Calls grow for treatment deintensification of HPV-positive OPC

Source: ww.pharmacytimes.com
Author: Bryan Fitzgerald, PharmD, BCOP
Health-System Edition, July 2021, Volume 10, Issue 4

Oropharyngeal cancer (OPC) is a type of head and neck cancer that affects structures in the back of the throat, including the base of the tongue, the posterior pharynx, the soft palate, and the tonsils.1 In the United States, rates of OPC are increasing each year, with an estimated 54,010 new cases in 2021.2 Well-established risk factors include alcohol abuse; exposure to tobacco, including chewing tobacco, cigarettes, and pipes; and infection with human papillomavirus (HPV).

With an estimated 43 million infections in 2018, HPV is the most common sexually transmitted infection in the United States.3 HPV infection is causally linked with cancers of the anogenital region, including anal, cervical, penile, vaginal, and vulvar cancers. When HPV is spread orally, infections can also lead to the development of OPC. In the United States, more than 70% of OPC cases are caused by HPV.4

HPV is a group of more than 100 viruses, including certain high-risk strains associated with the development of cancer. The HPV-16 strain is responsible for causing the majority of HPV-positive (HPV+) OPC cases, with HPV-18, HPV-33, and HPV-35 also contributing, albeit significantly less than HPV-16.1 In these high-risk HPV strains, the viral genome encodes several oncogenic proteins that inhibit tumor suppressor proteins, leading to chromosomal instability and malignancy in infected cells.

HPV+ OPC is considered a genetically distinct form of OPC. Compared with HPV-negative (HPC–) OPC cases, HPV+ OPC is associated with a favorable prognosis with improved rates of response prognosis with improved rates of response to treatment and overall survival. Because of the difference in tumor biology, the National Comprehensive Cancer Network (NCCN) has adopted different staging criteria for HPV+ and HPV– disease and recommends that HPV status be used to stratify patients with OPC.1

The treatment landscape for localized OPC typically involves a multidisciplinary approach consisting of chemotherapy, radiation, and/or surgery. For fit patients with locally advanced OPC who are able to tolerate intensive therapy, concurrent radiation with systemic high-dose cisplatin chemotherapy is the preferred treatment regimen.1 Unfortunately, treatment of OPC is associated with a high risk of treatment-related morbidity, which may leave patients cured of their malignancy but with lifelong complications, such as dysgeusia, dysphagia, and xerostomia, but also systemic complications from cisplatin chemotherapy, including hearing loss and neurotoxicity.

Because patients with HPV+ OPC are generally younger with more favorable prognoses, clinicians have hypothesized that less intensive treatment could result in fewer long-term complications from treatment but with continued favorable cancer-related outcomes.5 This concept, called deintensification, has become popular in recent years. Several strategies for treatment deintensification have been proposed, including reducing the dose of radiation; substituting cisplatin for an alternative agent with less toxicity, such as cetuximab; and surgical resection. Several phase 3 comparison trials have been conducted, and other trials are ongoing.

Aptly named De-ESCALaTE (NCT01874171), this phase 3 trial randomized patients with 334 HPV+ OPC to receive radiation plus cetuximab or cisplatin.6

Unfortunately, the trial results did not favor substitution of cisplatin with cetuximab. At 2 years, the incidence of severe toxicities did not significantly differ between cetuximab and cisplatin (P = .98), nor did rates of overall toxicities (P = .49). Significant differences in 2-year overall survival rates and recurrence rates were seen. However, these results favored cisplatin (HR, 5.0; P = .001 for overall survival; HR, 3.4; P = .0007 for recurrence).6

RTOG-1016 (NCT01302834) was a second phase 3 trial published comparing cetuximab with cisplatin in HPV+ OPC patients.7 This trial analyzed 805 patients who were randomized to receive radiation plus cetuximab or cisplatin. Similar to the De-ESCALaTE trial, the RTOG-1016 trial results favored cisplatin over cetuximab, with 5-year overall survival rates of 84.6% versus 77.9%.8

