Chemotherapy and radiation therapy issues: What audiologists need to know

Source: journals.lww.com
Author: A. Croutch, Carl AuD

With hearing loss, tinnitus, and imbalance as among the numerous side-effects of cancer treatment,1 audiologists play a critical role in monitoring patients receiving chemotherapy and radiation therapy. Sensorineural hearing loss (SNHL) attributed to chemotherapy and radiation therapy is usually permanent, making audiometric monitoring essential to detect its early occurrence.2

Cisplatin, carboplatin & radiation therapy
Chemotherapy is used to treat cancer, control the growth and spread of cancer cells, and ease cancer symptoms. Cisplatin and carboplatin are two common antineoplastic agents used to treat testicular, ovarian, breast, esophageal, lung, and head and neck cancers among others. Besides hearing loss, these can cause other side effects including kidney, gastrointestinal disorders, allergic reactions, decreased immunity to infections, and hemorrhaging. Cisplatin was first found to have cytotoxic properties in the 1960s, and in 1978 was the first platinum compound approved by the FDA for cancer treatment.3 On the other hand, carboplatin is less potent than cisplatin and does have fewer side effects, especially on kidney problems.3

Both drugs work by interfering with DNA repair mechanisms causing DNA damage and inducing apoptosis in cancer cells. Cancerous cells cannot limit cell division as do normal cells. Normal cells cease dividing when they encounter similar cells whereas cancerous cells do not. The effectiveness of chemotherapy is determined by its ability to damage the RNA or DNA that gives the cell instructions to copy itself. The cells will die if they are unable to divide. The more quickly they are dividing, the more effective is the chemotherapy.4

The incidence of hearing loss in post-chemotherapy patients is highly variable, ranging from 17% to 80% depending on the age, baseline hearing levels, and cisplatin dosage.5 Generally, those receiving a higher dose of cisplatin showed more hearing loss than those receiving a smaller dose.6,7

In addition to chemotherapy, a cancer patient may also be treated with radiation therapy (RT), which is the use of high-energy X-rays or other types of energy such as protons to kill cancer cells. RT also works by destroying the genetic material that regulates cell growth and division. The objective of RT is to kill fewer normal cells since it can damage both cancerous and normal cells. The incidence of SNHL ranges from 0-43% depending on the radiation dosage to the cochlea as well as age and baseline hearing levels.5 Radiation dosage reaching the cochlea may be higher when treating cancer of the nasopharynx, parotid salivary gland, and paranasal sinuses compared to other sites.7

RT can cause both SNHL and conductive hearing loss (CHL). SNHL may occur if the RT is directed near the cochlea, and CHL if it is near the Eustachian tube. Factors that may influence whether a hearing loss occurs include the strength and direction of the beam, location, size of the tumor, patient age, and pre-treatment hearing levels. The frequency of otitis media with effusion in head and neck cancer patients undergoing RT was found to be 39.3% with retracted tympanic membrane and 7.1% with air-fluid levels seen.8 Treatment of head and neck squamous cell carcinoma (HNSCC) patients using radiation can result in mixed (SNHL and CHL) hearing loss, which can be more severe in those with tumors near the ear as well as those treated with cisplatin.7

Stages & grades of cancer
Cancer has four stages: Stage 0 is when the cancer has not spread from its original location (in situ), Stage 1 is when a small cancer has not spread, Stage 2 is when it has grown but not spread, Stage 3 is when it may have spread to near-by tissues possibly the lymph nodes, and Stage 4 is when it has metastasized and spread to at least another body organ. Cancer is also divided into three grades, with the lower grades indicating a slower-growing malignancy and a high grade, a faster-growing one.9

Nasopharyngeal cancer (NPC) is frequently seen in head and neck clinics and offices. Tumors originating in the nasopharynx may be benign or malignant. The majority of nasopharyngeal cancers are nasopharyngeal carcinoma. A carcinoma is a cancer that originates in the epithelial cells, which line the internal and external surfaces of the body. A patient about to undergo chemotherapy and radiation therapy should be seen for a baseline audiogram prior to the initiation of any treatment. An in-depth history of any occupational or recreational noise exposure is essential.

Audiometric test battery
Both chemotherapy and noise exposure can result in high-frequency SNHL. Distinguishing between the two can be difficult, which is why obtaining a baseline audiogram and careful case history is essential. One tip-off may be the high-frequency notch seen between 3000 and 6000 Hz often present in cases of noise trauma.

Speech-in-noise testing should be done since understanding speech in background noise is a common complaint from most adults. Using the Quick Speech-in-Noise (Q-Sin) test may aid in the treatment of these patients.1 Extended high-frequency pure-tone audiometry (EHF-PT) and distortion-product otoacoustic emissions (DP-OAEs) are useful tests in monitoring these patients. Ototoxic effects frequently occur initially at frequencies above 8 kHz. EHF-PT are tested from 8-20 kHz and can often detect hearing loss in these ranges before it affects the speech frequencies. This will enable the oncologist to monitor the treatment and if possible, conserve the patient’s hearing. DP-OAEs are measured from 0.5-8 kHz. They can determine if the outer hair cells are intact since they are usually damaged prior to inner hair cells (IHC) and can result in a more severe hearing loss compared with outer hair cell damage. This may provide useful information to the oncologist. It is also an objective test and can be used regardless of the patient’s age or state of health.2

Criteria for change
In addition to baseline testing, follow-up testing should occur after each treatment, when the course of treatment is completed, and on an annual basis or sooner if indicated. A significant change is considered per the ASHA 1994 guidelines13:

