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Background: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). Methods: In this single‐institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012–03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression‐free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. Results: Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. Conclusions: In the largest study to date examining PBBMs in ICI‐treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker. [ABSTRACT FROM AUTHOR]

Background: Associations between peripheral blood biomarkers and oncologic outcomes were explored in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HN) and salivary gland cancer (SGC) treated with pembrolizumab and vorinostat on a phase II trial (NCT02538510). Experimental Design: Twenty‐five HN and 25 SGCs were treated with pembrolizumab and vorinostat. Baseline peripheral blood was available in 21 HN and 20 SGCs and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv4, objective response rate (ORR), overall survival (OS), and progression‐free survival (PFS). Results: Higher pretreatment neutrophil‐to‐lymphocyte ratio (NLR) and neutrophils, as well as lower pretreatment lymphocytes and T helper cells correlated with worse OS and PFS. Higher NLR further predicted increased rates of G ≥ 3AEs. No correlations with ORR were observed. Conclusions: In a prospectively evaluated cohort of HN and SGCs treated with pembrolizumab and vorinostat, we observed novel associations between peripheral blood biomarkers and oncologic outcomes and toxicities. [ABSTRACT FROM AUTHOR]

Background: Anti‐PD1 checkpoint inhibitors (ICI) represent an established standard‐of‐care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni‐ and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. Results: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty‐six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01–5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41–3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06–0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between toxicity and any patient characteristic. Conclusions: We observed inferior OS, ORR, and rates of UH among ICI‐treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor‐risk population. [ABSTRACT FROM AUTHOR]

PURPOSE Time from diagnosis to treatment has been associated with worse survival outcomes in non-small-cell lung cancer (NSCLC). However, little is known about the impact of delay in time to diagnosis. We aimed to evaluate the impact of time from radiographic suspicion to histologic diagnosis on survival outcomes using the US SEER-Medicare population database. METHODS We identified patients from the SEER-Medicare data set diagnosed with any stage NSCLC between January 1, 2011, and December 31, 2015, who received stage-appropriate treatment and had a computed tomography scan within 1 year of diagnosis. Time to confirmation was determined as the interval between most recent computed tomography imaging and date of histologic diagnosis. Our primary outcome was overall survival (OS). RESULTS In total, 10,824 eligible patients were identified. The median time to confirmation was 20 (range 0-363) days. Using multivariate Cox regression models, longer time to confirmation was associated with improved OS in all comers driven by stage IV patients after adjustment for age, sex, diagnosis year, histology, and comorbidity index. In a separate landmark analysis excluding patients deceased within 6 months of diagnosis, the association between time to diagnosis and survival was no longer evident. CONCLUSION Time to confirmation of NSCLC was inversely associated with OS in this US SEER population study. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that retrospective registry-claims databases may not be the optimal data source to study time to diagnosis as a quality metric because of the unaccounted confounding effects of tumor behavior. Prospective evaluations of clinically enriched data sources may better serve this purpose. [ABSTRACT FROM AUTHOR]

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation. [ABSTRACT FROM AUTHOR]

