OBJECTIVES: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets. STUDY DESIGN: Data mining of The Cancer Genome Atlas (TCGA). METHODS: 530 patients with HNSCC were pulled from the TCGA using cBioPortal. Primary tumor site data was available in 279 of the samples (52.6%), of which oral cavity was the most common site (61.6%) followed by larynx (25.8%). Other PD-1-sensitive tumors were analyzed to compare PD-L1 expression in HNSCC relative to other tumors including bladder, renal cell carcinoma, melanoma, and lung carcinomas. RESULTS: A significant fraction of HNSCC tumors have genetic alterations in PD-L1 (6.2%). HNSCC has the highest PD-L1 expression of all of the tumor types examined, with a median 60-fold increase. Several important genes were identified in this study including Caspase 7, ZFYVE9, and Plg-R(KT) that have a strong relationship with alterations in PD-L1. CONCLUSION: In light of the role of PD-1 and PD-L1 as key immunotherapy targets in HNSCC, several potential co-targets identified in this study warrant further investigation. Further, while the number of genetic alterations were small in head and neck carcinomas, alterations in PD-L1 expression were highly significant. LEVEL OF EVIDENCE: NA.

Objectives

Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets.

Study design

Data mining of The Cancer Genome Atlas (TCGA).

Methods

530 patients with HNSCC were pulled from the TCGA using cBioPortal. Primary tumor site data was available in 279 of the samples (52.6%), of which oral cavity was the most common site (61.6%) followed by larynx (25.8%). Other PD-1-sensitive tumors were analyzed to compare PD-L1 expression in HNSCC relative to other tumors including bladder, renal cell carcinoma, melanoma, and lung carcinomas.

Results

A significant fraction of HNSCC tumors have genetic alterations in PD-L1 (6.2%). HNSCC has the highest PD-L1 expression of all of the tumor types examined, with a median 60-fold increase. Several important genes were identified in this study including Caspase 7, ZFYVE9, and Plg-R(KT) that have a strong relationship with alterations in PD-L1.

Conclusion

In light of the role of PD-1 and PD-L1 as key immunotherapy targets in HNSCC, several potential co-targets identified in this study warrant further investigation. Further, while the number of genetic alterations were small in head and neck carcinomas, alterations in PD-L1 expression were highly significant.

Level of evidence

NA.

Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded. Results There were 30 acromegalics and 31 Cushing disease patients. When compared with controls, both acromegalics and Cushing disease patients had significantly wider piriform apertures and a longer distance from the piriform aperture to the anterior face of the sphenoid sinus (p < 0.05). Acromegalics had a significantly less acute angle (19 ± 3 degrees) from the anterior nasal spine to the sphenoid (p < 0.05). Cushing disease patients had significantly lower sphenoid sinus length and shorter nasal cavity height (p < 0.05). There were no differences in intercarotid distance or carotid canal width. Conclusions As acromegalics and Cushing disease patients have known anatomic variations, the skull base surgeon should be aware of these differences and adapt their techniques and approaches as needed.

Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded. Results There were 30 acromegalics and 31 Cushing disease patients. When compared with controls, both acromegalics and Cushing disease patients had significantly wider piriform apertures and a longer distance from the piriform aperture to the anterior face of the sphenoid sinus (p < 0.05). Acromegalics had a significantly less acute angle (19 ± 3 degrees) from the anterior nasal spine to the sphenoid (p < 0.05). Cushing disease patients had significantly lower sphenoid sinus length and shorter nasal cavity height (p < 0.05). There were no differences in intercarotid distance or carotid canal width. Conclusions As acromegalics and Cushing disease patients have known anatomic variations, the skull base surgeon should be aware of these differences and adapt their techniques and approaches as needed.

Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing ≥2 of four assessed activation markers) were similar between 18-49 and ≥50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.