radiation

Israeli company set to begin testing new radiation cancer therapy

Source: www.forbes.com
Author: Robin Seaton Jefferson

An Israeli medical technology company is set to begin testing its new radiation cancer therapy in leading medical centers in Italy. The Alpha DaRT (Dіffusіng Alpha-emіtters Radіatіon Therapy) device delivers high-precision alpha radiation that is released when radioactive substances decay inside the tumor and kills cancer cells while sparing the surrounding healthy tissue, the company says.

The company hopes to get approval from the European Commission by next year for the therapy.

Early results from an ongoing pre-clinical trial on patients with squamous cell carcinoma (SCC) tumors at the Rabin Medical Center in Israel and the IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori) in Italy showed a reduction in all tumor sizes and more than 70 percent of the tumors completely disappearing within a few weeks after treatment, NoCamels reported.

The therapy has already been tested on more than 6,000 animals and has been found “to be effective and safe for various indications, including tumors considered to be resistant to standard radiotherapy.” according to the breakthrough innovation news site NoCamels.

Alpha Tau Medical was founded in 2016 to focus on research and development as well as commercialization of its Alpha DaRT cancer treatment. The therapy was initially developed in 2003 by Professors Itzhak Kelson and Yona Keisari at Tel Aviv University.

According to the National Cancer Institute (NCI), cancers that are known collectively as head and neck cancers, or squamous cell carcinomas of the head and neck, usually begin in the squamous cells that line the moist, mucosal surfaces inside the head and neck (for example, inside the mouth, the nose, and the throat).

Head and neck cancers account for about 4% of all cancers in the United States, are more than twice as common among men as they are among women, and are more often diagnosed among people over age 50.

Cancers of the head and neck are further categorized by the area of the head or neck in which they begin including the oral cavity, pharynx (throat), larynx, paranasal sinuses and nasal cavity, and salivary glands. They can include hypopharyngeal cancer, laryngeal cancer, lip and oral, cavity cancer, metastatic squamous neck cancer with occult primary, nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, salivary gland cancer.

The Alpha DaRT treatment can be applied under local anesthesia in a short single session and can be combined with chemotherapy and immunotherapy to increase effectiveness, according to Alpha Tau Medical. The company reports Alpha DaRT can even trigger anti-tumor immunity for the elimination of distant metastases, NoCamels reported.

Clinical trials for Alpha DaRT will be conducted at the Sapienza University of Rome, which is initiating Alpha Tau’s clinical trial protocol for squamous cell carcinomas of the skin and oral cavity, and the IFO (Istituti Fisioterapici Ospitalieri), which is conducting its first study of Alpha DaRT for the treatment of cutaneous and mucosal malignant neoplasia (CMN).

Alpha Tau is also collaborating with key cancer physicians worldwide to investigate the Alpha DaRT as a treatment for other cancers, including pancreatic, breast and prostate, NoCamels reported.

November, 2018|Oral Cancer News|

A Look at Therapy Toxicities & Biology in Head & Neck Cancers

Source: journals.lww.com
Author: Valerie Neff Newitt

A measure of intrigue and discovery pertaining to head and neck cancer, spiked with compassion for patients struggling against treatment toxicities, helps quench the intellectual thirst of Yvonne Mowery, MD, PhD, Butler Harris Assistant Professor of Radiation Oncology at Duke University Medical Center, Durham, N.C.

Splitting time between the clinic and laboratory, Mowery is actively engaged in patient care as well as preclinical, translational, and clinical research. “I hope to get a better understanding of the biology of head and neck cancer and determine pathways that we can target to reduce metastatic spread of the disease and improve responsiveness to available treatments,” she told Oncology Times.

Long before reaching her current status as an award-winning investigator, Mowery grew up in Richmond, Va., in the midst of a “completely non-scientific” family. “I was an oddball,” she joked, while recalling her parents’ patience with her backyard composting experiments that became so foul-smelling that the health department was contacted. As a kid, her idea of a great present was an encyclopedia of science, and the thing that caught her eye at the toy store was a junior chemistry set.

Science was clearly her path when she headed to the University of Virginia. In her sophomore year, Mowery began working in a genetics lab. That’s where the lure of fruit flies took hold. “I looked at the development of their reproductive system and found that very interesting,” she recalled.

Nearing the completion of her undergraduate education, Mowery debated between attending medical school or graduate school. The eventual winner? Both. “I investigated physician-scientist training programs and arrived at Duke in 2004 to do a combined MD/PhD.” Today, Mowery spends 1 day a week in clinic where she sees patients, then moves to the lab for the remainder of the week to find strategies to improve patient care and develop therapies to deliver better outcomes for patients, both present and future.

Clinical Challenges
“I treat cancers primarily of the head and neck—such as oral cavity, larynx, tonsils, base of tongue, sinuses—with radiation therapy. I think of head and neck cancers as being in a ‘very high-stakes real estate’ area,” she said, “because they are often close to saliva glands, vocal cords, etc. This requires intricate planning for radiation treatment. Visualization of the tumor through fiberoptic laryngoscopy allows me to see a tumor responding to radiation and chemotherapy during the weeks of treatment; it is gratifying to watch it happen with your own eyes.”

Mowery said toxicity associated with treatment of this area of the body can be severe, partially due to the fact that it is typically “…one of the longer courses of radiation that we do—about 7 weeks, 5 days a week,” she explained. “Patients typically require pain medicine to eat and drink a soft diet, lose their sense of taste, and experience very dry mouth, sometimes requiring a feeding tube for nutrition. In addition, the skin on their neck often falls off.” Comparing it to severe sunburn, Mowery said skin typically blisters and peels off, leaving behind a neck that is “red, angry, and very uncomfortable. It just comes with the territory.”

In addition to these side effects, Mowery said there is also an unusual biological aspect to head and neck cancers which figures largely in her work. “Something very interesting scientifically drew me to these cancers,” she informed. “There are two main causes of cancer in this area: tobacco use and human papillomavirus (HPV). Outcomes for patients with HPV-positive oropharynx cancers are excellent; even when the cancer is locally advanced about 80-90 percent of patients are cured. But the tobacco-induced cancers, by contrast, do much worse (about 60% or less survival rate for locally advanced disease). Even if the tumor size is the same and the number of involved lymph nodes are the same, the biology is completely different for the HPV-related and the HPV-unrelated disease.”

