radiation

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|

New study analyzes physical therapy for head and neck cancer survivors

Source: www.curetoday.com
Author: Andrew J. Roth

The aftermath of treatment for head and neck cancer can be particularly difficult, according to Ann Marie Flores. Flores, assistant professor, Department of Physical Therapy, Movement & Rehabilitation Science, Bouvé College of Health Sciences, Northeastern University, conducted a pre-pilot study looking at early physical therapy education for this patient population.

CURE interviewed Flores about her poster, which she presented at the 8th Biennial Cancer Survivorship Research Conference in Washington, DC.

Could you first give some background about this study? How did it come to be?
It was a spinoff of some studies that I began in breast cancer. I conducted a literature review of rehab needs of breast cancer survivors about 10 years ago and found that there was very little out there. Then, when I started a rehab oncology program at a previous institution, the patient population that were referred to the program tended to not be breast cancer patients, because they physically and functionally tend to do well in aggregate. Most of my patients referred were those with head and neck cancer. I went through the same process to look through literature critically to figure out what exists in terms of physical therapy and rehabilitation-based approaches. I’ve updated this over a long period of time and this poster is a systematic review of the quality of evidence. I combined this literature and data review with talking to a focus group of cancer survivors.

What did you find?
I asked the focus group if they needed more information and the answer was “Yes!” over and over again. The majority of comments I heard were exactly about physical therapy, self-care and efficacy—things we specialize in. They were also adamant about oral health and dental care, understanding salivary function, tongue motion, muscles and more. We also heard a lot about emotional and social support. So many of these survivors said they felt they were losing their mind because no one around them understood what they were going through after treatment.

It was very interesting to see the concordance of the systematic review results with our focus groups.

What is it about this population that you think creates such a need for information?
Head and neck cancer survivors make up about 4 percent of all cancer survivors. What many of these patients have are multimodality therapies, highly disfiguring surgeries, surgeries that contribute to high rates of disability. Many patients also get chemotherapy and radiation. These survivors can have impairments that can compromise key functions of life—breathing, eating and speaking.

Can these patients get the services they need? Where?
They should be able to, yes. I am a long-standing member of the American Physical Therapy Association and we have a task force that specializes in head and neck studies. We’ve published four studies looking at measuring physical therapy–related impairments that we can rehabilitate, such as shoulder dysfunction, trismus and lymphedema. With trismus, patients can’t open their mouths. Many patients with head and neck cancer have either had muscle tissue removed or have highly scarred jaw muscles. And with lymphedema, you can get that in any part of your body, including the head and neck. Many patients will have lymph fluid collect in the under part of their neck.

For a patient who has finished treatment and facing some of these issues, where should he/she go for support?
As a patient, I’d tell my doctor that I need a referral to a physical therapist. In fact, the next steps following on our research will be to pilot test our patient education materials to determine their clinical feasibility, acceptability, and impact on PT outcomes. We want to ensure that these materials are patient-centered and relevant across the survivorship trajectory.

Heading back to the office following head and neck cancer

Source: blogs.biomedcentral.com
Author: Daniel Caley

In Cancers of the Head & Neck launching today publishes the first study looking at disability and employment outcomes in patients with head and neck cancer related to the human papillomavirus (HPV). Dr Shrujal Baxi, Section Editor for survivorship and patient related outcomes and author of this study, explains more about their work in this Q&A:

The rates of patients diagnosed with HPV-related head and neck cancer is rising annually. By 2020, there will be more cases of HPV-related head and neck cancer than HPV-related cervical cancer in the United States. Numerous studies have shown that most patients with this diagnosis are likely to be cured of their disease, placing an increased emphasis on quality of life and non-cancer outcomes in this population of survivors. The majority of patients diagnosed with HPV-related head and neck cancer are working-age adults and employment is a serious issue both financially and psychologically.

