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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.

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.

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

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

New cancer treatments may be on the horizon – thanks to success in mRNA vaccine trial

Source: www.goodnewsnetwork.org
Author: Andy Corbley

A personalized, mRNA vaccine, given to patients with particular kinds of aggressive cancers could leverage the immune system of the patient to kill the cancer on its own, and in doing so usher in a new epoch of cancer treatment.

Messenger RNA (ribonucleic acid) vaccines were what sparked the COVID-19 vaccine drives, as Pfizer and Moderna adapted the technology to create an emergency treatment to train the body to fight off the viral spike protein.

What most of us won’t know however, is that the mRNA vaccines were originally in development for aggressive cancer types.

Molly Cassidy, a mother studying for the Arizona Bar exam, is living proof that while the approach isn’t a panacea, it can clear away some of the most dreadful and fast cancers we know of.

After being diagnosed with head and neck cancer, she underwent surgery and chemotherapy. However it was only ten days after finishing chemo that she found a marble-like bump on her collarbone from the cancer’s swift return. Later examinations found it had spread from her ear all the way to her lungs, and she was told to get her affairs in order.

Cassidy was told she was eligible to join a clinical trial at the University of Arizona, testing an mRNA vaccine personalized to the cancer mutations of the host. By 27 weeks, Cassidy had received nine vaccine doses paired with an immunotherapy drug, and her CT scans were clear: the cancer had left her body.

Personalized Medicine
A personalized medicine approach to disease is challenging, however it could be said that the rise of cancer and of so many other diseases across the west is a result of the broader Western-health sector adopting a once-size fits all (or one-pill fits all) approach to everything from cancer to diet to mental health.

Precision or personalized medicine is becoming a little more common now, with many functional medicine clinics paying more attention to genetic phenotypes and other biomarkers before drafting a therapy plan. This approach recently broke ground in a huge way in the field of Alzheimer’s, and the USDA is using artificial intelligence based on demographics and other information to make more precise dietary guidelines.

Tailor-made mRNA vaccines are an exciting form of personalized medicine to treat cancer, and involve taking a tissue sample from the patient’s tumor and analyzing it for mutations. This not only hones the immune system into the cancerous cells, but differentiates them from healthy, non-cancerous cells.

The result is that the messenger RNA creates proteins shed from the exterior of the tumor and brings immune cells like T cells up to speed on how to fight it.

“One of the things cancer does is it can turn on signals to tell the immune system to quiet down so the cancer is not detected,” explains Daniel Anderson, a biotech scientist at MIT, to National Geographic. “The goal of an mRNA vaccine is to alert and gear up the immune system to go after the characteristic features of tumor cells and attack them.”

Currently, phase-one clinical trials are running for metastatic melanoma, GI-tract cancer, colorectal cancer, pancreatic and ovarian cancer, and non-small cell lung cancer.

One of the most exciting things, even in these early days of mRNA cancer vaccines, is that they will offer a chance at survival for advanced and incurable cancers, not only because they have the potential to be very effective, but also because patients, like in Cassidy’s case, will have no other options.

It’s likely the personalized mRNA vaccines will in practice be paired with immune checkpoint therapy—a breakthrough class of treatment that won the Nobel Prize in 2018. Similar to stem cell treatment, a patient’s T cells are drawn out before being multiplied in a lab, trained on the target cancer cell, and then reintroduced to help fight off the cancer.

Some animal studies have had success in this way, with one group of rats fighting off triple-negative breast cancer, and another group showing great success against cancer of the lymph nodes.

National Geographic concluded their feature on mRNA vaccines with a suggestion that based on early success, FDA-approval could be given in around five years.

2021-09-07T05:46:03-07:00September, 2021|Oral Cancer News|

Recognizing and treating oral leukoplakia in primary care

Source: www.clinicaladvisor.com
Authors: Christina Alvarez, PA-C, Corinne I. Alois, MS, PA-C, Louise Lee, EdD, MHA, PA-C

Oral leukoplakia is a common premalignant condition most commonly identified in the smoking patient population. Once oral leukoplakia is diagnosed, the fundamental goal is to minimize progression towards invasive carcinoma through the use of various treatment methods such as traditional scalpel excision, cryotherapy, and carbon dioxide (CO2) laser therapy.

Epidemiology and Pathogenesis of Oral Leukoplakia
Leukoplakia is defined as a white, painless, plaque most commonly occurring on the buccal mucosa, lateral tongue, or floor of the mouth.1 Leukoplakia is considered one of the most common oral potentially malignant disorders (OPMDs) with an estimated worldwide prevalence of 1.5% to 2.6%.1 This premalignant condition, which can lead to oral cancer, particularly squamous cell carcinoma, presents with various transformation rates ranging from 0.1% to 17.5%.2 Due to variability in transformation to malignancy, identification, treatment, and monitoring is imperative.

The etiology of oral leukoplakia is multifactorial and many cases are considered idiopathic; however, several strong risk factors are associated with this condition, the most common being chronic exposure to all forms of tobacco products, which cause mucosal irritation over time.1,2 Prolonged use of tobacco products is attributed to the conversion of normal cells to hyperplasia, dysplasia, and eventually carcinoma in situ or invasive carcinoma. It is reported that leukoplakia is 6 times more common in smokers than nonsmokers.1

Oral leukoplakia is most commonly seen in men aged 40 years and older, particularly after years of chronic tobacco use.1,2 Other common contributory risk factors include: alcohol use, betel nut use, genetics, poor oral hygiene, human papillomavirus (HPV), Epstein-Barr virus, and chronic candidiasis.1-6

Clinical Presentation
Because oral leukoplakia is a painless and generally asymptomatic condition, it often goes unnoticed unless careful inspection is taken by both patient and primary care provider. Upon inspection of the tongue, buccal mucosa, and floor of the mouth, a white patch will be seen that can vary in appearance. Leukoplakia presents in 3 different forms:

  • Homogenous: typically presents as a white, thin plaque that is even in color and smooth or wrinkled in appearance and consistent throughout; this form has a lower risk for malignancy1,2
  • Nonhomogenous: presents as a white lesion that is typically irregularly shaped with inconsistencies throughout and may show erythema; this form has a higher risk for malignancy1,2
  • Proliferative verrucous: presents as a white, hyperkeratotic, wart-like lesion. This form is aggressive, associated with HPV and EBV, and has a high malignancy rate.6

Diagnosis of Oral Leukoplakia
The differential diagnosis should include oral candidiasis, oral lichen planus, oral erythroplakia, oral hairy leukoplakia, or nicotine stomatitis in smokers.2,6,11 Scraping the lesion is important during the initial workup. In oral leukoplakia, the lesion will remain intact, while in oral candidiasis the plaque will be removed upon scraping and will bleed.2,11 A potassium hydroxide smear should be performed to identify Candida albicans as the causative agent. HIV testing may also be considered if suspicious of hairy leukoplakia or oral candidiasis without any known risk factors such as recent use of antibiotics, inhaled corticosteroids without use of a spacer, or chemotherapy.12 Other tests to consider for the workup of a white oral lesion may include hepatitis C antigen and antibody, which are linked to oral lichen planus and dermal lesions on the body.13 Lastly, because HPV is a risk factor for leukoplakia cases, clinicians should consider HPV testing.

Once other causes of white plaques have been ruled out through noninvasive testing, biopsy can be performed for a definitive diagnosis.2 Biopsy options include incisional and punch biopsy, which are performed to examine for histologic changes to the cells in the lesion. An excisional biopsy, which includes removal of the whole lesion, may be considered as well if the plaque is small in size. For larger lesions, an incisional biopsy is used and includes adjacent healthy tissue. Common histologic changes that are associated with oral leukoplakia seen on biopsy include loss of polarity of basal cells, nuclear hyperchromatism, nuclear pleomorphism, keratinization of cells, loss of intercellular adherence, increased nuclear-cytoplasmic ratio, and irregular epithelial stratification.2,7 A biopsy can also determine if the white lesion is benign, dysplastic, or has transformed to in situ or invasive carcinoma. The histologic results and lesion staging also play a key role in assessing which treatment options are most appropriate for the patient.

Although brush biopsy, in which a brush is swept along the lesion to collect cells, may be performed before surgical biopsy, evidence of the accuracy of this technique is mixed.2,8-10

Treatment Options for Oral Leukoplakia
As a premalignant condition with a high likelihood of progression to squamous cell carcinoma, immediate treatment of oral leukoplakia is encouraged. The main goal of treatment is to prevent further dysplasia and excision of moderate to severe dysplasia or carcinoma. A key aspect of management is removal of the primary source of irritation.2 This most commonly involves tobacco cessation as well as avoiding alcohol to help prevent further dysplastic changes to the tissue.

Surgical management is the gold standard for treatment of oral leukoplakia, however, patients may inquire about conservative options. Retinoids, beta carotene, and isotretinoin have been used to help reduce lesion size; however, clinical evidence on these treatments is very limited.3,14

A Cochrane review found that clinical improvement of lesions was achieved in studies using systemic vitamin A or retinoids (2 studies) and systemic beta carotene or carotenoids (1 study).14 Meta-analysis of 2 studies showed no benefit of beta carotene or carotenoids on the risk for cancer development.14,15 The review also reported lesion recurrence in 56% of patients treated with vitamin A and 54% of those given carotenoid management.14 Although the success and recurrence rates are variable and limited in study, it is important to discuss medical management as an alternative to surgical procedures. Clinicians should continue to discuss these options to provide patient-centered care, allowing patients to make informed decisions.

Surgical options for the treatment of oral leukoplakia include cryotherapy, diode laser therapy, CO2 laser therapy, and scalpel excision.2 Cryotherapy is a safe and simple selection in which a cryoprobe at a temperature of approximately -65 ºC is applied to the lesion to freeze and destroy the affected tissue.6 Diode laser therapy is another surgical option that involves the use of a concentrated beam of light for precise excision of the lesion with simultaneous hemostasis. Treatment with CO2 laser therapy allows for precise control of margins, minimal bleeding, decreased surgical time, minimal postoperative complications, and minimal scarring.15 Full excision involves the use of a scalpel to completely remove the lesioned area. Although a viable option, traditional scalpel removal is associated with increased intraoperative bleeding, postoperative infection, and possibly disfiguring results.

Comparison of CO2 Laser Therapy vs Cryotherapy
In a 2017 study, Natekar and colleagues compared outcomes of CO2 laser therapy, diode laser therapy, and cryotherapy in the treatment of oral leukoplakia (Figure).16 All 3 treatments were effective in the treatment of oral leukoplakia; however, both CO2 and diode laser therapies were associated with significantly lower rates of pain, hemorrhage, edema, and infection compared with cryotherapy (Table; P >.05). None of the patients in the laser therapy and cryotherapy groups developed scar formation compared with 30% of the cryosurgery group at 3 months; by 6 months all scars had resolved. None of the patients experienced recurrence at 6-month follow-up. While all treatment options should be considered for oral leukoplakia, postoperative risk and benefits should be discussed with patients to aid in the informed decision-making process.