In fact, the staging system was changed at the beginning of this year so that HPV-related cancers and HPV-negative cancers are staged differently. “HPV-positive cancers that used to be staged at IVA may now be staged at I or II, but they remain at stage IVA if the cancer is HPV-negative,” Mowery detailed.

Asked why tobacco-related cancer behaves so badly, Mowery answered, “We do not have a good understanding of that; it is something I am studying. We do know, however, that HPV-negative tumors exhibit a loss of function of the p53 gene, [which] is really the king of all tumor suppressors. In HPV-related tumors, p53 is usually genetically still intact but its activity is affected by HPV.”

She also commented that people still actively smoking during treatment tend to do much worse, likely due in part to having lower oxygen levels in the tumor, which in turn causes the radiation to work less effectively. “If we can figure out ways to make HPV-negative tumors behave more like HPV-positive tumors, outcomes would improve.”

From Clinic to Research
These realities on the clinical side have informed and inspired some of Mowery’s research efforts. One of her projects aims at reducing the toxicity of treatment while maintaining good outcomes in patients.

“A clinical trial that I am about to start will use PET/CT, a type of metabolic imaging, as an early litmus test to evaluate how patients are responding during treatment. If we find they are responding well, we will de-intensify and back off on the chemotherapy and radiation dose while still trying to achieve good outcomes,” Mowery explained.

She noted that because HPV-positive and HPV-negative cancers are still treated exactly the same way when not on a clinical trial, investigators also hope to find out if treatment can be de-intensified for the HPV-positive patients who tend to have more successful outcomes by virtue of their cancer type, thus allowing them to avoid some of the severe side effects.

“Of course, even in HPV-positive cancers, not every patient is cured,” cautioned Mowery, “so we want to see if we can identify, early on, who is going to do well and who, in contrast, still needs that full 7-week intensive course of radiation therapy and chemotherapy.”

Another clinical trial ongoing at Duke in which Mowery is involved is testing a drug called BMX-001 given to patients through a subcutaneous injection during radiation. “We hope the drug will reduce the—the inflammation and irritation of the lining of the mouth and throat during radiation—and dry mouth,” she said.

Mowery is also busy in lab with intensive work in developing new mouse models of both HPV-related and HPV-unrelated squamous cell carcinoma of the head and neck. “My objective is to develop a platform in which I can develop radiation with immunotherapy, as well as with chemotherapy and various novel systemic agents, to try to improve outcomes particularly for HPV-negative disease,” noted Mowery, also the winner of a 2017 Conquer Cancer Young Investigator Award. “I want to discover if there are ways that we can make our bodies and our immune system realize that these cells are not ‘self’ and activate the immune system to attack and eliminate them.”

Tobacco-related cancer is induced in mice by giving them a carcinogen present in tobacco, “… causing them to become like a tobacco chewer or smoker,” Mowery explained. “Having that exposure causes mutations in cells in the lining of their mouth.”

Mowery further said her research is taking advantage of large sequencing projects in which various head and neck tumors have been sequenced. These data are publicly available and published primarily by The Cancer Genome Atlas organization. “I have been able to see which genes are most commonly mutated and then can genetically engineer mice to have those mutations. In other words, I can specifically knock out certain genes in the head and neck to model the cancer in mice.”

This is extremely important because it allows Mowery and team to interrogate the biology of the mutations, and determine which genetic changes and pathways lead to the cancer spreading from its site of origin to the lymph nodes or the lungs. “It helps us to develop therapies to block the cancer and keep it at bay, and to determine if there are better ways to sensitize the cancer to radiation and chemotherapy,” she detailed. “And we have an opportunity to test drugs that we hope will help with side effects of radiation. We must make sure that drugs protecting normal tissue are not also protecting the tumor. Having great animal models of human cancer is really important to making progress.”

As if her work in head and neck cancer were not enough, Mowery is continuing an earlier effort begun in the lab of her research mentor David G. Kirsch, MD, PhD, by acting as radiation oncology principal investigator for a multi-site, international prospective randomized clinical trial investigating the combination of the immune checkpoint inhibitor pembrolizumab (anti-PD-1 antibody) and radiation therapy for patients with high-risk soft tissue sarcoma of the extremities. The researchers are also examining the biology behind the effects of radiation combined with pembrolizumab in a co-clinical trial using primary mouse models of sarcoma.

“We saw promising results combining them in this model. Our hope is by using this combination during the early stage of disease we may be able to eliminate those cells that have escaped the primary tumor before they cause a problem.”

Who Has Time for Hobbies?
Asked about her life outside of the clinic and lab, Mowery admitted that little time is left for hobbies. “I used to play tennis, but now I just enjoy watching it,” she said through a chuckle. “I splurged on a Labor Day vacation to the U.S. Open in New York. In my off time, I mostly read and spend time with my family. I am married; my wife is a nurse at Duke working in bone marrow transplant. We have no children.”

But the couple does have the patter of little feet in their midst. “We have two small dogs, Heidi and Cassie, a Maltese and a Maltese Shih Tzu mix—both less than 10 lbs.,” Mowery offered. “We live in downtown Durham, N.C., which is a burgeoning area. It’s kind of cool, and a little bit grungy—but in a good way. I love going for walks and checking out new restaurants. And I love food,” she added brightly.

After a brief pause, Mowery turned her thoughts again to patients. “There is one other clinical trial we’ve recently opened in the head and neck space. We are looking at financial toxicity of patients,” she said. “We are very concerned about the bills patients incur for cancer care and how that affects their quality of life.

“Unfortunately, some people just can’t afford to fill their whole prescription. Some take their drugs every other day because they are worried about cost. Some patients just do not follow through on therapy. We need to get a better sense of how much of that is going on and if there are early warning signs we can detect allowing us to intervene.”

Mowery added that better communications between health care providers and patients are needed to help patients better understand costs they face and identify resources that can help them.

“We just opened this survey-based pilot trial in June. We hope to have data next year and be able to develop a follow-up plan to employ the strategies that we find,” said Mowery. “There are a lot of ways we can try to help our patients.”