>= 20 dB change at one frequency
>= 10 dB change at two consecutive frequencies
No response at three consecutive frequencies where responses were previously obtained

Ototoxicity can be grouped by using at least 13 different classification systems based on changes from a baseline audiogram to those that focus on the functional impact of the hearing loss. These scales do not consider high-frequency audiometry.13

Despite these grading scales, most clinicians do not use them on a routine basis. How ototoxicity is defined is a significant part of the inconsistencies between pre- and post-clinical data across patient groups.13

Two commonly used ototoxic grading systems in use are the Common Terminology Criteria for Adverse Events version 4 (CTCAEv4) and the American Speech-Language-Hearing Association (ASHA) system. Each of these systems has certain shortcomings.13

To devise a more comprehensive system, Theunissen et al., purposed the TUNE grading system, which details the shortcomings of both the CTCAEv4 and the ASHA systems14 and propose seven different grade levels:

  • Grade 0: No hearing loss
  • Grade 1a: Threshold shift >= 10 dB at 8, 10, and 12.5 kHz OR subjective complaints in the absence of a threshold shift
  • Grade 1b: Threshold shift >= 10 dB at 1, 2, and 4 kHz
  • Grade 2a: Threshold shift >= 20 dB at 8, 10, and 12.5 kHz
  • Grade 2b: Threshold shift >= 20 dB at 1, 2, and 4 kHz
  • Grade 3: Hearing level >= 35 dB at 1, 2, and 4 kHz
  • Grade 4: Hearing level >= 70 dB at 1, 2, and 4 kHz

They feel this system can better assess the effects of hearing loss in daily life and can distinguish between mild, moderate, and severe degrees of ototoxicity compared to the current systems in use.14

Significant changes in DP-OAE findings were a reduction in the signal-to-noise ratio at f2 frequencies below 1 kHz of > 14 dB and a reduction of 7 dB of f2 frequencies above 1 kHz. These criteria were used by Yu, et.al.,2 but no standard criteria are available for defining changes in the DP-OAEs.15

The potential for hearing loss from chemotherapy and radiation therapy is dependent upon the patient’s baseline hearing levels and the strength and frequency of the treatments. Dosage is often determined by the patient’s body surface area indicated by m2. It is calculated by taking the square root of the product of the weight in kilograms times the height in centimeters divided by 3600. The average body surface area for adult men is 1.9 m2 and for women is 1.6 m2.16 Typical doses vary from 25-100 mg/m2. The frequency of treatments is also patient-specific. Chemotherapy is given in cycles—-typically one week of chemotherapy followed by three weeks of rest.

Treatment Options
SNHL may be treated with hearing aids, and CHL by medicine, myringotomy, or PE tube placement. If any hearing loss is found, treatment options should be discussed with the patient. In cases of SNHL that will benefit from amplification, the patient may wish to postpone it until after the cancer treatment has been completed. Some may wish to obtain hearing aids right away to better participate and understand their treatment options. In patients with CHL, a referral to HNS is usually indicated. At Kaiser Permanente, for example, patients with a unilateral CHL without an NPC diagnosis are referred to HNS as that may be an indication of NPC.

Overall, audiologists need to monitor hearing loss in cancer patients undergoing chemotherapy and radiation therapy and provide treatment and counseling when hearing loss has become inevitable.

References:
1. Baguley D, Prayuenyong P. Looking beyond the audiogram in ototoxicity associated with platinum-based chemotherapy. Cancer Chemother Pharmacol. 2020; 82(2): 245-250.

2. Yu K, Choi, C. et.al. Comparison of the effectiveness of monitoring cisplatin-induced ototoxicity with extended high-frequency pure-tone audiometry or distortion-product otoacoustic emission. Korean J of Audiology. 2014;18(2):58-68.

Source:
The Hearing Journal: September 2021 – Volume 74 – Issue 9 – p 44-45

2021-09-09T06:48:49-07:00September, 2021|Oral Cancer News|

A challenge to chew on: eating and drinking after cancer treatment

Source: www.curetoday.com
Author: Dara Chadwick, Heal

Exercise has always been part of Scott Wieskamp’s life. But after cancer treatment, the longtime runner and marathoner added a new element to his training regimen — exercises to strengthen and maintain his swallowing muscles.

“Every day while I’m driving to work, I open my mouth like I’m yawning to stretch all my facial muscles as much as I can,” says Wieskamp, 62, who lives just outside Lincoln, Nebraska. “I take my tongue and put it under the back of my lower teeth and push as hard as I can to exercise my tongue muscles. There’s about half a dozen things I do for a few minutes every day.”

Four years ago, Wieskamp was treated for oral cancer caused by the human papillomavirus. The aggressive treatment, which included 39 radiation sessions and several doses of the chemotherapy drug cisplatin, knocked out the cancer. But it also left Wieskamp unable to eat, and he lost 15 pounds in a matter of weeks.

“As you get radiation in the neck and throat area, it becomes painful to swallow,” he says. “I quit doing all that. I quit eating, quit swallowing — I couldn’t even drink.”

Because he was unable to get adequate nutrition, his doctors inserted a feeding tube so Wieskamp wouldn’t have to swallow. The tube stayed in place throughout his two months of treatment and for about a month after, he says.

Although his nutrition improved, Wieskamp says he was left with another problem: His muscles “forgot” how to swallow.

“I had to go to a speech-language pathologist to help me learn how to swallow again,” he says. “It was scary, painful and frustrating.”