Because of the De-ESCALaTE and RTOG-1016 results, experts advise against the substitution of cisplatin for chemoradiation regimens for patients with localized HPV+ OPC, and cisplatin plus radiation continues to be the preferred systemic treatment option per the NCCN guidelines.1,5 Because cisplatin continues to be standard of care for the treatment of localized OPC, the role of deintensification for patients with HPV+ OPC may lie in adjustments to surgical strategies or radiation therapy. Treatment deintensification should be pursued only through clinical trials, and experts encourage clinicians to conduct and analyze phase 2 trials before moving on to phase 3 studies.1,5

CONCLUSION
The treatment landscape of cancer is ever-changing. Specifically in localized HPV+ OPC, the difference in tumor biology presents a unique clinical area where reducing the intensity of treatment may be warranted, particularly with long- and short-term toxicities associated with cisplatin. Interestingly, phase 3 data have shown evidence of harm in removing cisplatin from chemoradiation regimens for HPV+ OPC; therefore, cisplatin-based chemoradiation remains the standard of care for these patients. Future trials may support treatment deintensification in ways other than removing cisplatin.

REFERENCES
1. NCCN. Clinical Practice Guidelines in Oncology. Head and neck cancers, version 3.2021. Accessed June 16, 2021. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf

2. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute. Accessed June 16, 2021. https://seer.cancer.gov/statfacts/html/oralcav.html

3. Genital HPV infection – fact sheet. CDC. Updated January 19, 2021. Accessed June 17, 2021. https://www.cdc.gov/std/hpv/stdfact-hpv.htm
4. HPV and oropharyngeal cancer. CDC. Updated September 3, 2020. Accessed June 17, 2021. https://www.cdc.gov/cancer/hpv/basic_info/hpv_oropharyngeal.htm

5. Mehanna H, Rischin D, Wong SJ, et al. De-escalation after DE-ESCALATE and RTOG 1016: a head and neck cancer intergroup framework for future de-escalation studies. J Clin Oncol. 2020;38(22):2552-2557. doi:10.1200/JCO.20.00056

6. Mehanna H, Robinson M, Hartley A, et al; De-ESCALaTE HPV Trial Group. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. doi:10.1016/S0140-6736(18)32752-1

7. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X

8. Gardasil 9. Prescribing information. Pfizer; 2017. Accessed June 23, 2021. https://www.fda.gov/fi les/vaccines,%20blood%20&%20biologics/published/Package-Insert—Gardasil.pdf

Factors identified for poor long-term survival in RT-treated patients with oropharyngeal cancer

Source: www.cancertherapyadvisor.com
Author: Susan Moench, PhD, PA-C

Specific patient- and treatment-related factors were identified as potential survival detriments for patients with a history of oropharyngeal cancer (OPC) who received radiation therapy (RT) and were alive for at least 5 years following diagnosis, according to findings from a retrospective database review published in Cancer. Specifically, older age at diagnosis (≥55 years; standardized mortality ratio [SMR], 3.68), status as a current or former smoker (SMR, 3.28 vs 7.43), and the presence of tonsil (SMR, 4.39) or base of tongue tumors (SMR, 3.10) or category T4 tumors (SMR, 5.43) correlated with a higher risk for death.

Previous research has demonstrated that patients with head and neck cancers who remain recurrence-free for 5 years following diagnosis have a very low risk of disease recurrence. However, less is known about the conditional long-term survival of this group of patients, represented by the 2-, 5- and 10-year overall survival (OS) probabilities for those without evidence of disease recurrence 5-years post-diagnosis. Furthermore, patient, disease-, and treatment-related factors associated with long-term survival in these patients are also not well understood.

Of the 1699 patients included in this analysis, all were newly diagnosed with squamous cell carcinoma OPC between 1980 and 2012, had no cancer event for the 5 years that followed OPC diagnosis, and had been treated with RT without surgery at the University of Texas MD Anderson Cancer Center in Houston, Texas.

Baseline characteristics of this patient cohort included a median age of 60 years. Most of the participants were men (>80%) and 55.9% of patients in the cohort were classified as a current/former smoker. Over 90% of patients were diagnosed with cancer at the base of the tongue or disease that involved the tonsil, and approximately two-thirds of patients had N2/N3 disease. Intensity-modulated radiation therapy (IMRT) was administered to 63.4% of patients. No evidence of disease recurrence was reported for 95% of the cohort at baseline.

