survival

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.

January, 2018|Oral Cancer News|

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.

October, 2017|Oral Cancer News|

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.

September, 2017|Oral Cancer News|

Incisionless robotic surgery offers promising outcomes for oropharyngeal cancer patients

Source: medicalxpress.com
Author: press release, Henry Ford Health System

A new study from researchers at Henry Ford Hospital finds an incisionless robotic surgery – done alone or in conjunction with chemotherapy or radiation – may offer oropharyngeal cancer patients good outcomes and survival, without significant pain and disfigurement.

Patients with cancers of the base of tongue, tonsils, soft palate and pharynx who underwent TransOral Robotic Surgery, or TORS, as the first line of treatment experienced an average three-year survival from time of diagnosis.

Most notably, the study’s preliminary results reveal oropharyngeal cancer patients who are p16 negative – a marker for the human papilloma virus, or HPV, that affects how well cancer will respond to treatment – have good outcomes with TORS in combination with radiation and/or chemotherapy.

“For non-surgical patients, several studies have shown that p16 positive throat cancers, or HPV- related throat cancers, have better survival and less recurrence than p16 negative throat cancers,” says study lead author Tamer Ghanem, M.D., Ph.D., director of Head and Neck Oncology and Reconstructive Surgery Division in the Department of Otolaryngology-Head & Neck Surgery at Henry Ford Hospital.

“Within our study, patients treated with robotic surgery had excellent results and survival, irrespective of their p16 status.”

Study results will be presented Sunday, Sept. 18 at the 2016 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) annual meeting in San Diego.

Led by Dr. Ghanem, Henry Ford Hospital in Detroit was among the first in the country to perform TORS using the da Vinci Surgical System. TORS offers patients an option to remove certain head and neck cancer tumors without visible scarring, while preserving speech and the ability to eat.

With TORS, surgeons can access tumors through the mouth using the slender operating arms of the da Vinci, thus not requiring an open skin incision.

Unlike traditional surgical approaches to head and neck cancer that require a large incision and long recovery, TORS patients are able to return to their normal lives only a few days after surgery without significant pain and disfigurement.

For the study, Dr. Ghanem and his colleagues wanted to take a closer look at the effectiveness of TORS for oropharyngeal cancer patients. They reviewed overall three-year survival, cancer control and metastasis, as well as the effect of p16 status on these variables.

The study included 53 Henry Ford oropharyngeal cancer patients who had TORS. Among them, 83 percent were male, 77 percent were Caucasian, and the mean age was 60.8 years. Thirty-seven percent had TORS alone, while more than 11 percent had TORS with radiation therapy, and more than half received chemotherapy and radiation therapy.

Thirty-seven percent had TORS alone, 11.4 percent received radiation therapy, and 50 percent received chemotherapy and radiation therapy. Eighty-one percent of patients had p16+ disease.

The study shows patients with a p16 negative marker had high survival (100 percent) and low cancer recurrence when TORS was the first line of treatment, as well as when TORS was followed by chemotherapy or radiation therapy.

The majority of patients (63 percent) were able to receive a lower dose of radiation after TORS, which reduces the risk of radiation side effects.

While Dr. Ghanem notes the study’s results are not enough to change clinical practice, it does demonstrate that TORS alone or in conjunction with adjuvant radiation or chemotherapy is an acceptable treatment option for oropharyngeal cancer patients regardless of p16 status.

September, 2016|Oral Cancer News|

Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com
Author: Laura Panjwani

Robert-Ferris

Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD.

“Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.”

The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator’s choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN.

The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator’s choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act.

Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN.

OncLive: What were the updated findings from CheckMate-141 presented at ASCO?

Ferris: The data that were presented at the 2016 ASCO Annual Meeting were further evaluations and follow-up on some preliminary data—originally presented at the 2016 AACR Annual Meeting—that listed the OS results.

