Interdisciplinary group focuses on developing personalized oral cancer vaccine

Source: web.musc.edu Author: Leslie Cantu Jason Newman, M.D., Angela Yoon, D.D.S., and Shikhar Mehrotra, Ph.D., are working together on a project to develop a personalized vaccine to prevent oral cancer from returning. Photo by Clif Rhodes Interdisciplinary innovation is a hallmark of MUSC Hollings Cancer Center, and it doesn’t get much more interdisciplinary than this – three people, one each with an M.D., a D.D.S., and a Ph.D., working together to develop a new type of personalized vaccine to prevent oral cancer recurrence. “The amazing thing to me is that Jason Newman and I started on the same day at MUSC, which was March 1 of last year. He came from UPenn. I came from Columbia, and Shikhar has been at MUSC forever. It's just three different people who never knew each other before that time, and then we somehow got together and the synergy was there,” said Angela Yoon, D.D.S. Yoon, a professor in the James B. Edwards College of Dental Medicine who focuses on cancer biomarkers and immunomodulatory therapy, is leading the effort in collaboration with the two professors from the College of Medicine: Jason Newman, M.D., Head and Neck Cancer Division director, and Shikhar Mehrotra, Ph.D., scientific director of the Center for Cellular Therapy. They’re getting their project started using funding provided by Hollings. Periodically, Hollings awards funds to MUSC departments as a way to reinvest in faculty members who are conducting cancer research. Participating in clinical trials and on scientific committees and writing new [...]

Cancer stem cells’ biomarker ALDH1&2 increased expression in erosive oral lichen planus compared to oral leukoplakia

Source: www.cureus.com Author: Zisis V, Giannakopoulos N N, Schmitter M, et al. Abstract Introduction: ALDH1&2 has been considered an oral cancer stem cell (CSC) marker. Oral carcinogenesis is a process that usually passes through oral potentially malignant disorders (OPMD). Oral lichen planus (OLP) consists of immune-related chronic disorders that have been included in the OPMDs due to their possible transformation into oral cancer. The aim of this study was to investigate the early presence of ALDH1&2 in OLP compared to early oral leukoplakias (OL), especially mildly and non-dysplastic OL. Materials and methods: The study type is experimental, and the study design is characterized as semiquantitative research which belongs to the branch of experimental research. The study sample consisted of paraffin-embedded OLP biopsy samples from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece, during the period 2009-2019. The study sample contained 24 cases of OLP (14 erosive and 10 reticular) and 30 cases of OL (16 cases of moderately and severely dysplastic OL and 14 cases of mildly and non-dysplastic OL). The CSC-related biomarker ALDH1&2 was examined using semiquantitative immunohistochemistry (monoclonal antibody sc-166362, Santa Cruz Biotechnology, Dallas, Texas, USA, 1:100). ALDH1&2 expression was evaluated through a scale of 1 to 3 depending on the percentage of positive epithelial cells and was compared to normal epithelium as well as cases of OL (the most prominent OPMD). The statistical analysis was performed with the Pearson chi-square test and the significance level was set at p≤0.05. [...]

Merck and Eisai say late-stage trial of treatment for head and neck cancer did not meet goals

Source: www.marketwatch.com Author: Ciara Linnane Merck & Co. Inc. and Eisai Co. Ltd. said Friday a late-stage trial of a treatment for head and neck cancer failed to meet its main goals and the companies have decided to shut it down. The Phase 3 trial sought to evaluate Merck’s Keytruda plus Lenvima, an orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, as a first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma. The primary endpoints were overall survival, progression-free survival and objective response rate. Two planned interim analyses conducted by an independent data monitoring committee found in the first analysis that Keytruda and Lenvima achieved a statistically significant improvement in PFS and ORR compared with Keytruda and placebo. But the second analysis, the two did not demonstrate an improvement in OS compared to KEYTRUDA plus placebo, “and the likelihood of reaching the protocol-specified threshold for statistical significance for OS was evaluated by Merck and Eisai and deemed to be low,” said the companies. The partners have decided to close the study and are informing investigators of that decision.

