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Machine learning improves the diagnosis of patients with head and neck cancers

Source: www.sciencedaily.com
Author: materials from Charité – Universitätsmedizin Berlin

Researchers from Charité — Universitätsmedizin Berlin and the German Cancer Consortium (DKTK) have successfully solved a longstanding problem in the diagnosis of head and neck cancers. Working alongside colleagues from Technische Universität (TU) Berlin, the researchers used artificial intelligence to develop a new classification method which identifies the primary origins of cancerous tissue based on chemical DNA changes. The potential for introduction into routine medical practice is currently being tested. Results from this research have been published in Science Translational Medicine.

Every year, more than 17,000 people in Germany are diagnosed with head and neck cancers. These include cancers of the oral cavity, larynx and nose, but can also affect other areas of the head and neck. Some head and neck cancer patients will also develop lung cancer. “In the large majority of cases, it is impossible to determine whether these represent pulmonary metastases of the patient’s head and neck cancer or a second primary cancer, i.e. primary lung cancer,” explains Prof. Dr. Frederick Klauschen of Charité’s Institute of Pathology, who co-led the study alongside Prof. Dr. David Capper of Charité’s Department of Neuropathology. “This distinction is hugely important in the treatment of people affected by these cancers,” emphasizes Prof. Klauschen, adding: “While surgery may provide a cure in patients with localized lung cancers, patients with metastatic head and neck cancers fare significantly worse in terms of survival and will require treatments such as chemoradiotherapy.”

When trying to distinguish between metastases and a second primary tumor, pathologists will usually use established techniques such as analyzing the cancer’s microstructure and detecting characteristic proteins in the tissue. However, due to the marked similarities between head and neck cancers and lung cancers in this regard, these tests are usually inconclusive. “In order to solve this problem, we tested tissue samples for a specific chemical alteration known as DNA methylation,” explains Prof. Capper who, like Prof. Klauschen, is a Scientific Member of the DKTK in Berlin. He adds: “We know from earlier studies that DNA methylation patterns in cancer cells are highly dependent on the organ in which the cancer originated.”

Working with Prof. Dr. Klaus-Robert Müller, Professor for Machine Learning at TU Berlin, the research group employed artificial intelligence-based methods to render this information useful in practice. The researchers used DNA methylation data from several hundred head and neck and lung cancers in order to train a deep neural network to distinguish between the two types of cancer. “Our neural network is now able to distinguish between lung cancers and head and neck cancer metastases in the majority of cases, achieving an accuracy of over 99 percent,” emphasizes Prof. Klauschen. He continues: “To ensure that patients with head and neck cancers and additional lung cancers will benefit from the results of our study as quickly as possible, we are currently in the process of testing the implementation of this diagnostic method in routine practice. This will include a prospective validation study to ensure that the new method can be made available to all affected patients.”

Having worked alongside the researchers from Charité, the Director of the Berlin Center for Machine Learning (BZML), Prof. Müller, is similarly delighted at their results: “Artificial intelligence is playing an increasingly important role, not only in our daily lives and in industry, but also in natural sciences and medical research. The use of artificial intelligence is, however, particularly complex within the medical field; this is why, until now, research findings have only rarely delivered direct benefits for patients. This could now be about to change.”

September, 2019|Oral Cancer News|

HPV ‘Herd Immunity’ Is on the Rise Among Adults

Source: www.webmd.com
Author: Dennis Thompson, HealthDay Reporter

The United States could be approaching a state of herd immunity against human papillomavirus (HPV), a virus linked to several cancers.

Oral HPV infections declined by 37% among unvaccinated 18- to 59-year-old men between 2009 and 2016, according to a Sept. 10 report in the Journal of the American Medical Association.

That included a decline in infections of HPV16, the strain found in more than 9 out of 10 cases of head and neck cancer related to the virus, said senior researcher Dr. Maura Gillison, a professor of medicine at MD Anderson Cancer Center in Houston.

Researchers say men are benefitting from increased HPV vaccination rates among American women, who receive the vaccine to prevent virus-caused cervical cancer.

“In contrast to cervical cancers, we have no means by which to screen for HPV-positive head and neck cancers,” Gillison said. “The vaccine is our best hope for prevention.”

HPV vaccination has been recommended for girls since 2006 and for boys since 2011. The virus has been linked to cancers of the cervix, penis, anus, mouth and throat.

Vaccination rates among boys and girls are steadily rising, according to the U.S. Centers for Disease Control and Prevention.

About half of teens were up to date on the HPV vaccine in 2017, and two-thirds of 13- to 17-year-olds had received the first dose to start the series. On average, the percentage of teens who started the HPV vaccine series rose by 5 percentage points each year between 2013 and 2017, the CDC says.

“At least 75% vaccine coverage of boys and girls would be necessary to eradicate HPV16, the HPV type that is most likely to lead to cancer development,” Gillison said.

But vaccination rates have lagged among males.

To see if males are receiving some protection from greater HVP vaccination among females, Gillison and her colleagues reviewed U.S. federal health survey data gathered between 2009 and 2016.

