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Absent p53, oral cancers recruit and reprogram nerves to fuel tumor growth

Source: medicalxpress.com
Author: by University of Texas M. D. Anderson Cancer Center

Loss of an important tumor-suppressing gene allows head and neck cancer to spin off signals to nearby nerves, changing their function and recruiting them to the tumor, where they fuel growth and cancer progression, researchers from The University of Texas MD Anderson Cancer Center report in the journal Nature today.

By cracking the mechanism that launches neuronal invasion of tumors, a known marker of poor prognosis for patients, the team has uncovered possible avenues to block the process, including the use of drugs commonly used to treat blood pressure and irregular heartbeat.

“Tons of studies show that patients who have lots of nerves in their tumor are doing worse—recurrence rates are higher, survival is shorter,” says co-first author Moran Amit, M.D., Ph.D., assistant professor of Head and Neck Surgery. “Nerve endings found in surgically removed tumors can’t be easily characterized or tracked back to their source, so it’s been a neglected field, a neglected hallmark of cancer.”

“When surgeons remove head and neck cancers and find a high degree of nerve invasion, post-surgical radiation sometimes is effective,” said co-senior author Jeffrey Myers, M.D., Ph.D., chair of Head and Neck Surgery. “But we really haven’t understood whether the tumor was growing into the nerves or the nerve growing into the tumor and what signaling drove those interactions.”

Co-senior author George Calin, M.D., Ph.D., professor of Experimental Therapeutics and an expert on non-coding RNAs added that the paper “puts together for the first time the mechanism of involvement of neurons in tumor generation, a new hallmark of cancer.”

The team found that the neurons that invade the tumor are adrenergic nerves, which are involved in stress response. These nerves’ neurotransmitters—adrenaline (epinephrine) and noradrenaline (norepinephrine) – are susceptible to drugs known as alpha and beta blockers, long used to treat high blood pressure and irregular heartbeats.

In the study, mice with oral cancer treated with the adrenergic blocker carvedilol had sharply lower tumor growth and cancer cell proliferation. Myers says the team is working to develop clinical trials of adrenergic blockers, most likely in combination with other drugs.

“We used to think that nerves are just randomly growing into the tumor, and that’s completely wrong,” Amit says.

Loss of p53 flips a microRNA switch to re-program neurons
Damage to the p53 gene is a major characteristic of head and neck cancers. A tumor-suppressing master transcriptional gene that governs the expression of many other genes, p53 is also mutated in a variety of cancers.

The team found high density of neurons in p53-deficient mouse models and human xenograft tumors of oral cavity squamous cell carcinoma (OCSCC) as well as increased neural growth in clusters of nerves exposed to p53-deficient OCSCC.

The researchers also discovered that oral cancer communicates with nerves by launching extracellular vesicles—membrane balls that carry various molecules—packed with microRNAs to connect with the nerves. The miRNA cargo varied depending on p53 status of the tumors.

“When you have intact p53, you have specific types of microRNAs that keep neurons in a quiescent state,” Amit says. “Once you lose p53, the micro RNA population within the exosomes changes and then you get positive signals to induce nerve growth.”

Investigators identified adrenergic nerves extending into the tumors and suspected they were extensions of pre-existing nerves. However, when they cut adrenergic nerves before inducing tumors in mice, adrenergic nerves still appeared in the tumor and the tumors still grew.

Subsequent experiments showed the miRNAs in vesicles from p53-deficient tumors were connecting instead with existing sensory nerves, a different nerve type, and actually changing them into the adrenergic type. These neo-adrenergic nerves then invaded the tumor.

To confirm this finding, they cut sensory nerves ahead of inducing p53-deficient tumors in mice. Without the sensory nerve targets for the vesicles, the tumor shrank.

Impact of adrenergic nerve density on patients
To validate the impact of their findings on people with OCSCC, the researchers analyzed the presence of adrenergic nerves in the tumors of 70 patients who were treated at MD Anderson. Adrenergic nerve density in the tumors was associated with lower recurrence-free survival and overall survival.

The statistical significance of the adrenergic nerve densities held up in multivariable analysis after adjustment for other variables, such as age, sex, cancer stage, surgical margin status, overall neuronal invasion and treatment type. They suggest nerve density measurements merit exploration as a predictive marker of oral cancer aggressiveness. Myers, Calin, Amit and colleagues believe the paper opens up a new area for cancer researchers.

“Neurons control everything that we do in everyday life,” Amit says. “They control our voluntary and involuntary bodily functions, so it’s intuitive that they are involved in cancer.”