Wieskamp’s swallowing challenges aren’t uncommon. After treatment, survivors of cancer may experience not only difficulty swallowing but also dry mouth and changes in taste, smell, digestion or bowel habits. Any of these changes can make eating and drinking a struggle, which then makes it difficult to get adequate nourishment.

When you’re not getting the nutrients you need, it’s hard for the body to regain strength and rebuild cells, according to Rachel Wong, an oncology dietitian at the Georgetown Lombardi Comprehensive Cancer Center at MedStar Georgetown University Hospital in Washington, D.C.

“Patients can experience delayed healing and recovery caused by poor nutrition post treatment” she says. “A rapid decline in weight from inadequate nutrition often results in both fat and muscle loss, causing significant fatigue and weakness, which can greatly impact one’s ability to accomplish tasks and resume a normal way of living.”

“It can be possible that patients find delayed healing and delayed recovery because of poor nutrition post treatment,” she further explains. “If you’ve lost a lot of weight and you’ve lost muscle, you may sleep a lot during the day.”

Eating challenges can also make it tough for survivors of cancer to enjoy time with family and friends, Wieskamp says. After treatment, he didn’t look forward to social occasions like he used to. “People say, ‘Hey, let’s meet for coffee’ or ‘Let’s have family over and we’ll have a meal,’” he says. “Our lives revolve around food.”

IMPACTS FROM CANCER TREATMENT
Some types of cancer require treatments that are more likely to affect how people eat and drink. According to Dr. David G. Pfister, medical oncologist and chief of the Head and Neck Oncology Service at Memorial Sloan Kettering Cancer Center in New York City, treatments for cancers of the head and neck pose particular challenges because they can affect swallowing, taste and smell.

For example, surgery in certain areas of the head and neck can disrupt structures used in swallowing, such as the throat and tongue. In addition, oral mucositis — mouth pain, sores and infection — can develop after radiation and chemo- therapy. Some survivors experience damage or changes to their salivary glands, which can make the mouth exceptionally dry. This can also predispose them to dental problems.

Jean DiNapoli, 62, of Newburgh, New York, says trying to swallow after completing 30 rounds of radiation for oropharyngeal cancer (a type of cancer found in an area of the throat called the oropharynx) was like “swallowing glass.” She also experienced mouth sores and thrush, a yeast infection that develops in the mouth, along with significant dry mouth.

DiNapoli, who is now seven years post treatment, says she lost about 35 pounds immediately following radiation.

“I could have gotten a feeding tube, but I really didn’t want it,” she says. “I didn’t want my muscles to atrophy.”

Pfister says the decision to place a feeding tube is one that doctors make carefully. “Not that long ago, when significant swelling, pain and weight loss were expected, we would prophylactically put in a feeding tube to get patients over the hump, so to speak,” he says. But doctors found that people would soon start taking all their calories through the tube, leading to the exact problem DiNapoli feared — muscle atrophy.

“Your swallowing muscles are like any other muscle. If you don’t use it, you lose it,” Pfister says, adding that it’s critical to make swallowing therapy a routine part of treatment along with good pain control. “We evaluate every patient in an individualized way. (Although) there clearly are settings where we put in a feeding tube, we’re more selective.”

After her treatment ended, DiNapoli worked with a speech pathologist once a week for a couple of months to regain strength in her tongue muscles and improve her ability to swallow. “I did different exercises, such as swallowing with my tongue between my teeth,” she says. “I also had the help of a good nutritionist.”

MANAGING EATING CHALLENGES
Registered dietitian nutritionists trained in mitigating the impact of cancer treatments can help survivors find new ways not only to get nourishment but also to enjoy food again. Annette Goldberg, a senior nutritionist at Dana-Farber Cancer Institute in Boston, says choosing the tools to help individuals bring their symptoms under control can be a bit of a puzzle. It depends on factors such as their overall health prior to treatment, the type of cancer and treatment they had, and the social support system they have.

“Sometimes I’ll ask patients if they live alone, and they’ll wonder why I’m asking that question,” she says. “I want to make sure they have the proper support. If you’re not feeling well, you don’t want to do anything.” That includes cooking, she says.

Maureen Gardner, a clinical oncology nutritionist at Florida Cancer Specialists & Research Institute in Tampa, says survivors who’ve had cancers in the gastrointestinal (GI) tract or treatment for any cancer in areas near the GI tract — such as prostate, ovarian or uterine cancer — may experience ongoing effects on how food is digested and eliminated. Some survivors may experience weight gain, such as breast cancer survivors who are on long-term hormone therapies or those who have entered menopause. Other people may experience ongoing diarrhea or dumping syndrome — when food moves too quickly from the stomach to the small intestine — after being treated for GI cancers.

Gardner says dietary changes, both in what and how patients eat, can help manage eating challenges after cancer treatment ends. If you have dry mouth, try to:

• Focus on hydration. In addition to drinking water, Goldberg recommends keeping your mouth clean and avoiding toothpastes and mouthwashes that are too harsh.

• Boost saliva production. Tart foods can stimulate the salivary glands, Goldberg notes. Adding tart lemon juice to water or chewing a strong sugarless mint gum can help.

• Add soft, moist foods to your diet. Wong recommends adding extra sauces or broth or even cream to casserole-type dishes or when having drier foods like meat, potatoes and rice.

“Drinking fluids along with your meals can certainly help improve the moisture content in the mouth and make swallowing easier,” Wong says. “Just having a glass of water, juice or any type of liquid in between each bite can really help get the food down.”