Machine learning in the detection of oral lesions with clinical intraoral images

Source: www.cureus.com Author: Karthikeyan Ramalingam et al. Abstract from article: Introduction: Artificial intelligence in oncology has gained a lot of interest in recent years. Early detection of Oral squamous cell carcinoma (OSCC) is crucial for early management to attain a better prognosis and overall survival. Machine learning (ML) has also been used in oral cancer studies to explore the discrimination between clinically normal and oral cancer. Materials and methods: A dataset comprising 360 clinical intra-oral images of OSCC, Oral Potentially Malignant Disorders (OPMDs) and clinically healthy oral mucosa were used. Clinicians trained the machine learning model with the clinical images (n=300). Roboflow software (Roboflow Inc, USA) was used to classify and annotate images along with Multi-class annotation and object detection models trained by two expert oral pathologists. The test dataset (n=60) of new clinical images was again evaluated by two clinicians and Roboflow. The results were tabulated and Kappa statistics was performed using SPSS v23.0 (IBM Corp., Armonk, NY). Results: Training dataset clinical images (n=300) were used to train the clinicians and Roboflow algorithm. The test dataset (n=60) of new clinical images was again evaluated by the clinicians and Roboflow. The observed outcomes revealed that the Mean Average Precision (mAP) was 25.4%, precision 29.8% and Recall 32.9%. Based on the kappa statistical analysis the 0.7 value shows a moderate agreement between the clinicians and the machine learning model. The test dataset showed the specificity and sensitivity of the Roboflow machine learning model to be 75% and 88.9% respectively. Conclusion: In [...]

Best practices for immunotherapy for metastatic head and neck cancer

Source: www.medpagetoday.com Author: Mark L. Fuerst , Contributing Writer, MedPage Today Immunotherapy with anti–programmed cell death protein 1 (PD-1) immune checkpoint inhibitors (ICIs) is now an essential treatment for patients with recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), and ICIs also show promise for patients with nasopharyngeal carcinoma and other rare head and neck cancer types. A recently released ASCO Guideline on immunotherapy and biomarker testing in recurrent and metastatic HNSCCs provided evidence-based recommendations. A new related document by expert panel co-chairs Emrullah Yilmaz, MD, PhD, of the Cleveland Clinic, and Loren K. Mell, MD, of the University of San Diego, and colleagues poses questions and answers about the guideline. The following is a summary: For patients with recurrent and metastatic head and neck cancer, which biomarkers should be used in the selection of anti–PD-1 immune checkpoint inhibitor therapy? We recommend programmed death ligand 1 (PD-L1) combined positive score (CPS) testing for recurrent and metastatic HNSCC. PD-L1 reports come via immunohistochemistry using CPS or tumor proportion score. CPS has emerged as a preferred biomarker in HNSCC and has been used in landmark head and neck clinical trials such as KEYNOTE-048. Tumor mutational burden (TMB), another emerging biomarker for predicting response to anti–PD-1 ICIs, was studied in KEYNOTE-158. TMB is not used routinely in HNSCC, but may help in cases where PD-L1 CPS is unavailable or for rare head and neck cancers. In first-line treatment of patients with PD-L1 CPS ≥ 1 recurrent and metastatic HNSCC, can pembrolizumab [...]

Running can help cut risk of 9 different cancers in men: study

Source: runningmagazine.ca Author: Paul Baswick Maintaining high levels of cardiorespiratory fitness in young adulthood can help men lower their risk of developing nine different forms of cancer later in life, according to research released this week. In a study published in the British Journal of Sports Medicine, researchers analyzed the rates of cancer in a cohort of more than a million men in Sweden over an average period of 33 years, beginning at age 18. Using the results from fitness tests that were used to gauge the men’s suitability for military service—assessments that were formerly mandatory in Sweden—researchers divided the participants into low, moderate and high levels of cardiorespiratory fitness, and compared cancer rates among men in these groups in later life. The researchers found the men who showed the highest levels of fitness in young adulthood had a 20 per cent lower risk of kidney cancer and a 19 per cent lower risk of head and neck cancer compared to men in the low-fitness category. The study also suggests high cardiorespiratory fitness can play a major role in reducing the risk of gastrointestinal cancers. Participants in the high-fitness category saw their risk of cancer of the liver, the bile ducts, the esophagus and the gallbladder slashed by nearly 40 per cent, and their risk of stomach and colon cancer reduced by 20 per cent. The greatest difference was seen in rates of lung cancer. The study shows men in the high-fitness category cut their risk of lung cancer by [...]

Hollings head-and-neck team leads trial to reduce delays in care

Source: web.musc.edu Author: Leslie Cantu Beginning radiation therapy on time is critical for people with head and neck cancer. Delays in starting radiation therapy after surgery are associated with worse outcomes – and yet half of patients across the country don’t start radiation therapy when they should. A multidisciplinary team at MUSC Hollings Cancer Center has spent the last five years bringing this issue to light. Now, the team, led by Evan Graboyes, M.D., has been awarded a $3.5 million grant to test an approach for reducing those delays, which should improve outcomes. Called ENDURE, for Enhanced Navigation for Disparities and Untimely Radiation thErapy, the approach addresses the issue at three levels: organization, team and patient. New benchmark Reducing delays in moving to radiation from surgery has become a focus for cancer centers since November 2021, when the Commission on Cancer added a quality measure that grades centers on how many patients with head and neck squamous cell carcinoma begin radiation within six weeks of surgery. The commission accredits cancer programs, and this is the first time it’s included a head and neck cancer benchmark in its quality measures. The work of the Hollings team, which began when Hollings awarded Graboyes a K12 Paul Calabresi Career Development Award for Clinical Oncology in 2018, has been instrumental in providing the rationale for this new benchmark. Since that first grant award to Graboyes, the team has published 10 peer-reviewed publications showing that the time to starting radiation is a key measure, and [...]