They found that by 2016, about 15% of women and 6% of men had received the vaccine.

Despite lower vaccination rates among males, oral HPV infections declined from 2.7% to 1.6% in men between 2009 and 2016.

Interestingly, prevention of oral HPV infections and the head and neck cancers they cause is not listed as a reason to get the vaccine, Gillison said. No clinical trials have been undertaken to show that the HPV vaccine could prevent such cancers.

The decrease in HPV infections among the unvaccinated men is consistent with a decline in genital HPV infections among unvaccinated women between 2004 and 2014, the researchers noted.

“This study demonstrates that even with suboptimal uptake of the HPV vaccine, important gains are being made in herd immunity against oral HPV types included in the vaccine,” said Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore. He was not involved with the study.

“Oral HPV infection is a major factor in the development of head and neck cancer, and this vaccine has the potential to be game-changing as more individuals are vaccinated,” Adalja said.

HPV-positive head and neck cancers are the most rapidly rising cancers in the United States among men under age 60, Gillison said.

She called on doctors to use the data from this and other studies to promote HPV vaccination.

“I can guarantee that all of my patients diagnosed with HPV-positive head and neck cancer would exchange two or three shots for three months of toxic cancer therapy in a heartbeat,” she said.

“The HPV vaccine, together with the hepatitis B vaccine, are the two most important advances in the history of cancer prevention, period,” Gillison concluded.

September, 2019|Oral Cancer News|

Say No to Glow: Reducing the Carcinogenic Effects of ALDH2 Deficiency

Source: blogs.plos.org
Author: Catherine Chang et al.

Turning red after consuming alcohol may seem like a mere social inconvenience. Yet, behind this red complexion lies a far more serious problem. ALDH2 deficiency, more commonly known as Alcohol Flushing Syndrome or Asian Glow, is a genetic condition that interferes with the metabolism of alcohol. As a result, people with ALDH2 deficiency have increased risks of developing esophageal and head and neck cancers . Globally, this deficiency affects 540 million people — 8% of the world population. In East Asia (which includes Japan, China, and Korea), this is a much bigger problem, where 36% of the population is affected [1]. In our home, Taiwan, approximately 47% of the population carries this genetic mutation — the highest percentage in the world [2]!

Normally, ethanol is first converted to acetaldehyde (a toxic intermediate) by the enzyme alcohol dehydrogenase (ADH). A second enzyme, aldehyde dehydrogenase 2 (ALDH2), then converts toxic acetaldehyde into acetate, a compound which can be safely metabolized in the body. For people who carry wild type ALDH2*1, acetaldehyde can be broken down quickly. People with ALDH2 deficiency, however, have a point mutation which leads to the less efficient mutant ALDH2*2 [3], [4]. Enzymatic activity in ALDH2-deficient individuals can be as low as 4% compared to wild type [4], [5], [6], [7]. As a result, acetaldehyde accumulates and induces an inflammatory response that causes the skin to flush after drinking alcohol [8]. Turning red is the most obvious result of ALDH2 deficiency, but symptoms also include headaches, dizziness, hypotension, and heart palpitations [5], [9].

Acetaldehyde accumulates in ALDH2-deficient individuals. Ethanol is first converted to a toxic intermediate, acetaldehyde, by ADH, then converted to acetate by wild type ALDH2*1. The mutant form, ALDH2*2, cannot fully convert acetaldehyde into acetate, and toxic acetaldehyde accumulates as a result.

For people who are ALDH2-deficient and drink, acetaldehyde can accumulate to toxic levels. The International Agency for Research on Cancer classifies acetaldehyde associated with alcohol consumption as a Group 1 carcinogen [10]. Acetaldehyde levels over 50 μM are considered toxic and cause mutations in DNA, and studies show that the strongest effects are seen in the mouth [11], [12]. After consuming roughly 2 to 3 servings of alcohol (0.5-0.6 g alcohol/kg body weight), salivary acetaldehyde levels in ALDH2-deficient individuals reached over 100 μM, compared to normal levels of <20 μM without drinking [13], [14], [15], [16]. Because of the increased salivary acetaldehyde, people with ALDH2 deficiency are 2 to 8 times more likely to develop head and neck cancers (including oral cancer, pharyngeal cancer, laryngeal cancer, etc.), and 2 to 12 times more likely to develop esophageal cancer compared to people with normal ALDH2*1 [17-25].

Our ALDH2*1 probiotic candy significantly reduces acetaldehyde levels in simulated oral conditions. (A) The conversion of acetaldehyde to acetate by ALDH2 uses NAD+ and produces NADH. (B) Experimental setup. The candies were dissolved, the probiotic (Nissle) was lysed to release ALDH2 enzymes, and the supernatant was placed into artificial saliva. NADH concentration was measured by taking absorbance readings at 340 nm. (C) Enzymatic activity of ALDH2*1 and ALDH2*2 from the probiotic candies. A negative control of candy without Nissle was also included (gray). Under these conditions, the ALDH2*1 candies metabolized significantly more acetaldehyde compared to both the ALDH2*2 candies and the negative control. Error bars represent standard error.