How can treatment for head and neck cancer impact employment?
Treatment for head and neck cancer often involves a combination of chemotherapy and radiation given over a six to seven week period, often known as concurrent chemoradiation or combined modality chemoradiation. This process is considered toxic and can impact a patient’s ability to function normally including speaking, chewing, breathing and swallowing. Many patients require numerous supportive medications to get through treatment including narcotics for pain and anti-nausea medications. Patients can lose on average 10-15% of their weight within a few months and can suffer from severe fatigue and post-treatment depression.

Who was in your study?
We included 102 participants with HPV-related head and neck cancer treated with chemoradiation at our institution who were employed full-time for pay at the time of diagnosis.

How did the treatment impact employment?
97% of patients had to change their employment responsibilities in some way from reducing work, taking a break and then returning at a later date, or stopping altogether and not returning. There were 73 patients that stopped but eventually returned to work after treatment, and they required a median of 14.5 weeks to return. This is longer than the 12 weeks currently allowed according to the Family Medical Leave Act (FMLA).

Eight patients stopped working altogether and never went back. Eight patients stopped working during treatment and never returned to work. Aside from younger age predicting extra time off before returning to work, we did not find a patient, treatment or disease factor that accounted for needing extra time off.

What happened to these patients?
The majority of patients who returned to work continued. At nearly two years from completion of treatment, 85% of the original 102 patients were working for pay. Overall, survivors were doing very well in terms of quality of life with the majority not having any major limitations secondary to their treatment.

There were a group of survivors who were dissatisfied with their ability to work. Some were working but not satisfied with their abilities, while others were looking for work. Compared to those who were satisfied with their abilities, those that were unsatisfied were more likely to have more functional problems and more head and neck specific late toxicities from their treatment.

What does this mean for patients and providers?
I think that this study provides some guidance for patients and providers as they prepare for chemoradiation to treat HPV-related head and neck cancer. It is hopeful that most patients will return to work, but realistic expectations of ability to work will help in treatment planning. Employment is another reason why managing late toxicities remains an important aspect of optimal care for head and neck cancer survivors.

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.

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|

Study supports immunotherapy/radiation combo in head and neck cancer

Source: www.onclive.com
Author: Laura Panjwani

There may be potential synergy between radiation therapy, given with or without chemotherapy, and immune checkpoint inhibitors in patients with squamous cell carcinoma of the head and neck (SCCHN), according to results of a prospective study.

The study, which was presented at the the 2016 Multidisciplinary Head and Neck Cancer Symposium in February 2016, examined blood samples from 16 consecutive patients with SCCHN undergoing curative-intent radiation therapies.

Samples were obtained at week 1 and week 6 to 7. Patients received a median of 70 Gy for disease in the oropharynx (n = 12, 75%), nasopharynx (n = 2, 12%), larynx (n = 1, 6%), or oral cavity (n = 1, 6%). The majority of patients had stage IV disease that was metastatic to regional lymph nodes and received concurrent platinum-based chemotherapy.

The analysis found that, during radiation treatment, circulating CD8-positive T-effector cells increased (P = .01), as did CD4-positive PD-1–positive cells (P = .02), CD8-positive LAG3-positive cells (P = .02), and regulatory T cells (P = .04). sPD-L1 levels also increased, mirroring increases in CD8-positive T cells over the course of therapy (P = .047).

While the extent to which these systemic changes reflect changes in the tumor microenvironment is unknown, the study authors noted that these findings support the “complex immunologic effects of fractionated chemoradiation therapy and mechanisms for potential synergy between chemotherapy, radiation treatment, and immunotherapy in SCCHN.”

To learn more about the impact of the research, OncLive spoke to one of the study’s authors, Jonathan D. Schoenfeld, MD, physician, assistant professor of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, who presented the findings at the meeting.

OncLive: What were the goals of this study?