At a median follow-up time of 6.7 years following 5 years of recurrence-free survival, the unadjusted 2-, 5-, and 10-year conditional OS rates for the overall patient cohort were 94%, 83%, and 63%, respectively. Of note, these conditional OS rates were lower than the survival rates of the general population.

The standardized mortality ratios (SMRs) for all-cause death, representing the ratio of the observed number of deaths in the study cohort and the number of deaths that would be expected in the general population, controlled for study year, age, and sex, was 3.95 for the full-study population (P <.0001). An analysis of SMRs for specific patient subgroups further revealed that the SMRs were 7.43, 3.28, and 2.75 for current, former, and never smokers, respectively (all P <.0001). The SMRs were 2.34 and 5.17 for patients treated with and without IMRT (all P <.0001). Regarding Gy doses, the SMRs were 2.43 for patients who received RT doses of 66 Gy or less, 4.40 for those who received doses of 66 to 70 Gy, and 4.97 for those who received doses exceeding 70 Gy, respectively (all P <.0001). Among those who received chemotherapy, the SMR was 3.65; in patients whose treatment regimen did not include chemotherapy, the SMR was 4.16 (all P <.0001). In their concluding remarks, the study investigators noted that “the overall 10-year conditional survival rate (15 years from diagnosis) was 63% among 1699 patients with OPC treated with radiation and cancer-free 5 years after diagnosis. Patients treated with IMRT and those with less tobacco exposure had better outcomes but still had poorer outcomes when compared with the general population.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry and/or the medical device industry. Please see the original reference for a full list of disclosures.

Reference
Dahlstrom KR, Song J, Thall PF, et al. Conditional survival among patients with oropharyngeal cancer treated with radiation therapy and alive without recurrence 5 years after diagnosis. Cancer. Published online December 11, 2020. doi:10.1002/cncr.33370

Study shows checkpoint inhibitor prolongs survival in patients with certain head and neck cancers

Source: medicalxpress.com
Author: Anne Doerr, Yale University

The checkpoint inhibitor pembrolizumab (Keytruda) increases the survival time of patients with advanced head and neck cancers, according to a new global study led by Yale Cancer Center (YCC). The data was published today in the journal The Lancet.

The findings of the phase 3 study show that, compared to the standard therapy, overall survival was significantly improved for participants with previously untreated recurrent or metastatic head and neck cancers.

“This research demonstrates that this checkpoint inhibitor, with or without chemotherapy, should be the first drug used for these types of cancers,” said the study’s lead investigator, Barbara Burtness, M.D., a professor of medicine (medical oncology) and co-leader of developmental therapeutics at YCC. “This is a very positive advance in treatment for our patients.”

Burtness added that early results from this clinical trial, KEYNOTE-048, led to FDA approval earlier this year of pembrolizumab as first-line therapy in untreated recurrent or metastatic head and neck squamous-cell carcinoma, which include cancers of the oral cavity, oropharynx, hypopharynx and larynx.

While the median survival benefit was calculated in months, some patients treated with pembrolizumab lived much longer and did significantly better than patients who were not treated with the checkpoint inhibitor, Burtness noted.

The study looked at 882 participants enrolled in 200 medical centers in 37 countries, who were randomly assigned to one of three different groups: those receiving pembrolizumab, those treated with pembrolizumab and chemotherapy, and those getting the standard therapy with cetuximab and chemotherapy. Cetuximab is a drug designed to shut down a protein which makes cancer cells more responsive to growth factors. The chemotherapy used was platinum and 5-fluorouracil.

Pembrolizumab used alone improved average survival to 14.9 months, compared to 10.7 months for standard therapy. Use of pembrolizumab combined with chemotherapy improved survival to an average of 13 months.

Furthermore, survival differences between patients treated with pembrolizumab and those who weren’t remained apparent years after treatment.

Investigators found that at three years, 33 percent of patients treated with pembrolizumab monotherapy were alive, as well as about 26 percent of participants in the pembrolizumab/chemotherapy groups, compared with only 8 percent of those in the standard treatment group.

“The difference with immunotherapy is the durability of the effect it has on survival,” Burtness said. “These agents seem to change the tumor microenvironment, altering the natural history of the cancer.”