To directly address the increased esophageal and head and neck cancer risks, we developed a probiotic (E. coli Nissle 1917) candy carrying recombinant human ALDH2*1 to maintain normal acetaldehyde levels in the mouths of ALDH2-deficient individuals. We tested the candy’s ability to break down acetaldehyde by measuring NADH, a byproduct of acetaldehyde metabolism. In simulated oral conditions, we observed a significant decrease in acetaldehyde levels when we added the contents of our ALDH2*1 candy (compared to the mutant ALDH2*2 or control candy). Through mathematical modeling, we also determined the exact amount of recombinant ALDH2*1 needed in each piece of candy. Our modeling shows that if a consumer eats our candy while drinking, the released ALDH2*1 will be able to combat the high salivary acetaldehyde levels and match the normally low levels found in wild type individuals.

 

Our final product, an ALDH2*1 probiotic candy!

Nearly half of Taiwan’s population is ALDH2 deficient. To combat the increased cancer risks associated with this deficiency, we developed and tested a method to regulate acetaldehyde levels in ALDH2-deficient individuals.

The TAS_Taipei iGEM Team have produced a full research article detailing their project. You can access that article here.

Note:Please note that the team’s full research article has not been peer-reviewed.

Authors: Catherine Chang, Tim Ho, Iris Huang, Justin Wu

References:
1. Brooks PJ, Enoch MA, Goldman D, Li TK, Yokoyama A. (2009). The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med. 24;6(3):e50.

2. Chang JS, Hsiao JR, Chen CH. (2017). ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective. J Biomed Sci. 24(1):19.

3. Larson HN, Weiner H, Hurley TD. (2005). Disruption of the Coenzyme Binding Site and Dimer Interface Revealed in the Crystal Structure of Mitochondrial Aldehyde Dehydrogenase “Asian” Variant. J Biol Chem. 280(34):30550-6.

4. Farrés J, Wang X, Takahashi K, Cunningham SJ, Wang TT, Weiner H. (1994). Effects of changing glutamate 487 to lysine in rat and human liver mitochondrial aldehyde dehydrogenase. A model to study human (Oriental type) class 2 aldehyde dehydrogenase. J Biol Chem. 13;269(19):13854-60.

5. Chen CH, Ferreira JCB, Gross ER, Mochly-Rosen D. (2014). Targeting Aldehyde Dehydrogenase 2: New Therapeutic Opportunities. Physiol Rev. 94(1):1-34.

6. Zhou J, Weiner H. (2000). Basis for half-of-the-site reactivity and the dominance of the K487 oriental subunit over the E487 subunit in heterotetrameric human liver mitochondrial aldehyde dehydrogenase. Biochemistry. 39(39):12019-24.

7. Gross ER, Zambelli VO, Small BA, Ferreira JCB, Chen CH, Mochly-Rosen D. (2015). A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant. Annu Rev Pharmacol Toxicol. 55:107-27.

8. Ijiri I. (1999). [Biological actions of acetaldehyde]. Nihon Hoigaku Zasshi. 53(3):285-95.

9. Lai CL, Yao CT, Chau GY, Yang LF, Kuo TY, Chiang CP, Yin SJ. (2014) Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver. Alcohol Clin Exp Res. 2014 Jan;38(1):44-50.

10. International Agency for Research on Cancer. (n.d.). List of Classifications, Volumes 1-122. Retrieved from https://monographs.iarc.fr/list-of-classifications-volumes/ .

11. Yamaguchi H, Hosoya M, Shimoyama T, Takahashi S, Zhang JF, Tsutsumi E, Suzuki Y, Suwa Y, Nakayama T. (2012). Catalytic removal of acetaldehyde in saliva by a Gluconobacter strain. J Biosci Bioeng. 114(3):268-74.

12. Kocaelli H, Apaydin A, Aydil B, Ayhan M, Karadeniz A, Ozel S, Yilmaz E, Akgün B, Eren B. (2014) Evaluation of potential salivary acetaldehyde production from ethanol in oral cancer patients and healthy subjects. Hippokratia. 18(3): 269–274.

13. Homann N, Jousimies-Somer H, Jokelainen K, Heine R, Salaspuro M. (1997a). High acetaldehyde levels in saliva after ethanol consumption: methodological aspects and pathogenetic implications. Carcinogenesis. 18(9):1739-43.

14. Yokoyama A, Tsutsumi E, Imazeki H, Suwa Y, Nakamura C, Mizukami T, Yokoyama
(2008). Salivary acetaldehyde concentration according to alcoholic beverage consumed and aldehyde dehydrogenase-2 genotype. Alcohol Clin Exp Res. 32(9):1607-14.

15. Lachenmeier DW, Monakhova YB. (2011). Short-term salivary acetaldehyde increase due to direct exposure to alcoholic beverages as an additional cancer risk factor beyond ethanol metabolism. J Exp Clin Cancer Res. 30 (3).

16. Stornetta A, Guidolin V, Balbo S. (2018). Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity. Cancers (Basel). 10(1). pii: E20.