Schoenfeld: Immunotherapy, particularly immune checkpoint blockade, is demonstrating some exciting results in head and neck cancer. Largely, that work has been done in metastatic head and neck cancer. Our goal was to look at the immunologic effects of a treatment that is commonly given to patients with early-stage head and neck cancer: chemotherapy and radiation.

We found that the combination of chemotherapy and radiation—and in some cases, just radiation alone—led to immune effects that we could see not just in the site where we were radiating, but also if we looked at markers in the peripheral blood.

One of the interesting things that we found was that radiation, with or without chemotherapy, has the potential to increase the number of tumor antigens that were targeted by the host immune response. One of the ways that we hope to use radiation in the future is to stimulate an initial immune response.

Based on the data that is emerging with PD-1 inhibitors, we know that the majority of patients will not respond to these agents. We need to determine if we can use radiation and chemotherapy to increase the number of responders initially that can then be stimulated even further with immune checkpoint blockade.

What immune effects were investigated?
We looked at a variety of effects. We looked at chemokines, which are cytokines that could mediate effects outside of the radiation treatment field. We looked at circulating T cells, including CD8-positive T cells, CD4-positve T cells, and markers of activated T cells.

We also looked at potentially inhibitory T cells as well, including T-regulatory cells, T cells that were expressing checkpoint receptors, and myeloid-derived suppressor cells. We also looked, in more detail, at the types of T-cell receptors that were expressed on the surface of these T cells, and it looked like the combination of radiation and chemotherapy could change the clonality of the receptor on these T cells, suggesting that radiation or targeted tumor death could stimulate a more targeted immune response.

What can a community oncologist take away from these findings?

Chemotherapy and radiation have long been appreciated for their immunosuppressive effects. We all know that when you treat someone with radiation or chemotherapy, you can see a decrease in cytopenia and lymphocytes.

We are now learning that certain types of chemotherapy and radiation, given in the proper circumstance, can cause immunogenic cell death. That can possibly synergize with the newer types of immune checkpoint blockade that are being developed.

One of our study’s findings was that we saw an increase in T cells expressed in the PD-1 receptor. Those could potentially be targeted with new checkpoint inhibitors that target the PD-1 receptor. As we develop these therapies even further, there are exciting new combinations between immunotherapies and some of the traditional therapies that have long been used for head and neck cancer with potential.

In melanoma, there are case reports of patients who have progressed on immune checkpoint blockade and are then treated with high-dose palliative radiation that then began to experience a response outside of the radiation treatment field. That is a very exciting avenue of research for head and neck cancer, as well. Can we take patients who don’t respond to the current checkpoint inhibitors that we have and use radiation in a targeted way to stimulate a broader immune response?

Radiation and chemotherapy are a backbone of some of the definitive treatments currently used for head and neck cancer. There is a lot of interest with the success of PD-1/PD-L1 inhibitors to integrate these into the definitive management, and combine them the proper way with chemotherapy and radiation to better maximize our results.

Chemotherapy and radiation are still very important for patients with curative head and neck cancer, but perhaps we should be giving these treatments in a different way—different types of radiation and chemotherapy and different targets for radiation. All of these things need to be explored, as new therapies, such as immune checkpoint inhibitors, are developed in this disease.

What impact will immunotherapy will have in head and neck cancer?
It will have a huge impact. Exciting data are emerging in metastatic head and neck cancer that show that PD-1 inhibitors offer real benefit to patients. Many of these patients had very few other treatment options and could obtain a survival benefit after treatment with PD-1 inhibitors. That opens up a whole new realm of opportunities to study immunotherapy in different settings, in different groups of patients, and in combination with other agents.

Source:
Sridharan V, Margalit D, Curreri S, et al. Systemic immunologic effects of definitive radiation in head and neck cancer. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 2.

April, 2016|Oral Cancer News|

Forgotten patients: New guidelines help those with head-and-neck cancers

Source: www.fredhutch.org
Author: Diane Mapes and Sabrina Richards

Stigma, isolation and medical complexity may keep patients from getting all the care they need; recommendations aim to change that.