February, 2020|Oral Cancer News|

FDA grants fast track designation to NBTXR3 in locally advanced head and neck cancers

Source: www.targetedonc.com
Author: Nichole Tucker

An FDA Fast Track Designation was granted to the first-in-class radioenhancer NBTXR3 with or without cetuximab (Erbitux) for the treatment of patients with locally advanced head and neck squamous cell cancer who are not eligible for platinum-based chemotherapy, according to a press release from Nanobiotix.1

NBTXR3 showed preliminary signals of antitumor activity in this patient population in a phase I study of 12 patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). Specifically, 10 of the 11 evaluable patients had a complete response (CR) or a partial response to treatment, which included 2 CRs at dose levels ≤10% and 5 CRs at dose levels >10%.2

Treatment with NBTXR3 was also found to be safe and tolerable in patients with HNSCC. There were no serious adverse events or dose-limiting toxicities (DLTs) observed, which allowed patients to continue with their treatment as planned. The adverse events found to be related to injection with NBTXR3 included grade 1/2 injection pain and tumor hemorrhage.

Patients in the study received either a single intratumor injection or single-arterial injection of NBTXR3 on day 1 followed by intensity-modulated radiation therapy 2 hours later, which lasted for up to 7 weeks. Radiotherapy was continued in all patients unless their tumor did not shrink by 50% of the baseline size. Those patients who did achieve the tumor shrinkage goals then received salvage tumor surgery.

The primary end point of the study was the determination of the recommended dose of the drug and early dose-limiting toxicities. Secondarily, the investigators evaluated safety and tolerability, objective response rate, local progression-free survival, progression-free survival, kinetics profile, and the feasibility of local administration of NBTXR3.

Patients aged 70 years or older who were intolerant to cisplatin or cetuximab or that could not receive the combination of chemoradiation were eligible for treatment in the study. Patients were required to have histologically or cytologically confirmed squamous cell carcinoma of the oral cavity or oropharynx; have a T3 or T4 primary tumor or stage III or IVA disease; be clinically eligible for intra-arterial or intratumor implantation by injection; have a Karnofsky performance status ≥70; and have adequate bone marrow, kidney, and liver function.

The study excluded patients who had prior radiotherapy; tumor-related dyspnea; prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer; concurrent treatment with any other anticancer therapy; tumor-related dyspnea; tumor ulceration which implies vascular risk; non-measurable disease; and those with infections and illnesses that may have interfered with treatment.

The data from this trial are part of a proof-of-concept for launching a phase III study in which NBTXR3 will undergo further assessment for the treatment of head and neck cancers.3

References
1. Nanobiotix announces fast track designation granted by US FDA for investigation of first-in-class nbtxr3 in head and neck cancer [news release]. Cambridge, Massachusetts: Nanobiotix; February 10, 2020. https://bit.ly/2vpwDQU. Accessed February 10, 2020.
2. Le Tourneau C, Calugaru V, Jouffroy T, et al. A phase 1 trial of NBTXR3 nanoparticles activated by intensity-modulated radiation therapy (IMRT) in the treatment of advanced-stage head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2017;35(suppl 5;abstr 6080). doi: 10.1200/JCO.2017.35.15_suppl.6080.
3. Nanobiotix announces plan for global phase III head and neck cancer registration trial along with overall development update [news release]. Cambridge, Massachusetts: Nanobiotix; January 7, 2020. https://bwnews.pr/2Hczpfc. Accessed February 10, 2020.

February, 2020|Oral Cancer News|

Surveillance of ctDNA in HPV-positive head and neck cancers may predict recurrence

Source: www.targetedonc.com
Author: Nichole Tucker

The detection of circulating tumor DNA (ctDNA) in human papillomavirus (HPV) with an experimental blood test has been associated with high positive predictive value (PPV) and negative predictive value (NPV) for identifying disease recurrence in HPV-positive oropharyngeal cancer, according to a press release from the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center.1

“The major utility of this test is it’s going to improve our ability to monitor patients after they complete treatment,” said Bhisham Chera, MD, associate professor in the UNC School of Medicine Department of Radiation Oncology. “Currently, our methods to assess whether the cancer has recurred are invasive, expensive and not always accurate.”