17. Chao YC, Wang LS, Hsieh TY, Chu CW, Chang FY, Chu HC. (2000). Chinese Alcoholic Patients with Esophageal Cancer are Genetically Different from Alcoholics with Acute Pancreatitis and Liver Cirrhosis. Am J Gastroenterol. 95(10):2958-2964.

18. Yang SJ, Wang HY, Li XQ, Du HZ, Zheng CJ, Chen HG, Mu XY, Yang CX. (2007). Genetic Polymorphisms of ADH2 and ALDH2 Associated with Esophageal Cancer Risk in Southwest China. World J Gastroenterol. 13(43):5760-5764.

19. Yokoyama A, Muramatsu T, Omori T, Yokoyama T, Matsushita S, Higuchi S, Maruyama K, Ishii H. (2001). Alcohol and Aldehyde Dehydrogenase Gene Polymorphisms and Oropharyngolaryngeal, Esophageal and Stomach Cancers in Japanese Alcoholics. Carcinogenesis. 22(3): 433-439.

20. Matsuo K, Hamajima N, Shinoda M, Hatooka S, Inoue M, Takezaki T, Tajima K. (2001). Gene-Environment Interaction between an Aldehyde Dehydrogenase-2 (ALDH2) Polymorphism and Alcohol Consumption for the Risk of Esophageal cancer. Carcinogenesis. 22(6): 913-916.

21. Cui R, Kamatani Y, Takahashi A, Usami M, Hosono N, Kawaguchi T, Tsunoda T, Kamatani N, Kubo M, Nakamura Y, Matsuda K. (2009). Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk. Gastroenterology. 2009 Nov;137(5):1768-75.

22. Lee CH, Lee JM, Wu DC, Goan YG, Chou SH, Wu IC, Kao EL, Chan TF, Huang MC, Chen PS, Lee CY, Huang CT, Huang HL, Hu CY, Hung YH, Wu MT. (2007). Carcinogenetic impact of ADH1B and ALDH2 genes on squamous cell carcinoma risk of the esophagus with regard to the consumption of alcohol, tobacco and betel quid. Int J Cancer. 122(6):1347-56.

23. Wu M, Chang SC, Kampman E, Yang J, Wang XS, Gu XP, Han RQ, Liu AM, Wallar G, Zhou JY, Kok FJ, Zhao JK, Zhang ZF. (2013). Single nucleotide polymorphisms of ADH1B, ADH1C and ALDH2 genes and esophageal cancer: a population-based case-control study in China. Int J Cancer. 132(8):1868-77.

24. Huang CC, Hsiao JR, Lee WT, Lee YC, Ou CY, Chang CC, Lu YC, Huang JS, Wong TY, Chen KC, Tsai ST, Fang SY, Wu JL, Wu YH, Hsueh WT, Yen CJ, Wu SY, Chang JY, Lin CL, Wang YH, Weng YL, Yang HC, Chen YS, Chang JS. (2017). Investigating the Association between Alcohol and Risk of Head and Neck Cancer in Taiwan. Sci Rep. 7(1):9701.

25. Hiraki A, Matsuo K, Wakai K, Suzuki T, Hasegawa Y, Tajima K. (2007). Gene–gene and gene–environment interactions between alcohol drinking habit and polymorphisms in alcohol-metabolizing enzyme genes and the risk of head and neck cancer in Japan. Cancer Science. 98: 1087-1091.

September, 2019|Oral Cancer News|

Light therapy could prevent cancer treatment-related oral mucositis

Source: www.healio.com
Author: Jennifer Southall

Light therapy appeared to be an effective intervention for the prevention of painful oral mucositis associated with cancer treatment, according to results of a systematic review and meta-analysis.

“Many patients [with cancer] can now benefit from this treatment,” Praveen R. Arany, DDS, PhD, assistant professor of oral biology and biomedical engineering at University at Buffalo School of Dental Medicine, said in a press release. “The staggering breadth of clinical application for photobiomodulation therapy, or light therapy, has been both a boon and a bane for the field. Several anecdotal clinical reports have been plagued with questionable rationales and inconsistent outcomes, often relegating this treatment to a pseudoscience.”

Arany and colleagues systematically reviewed published literature in an effort to update the evidence-based clinical practice guidelines on the use of photobiomodulation — including laser and other light therapies — for the prevention and treatment of oral mucositis among patients with cancer. Patients underwent treatment with hematopoietic stem cell transplantation, head and neck radiotherapy, or head and neck radiotherapy plus chemotherapy.

Study findings supported the use of photobiomodulation therapy for the prevention of oral mucositis among certain patients with cancer.

HemOnc Today spoke with Arany about the research and the clinical implications of the findings.

Question: What prompted this research?
Answer: The current forms of cancer treatment are all essential to reduce cancer burden. Unfortunately, complications from these treatments include oral mucositis pain. This not only has a significant impact on quality of life, but also often requires treatment with opioids. The pain and discomfort can be so severe it may even interrupt treatment, which can be lethal. There are no targeted treatments for this condition. We commonly use a mouthwash, which provides relief from symptoms. In contrast to this, there is increasing evidence for the use of light therapy based on precise biological mechanisms.