November, 2018|Oral Cancer News|

Lowering Radiation Dose Could Improve QoL, Cut Costs in Oral Ca

Source: MedPage Today, Medpage.com
Date: October 25th, 2018
Author: Elizabeth Hlavinka

SAN ANTONIO — Radiation de-intensification was tied to a quicker rebound in a number of quality of life (QoL) measures and reduced costs for patients with HPV-associated oropharyngeal cancer, a pair of studies found.

With lower doses of radiotherapy (RT), QoL measures including speech, pain, and socialization still generally worsened after treatment, but returned to baseline within 3 to 6 months, reported Kevin Pearlstein, MD, of the University of North Carolina in Chapel Hill.

And more aggressive de-intensification led to a 22% cost reduction for treatment overall ($45,884 versus $57,845 with standard care), with 33% lower costs for RT itself and 50% lower costs for post-treatment care (P=0.01), according to findings presented by Mark Waddle, MD, of the Mayo Clinic in Jacksonville, Florida.

The studies were presented here at the American Society for Radiation Oncology (ASTRO) meeting during a session on improving outcomes while minimizing toxicity in oropharyngeal cancer.

In the research from Pearlstein’s group, patients reported global QoL scores of 81 at baseline (using the 100-point EORTC QLQ-C30 questionnaire, where higher scores connote better health), which dipped to 69 at 3 months post-treatment, then rose to 75 at 6 months. Global QoL scores increased to 82 and 84 by months 12 and 24, respectively.

Common long-term side effects such as sticky saliva, taste, and ability to swallow did not return to baseline within months 3 to 6, but continued to improve between months 12 and 24. Pearlstein noted that swallowing took longer to return to baseline, typically between 1 to 3 years.

“This highlights the possibility that there can be improvement in these symptoms with longer-term follow-up,” he said.

Although oropharynx cancers associated with HPV generally have a more favorable prognosis compared with those that are not, the treatment is similar for both. As a result, these lower-risk patients still typically experience symptoms of dysphagia, dry mouth, and taste changes for upwards of 1 year after treatment, Pearlstein said.

While standard treatments typically include 70 Gy RT along with 100 mg/m2cisplatin, this study investigated whether patients given 60 Gy RT along with weekly 30 mg/m2 doses of cisplatin would result in improved QoL. Cisplatin-intolerant patients were treated with cetuximab, and patients who could not tolerate either did not receive chemotherapy.

The authors also conducted a multivariate analysis that controlled for type of chemotherapy, gender, and age. Those with with worse baseline symptoms of dry mouth, taste, and sticky saliva were more likely to return to baseline function at 12 months (ORs of 1.06, 1.09, and 1.02, respectively). Similar associations for sticky saliva and swallowing were found among patients who underwent unilateral neck RT.

“One obvious limitation is that we don’t have a direct comparison with standard intensity chemotherapy/radiotherapy,” Pearlstein said. “However, when we view these findings in the context of what we already know for patients with head and neck cancer, we do feel our findings suggest that patients who receive de-intensified chemotherapy/radiotherapy may benefit from faster return to baseline quality of life, continue improvement in symptoms over time, and less long-term morbidity.”

To conduct the study, the researchers collected data from two de-intensification phase II trials that took place from 2012 to 2017. A total of 126 patients were included, a majority of which were ages 60 and over (53%) and were non-smokers (63%). Patients were followed for an average of 25 months.

Cost of Treatment

De-intensification of radiation may also benefit these patients by decreasing total treatment costs, according to an analysis of a prospective phase II study.

“Several studies have or are investigating de-escalation of treatment to reduce toxicity while maintaining outcomes,” Waddle said during his presentation. “However, those studies haven’t investigated the cost of care that may be associated with de-escalation of treatment.”

He reported that the median cost was $17,309 for RT among those who received de-escalated doses compared with $28,161 with standard treatment (P<0.0001). The per-patient costs were $797 versus $933 per month, respectively, in the first 6 months after treatment and $518 versus $611 in the 16 to 24 months after treatment.

Among the post-treatment savings, gastrointestinal-related costs were 79% lower (P<0.01), hospitalization costs were 40% lower, and emergency department visit costs were 90% lower.

This study obtained data from the MC1273 trial, in which 68 patients received aggressive de-escalated doses of RT (30-36 Gy), and then compared the costs to 84 patients treated with standard of care (60-66 Gy). The average patient age was 58.5 years and the majority of them were white men.

October, 2018|Oral Cancer News|

RJR Slapped with $6.5M verdict over musician’s mouth cancer

Source: blog.cvn.com
Author: Arlin Crisco

R.J. Reynolds was hit with a $6.5 million verdict Tuesday for the part jurors found the company played in the mouth cancer a Florida musician developed after years of smoking. Harewood v. R.J. Reynolds, 2007-CA-46331.

The award followed the Florida 11th Circuit Court jury’s conclusion that nicotine addiction and cigarettes caused the oral cancer doctors diagnosed Glenn Simmons with in 1995. Simmons, a bassist in bands throughout much of his life, began smoking as a teenager and smoked about a pack a day for decades. He died in 2003, at age 48, from complications related to cancer-related radiation therapy. Monday’s verdict found Reynolds liable on fraud and conspiracy claims related to a sweeping scheme to hide the dangers of cigarettes. However, while jurors awarded Simmons’ daughter, Hanifah Harewood $6.5 million in compensatory damages, they rejected a claim for punitives in the case.

The case is one of thousands of Florida’s Engle progeny lawsuits against the nation’s tobacco companies. They stem from a 2006 Florida Supreme Court decision decertifying Engle v. Liggett Group Inc., a class-action tobacco suit originally filed in 1994. Although the state’s supreme court ruled that Engle progeny cases must be tried individually, it found plaintiffs could rely on certain jury findings in the original case, including the determination that tobacco companies had placed a dangerous, addictive product on the market and had conspired to hide the dangers of smoking through much of the 20th century.

In order to be entitled to those findings, however, each Engle progeny plaintiff must prove the smoker at the heart of their case suffered from nicotine addiction that legally caused a specific smoking-related disease.

