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Wednesday Weekly - 31 May 2017

If there is any overall message to take from trawling through the libraries of news stories about head and neck cancer it is that a lot of people in a lot of countries are working on the most effective forms of treatment. That can range from drug treatment to robotic surgery and more, supporting the patient during and following treatment is another issue and one that groups like this network are constantly advocating for.

Meanwhile consider; Everything in the universe is either a potato or not a potato or maybe, If the grass is always greener on the other side of the fence, who the hell built that fence?

When traditional cancer therapy doesn't work

(U.S.) Head and neck cancers are the sixth most common cancers worldwide, in large part due to the presence of the HPV virus. Now, researchers are testing an immunotherapy treatment they say is highly effective for patients with cancer that spreads or comes back.

Sixty-six-year-old Leonard Monteith led a healthy lifestyle. That's why sudden problems with his mouth caught his attention
Doctors found an inch-wide tumor at the base of Leonard's tongue. He was diagnosed with HPV positive cancer.

Nabil Saba, M.D., FACP, a medical oncologist at Emory University Winship Cancer Institute in Atlanta, Georgia, explained, "The traditional treatment for head and neck cancer is really toxic and exhaustive and leads to side effects that are very significant."

After treatment, Leonard's cancer went away for six months, but then it came back in his lungs. Dr. Saba is a nationally-known expert in the treatment of head and neck cancers. He thought Leonard would be a good candidate for a new therapy.

"Immunotherapy is really, I think, a complete game changer," said Saba.

Dr. Saba said two separate immunotherapy drugs are showing real promise. A drug called Nivolumab blocks the cancer receptors, allowing the body's immune system to fight the cancer. Another drug, Pembrolizumab also works in a similar way. Because the trials are ongoing, Dr. Saba can't say which specific drug Leonard was on.

Doctors say the survival rates for patients who continued on Nivolumab were twice of those who did not take the immunotherapy drug. Twenty percent of the patients on the drug had their tumors shrink.

Full story:


PD-L1 Fuels RT Failure in Head and Neck Cancer(California)

Radiation resistance in human papillomavirus (HPV)-negative head and neck cancer had a significant association with increased expression of the immune checkpoint protein PD-L1, examination of cell lines and tumor specimens showed.

Analysis of tumor specimens from three cohorts of patients with HPV-negative disease showed treatment failure rates of 50% to 70% in specimens with high PD-L1 expression as compared with 20% to 25% for specimens with low PD-L1 expression. The findings were supported by evidence of high PD-L1 expression in HPV-negative cell lines with acquired radioresistance.

PD-L1 expression -- and by extension, treatment failure -- appeared to be mediated by Axl and PI3K signaling, Heath D. Skinner, MD, PhD, of the MD Anderson Cancer Center in Houston, and colleagues concluded in Clinical Cancer Research.

"We identified and validated PD-L1 as a significant biomarker of treatment failure in HPV-negative head and neck squamous cell carcinoma (HNSCC) following radiotherapy," the authors said. "This phenomenon appears to be linked to Axl/PI3 kinase signaling within the tumor. These findings provide a strong rationale for the combination of immune checkpoint blockade and radiation in this setting, as well as potentially utilizing Axl or PI3 kinase blockade to affect both tumor radiosensitization and immune response."

The results informed a key challenge in the treatment of head and neck cancer, identifying patients with an increased risk of local failure, said Avraham Eisbruch, MD, of Michigan Medicine in Ann Arbor.

"This work is very interesting, as it highlights adaptive immune evasion as a mechanism for resistance to radiotherapy,which is an important treatment modality in head and neck cancer," said Eisbruch, who was not involved in the study. "More work will be needed to validate these findings prospectively and also to see if they extend to HPV-positive patients, who also have about a 10% risk of locoregional recurrence."

If additional preclinical work confirms the associations between Axl, PI3K signaling and PD-L1, targeting those pathways with small-molecule inhibitors might improve activation of antitumor host immunity, added Terrence Williams, MD, of Ohio State University in Columbus.

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