DiNapoli says she drank lots of water to relieve her dry mouth. She also tried different lozenges, mouthwashes and gels. “I still use XyliMelts,” she says. “I put (one) in my mouth at night and it slowly dissolves.”

Some survivors experience changes in taste and smell that affect the way they experience food. “I lost my sense of taste right after radiation,” DiNapoli says. “Everything tasted like paste. But then my sense of taste came back so strong that spicy food was overly spicy. And my sense of smell is stronger.”

“I tell patients that your taste buds and smell will constantly change,” Wong says, encouraging people to keep a running list of things that work well and things that don’t. “In my experience, a list of what works gives you the motivation to keep trying new things.”

If you’ve had changes in taste and smell that affect how you experience food, try experimenting with seasonings. Adding spices such as basil, pepper or dill can make food more sweet, savory or salty and improve its flavor. Wong also recommends adding different types of sauces, such as ranch, barbecue, or sweet and sour to help bring out the flavor in foods and add some moisture.

If you’re experiencing ongoing GI symptoms such as diarrhea, Goldberg recommends talking to your doctor or nutritionist about supplements that might help, such as banana flakes. “It’s a product that’s made from dehydrated bananas, which contain several soluble fibers including pectin. The soluble fiber absorbs fluid to help firm the stool,” she says. “A combination of foods, maybe some supplements and working with your care team can help.”

IMPROVEMENTS WITH TIME
Although eating and drinking can be difficult during active treatment and the weeks immediately after, strengthening exercises and dietary changes can help most people overcome these challenges with time. Addressing issues right from the start can help the healing process, Wong says.

“Getting guidance from a dietitian can impact how patients recover after their treatment,” she says, adding that it’s important for doctors to talk with patients about challenges they might experience. She also recommends resources such as the American Institute for Cancer Research and the American Cancer Society for advice on managing eating challenges after treatment.

Support groups — both online and in person — can also help. DiNapoli and Wieskamp are members of an organization called Support for People with Oral and Head and Neck Cancer (SPOHNC). Both say SPOHNC has been incredibly helpful as they’ve healed.

“I would tell most people that I’m 100% normal, but I’m not 100% the same,” Wieskamp says. “My brain has had to learn that things that used to taste one way taste a little different today. But I’m only one person. You could probably interview 20 people and they may have 20 different answers.”

Cancer survivors’ tongues less sensitive to tastes than those of healthy peers

Source: www.eurekalert.org
Author: University of Illinois at Urbana-Champaign, News Bureau

Most survivors of squamous cell head and neck cancers report that their sense of taste is dulled, changed or lost during radiation treatment, causing them to lose interest in eating and diminishing their quality of life.

In a study of taste and smell dysfunction with 40 cancer survivors, scientists at the University of Illinois Urbana-Champaign found that the tips of these individuals’ tongues were significantly less sensitive to bitter, salty or sweet tastes than peers in the control group who had never been diagnosed with cancer.

In a paper published in the journal Chemical Senses, the U. of I. team said this diminished taste sensitivity suggested that the taste buds on the front two-thirds of the cancer survivors’ tongues or a branch of the chorda tympani facial nerve, which carries signals from the tip of the tongue to the brain, may have been damaged during radiation therapy.

“While most studies suggest that patients’ ability to taste recovers within a few months of treatment, patients report that they continue to experience taste dysfunction for years after treatment ends,” said M. Yanina Pepino, a professor of food science and human nutrition at the U. of I. “Our primary goal in this study was to test the hypothesis that radiation therapy is associated with long-term alterations in patients’ senses of smell and taste.”

While undergoing radiation and/or chemotherapy, head and neck cancer patients may lose taste buds, triggering a transient reduction in their ability to taste – a condition called hypogeusia – or their perception of tastes may be altered, a condition called dysgeusia that can also occur when nerves are damaged during cancer surgery, she said.

“Taste buds’ average lifespan of about 10 days enables rapid recovery from injury if the stem cells are preserved, yet it also makes the short-lived and long-lived cells within taste buds particularly vulnerable to the direct cytotoxic and anti-proliferative effects of chemotherapy and radiotherapy,” Pepino said.

Prior studies that explored taste loss and perception in these patients showed mixed results. Many of these studies involved “whole mouth” experiments that may not have detected regional damage to the taste buds at the front of the tongue or to the chorda tympani section of the facial nerve, said graduate student Raul Alfaro, the lead author of the study.

The U. of I. team assessed participants’ smell and taste functions separately and explored whether sensory interactions between taste and retronasal odors – aromas from food and beverages that are perceived in the oral cavity while eating or drinking – differed for the cancer survivors and the people in the control group.

The team assessed participants’ ability to taste regionally by applying cotton swabs soaked in flavored solutions to the tips of their tongues.

They also evaluated participants’ whole-mouth taste function by having them swish solutions around in their mouths for five seconds and spit them out. For this test, the participants were presented with nine cups of liquids that contained both taste and smell sensory components. The cups contained two concentrations of strawberry extract in a sucrose solution, lemon extract in citric acid, salt in a vegetable broth and caffeinated instant coffee. They also received one cup of deionized water.

After sipping each sample, participants were asked to identify its taste quality – sweet, salty, bitter, umami (savory) or no sensation – and to rate the smell and taste intensity of the sample on a scale that ranged from “no sensation” to “strongest of any kind.”

Participants tasted the samples twice – once wearing a nose clip and once without – to determine whether their taste perception differed when the nose clip blocked their retronasal olfactory cues.