Q: Can you explain the rationale for this therapy?
A: This treatment has been shown to modulate various biological signaling pathways in cells that results in a positive response, such as alleviation of pain or inflammation. In addition, our lab uncovered a mechanism involving direct activation of a growth factor capable of stimulating wound healing and tissue regeneration. A combination of these responses is responsible for therapeutic benefit in oral mucositis pain.

Q: How did you conduct the study?
A: For the systematic review and meta-analysis, we looked at previously published human clinical studies that focused on how light therapy was used for the prevention of oral mucositis pain. We used the evidence from all studies to establish guidelines, re-analyzing data from each study to develop the final recommendations.

Q: What did you find?
A: There is significant evidence to use photobiomodulation therapy, or light therapy, for the prevention and treatment of oral mucositis pain when patients undergo radiation plus chemotherapy, as well as radiation alone and HSCT. In some instances, photobiomodulation therapy also was used as a preventive measure before and during cancer treatments to reduce the risk for oral mucositis pain.

Q: What will subsequent research entail?
A: The major finding was this treatment is effective. However, most of the studies that we reviewed were performed outside of the United States — including in Brazil, Europe and Asia. It is necessary to conduct studies in the U.S. in a more controlled manner with new devices available. This will be the primary focus of future human clinical research. Preliminary research studies have addressed potential effects of this treatment on tumors and the data are very promising, noting few — if any — deleterious side effects.

Q: Is there anything else that you would like to mention?
A: This is a noninvasive and nonpharmacological approach. This is especially important in the context of opioids in cancer care. Clearly, opioids are effective drugs that have an essential role in pain management. Unfortunately, they have a high threshold for abuse. The use of photobiomodulation therapy can reduce this incidence because patients will not be exposed to opioids. Besides mucositis, photobiomodulation therapy also has been noted to reduce hair loss, depression and fatigue — all key concerns for patients undergoing cancer treatment. Hopefully, we soon will see other published reports that will lead to improved cancer care using this simple but potent new technology. – by Jennifer Southall

Reference:
Zadik Y, et al. “Systematic review of photobiomodulation for the management of oral mucositis in cancer patients and clinical practice guidelines” Support Care Cancer. 2019;doi:10.1007/s00520-019-04890-2.

September, 2019|Oral Cancer News|

Minority, low-income individuals less likely to receive oral cancer screening

Source: medicalxpress.com
Author: staff

Despite a recent dental visit, more individuals of a minority race/ethnicity and low socioeconomic status report not receiving an oral cancer screening exam, according to a study published online Aug. 20 in the American Journal of Preventive Medicine.

Avni Gupta, B.D.S., M.P.H., from Brigham and Women’s Hospital in Boston, and colleagues analyzed data from individuals aged 30 years or older who received a dental visit in the previous two years. The likelihood of intraoral and extraoral cancer screening exams was assessed, while adjusting for age, sex, race/ethnicity, education, marital status, poverty income ratio, health insurance, tobacco smoking, and alcohol consumption.

Overall, 37.6 and 31.3 percent of individuals reported receiving an intraoral and extraoral cancer screening exam, respectively. The researchers found that the likelihood of having received intraoral or extraoral cancer screening exams was lower for minority racial/ethnic groups versus white, non-Hispanics; those with less education versus more education; those who were uninsured and Medicaid-insured versus privately insured; and low-income versus high-income participants. The likelihood of being screened did not differ based on smoking status, while the likelihood was increased for alcohol consumers. Less-educated and low-income subgroups were less likely to be screened.

“Efforts to both educate patients about requesting oral cancer screening in dental offices and adequately train dental professionals on culturally sensitive communications might be an effective means to increase oral cancer screening exams among minority high-risk populations,” the authors write

August, 2019|Oral Cancer News|

Palbociclib plus cetuximab shows antitumor activity among head and neck cancer subset

Source: www.healio.com
Author: Adkins D, et al.

A combination of palbociclib and cetuximab demonstrated substantial antitumor activity among patients with platinum- or cetuximab-resistant HPV-unrelated head and neck squamous cell carcinoma, according to results of a multigroup phase 2 trial published in The Lancet Oncology.

“Currently, effective therapeutic options for patients with cetuximab-resistant HNSCC are few. Traditional chemotherapy has marginal activity, with 6% of patients or fewer achieving a tumor response,” Douglas R. Adkins, MD, professor in the oncology division of the department of medicine at Washington University School of Medicine in St. Louis, and colleagues wrote. “The most effective therapy for these patients might be pembrolizumab [Keytruda, Merck] or nivolumab [Opdivo, Bristol-Myers Squibb], which have resulted in responses in 11% to 16% of patients and median OS of 6.9 months to 8 months. Novel treatment strategies are needed for patients with recurrent or metastatic HNSCC.”

The combination of the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib (Ibrance, Pfizer) and epidermal growth factor receptor inhibitor cetuximab (Erbitux, Eli Lilly) appeared safe and tolerable in the phase 1 portion of the multicenter trial, conducted across eight U.S. university sites.

