Objectives/Hypothesis
A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to ...improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC).
Study Design
Prospective cohort study.
Methods
A panel of 130 serum biomarkers, previously selected for cancer detection using microarray‐based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave‐one‐out cross‐validation model. Survival curves were estimated according to the Kaplan‐Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models.
Results
Poor overall survival was associated with African Americans (hazard ratio HR for death = 2.61; 95% confidence interval CI: 1.58‐4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40‐5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54‐17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival.
Conclusions
The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted.
Level of Evidence
NA Laryngoscope, 124:1819–1826, 2014
BackgroundImmuno-STATsTM are novel, modular fusion proteins designed to selectively activate tumor-antigen-specific CD8+ T cells. Human papillomavirus (HPV) associated cancers serve as a model system ...to assess the safety and efficacy of the Immuno-STAT platform. CUE-101 is comprised of human leukocyte antigen (HLA) complex, HLA A*0201, a peptide epitope derived from the HPV type 16 E7 protein, and 4 molecules of a reduced affinity human interleukin-2 (IL2) designed to bind and activate HPV-specific T cells for eradication of HPV16-driven cancers. In preclinical studies CUE-101 demonstrated selective binding, activation, and expansion of HPV16 E7-specific CD8+ T cells, which translated into anti-tumor activity.1MethodsCUE-101-01 is a first-in-human (FIH) phase 1 study in patients diagnosed with HPV16+ recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) refractory to one or more lines of therapy. Trial eligibility includes MHC class I type HLA-A*0201 and a diagnosis of an HPV16+ HNSCC, as assessed by p16 IHC and confirmed by HPV16 mRNA ISH. CUE-101 is administered intravenously over 60 minutes every 21 days. Objectives include determination of safety, pharmacodynamics (PD), pharmacokinetics (PK), recommended phase 2 dose (RP2D), and preliminary anti-tumor activity. The safety results from treated participants will be presented.Results19 participants have received CUE-101 monotherapy as of August 7, 2020. Doses ranging from 0.06 to 1 mg/kg were determined to be safe and well-tolerated, enabling dose escalation to 2 mg/kg. Preliminary PK data demonstrate dose-dependent increases in drug exposure which are sustained upon repeat dosing, and low inter-subject variability. Preliminary data from systemic blood analyses show early signals of expansion of HPV-16 E711-20-specific CD8+ T cells. Stable disease (SD), as determined by RECIST 1.1, was observed in several participants in these early dose cohorts, with one subject maintaining SD up to 19 weeks. The maximum tolerated dose (MTD) has not yet been reached. As of May 14, 2020 (the development safety update report (DSUR) data-lock date), no dose limiting toxicities and the following adverse events were observed in the first 12 patients treated with CUE-101: fatigue (n=3), decreased appetite (n=1), arthralgia (n=1), muscular weakness (n=1), parasthesia (n=1), bullous pemphigoid (n=1), and infusion-related reactions (n=1).ConclusionsCUE-101 is a novel agent that is demonstrating acceptable tolerability, favorable PK, and preliminary PD signals that support selective activation of tumor-specific T cells. Neither the MTD nor the monotherapy RP2D have been established. PD and PK analyses are ongoing as dose escalation continues.AcknowledgementsThe authors would like to thank all the patients who are participating in this study. The study is sponsored by Cue Biopharma.Trial RegistrationClinicalTrials. gov NCT03978689Ethics ApprovalThis study was approved by Ethics and Institutional Review Boards (IRBs) at all study sites; IRB reference numbers: DF/HCC IRB# 19-374 (Massachusetts General Hospital), HRPO# 201905108 (Washington University School of Medicine), IRB 191714 (Vanderbilt University Medical Center Vanderbilt-Ingram Cancer Center), Advarra Pro00037736 (Moffitt Cancer Center), IRB(IRBMED) HUM00165746 (University of Michigan Comprehensive Cancer Center), 2019-087 (Karmanos Cancer Institute), WIRB IRB00112341(Winship Cancer Institute/Emory University), WIRB 2000026098 (Yale Cancer Center), WIRB STUDY00008948 (University of Washington, Seattle ), WIRB 1908869642 (University of Arizona Cancer Center, IRB 20-073 (Memorial Sloan Kettering Cancer Center), 2019-0578 (The University of Texas MD Anderson Cancer Center), IRB 52744 (Stanford University School of Medicine).ReferenceQuayle SN, Girgis N, Thapa DR, et al. CUE-101, a Novel HPV16 E7-pHLA-IL-2-Fc Fusion Protein, Enhances Tumor Antigen Specific T Cell Activation for the Treatment of HPV16-Driven Malignancies. Clin Cancer Res 2020;26:1953–64.
Head and Neck Cancer Svider, Peter F; Blasco, Michael A; Raza, S Naweed ...