In a prospective biomarker clinical trial published in the Journal of Clinical Oncology, investigators obtained 1006 blood samples for their analysis, 999 of which were evaluable for plasma circulating tumor human papillomavirus DNA (ctHPVDNA). The goal was to determine if surveillance of ctHPVDNA can facilitate earlier detection of recurrence compared with normal clinical follow-up.2

Patients were followed for a median of 23.7 months (range, 6.1-54.7 months), and out of 115 patients, 13% developed disease recurrence (n = 15). Of these recurrences, 1 was local only, 1 was regional only, 10 were distant only, 1 was local and distant, and the remaining 2 were regional and distant. Following treatment, 87 patients had undetectable ctHPVDNA, and none developed recurrence (95% CI, 96%-100%). The development of a positive ctHPVDNA occurred in 28 patients during post-treatment surveillance.

The median time to abnormal ctHPVDNA signal was 12.3 months after complete chemoradiotherapy (CRT; range, 2.6-29.1 months). Sixteen patients had 2 consecutive positive ctHPVDNA results, and 15 of those patients developed biopsy-proven recurrence. The 2 ctHPVDNA blood tests that were consecutively positive had a PPV of 54% (95% CI, 0.339-0.725). A 3.9-month median lead time between ctHPVDNA positivity and biopsy-proven recurrence was observed (range, 0.37-12.9). the actuarial 2-year response-free survival (RFS) rate was 30% in patients who had an abnormal blood test during post-treatment surveillance compared with 100% among the remaining participants (P <.001).

In the study, CRT included cetuximab 250 mg/m2, carboplatin AUC 1.5, and paclitaxel 45 mg/m2. Patients received intravenous chemotherapy during intensity-modulated radiotherapy treatment, which was given weekly. There were 6 doses of chemotherapy in total.

The secondary end points of the study were local control rate, regional control rate, local-regional control rate, distant metastasis-free survival, OS, head and neck quality of life assessments, and speech and swallowing function.

Patients aged 18 years and older were eligible to enroll if they had T0-3, N0 to N2c, M0 squamous head and neck cancer, HPV and p16 positivity, radiologically confirmed hematogenous metastasis within 12 weeks before treatment, and ECOG performance status of 0 to 1, and adequate bone marrow, renal, and hepatic function. Individuals with prior history of radiation to the head and neck, head and neck cancer, those with unresectable disease, severe comorbidity, or known human immunodeficiency virus, or those taking disease-modifying rheumatoid drugs were excluded from the study.

Based on this research the investigators reported a 99% accuracy in confirming whether or not patients remained recurrence-free with their screening method, compared with other methods. For patients who had 2 HPV-positive blood tests, the accuracy was said to be 94%.1

“With this new technology, it offers a noninvasive way to accurately monitor patients for cancer recurrence,” Chera said. “In the long run, blood-based surveillance could be more effective, and possibly help us to detect cancer sooner.”

References
1. Study finds blood test accurately tracks HPV-linked head and neck cancer [news release]. Chapel Hill, North Carolina: University of North Carolina Lineberger Comprehensive Cancer Center; February 4, 2020. https://bit.ly/2tzlw7x. Accessed February 6, 2020.
2. Chera BS, Kumar S, Shen C, et al. Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer. J Clin Oncol. doi: 10.1200/JCO.19.01598.

February, 2020|Oral Cancer News|

Botanical drug is shown to help patients with head and neck cancers

Source: newsroom.ucla.edu
Author: Duane Bates, UCLA Research Brief

Findings
In a UCLA-led phase I clinical trial, a new plant-based drug called APG-157 showed signs of helping patients fight oral and oropharyngeal cancers. These cancers are located in the head and the neck.

APG-157 is made up of multiple compounds produced by plants, including curcumin. UCLA Jonsson Comprehensive Cancer Center researchers found that treatment with this botanical drug resulted in high concentrations of curcumin and its byproducts circulating in the blood and absorbed by tumor tissues within three hours after being taken orally.

APG-157 reduced the concentration of cytokines — proteins involved in inflammation — in the saliva when administered to cancer patients. The therapy also reduced the relative abundance of Bacteroides species, a group of gram-negative bacteria. Gram negative refers to a group of dangerous bacteria that have an outer layer which hides them from the immune system. The relative abundance of gram-negative bacteria compared to the presence of other types of bacteria is correlated with oral cancer.

APG-157 also resulted in the expression of genes that are associated with attracting immune system T cells to the tumor area. This therapy could have a beneficial effect when used in combination with immunotherapy drugs that help immune system T cells recognize and kill tumors.

The treatment did not have any adverse effects on the study’s participants.