At ASCO, we recapped the primary endpoint of OS as an important endpoint for immunotherapies because response rate and progression-free survival may not be as accurate. Ultimately, the FDA and people at large want OS. In this study, OS was 36% at 1 year in the nivolumab-treated arm and 16.6% in the comparator arm, which was investigator’s choice of single-agent chemotherapy, consisting of methotrexate, docetaxel, or cetuximab. In this phase III randomized trial, nivolumab was given in a 2:1 randomization: 240 patients received nivolumab and 120 received investigator’s choice.

Also at ASCO, we presented further evaluations consisting of what the regimens are in the comparator arm. There was about 20% each of docetaxel and methotrexate and 12% of cetuximab. Approximately 60% of the patients had prior cetuximab exposure and we stratified by cetuximab as a prior therapy. We also demonstrated the ORR, which was 13.3% in the nivolumab-treated arm versus 5.8% in the investigator’s choice arm.

Therefore, there was an improvement in overall response, but the difference seemed more modest than the OS benefit—which was a doubling—with 20% more patients alive at 1 year. This reinforces the concept that perhaps response rate may not be the best endpoint. Progression-free survival (PFS) was double at 6 months, with about 20% in the nivolumab arm versus about 9.9% in the investigator’s choice arm. The median PFS was not different, but the 6-month PFS was twice as high. The time to response was about 2 months in each arm at the first assessment.

Your analysis also looked at biomarkers. Can you discuss these findings and their significance?

The p16 or HPV-positive group had a better hazard ratio for OS than the overall study population. The hazard ratio was .73 for the overall population, using a preplanned interim analysis. With the HPV-positive group, we had a hazard ratio of .55 and the HPV-negative group had a hazard ratio of .99. It is still favoring the nivolumab-treated patients but, with the curves separated earlier in the HPV-positive group, one could see the improvement with nivolumab at about 1 to 2 months. It took 7 or 8 months with the HPV-negative group to show a separation of the curves in favor of nivolumab.

We looked at PD-L1 levels, and PD-L1—using a 1% or above level—had an improvement in the PD-L1–positive patients in favor of nivolumab in terms of OS and ORR. When we looked at 5% and 10% thresholds of PD-L1, the OS did not seem to improve. Therefore, in all levels above 1%, the OS was similarly beneficial over the PD-L1 less-than-1% group. However, essentially all levels of PD-L1–positivity and PD-L1–negativity still favored nivolumab, but the benefit was more when its levels were greater than 1%.

We could combine HPV status with PD-L1 status and look at subsets; however, essentially every subset benefited, whether it was PD-L1–negative or positive. This indicates that, in this group of patients, who progress within 6 months of platinum-based therapy, that no current systemic therapeutic options benefit patients as well as nivolumab.

With regard to these findings, what are you most excited about?

Head and neck cancer is a difficult disease. Until recently, we didn’t know the impact of this enrichment for HPV-positive virus-induced subsets and we didn’t know if this was an immune responsive cancer. Clearly, it is. We have all of the hallmarks that we have seen for a bright future—based on the melanoma data—and a series of other cancers indicating response rates in the 15% to 20% range, suggesting that we now have a platform of the PD-1 pathway to combine with other checkpoints and to integrate earlier in disease with radiation and chemotherapy.

We have a demonstration of head and neck cancer as an immune-responsive cancer. We are beginning to get an idea of the biomarkers and starting to be able to segment patients who will benefit. Now, we have a large comparative trial with an OS endpoint and tissue to look at biomarkers to try and understand what the best future combinations will be.

What are some questions that you still hope to answer regarding nivolumab in head and neck cancer?

We have to get down deeper into the nonresponders. We should acknowledge that the majority of patients neither had a response nor benefited. Understanding who is more likely to benefit is useful, but we also need to understand the levels of alternative checkpoint receptors or other biomarkers of resistance.

We have sequential lymphocyte specimens from the peripheral blood, tissues, and serum so those are intensively under evaluation. There are interferon gamma signatures that have risen from the melanoma checkpoint field that will certainty be applied, as well.

*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

August, 2016|Oral Cancer News|

Type 2 diabetes drug could be beneficial for head and neck cancer patients

Source: www.eurekalert.org
Author: press release

Researchers at the University of Cincinnati (UC) College of Medicine have found that adding increasing doses of an approved Type 2 diabetes drug, metformin, to a chemotherapy and radiation treatment regimen in head and neck cancer patients is not well tolerated if escalated too quickly, but allowing slower escalation could be beneficial.

