Immunotherapy in head and neck squamous cell carcinoma: An updated review.

Squamous cell cancer of the head and neck (HNSCC) is the sixth most common cancer and is associated with significant morbidity and mortality. The tumor microenvironment for HNSCC is a complex interplay of immune cells, stromal cells, and cytokines amongst others. Immunotherapy acts as an effective antineoplastic agent by influencing this complex environment and includes immune checkpoint inhibitors (ICI). ICI have been approved in the frontline setting for recurrent and metastatic (R/M) HNSCC as well as platinum-refractory (second line) R/M HNSCC. However, recent clinical studies highlight that the response to immunotherapy varies, and different ICI, as well as different combination strategies play a crucial role in augmenting the efficacy of immunotherapy. An in-depth analysis and focused study of the immune contexture in patients with HNSCC receiving ICI remains critical. Many novel immunotherapies including CAR-T cell therapy, oncolytic virus therapy, and vaccines are underway. Ongoing trials are testing ICI in the neoadjuvant and adjuvant settings. Furthermore, identifying better biomarkers to target population that benefits from immunotherapy is of paramount importance. Pioneering the optimal combination regimen utilizing new novel immunotherapy has recently become a paradigm shift in the HNSCC treatment landscape. Herein, we summarize the clinical development with all ongoing clinical trials of immunotherapy in HNSCC.

Duration of treatment in oncology clinical trials: does the duration change when the same drug moves from the experimental arm to the control arm?

BACKGROUND: When a new drug comes to the market, the incentive for the sponsoring company is to maximize the treatment duration in order for the patient to reap the full therapeutic benefit of the product and achieve a positive trial result. We sought to enumerate instances when an already-approved oncology drug was used as a comparator for a newer drug seeking approval and compare the duration of treatment when it is used in the intervention arm to when it is used as a comparator. PATIENTS AND METHODS: In a cross-sectional analysis, we searched drug approval announcements for advanced, metastatic, or unresectable cancers between 2009 and 2020. We included studies reporting on an approved drug and studies reporting on when the same drug was used as a comparator for other drugs seeking Food and Drug Administration (FDA) approval. We examined median progression-free survival and duration of treatment for when the drug was initially approved and for when the drug was used as a comparator for other drugs that were seeking approval. RESULTS: Of the 23 instances when an approved drug was later used as a comparator against a newer drug seeking FDA approval, we found 11 instances (47.8%) where the drug, when used as a comparator arm, had a shorter duration of treatment than when it was used in the intervention arm. The median duration of treatment in the study initially testing the drug was 6.0 months (range: 2.2-12.7 months), whereas the median duration of treatment when the same drug was used as a comparator was 4.9 months (range: 1.7-12.0 months). CONCLUSIONS: These results suggest that there is bias in how long a patient receives a given therapy, and this bias favors the newer therapy. Clinical trialists should seek to utilize methodology that reduces bias so that the relative efficacy of newer drugs can be objectively assessed.

Shape Features of the Lesion Habitat to Differentiate Brain Tumor Progression from Pseudoprogression on Routine Multiparametric MRI: A Multisite Study.

BACKGROUND AND PURPOSE: Differentiating pseudoprogression, a radiation-induced treatment effect, from tumor progression on imaging is a substantial challenge in glioblastoma management. Unfortunately, guidelines set by the Response Assessment in Neuro-Oncology criteria are based solely on bidirectional diametric measurements of enhancement observed on T1WI and T2WI/FLAIR scans. We hypothesized that quantitative 3D shape features of the enhancing lesion on T1WI, and T2WI/FLAIR hyperintensities (together called the lesion habitat) can more comprehensively capture pathophysiologic differences across pseudoprogression and tumor recurrence, not appreciable on diametric measurements alone. MATERIALS AND METHODS: A total of 105 glioblastoma studies from 2 institutions were analyzed, consisting of a training (n = 59) and an independent test (n = 46) cohort. For every study, expert delineation of the lesion habitat (T1WI enhancing lesion and T2WI/FLAIR hyperintense perilesional region) was obtained, followed by extraction of 30 shape features capturing 14 "global" contour characteristics and 16 "local" curvature measures for every habitat region. Feature selection was used to identify most discriminative features on the training cohort, which were evaluated on the test cohort using a support vector machine classifier. RESULTS: The top 2 most discriminative features were identified as local features capturing total curvature of the enhancing lesion and curvedness of the T2WI/FLAIR hyperintense perilesional region. Using top features from the training cohort (training accuracy = 91.5%), we obtained an accuracy of 90.2% on the test set in distinguishing pseudoprogression from tumor progression. CONCLUSIONS: Our preliminary results suggest that 3D shape attributes from the lesion habitat can differentially express across pseudoprogression and tumor progression and could be used to distinguish these radiographically similar pathologies.