Treatment Challenges With CO2 Laser Therapy
One challenge facing clinicians is deciding which patients may benefit from CO2 laser therapy. In a case study published by Pedrosa and colleagues, 59 patients with oral leukoplakia underwent 3 treatments of CO2 laser therapy, with 4-week intervals between each session.17 Results from this study show that 94% of patients with no or low-grade dysplasia were disease-free at 6-month follow-up. Lesion relapse at the treatment site occurred in 24 people (41%) at approximately 17 months postoperatively, and 25% of those patients (n=6) experienced transformation to squamous cell carcinoma.17

Initial histology from those patients who transformed to SCC revealed moderate- to high-grade dysplasia prior to CO2 laser treatment. CO2 laser therapy can still be used for moderate- to high-grade dysplasia; however, the increased recurrence rate should be discussed with the patient as well as the possible need for additional treatment with the more aggressive modality of traditional scalpel excision.

Another challenge of the CO2 laser, as well as for all therapies, is providing full application and treatment to all dysplastic cells. Due to the possibility of incomplete treatment, an extension of margins should be performed at least 3 mm beyond the lesion.15 The extension of laser therapy can further ensure destruction of dysplastic cells surrounding the lesion and aid in minimizing recurrence rates.

Prevention of Oral Leukoplakia
Primary care providers can aid in the primary prevention of oral leukoplakia by routinely screening their patients for this condition; risk factors include the use of tobacco products and excess alcohol consumption. Additionally, while taking a patient’s history, providers should inquire about oral hygiene routine, regularity of dental care visits, and any barriers that may affect the ability to receive oral health care. The survey by the American Dental Association showed that only 58% of respondents reported visiting a dentist at least once per year.18

If a patient is unable to visit a dentist biannually or maintain proper oral hygiene, the primary care provider can begin dental patient education and refer the patient to alternative and more affordable care options, such as public dental clinics or dental schools that can aid in oral health for minimal fees. Patient education should be offered to all individuals regarding the development of oral cancers caused by tobacco products and heavy alcohol use. If applicable, the provider can develop a treatment plan, counsel, or refer the patient for nicotine and or alcohol dependence.

Secondary prevention refers to monitoring the disease. Patients diagnosed with oral leukoplakia require frequent oral cavity examinations to identify any possible changes; especially because clinically lesions are asymptomatic. Thus, it is essential for primary care clinicians to be proactive and assess the oral cavity in all patients, especially those with risk factors, to promptly diagnose conditions such as oral leukoplakia. The earlier leukoplakia is diagnosed, the sooner treatment options can be discussed and performed.

Leukoplakia is one of the most common oral disorders that may progress to carcinoma. When discussing treatment options with patients, it is essential to discuss the risks and benefits associated with each possible procedure. It is also critical for clinicians to emphasize the importance of health care maintenance, including cessation of smoking and frequent follow-up with primary care providers and dentists, even after treatment, for inspection of new lesions or possible recurrence.Conclusion

Christina Alvarez, PA-C, is an Internal Medicine and Pediatrics Physician Assistant and graduate from the St. John’s University Class of 2020 Physician Assistant Program in Queens, New York; Corinne I. Alois, MS, PA-C, is an assistant professor at St. John’s University Physician Assistant Program; Louise Lee, EdD, MHA, PA-C, is an associate professor and director of PA studies at St. John’s University.

1. Vail M, Robinson S, Condon H. Recognition of oral potentially malignant disorders and transformation to oral cancer. JAAPA. 2020;33(11):14-18. doi:10.1097/01.JAA.0000718268.52634.59

2. Mohammed F, Fairozekhan AT. Oral leukoplakia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Updated July 27, 2021. https://www.ncbi.nlm.nih.gov/books/NBK442013/

3. Guimarães LM, Diniz MG, Rogatto SR, Gomez RS, Gomes CC. The genetic basis of oral leukoplakia and its key role in understanding oral carcinogenesis. J Oral Pathol Med. 2021 Aug;50(7):632-638. doi: 10.1111/jop.13140.

4. Macigo FG, Gathece LW, Guthua SW, Njeru EK, Wagaiyu EG, Mulli TK. Oral hygiene practices and risk of oral leukoplakia. East Afr Med J. 2006;83(4):73-8. doi:10.4314/eamj.v83i4.9419

5. Shang Q, Peng J, Zhou Y, Chen Q, Xu H. Association of human papillomavirus with oral lichen planus and oral leukoplakia: a meta-analysis. J Evid Based Dent Pract. 2020;20(4):101485. doi:10.1016/j.jebdp.2020.101485

6. Cleveland Clinic. Leukoplakia. Updated August 6, 2020. Accessed August 25, 2021. https://my.clevelandclinic.org/health/diseases/17655-leukoplakia

7. Parlatescu I, Gheorghe C, Coculescu E, Tovaru S. Oral leukoplakia – an update. Maedica (Bucur). 2014;9(1):88-93.

8. Kujan O, Idrees M, Anand N, Soh B, Wong E, Farah CS. Efficacy of oral brush cytology cell block immunocytochemistry in the diagnosis of oral leukoplakia and oral squamous cell carcinoma. J Oral Pathol Med. 2021;50(5):451-458. doi: 10.1111/jop.13153

9. Alsarraf A, Kujan O, Farah CS. Liquid-based oral brush cytology in the diagnosis of oral leukoplakia using a modified Bethesda Cytology system. J Oral Pathol Med. 2018;47(9):887-894. doi:10.1111/jop.12759

10. Reddy SG, Kanala S, Chigurupati A, Kumar SR, Poosarla CS, Reddy BV. The sensitivity and specificity of computerized brush biopsy and scalpel biopsy in diagnosing oral premalignant lesions: A comparative study. J Oral Maxillofac Pathol. 2012;16(3):349-353. doi:10.4103/0973-029X.102482

11. Mortazavi H, Safi Y, Baharvand M, Jafari S, Anbari F, Rahmani S. Oral white lesions: an updated clinical diagnostic decision tree. Dent J (Basel). 2019;7(1):15. doi:10.3390/dj7010015

12. Rathee M, Jain P. Hairy leukoplakia. In: StatPearls [Internet]. StatPearls Publishing; 2021 Jan-. Updated April 17, 2021. Accessed August 25, 2021. https://www.ncbi.nlm.nih.gov/books/NBK554591/