These findings are being presented via poster June 4 at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting: Collective Wisdom, being held June 3-7 in Chicago.

Trisha Wise-Draper, MD, PhD, assistant professor in the Division of Hematology Oncology at the UC College of Medicine, a member of both the Cincinnati Cancer Center and UC Cancer Institute and principal investigator on this study, says retrospective studies have shown improved outcomes in tumors treated with chemotherapy and radiation if they were also on metformin for diabetes.

“In head and neck squamous cell carcinoma, which develops in the mucous membranes of the mouth, nose and throat, diabetic patients taking a medication called metformin had better overall survival compared to those not on metformin when also treated with chemotherapy and radiation,” she says. “Additionally, pancreatic cancer patients treated with chemotherapy and metformin required higher doses of metformin–1,000 milligrams twice a day–to experience positive results.

“In basic science studies, metformin has been shown to stop mTOR, a molecular pathway present and active in this type of head and neck cancer, and pretreatment with metformin resulted in a decrease in the occurrence of oral cavity tumors in animal models. In this study, we wanted to see if the combination of escalating doses of metformin with the chemotherapy agent cisplatin and radiation for head and neck cancer tumors in non-diabetic patients would be effective.”

Wise-Draper says that metformin, which is an approved Type 2 diabetes medication, was provided by their investigational pharmacy. Metformin was administered orally in escalating doses for 7 to 14 days prior to starting the cisplatin and radiation and continued throughout standard treatment. Blood samples were collected before and after metformin treatment as well as during chemotherapy. Flow cytometry, a technique used to count cells, was used to detect the percent of circulating immune activated cells, and clinical laboratory tests including glucose, B12 and C-peptide (an amino acid that is important for controlling insulin) were performed.

“This is part of an ongoing clinical trial,” says Wise-Draper. “We found that eight patients with advanced head and neck cancer have been enrolled so far; we plan to have 30 total. Due to the relatively quick escalation of metformin, the patients’ tolerance was poor with higher doses of metformin when initiated 7 days prior to their chemotherapy and radiation therapy regimen.

“Therefore, the protocol was modified to allow slower escalation over 14 days. The most common toxicities observed included nausea (71 percent of patients) and vomiting (43 percent of patients), increase in creatinine (57 percent of patients), decreased white blood cell count (43 percent of patients) and pain when swallowing (43 percent of patients) with only nausea being directly attributed to metformin and the rest attributed to cisplatin and radiation.”

She adds that there wasn’t a substantial change in T cell or glucose levels with administration of metformin in the small sample of patients but that there were increased C-peptide levels in response to metformin administration.

“These results show that the combination of metformin and cisplatin and radiation was poorly tolerated when metformin was escalated quickly. However, there has been no significant increase in side effects thus far with the addition of metformin,” Wise-Draper says. “The trial is continuing with escalation of metformin over a longer period of time to provide more data; we will also try to increase our sample size.”

Note:
This research is being funded by the UC Cancer Institute. Wise-Draper cites no conflict of interest.

BMS gets US breakthrough status for head & neck cancer

Source: pharmatimes.com
Author: Selina McKee

US regulators have awarded Bristol-Myers Squibb’s immunotherapy Opdivo a breakthrough designation for the potential indication of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The move, which should help expedite the drug’s development and review, comes after preliminary clinical evidence indicated it could offer a substantial survival benefit to patients with the condition who have already received platinum-based therapy.

A first look at the data from the Phase III CheckMate-141 trial, stopped early in January 2016 after meeting its primary endpoint of overall survival, showed that patients treated with Opdivo (nivolumab) experienced a 30 percent reduction in the risk of death compared to the investigator’s choice of therapy (methotrexate, docetaxel, or cetuximab), with a median overall survival of 7.5 months versus to 5.1 months.