Background
Cancers of the head and neck account for 4% of all cancers. About 650,000 new cases are reported each year around the world. People with advanced head and neck cancers have a low survival rate and current treatment options such as surgery, radiation and chemotherapy can have adverse effects. Therefore, more effective and less toxic therapies are needed to help improve the quality of life and outcome for those with these cancers.

APG-157 is a botanical drug developed under the FDA’s Botanical Drug Guidance, which includes requirements for production of plant-based therapies that are marketed as prescription medications. The drug is made up of botanical compounds including curcumin from the Curcuma longa plant, which is commonly referred to as turmeric and is a member of the ginger family.

Curcumin is one of the medicinally active or therapeutic molecules that has been tested as a possible treatment to help fight multiple cancers because it is an antioxidant that reduces swelling and inflammation. However, there is poor absorption into the bloodstream when curcumin is taken orally. In this study, UCLA researchers found that when APG-157 is taken through oral mucosal absorption, patients have high levels of curcumin circulating in their blood and absorbed by cancer tissues.

Method
UCLA researchers conducted the study of APG-157 comparing 12 people who had oral and oropharyngeal cancer with a control group of 13 people who did not have cancer. The reason both the people with cancer and without cancer were part of the study was to show that the drug was not toxic to either people with cancer or those without cancer.

The medication was given each hour for three hours and was delivered as a lozenge that slowly dissolved in the mouth. Blood and saliva samples were collected beforehand — each of the three hours the medication was administered — and 24 hours after the last dosage. The medication was given to 12 people (some who had cancer and some who did not) and a placebo was given to 13 people. Blood and electrocardiogram tests did not show increased toxicity in the people who took the active medication in comparison with the people who took the placebo, regardless of whether they had cancer or not.

For the cancer patients who took the medication, there was a decrease in Bacteroides and an increase in T cells in the tumor tissue as compared to cancer patients who took the placebo. Neither the subjects nor the investigators knew whether the drug or a placebo was given when reviewing the blood and saliva test results of the blinded study.

Impact
APG-157 is a botanical drug that has low toxicity. It works effectively to reduce inflammation that contributes to the growth of cancer cells. It also attracts T cells to the tumor micro-environment. When used in combination with immunotherapy drugs, APG-157 might have the ability to make the immune system more effective in attacking head and neck cancers. With potential to inhibit the growth of Bacteroides species, APG-157 could also improve cancer therapy through oral microbial changes.

Authors
Dr. Marilene Wang from UCLA was the corresponding author. Other UCLA authors include: Saroj Basak, Alexander Yoon, Marco Morselli, Chan Jeong, Anela Tosevska, Tien Dong, Hassan Nasser, Venu Lagishetty, Rong Guo, Dipti Sajed, Kym Faull, Jonathan Jacobs, Matteo Pellegrini, Daniel Sanghoon Shin and Eri Srivatsan. Authors from Uniformed Services University of the Health Sciences in Maryland and Aveta Biomics also participated in the study.

Journal
The research is published in CANCER, a journal published by the American Cancer Society.

Funding
Funding for the study was provided by Aveta Biomics.

Disclosures
Authors Parag Mehta, Sharmila Mudgal and Luis Avila are employed by Aveta Biomics. They had no role in the recruitment of people for this study or the collection and analyses of the samples. They, as with all the authors, did not have any information on the subjects, therapy or placebo given until completion of the study.

February, 2020|Oral Cancer News|

Curcumin has anti-proliferative and pro-apoptotic effects on tongue cancer in vitro: a study with bioinformatics analysis and in vitro experiments

Source: www.dovepress.com
Authors: Chao Ma,1 Zongming Zhuang,1 Qisheng Su,2 Jianfeng He,1 Haoyu Li1

Purpose:
This study focused on the mechanism underlying the therapeutic effect of curcumin against tongue cancer (TC). Accepted for publication in Drug Design, Development and Therapy, Volume 14.

Methods:
Target genes of TC and curcumin were identified, respectively. Three datasets of TC from Gene Expression Omnibus were included, and then the differentially expressed genes were collected. After combing the data from The Cancer Genome Atlas, bioinformatics analyses were performed to investigate hub genes in terms of the functions and correlations. The proliferation and migration of TC cells were evaluated with CCK-8 assay and scratch wound healing assay, respectively. Cell apoptosis was evaluated by TUNEL assay, flow cytometry and Western blot. Cell cycle was determined by flow cytometry.