Like many cancer patients, Jennifer Giesel has side effects from treatment.

There’s the neuropathy in her hands, a holdover from chemo. There’s jaw stiffness from her multiple surgeries: an emergency intubation when she couldn’t breathe due to the golf ball-sized tumor on her larynx and two follow-up surgeries to remove the cancer. And then there’s hypothyroidism and xerostomia, or dry mouth, a result of the 35 radiation treatments that beat back the cancer but destroyed her salivary glands and thyroid.

“I went to my primary care doctor a couple of times and mentioned the side effects,” said the 41-year-old laryngeal cancer patient from Cleveland, who was diagnosed two years ago. “She was great but she didn’t seem too knowledgeable about what I was telling her. She was like, ‘Oh really?’ It was more like she was learning from me.”

Patients like Giesel should have an easier time communicating their unique treatment side effects to health care providers with the recent release of new head-and-neck cancer survivorship guidelines. Created by a team of experts in oncology, primary care, dentistry, psychology, speech pathology, physical therapy and rehabilitation (with input from patients and nurses), the guidelines are designed to help primary care physicians and other health practitioners without expertise in head-and-neck cancer better understand the common side effects resulting from its treatment. The goal is that they’ll then be able to better make referrals or offer a holistic plan for patients to get the support they need.

“Head-and-neck cancer survivors can have enormous aftereffects from the disease and treatment by virtue of the location of the primary tumor,” said Dr. Gary Lyman, a public health researcher with Fred Hutchinson Cancer Research Center who helped create the guidelines. “There are functional interruptions, like losing the ability to talk, eat or taste. And some of the surgeries can be disfiguring.

“I’m really glad the American Cancer Society decided to take this on,” he said. “These guidelines are sorely needed, long overdue and will serve cancer patients who are incredibly affected — both physically and emotionally.”

Currently, there are more than 430,000 head-and-neck cancer, or HNC, survivors in the U.S., accounting for around 3 percent of the cancer patient population.

As with many other cancers, HNC is an umbrella term for a number of different malignancies, including cancers that develop in or around the mouth, tongue, throat, nose, sinuses or larynx. Brain, thyroid and esophageal cancer are not considered head-and-neck cancers.

HNC has traditionally been linked to tobacco and alcohol use, and about 75 percent of HNC are related to these risk factors. Increasingly, though, human papillomavirus, or HPV, is causing a significant number of head-and-neck cancers (another reason why the HPV vaccine is such an important prevention tool).

An isolating group of diseases
For some patients with HNC, there can be a certain amount of stigma and isolation, due to its association with drinking and smoking. Treatment can also isolate patients since it sometimes mars a person’s appearance or alters their speech.

Some patients, literally, have no voice.

HNC’s complicated nature — it’s not one disease but several, all of which behave and respond to treatment differently — also results in very small patient populations, which can hinder research.

“Head-and-neck cancer patients have historically been somewhat ignored,” said Lyman, an oncologist with Seattle Cancer Care Alliance, Fred Hutch’s treatment arm. “Many view this as a lifestyle-associated cancer, like lung cancer, heavily influenced by tobacco exposure and [drinking] alcohol to excess. And people may have difficulty dealing with the appearance of some of the more severely affected patients.”

t’s a sentiment echoed by Dr. Eduardo Méndez, a Fred Hutch clinical researcher and head-and-neck cancer surgeon at SCCA.

“It’s in a location that affects your appearance, it affects your ability to speak and to swallow, and those are all things that you need to interact with others,” he said. “It can have an effect of shutting you down from the rest of society. Even the treatment for head-and-neck cancer can have consequences that affect those very same things that the tumor was affecting — swallowing, speech, appearance.”

Not surprisingly, many HNC survivors suffer from depression and/or body image and self-esteem issues after diagnosis and treatment.