Key to the seven-day Simmons trial was the link between his smoking and his mouth cancer. During Monday’s closings, Reynolds’ attorney, King & Spalding’s Randall Bassett, argued the cancer’s location and Simmons’ relatively young age at diagnosis were inconsistent with smoking-related oral cancer. Bassett noted that defense expert Dr. Samir El-Mofty, an oral pathologist from Washington University, concluded Simmons’ cancer stemmed from an infection related to a tooth extraction. “Not a cancer caused by smoking, but a cancer caused by a virus that sometime along the way Mr. Simmons had been exposed to,” Bassett said.

But Harewood’s attorney, Koch, Parafinczuk, Wolf & Susen’s Austin Carr reminded jurors that Simmons’ treating physician, Dr. Francisco Civantos, a South Florida otolaryngologist, believed cigarettes caused Simmons’ cancer. “Dr. Civantos is the more credible, experienced, the more competent physician and surgeon,” Carr said during Monday’s closings. “He is the doctor that you should believe over [the defense] witness.”

September, 2018|Oral Cancer News|

Head and neck Cancer: Overcoming Challenges in Treatment

Source: www.curetoday.com
Author: staff

Itzhak Brook, M.D., M.Sc., shares the story of his initial diagnosis and treatment for cancer of the head and neck, outlining the challenges that came along with treatment, with fellow board member of the Head and Neck Cancer Alliance Meryl Kaufman, M.Ed., CCC-SLP, BRS-S.

Transcript:
Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Dr. Brook, can you please share your story about your cancer diagnosis in 2006 and the treatment that followed and also the subsequent surgery that you went through?

Itzhak Brook, M.D., M.Sc.: Once I learned I had cancer and my doctors removed it when they had to biopsy, I needed to receive radiation therapy. I did not get any chemotherapy, and the radiation therapy lasted six weeks, five days a week. It was very difficult to experience the radiation, and the side effects start to accumulate within a few days. And I had to deal with inflammation of the mouth, mucositis, difficulty in swallowing and pain in my throat, and I experienced a burning of the skin around the area of radiation, weakness and then difficulty maintaining intake of food. After a while, I could lose weight, and I tried to persevere because I knew that I had to receive the treatment to get better and soldier through it until it was over.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Exactly. And some people have such severe side effects from the radiation that they actually require a feeding tube to support them during their treatment. In that case, often patients are encouraged to eat and drink and use that feeding tube to supplement what they’re able to eat and drink. Did you find that there were certain foods that were difficult for you to swallow and you needed to avoid during that time?

Itzhak Brook, M.D., M.Sc.: I was fortunate that I was able to maintain my hydration and nutrition without the feeding tube. And in my trial and error, I found solid food, cold food, such as watermelon, ice cream and sour cream. I tried to consume high-calorie food so that even though I don’t eat as much, I would still take calories in and not lose a lot of weight. I was lucky I lost only 5 pounds, but some people lose more. The most important thing is to stay hydrated, get enough food and get enough water, which at that time was a real challenge, as the nausea increased over time. But fortunately, I had a very good support system in the place where I got it. I had a radiation oncologist who had advised me and told me and helped me cope with the side effects.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Exactly. And how important was your support system at home? Who supported you and helped get you through that treatment?

Itzhak Brook, M.D., M.Sc.: Obviously, that’s very, very important. My wife and children were very supportive of me, and they knew that I was going through a rough time and tried to help me in all the other ways possible. Also, at work, I got a lot of understanding and support from my team of co-workers. I was then in the military. I was in the U.S. Navy and got my treatment at Walter Reed, and they were very, very helpful in trying to ease it.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: And then when the cancer came back, you faced a laryngectomy. Can you talk to us about what that meant to you and what sort of associated fear and stigma you experienced?

Itzhak Brook, M.D., M.Sc.: Well, the most important thing was that they caught the cancer, and that was because I saw an otolaryngologist every month, and this is done for the first year and second year because that’s the time when more recurrences happen, in those two years. And when the cancer was diagnosed, they tried to remove it through an endoscopy and direct biopsy, but it was already too difficult, as it had gotten into the areas where simple procedures couldn’t work. And then they realized that I needed an experienced physician to do it, and I went for a second opinion to another otolaryngologist in a different city. And he referred me to another one because he felt that person would be the best to do it.

And fortunately, we have fewer laryngectomies today, partly because of the experience in doing it is less prevalent and you need to find what I found: the person who knew it best. And they finally removed it, but the understanding that I needed laryngectomy was very difficult. I suddenly realized that my voice would be lost, and I like to speak. Like anyone, I like to lecture, and accepting that I would have to lose my voice was very difficult. I remember that as a medical student some 50 years ago, when I saw laryngectomies, I said to myself, “If I ever have to make a choice, I would never give up my choice even if it cost me my life.” But once I had a choice and I also understood that I could still speak—differently, but I could speak—I made the decision very quickly. There was no doubt in my mind that in order to stay alive, I was going to do it, and I don’t regret it.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: That’s so important for people to understand that there is life after laryngectomy or glossectomy, in the case of having your tongue removed or part of your jaw. There is life, there is rehabilitation and there are ways to go about learning how to speak and swallow again in the face of these challenges. What is something that you wish you had known prior to the diagnosis or during that time period that you can give to other people facing the same situation?

Itzhak Brook, M.D., M.Sc.: I wish I had known that I needed to go to the best physicians who are experienced in the field to do the procedure, and I should not have avoided to make the decision right away but take the time to search for the best person who could help me. I also wish that I had known that even though I was prepared for the procedure, my physicians, nurses and speech pathologists did prepare me, helped me, and they explained to me that experiencing this is completely different from all the words and explanations. And it’s still a very difficult period to undergo this major surgery and be in the hospital completely helpless. But it was worth it because even though it was difficult, I got my life back, and I still believe that life is a very, very precious thing. And if you need to lose something to gain life, it’s worth it.

September, 2018|Oral Cancer News|

Head and neck cancer: Novel treatment approaches

Source: www.curetoday.com
Author: staff

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S, and Itzhak Brook, M.D., M.Sc., board members of the Head and Neck Cancer Alliance, share insight into the role of novel treatment approaches like immunotherapy, robotic surgery and de-escalation in the management of cancers of the head and neck.