Results:
In this study, 15 hub genes were identified (TK1, TDRD3, TAGLN2, RNASEH2A, PDE2A, NCF2, MAP3K3, GPX3, GPD1L, GBP1, ENO1, CAT, ALDH6A1, AGPS and ACACB). They were mainly enriched in oxygen-related processes, such as oxidation-reduction process, reactive oxygen species metabolic process, hydrogen peroxide catabolic process, oxidoreductase activity and Peroxisome-related pathway. The expression levels of hub gene mRNAs were positively correlated with each other’s expression levels. None of the hub genes was correlated with prognosis (P > 0.05). Curcumin significantly inhibited CAL 27 cell proliferation and migration (P < 0.05), but significantly promoted cell apoptosis (P < 0.05). Conclusion: Curcumin has potential therapeutic effect on treating TC by suppressing cell proliferation and migration, as well as promoting apoptosis through modulating oxygen-related signaling pathways.

Notes:
1 Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China;
2 Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China

February, 2020|Oral Cancer News|

What parents need to know about the HPV vaccine

Source: www.news-medical.net
Author: University of Chicago Medical Center, reviewed by Kate Anderton, B.Sc. (Editor)

The vaccine that prevents infection from human papillomavirus (HPV) is nothing short of a medical marvel. “It’s one of the most effective vaccines we have against any disease or infection. And it prevents cancer,” said Andrea Loberg, MD, clinical associate of obstetrics and gynecology.

Pre-teens and teens who are vaccinated against HPV can be spared some of the deadliest, most disfiguring and hard-to-treat cancers-;those of the cervix, vagina, vulva, penis, anus, mouth and throat. Over 90% of cancers caused by HPV can be prevented-;29,000 cases of cancer per year-;with the HPV vaccine.

Concerns about sexual promiscuity
To some parents, however, the HPV vaccine may be an uncomfortable reminder that their child will be moving into adulthood and may choose to express his or her sexuality. HPV is transmitted by oral, vaginal and anal sex and other intimate skin-to-skin contact, and it is extremely prevalent; about 80% of people will be exposed to the virus in their lifetime.

Condoms reduce but don’t eliminate the risk of HPV infections because the virus lives in both oral and genital tissues. Condoms do not cover the entire genital area of either gender. Nor are same-sex female partners protected from contracting the virus, which often causes no symptoms until precancerous lesions or cancer show up years later. “It’s hard for parents to think about our kids becoming sexually active, but we also want them to have fulfilling lives,” said Truehart, whose own two teenagers have received the HPV vaccine. “We want to make sure they are protected before they start having sex.”

The recommended age for receiving the HPV vaccine is 11 or 12, when children are also scheduled to receive the Tdap vaccine (tetanus, diphtheria and pertussis) and the meningitis vaccine. But the two-dose vaccine-;the second dose is given six to 12 months after the first-;can be given to children as young as nine. Teens older than 15 and men and women need three doses of the vaccine to develop an immunity against HPV.

“Pre-teens have a more robust response to the vaccine and generate enough antibodies to protect against HPV after two immunizations, whereas older kids and adults need three doses to get the same immune response,” said Truehart. Another reason not to delay getting the HPV vaccine: an older teen may not want to wait six months or more to be fully immunized against HPV once he or she is on the verge of becoming sexually active. “It’s important for kids to be immunized before they are exposed to HPV,” Truehart said.

Not just for girls
When the U.S. Food and Drug Administration approved the HPV vaccine in 2006, it was recommended for girls and women to protect against cervical cancer. Three years later, the vaccine was approved for boys and men, based on evidence that males are also susceptible to HPV-related cancers. “Cancers caused by HPV affect women and men in equal numbers,” said Loberg. “Each year, there are approximately 10,800 cases of cervical cancer diagnosed in women, and 9,600 cases of head and neck cancer diagnosed in men.” And while there is a screening test for cervical cancer to catch and treat it early, there are no such screening tests for any of the other HPV-related cancers. And because most HPV infections are asymptomatic, people may be unwittingly transmitting the infection to their sexual partners.

HPV also causes genital warts which, although not harmful in most people, can be embarrassing and unsightly. In some cases, however, genital warts can be extremely painful and may even require surgery to remove them. For people with autoimmune disorders or who take medications that compromise their immune system, genital warts can be very difficult to manage, said Loberg. Out of more than 150 strains of HPV, the vaccine targets the most prevalent and harmful ones: two strains that cause genital warts and seven strains that cause various types of cancer.

No serious side effects
Despite HPV being the most common sexually transmitted infection, HPV-related cancers are relatively uncommon because in about 90% of people exposed to HPV, their immune systems clear the virus from their bodies before it causes cancer or precancer. “But we don’t know which individuals will develop a persistent infection, so why take that gamble when cancer can be the consequence?” said Loberg.