Otolaryngology-head and neck surgery,
01/2017, Letnik:
156, Številka:
1
Journal Article
Recenzirano
Despite a considerable expansion in our therapeutic repertoire for management of other malignancies, mortality from head and neck cancer (HNC) has not significantly improved in recent decades. Upon ...normalizing National Institutes of Health-awarded R01 and R01-equivalent grants by incidence, thyroid cancer ($214) and HNC ($1329) received the fewest funding dollars. Upon adjusting funding totals by mortality, HNC was 7th out of 9 cancers evaluated ($6138). These findings highlight HNC as an underfunded disease versus other cancers. As data detailing grant applications (including unsuccessful grants) are not publicly available, it is not clear if these disparities stem from fewer applications or fewer opportunities. Our hope is that this commentary will spur further investigation into strategies to increase HNC inquiry and funding for trainees as well as early-stage and established investigators.
Immune checkpoint inhibitors (ICIs) are the newest class of anticancer drugs. Pneumonitis is increasingly being recognized as a potential complication of these agents.
We conducted a retrospective ...study of patients who received ICIs at a comprehensive cancer center. We collected data on demographics, type of malignancy, type of ICI agent, incidence of pneumonitis up to 6 weeks after receiving ICI agent, clinical characteristics, and risk factors for overall survival in patients who develop pneumonitis.
A total of 654 patients received ICIs during the study period. The most common type of cancer for which ICI was given was adenocarcinoma of the lung (29%), followed by renal cell cancer (12%) and squamous cell lung cancer (12%). Among the study patients, 41% received nivolumab and 32% received pembrolizumab. Other patients in the study received combination of ICIs or ICI plus chemotherapeutic agent, or were part of clinical trial involving ICI. Overall 42 (6.4%) patients developed pneumonitis within 6 weeks after the last dose of treatment of any ICI agent. Of these, 81% of patients had Grade ≥ 2 pneumonitis and 45% of these required hospital admission for pneumonitis, with 10% of them requiring admission to intensive care unit. Overall, patients who received pembrolizumab-containing regimen, had prior chemotherapy, or who never had cancer-related surgery had increased risk of death.
Our large retrospective study shows real-life data of incidence of pneumonitis in patients who are treated with ICIs for cancer treatment. Our data indicate that the incidence of pneumonitis is overall lower than that reported previously with relatively good outcomes.
Purpose. To explore the safety and efficacy of gemcitabine and docetaxel (GEMDOC) in previously treated patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). ...Patients and Methods. Patients with advanced SCCHN previously pretreated with one or two lines of palliative chemotherapy were treated with gemcitabine and docetaxel until disease progression. Results. Thirty-six patients were enrolled, and 29 were response evaluable. 16 (55%) experienced clinical benefit (response or stable disease). Six (21%) patients achieved partial response (PR), none achieved complete response (CR), and the overall response rate (ORR) was 21% (95% CI: 0.10–0.38). Ten (28%) patients had stable disease. The median response duration (RD) for the 6 PR patients was 3.2 months (80% CI: 2.0–6.1 months). Median overall survival was 4.2 months (95% CI: 2.4–7.0 months). Among the 33 treated patients: 13 (39%) patients had grade 3-4 anemia, 10 (30%) had grade 3-4 neutropenia. Conclusion. The study drugs were relatively safe, and the clinical benefit (PR + SD) rate was 55%. However, the efficacy objective for this regimen was not met. Given the good safety profile, further investigation of this regimen with the addition of a targeted agent may lead to better efficacy.
To investigate the existence of quantum metabolic values in various subtypes of non-Hodgkin's lymphoma (NHL).
Fifty-eight patients with newly diagnosed NHL and positron emission tomography (PET) ...performed within three months of biopsy were included. The standardized uptake value (SUV) from PET over the area of biopsy and serum glucose Glc were recorded. The group glucose sensitivity(G) for indolent and aggressive NHL was obtained by linear regression with ln(SUV) = G x lnGlc + C, where C is a constant for the group. Finally, the individual's glucose sensitivity (g) was obtained by g = {ln(SUV)-C}/lnGlc, along with their means in various subtypes of NHL. To further investigate the influence of extreme Glc conditions, the SUVs corrected by the individually calculated g at various glucose levels, Glc' using SUV' =SUV x {Glc'/Glc}(g), were compared to the original SUVs for both indolent and aggressive NHL.
The averaged g (=G) for aggressive was significant different from that for indolent NHL (-0.94 +/- 0.51 vs. +0.13 +/- 0.10, respectively, p < 0.00005). There were significant differences in SUV for Glc < 80 or >110 mg/dl for both types of NHL. Unlike overlap among SUVs between NHL subtypes, the g value clearly categorized them into two distinct groups with positive (near-zero) and negative g values (around -1) for the indolent and aggressive NHLs, respectively.
Distinct quantum metabolic values of -1 and 0 were noted in NHL. Aggressive NHL has a more negative value (or higher glucose sensitivity) than that of indolent and, thus, is more susceptible to extreme glucose variation.
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