Transcript:
Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Dr. Brook, traditionally the treatment for head and neck cancer has been surgery, radiation, chemotherapy or some combination of those three. But there are some new and emerging treatment approaches to head and neck cancer along with many other cancers. Can you tell us a little bit about immunology? What is immunotherapy in the care of the head and neck cancer patient?

Itzhak Brook, M.D., M.Sc.: Most days, we don’t get cancer because our immune system is like the police department of our body. They detect cancer early and eliminate it. Unfortunately, in the case of cancer, the cancer cells can fool the immune system, and they go undetected and cause the disease. The main advantage of immunotherapy is that we are using the body’s defenses, the immune system, to kill the cancer in a much better way than the chemotherapy. Chemotherapy destroys the cancer cells, but it also affects the body cells. Immunotherapy is more precise. It is directed only to the cancer cells, so the rest of the body stays unscathed. That’s the beauty of immunotherapy. So, immunotherapy is an evolving field in cancer. They have many, many new drugs in the pipeline, and many studies are being done. But right now, there are several drugs that are good and seem to help in a patient with cancer, cancer that has already spread or that surgery cannot reach. The body’s own immunity would reach it.

One of them is monoclonal antibodies that were developed specifically for the cancer cells, and the other one is checkpoint inhibitors, which overcome the attempt by the cancer cells to fool the immune system and protect the cancer cells from their own immunity. So, by blocking those checkpoints, the body’s own immunity comes in and destroys the cancer cells. Those drugs are very promising because first of all, they are more effective in getting only the cancer cells. They do cause fewer side effects, and we are hopeful that they would be the new armamentarium that we will have for head and neck cancer.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: So, would you say that’s something you should ask your physician about to find out what clinical trials and what types of medications are offered for your specific type of cancer at the time of diagnosis?

Itzhak Brook, M.D., M.Sc.: Absolutely, and that is depending on your own illness, on the seriousness or stage of the illness. And your physician would be able to consult the right specialist to tailor the specific treatment for you, and that’s very important because now we have a new tool that can augment the chemotherapy. And many of those treatments are given in combination. Conventional treatment with chemotherapy plus immunotherapy seems to work very well in many patients.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Yes. The future is exciting in that regard. In the case of the HPV-positive oropharyngeal cancers, there has also been a lot of interest and push toward robotic surgery in caring for that patient population. I know that that’s not for everybody, and it’s more suited for some of the smaller tumors because of the side effects that might go along with it. What is your understanding of the role of robotic surgery in the care of head and neck cancer patients?

Itzhak Brook, M.D., M.Sc.: Robotic therapy is an amazing new procedure. It’s being done using the robotic tools that are able to do the surgery in a much less invasive way without traumatizing many of the normal tissues of the body. They cause less damage. The recovery period is shorter, and patients benefit from it tremendously. In that procedure, there is a robotic machine that the surgeon operates, and it allows very, very precise ability to cut the cancer out, and it does cause less long-term damage to the tissues and less deformity, you may say. And that’s a wonderful tool. But unfortunately, as you said, it is limited to areas of the body that the robot can reach. And when the cancer is in places that are not reachable by the robotic approach, one needs to use the conventional approach. But even in that area, there is a development of using endoscopic surgery where one can use a laser and the endoscopic approach, or the laser can kill or burn out the cancers that are more deeply located in the throat, again saving major surgery and even saving removal of the larynx from patients.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: That’s right. And also, there’s a push toward de-escalation of the radiation and the chemotherapy in some of these HPV-positive patients, as well, because the tumors are more responsive to the treatment. So, there are many studies going on looking at whether we can do less treatment for the different types of diseases. As you spoke earlier, I think finding the right specialists is important; not everybody is a specialist in all these new and advanced technologies. If you’re looking for robotic surgery, find that specialist that really does a lot of robotic surgery and is an expert in that field. The same is true for the immunotherapy and other treatment approaches as well. So, I think being your own advocate, again, to find these different alternative options and these new treatments in clinical trials becomes exceedingly important in the age of all these new discoveries.

Itzhak Brook, M.D., M.Sc.: Fortunately, the knowledge of experience in those procedures, the laser and the robotic surgery, is becoming more prevalent in the United States. And when I had my cancer, when I needed to make choices 10 years ago, there were only a handful of experts. But right now, almost every major medical center has an expert in those fields, so it’s more available for people.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Absolutely. So, even if you have to travel a distance to get to those major medical centers, it’s worth the effort and travel and time to be able to seek these other opinions and see what your other options are before pursuing your treatment.

Itzhak Brook, M.D., M.Sc.: Absolutely.

Meryl Kaufman, M.Ed., CCC-SLP, BRS-S: Yes, I agree.

September, 2018|Oral Cancer News|

Cancer biology graduate student travels ‘ROCKy’ road toward a cure for post-radiation dry mouth

Source: medicalxpress.com
Author: staff, University of Arizona

The United States is in the midst of a head-and-neck cancer epidemic. Although survival rates are relatively high—after treatment with chemotherapy and radiation—survivors can suffer permanent loss of salivary function, potentially leading to decades of health problems and difficulties eating.

It is unknown why the salivary gland sometimes cannot heal after radiation damage, but Wen Yu “Amy” Wong, BS, a University of Arizona cancer biology graduate student, may have taken a step toward solving that riddle.

Radiation often comes with long-term or even permanent side effects. With a head-and-neck tumor in radiation’s crosshairs, the salivary gland might suffer collateral damage.

“When you get radiation therapy, you end up targeting your salivary glands as well,” Wong said. Losing the ability to salivate predisposes patients to oral complications and an overall decrease in their quality of life. “Salivary glands help you digest food, lubricate your mouth and fight against bacteria. After radiation, patients could choke on their food because they can’t swallow. They wake up in the middle of the night because their mouth is so dry. They often get cavities.”

Favorite foods may lose their flavor. “Saliva produces certain ions that help you taste,” she said. “Patients lose the ability to enjoy food. The best steak is very bland to them.”

The quest to restore salivary function in post-radiation head-and-neck cancer patients starts with learning why the salivary gland is unable to heal itself after radiation damage.