When parents ask whether the HPV vaccine is safe, Loberg’s ready answer is that “it’s incredibly safe.” More than 270 million doses of the HPV vaccine have been distributed worldwide since 2006, and there have been no serious side effects. One study that examined data from more than 56 million doses of HPV vaccine administered in the U.S. found that some girls became dizzy or fainted 15 minutes after receiving the vaccine. “That is the only side effect that we see,” other than mild side effects typical of other vaccines, such as fever, headache, and pain and redness at the injection site, said Loberg.

Pediatricians and primary care providers should be recommending the HPV vaccine for children, but if not, parents should bring it up.

“There is absolutely no downside to getting the HPV vaccine, and the upside is preventing your child from getting a deadly or disfiguring cancer,” she said.

January, 2020|Oral Cancer News|

Ask the Doctors: Dysphagia common in elderly

Source: journalstar.com
Author: askthedoctors@mednet.ucla.edu

Dear Doctor: Why do the elderly often have a hard time swallowing, and sometimes experience a feeling that food is stuck in their throats? I heard there’s a procedure to stretch the throat. Does it help?

Dear Reader: The condition you’re asking about is known as dysphagia, which refers to difficulty in swallowing. Patients may have trouble starting a swallow, or problems with the esophagus, which is the muscular tube that connects the throat with the stomach.

The origins of the disorder fall into several basic categories. There are neurological causes, such as stroke, Parkinson’s disease, multiple sclerosis, dementia and head injury. Certain muscular conditions can affect the proper functioning of the esophagus. So does obstruction, which can result from a narrowing of the esophagus, or from inflammation. These can be caused by head and neck cancers, radiation therapy, tuberculosis and chronic acid reflux.

Although dysphagia can affect people of all ages, you’re correct that it’s seen more often in older adults. This is commonly due to age-related changes in the body, such as loss of muscle tone, mass and strength, and changes to nerve function. Still, dysphagia is not considered to be a normal sign of aging.

Understanding dysphagia starts with the mechanics of swallowing. We tend to think of it as the “gulp” that empties the mouth. But that’s just the first step of a complex process.

A successful swallow moves the contents of your mouth through the throat, and all the way down to the stomach. This happens when a ring of muscles known as the upper esophageal sphincter and located at the lower end of the throat, open. Next, coordinated contractions along the length of the esophagus send the food to a second ring of muscles known as the lower esophageal sphincter. This leads to the stomach. At the same time, muscles and specialized structures within the throat prevent anything from getting into the nose, voice box and windpipe.

Symptoms of dysphagia can include pain while swallowing, struggling or being unable to swallow, feeling as though food is stuck in the esophagus, coughing or gagging when trying to swallow, regurgitation or frequent heartburn. Some people may experience drooling or develop a hoarse voice. Diagnosis of the condition includes a physical exam and any of a variety of tests that may include X-rays, muscle tests and swallowing studies.

Treatment depends on the specific cause of the condition. Patients may be asked to change their diet, use certain exercises and techniques that help with swallowing coordination or manage acid reflux with medication.

The procedure you asked about, known as esophageal dilation, is useful when dysphagia results from a narrowing of the esophagus. It involves the use of an endoscope and either plastic dilators or a special balloon to slowly and gradually stretch the esophagus. Complications, which are rare, include bleeding and tears or holes in the esophagus. In most cases, the patient is able to resume normal eating and drinking the following day.

January, 2020|Oral Cancer News|

Study explores correlation between Medicaid expansion and disease stage and time to treatment initiation in head and neck cancer

Source: www.docwirenews.com
Author: Kaitlyn D’Onofrio

A new study examined the relationship between Medicaid expansions as part of the Affordable Care Act (ACA) with stage at diagnosis and time to treatment initiation (TTI) for head and neck squamous cell carcinoma (HNSCC) patients.

“Medicaid expansions as part of the Patient Protection and Affordable Care Act (ACA) are associated with decreases in the percentage of uninsured patients who have received a new diagnosis of cancer. Little is known about the association of Medicaid expansions with stage at diagnosis and time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC),” the study authors explained.