Patients treated with pembrolizumab alone experienced fewer side effects, and participants in the other two groups experienced about the same level of adverse effects.

2019-11-05T04:25:49-07:00November, 2019|Oral Cancer News|

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

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

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

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

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

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

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

2019-09-13T05:44:12-07:00September, 2019|Oral Cancer News|

Merck’s Keytruda wins FDA approval to treat head and neck cancer

Source: www.pharmalive.com
Author: staff, Reuters Health

Merck & Co Inc said on Tuesday its blockbuster cancer drug Keytruda won approval from the U.S. Food and Drug Administration to treat a type of head and neck cancer.

The drug was approved for use as a monotherapy, as well as in combination with a common chemotherapy regimen, to treat previously untreated patients with head and neck squamous cell carcinoma, Merck said.

The approval is based on results from a late-stage trial, where Keytruda showed a significant improvement in overall survival in cancer patients, Merck said.

Keytruda, a type of immunotherapy called a PD-1 inhibitor, is already an approved treatment for several forms of cancer, including lung and skin cancers.

Head and neck cancer includes tumors in the mouth, tongue, nose, sinuses, throat and lymph nodes in the neck.

Merck estimates that there will be more than 65,000 new cases of head and neck cancer diagnosed in 2019 in the United States.

Keytruda works by increasing the ability of patients’ immune system to help detect and fight tumor cells.

The drug has been amassing approvals as a standalone therapy and in combination with other drugs to treat several forms of cancer. It is the leading immunotherapy for treating lung cancer, ahead of rival drugs from Bristol-Myers Squibb, Roche and AstraZeneca.

Keytruda, first approved for advanced melanoma in 2014, is Merck’s most important growth driver. It has overtaken Bristol’s Opdivo as the industry’s immuno-oncology leader with sales expected to top $10 billion this year and $20 billion in 2024, according to IBES data from Refinitiv.

Keytruda brought in revenue of $7.17 billion for Merck in 2018, while Bristol’s Opdivo earned $6.74 billion.

How aspirin may benefit some people with head and neck cancer

Source: www.medicalnewstoday.com
Author: Catharine Paddock PhD, fact checked by Paula Field

Recent research has tied regular use of nonsteroidal anti-inflammatory drugs, such as aspirin, to longer survival in some people with head and neck cancer.

The researchers propose that there should now be a clinical trial to test the effectiveness and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) for this purpose. They suggest that the effect that they observed is likely due to the NSAIDs reducing prostaglandin E2, a molecule that promotes inflammation. A paper on their findings now features in the Journal of Experimental Medicine.

Head and neck cancers are cancers in which tumors develop in the nose, sinuses, larynx, throat, and mouth. In most cases, the tumors arise in the flat thin squamous cells that form the tissue lining of surfaces. For this reason, they bear the name head and neck squamous cell carcinomas (HNSCCs).

In the United States, people with HNSCCs account for around 4 percent of all those with cancer. These types of cancer also tend to have a lower rate of survival compared with many other types. The main risk factors for HNSCC are tobacco use, heavy use of alcohol, sun exposure, and infection with the human papillomavirus (HPV).

Aspirin and HNSCC
Previous research has suggested that taking aspirin regularly can reduce the risk of developing HNSCCs. However, the recent study is the first to link the use of aspirin and other NSAIDs to longer survival in some people who already have HNSCC.

It found that, among people with HNSCC and alterations in the PIK3CA gene, those who regularly used NSAIDs had a longer overall survival rate than those who did not. Regular use of NSAIDs appeared to make no difference to survival in people with HNSCC who did not have any PIK3CA gene alterations.

The researchers defined regular use of NSAIDs as using them at least twice a week for 6 months or longer.

“The present study,” says senior study author Prof. Jennifer R. Grandis M.D., who works in the Department of Otolaryngology at the University of California, San Francisco, “is the first to demonstrate that regular NSAID usage confers a significant clinical advantage in patients with PIK3CA-altered HNSCC.”

PIK3CA and cancer
The PIK3CA gene contains DNA code for the “catalytic subunit” of the signaling enzyme PI3K. The catalytic subunit is the trigger for the enzyme, which activates various signaling reactions in cells. Signals from PI3K are essential for cell survival and activities, such as growth, division, movement, material transport, and protein production. Around 35 percent of people with HNSCC have tumors that harbor “activating mutations” of PIK3CA note the authors.