When participants’ sense of taste was assessed using the whole-mouth test with or without the nose clip, they similarly rated the taste and smell of nearly all of the samples.

However, when participants’ sense of taste was assessed regionally at the tip of the tongue, the cancer survivors were more likely to respond they did not perceive a taste or to misidentify the taste quality – such as bitter, salty or sweet – of multiple samples.

“Although the results from the whole-mouth taste test suggested that head and neck cancer survivors’ taste function was normal and well preserved, results from the regional tests indicated that they had some deficits,” Pepino said. “Subtle taste dysfunction in the tip of the tongue persisted for several months after they completed their oncology treatments.

“Taste dysfunction at the tip of the tongue might sound unimportant; however, there is an elegant cross-talk between the nerves that conveys signals from the tip and the back of the tongue, such that taste signals in the tip of the tongue inhibit signaling from the back. This system allows taste intensity to remain constant in the whole mouth, even when taste signaling coming from the tip of the tongue is reduced. However, reduced signal input can also lead to phantom tastes, metallic taste and other oral symptoms.”

Notes:
Additional co-authors of the study were food science and human nutrition professor Anna E. Arthur, who is also the Sylvia D. Stroup Scholar in Nutrition and Cancer, and an oncology dietitian with the Carle Cancer Center; Dr. Kalika P. Sarma, a radiation oncologist at Carle Foundation Hospital and a clinical assistant professor in the Carle Illinois College of Medicine; and then-research fellow Sylvia L. Crowder.

The work was supported by grants from the U.S. Department of Agriculture National Institute of Food and Agriculture, the Academy of Nutrition and Dietetics, and the Division of Nutritional Sciences at the U. of I.

Crowder’s work on the project was supported by a Carle Illinois Cancer Scholars for Translational and Applied Research Fellowship, as well as a grant from the National Cancer Institute.

Personalized 3D-printed shields protect healthy tissue during radiotherapy

Source: physicsworld.com
Author: Jigar Dubal

Personalized 3D-printed devices for radioprotection of anatomical sites at high risk of radiation toxicity: intra-oral device (A), oesophageal device (B) and rectal device (C) generated from patient CT images. The area for protection is highlighted in red. (Courtesy: CC BY 4.0/Adv. Sci. 10.1002/advs.202100510)

One of the primary goals of radiation therapy is to deliver a large radiation dose to cancer cells whilst minimizing normal tissue toxicity. However, most cancer patients undergoing such treatments are likely to experience some side effects caused by irradiation of healthy tissue. The extent of this damage is dependent on the treatment location, with the most common toxicities involving the oral cavity and gastrointestinal tract.

Materials with a high atomic number (Z), often known as radiation-attenuating materials, can be used to shield normal tissue from radiation. However, integrating such materials into current patient treatment protocols has proven difficult due to the inability to rapidly create personalized shielding devices.

James Byrne and colleagues at Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital and MIT have addressed this need. The team has developed 3D-printed radiation shields, based on patient CT scans, incorporating radiation-attenuating materials to reduce the toxicity to healthy tissue.

Producing personalized 3D-printed shielding
Before a patient undergoes radiotherapy, they undergo CT scans to provide anatomical information that is used to plan their treatment. Byrne and his colleagues utilize these CT images to design personalized radio-protective devices, which they produce through 3D printing.

To determine the most appropriate shielding materials for the device, the researchers tested various elements and alloys, including liquids, with a high Z number. They characterized these materials by measuring their relative mass attenuation coefficients. From this, the team determined that elemental materials demonstrated greater radiation shielding than alloys or composites, and that mercury largely outperformed all other liquids. They then incorporated the high-Z materials into the personalized 3D-printed devices. The devices were made such that the shielding material could be removed to reduce artefacts during CT imaging and replaced prior to treatment.

To evaluate the device’s ability to shield healthy tissue from radiation, the team treated 14 rats with single-dose irradiation, half with and half without radio-protective devices in place, and examined the incidence of toxicities such as oral mucositis and proctitis.

The group also simulated clinical radiation treatments by modelling the radio-protective devices in the treatment planning software. The dose distributions with and without shielding were compared to evaluate the dosimetric impact of the device. The researchers simulated treatments of prostate and head-and-neck cancer patients, selecting the appropriate positioning of the device based on the regions of increased radiation exposure.

Evaluation of radio-protective devices
Histopathological analysis revealed that only one of seven rats with radio-protective devices in place during treatment suffered ulceration on the surface of the tongue. In contrast, all seven control rats, with no device in place, experienced extensive ulcerations on the tongue surface.

The clinical simulations identified that using radio-protective devices during prostate cancer treatment could reduce the dose to healthy tissue by 15% without reducing the dose delivered to the tumour. For the head-and-neck cancer treatment, the dose absorbed by inner-cheek tissue was reduced by 30%.

The results clearly show that the radio-protective devices may improve patient comfort throughout the course of treatment. “Our results support the feasibility of personalized devices for reduction of radiation dose and associated side effects” claims Byrne.

Future clinical implementation
The benefits of using 3D-printed radio-protective devices in the clinic are clear. “This personalized approach could be applicable to a variety of cancers that respond to radiation therapy,” says Byrne.

The researchers acknowledge that full clinical translation of 3D-printed shielding devices will require further development. “Given the small sample size of our dosimetric studies, further investigation in larger cohorts is needed to validate these approaches,” they say.

The researchers publish their findings in Advanced Science.