The study authors performed a retrospective cohort study at Commission on Cancer-accredited facilities. A total of 90,789 HNSCC patients aged between 18 and 64 years who received a cancer diagnosis between Jan. 1, 2010, and Dec. 31, 2016, were identified using the National Cancer Database. The primary outcomes were health insurance coverage, stage at diagnosis, and TTI. The researchers figured out the absolute percentage change in health insurance coverage, crude and adjusted difference in differences (DD) in absolute percentage change in coverage, stage at diagnosis and TTI before (2010-2013) and after (2014-2016) the ACA took effect for Medicaid expansion and nonexpansion states.

Of the 90,789 HNSCC patients (mean [SD] age, 54.7 [7.0] years) included in the analysis, the majority (n = 70,907, 78.1%) were male, and most (n = 72,911, 80.3%) were non-Hispanic white. More than half (n = 52,142, 57.4%) were aged between 55 and 64 years, and about three-fifths (n = 54,940, 60.5%) lived in a Medicaid expansion state. Following the implementation of the ACA, the percentage of HNSCC patients with Medicaid, compared to nonexpansion states, increased more in expansion states (adjusted DD, 4.6 percentage points; 95% confidence interval [CI], 3.7–5.4 percentage points). In expansion states, compared to nonexpansion states, there was a greater increase in the percentage of patients with localized disease (defined as American Joint Committee on Cancer stage I-II) at diagnosis in the overall cohort (adjusted DD, 2.3 percentage points; 95% CI, 1.1–3.5 percentage points) as well as a subset of patients with nonoropharyngeal HNSCC (adjusted DD, 3.4 percentage points; 95% CI, 1.5–5.2 percentage points). In the entire study cohort, there was no significant different in mean TTI between expansion and nonexpansion states (adjusted DD, –12.7 percentage points; 95% CI, –27.4 to 4.2 percentage points), but improvements were observed in the nonoropharyngeal HNSCC subset (adjusted DD, –26.5 percentage points; 95% CI, 49.6 to –3.4 percentage points).

The study appeared in JAMA Otolaryngology-Head & Neck Surgery.

“Medicaid expansions were associated with a significantly greater increase in the percentage of Medicaid-insured patients with HNSCC, an increase in localized diseases at diagnosis for the overall cohort, and improved TTI for patients with nonoropharyngeal HNSCC. Selective state-level uptake of Medicaid expansion may exacerbate existing regional disparities in access to care and outcomes among patients with HNSCC,” concluded the study authors. “As data mature, additional research addressing the associations of Medicaid expansions with disparities and survival after diagnosis is warranted.”

January, 2020|Oral Cancer News|

Healthy diet may avert nutritional problems in head, neck cancer patients

Source: medicalxpress.com
Author: University of Illinois at Urbana-Champaign

At least 90 percent of head and neck cancer patients develop symptoms that affect their ability or desire to eat, because of either the tumor itself or the surgery or radiation used to treat it. These problems, called nutrition impact symptoms, have wide-ranging negative effects on patients’ physical and mental health and quality of life.

However, patients who eat foods high in antioxidants and other micronutrients prior to diagnosis may reduce their risks of developing chronic nutrition impact symptoms up to one year after being diagnosed with head or neck cancer, according to a recent study led by researchers at the University of Illinois.

The scientists analyzed the dietary patterns of 336 adults with newly diagnosed head and neck cancers and these patients’ problems with eating, swallowing and inflammation of the digestive tract. This painful inflammatory condition, called mucositis, is a common side effect of radiation treatment and chemotherapy.

The mitigating effects of a healthy diet were particularly significant in people who had never smoked and in patients who were underweight or normal weight at diagnosis, who often experience the greatest eating and digestive problems during treatment, said Sylvia L. Crowder, the paper’s first author.

Crowder is a research fellow in the Cancer Scholars for Translational and Applied Research program, a collaborative initiative of the U. of I. and Carle Foundation Hospital in Urbana, Illinois.

“While previous work has established that the presence of nutrition impact symptoms is associated with decreased food intake and weight loss, no studies have examined how pre-treatment dietary intake may influence the presence of these symptoms later in the course of the disease,” Crowder said.

In the early 2000s, researchers hypothesized that consuming antioxidant supplements might protect patients’ normal cells from damage during radiotherapy, enabling them to better tolerate treatment and higher dosages.

Accordingly, prior research by Anna E. Arthur, a professor of food science and human nutrition at the U. of I. and the current study’s corresponding author, indicated that eating a diet of whole foods abundant in antioxidants and phytochemicals improved recurrence and survival rates in head and neck cancer patients.

Like Arthur’s prior research, the new study was conducted with patients of the University of Michigan Head and Neck Specialized Program of Excellence.