13. Arnold DL, Krishnamurthy K. Lichen planus. In: StatPearls [Internet]. StatPearls Publishing; 2021 Jan-. Updated August 11, 2021. Accessed August 25, 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526126/

14. Lodi G, Franchini R, Warnakulasuriya S, et al. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database Syst Rev. 2016;7(7):CD001829. doi:10.1002/14651858.CD001829.pub4

15. Romeo U, Mohsen M, Palaia G, Bellisario A, Del Vecchio A, Tenore G. CO2 laser ablation of oral leukoplakia: with or without extension of margins? Clin Ter. 2020;171(3):e209-e215. doi:10.7417/CT.2020.2215

16. Natekar M, Raghuveer HP, Rayapati DK, et al. A comparative evaluation: Oral leukoplakia surgical management using diode laser, CO2 laser, and cryosurgery. J Clin Exp Dent. 2017;9(6):e779-e784. doi:10.4317/jced.53602

17. Pedrosa A, Santos A, Ferreira M, Araújo C, Barbosa R, Medeiros L. Is carbon dioxide laser vaporization a valuable tool in the management of oral leukoplakia? A survey at an oncology hospital. Lasers Med Sci. 2015;30(5):1629-30. doi:10.1007/s10103-014-1551-2

18. American Dental Association. Survey: more Americans want to visit the dentist. ADANews. March 21, 2018. Accessed August 25, 2021. https://www.ada.org/en/publications/ada-news/2018-archive/march/survey-more-americans-want-to-visit-the-dentist

2021-09-05T08:19:58-07:00September, 2021|Oral Cancer News|

Study: HPV vaccination will reduce throat and mouth cancers, but overall impact will take 25-plus years to see

Source: www.newswise.com
Author: Johns Hopkins Bloomberg School of Public Health

Vaccinations against human papillomavirus (HPV), a major cause of throat and back of mouth cancers, are expected to yield significant reductions in the rates of these cancers in the U.S., but will not do so until after 2045, according to a new modeling study from researchers at the Johns Hopkins Bloomberg School of Public Health. HPV is the most common sexually transmitted infectious virus worldwide. HPV infections are often silent, and while most infections clear, some are chronic and can trigger cancers including mouth and throat (oropharyngeal), and cervical cancer because they disrupt DNA and inhibit tumor-suppressor proteins in the cells they infect. Although there is no cure for existing HPV infections, new infections are preventable with vaccines, the first of which entered use in the U.S. in 2006.

In the new study, the Bloomberg School researchers analyzed national databases on oropharyngeal cancer cases and HPV vaccinations, and projected the impact of HPV vaccination on the rates of these cancers in different age groups. They estimated that the oropharyngeal cancer rate would nearly halve between 2018 and 2045 among people ages 36–45. However, they also projected that the rate in the overall population would stay about the same from 2018-2045, due to still-rising rates of these cancers in older people, where most of these cancers occur.

The study appears online September 2 in JAMA Oncology.

“We estimate that most of the oropharyngeal cancers from 2018 to 2045 will occur among people who are 55 years and older and have not been vaccinated,” says study lead author Yuehan Zhang, a PhD candidate in the research group of Gypsyamber D’Souza, PhD, professor in the Department of Epidemiology at the Bloomberg School.

“HPV vaccination is going to work to prevent oropharyngeal cancers, but it will take time to see that impact, because these cancers mostly occur in middle age,” D’Souza says.

Oropharyngeal cancer is the most common HPV-related cancer, and according to the Oral Cancer Foundation there are more than 50,000 new cases of it in the U.S. each year. Alcohol and tobacco use also are risk factors, but are seen as increasingly less important than HPV.

Vaccination is a powerful medical weapon against this family of viruses, but has one major shortcoming: It can prevent, but not treat. In other words, it does not work against established HPV infections or against cells that have been transformed by HPV and are on their way to forming tumors. Thus it is recommended chiefly for the young who are not yet exposed to sexually transmitted HPV. (Most people who were already adults when HPV vaccination became available have never been vaccinated, and thus remain at risk for these cancers.)

For the study, the researchers estimated current and future HPV vaccination rates using data from surveys conducted by the U.S. Centers for Disease Control and Prevention, and projected oropharyngeal cancer rates based on past and current incidence data from the National Cancer Institute.

They estimated that the rates of vaccination by 2045, for different age groups—given the emphasis on vaccinating the young—will amount to about 72 percent of people ages 36–45, 37 percent of those ages 46–55, 9 percent of those ages 56–69, and 0 percent of people ages 70–83 being vaccinated.

These projections show continuing high oropharyngeal cancer rates in older, mostly unvaccinated groups, and almost no change in the overall U.S. rate of these cancers—14.3 per 100,000 assuming no vaccination; and 13.8 per 100,000, with vaccination, in 2045.

However, they foresaw the rates of new oropharyngeal cancers would fall substantially in the relatively well vaccinated 36–45 and 46–55 age groups during the 2018–2045 period: from 1.4 to 0.8 per 100,000; and from 8.7 to 7.2 per 100,000, respectively.

The results suggest, though, that by 2045 HPV vaccination will have begun to make a significant impact. “Our projections suggest that by around 2033, nearly 100 cases of oropharyngeal cancer will be prevented each year, but by 2045 that figure will have increased by about ten times,” Zhang says.

“Projected Impact of HPV Vaccination on Oropharynx Cancer Incidence in the United States: 2020-2045” was co-authored by Yuehan Zhang, Carole Fakhry, and Gypsyamber D’Souza.

Funding was provided by the National Institute of Dental and Craniofacial Research (R35DE026631).