For phase 2, Adkins and colleagues divided 62 patients with HPV-unrelated HNSCC (median age, 66 years; interquartile range [IQR], 58-70; 71% men) into two groups: those who were platinum-resistant (group 1; n = 30) and those who were resistant to cetuximab (group 2; n = 32). Primary tumor sites included the oral cavity (42%) and larynx (29%), and 81% of patients had received one or two prior lines of treatment for metastatic or recurrent disease.

All participants received oral palbociclib (125 mg daily on days 1-21) and IV cetuximab (400 mg/m2 on day 1 of cycle one, followed by 250 mg/m2 once weekly) in 28-day cycles. Objective response, defined as complete and partial responses per RECIST 1.1 criteria, served as the primary endpoint.

Researchers followed patients in group 1 for a median 5.4 months (IQR, 4.4-12.1) and those in group 2 for a median 5.5 months (IQR, 4.3-8.3).

Among 28 evaluable group 1 patients, 11 (39%; 95% CI, 22-59) attained an objective response, including three complete responses. Repeat scans confirmed all but one of the responses. Half of the group 1 patients (n = 14) had stable disease and three (11%) demonstrated progressive disease. Median duration of response was 4 months (IQR, 1.8-5.6), median PFS was 5.4 months (95% CI, 3.4-7) and median OS was 9.5 months (95% CI, 5.3-16.5).

Palbociclib plus cetuximab shows antitumor activity among head and neck cancer subsetAmong 27 evaluable group 2 patients, five (19%; 95% CI, 6-38) achieved an objective response, including one complete response. Four of the responses were later confirmed. Thirteen of the group 2 patients (48%) had stable disease and nine (33%) demonstrated progressive disease. Median duration of response was 6 months (IQR, 2-15.5), median PFS was 3.7 months (95% CI, 2.9-4.3) and median OS was 6.3 months (95% CI, 4.9-10).

In each group, only one patient with a tumor response previously had received immunotherapy.

The most prevalent grade 3 to grade 4 adverse event associated with palbociclib was neutropenia, which occurred in 34% (n = 21) of all patients. The researchers did not document any treatment-related deaths.

The researchers cited various limitations to their study, including its single-group design, and noted that the results will need to be confirmed in a controlled trial with a larger sample size. They acknowledged that immunotherapy might have affected OS outcomes, and that the study design did not permit the evaluation of whether palbocilib’s antitumor activity occurred directly or by reversal of primary cetuximab resistance.

These data suggest a need for further study of palbociclib in patients with recurring or metastatic HNSCC, according to a related editorial by Garth W. Strohbehn, MD, hematology/oncology fellow at University of Chicago, and Everett E. Vokes, MD, professor of medicine and radiation oncology physician-in-chief at University of Chicago Medicine.

“However, we should be circumspect about the prospect of CDK 4/6 inhibitors as standardized, cost-effective therapies in recurrent and metastatic HNSCC,” the authors wrote. “Bringing this class of drugs to head and neck oncology clinics, as either monotherapies or immunotherapy partners, will require appropriately controlled studies linked to biomarker evaluation with both survival and cost-effectiveness endpoints.” – by Jennifer Byrne

Source:
Adkins D, et al. Lancet Oncol. 2019;doi:10.1016/S1470-2045(19)30405-X.
Strohbehn GW and Vokes EE. Lancet Oncol. 2019;doi:10.1016/S1470-2045(19)30484-X.

Disclosures: Adkins reports research funding from Pfizer as part of the work presented in the study; personal fees for advisory/consultant roles from Celgene, Cue Biopharma, Eli Lilly, Loxo Oncology, Merck and Pfizer; and research funding from AstraZeneca, Atara, Blueprint Medicine, Bristol-Myers Squibb, Celgene, CellCeutix, Celldex, Eli Lilly, Enzychem, Exelixis, Gliknik, Kura, Matrix Biomed, Medimmune Innate, Novartis, Pfizer and Polaris outside the submitted work. Please see the study for all other authors’ relevant financial disclosures. Vokes reports consultant/advisory roles with AbbVie, Amgen, AstraZeneca, Bristol-Myers, Celgene, EMD Serono, Genentech, Merck, Novartis and Regeneron. Strohbehn reports no relevant financial disclosures.

August, 2019|Oral Cancer News|

Israeli researchers find new way to eliminate drug-resistant cancerous tumors

Source: www.xinhuanet.com
Author: Wu Qin

Israeli researchers have found a way to deal with cancerous tumors that have developed drug resistance, Israel’s Ben-Gurion University (BGU) reported on Tuesday. The study was conducted by researchers from BGU and the Soroka Medical Center – both located in the southern city of Beer Sheva – and published in the journal JCI Insight.

The researchers were able to suppress a drug-resistant protein found on the wall of head and neck cancer cells, resulting in shrinkage and even disappearance of the tumors.

Head and neck cancer is considered deadly, with low survival rates, while the efficacy of existing treatments is inadequate.