New therapy shortens treatment for HPV-related cancers of the tonsils, tongue

Source: medicalxpress.com
Author: From Mayo Clinic News Network, Mayo Clinic News Network

Patients with HPV-related oropharyngeal cancer who undergo surgery and are treated with chemotherapy, may be able to forgo significant radiation therapy without increasing the risk of their cancer spreading, according to the results of a clinical trial led by researchers at Mayo Clinic.

“We found that decreasing the amount of radiation therapy after a minimally invasive robotic surgery improved the quality of life of patients with HPV-related oropharyngeal cancer while delivering excellent cure rates,” says Dr. Eric Moore, a Mayo Clinic otolaryngologist. “In essence, we found exactly the right amount of treatment to deliver without over-treating these patients.”

Dr. Moore and his colleagues compared 79 patients treated at Mayo Clinic for HPV-related tonsil and tongue cancer with surgery and two weeks of radiation therapy to a group of 115 patients with the same cancer who were treated with surgery, and the standard six weeks of radiation therapy and chemotherapy.

Dr. Moore and his colleagues found no decrease in survival or cancer recurrence in the group that received two weeks of radiation therapy, compared to the group that received six weeks of radiation therapy. He says that by decreasing the amount of radiation therapy after minimally invasive robotic surgery, physicians were able to improve the quality of life of patients and achieve excellent cure rates.

“In essence, we found exactly the right amount of treatment to deliver without overtreating,” says Dr. Moore.

Dr. Moore says Mayo Clinic now offers dose de-escalation radiation therapy to appropriately selected patients with HPV-related cancers of the tonsils and tongue.

“This approach shortens the treatment time for these patients by several weeks and reduces side effects without sacrificing the effectiveness of the treatment,” Dr. Moore says.

A new method for fighting ‘cold’ tumors

Source: www.eurekalert.org
Author: news release University of Colorado Anschutz Medical Campus

Not all cancerous tumors are created equal. Some tumors, known as “hot” tumors, show signs of inflammation, which means they are infiltrated with T cells working to fight the cancer. Those tumors are easier to treat, as immunotherapy drugs can then amp up the immune response.

“Cold” tumors, on the other hand, have no T-cell infiltration, which means the immune system is not stepping in to help. With these tumors, immunotherapy is of little use.

It’s the latter type of tumor that researchers Michael Knitz and radiation oncologist and University of Colorado Cancer Center member Sana Karam, MD, PhD, address in new research published this week in the Journal for ImmunoTherapy of Cancer. Working with mouse models in Karam’s specialty area of head and neck cancers, Knitz and Karam studied the role of T cells in tumor treatment.

“What we found is that the cells that normally tell the T cell, ‘Hey, here’s a tumor — come and attack it,’ are being silenced,” Karam says.

She and her team found that regulatory T cells (Tregs), a specialized T cell type that suppresses immune response, are essentially telling the T cells to stop fighting the cancer.

“Tregs normally serve as an important balance in a healthy immune system,” Knitz says. “They prevent autoimmune disease and put the brakes on the T cells when needed. However, in many tumors, Tregs are too numerous or overly suppressive, bringing the T cell response to a halt.”

Using medication that deactivates the Tregs can help boost the immune response in patients with cold tumors, the researchers found, as can radiation treatment that causes enough injury that the immune cells known as dendritic cells work to put the regular T cells into fight mode.

But this is only part of the story. The T cells need to know what to attack. “You need the radiation to create injury and bring in the immune cells so that the tumor can be recognized and targeted,” says Karam, also an associate professor of radiation oncology at the University of Colorado School of Medicine. “That way, the dendritic cells trigger the immune system to produce a lot of T cells, similar to what a vaccine does. Those T cells then go back to the tumor to kill cancer cells. The pieces are already in place; they just need the proper signals. Activating the dendritic cells is a crucial step in allowing radiation to heat up these cold tumors.”

Importantly, Karam and her team, which includes post-doctorate fellow Thomas Bickett, found that the radiation must be administered in a specific way.

“A specific dosing is needed,” Karam says. “You have to pulse it. You can’t just give one dose. You have to give it again and combine it with things that remove the suppression — the Tregs — while simultaneously keeping those antigen-presenting dendritic cells active and on board.”

Karam says the next step in her research is clinical trials she hopes will eventually change the treatment paradigm from surgery and weeks of chemotherapy and radiation to just three sessions of radiation and immunotherapy, then surgery. She is driven to change the standard of care for cold tumors, she explains, because of the horrendous effects they have on patients.

“These tumors resemble those in patients who are heavy smokers,” she says. “They’re very destructive to bone and muscle, infiltrating the tongue, jaw, gum, and lymph nodes. It’s horrible. We have very high failure rates with them, and the treatment often involves removing the tongue and weeks of radiation and chemotherapy, only for the patient to fail. I’m confident that we can do better for our patients.”

Patients with oral cancer may get relief from dry mouth through MU research

Source: www.columbiamissourian.com
Author: Tia Alphonse

Gary Rackers bit his tongue one night, and it began to bleed. Thinking it wasn’t serious, he waited a couple of weeks, but something still didn’t feel right.

So, he asked his wife to take a look. She was shocked, Rackers said. His tongue was black.

After seeing his family physician and a local ear, nose and throat doctor in Jefferson City, Rackers was referred to Ellis Fischel Cancer Center. There, he connected with a physician who specialized in surgical treatment for patients with head and neck cancers. He was diagnosed with squamous cell carcinoma — a common oral cancer. The doctor ended up surgically removing half of Rackers’s tongue and nearly all of his teeth, and he began radiation and chemotherapy treatments.