2021-09-03T12:26:37-07:00September, 2021|Oral Cancer News|

Immunotherapy for HPV+ head and neck cancer: Awakening the force within

Source: medicalxpress.com
Author: Emory University

A new study from scientists at Emory Vaccine Center and Winship Cancer Institute of Emory University reports that the immune cells that are the major targets of immune checkpoint inhibitors are present in tumors from head and neck cancer patients.

The study focuses on head and neck tumors that are positive for human papillomavirus (HPV), which is becoming one of most common types of head and neck cancers treated in the Western world. The results are scheduled for publication in Nature.

It suggests checkpoint inhibitors, which have transformed the treatment of several types of cancer, could be uniquely effective against this type of head and neck cancer. The results also indicate that the experimental approach of therapeutic vaccination for HPV+ cancer could be broadened to include more elements of the virus, to potentially trigger a broader and stronger immune response.

Researchers from Rafi Ahmed’s lab at Emory Vaccine Center collaborated with the co-directors of the Winship Head and Neck Cancers working group, oncologists Nabil Saba, MD and Mihir Patel, MD, to obtain samples from patients with head and neck tumors early in the course of treatment.

“About five years ago, we began to have an influx of patients that sought out our center for surgical treatment,” Patel says. “We often heard some variation of a similar story: I was sick with cold-like symptoms and once that resolved this I noticed swelling in a lymph node on the side of my neck. Stories like this made us think about how the immune system might play a unique role, different than typical smoking-related head and neck cancers.”

The team wanted to learn more about the different kinds of CD8 or “killer” T cells present within the cancers; CD8 T cells are specialized immune cells capable of detecting and killing virus-infected or tumor cells, if they are not constrained by regulatory signals. The inhibitory receptor PD-1 is highly expressed on exhausted CD8 T cells in chronic viral infections and cancer, and stem-like PD-1+ CD8 T cells are crucial for maintaining tumor-specific CD8 T cell responses. The majority of currently available checkpoint inhibitors, such as pembrolizumab and nivolumab, block the PD-1 signaling pathway.

“Our results show that a subset of HPV-specific CD8 T cells in the tumor exhibits a striking resemblance to the stem-like CD8 T cells our lab has previously defined in mouse models as proliferating in response to PD-1 blockade,” says Andreas Wieland, Ph.D., co-lead author of the paper and an instructor in Ahmed’s lab.

“It is reasonable to assume that these cells would similarly provide a proliferative burst in response to PD-1 blockade in these patients. However, this remains to be formally tested.”

HPV-positive tumors do have a relatively good response to conventional forms of treatment such as radiation and chemotherapy, Wieland adds. The group of patients studied at Winship was treatment-naïve when tumor samples were obtained; how radiation and chemotherapy affect the number and phenotype of T cells in the tumor needs additional investigation.

“These findings greatly enhance our understanding of CD8 T cell responses in the tumor micro-environment in HPV-related oropharynx cancers, and likely other virally mediated tumors,” Saba says. “It confirms the existence of the different lineages necessary for an effective T cell specific anti-tumor response. Taking advantage of the local immune-response by avoiding its possible early elimination by traditional therapeutic modalities may pave the way to an improved clinical outcome for patients. It may have implications for how best to incorporate immunotherapy in the treatment of other virally mediated tumors.”

“We now have an inclination that incorporating immune therapy with PD-1 blockade prior to surgery or radiation may benefit patients,” Patel says. “We are actively in the process of developing ‘window of opportunity’ studies to understand this.

Looking at both primary tumors and metastatic lymph nodes, the researchers were able to detect both tumor-specific stem-like CD8 T cells, which can proliferate in response to HPV peptides, and more terminally differentiated cells that do not proliferate. In contrast to significant numbers of tumor-specific CD8 T cells in the tumors, tumor-specific cells appeared at a very low abundance in patients’ blood, suggesting that they preferentially reside in tumors. The team also found that the different CD8 T cell subsets in the tumor microenvironment differ in their localization, with stem-like cells residing in distinct niches within the stroma and away from the tumor cells themselves.

Concentrating on HPV-positive tumors in this study facilitated the study of tumor-specific T cells with defined specificities across several patients as the virus is providing a defined set of tumor-associated antigens, whereas in other types of cancer the antigens caused by mutations will vary from individual to individual.

Co-first authors of the paper are Haydn Kissick, Ph.D., assistant professor of urology and microbiology and immunology, and Christiane Eberhardt, MD, a former postdoctoral fellow in Ahmed’s lab who is now at the University of Geneva. Patel is also associate professor of otolaryngology at Emory University School of Medicine. Saba is professor and Vice Chair in the Department of Hematology and Medical Oncology.

2021-09-02T20:07:01-07:00September, 2021|Oral Cancer News|

AI can lend a hand in diagnosis, prognosis of oral SCC

Source: www.auntminnie.com
Author: Erik L. Ridley, AuntMinnie.com staff writer

Radiology and pathology artificial intelligence (AI) algorithms can help in diagnosing and assessing the prognosis of oral squamous cell carcinoma (SCC), according to a literature review published August 19 in JAMA Otolaryngology — Head & Neck Surgery.

After reviewing published studies in the literature on the use of AI with pathology and radiology images in patients with oral SCC, researchers from the University of Hong Kong concluded that the technology yielded good classification accuracy.

“The successful use of deep learning in these areas has a high clinical translatability in the improvement of patient care,” wrote the authors, led by first author Chui Shan Chu and senior author Dr. Peter Thomson, PhD.

In radiology applications for oral SCC, a convolutional neural network (CNN) was able to predict disease-free survival with 80% accuracy, sensitivity, and specificity from PET images, the researchers reported. Another CNN showed lower performance — 66.9% sensitivity, 89.7% specificity, and 84% accuracy — when used on CT for predicting disease-free survival. A deep-learning algorithm also yielded 90% sensitivity for detecting lymph node metastasis from oral SCC on CT.

