Head and neck squamous cell carcinoma

Nivolumab Demonstrated Survival Benefit, Good Tolerance in Refractory HNSCC

Source: www.asco.orgAuthor: Tim Donald, ELS In the phase III comparative CheckMate 141 trial, nivolumab demonstrated a “significant improval in survival” in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), compared with therapy of the investigator’s choice, according to Robert L. Ferris, MD, PhD, FACS, of the University of Pittsburgh Cancer Institute (Abstract 6009). There were fewer treatment-related adverse events with the PD-1 inhibitor than with investigator’s choice therapy, Dr. Ferris said, and nivolumab stabilized patient-reported quality-of-life outcome measures, whereas the investigator’s choice therapy led to meaningful declines in function and worsening of symptoms. Dr. Robert L. Ferris “Nivolumab is a new standard-of-care option for patients with refractory or metastatic HNSCC after platinum-based therapy,” Dr. Ferris said. Dr. Ferris presented the trial results at the “Harnessing the Immune System in Head and Neck Cancer: Evolving Standards in Metastatic Disease” Clinical Science Symposium on June 6. He noted that in this trial of patients whose disease had progressed after platinum-based therapy, nivolumab doubled the 1-year overall survival (OS) rate, with 36.0% OS for the immunotherapeutic drug compared with 16.6% for the investigator’s choice therapy. These top-line results were presented at the 2016 American Association of Cancer Research meeting1; Dr. Ferris presented data the additional endpoints of quality of life, correlative biomarkers, and safety. There is an extremely poor prognosis for patients with platinum-refractory recurrent or metastatic HNSCC, with median OS of 6 months or fewer. Previous research, by Dr. Ferris and others, has shown that HNSCC can express T-cell [...]

Charlotte Parker2016-06-07T16:35:54-07:00June, 2016|Oral Cancer News|

Research Leader Discusses FDA-Funded Immunotherapy for Head and Neck Cancer

Source: www.onclive.comAuthor: Gina Columbus Brett Miles, MD, DDS The investigational immunotherapy axalimogene filolisbac (ADXS11-001) has emerged as a potentially practice-changing agent in the treatment of HPV-related oropharyngeal cancer. Shown to generate T cells directed against a cancer antigen and neutralize suppressor regulatory T cells and myeloid-derived suppressor cells that protect the tumor microenvironment from an immunologic attack and contribute to tumor growth, ADXS11-001 is the first of its kind—a therapeutic vaccine for the disease. The agent is being examined in an ongoing phase II trial, which was reported as one of 18 recipients of research grants recently awarded by the FDA’s Office of Orphan Product Development. The grants, given to sites for product development in rare diseases, total more than $19 million. The ADXS11-001 grant provides collaborating researchers from Baylor College of Medicine and the Icahn School of Medicine at Mount Sinai with more than $1.1 million over 3 years. Eligible patients for the phase II study are newly diagnosed with stage II to IV HPV16-positive oropharynx squamous cell carcinoma who are scheduled to receive ablative transoral robotic surgery. In an interview with OncLive, the study’s surgical principal investigator, Brett Miles, MD, DDS, associate professor of Otolaryngology Head and Neck Surgery, co-chief, Division of Head and Neck Oncology, Icahn School of Medicine at Mount Sinai, discusses the potential of ADXS11-001 in HPV-associated head and neck cancer and other emerging therapies and treatment strategies. OncLive: Congratulations on your study being awarded a research grant from the FDA. How does it [...]

Charlotte Parker2015-09-29T11:26:02-07:00September, 2015|Oral Cancer News|

Integrative and Comparative Genomic Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas

Source: http://clincancerres.aacrjournals.org/Authors: Tanguy Y. Seiwert, Zhixiang Zuo, Michaela K. Keck, Arun Khattri, Chandra S. Pedamallu, Thomas Stricker, Christopher Brown, Trevor J. Pugh, Petar Stojanov, Juok Cho, Michael S. Lawrence, Gad Getz, Johannes Brägelmann, Rebecca DeBoer, Ralph R. Weichselbau, Alexander Langerman, Louis Portugal, Elizabeth Blair, Kerstin Stenson, Mark W. Lingen, Ezra E.W. Cohen, Everett E. Vokes, Kevin P. White, and Peter S. Hammerman Abstract Purpose: The genetic differences between human papilloma virus (HPV)–positive and –negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown. To identify differential biology and novel therapeutic targets for both entities, we determined mutations and copy-number aberrations in a large cohort of locoregionally advanced HNSCC. Experimental Design: We performed massively parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal samples (42.5% HPV-positive). Mutations and copy-number aberrations were determined and results validated with a secondary method. Results: The overall mutational burden in HPV-negative and HPV-positive HNSCC was similar with an average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer-associated genes. HPV-negative tumors showed a mutational spectrum concordant with published lung squamous cell carcinoma analyses with enrichment for mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA, and NOTCH genes. HPV-positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in PIK3CA, KRAS, MLL2/3, and NOTCH1 were enriched in HPV-positive tumors. Currently targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3, EPHA2, and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative tumors, whereas 17.6% of HPV-positive tumors harbored mutations in fibroblast growth factor receptor [...]

Charlotte Parker2015-02-05T14:34:06-07:00February, 2015|Oral Cancer News|

Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling

Source: http://cancerres.aacrjournals.org Authors: Faina Linkov, Alex Lisovich, Zoya Yurkovetsky, Adele Marrangoni, Lyudmila Velikokhatnaya, Brian Nolen, Matthew Winans, William Bigbee, Jill Siegfried, Anna Lokshin, and Robert Ferris Abstract: Squamous cell carcinoma of the head and neck cancer (SCCHN) is an aggressive disease which has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multi-analyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients prior to treatment (active disease group), 103 patients who were successfully treated (no evidence of disease, NED, group), and 117 smoker controls without evidence of cancer. The multi-marker panel offering the highest diagnostic power was comprised of 25 biomarkers, including EGF, EGFR, IL-8, tPAI-1, AFP, MMP-2, MMP-3, IFN-α, IFN-γ, IP-10, RANTES, MIP-1α, IL-7, IL-17, IL-1Rα, IL-2R, G-CSF, mesothelin, IGFBP-1, E-selectin, cytokeratin (CK)19, V-CAM, and CA-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%, and 92% of patients in the active disease group correctly classified from a [...]

Charlotte Parker2014-10-10T11:05:56-07:00October, 2014|Oral Cancer News|

Protein Deters Head, Neck Cancer Growth, Study Shows

Source: JADA (Journal of the American Dental Association) Scientists at the National Institute of Dental and Craniofacial Research found that blocking a certain protein inhibited the proliferation of head and neck squamous cell carcinoma, according to a study published in the February issue of Molecular Oncology. In an experiment involving tissue samples of hundreds of head and neck cancer patients, an NIDCR team led by Silvio Gutkind, PhD, chief of NIDCR’s Oral and Pharyngeal Cancer Branch, found that p38 kinase was active in most samples. They reported that the most malignant tissue samples had the highest activity of p38, and the least malignant samples had the lowest p38 activity. The normal oral tissue used as a control had no p38 activity. When researchers turned off p38 activity in human oral cancer cells and transplanted these cells into laboratory mice, they found that the oral cancer cells without p38 activity were smaller than those with p38 activity. In addition, turning off p38 activity lessened the growth of new blood vessels, which cancers rely on for growth and the ability to spread to other parts of the body. In the next phase of the study, they tested SB203580—a drug that is known to block p38 activity. SB203580 reduced the growth of head and neck cancer cells in the laboratory. When the NIDCR team then used SB203580 to treat human head and neck cancers that had been transplanted into lab mice, they found that SB203580 made the cancers smaller. The next step, Dr. [...]