Since then, Rackers said he‘s had 33 radiation treatments and three rounds of chemotherapy. He is pleased and proud of the work his physician did, he said. Because of her, he’s in the recovery phase: “I’m doing good…and I’m feeling good.”

Many head and neck cancer patients like Rackers lose their ability to produce saliva after radiation treatment. He said it doesn’t affect him much during the day, but his mouth gets quite dry at night. Dry mouth frequently disturbs his sleep, he said, causing him to often fetch water or juice for relief.

“If I could get through the night,” he said, the days are easy.

MU researcher and former dentist Olga Baker hopes to help patients like Rackers by dedicating her efforts to something most of us take for granted — saliva. Through her research, she hopes to find better solutions to combat dry mouth, particularly among cancer patients whose glands have been destroyed by radiation therapy.

When she practiced dentistry, Baker said she encountered many patients who struggled with dry mouth. Although the condition is often viewed as insignificant, those who underproduce saliva often develop mouth sores, cavities and a host of other issues. Baker said she has even worked with patients who have trouble talking because their inner cheeks stick to their teeth without natural lubrication from saliva. She has also treated patients who feel as if they are choking at night without the fluid to keep their airways moist.

Multiple groups of people suffer from chronic dry mouth. Patients who undergo radiation treatment for neck and head cancer are among a common group that often loses the function of salivary glands. After treatment, many of these glands stop working and can no longer naturally produce saliva, Baker said. She has seen patients who suffer from Sjögren’s syndrome, an autoimmune disease that causes inflammation that destroys the salivary glands. Other patients are born without functioning salivary glands at all.

“For these patients, there is no cure,” Baker said. “So, we’re working on different options.”

In the past, she worked to produce artificial saliva from plant-based resources and researched resolvins, lipids derived from the Omega-3 fatty acids commonly found in fish oil. This can be a potential treatment for dry mouth in Sjögren’s syndrome patients. These kind of solutions provide temporary relief, working as a spray that can be applied throughout the day to mimic the effects of saliva lubrication.

Baker’s current research into saliva production is dedicated to finding a more long-term solution to dry mouth, specifically for patients whose glands have been destroyed by radiation therapy. The therapy Baker is researching uses a specialized hydrogel that targets the affected glands. She has zeroed in on a protein called laminin-111, which is important to the embryonic process and has long been associated with regenerative properties. Baker said her previous research found that the protein helped restore salivary gland function when only single molecules were used.

She looked at recent studies on the way trimers, a combination of three molecules of a given protein, could give greater results than single molecules. She became interested in testing trimers of laminin-111 on salivary glands to see whether the protein could further restore salivary function in mice.

The experiment tested mice that had undergone radiation treatment and lost salivary function. Proteins from the treatment are put into hydrogels to make a more efficient delivery system. The gel was applied to the mice, and their saliva secretion was monitored. The treatment has proved effective in mice that lose salivary gland function due to radiation. Baker said the next step is to expand her research into larger animals and ultimately do clinical trials on human patients.

Meanwhile, Rackers is adjusting to his recovery. He said he no longer eats spicy foods, and he can’t stand the tanginess of condiments like barbecue and mustard. He can, however, still enjoy most foods.

“Tonight, I’m making smoked sausage, fried potatoes and steamed vegetables,” he said. “And I can eat that.”

2021-02-04T20:59:31-07:00February, 2021|Oral Cancer News|

University of Cincinnati research unveils possible new combo therapy for head and neck cancer

Source: www.eurekalert.org
Author: Research News, University of Cincinnati

Head and neck cancer is the sixth most common cancer worldwide, and while effective treatments exist, sadly, the cancer often returns.

Researchers at the University of Cincinnati have tested a new combination therapy in animal models to see if they could find a way to make an already effective treatment even better.

Since they’re using a Food and Drug Administration-approved drug to do it, this could help humans sooner than later.

These findings are published in the journal Cancer Letters.

Christina Wicker, PhD, a postdoctoral fellow in the lab of Vinita Takiar, MD, PhD, led this research which she says will hopefully extend the lives of patients one day.

“Head and neck cancer, like any cancer, is truly life-altering,” she says. “Head and neck cancer could impact your throat, tongue or nose, and patients often can’t swallow, talk or eat; it truly takes away some of the most social, enjoyable parts of life.”

Researchers in this study combined radiation therapy with a drug (telaglenastat) that stops a key enzyme in a cell pathway that becomes altered in cancer cells, causing those cells to grow rapidly and resist treatment. Wicker says this drug has already been studied in multiple clinical trials to see if it could improve treatment of various cancers.

“Until now, no one has examined if this drug has the potential to improve radiation treatment in head and neck cancer. Most importantly, this drug compound has been well tolerated by patients and causes minimal side effects,” she says.

Using animal models, researchers found that the drug alone reduced the growth of head and neck cancer cells up to 90%, and it also increased the efficacy of radiation in animals with head and neck tumors by 40%.

“With these results, and especially with previous clinical trials showing that the drug is well tolerated by patients, there is the potential to move more rapidly into head and neck cancer clinical trials,” Wicker says. “In the future, we hope this drug will be used to make radiation treatments for head and neck cancer even more effective.”

Currently, the most common treatment for that cancer is radiation therapy, but the cancer eventually returns in up to half of patients, Wicker says, and often it doesn’t respond as positively to treatment the second time around.