In addition to providing prognosis predictions, AI could help facilitate personalized treatment from CT images, according to the researchers. One model was 76% accurate for predicting xerostomia, or dry mouth, an adverse effect of radiotherapy caused by toxicity. Another study determined that radiation dose distribution is the most crucial factor for predicting toxicity.

The researchers noted that, to the best of their knowledge, no studies have utilized deep learning with MRI in oral SCC applications.

As for pathology, AI has most frequently been used to facilitate oral SCC diagnosis by classifying cell type and differentiating tumor grade on digital hematoxylin and eosin-stained tissue images. A CNN algorithm, for example, achieved 96.4% accuracy for differentiating cancer cells from six different types of nontumor cells. Another algorithm was 84.8% accurate for differentiating head and neck SCC from thyroid cancer and metastatic lymph node from breast cancer.

What’s more, other classifiers stratified oral SCC images into four classes with 97.5% accuracy and classified hematoxylin and eosin-stained oral tissue images as either normal or dysplasia with 89% accuracy. In addition, an algorithm was able to predict survival with an average accuracy of 80%.

“In oral cancer research, particularly that related to SCC, deep learning with the use of readily available clinical images derived from hematoxylin and eosin-stained pathological sections and CT-based radiography is demonstrated to have the potential to aid clinical decision-making with regard to cancer diagnosis, prognosis prediction, and treatment guidance,” the authors wrote.

Once their accuracy is validated in different patient cohorts, deep-learning algorithms could be used as a decision-support tool for clinicians, according to the researchers. More research will be needed, however, to determine how to best implement AI into the routine clinical workflow.

“To expand the application of deep learning, it can be used to infer tumor biology information based on the expression-level alterations or mutations of targetable molecules for immunotherapy and targeted therapy,” the authors wrote. “If this approach is successful, it is economical and time-saving to reveal molecular information of tumors without using additional costly molecular assays.”

UAB adds personalized touch to cancer treatment with adaptive radiation

Source: www.uab.edu
Author: Bob Shepard

They are calling it radiation oncology’s contribution to personalized medicine. — called by some the holy grail of radiation therapy — has come to the University of Alabama at Birmingham O’Neal Comprehensive Cancer Center in the form of the newest radiation delivering tool, a system called Ethos from Varian.

Simply put, a linear accelerator is the machine that is used to deliver radiation therapy to destroy a tumor. In standard radiation therapy, the medical team uses sophisticated imaging to pinpoint the location of a tumor, then develops a precise approach to target that tumor with radiation.

“Patients typically get a CT scan so the radiation team can map out their strategy, a process that can take one to two weeks,” said Dennis Stanley, Ph.D., an assistant professor and medical physicist in the UAB Department of Radiation Oncology. “Then, most patients get radiation for around six weeks, usually five days a week.”

But in that time from initial CT screening to the end of treatment, things can change.

“A patient’s anatomy can change over this time period,” Stanley said. “Weight gain or loss, shifting of tissues following eating and drinking. Anatomy can change as quickly as day-to-day.”

Adaptive therapy simply means the radiation plan can adapt to those changes. The Ethos system is the first machine that can quickly scan a patient while they are on the treatment table prepping for their next treatment, and allow for fine-tuning of the already established treatment plan. Instead of following a rigid treatment plan over the course of several months, adaptive therapy can make adjustments to the plan as needed on a weekly or even daily basis.

“We can re-image the patient while they are on the table, and compare the patient’s initial anatomy to the patient’s current anatomy,” said Samuel Marcrom, M.D., assistant professor in the Dept. of Radiation Oncology. “If there have been changes, we can tweak the plan almost instantaneously. The result is a more accurate radiation treatment based on real-time information, creating an opportunity for more radiation to be delivered to the tumor with less radiation delivered to healthy tissue nearby. It is a personalized medicine approach for radiation oncology.”

UAB Medicine and the Department of Radiation Oncology are among the first in the nation to install an Ethos system. There are only 12 currently operating in the United States.

UAB used the Ethos system for the first time on Aug. 10. Stanley and Marcrom say it can be useful for many types of cancers, especially for prostate and cervical cancers due to the propensity of the internal anatomy to change over time in the pelvis. UAB will first treat pelvic tumors with Ethos, gradually moving toward lung and chest cavity cancers. Ethos is also suited for head and neck cancers.

Ethos is the newest tool in the rapidly advancing field of radiation oncology. UAB added proton therapy in March 2020 when Proton International at UAB became the first proton therapy center in Alabama. Proton therapy uses highly precise proton beams instead of traditional X-rays to treat the tumor, leading to more precise and conformal treatment of the tumor with less dose to normal tissues.

“Ethos is another tool that helps aim radiation at the tumor target and avoid healthy tissue, much as proton therapy does,” Stanley said. “This is a valuable option for patients who are not candidates for protons, or any of our other radiation delivery systems.”

UAB’s Ethos system is the first in the world to use the Varian Identify Surface imaging system in conjunction with the Ethos delivery system for patient monitoring and localization. This allows for more accurate positioning and monitoring of patients throughout the course of treatment without adding any extra radiation.

“Ethos gives us options that we haven’t had before,” Marcrom said. “We are able to treat a patient’s cancer based on what it looks like right now, not what it looked like days or weeks earlier. That is a significant advantage.”

The British start-up that’s given Val Kilmer his voice back

Source: www.dailymail.co.uk
Author: Jonathan Chadwick for MailOnLine

A British artificial intelligence (AI) company has recreated Hollywood actor Val Kilmer’s voice – with amazingly realistic results. London-based firm Sonantic used the actor’s voice recordings from throughout his career, which were fed to their AI to create the lifelike yet artificial mock-up.