Johns Hopkins engineers develop deep-learning technology that may aid personalized cancer therapy

Source: scitechdaily.com Author: by Johns Hopkins Medicine Cytotoxic CD8+ T-cells recognizing cancer cells by receptor binding neoantigens. Credit: Image generated by DALL-E 2 from OpenAI A team of engineers and cancer researchers from Johns Hopkins has developed a deep-learning technology capable of accurately predicting protein fragments linked to cancer, which might trigger an immune system response. Should this technology prove successful in clinical tests, it could address a significant challenge in the creation of personalized immunotherapies and vaccines. In a study published July 20 in the journal Nature Machine Intelligence, investigators from Johns Hopkins Biomedical Engineering, the Johns Hopkins Institute for Computational Medicine, the Johns Hopkins Kimmel Cancer Center, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy show that their deep-learning method, called BigMHC, can identify protein fragments on cancer cells that elicit a tumor cell-killing immune response, an essential step in understanding response to immunotherapy and in developing personalized cancer therapies. “Cancer immunotherapy is designed to activate a patient’s immune system to destroy cancer cells,” says Rachel Karchin, Ph.D., professor of biomedical engineering, oncology, and computer science, and a core member of the Institute for Computational Medicine. “A critical step in the process is immune system recognition of cancer cells through T cell binding to cancer-specific protein fragments on the cell surface.” The cancer protein fragments that elicit this tumor-killing immune response may originate from changes in the genetic makeup of cancer cells (or mutations), called mutation-associated neoantigens. Each patient’s tumor has a unique set of such neoantigens [...]

Henry Ford Health joins study to improve body image among head and neck cancer survivors

Source: www.dbusiness.com Author: Tim Keenan Henry Ford Health in Detroit is the first health care system in Michigan to join a multi-center study led by the Medical University of South Carolina (MUSC) Hollings Cancer Center aimed at improving the body image of head and neck cancer survivors. Known as the Building a Renewed Image after Head and Neck Cancer Treatment (BRIGHT) trial, the study was developed with extensive input from survivors of head and neck cancer, caregivers, oncologists, and psychologists to help identify the most effective ways to manage concerns about body image among survivors of head and neck cancer. Individuals who have undergone treatment for head and neck cancer often experience changes to their physical appearance, independence, and ability to do certain tasks, such as eating or speaking. The BRIGHT trial is studying two six-week telemedicine-based programs to help head and neck cancer survivors adapt their thoughts, behaviors, and coping skills to their new circumstances. “Among survivors of head and neck cancer, body image can play a significant role in quality of life,” says Dr. Steven Chang, co-investigator of the BRIGHT trial and vice chair of the Department of Otolaryngology Head and Neck Surgery at Henry Ford Health. “Studies have shown that approximately one in four survivors struggle with clinically significant body image distress, with younger patients, patients who have had extensive surgery, and patients who had wound healing problems at the highest risk. We are eager to participate in this important study, which has the potential to positively [...]

New classification method for HPV-associated head and neck cancers

Source: www.techexplorist.com Author: Vidya Nagalwade Over the past few decades, the number of cases of head and neck squamous cell carcinoma (HNSCC) related to the human papillomavirus (HPV+) has risen significantly and is still rising. The human papillomavirus (HPV) has been linked to an increase in cancer of the throat and tonsils, which is projected to become the most common form of head and neck cancer by 2030. Identifying the right patients with HPV-related cancers is a major challenge in reducing treatment intensity. A new study identifies a subclass of HPV+ head and neck squamous cell carcinomas (HNSCC). It shows that treatment depends on the tumor type. The data show two distinct subtypes of HPV+ HNSCC, each with its features and treatment responses. The researchers examined data from 104 HPV+ HNSCC tumors and two publically available sources to find gene expression patterns that might reliably distinguish distinct tumor types. Among the 22 modules tested, one accurately classified HPV+ HNSCC tumors based on a different gene expression pattern. The NFKB classifier accurately predicted a favorable result in patients treated in the ECOG-ACRIN Cancer Research Group trial E1308, even with low-dosage radiation. Barbara Burtness, a Professor of Medicine at Yale School of Medicine, said, “This discovery opens new opportunities for treatment personalization, as we can now better understand the distinct requirements for tumor development in each subclass.” The findings have significant clinical implications. Clinicians treating HPV+ HNSCC are constantly looking for biomarkers that can be used to determine treatment intensity. The new [...]

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