Safety signals were also looking good, with treatment-related adverse events (TRAEs) of any grade occurring in 58.9 percent of patients on Opdivo versus 77.5 percent of patients on investigator’s choice. Grade 3-4 TRAEs were reported in 13.1 percent of patients on Opdivo compared to 35.1 percent taking the investigator’s choice, while two drug-related deaths were reported as related to Opdivo (pneumonitis and hypercalcaemia), and one Grade 5 event of lung infection in the comparator arm.

The findings are particularly pertinent given the particularly bleak outlook for patients whose disease has progressed after platinum therapy and lack of systemic therapies to improve survival, and thus significant unmet medical need for new options.

Head and neck cancer is the seventh most common cancer globally, with an estimated 400,000 to 600,000 new cases per year and 223,000 to 300,000 deaths per year. The five-year survival rate is reported as less than 4% for metastatic Stage IV disease.

Opdivo is already available in the US to treat certain forms of melanoma, non-small cell lung cancer and renal cell carcinoma. This marks its fifth breakthrough designation from the FDA, and follows that for classical Hodgkin lymphoma issued just days ago.

April, 2016|Oral Cancer News|

Chemotherapy + radiation may improve survival for some elderly

Source: journals.lww.com
Author: Carlson, Robert H., Oncology Times

Because the toxicity of concurrent chemoradiation is greater than radiation therapy alone for definitive head and neck cancer treatment, many clinicians have reservations about offering chemoradiotherapy for elderly head and neck cancer patients.

But a new study shows that combining chemotherapy with radiation therapy improves survival rates for those head and neck cancer patients ages 71 to 79 years who have low comorbidity scores and advanced disease stage, with survival rates similar to that of younger patients.

The study, which used data from the National Cancer Data Base (NCDB), suggests elderly patients are being underrepresented in prospective clinical trials that have defined standards of care for head and neck cancer.

“In the era of improved radiation techniques, improved systemic therapy, and better supportive care, we found that chemoradiotherapy does, in fact, improve survival for a large segment of this population,” said Sana Karam, MD, PhD, Assistant Professor of Radiation Oncology at the University of Colorado School of Medicine in Aurora, and senior author on the study.“

“These findings challenge historical data demonstrating no benefit of chemoradiotherapy for patients older than 70 years,” Karam said.

The study was presented at the 2016 Multidisciplinary Head & Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology (ASTRO) and the American Society of Clinical Oncology (ASCO). First author is Arya Amini, MD, a fourth-year resident in the Department of Radiation Oncology at the University of Colorado School of Medicine.

Before the meeting, Karam discussed the study in an online audio preview for the press.

She said current guidelines for treatment of elderly head and neck cancer are based on trials that are included in the MACH-NC meta-analysis of 16,485 patients in 87 randomized trials (Radiotherapy and Oncology 2009;92:4-14).

While the meta-analysis confirmed a benefit of concomitant chemotherapy in locally-advanced head and neck cancer greater than the benefit with induction chemotherapy, it showed those benefits decreasing with age with no overall survival benefit for patients age 71 and above.

“But only 4 percent of the patients in this meta-analysis were age 71 and above, compared with 9 percent of the 2010 U.S. Census,” Karam pointed out. “The meta-analysis was underpowered, yet it has set our clinical practice guidelines.”

The researchers examined records from the NCDB for patients older than between 1998 and 2011. From 1998-2011, 23 percent of patients in the database were over age 70. Cases for these elderly patients were stratified by whether or not they received chemotherapy concurrent with radiotherapy.

All patients received definitive radiotherapy (66.0-81.6 Gy in 1.2-2.0 Gy fractions). Concurrent chemoradiation was defined as beginning a course of chemotherapy 14 days before or after the start of radiotherapy.

Karam said 68 percent of the patients received radiotherapy alone, and 32 percent received chemoradiotherapy.

Five-Year Survival Improved If Comorbidity Low
The study showed that five-year survival in head and neck cancer patients ages 71 to 79 years was 30.3 percent with concomitant chemotherapy and radiotherapy, versus 15.2 percent for radiotherapy alone.