“When [traditional] drugs are less effective, cancer growth becomes difficult to control, which can lead to the cancer quickly spreading to other organs,” she says. “It is very important that scientists and clinicians develop new cancer treatments to improve treatment of this type of cancer, and hopefully our findings will provide one more option to help patients.”

UK Innovators target nanoparticles at inoperable cancers

Source: www.politicshome.com
Author: from Medicines Discovery Catapult

At a point of critical clinical need for improved treatments for pancreatic and head and neck cancers, a partnership of healthcare innovators set out to revolutionise radiotherapy for inoperable, and the most difficult to treat tumours.

With the aim of achieving a higher quality of life for those with unfavourable prognoses, this project, funded by Innovate UK, the UK’s innovation agency, brings together partners with a wealth of experience and specialist know-how in the areas of nanoparticle development, drug delivery and bioimaging.

The pioneering work being conducted will target cancerous cells more selectively, enabling a reduced dose of radiation, which would lower the toxic effects a patient receives as a result.

This targeted approach will employ Xerion Healthcare’s non-toxic radiosensitiser – this heightens the cells’ sensitivity to radiotherapy, increasing the likelihood of successful treatment while reducing the often devastating side effects.

To ensure the nanoparticles carrying the therapeutic agent reaches deep inside the tumour, Active Needle Technology’s unique delivery system conveys the treatment to the cancerous cells with the assistance of ultrasonic vibrations, which not only allow accurate placement, but also enables an optimal distribution throughout the tumour and limits damage of healthy cells in the process.

Medicines Discovery Catapult’s (MDC) advanced pre-clinical imaging suite and state-of-the-art expertise in complex medicines validation will undertake in-life imaging of the nanoparticle distribution, allowing the partners to validate its biodistribution in tumour and across other tissues and organs.

Ian Quirk, CEO of Active Needle Technology said:

“For patients suffering from a range of late stage cancers, treatment options can be limited. The effectivity and accuracy of Active Needles delivery of Xerion Healthcare’s ground-breaking new anti-cancer treatment is poised to revolutionise radiotherapy, and offer the hope of recovery for vast numbers of patients. We’re delighted to be working with Medicines Discovery Catapult to take the technology one step closer to the clinic.”

Dr Gareth Wakefield, Chief Technology Officer from Xerion Healthcare said:

“Effective direct tumoural delivery of anti-cancer agents is a key stepping stone to getting our nanoparticle products into clinical trials and into treatment programs for patients with inoperable tumours. Partnering with Active Needles unique ultrasonic delivery system and MDC’s real time imaging allows us to optimise the delivery system for maximum efficacy.

“Late presenting inoperable tumours require very high dose radiotherapy for successful treatment. This can often have very severe side effects or simply not be possible due to nearby sensitive organs. This project gives us a way to boost the effectiveness of the treatment without increasing the whole body dose.”

Professor Peter Simpson, Chief Scientific Officer at Medicines Discovery Catapult (MDC) said:

“MDC is pleased to be providing our state of the art imaging facilities and complex medicines expertise in this exciting collaboration with Active Needle Technology and Xerion Healthcare – to assess the biodistribution and efficacy of this nanoparticle approach.

“Complex medicines have the potential to address patients’ problems which conventionally administered small molecules and monoclonal antibodies cannot. This project is a very encouraging example of exploring how using an advanced drug delivery technology could improve drug biodistribution, and so improve the targeting and efficacy of potentially toxic therapeutics.”

Although great progress has been made in the treatment of some common cancers, there remain many indications where there has been little improvement in care over decades. Pancreatic cancer is on course to become the second leading cause of cancer mortality by 2030 with head and neck cancer currently seeing a 50% mortality rate. It has never been more timely or pertinent for research in this space to be undertaken.

2020-12-19T08:18:56-07:00December, 2020|Oral Cancer News|

FDA clears IND application for cell therapy to treat radiotherapy-induced dry mouth

Source: www.healio.com
Author: staff

The FDA cleared an investigational new drug application for a mesenchymal stromal cell therapy to treat radiotherapy-induced xerostomia, also known as dry mouth.

Researchers at University of Wisconsin Carbone Cancer Center developed the therapy, which uses the patient’s interferon-gamma activated marrow stromal cells.

Xerostomia is a one of the most common adverse effects of radiation therapy for head and neck cancers and may cause difficulties eating, speaking and sleeping, in addition to oral health complications.

“There is a critical need for improved treatments for this condition,” Randy Kimple, MD, PhD, associate professor of human oncology at University of Wisconsin School of Medicine, said in a press release. “For most patients, the best care we can provide currently is to encourage them to eat specially prepared food, suck on hard sugar-free candies and carry a water bottle with them all day.”

Kimple told Healio the therapy process involves the patient undergoing a bone marrow biopsy to harvest mesenchymal stromal cells.

Kimple — who will lead the forthcoming phase 1 trial for the therapy — said the cells will be prepared by the Program for Advanced Cell Therapy’s lab at UW Health’s University Hospital. Patients will receive the therapy via injection into the submandibular gland after completion of radiation therapy.

The phase 1 trial soon will begin enrolling up to 30 patients and will be conducted by University of Wisconsin School of Medicine and Public Health as a single-center study of patients treated at Carbone Cancer Center.

Study participants will be monitored for safety and development of adverse effects after receiving the cell therapy injection.

“Patients will also provide samples of their saliva and complete quality-of-life questionnaires to help determine if the treatment is effective,” Kimple said.

Researchers hope to complete the first phase of the trial within a year, according to Kimple.

2020-09-12T10:26:52-07:00September, 2020|Oral Cancer News|
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