Wong’s study may have helped to unravel this mystery. Her team looked closely at two proteins, E-cadherin and β-catenin, which allow communication between cells. Normally, these proteins bind cells together, but after radiation damage, these connections are severed. “Think of them as telephone wires,” Wong said. “Radiation is like lightening hitting a telephone pole. That breaks the ability of one friend to talk to another on the other side of the city.”

Just as a maintenance crew can repair downed telephone poles after a storm, the body is able to heal itself after injury. Unfortunately, in post-radiation dry mouth, salivary glands’ ability to regenerate might be blocked.

In the lab, Wong was able to artificially force the regeneration of salivary glands, allowing her to learn where there are obstructions in the regeneration process. Wong particularly was interested in something called the ROCK pathway, which might go awry in the wake of radiation, blocking E-cadherin and β-catenin from reuniting.

“If I use an inhibitor to prevent this ROCK signaling pathway, these two proteins come back together,” Wong said.

The next step is to learn more about how a defective ROCK pathway blocks salivary glands’ natural ability to regenerate following radiation damage. Unlocking this secret could uncover novel ways to treat or cure post-radiation dry mouth.

Earlier this month, Wong and her co-authors were recognized by the American Physiological Society for their investigation, which was published in June by the American Journal of Physiology—Regulatory, Integrative and Comparative Physiology. Wong, along with Maricela Pier, BS, a research specialist with the UA College of Medicine—Tucson Department of Cellular and Molecular Medicine, and Kirsten Limesand, Ph.D., of the UA Cancer Center and professor of nutritional sciences with the UA College of Agriculture and Life Sciences, was selected for the APSselect award, given to the best articles in physiological research.

Wong selected Dr. Limesand’s lab as her “home base” throughout her graduate studies because “I wanted to connect with a woman in science who understands the difficulties. She was very easy to talk to, and the people in the lab provide a very nurturing environment. She is a great mentor.”

Dr. Limesand takes her role as a mentor seriously, and finds it deeply satisfying.

“Hands down, the most rewarding aspect of my career is training students,” Dr. Limesand said. “They’re our next generation of scientists, tackling the big questions that need to be solved.”

Dr. Limesand is a professor with the UA Cancer Biology Graduate Interdisciplinary Program, which emphasizes translational research to address significant problems relating to cancer development and treatment. Students are prepared for careers in cancer research through an interdisciplinary approach involving faculty members from a wide range of disciplines.

“I have students from cancer biology and physiological sciences, and I’ve been on committees of genetics students and immunobiology students,” said Dr. Limesand. “These diverse perspectives add to the research we’re doing.”

August, 2018|Oral Cancer News|

Smarter cancer treatment: AI tool automates radiation therapy planning

Source: news.engineering.utoronto.ca
Author: Brian Tran

Aaron Babier (MIE PhD candidate) demonstrates his AI-based software’s visualization capabilities. (Credit: Brian Tran)

Beating cancer is a race against time. Developing radiation therapy plans — individualized maps that help doctors determine where to blast tumours — can take days. Now, Aaron Babier (MIE PhD candidate) has developed automation software that aims to cut the time down to mere hours.

He, along with co-authors Justin Boutilier (MIE PhD 1T8), supervisor Professor Timothy Chan (MIE) and Professor Andrea McNiven (Faculty of Medicine) are looking at radiation therapy design as an intricate — but solvable — optimization problem.

Their software uses artificial intelligence (AI) to mine historical radiation therapy data. This information is then applied to an optimization engine to develop treatment plans. The researchers applied this software tool in their study of 217 patients with throat cancer, who also received treatments developed using conventional methods.

The therapies generated by Babier’s AI achieved comparable results to patients’ conventionally planned treatments. — and it did so within 20 minutes. The researchers recently published their findings in Medical Physics.

“There have been other AI optimization engines that have been developed. The idea behind ours is that it more closely mimics the current clinical best practice,” says Babier.

If AI can relieve clinicians of the optimization challenge of developing treatments, more resources are available to improve patient care and outcomes in other ways. Health-care professionals can divert their energy to increasing patient comfort and easing distress.

“Right now treatment planners have this big time sink. If we can intelligently burn this time sink, they’ll be able to focus on other aspects of treatment. The idea of having automation and streamlining jobs will help make health-care costs more efficient. I think it’ll really help to ensure high-quality care,” says Babier.

Babier and his team believe that with further development and validation, health-care professionals can someday use the tool in the clinic. They maintain, however, that while the AI may give treatment planners a brilliant head start in helping patients, it doesn’t make the trained human mind obsolete. Once the software has created a treatment plan, it would still be reviewed and further customized by a radiation physicist, which could take up to a few hours.

“It is very much like automating the design process of a custom-made suit,” explains Chan. “The tailor must first construct the suit based on the customer’s measurements, then alter the suit here and there to achieve the best fit. Our tool goes through a similar process to construct the most effective radiation plan for each patient.”

Trained doctors, and often specialists, are still necessary to fine-tune treatments at a more granular level and to perform quality checks. These roles still lie firmly outside the domain of machines.

For Babier, his research on cancer treatment isn’t just an optimization challenge.

“When I was 12 years old, my stepmom passed away from a brain tumour,” Babier shares.

“I think it’s something that’s always been at the back of my head. I know what I want to do, and that’s to improve cancer treatment. I have a family connection to it. It adds a human element to the research,” says Babier.

August, 2018|Oral Cancer News|

Silent no more: Woman lends voice to hope after cancer

Source: health.ucsd.edu
Author: Yadira Galindo

Singing hymns in church has always brought Cynthia Zamora joy. Today, her once sharp intonation has given way to a raspy voice. But Zamora is thankful that she has a voice at all after spending three months without the ability to utter even one syllable.

“I miss going to church and singing with people,” said Zamora. “Although, if I am in the back I’m still singing. I’m just hoping they don’t hear what sounds like a 13-year-old pubescent boy back there, because that’s how I sound. I know God thinks it’s beautiful, so I don’t worry about it. I just go on with life.”

In 2017, Zamora bit her tongue while sleeping, splitting her tongue nearly in half. She was referred to a specialist when her wound would not heal. They found a 5.4-centimeter tumor that enveloped more than half of her tongue. To save her life, her surgeon, Joseph Califano, MD, delivered grim news: Zamora would have to undergo a glossectomy — the surgical removal of all or part of the tongue.