Colorectal cancer studies have also revealed links between regular NSAID use and improved survival in people who have altered PIK3CA genes. However, they did not explain the underlying mechanism.

Prof. Grandis and colleagues examined medical records and tumor tissue samples belonging to 266 people with HNSCC. The tissue samples came from tumors that surgeons had removed. In most cases, the individuals then received treatment with chemotherapy, or radiotherapy, or both.

Overall survival rose from 45-78 percent
The investigators used the tissue samples to determine which people had altered PIK3CA genes. They then correlated these results against patterns of NSAID use from the medical records.

The analysis revealed that that overall survival increased from 45 to 78 percent in those who regularly took NSAIDs and whose tumors showed that they had an altered PIK3CA gene.

The researchers tested for two types of PIK3CA alterations: mutations and amplifications. They found that the type of alteration did not change the benefit to overall survival. Mutations are alterations in the “spelling” of DNA code, whereas amplification is when DNA sequences repeat. Amplification can lead to increased production of proteins.

The team then tested the effect of NSAIDs on a mouse model. They injected mice with cancer cells containing an altered PIK3CA gene. The mice that received NSAIDs grew much smaller tumors.

NSAIDs block prostaglandin E2 production
Further examination of the mice led the team to suggest that the NSAIDs reduced tumor growth by blocking prostaglandin E2 production.

Prostaglandin E2 has come up in studies of other cancers that have raised the possibility that a PI3K signaling pathway triggers this inflammation-promoting molecule.

The new findings suggest that the benefit of NSAIDs on survival might extend to other types of cancer where there is an altered PIK3CA gene. The discovery about NSAIDs blocking prostaglandin E2 in mice might explain the drugs’ mechanism of action in people with colorectal cancer and altered PIK3CA genes.

Prof, Grandis concludes that they could not make any “specific recommendations” about the use of NSAIDs because of lack of consistency in the dosage, timing, and type of NSAIDs covered by their study.

“But the magnitude of the apparent advantage, especially given the marked morbidity and mortality of this disease, warrants further study in a prospective, randomized clinical trial.”

Restaging raises hope against HPV oral cancer

Source: atlantajewishtimes.timesofisrael.com
Author: Cady Schulman

Jason Mendelsohn was diagnosed with Stage 4 tonsil cancer from HPV in 2014 after finding just one bump on his neck. He survived thanks to a variety of treatments, including a radical tonsillectomy and neck dissection to remove 42 lymph nodes, seven weeks of chemotherapy, radiation and a feeding tube.

But if Mendelsohn’s cancer had been discovered today, just four years later, it would have been classified as Stage 1. That’s because HPV-related oral cancers now have a high survival rate through a better response to treatment, said Meryl Kaufman, a speech pathologist specializing in head and neck cancer management who worked for Emory University’s department of head and neck surgery for 10 years.

“Cancer staging is taking into account the HPV-related cancers,” said Kaufman, who now owns her own practice. “It was kind of all lumped together. The survival rates for people who have HPV-related cancers are much higher than the typical head and neck cancers associated with smoking and drinking.”

For Mendelsohn, finding out that patients with HPV-related cancers likely face easier treatments and higher success rates made him extremely happy.

“If I was diagnosed and I heard Stage 1 instead of Stage 4, while it’s still cancer, it would make me feel like I could beat it,” said Mendelsohn, who made a video for his children a month after his diagnosis with advice for their lives after he was gone. “When I hear Stage 4 to Stage 1, I think people have hope they can beat it. My hope is that it will give people hope that they can beat this.”

As a cancer survivor, the Florida resident wants to give hope to other patients. He talks to people throughout the world every month and is creating a worldwide survivor patient network to connect cancer survivors with patients.

“While cancer is scary, Stage 1 is a lot less scary than Stage 4,” Mendelsohn said. “Stage 4 was overwhelming. When I was looking for information, there was nothing out there that made me feel like I was going to be OK. What I’m trying to do is give people hope and let them know that it’s all temporary.”

Another way Mendelsohn is trying to reach those affected by cancer is through his website, supermanhpv.com. He shares his story, news articles featuring him and oral cancer caused by HPV, and information for survivors, patients and caregivers.