PURPOSE: The costs associated with clinical trial enrollment remain uncertain. We hypothesized that trial participation is associated with decreased total direct medical costs to health care payers in metastatic non--small-cell lung cancer. METHODS: In this retrospective cohort study, we linked clinical data from electronic medical records to sociodemographic data from a cancer registry and claims data from Medicare and two private insurance plans. We used a difference-in-difference analysis to estimate mean per patient per month total direct medical costs for patients enrolled on a second-line (2L) trial versus patients receiving standard-of-care 2L systemic therapy. RESULTS: Among 70 eligible patients, the difference-in-difference of mean per patient per month total direct medical costs between 2L trial participants and nonparticipants was --$6,663 (P = .01), for a mean savings of $45,308 per patient for the duration of 2L trial therapy. In a secondary analysis by primary insurance payer, this difference-in-difference was --$5,526 (P = .26) for patients with commercial insurance and --$7,432 (P = .01) for patients with Medicare. CONCLUSION: Participation in a 2L trial was associated with a $6,663 per month cost savings to health care payers for the duration of trial participation. Further studies are necessary to elucidate differences in cost savings from trial participation for Medicare and commercial payers. If confirmed, these results support health care payer investment in programs to improve clinical trial access and enrollment. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy is effective in improving survival of resectable NSCLC. Based on findings in the adjuvant and metastatic setting, FDG positron emission tomography (PET) scans may offer early prognostic or predictive value after one cycle of induction chemotherapy.Methods: In this phase II non-randomized trial, patients with AJCC version 6 stage IB to IIIB operable NSCLC were treated with 3 cycles of cisplatin and pemetrexed neoadjuvant chemotherapy. Patients underwent FDG-PET scanning prior to and 18 to 21 days after the first cycle of chemotherapy. Investigators caring for patients were blinded to results, unless the scans showed evidence of disease progression. FDG-PET response was defined prospectively as a ≥ 20% decrease in the SUV of the primary lesion.Results: Between October 2005 and February 2010, 25 patients enrolled. Fifty two percent were female, 88% white, and median age was 62 years. Histology was divided into adenocarcinoma 66%, not otherwise specified (NOS) 16%, squamous cell 12%, and large cell 4%. Stage distribution was: 16% IB, 4% IIB, and 79% IIIA. Treatment was well tolerated and only one patient had a grade 4 toxicity. The median follow up was 95 months. The 5 year progression free survival (PFS) and overall survival (OS) for the entire population were 54 and 67%, respectively. Eighteen patients had a baseline FDG-PET scan and a repeat scan at day 18-21 available for comparison. Ten patients (56%) were considered metabolic responders on the day 18-21 FDG-PET scan. Responders had a 5 year PFS and OS of 60 and 70%, respectively, while the percentage for non-responders was 63 and 75% (p = 0.96 and 0.85).Conclusions: This phase II trial did not demonstrate that a PET scan after one cycle of chemotherapy can predict survival outcomes of patients with NSCLC treated with neoadjuvant chemotherapy.Trial Registration: NCT00227539 registered September 28th, 2005. [ABSTRACT FROM AUTHOR]

The article presents a study on patient-reported quality of life (PRQOL) for head and neck cancer patients, focusing on racial disparities in the results. It looks at how scores were different before and after chemoradiation before examining why black patients had lower PRQOL scores and survival rates.

The article offers information on a study which examines the microtubule inhibitor eribulin in recurrent and metastatic salivary gland cancers (RMSGCs), that is a disease where no therapeutic standard exists. It mentions that adenoid cystic carcinomas (ACCs) are generally felt to be insensitive to cytotoxic chemotherapy due to their relatively slow growth pattern.

Since the beginning of the 21st century, the treatment of lung cancer has changed dramatically. New treatments are improving survival outcomes for patients but have led to dramatic increases in cost. In a value‐based payment system, patients should have access to comprehensive outcome measurements, including survival rates, quality of life, and cost. High value in cancer care will optimize the outcomes that matter to patients relative to cost. [ABSTRACT FROM AUTHOR]

BACKGROUND Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 (VEGFR1-VEGFR3), fibroblast growth factor receptors 1 through 4 (FGFR1-FGFR4), platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) signaling networks implicated in tumor angiogenesis. Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced, radioiodine-refractory, differentiated thyroid cancer (RR-DTC). METHODS Fifty-eight patients with RR-DTC who had disease progression during the previous 12 months received lenvatinib 24 mg once daily in 28-day cycles until disease progression, unmanageable toxicity, withdrawal, or death. Previous VEGFR-targeted therapy was permitted. The primary endpoint was the objective response rate (ORR) based on independent imaging review. Secondary endpoints included progression-free survival (PFS) and safety. Serum levels of 51 circulating cytokines and angiogenic factors also were assessed. RESULTS After ≥14 months of follow-up, patients had an ORR of 50% (95% confidence interval [CI], 37%-63%) with only partial responses reported. The median time to response was 3.6 months, the median response duration was 12.7 months, and the median PFS was 12.6 months (95% CI, 9.9-16.1 months). The ORR for patients who had received previous VEGF therapy (n = 17) was 59% (95% CI, 33%-82%). Lower baseline levels of angiopoietin-2 were suggestive of tumor response and longer PFS. Grade 3 and 4 treatment-emergent adverse events, regardless of their relation to treatment, occurred in 72% of patients and most frequently included weight loss (12%), hypertension (10%), proteinuria (10%), and diarrhea (10%). CONCLUSIONS In patients with and without prior exposure to VEGF therapy, the encouraging response rates, median time to response, and PFS for lenvatinib have prompted further investigation in a phase 3 trial. Cancer 2015;121:2749-2756. © 2015 American Cancer Society [ABSTRACT FROM AUTHOR]