Charlotte Parker2014-03-03T17:26:04-07:00March, 2014|Oral Cancer News|

PTEN loss, PIK3CA mutation predicted resistance to cetuximab in HNSCC

June 2, 2013Source: Helio.com CHICAGO — PTEN loss or PIK3CA mutation predicted resistance to treatment with cisplatin plus cetuximab in a cohort of patients with head and neck squamous cell carcinoma, according to phase 3 study results presented at the ASCO Annual Meeting. “Cetuximab is the only targeted therapy in use in head and neck cancer, and although it prolongs survival, the effects are modest. For patients who receive [cetuximab] in the setting of metastatic or recurrent disease, median survival remains less than 1 year,” Barbara Burtness, MD, a medical oncologist at Fox Chase Cancer Center who specializes in head and neck cancers and a HemOnc Today Editorial Board member, said in an interview. “In colon cancer, patients are tested for KRAS mutations to detect patients with upfront resistance to cetuximab, but KRAS mutation is rare in head and neck cancer, and we haven’t had a biomarker to separate the sensitive from resistant patients.” Burtness and colleagues compared cisplatin plus placebo vs. cisplatin plus cetuximab (Erbitux, Eli Lilly) in 117 patients. The researchers also assessed PIK3CA mutations and loss of PTEN expression in the cohort. Results indicated that 34% of tumors studied had a loss of PTEN expression and 4% had PIK3CA mutations in the three hotspots studied. Researchers did not observe any statistically significant differences in OS, PFS or overall response rates. However, among patients with PIK3CA and PTEN expression, median PFS was 4.2 months for those assigned to cetuximab vs. 2.9 months for those assigned to placebo (adjusted [...]

Charlotte Parker2013-06-03T10:20:56-07:00June, 2013|Oral Cancer News|

New Guidelines for Head & Neck Cancer Reirradiation

Source: PhysciansWeekly.com Recurrent and second primary head-and-neck squamous cell carcinomas arising within or close to previously irradiated areas are a significant clinical challenge. The American College of Radiology published appropriateness criteria for recurrent head and neck cancer after prior definitive radiation. Recurrent and second primary head-and-neck squamous cell carcinomas (HNSCC) arising within or close to previously irradiated areas are a significant clinical challenge. Salvage surgical resection is the standard of care, but reirradiation is the only potentially curative treatment when surgery is not an option. Reirradiation is more challenging than initial treatment because of the side effects of prior therapy and concerns about the risks of high cumulative radiation doses to normal structures. Multi-institutional trials and large single institutional experiences have demonstrated that aggressive reirradiation, most often with chemotherapy, is feasible and provides durable locoregional control in some patients. An Expert Consensus on Reirradiation In the August 1, 2011 International Journal of Radiation Oncology * Biology * Physics, the American College of Radiology (ACR) published appropriateness criteria for recurrent head and neck cancer after prior definitive radiation. The ACR expert panel recommended that patient evaluation and reirradiation for HNSCC be performed at a tertiary care center with a head and neck oncology team that is equipped with the resources and experience to manage the complexities and toxicities of retreatment. Evaluation of Patients with Head & Neck Cancer Patient evaluation is important in assuring only appropriate patients are offered reirradiation. Evaluation should include careful restaging imaging, a detailed history and assessment [...]

Charlotte Parker2012-08-20T10:43:31-07:00August, 2012|Oral Cancer News|

Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 Immunohistochemistry, Consensus PCR HPV-DNA, and In Situ Hybridization

Source: 7thspace.com Recent emerging evidences identify Human Papillomavirus (HPV) related Head and Neck squamous cell carcinomas (HN-SCCs) as a separate subgroup among Head and Neck Cancers with different epidemiology, histopathological characteristics, therapeutic response to chemo-radiation treatment and clinical outcome. However, there is not a worldwide consensus on the methods to be used in clinical practice. The endpoint of this study was to demonstrate the reliability of a triple method which combines evaluation of: 1. p16 protein expression by immunohistochemistry (p16-IHC); 2. HPV-DNA genotyping by consensus HPV-DNA PCR methods (Consensus PCR); and 3 viral integration into the host by in situ hybridization method (ISH). This triple method has been applied to HN-SCC originated from oral cavity (OSCC) and oropharynx (OPSCC), the two anatomical sites in which high risk (HR) HPVs have been clearly implicated as etiologic factors. Methylation-Specific PCR (MSP) was performed to study inactivation of p16-CDKN2a locus by epigenetic events. Reliability of multiple methods was measured by Kappa statistics. Results: All the HN-SCCs confirmed HPV positive by PCR and/or ISH were also p16 positive by IHC, with the latter showing a very high level of sensitivity as single test (100% in both OSCC and OPSCC) but lower specificity level (74% in OSCC and 93% in OPSCC).Concordance analysis between ISH and Consensus PCR showed a faint agreement in OPSCC (kappa = 0.38) and a moderate agreement in OSCC (kappa = 0.44). Furthermore, the addition of double positive score (ISHpositive and Consensus PCR positive) increased significantly the specificity of HR-HPV detection on [...]