The site also features Mendelsohn’s blog, putting himself out there so people can see that someone who, just four years ago, was diagnosed with Sage 4 cancer is now a Peloton-riding, travel-loving cancer advocate.

“People see me and say (they) can’t believe (I) had cancer three to four years ago,” Mendelsohn said. “I was in bed 18 hours a day for a month. I was choking on my saliva for a month. I was consuming five Ensures a day and two Gatorades a day through a feeding tube in my stomach. If people going through that can see me working out, going on the bourbon tour in Louisville. I’ve been on an Alaskan cruise. I’ve been to the Caribbean. I’ve been to the Grand Canyon.”

Mendelsohn, who started his campaign to raise awareness of HPV and oral cancer by raising money for the Ride to Conquer Cancer in Washington, now serves on the board of the Head and Neck Cancer Alliance. The organization’s goal is to advance prevention, detection, treatment and rehabilitation of oral, head and neck cancers through public awareness, research, advocacy and survivorship.

“I feel like it’s gone from me raising money for a bike ride to me on two boards helping create awareness and raise inspiration and creating a survivor patient network,” Mendelsohn said. “Now it’s not about me and my three doctors. Now it’s about helping people with diagnosis globally. There are great doctors. I think we’re going to do great things.”

One way to help prevent children from getting cancer caused by HPV when they grow up is the Gardasil vaccine, which protects against HPV Strain 16, which causes oral cancer. Mendelsohn said 62 percent of college freshmen and three-quarters of adults by age 30 have HPV.

But he doesn’t tell people to get the vaccine. Instead, he advises parents to talk to their kids’ doctors about the benefits and risks.

“I talk about the importance of oral cancer screenings when they’re at the dentist,” he said. “And if you feel a bump on your neck, go to your ENT. I had no symptoms and just a bump on my neck, but I was diagnosed with Stage 4. I’ve had so many tell me that they didn’t know the vaccine is for boys. They thought it was just for girls.”

Kaufman said that the HPV vaccine is recommended for use in boys and girls and that it’s important for the vaccine to be given before someone becomes sexually active. The vaccine won’t work if a person has already been exposed to HPV, as most sexually active adults have been, she said.

Men are much more likely to get head and neck cancer from HPV.

“Usually your body fights off the virus itself, but in some people it turns into cancer,” Kaufman said. There hasn’t been specific research that the HPV vaccine will protect you from head and neck cancer, she said, “but if you’re protected against the strains of HPV that cause the cancer, you’re probably less likely to get head and neck cancer.”

Treatment for this cancer isn’t easy, Kaufman said. Radiation to the head and neck can affect salivary glands, which can cause long-term dental and swallowing issues. Treatment can affect the skin, taste and the ability to swallow.

“A lot of people have tubes placed,” she said. “It’s not easy. It depends on how well you respond to the treatment.”

While getting the vaccine can help protect against various cancers, awareness about head and neck cancer is the key. And knowing the signs and symptoms — such as sores in the mouth, a change in voice, pain with swallowing and a lump in the neck — is important.

“If one of those things lasts longer than two weeks, you should go to your doctor,” Kaufman said. “This can affect nonsmokers and nondrinkers. It’s not something that people expect. The more commonplace it becomes and the less stigma, the better.”

Study provides new guidelines for assessing severity of head and neck cancers

Source: eurekalert.org
Author: press release Cedars-Sinai Medical Center

Cedars-Sinai investigators have developed a new, more accurate set of guidelines for assessing the severity of head and neck cancers and predicting patient survival.

The new guidelines, outlined in a study recently published in the Journal of Clinical Oncology, center around counting the number of malignant lymph nodes found in each patient.

“The greater the number of malignant lymph nodes, the less favorable the patients’ chances of survival,” said Allen S. Ho, MD. Ho is director of the Head and Neck Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai and lead author of the study. “This new approach could dramatically simplify staging systems.”

For decades, doctors have determined the stage and predicted the progression of head and neck cancers based primarily on nodal size, location and how far the cancer has spread beyond the lymph nodes, but they have given less importance to the number of cancerous nodes. As a result, staging and treatment recommendations, based on current national guidelines, “are the same whether a patient has two or 20 positive lymph nodes,” said Zachary S. Zumsteg, MD, assistant professor of Radiation Oncology at Cedars-Sinai and the study’s senior author.