“By the time I saw her she was really having a hard time speaking and swallowing,” said Califano, director of the Head and Neck Cancer Center at UC San Diego Health. “With Cynthia that was a difficult discussion because it was unclear how much tongue we would save and how good the function would be with the remaining tongue that would be preserved.”

A multidisciplinary team of experts that included medical oncology, surgical oncology, reconstructive surgery, radiation oncology, speech therapy, nutrition, psychiatry and a host of others came together to design a comprehensive plan to eradicate an aggressive, stage IV squamous cell carcinoma and deliver the best quality of life for a woman who was about to undergo a catastrophic surgery.

“The tongue is critical. It’s one of the strongest muscles we have in our body. In speech, our tongue is moving so rapidly within the confines of our mouth in order to generate and make certain sounds in conversation that we find it’s hard to grasp how complex that action is,” said Liza Blumenfeld, speech-language pathologist at Moores Cancer Center at UC San Diego Health. “Without a tongue you’re having to compensate for all of that movement with other structures, your lips, your cheeks and your jaw.”

During a 12-hour surgery, Califano would remove a large portion of Zamora’s tongue and place a breathing tube and feeding tube before a reconstructive microsurgeon would step in to replace the portion of tongue that was removed.

“The primary goal of surgery is to remove the cancer as best we can while sparing as much normal tissue as possible,” said Califano. “It was a challenging surgery in that we had to cut just right to save enough tongue so that she would have some function and we could still get well around the tumor. We were able to save less than half her oral tongue. That wasn’t a lot.”

Ahmed Suliman, MD, a plastic surgeon who specializes in reconstruction after cancer treatment, was tasked with reconstructing her tongue.

“When you remove the majority of the tongue you can’t really function,” said Suliman. “You can’t swallow and articulation is limited. We had to rebuild a tongue to provide bulk so that Cynthia could move food in her mouth in order to swallow and to speak.”

He used a method called anterolateral thigh perforator flap (ALT). Suliman cut a 6 by 8 centimeter tissue of skin and fat from Zamora’s leg to shape and create a new tongue. The replacement tongue does not move, but because Califano was able to spare the base of her original tongue, Suliman was able to reconstruct using the remaining tongue base to preserve some movement for Zamora. Suliman sutured the new tongue, attaching one artery and a vein from the neck using a microscope.

The reconstructive surgery and dissection of cancerous tissue in her tongue and lymph nodes left Zamora temporarily unable to walk, talk or eat. One of the advantages of performing an ALT is that minimal thigh muscle, or none at all, is cut when extracting tissue for the new tongue. This allows for a faster recovery because Zamora did not lose leg muscle function, so with physical therapy Zamora was on her feet fairly quickly.

Skin and fat tissue are more resilient to radiation therapy than muscle, said Suliman, making this tissue more ideal for someone like Zamora, who received treatment following surgery.

“The success of management of these advanced cancers rely on the coordinated efforts of a multi-disciplinary oncologic team,” said Suliman. “This leads to better planned surgery, good preoperative and post-operative care, and follow up. The success of complex cases is higher and outcomes are better, as demonstrated by Cynthia.”

While Zamora was undergoing physical therapy and speech therapy, she was also undergoing chemotherapy, radiation and was receiving an experimental immunotherapy called Pembrolizumab (Keytruda), an antibody that inhibits the abnormal interaction between the molecule PD-1 on immune cells and the molecule PD-L1 on cancer cells, allowing the immune cells to recognize and attack tumors. Pembrolizumab is FDA-approved for some cancers, such as melanoma but is still under a clinical trial for squamous cell carcinoma of the head and neck .

While Zamora continued aggressive treatment and attended physical therapy, she also met with Blumenfeld.

“Teaching somebody to regain their speaking and swallowing abilities during head and neck cancer treatment is really difficult,” said Blumenfeld. “Being able to understand what their abilities were like before, and being able to understand what their new normal looks like, helps us play on their strengths and their ability to compensate with other structures.”

Blumenfeld and Zamora worked together targeting the sounds that she had problems expressing. Zamora had to slow her speech and exaggerate each sound, compensating with her vocal chords for sounds she can no longer make with her tongue.

It is a tedious process but in three months Zamora was speaking well again.

“Previously, I was well pronounced with an expansive vocabulary. I had to be patient with myself and use more expressions in my eyes, hands and face. Sometimes I have to pick words I wouldn’t normally use because I can’t use my original vocabulary. Quality is better than quantity,” said Zamora.

“You have to want to be able to communicate in order to talk, and I wanted that more than anything, because I am a person who loves to communicate. I haven’t got singing down yet, but hopefully that will come.”

Zamora’s vocal chords are healthy and with time, patience and modifying her technique, Blumenfeld thinks that Zamora will be singing “proudly, loudly sometime soon.”

“There are people that come into your life as patients and your mind is blown by their strength of character, their humor, their wisdom, and their willingness to fight. Cynthia really embodies all of those things,” said Blumenfeld. “From the first day she was insistent that she was going to come out of this as a stronger, better person. She has really shown me, even in my own personal life, to never give up and to set your mind on a set target, and you simply do not deviate from that.”

In addition to regaining her speech, Zamora would need to relearn to eat. This was her last hurdle to recovery. It was only in early 2018 that she began to eat without a feeding tube.

“I would encourage everybody to think for a moment of what life would be like. Grab your tongue with your teeth and try to talk without a tongue. Try to think about, when you take a bite of a sandwich, everything that’s going on in your mouth,” said Blumenfeld. “In order for us to be able to chew, we have to be able to manipulate food, move it from one side of our mouth to the other side of the mouth. We have to be able to organize all that food on top of our tongue and propel that food backwards in order to swallow it. Without a tongue that becomes almost an impossible task.”

Thankfully, Zamora mastered the ability to eat again and laughs when recalling eating half a lava cake in front of her shocked family during a restaurant outing. She eats crispy fried chicken and just about anything she wants.

