William A. Bulman

BACKGROUND: One immunotherapeutic agent for patients with advanced non-small cell lung carcinoma, pembrolizumab, has a companion immunohistochemistry (IHC)-based assay that predicts response by quantifying programmed death-ligand 1 (PD-L1) expression. The current study assessed the feasibility of quantifying PD-L1 expression using cytologic non-small cell lung carcinoma specimens and compared the results with those from small biopsy and surgical resection specimens. METHODS: PD-L1 expression was quantified using the IHC-based 22C3 pharmDx assay, with "positivity" defined as staining in ≥50% viable tumor cells; ≥ 100 tumor cells were required for test adequacy. For cytology specimens, IHC was performed on cell block sections. RESULTS: A total of 214 specimens were collected from 188 patients, 206 of which (96%) were found to be adequately cellular, including 36 of 40 cytology (90%) and 69 of 72 small biopsy (96%) specimens. There was no significant difference noted with regard to the feasibility of PD-L1 IHC on small biopsy specimens compared with surgical resection specimens (P = .99), or between the percentage of PD-L1-positive cytology and histology (including surgical resection and histologic small biopsy) specimens (P = .083). PD-L1 expression was found to be concordant among samples from 21 of 23 patients from whom > 1 specimen was collected (91%). There also was no significant difference observed with regard to rates of PD-L1 positivity when comparing age, sex, diagnosis, and specimen site. CONCLUSIONS: Quantification of PD-L1 expression is feasible on cytology specimens, and the results are comparable to those obtained from surgical resection and small biopsy specimens, including in matched specimens and using a single predictive IHC marker. Future studies will be necessary to determine the comparative value of other antibodies and their ability to predict response to immunotherapy. Cancer Cytopathol 2017;125:896-907. © 2017 American Cancer Society.

Recent advances in therapy for non-small cell lung carcinoma have shown that a personalized approach to treatment has the potential to significantly reduce lung cancer mortality. Concurrently, endoscopic ultrasound transbronchial needle aspiration has emerged as an accurate and sensitive tool for the diagnosis and staging of this disease. As knowledge of the molecular mechanisms that drive lung cancer progression increases, the amount of information that must be derived from a tumor specimen will also increase. Recent clinical studies have demonstrated that small specimens acquired by endoscopic ultrasound transbronchial needle aspiration are sufficient for molecular testing if specimen acquisition and processing are done with these needs in mind. Optimum use of this procedure requires a coordinated effort between the bronchoscopist and the cytopathologist to collect and triage specimens for diagnostic testing. When feasible, rapid onsite evaluation should be performed to assess the specimen for both diagnostic quality and quantity and to allocate the specimen for cell-block and possible immunohistochemistry and molecular studies. It is necessary for pulmonologists and bronchoscopists to understand the rationale for histologic and molecular testing of lung cancer diagnostic specimens and to ensure that specimens are acquired and processed in a fashion that provides information from small cytologic specimens that is sufficient to guide treatment in this era of targeted therapy.

Summary The development of the U-shaped Unit Rod for posterior spinal arthrodesis is a recent advance in the treatment of spinal deformity in patients with cerebral palsy. The results of 15 patients who underwent arthrodesis with dual Luque rod instrumentation (group I) are compared with the results of 15 patients in whom Unit Rod instrumentation was used (group II). The two treatment groups were similar with respect to age, gender, major spinal curve, and degree of pelvic obliquity. The Unit Rod instrumentation allowed significantly greater correction of both the major curve and pelvic obliquity, as assessed on postoperative radiographs. The mean postoperative major curve in group I was 44.1°, compared with 31.7° in group II (mean corrections of 48.6 and 61.7%, respectively). The mean angle of postoperative pelvic obliquity in group I was 12.6°, compared with 5.2° in group II, corrections of 49.5 and 79.3%, respectively. Sagittal-plane alignment was improved to a similar degree in both groups in those patients with preoperative imbalance and maintained in the remainder of patients.

The development of the U-shaped Unit Rod for posterior spinal arthrodesis is a recent advance in the treatment of spinal deformity in patients with cerebral palsy. The results of 15 patients who underwent arthrodesis with dual Luque rod instrumentation (group I) are compared with the results of 15 patients in whom Unit Rod instrumentation was used (group II). The two treatment groups were similar with respect to age, gender, major spinal curve, and degree of pelvic obliquity. The Unit Rod instrumentation allowed significantly greater correction of both the major curve and pelvic obliquity, as assessed on postoperative radiographs. The mean postoperative major curve in group I was 44.1 degrees, compared with 31.7 degrees in group II (mean corrections of 48.6 and 61.7%, respectively). The mean angle of postoperative pelvic obliquity in group I was 12.6 degrees, compared with 5.2 degrees in group II, corrections of 49.5 and 79.3%, respectively. Sagittal-plane alignment was improved to a similar degree in both groups in those patients with preoperative imbalance and maintained in the remainder of patients.