With the new system, based on the number of cancerous lymph nodes, patients are separated into similarly sized groups with distinct outcomes, Zumsteg said. “Our study demonstrated a better way to assess cancer severity, which will improve our ability to predict outcomes and give patients more personalized treatment.”

The Cedars-Sinai study involved reviewing data of 14,554 U.S. patients identified in the National Cancer Database who were treated for squamous cell carcinoma of the oral cavity (mouth, gum and tongue) between 2004 and 2013.

The data showed that an increased risk of death was associated with each additional cancerous lymph node found. The investigators concluded that the number of cancerous lymph nodes is a predominant, independent factor associated with death in those patients. The study also identified an ultra-high-risk group of patients with five or more cancerous lymph nodes.

Head and neck cancers occur in the lips, tongue, gums, bottom of the mouth, throat, larynx, nasal cavity and salivary glands. About 63,000 people developed head and neck cancers in the U.S. in 2017. More than 13,000 deaths from those cancers occurred during that period, according to the American Society of Clinical Oncology.

“Although considering the number of cancerous lymph nodes in staging is a simple concept that many head and neck cancer specialists have assumed to be true for years, data has been limited until now,” Zumsteg said. The study authors said they hope that, based on the new data, the number of positive nodes in staging will now be incorporated into clinical practice.

Notes:
1. Research reported in this publication was supported in part by the National Institutes of Health under award number R01 CA188480-01A1, National Center for Advancing Translational Sciences under award numbers UL1TR000124 and UL1TR001881-01, the Donna and Jesse Garber Award for Cancer Research and the Health Network Foundation Service Excellence Award.

Disclosure: Dr. Zumsteg serves on the external advisory board of the Scripps Proton Therapy Center and has been a paid consultant for EMD Serono.

Number of metastatic nodes a predictor for survival in oral cancer

Source: www.onclive.com
Author: Jason Harris

The presence of metastatic lymph nodes was directly correlated with poorer survival in patients with oral cancer. Mortality risk rose continuously with the number of metastatic nodes without plateau, according to findings published in the Journal of Clinical Oncology.

Investigators found that the effect was most pronounced with up to 4 lymph nodes (hazard ratio [HR], 1.34; 95% CI, 1.29-1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20-1.65; P <.001) and lower neck involvement (HR, 1.16; 95% CI, 1.06-1.27; P <.001) were also predictors for increased mortality.

Citing the need for more precise staging metrics and treatment stratification, the investigators assessed the effect of quantitative metastatic nodal burden in a large population of patients with oral cavity cancer. Researchers selected oral cavity cancers because of their surgical treatment paradigm with more complete pathologic nodal data.

“Metastatic nodal burden is a central predictor of mortality in patients with oral cavity cancer, with each additional metastatic lymph node conferring escalated risk of mortality,” first author Allen S. Ho, MD, Department of Surgery, Cedars-Sinai Medical Center, and co-investigators wrote. “Classic factors such as lymph node size and contralateral nodal metastasis lack independent prognostic value when accounting for number of metastatic nodes.”

“Our data suggest that deeper integration of quantitative nodal burden could better calibrate the wide spectrum of risk that staging systems presently capture. Such adjustments would be a promising means to more effectively articulate patient prognosis, tailor clinical trial design, and ultimately advance clinical decision making,” added Ho et al.

Investigators at Cedars-Sinai Medical Center in Los Angeles examined data collected in the National Cancer Data Base on adult patients with oral cavity squamous cell carcinoma who underwent upfront surgical resection for curative intent (N = 14,554) from 2004 to 2013. Patients were segregated into node-negative (n = 7906) or node-positive (n = 6648) groups.

Median overall survival was 68.3 months (95% CI, 64.4-71.7), with a median follow-up of 46.5 months (95% CI, 45.7-47.3).

The mean number of lymph nodes examined was 32.1 (standard deviation [SD], ±17.4). Among patients with node-positive disease who had known data, the mean number of identified positive metastatic nodes was 3.3 (SD, ±4.3), 17.2% had lower neck (level 4-5) involvement, 45.2% demonstrated extranodal extension, and 13.3% harbored contralateral nodal involvement.