“I struggle with body image issues every day,” said Beci Steelman, a 42-year-old court clerk from Bushnell, Illinois, who went through radiation and eight surgeries, including a total right maxillectomy (a surgery of the upper jaw), after being diagnosed with a rare head and neck tumor in 2010.

“You can see that my eye looks like someone’s pulling it halfway down my cheek,” she said. ”My mom and I just call it my googly eye and joke that I have ‘really good face days’ and others that are just ‘face days.’ Clearly something’s not right. When I smile, you can see a bit of metal from the obturator, this weird rubbery dental piece that plugs the hole in the roof of my mouth. Some days I just feel like I’m so ugly.”

Holistic approach benefits patients
There is good news with these cancers: most patients are diagnosed with HNC in its early, most curable stages.

“The majority will be completely functional and normal [after treatment],” said Dr. Christina Rodriguez, the medical oncologist who oversees the majority of HNC patient care at SCCA.

According to the National Comprehensive Cancer Network, around 80 to 90 percent of early stage patients (stage 1 and 2) go into remission after receiving surgery or radiation. Advanced stage patients (stage 3 and 4) receive more aggressive treatment and have lower cure rates, with the exception of patients with HPV-related head-and-neck cancers. Their 5-year cure rates are close to 90 percent.

But even those who go into remission may have to contend with a constellation of difficult side effects.

The head and neck area is “like a fine-tuned machine,” said Dr. Keith Eaton, a medical oncologist at SCCA and Fred Hutch who specializes in lung cancer and HNC. “There are so many dedicated structures that we can’t do without. If you get rid of half your liver, not a problem. If your epiglottis doesn’t work, you aspirate.”

In addition to trouble with swallowing and speech, stiffness in the jaw and problems with shoulder and neck mobility, HNC patients can be left with hypothyroidism, hearing loss, taste issues, periodontitis and lymphedema, the swelling that comes after lymph nodes are surgically removed, a common step in cancer treatment. Because of this complexity, patients need a holistic approach, said Méndez.

Steelman’s cancer extended to the orbital floor of her right eye which meant she had to undergo extensive surgery to her face including the removal of four back teeth, an incision to the roof of her mouth and the shortening of a jaw muscle.

“They got the tumor out and then put me back together,” she said. “I feel like Humpty Dumpty.”

She now wears a prosthetic (which requires daily maintenance) and has had injectable fillers to help with the atrophy around her right eye (an implant in the area became infected and had to be removed). She’s lost hearing in her right ear, her speech is sometimes “a little marble-y,” she has dry mouth from damage to her salivary glands and her jaw will not open as wide as it once did.

Steelman tapped a number of specialists to help her deal with these issues, including an otolaryngologist (ear, nose and throat doctor), speech pathologist, a prosthodontist (an expert in the restoration and replacement of teeth) and a plastic surgeon.

“You have to be your own advocate,” she said. “You learn that very quickly.”

Get help early
Physical therapists, speech pathologists, dietitians and providers with expertise in palliative and pain care (also called supportive care) can improve survivors’ quality of life enormously, especially when therapy is started early.

“Careful — and early — attention to side effects and treatment-related complications can help optimize survivors’ quality of life,” said Eaton, the SCCA oncologist.

Dr. Elisabeth Tomere, a physical therapist at SCCA, said she and her colleagues prescribe exercises that help patients regain strength, range of motion and tissue flexibility that surgery and/or radiation may have diminished. Some patients, for instance, need help building up their trapezius muscle to improve shoulder function they have lost after neck surgery. Others need to learn movements that strengthen the front of their necks and the muscles needed to maintain posture.

Patients with lymphedema in the face and neck — a common side effect from HNC treatments — can also benefit from early intervention by a physical therapist, said Tomere.

“These issues are all helpful to address as quickly as possible so they’re not ongoing,” she said, adding that it may take up to two years for patients to mentally and physically recover from treatment.

“We try to give people a realistic timeline,” she said.