Data on patients’ tumor sites, stages and treatment were obtained from their medical records. More than half of these patients had stage 4 tumors at diagnosis.

Prior to starting cancer treatment and again one year post-diagnosis, the patients completed a questionnaire on their diet, tobacco and alcohol use, and quality of life. Patients reported whether they experienced any of seven nutrition impact symptoms—such as pain or difficulty chewing, tasting or swallowing foods and liquids—and rated on a five-point scale how bothersome each symptom was.

In analyzing the patients’ eating habits, the scientists found that they followed either of two major dietary patterns—the Western pattern, which included high amounts of red and processed meats, fried foods and sugar; or the prudent pattern, which included healthier fare such as fruits and vegetables, fish and whole grains.

Patients who ate healthier at diagnosis reported fewer problems with chewing, swallowing and mucositis one year after treatment, the scientists found.

“While the origin and development of nutrition impact symptoms are complex and varied, they generally share one common mechanism—cell damage due to inflammation,” said Arthur, who is also an oncology dietitian with the Carle Cancer Center. “The prudent dietary pattern has the potential to reduce inflammation and affect the biological processes involved in the pathogenesis of these symptoms.”

The scientists hypothesized that some patients may begin eating healthier after being diagnosed with cancer, potentially counteracting the pro-inflammatory effects of their previous dietary habits.

Reverse causation was possible too, they hypothesized—patients’ lack of symptoms may have enabled them to consume a broader range of foods, including healthier whole foods, before their cancer was discovered.

January, 2020|Oral Cancer News|

Alcohol use high among cancer survivors

Source: www.medwirenews.com
Author: Shreeya Nanda

Over half of cancer survivors report being current drinkers, including about a fifth who appear to engage in excessive drinking behaviors, finds a US study.

“Given that alcohol intake has implications for cancer prevention and is a potentially modifiable risk factor for cancer-specific outcomes, the high prevalence of alcohol use among cancer survivors highlights the need for public health strategies aimed at the reduction of alcohol consumption,” write the study authors in JNCCN—Journal of the National Comprehensive Cancer Network.

They used data from 34,080 participants of the US National Health Interview Survey interviewed between 2000 and 2017 who reported a history of cancer.

In all, 56.5% of the total cohort reported being current drinkers, including 34.9% who exceeded moderate drinking limits – defined as a daily intake of more than one drink for women and more than two drinks for men – and 21.0% who engaged in binge drinking, which was defined as at least five drinks per day on at least one occasion in the past year.

Researcher Nina Sanford (University of Texas Southwestern Medical Center, Dallas, USA) and colleagues caution that for the blood alcohol concentration to reach the threshold for binge drinking, drinks generally need to be consumed within 2 hours, but the survey did not collect information on the duration of alcohol intake and therefore participants who reported binge drinking may not have reached the biologic threshold.

They also investigated factors linked to alcohol use, finding that younger age (18–34 years vs other age groups), current or former smoking status, and later survey period (2010–2014 and 2015–2017 vs 2000–2004) were significantly associated with a greater likelihood of current drinking, exceeding moderate drinking limits, and binge drinking.

For other factors, such as sex and ethnicity, associations were observed for some of the levels of current drinking but not all – for instance, female sex was significantly associated with exceeding moderate limits, but male sex was a significant predictor of reporting current drinking and binge drinking.

The prevalence rates and predictive factors were similar in sensitivity analyses that included just the 20,828 participants who had been diagnosed at least 5 years prior to survey administration.

“By reporting the demographic and socioeconomic variables associated with alcohol intake, our work begins to identify subgroups toward whom alcohol-based interventions could be targeted, and could serve as a benchmark for assessing changes in drinking behavior in the population of patients with cancer,” say Sanford et al.

Individuals with a history of cervical or testicular cancer were significantly more likely to report current drinking, exceeding moderate limits, and binge drinking compared with participants reporting other tumor types. Additionally, those with a history of head and neck cancer or melanoma were also significantly more likely to report binge drinking.

This finding is “likely a reflection of the predominant demographic characteristics—particularly younger age—associated with these cancer diagnoses, rather than an intrinsic association between cancer type and alcohol use,” comment the researchers.

Sanford and colleagues highlight the need for further research, “including large-scale systems-based research on alcohol use in cancer survivors.”

And they conclude: “For the time being, because oncologists have a responsibility to promote the overall health and well-being of their patients, efforts should be undertaken to accurately assess alcohol intake among cancer survivors and to inform these individuals of the potential harms associated with continued drinking.”

January, 2020|Oral Cancer News|