One of the new treatments currently being given to patients is a drug called BYL719, which inhibits a signal transmission pathway in the cells. This pathway, called phosphoinositide 3-kinases (PI3K), is increased in head and neck cancer patients and leads to the rapid progression of the disease.

The first clinical study using the drug indicated an improvement in patients’ condition; however, many of the cancer cells developed drug resistance.

Previous research has shown that resistance to the treatment is caused by the rise of the AXL protein, which is located on the cancer cell’s wall and causes the growth and survival of the cancer cells.

The new study found that suppressing AXL expression through genetic engineering or drug inhibition restored the cancer cells’ susceptibility to the drug and significantly stopped the disease, to the extent of tumor shrinkage and disappearance.

This suppression was also effective in mice with tumors taken from head and neck patients who underwent surgeries at Soroka Medical Center.

August, 2019|Oral Cancer News|

Which HPV vaccination schedule is best: 1, 2 or 3 doses?

Source: www.precisionvaccinations.com
Author: Don Ward Hackett

A new cervical cancer prevention study of women first offered Human Papillomavirus (HPV) vaccine found that 1-dose of quadrivalent HPV vaccine was as effective as 3-doses at preventing histologically confirmed, high–grade cervical lesions.

This Australian study’s finding published online on July 15, 2019, supports the hypothesis that the 1-dose HPV vaccination schedule may be a viable strategy when working towards the global elimination of cervical cancer.

These researchers said ‘If one dose could prevent precancerous cervical lesions, then global cervical cancer prevention would be greatly facilitated.’

This is an important goal since about 90 percent of cervical cancer cases are caused by HPV. This study included 250,648 women in Australia with 19.5 percent unvaccinated, 69.8 percent had received 3-doses, 7.3 percent 2-doses, and 3.4 percent just 1-dose of the HPV vaccine.

This study’s limitations include some degree of under–linkage and inaccurate data linkage because Australia does not have a unique national identifier, which impacts the classifications of vaccinated women as unvaccinated.

Additionally, these researchers said ‘we believe that these data support decision-makers to consider how a 1-dose HPV vaccination schedule, or a planned schedule with a 3–5 year interval between doses, could reduce vaccine demand globally, which currently exceeds vaccine supply.’

But the Gardasil 9 vaccine manufacturer appears to be resolving this supply/demand imbalance. During July 2019, Merck said it is spending $1.68 billion, opening 2 new Gardasil production plants, and adding 525 related jobs.

To clarify the Gardasil 9 vaccine dosing schedule, the Centers for Disease Control and Prevention (CDC) publish the following information:

Who should still receive a 3-dose schedule?
The CDC continues to recommend a 3-dose schedule for persons starting the HPV vaccination series on or after the 15th birthday, and for persons with certain immunocompromising conditions. The 2nd vaccine dose should be given 1–2 months after the 1st dose, and the 3rd dose, should be given 6 months after the first dose.

Who should receive just 2-doses?
Two doses of the HPV vaccine are recommended for all boys and girls at ages 11-12; the vaccine can be given as early as age 9. If you wait until they’re older, they may need three doses instead of two.

In the USA, HPV vaccines have been licensed for use among women since 2006 and among men since 2010.

HPV infections are so common that nearly all men and women will get at least one type of HPV at some point in their lives. Nearly 80 million Americans are currently infected with some type of HPV, says the CDC. About 14 million Americans, including teens, become infected each year. HPV is spread through intimate skin-to-skin contact. You can get HPV by having vaginal, anal, or oral sex with someone who has the virus.

Cervical cancer is the only type of HPV cancer with a recommended screening test. The other types of HPV cancer may not be detected until they cause health problems. HPV vaccination helps prevent these cancers by preventing infections that cause these cancers, says the CDC. HPV vaccines, like any medicine, can cause side effects, which you are encouraged to report to the CDC or a healthcare provider.

August, 2019|Oral Cancer News|

How clean is your toothbrush?

Source: versionweekly.com
Author: rajathe

Dental care has become increasingly difficult in this fast-paced era and due to the scarcity of time. Therefore, following minute steps or procedures could be highly effective to evade colossal dental problems and save time in the long run. And an effective measure towards this, is to sanitize your toothbrush. The mouth contains bacteria and so does the bathroom. So, it is impossible for the toothbrush to stay sanitized with just a water wash after cleansing the teeth.

Toothbrush sanitizing ¡s not synonymous to sterilizing. Sanitation helps in getting rid of almost 99.9 percent of bacteria whereas sterilization kills living organisms. Brushing our teeth is quite vital ¡n our day-to-day life in order to keep and maintain personal oral hygiene and for the removal of plaque. And for this, certain appropriate measures need to be taken.

As a result of a recent research, scientists have found that toothbrushes engulf microorganisms that can result in an oral, dental or infection of some kind. We are acquainted with the fact that an oral cavity is an umbrella to hundreds of different types of microorganisms, which in a way gets transferred to the toothbrush. There is also a probability that the microorganisms in the environment make room for itself on the toothbrush on its own. Also, toothbrushes may even have bacteria on them right out of the box since they are not required to be sold in a sterile package.