Film producers could potentially use the tool – described as ‘Photoshop for voice’ – for voiceovers if they have a role in mind that would be suited to Kilmer’s tones.

Kilmer, whose career has spanned nearly four decades, has starred in blockbusters such as Top Gun, Willow, The Doors, Tombstone and Batman Forever. But after undergoing a tracheotomy in 2014 as part of his treatment for throat cancer, Kilmer’s voice is now barely recognisable.

Val Kilmer, pictured here in 2019, underwent a tracheotomy in 2014 as part of his treatment for throat cancer and now speaks with a voice box. Getty Images

Luckily, Kilmer himself is also able to use the AI tool in his personal life, to help him communicate, rather than relying on a voice box to speak.

The artificial voice, which speaks in the first person as Kilmer in Sonantic’s video, could easily be mistaken for the real thing.

Praising the results, the real Val Kilmer said: ‘I’m grateful to the entire team at Sonantic who masterfully restored my voice in a way I’ve never imagined possible.

As human beings, the ability to communicate is the core of our existence and the effects from throat cancer have made it difficult for others to understand me.

‘The chance to tell my story, in a voice that feels authentic and familiar, is an incredibly special gift.’

Sonantic CTO and co-founder John Flynn described the ambitious project in a blog post on his company’s website.

The firm is mostly used to working with video game studios like Obsidian, Embark, Sumo Digital to record dialogue for their characters.

Flynn told MailOnline his firm were approached by Kilmer’s team late last year as they were creating the Amazon Prime documentary, Val.

‘We all came together – Val as someone who’d lost their voice and Sonantic as a company who creates best in class quality voices,’ he said.

As human beings, the ability to communicate is the core of our existence and the effects from throat cancer have made it difficult for others to understand me.

‘The chance to tell my story, in a voice that feels authentic and familiar, is an incredibly special gift.’

Sonantic CTO and co-founder John Flynn described the ambitious project in a blog post on his company’s website.

The firm is mostly used to working with video game studios like Obsidian, Embark, Sumo Digital to record dialogue for their characters.

Flynn told MailOnline his firm were approached by Kilmer’s team late last year as they were creating the Amazon Prime documentary, Val.

‘We all came together – Val as someone who’d lost their voice and Sonantic as a company who creates best in class quality voices,’ he said.

For the project, Sonantic gathered audio recordings of the actor from his films, which were digitally ‘cleaned’ to remove background noise. Next, the experts generated transcripts from the audio before pairing the audio and text together in short chunks that could be fed to the AI during its training.

The firm generated more than 40 different voice models and selected the ‘best, highest-quality and most expressive one’. The results left Kilmer’s son, Jack, close to tears.

‘We’d worked on the voice model and heard it so many times, but when we played it for Val and his team it was incredibly emotional for us,’ Flynn told MailOnline.

‘I remember talking to Jack after presenting the voice model, and him telling us how powerful it was, like it was the first time he’d heard his dad’s voice in years, so he was quite moved.’

Kilmer will be able to use the AI model in both his professional and personal life, according to Flynn.

‘Kilmer can take part in TV or film productions that require voice overs or replacement dialogue that will be created by Sonantic’s easy-to-use computer app,’ he told MailOnline. ‘He can license that audio to different productions and studios.

‘The voice model can be used as a personalised replacement to robotic speech generating devices and help him communicate in his day-to-day life.’

The CTO wouldn’t reveal to MailOnline whether his firm is working with any other actors in a similar way.

‘We believe actors will always work real-life jobs but this gives them the opportunity to earn money doing virtual work too,’ he said.

‘For example, they can turn up for an important audition while their voice model works on an advertisement or other work.’

Amazon Prime Videos’ autobiographical documentary of Val Kilmer’s life, ‘Val’, was released on August 6.

The film contains thousands of hours of footage ranging from home videos to test shots for his iconic films such as Top Gun.

Study explores the effect of graphic warning labels on cigarette packaging among US smokers

Source: www.news-medical.net
Author: Reviewed by Emily Henderson, B.Sc

Purchase a pack of cigarettes in Australia and be prepared to be accosted with graphic warning labels depicting the dangers of tobacco use – including images of gangrene of the foot, a newborn with a breathing tube and throat cancer.

“Graphic warning labels are used in more than 120 countries to counter marketing that promotes cigarette smoking. We wanted to know what effect such cigarette packaging would have on United States smokers,” said David Strong, professor at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego.

Graphic warning labels were mandated by the United States Congress in 2009 but implementation has been stopped pending the outcome of legal challenges to the law by the tobacco industry.

In a paper published online in JAMA Network Open on Aug. 4, 2021, Strong and colleagues at UC San Diego Moores Cancer Center, California State University San Marcos, San Diego County Public Health Services, and San Diego State University, demonstrated that graphic warning labels are effective reminders of the negative health consequences of smoking.

“Graphic warning labels caused daily smokers in the United States to perceive cigarettes to be less positive and it increased their concerns about the health effects of smoking on both themselves and their loved ones,” said corresponding-author John P. Pierce, Distinguished Professor at the Herbert Wertheim School of Public Health.

The study manufactured special cigarette packs that incorporated the graphic warning labels used on cigarette packs in Australia (under license from the Australian government). Study participants were 357 smokers living in San Diego who agreed to purchase their preferred brand of cigarettes from a study website. Participants were randomized to receive their cigarettes in one of three pack designs: in package with a graphic warning label, with a blank pack, or in a standard commercially available U.S. pack.

During the study, participants were queried by interactive text messaging about concerns over health risks and about their perceptions of the most recent cigarettes that they smoked. Changes in consumption and smoking status were assessed at the end of the three-month intervention.

Participants who received cigarettes in the standard pack or a blank pack had no change in their positive perceptions of their cigarettes, while smokers randomized to the graphic warning label arm perceived their cigarettes less favorably. Health concerns increased in all three groups, likely due to the intervention that made them think about health consequences more often, said the study authors.