In univariate analysis, the number of metastatic lymph nodes strongly predicted poorer survival. Estimated 5-year OS was 65.3% for patients with no metastatic lymph nodes compared with 27.5% for patients with 4 metastatic nodes and 9.7% for those with 10 or more. After adjusting for potential confounders in a multivariable model, investigators found that the number of positive metastatic lymph nodes remained closely linked with OS (P <.001).

Investigators noted a change point when 4 metastatic nodes were identified. HR per metastatic lymph node increased steeply up to 4 metastatic LNs (HR, 1.34; 95% CI, 1.29-1.39; P <.001). Beyond that number, each additional metastatic lymph node increased the risk for death more slowly (HR, 1.03; 95% CI, 1.02-1.04; P <.001).

Investigators found an association between an increasing number of lymph nodes examined and improved OS in multivariable analyses (P <.001). A multivariable model with a three-knot restricted cubic spline function showed that, from a baseline of 10 lymph nodes examined, the risk for death declined continuously with each additional node harvested up to a change point at 35 nodes (HR, 0.98; 95% CI, 0.98-0.99; P <.001). There was no significant improvement in survival beyond that change point (HR, 1.00; 95% CI, 0.99-1.00; P = .126).

After adjusting for covariates, including positive metastatic lymph nodes and number of total nodes examined, both extranodal extension (HR, 1.41; 95% CI, 1.20-1.65; P <.001) and lower neck involvement (HR, 1.16; 95% CI, 1.06-1.27; P <.001) were independently associated with mortality risk. Lymph node size and contralateral lymph node involvement (N2c disease) had no significant impact on survival.

Reference:
Ho AS, Kim S, Tighiouart M, et al. Metastatic lymph node burden and survival in oral cavity cancer [published online September 7, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016. 71.1176.

Halving radiation therapy for HPV-related throat cancer offers fewer side effects, similar outcomes

Source: www.eurekalert.org
Author: Mayo Clinic press release

Mayo Clinic researchers have found that a 50 percent reduction in the intensity and dose of radiation therapy for patients with HPV-related throat cancer reduced side effects with no loss in survival and no decrease in cure rates. Results of a phase II study were presented today at the 59th Annual Meeting of the American Society for Radiation Oncology in San Diego by Daniel Ma, M.D. a radiation oncologist at Mayo Clinic.

“A common approach for treating HPV-related throat cancer is a combination of surgery followed by daily radiation therapy for six to 6½ weeks,” says Dr. Ma. “However, the radiation treatment can cause a high degree of side effects, including altered taste, difficulty swallowing, dry mouth, stiff neck and damage to the jaw bone.” Dr. Ma says that patients with HPV-related throat cancer tend to be young and, once treated, are likely to live a long time with possibly life-altering side effects from the standard treatment. “The goal of our trial was to see if an aggressive reduction of radiation therapy (two weeks of radiation twice daily) could maintain excellent cure rates, while significantly reducing posttreatment side effects, improving quality of life and lowering treatment costs.”

Researchers followed 80 patients with HPV-related oropharyngeal squamous cell cancer with no evidence of residual disease following surgery and a smoking history of 10 or fewer pack years. That’s the number of years smoking multiplied by the average packs of cigarettes smoked per day.

At two years following the aggressively de-escalated treatment, the rate of tumor control in the oropharynx (throat) and surrounding region was 95 percent. Of the 80 patients in the trial, only three experienced a local cancer recurrence. One patient experienced a regional cancer recurrence. Patient quality of life largely improved or did not change following treatment, except for some dry mouth.

“Patients in our trial had a very dramatic reduction in side effects, compared with standard treatment,” says Dr. Ma. “For example, no patient in our trial needed a feeding tube placed during dose-reduced treatment; whereas, close to a third of patients had feeding tubes placed with traditional radiation therapy doses on other recent clinical trials.” Dr. Ma says the reduction in side effects did not lead to any reduction in cure rate, as survival rates were similar to traditional survival rates for HPV-related throat cancer.

2017-09-26T07:17:21-07:00September, 2017|Oral Cancer News|
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