Toothbrush Hygiene
Our schedules are so busy that we have time for nothing and that leads to the negligence of petty issues like washing toothbrush properly, which in turn contributes to dental problems. The majority of us simply clean or scrub the head of the toothbrush only once after we complete the brushing process. It would be more hygienic if the toothbrush could be rinsed in lukewarm water to get rid of food debris and leftover toothpaste in the bristles.

Clinically there is no evidence that if a toothbrush is soaked in antibacterial mouthwash ¡t would deliver positive results but it won’t disrupt the toothbrush in any way either.

The proper procedures for sanitizing the toothbrush is as follows:

  • Keep the toothbrush immersed in the mouthwash and warm water mix
  • Take the brush out of the solution after 15 minutes
  • Don’t keep it immersed for too long, or it will destroy the bristles
  • Don’t reuse the mixed solution as it defeats the cleansing or sanitizing process

Gum disease (periodontal) and health complications share a strong alliance and result in hazardous diseases such as stroke, heart disease, etc. It also affects pregnant women in terms of low birth weight and pre-term babies. Research shows that 90 per cent of diseases and health hazards are likely to have oral manifestations like swollen mouth ulcers, gums, excessive gum problems, and dry mouth. Other diseases include diabetes, leukaemia, pancreatic cancer, oral cancer, kidney disease and heart disease.

A dentist may be a saviour if a proper diagnosis can be conducted from the roots in its infant stages. Routine visits to a dentist can also help in keeping one’s smile attractive. This would also enable dentists to foretell a lot more about one’s health which includes whether or not one may develop a disease like diabetes in the near future.

Research has proven that our mouth acts like a mirror that reflects the condition of the body. On the contrary, poor oral health, heralds a plethora of health problems. And, good oral health keeps diseases from occurring.

Recommendations
According to dentists, the growth and abundance of bacteria on toothbrushes requires dark, warm and humid conditions. Veiling a toothbrush in a dosed area can invite problems. One should always keep the toothbrush dry, airy and in a holder that does not come in contact with the bristles or other toothbrushes. The toothbrush should be replaced every three to four months. Also, keep in mind that the sharing of toothbrushes contribute to the problem on a massive scale.

Precautions
If anyone in the family gets infected because of a contagious agent, following some preventive measures can help. Replacing toothbrushes every three to four months, purchasing expendable toothbrushes and using an antibacterial mouthwash for rinsing and soaking is beneficial. Also, you need to know that a UV sanitizer will not result in a maximum removal of germs. Another flaw in the usage of UV sanitizer is that the ultraviolet light may destroy the bristles.

August, 2019|Oral Cancer News|

Psychological impact of head and neck cancers

Source: pharmafield.co.uk
Author: Emma Morriss

Bristol-Myers Squibb (BMS), in partnership with patient groups The Swallows and the Mouth Cancer Foundation, have announced the results from a patient survey into the psychological impact of head and neck cancers. The research explored the long-term burden of treatment on head and neck cancer patients.

After undergoing treatment for head and neck cancer, which can include surgery, chemotherapy or radiotherapy, many patients report an ongoing impact on their day-to-day life. However, 55% of the 118 patients surveyed indicated they did not receive the right level of information in preparation for the complications encountered from treatment.

There are around 11,900 new head and neck cancer cases in the UK every year and the incidence of head and neck cancer has increased by 32% since the early 1990s.

Following treatment, the survey showed 56% of patients had problems with simple things like swallowing, often experiencing severe pain, while two-thirds of patients experienced changes in their voice or speech. The survey also showed self-reported change from pre- to post- treatment in vital areas including a drop in the ability to communicate (37%), memory loss (21%), and trouble sleeping (20%).

As well as physical symptoms, treatment can have severe implications on mental health too. 52% of patients reported feelings of anxiety before treatment, which only reduced to 48% following treatment. However, emotional and psychological support was only offered to 46% of patients.

A majority of patients did receive access to a clinical nurse specialist, however there was still 23% who were not offered this service. Clinical nurse specialists use their skills and expertise in cancer care to provide physical and emotional support, coordinate care services and inform and advise patients on clinical as well as practical issues, which have been shown to lead to more positive patient outcomes.

“These results show the impact treatment may have on head and neck cancer patients. The continued problems and symptoms experienced by patients after treatment significantly impacts patients’ daily life. We also know physical disfigurement can increase social anxiety. It is important that we raise the awareness of this and work together to provide solutions to improve and support patient outcomes.” said Mouth Cancer Foundation, Clinical Ambassador, Mr Mahesh Kumar.

“With the incidence of head and neck cancers increasing, it is vital we understand what we can do to help patients. We are so pleased to have worked in collaboration with BMS and the Mouth Cancer Foundation to help raise awareness of this disease and understand where patients might need more help to reduce the impact on their lives. We know head and neck cancers, and the associated complications, do not get a lot of attention so it’s crucial for awareness days such as World Head and Neck Cancer Day to be used to shine a light on the disease. By doing so, it will help to improve detection, treatment and outcomes for patients.” commented Chris Curtis, Chairman of The Swallows.