“While these labels make smokers more likely to think about quitting, it did not make them more likely to make a serious quit attempt, nor was it sufficient to help them quit their nicotine addiction. Thus, graphic warning labels are an integral component of tobacco control strategies but they are only one tool for governments to reduce the societal costs from the death and disease caused by tobacco smoking.”
Karen Messer, senior-author, professor of biostatistics, Herbert Wertheim School of Public Health

Journal reference:
Strong, D.R., et al. (2021) Effect of Graphic Warning Labels on Cigarette Packs on US Smokers’ Cognitions and Smoking Behavior After 3 Months. JAMA. doi.org/10.1001/jamanetworkopen.2021.21387.

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Val Kilmer’s kids describe watching their father battle throat cancer in ‘Val’: ‘It’s incredibly difficult’

Source: www.yahoo.com
Author: Ethan Alter·Senior Writer, Yahoo Entertainment

It’s not easy for any child to watch their parent battle a serious illness. But it can be an even bigger challenge when that parent is also a public figure with an innately curious fanbase. That’s the situation that Jack and Mercedes Kilmer have lived with for the past few years as their father — Top Gun star Val Kilmer — has waged a public and private battle with throat cancer. Kilmer’s health struggles, which have affected his ability to speak, are put on full view in the highly personal new documentary Val, premiering on Aug. 6 on Prime Video. His adult children associate produced and appear extensively in the film, which includes footage of the actor at some of the lowest moments in his illness.

“It’s incredibly difficult,” Mercedes Kilmer tells Yahoo Entertainment about watching her father in those moments. “Especially for him because his work is his voice. [Because of] his training as an actor… he has such a natural faculty for speech, and I don’t think he honestly would have survived… were it not for his dedication to developing that muscle of his voice.”

Since Kilmer now speaks with the aid of a voice box following his recent tracheotomy, Jack Kilmer acts as his father’s voice in Val. The younger Kilmer narrates his dad’s life story as it plays out via home movies shot by Kilmer on his various movie sets, alongside new footage filmed by directors Leo Scott and Ting Poo. “He’s such a force of nature,” his son says. “He’ll be at his lowest in the hospital cracking jokes, and having the whole staff in fits of laughter. We were more worried about people’s reaction [to his illness] than actually going through the process with him, but people ended up being just nothing but supportive and cool.”

Raised as a Christian Scientist, Kilmer told The New York Times last year that he initially was reluctant to seek medical care after he was diagnosed with throat cancer in 2014. In that same interview, he suggested that his children ultimately convinced him to pursue treatment, and also attributed his healing to prayer as opposed to medical procedures. “I prayed, and that was my form of treatment,” he remarked, adding that he considered procedures like his tracheotomy to have “caused my suffering.”Jack Kilmer acts as his father’s voice in Val. The younger Kilmer narrates his dad’s life story as it plays out via home movies shot by Kilmer on his various movie sets, alongside new footage filmed by directors Leo Scott and Ting Poo. “He’s such a force of nature,” his son says. “He’ll be at his lowest in the hospital cracking jokes, and having the whole staff in fits of laughter. We were more worried about people’s reaction [to his illness] than actually going through the process with him, but people ended up being just nothing but supportive and cool.”

Val Kilmer in a scene from the documentary, Val. (Photo: Courtesy of Amazon Studios)

Asked what those early conversations about seeking medical treatment were like, his children offer a somewhere different account of what happened. “We both have always respected his beliefs, something that’s deeply important to me is bodily autonomy,” says Mercedes Kilmer. “I’ve always wanted him to get better and I’ve always, really cared what’s going on with his health, but I deeply respect the way that he’s dealt with it and I respect his right to heal however he feels is best.” Adds Jack: “I mean, who wants to go to the doctor? It sucks, you know?”

But Val isn’t just a chronicle of Kilmer’s health struggles: it’s also a first-hand account of his film career, covering such favorites as Tombstone, The Doors and, of course, Top Gun. The actor had a camcorder with him throughout the shoot of Tony Scott’s 1986 favorite — which recently celebrated its 35th anniversary — and that never before seen footage of Kilmer partying alongside a young Tom Cruise, Anthony Edwards and Rick Rossovich provides some of Val’s most memorable moments. And the filmmakers tease that there’s even more they couldn’t include. “There’s several hours worth of that material,” director Leo Scott says. “It’s very iconic. We probably could have made a half-hour version of that if we wanted to!”

Perhaps that Top Gun-only cut of Val can precede the release of the highly-anticipated sequel, Top Gun: Maverick, which is scheduled for a November release after being repeatedly delayed by the coronavirus pandemic. Top Gun producer Jerry Bruckheimer already promised Yahoo Entertainment that Kilmer will reprise his signature role as Cruise’s onscreen nemesis, Iceman. “No spoilers, but he’s in the movie,” he teased last year.

Kilmer’s kids can confirm their father’s appearance since they were on set when he filmed his cameo. “We were this close to Tom’s face,” Jack remembers. “He came up and hugged me and just looked me right in the eyes. It was very surreal!” Mercedes recalls how thrilled she was to see her father reunited with the Top Gun crew. “It was really beautiful… I had never seen all of the behind-the-scenes stuff of Top Gun, but my dad filmed all of it, and you can see the guys horsing around on set. And they’re all exactly the same when they’re together now.”

As for what the future holds for their father, the siblings suggest that he’ll find other creative avenues beyond the big screen. “Acting is just one of the things that he does,” notes Jack. “He thrives in doing a lot of other creative things.” Adds his sister: “He never stops working, never! He has a lot of stuff in the works. As for acting, he can’t perform the way that he used to, but everything he does is kind of an extension of that. And you see that throughout this film: this collage of different characters and identities makes up the person that he is.”

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