Background Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by bone marrow failure and increased risk of cancers including acute myelogenous leukemia and various solid tumors, especially head and neck cancer. Management of head and neck cancer in the setting of FA is complicated by pancytopenia, poor tolerance of chemotherapy, and potentially increased radiosensitivity. There are limited reports on tolerance of radiotherapy (RT) in patients with FA. Methods We report a case of a patient with FA who presented with a small oral tongue cancer that was excised. He rapidly developed extensive locoregional recurrence and underwent surgical resection followed by postoperative RT with concurrent cetuximab. Results Both RT and cetuximab were well tolerated with manageable toxicities. Unfortunately, the patient died of early locoregional disease progression. Conclusions RT with concurrent cetuximab was well tolerated and may be an appropriate option in patients with FA. However, many patients have a poor prognosis due to aggressive disease. © 2012 Wiley Periodicals, Inc. Head Neck 35: E292-E298, 2013 [ABSTRACT FROM AUTHOR]

Background: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). Methods: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. Results: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. Conclusions: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. Trial Registration: ClinicalTrials.gov NCT01011075 [ABSTRACT FROM AUTHOR]

Background. Paclitaxel is not considered to be an active drug in adenoid cystic carcinoma (ACC) of the salivary glands. We report 2 consecutive cases of patients with ACC who responded to paclitaxel. Methods. The patients were: (1) a 58-year-old man with recurrent ACC who developed pulmonary metastases, had progressive disease after a good response to first-line chemotherapy, and then achieved a partial response to weekly single- agent paclitaxel; and (2) a 46-year-old woman with extensive thoracic ACC metastases who achieved a significant response after 2 cycles of paclitaxel chemotherapy. Results. The first patient died of progressive disease approximately 4 months after completing paclitaxel therapy, and the second patient had disease control after 6 cycles of paclitaxel. Conclusions. Systemic weekly paclitaxel produced a significant response in 2 patients with ACC of the head and neck, and its use in this disease merits further study. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [ABSTRACT FROM AUTHOR]

Background: Squamous cell carcinoma of the skin (SCCS) is rarely encountered by medical oncologists owing to success of local therapies. When advanced SCCS requires systemic palliation, treatment with conventional chemotherapy, such as cisplatin, is often precluded by a patient's age or medical comorbidities. Cetuximab is a human and mouse chimeric antibody against epidermal growth factor receptor, a tyrosine kinase receptor richly expressed by SCCS cells, including lymph node metastases. This drug, approved for treatment of squamous cell carcinoma of the upper aerodigestive tract as well as colorectal cancer, is well tolerated. Toxic effects include acneiform rash and diarrhea. Preclinical data suggest that epidermal growth factor receptor is important in SCCS carcinogenesis. Observations: Herein, we report 2 cases of elderly patients with extensive, in-transit recurrence of SCCS who have been treated with palliative cetuximab. The drug was well tolerated, with the exception of acneiform rash requiring dose reduction in 1 patient. Both patients had excellent responses to cetuximab: the first patient had complete response by week 16 of treatment and the second a near-complete response by week 12. In both cases, initial response to cetuximab was evident by week 4 of therapy. Conclusions: To our knowledge, these are the first reported cases of cetuximab use in patients with SCCS. The encouraging responses justify the prospective study of cetuximab in SCCS. [ABSTRACT FROM AUTHOR]