The new ACS guidelines should help providers without expertise in head-and-neck cancers find the right specialists for their patients, she said.

Cancer physical therapy, while new, is becoming more standard. Both the American Physical Therapy Association and the Lymphology Association of North America allow providers or patients to search for specialized physical therapists near them — a boon to primary care providers who are not “connected to that world,” said Tomere.

Dietitians can play a key role, too, since many HNC patients struggle to eat. Treatments can cause dry mouth, taste changes or make chewing difficult. Food can become unappetizing or difficult to ingest.

“There’s an emotional component. Food becomes medicine,” said Linda Kasser, an SCCA dietitian and specialist in oncology nutrition. Patients must eat to keep their weight up, “but it can become exhausting … Sometimes they need to force themselves to eat. They feel pressured, which can contribute to family tensions and even food aversions.”

Dietitians can offer approaches to help patients maintain their weight and strength, from using new cooking strategies to make food more palatable to recommending temporary feeding tubes inserted into the stomach that help patients avoid the pain of chewing and swallowing altogether. They also help alleviate patients’ worries about food and separate “nutrition fallacy from fact,” said Kasser.

Not surprisingly, communication is strongly emphasized in the guidelines.

“We wanted to make sure that there is open communication between the providers and caregivers,” said Lyman. “That there’s a care plan that the patient understands and the caregiver understands. All the different specialists involved in the care should be on the same page.”

The new guidelines also emphasize lifestyle choices that will help to reduce the risk of HNC recurrence and secondary cancers: smoking cessation, limiting use of alcohol, regular exercise and good oral hygiene.

Exciting new research
Chemotherapy, radiation and surgery remain the standard of care for HNC — and drive many of the side effects covered by the new ACS care guidelines — but recent advances are making researchers like Méndez very optimistic for future care.

Thanks to advances in genomics, researchers now know that the mutations found in head and neck tumors vary widely.

“One size will not fit all,” said Méndez. “Treatment will have to be individualized.”

Méndez is leading efforts at Fred Hutch to develop tailored therapies based on the cancer’s genomic mutations, zeroing in on cancer cells’ “Achilles heels” — molecular pathways that tumor cells rely on to survive but that normal cells can do without. The approach is already paying dividends: Méndez is currently leading a clinical trial of a drug he and his team identified that exploits a vulnerability unique to head and neck tumors missing a key gene called p53.

“Once we understand the genotype driving tumor growth, strategies [for treatment] can become more targeted, more effective and less toxic,” he said.

New robotic-assisted surgery has also transformed the procedure for certain patients with tumors in the larynx and at the base of the tongue, allowing surgeons to perform fewer incisions and better preserve functions like swallowing and speech, he said.

Immunotherapy also looks like a very promising path to better HNC treatments.

“New immunotherapy drugs are getting FDA approval for head and neck cancer,” said Méndez. “I think in the next few years we will see it moving to a first-line therapy. It’s a very exciting time for head and neck cancer.”

For patients like Steelman and Giesel, that’s great news.

“I had a social worker who helped me get through the thick of [treatment], but nobody talked about what it would be like when treatment was over,” said Giesel, who had to teach herself how to swallow food a new way (she no longer has an epiglottis). “I thought I’d be returned to myself and I’d be fine, but it was not like that in any way.”

These new guidelines, she said, will help patients like her get the help they truly need.

“Primary care doctors need to know about the physical and emotional effects,” she said. ”I have a lot of good support and know how to ask for help, but I can’t imagine how [patients] who don’t know how to ask for help explain how they’re feeling.”

Do you or someone you love have a head-and-neck cancer? Join the conversation about treatment challenges and how the new guidelines might help on our Facebook page.

About the authors:
Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor and patient advocate, she writes the breast cancer blog doublewhammied.com and tweets @double_whammied. Reach her at dmapes@fredhutch.org.