Charlotte Parker2012-02-29T17:24:29-07:00February, 2012|Oral Cancer News|

Palliation Trumps PET in Prolonging Head and Neck Cancer Survival

Source: Elsevier Global Medical News. 2012 Feb 23, D McNamara MIAMI BEACH (EGMN) - Using PET scans to diagnose distant metastasis in patients with advanced head and neck squamous cell carcinoma does not significantly prolong life expectancy, compared with other imaging techniques, according to a retrospective study. Palliative chemotherapy did make a difference, however, significantly increasing life expectancy by 215 days in patients who received it, Dr. Matthew E. Spector and colleagues from the University of Michigan, Ann Arbor, reported at a meeting of the Triological Society. "Over 90% of patients at University of Michigan have at least one PET scan at some point in their treatment," Dr. Spector said. Increased sensitivity is one reason for such widespread adoption of the imaging technique. "We were wondering, while it may be more sensitive to identify distant metastatic disease, was it changing what we were doing?" In a retrospective look at 170 patients with such cancers at their institution, researchers found no significant difference in median survival between patients who had a PET scan (168 days) and those who did not (193 days). Determination of any survival difference was a primary aim of the study. "A lot of studies have looked at PET scans, and we know in up to one-third of cases it may change our decisions," Dr. Spector said. For example, a negative PET scan might mean definitive treatment, whereas a positive PET finding might lead to palliative therapy. However, "no one has looked at the impact of the PET findings on the life expectancy after diagnosis." All patients in the study had a distant metastasis diagnosis. "We found PET was more [...]

Charlotte Parker2012-02-27T11:42:48-07:00February, 2012|Oral Cancer News|

Timing of Post-TX Imaging Key in Head, Neck Cancer

Source: MedScape Today Summary The investigators report on a systematic review and meta-analysis of 51 studies involving 2335 patients with head and neck squamous cell carcinoma who underwent post-treatment or surveillance with 18F-fluorodeoxyglucose (FDG) PET or FDG-PET/CT. The random-effects model-weighted mean pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detection of residual disease at the primary tumor site were 79.9% (95% CI, 73.7%-85.2%), 87.5% (95% CI, 85.2%-89.5%), 58.6% (95% CI, 52.6%-64.5%), and 95.1% (95% CI, 93.5%-96.5%), respectively. The respective values for detection of residual post-treatment neck nodes were 72.7% (95% CI, 66.6%-78.2%), 87.6% (95% CI, 85.7%-89.3%), 52.1% (95% CI, 46.6%-57.6%), and 94.5% (95% CI, 93.1%-95.7%). In a subgroup analysis on timing of PET after completion of therapy, scans performed after 12 weeks had significantly higher diagnostic performance than scans done within 12 weeks, but only for residual neck nodes and not for residual disease at the primary tumor site. No statistically significant difference in diagnostic accuracy was noted between stand-alone PET and PET/CT. Viewpoint Well-performed systematic reviews and meta-analyses are important contributions to the literature.[1] In this meta-analysis, the diagnostic performance of dedicated PET and PET/CT with FDG was investigated by pooling the data from a relatively large cohort of patients with head and neck cancer who had been treated with chemoradiation. The pooled evidence demonstrated good diagnostic performance for FDG-PET and FDG-PET/CT, regardless of the type of scanner, with very high NPV but somewhat suboptimal PPV; this is due to the nonspecificity of FDG, [...]

Charlotte Parker2012-02-22T09:47:08-07:00February, 2012|Oral Cancer News|