“With a little patience and care, and one step, baby steps, along the way, you can do anything,” said Zamora. “Look at me. I had no tongue, and I’m talking. I’m eating. I’m drinking. I’m doing great. There is life after this surgery. Don’t give up. Keep going. Be strong. Be stubborn. You can do it, you can.”

State not allowed to investigate death at cancer center

Source: kdvr.com
Author: Rob Low

Lakewood, Colo. – When 80-year-old Virginia Cornelius died at a Rocky Mountain Cancer Care Centers’ location in Lakewood on February 27, the on-site doctor insisted it must’ve been a heart attack.

But the adult children of Cornelius aren’t convinced and tell the FOX31 Problem Solvers their efforts to find the truth have been stymied, partly because cancer centers generally aren’t regulated by the Colorado Department of Public Health and Environment.

Cornelius was receiving radiation treatment for cancer of the larynx in her throat. But her daughter, Susan Hutt, says her mother’s general health on February 27 was fine.

“They took her vital signs. They were better than mine,” Hutt said.

She said she was later told by a radiation tech that her mother was having trouble swallowing just before the procedure began but the treatment was allowed to continue anyway, when something went very wrong inside the patient room.

“All the sudden the door flies open and a curtain and the therapist is screaming in the hall, somebody call 911, somebody find the doctor,” remembered Hutt.

Hutt and her brother Gary Cornelius always sat in a waiting area next to the radiation room for all of their mother’s treatments having no idea that during every procedure their mother’s hands were strapped to a bed.

“We walk in and there is our mother on the table, hands restrained, the mask for radiation therapy with the oxygen that goes into it is up on a table, is hanging up above her. And there is no one in there. She is not responsive, but no one is doing CPR,” said Hutt.

Hutt said it appeared the radiation tech ran out of the room without ever performing CPR.

“Minutes are passing before the tech returns with not a code cart, which I would expect as I’m a nurse in a hospital and they are readily available, but what looked like a fishing tackle box. She puts it on the floor and can’t open it,” Hutt said.

By the time paramedics arrived her mother was dead.

According to the 911 call obtained by the Problem Solvers, a dispatcher is heard advising paramedics, “They (Rocky Mountain Cancer Care Centers) are asking that you not walk through the main lobby, they don’t want that, they want you to go through the back door. I’m not sure why.”

Hutt says she found that suspicious but what she said was even more concerning was learning the “Code Blue” panic button on the wall, which meant to summon emergency help, didn’t work. Plus, the radiation tech who had been treating her mother left before the Jefferson County Coroner arrived.

“Extremely suspicious, that the person present that finds a person down is not able to be interviewed by the coroner,” said Hutt.

The coroner’s report listed the final cause of death as “Acute Heart Failure.” But no autopsy was done.

Minutes after their mother’s death and in a state of shock, Hutt and her brother Gary Cornelius said the cancer care center’s on-site doctor convinced them no autopsy was needed. It’s a decision they now regret.

Several weeks after their mother’s death, Hutt and her brother were able to obtain their mother’s radiation logs.

According to the logs shared with the Problem Solvers, Virginia Cornelius’ treatments normally lasted three to four minutes. But on the day of her death, the treatment appeared to have lasted ten minutes.

Hutt and her brother wonder if their mother received too much radiation at once, or worse was forgotten about and possibly left to choke to death, unable to sit up and remove her oxygen mask.

“A side effect of head and neck radiation is a mucus that is so thick you don’t just clear your throat and get rid of it,” said Hutt.

More than three hours after Virginia died, her radiation log shows someone made new entries at 6:03 p.m., 6:05 p.m., and 6:07 p.m.

Hutt and her brother wonder if someone was attempting to recreate their mother’s chart after the fact. The siblings filed a complaint with the Colorado Department of Public Health and Environment but were shocked to learn the agency was powerless to investigate.

“We have no jurisdiction,” confirmed Dr. Randy Kuykendall. He’s the Director of Health Facilities and Emergency Medical Services for CDPHE.

Dr. Kuykendall says the state can investigate potential wrong-doing inside a hospital because CDPHE licenses hospitals. But he admits all 20 Rocky Mountain Cancer Centers in Colorado aren’t licensed or accredited by anyone.

It’s easy to be confused.

After all there’s a sign outside St. Anthony’s Hospital with an arrow that states “St. Anthony’s Cancer Center,” but it’s really pointing to Rocky Mountain Cancer Centers which isn’t owned or operated by the hospital even though they’re physically connected.

Rocky Mountain Cancer Centers is owned by U.S. Oncology and leases space inside the medical complex but faces none of the regulations of an actual hospital, like having a cardiac crash cart on site or a defibrillator.

“So this cancer care center doesn’t have to have a panic button, doesn’t have to have any of these emergency procedures or policies in place?” asked investigative reporter Rob Low to Kuykendall, who responded, “That would be correct, Rob.”

“We cannot allow these centers just to focus on profits over patient safety. Unfortunately, that`s a real concern,” said Hollynd Hoskins a medical malpractice attorney, who added, “If you have a facility that is not accredited and has no oversight by the state, they could be cutting corners and they could be hiring just techs at a cheaper wage rate than you would have to pay a qualified registered nurse and unfortunately that is a threat to patient safety.”

The Problem Solvers had lots of questions for Rocky Mountain Cancer Centers but Executive Director Glenn Balasky would only release a statement, that reads in part, “For a number of reasons, we cannot discuss the care provided to any particular patient treated at Rocky Mountain Cancer Centers. We can however assure you that patient care remains one of our highest priorities.”

Hutt finds it curious that Rocky Mountain Cancer Centers won’t discuss her mother’s care with the Problem Solvers when she’s willing to sign a consent form releasing RMCC from patient confidentiality restrictions.

“What’s really hard for me, I picture my mother restrained on a table with no monitor, choking to death and they brush it off like she was 80 she had a heart attack. It`s over and done. We`ll report what we want to,” said Hutt.

After repeated phone calls from FOX31, Rocky Mountain Cancer Centers had its attorney call Hutt and her brother Gary Cornelius.

The siblings told the Problem Solvers the attorney and an office manager for the cancer center told them safety changes have been made because of their mother’s death.

As for regulating cancer centers, that would take state legislation and so far lawmakers have no appetite to regulate them.