Sabrina Richards is a staff writer at Fred Hutchinson Cancer Research Center. She has written about scientific research and the environment for The Scientist and OnEarth Magazine. She has a Ph.D. in immunology from the University of Washington, an M.A. in journalism and an advanced certificate from the Science, Health and Environmental Reporting Program at New York University. Reach her at srichar2@fredhutch.org.

Note:
1. Original article available at: http://www.fredhutch.org/en/news/center-news/2016/04/new-survivorship-guidelines-spotlight-head-and-neck-cancers.html

April, 2016|Oral Cancer News|

Patient survives stage IV, inoperable throat cancer in clinical trial

Source: medicalxpress.com
Author: staff

It took a white lie to get David Polisini, 79, to a doctor in 2004, after months of being unable to swallow.

“Two of my daughters, Toni and Susie, showed up on my back porch and told me to put my jacket on,” he says. “They told me we were just going for a ride, but the next thing I knew, we were pulling into the Clermont Mercy Hospital.”

Polisini says tests ordered in the emergency room uncovered a tumor in his throat.

“It was the size of a golf ball,” he says, adding that he then scheduled an appointment with his primary care physician, Francis Dumont, MD. “I was then referred to an ear, nose and throat physician within his group who said I needed to see someone at the University of Cincinnati (UC) Cancer Institute.”

A biopsy was performed, and a diagnosis was confirmed—it was Stage IV cancer.

“I began seeing Dr. (Bill) Barrett who explained that I would need to go through very aggressive radiation along with chemotherapy five days a week for three months,” he says. “I’d drive myself every day to every visit in my little Miata. The therapy really zapped my strength, but I’m here because of it.

“I really don’t think I realized how much trouble I was in with Stage IV inoperable cancer, but I knew I had to do what I had to do to get through it.”

The radiation and chemo regimen was a Phase III clinical trial at UC, studying the effects of the use of both radiation and chemotherapy for advanced head and neck cancers.

Besides his family, Polisini credits Barrett, chair and professor of the UC Department of Radiation Oncology and director of the UC Cancer Institute, as well as the staff and care providers at the Barrett Center, where he received treatment, with being a tremendous support.

“Dr. Barrett was there with me every step of the way,” he says. “He was so dedicated to helping me, as were the other nurses and staff at UC. I’m just so impressed with everyone who works there. They stood by me the whole time, and more than 10 years later, I’m doing fine, and the cancer hasn’t come back. To me, Dr. Barrett is an angel come to Earth.”
The clinical trial seems to have worked, and Polisini, who lives in Clermont County, says that while he has a primarily liquid diet, he doesn’t regret a thing.

“By golly, I’ll trade the ability to eat with the ability to get up every morning,” he says. “I have the energy to do the things I want and have to do. I go to the ‘Y’ every other day to exercise. I do my own house and lawn work. I just put a new floor on my front porch. I can only do these things because of the outstanding treatment I received at the UC Cancer Institute and the Barrett Center.”

And he warns others to not ignore symptoms, like he did.

“If you have something wrong, see a doctor right away, unlike I did,” he says. “I’m just thankful for my daughters and Dr. Barrett for helping me.”

March, 2016|Oral Cancer News|

Immunotherapies gaining traction in head and neck cancers

Source: www.targetedonc.com
Author: Greg Kennelty

An explosion of immunotherapies is on the horizon for patients with metastatic head and neck cancer, specifically as phase III trials begin to report findings for PD-1 inhibitors. This upcoming wave of new therapies places importance on understanding optimal treatment settings and adverse events associated with these therapies.

In late January, the phase III CheckMate-141 trial investigating the anti–PD-1 agent nivolumab was stopped early, due to a substantial improvement in the primary endpoint of overall survival (OS). The drug was put up against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel following progression on a platinum-based therapy.

At this time, data from the study have not yet been released but are being prepared for future presentation. Findings from the study are being discussed with the FDA and other health authorities.

