatments and potential prognostic implications of having cutaneous side effects.

Background Despite progress of immune checkpoint blockade therapies, many patients with non-small cell lung cancer (NSCLC) do not receive durable clinical benefit from these agents, and even in those who do respond initially, acquired resistance and tumor recurrence can develop. Pepinemab is an IgG4 humanized monoclonal antibody targeting semaphorin 4D (SEMA4D, CD100). In vivo preclinical studies demonstrated antibody blockade of SEMA4D promoted immune infiltration and reduced function and recruitment of immunosuppressive myeloid cells within the tumor [1,2]. Importantly, preclinical combinations of anti-SEMA4D with various immunotherapies enhanced T cell infiltration and activity, as well as durable tumor regression. Methods The CLASSICAL-Lung clinical trial evaluates the combination of pepinemab with anti-PD-L1 antibody avelumab to couple beneficial modifications of the immune microenvironment via pepinemab with immune activation via checkpoint inhibition. This ongoing phase 1b/2, open label, single arm, first-in-human combination study is designed to evaluate the safety, tolerability and efficacy of the combination in patients with advanced (stage IIIB/ IV) NSCLC, including a dose escalation cohort and expansion cohorts consisting of 1) 17 immunotherapy-naive patients and 2) 33 patients whose tumors progressed during or following immunotherapy (IO failure). Results The combination was well tolerated with no concerning safety signals identified to date. No patient experienced a treatment-related adverse event leading to permanent treatment discontinuation or death and the most frequent related AEs were grades 1 or 2 fatigue, pyrexia, or chills. Interim analysis focused on the IO failure cohort which included 22 evaluable patients. Two patients experienced a partial response (PR) with 49% and 37% tumor reduction on study following acquired resistance to prior treatment with pembrolizumab. In addition, stable disease of at least 8 weeks was observed in 11 patients and 4 patients have remained on study for >=20 weeks. Analysis of pre-and on-treatment lung biopsies demonstrated no or low tumor burden detected in 2 patients with PR, and interestingly no detectable tumor was observed in the biopsies from 3 of 4 patients with stable disease. Conclusions Preliminary data suggest the combination of pepinemab plus avelumab is well tolerated and shows initial signals of antitumor activity in patients with IO failure. We will present updated clinical response data, as well as additional immunophenotyping of tissue biopsies, including but not limited to activated T cells, regulatory T cells, DCs, monocytes, macrophages, and importantly myeloid-derived suppressor cells (MDSCs)