“Our results showed clearly a significant overall survival benefit with the addition of chemotherapy to radiation therapy,” Karam said.

Chemoradiotherapy was associated with improved survival when patients had comorbidity scores of zero or one, and advanced disease stage.

The researchers also found an overall survival benefit of chemoradiotherapy for patients treated with intensity modulated radiotherapy.

But patients who did not see an overall survival benefit from chemoradiotherapy tended to be ages 79 or older, had a comorbidity score of two or greater, or presented with T-I or T-II disease.

The trend toward worse overall survival for patients with multiple comorbidities was only marginally significant, Karam added.

“These findings may aid clinicians in discussing treatment options with their elderly head and neck cancer patients, and they could guide future prospective trials to confirm the benefit of multimodality treatment in elderly patients, not only for head and neck cancer, but for other cancer sites as well,” Karam said.

Comorbidity, Not Age
In an online audio preview of the meeting for the press, moderator Christine G. Gourin, MD, Associate Professor of Narratology-Head and Neck Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, said, “These data show us that the key factor is not age, but comorbidity. As we age, we collect comorbidities, and that’s what is probably more significant.”

Gourin commented on the MACH-NC meta-analysis, “that we all know is used by our colleagues in Europe to support not using chemotherapy in elderly patients.

She said her own research using the SEER (Surveillance, Epidemiology and End Results) Medicare database found survival results can differ by tumor site—chemoradiation is superior to radiation in oropharyngeal cancer in terms of survival, she said; but in larynx cancer, overall survival is actually worse for chemoradiation.

Those differences were due to late toxicity of treatment, aspiration pneumonia, and dyspepsia.

Karam said her research also found differences between those two tumor sites, but that chemoradiotherapy improved overall survival for both subsets nonetheless.

“There are many differences in the data sets between the NCDB and SEER Medicare databases, including the historic staging analysis. The patient populations are a little different; our reviewers picked up on that when we were submitting the manuscript.”

“Unfortunately, we don’t have a clear cut variable for toxicity, but we did look at time to completion of radiotherapy. We found that patients who got concurrent chemoradiation had a longer time to completion of radiotherapy, suggesting perhaps more treatment breaks.”

“But even after controlling for treatment breaks, we still saw an overall survival advantage regardless of the subset, except for the very elderly and those with multiple comorbidities,” Karam said.

Source:
Oncology Times: 25 April 2016 – Volume 38 – Issue 8 – p 27
doi: 10.1097/01.COT.0000482924.27883.03

April, 2016|Oral Cancer News|

Having a partner increases cancer survival rates: Australian study

Source: www.theaustralian.com.au
Author: Sean Parnell

People diagnosed with cancer are more likely to die if they do not have a partner, according to a new Australian study.

Researchers from Cancer Council Queensland and Queensland University of Technology examined 176,050 cases of the 10 most common cancers in Queensland, diagnosed between 1996 and 2012. They found the chance of death was 26 per cent higher for men who did not have a partner compared to those who did, and 20 per cent higher for women who did not have a partner, across all cancers.

“The reasons for higher survival in partnered patients still remains unclear, but are likely to include economic, psychosocial, environmental, and structural factors,” CCQ professor Jeff Dunn said yesterday.

“Having a partner has been linked to a healthier lifestyle, greater financial resources and increased practical or social support while undergoing treatment.

“Support from a partner can also influence treatment choices and increase social support to help manage the psychosocial effects of cancer.”

The increased risk varied depending on the type of cancer. For men without a partner, it ranged from 2 per cent for lung cancer to 30 per cent for head and neck cancer, while for women without a partner it ranged from 2 per cent for kidney and lung cancer to 41 per cent for uterine cancer.

“Health professionals managing cancer patients should be aware of the increased mortality risk among unpartnered patients, and tailor follow-up treatment accordingly,” Professor Dunn said.

Of the 176,050 patients analysed for the study, 68 per cent had a partner, which included those who were married or in a de facto relationship. The researchers published their findings in the journal Cancer Epidemiology and suggested a better understanding of the relationship factor might help improve cancer management and outcomes.

March, 2016|Oral Cancer News|