In addition to nivolumab, the PD-1 inhibitor pembrolizumab (Keytruda) demonstrated encouraging activity in patients with with advanced PD-L1–positive esophageal carcinoma during the phase Ib KEYNOTE-028 study. Additionally, the agent was effective for patients with squamous cell carcinoma of the head and neck in the phase I KEYNOTE-012 study.

In the head and neck cancer population, the objective response rate with pembrolizumab was 24.8% in 117 evaluable patients. Tumor shrinkage was experienced by 56% of patients and another 25% had stable disease. The response rate seen with pembrolizumab was similar, regardless of HPV infection status. In those with HPV-positive disease, the ORR was 20.6% compared with 27.2% in the negative group.

To gain further insight, Targeted Oncology spoke with head and neck cancer expert Barbara Burtness, MD, professor of Medicine (Medical Oncology), Clinical Research Program Leader, Head and Neck Cancers Program, co-director, Developmental Therapeutics Research Program, Yale Cancer Center.

TARGETED ONCOLOGY: Can you give us an overview of where immunotherapy is currently in head and neck cancer?

BURTNESS: The first trials for immunotherapy in head and neck cancer began two or three years ago and we now have sufficient reason to believe that these therapies are going to be active in the cancer. For example, there is the KEYNOTE-012 trial, which was a trial of pembrolizumab given to an expansion cohort of either HPV-positive or HPV-negative head and neck cancer. The response rate there was about 25%.

There is some reason to believe that if either PD-L1 or PD-L2 are expressed, that that would predict for a higher response rate. There are now phase III trials going forward for both platinum-refractory disease and for first-line patients looking at pembrolizumab compared with chemotherapy.

There are also data with MEDI4736, which if a patient is expressing PD-L1, appears to have a pretty high response rate of about 50% in a small group of patients. There are currently ongoing trials looking at the combination of MEDI4736 with tremelimumab, though we don’t have any data on that just yet.

Then there are novel strategies people have for trying integrate immunotherapy with standard treatment. We have some reason to believe that when head and neck cancer is treated with radiation there is upregulation in tumor-infiltrating lymphocytes and PD-L1. There are trials now moving forward that are integrating immune checkpoint inhibitors together with chemoradiation, or taking patients who have completed their chemoradiation but have persistent disease and exposing them to pembrolizumab in that setting.

The last thing is there is some evidence that siltuximab can upregulate a co-stimulatory molecule, CD137. There are some trials looking at co-targeting EGFR and CD137.

TARGETED ONCOLOGY: What are the side effects in immunotherapy?

BURTNESS: The one thing community oncologists should be aware of is toxicities. As these drugs roll out, these toxicities that will be present are a lot different to manage than the usual cytotoxic agent toxicities. There are a lot of unusual or unexpected side effects that are autoimmune in nature.

The most common toxicity is fatigue. Across all the patients with head and neck cancer who received pembrolizumab, about 17% of them had grade 3 or 4 toxicities. This is a lot easier to tolerate than chemotherapy or chemoradiation. The other things that you might look for are pneumonitis, nephritis, pancreatitis with diabetic symptoms, thyroiditis, and a variety of unusual autoimmune side effects.

TARGETED ONCOLOGY: What do you see as the overall potential for immunotherapy in head and neck cancer?

BURTNESS: Everybody with biomarker expression of either the ligands or the targets in this pathway is likely to be exposed to these drugs in the future. The challenge for us is going to be to figure out, for those patients who are not PD-L1 expressing or who don’t have tumor-infiltrating lymphocytes, other ways that we can prime patients for immunotherapy with our standard treatments. It’s speculative – it’s not something that people are doing in clinics now, but the first trials of those approaches are starting.

There is also ADXS11-001 that is fused to the E7 oncogene from HPV. The idea is that that would increase antigenic presentation and then the immune checkpoint inhibitor could potentially be more effective. That treatment is still in phase I.

February, 2016|Oral Cancer News|