Liquid biopsy accurately detects HPV+ oropharyngeal cancer recurrence

Source: www.medpagetoday.org
Author: Zeena Nackerdien PhD, CME Writer, MedPage Today

In general, HPV-positive OPSCC has a favorable prognosis as compared with HPV-negative disease, which has supported efforts to de-intensify treatment regimens to reduce exposure to potentially toxic therapies. Positron emission tomography/computed tomography (PET/CT) imaging 3 months after definitive treatment is standard for response assessment in many cases.

However, the disease will recur in up to 25% of patients, depending on clinical risk factors and tumor biology. The latency period prior to OPSCC recurrence is 2 years for many patients, but rare case reports have described latency periods exceeding 5 years.

Currently, National Comprehensive Cancer Network (NCCN) guidelines recommend surveillance of patients with HPV-associated OPSCC every 1 to 3 months for the first year, every 2 to 6 months for the second year, every 4 to 8 months for years 3 to 5, and then once a year thereafter.

Because the oropharynx can be a difficult anatomic location to evaluate — a process that may be further obscured by treatment-related tissue changes — radiologic imaging studies have been used in cancer surveillance for this disease.

According to study findings published in the Journal of Clinical Oncology, a blood test for tumor-associated HPV-DNA had near-perfect accuracy for identifying OPSCC patients at high risk of recurrence after treatment.

The findings have clear and immediate implications for clinical practice, including earlier initiation of salvage therapy for patients with recurrent disease, reported Bhishamjit S. Chera, MD, of the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and colleagues.

The negative predictive value (NPV) of 100% and positive predictive value (PPV) of 99% of recurrence detection by this method compared favorably with alternative and emerging post-treatment surveillance strategies.

The findings extended those of a previous report, which showed that a persistently negative ctHPV-DNA test ruled out disease recurrence.

“With regard to how this is applicable to clinical practice, I think it improves the effectiveness, it improves the efficiency, and it reduces the cost and financial toxicity to patients,” Chera told MedPage Today.

Chera and colleagues prospectively evaluated a ctHPV-DNA liquid biopsy in 115 patients who had completed definitive chemoradiotherapy for HPV-positive OPSCC. Each patient had PET/CT imaging 3 months after finishing treatment. The researchers tested patients for ctHPV-DNA at 6- to 9-month intervals.

During a median follow-up of 23 months, 28 patients tested positive for ctHPV-DNA, indicating a possible recurrence, including 16 patients who had two consecutive positive tests. Also during follow-up, 15 patients developed biopsy-proven recurrence of OPSCC; all 15 had two consecutive positive tests for ctHPV-DNA. The median time from ctHPV-DNA positivity to recurrence was 3.9 months.

Consecutive positive tests had a PPV of 94%. The previous report from the study showed that a negative test had an NPV of 100%.

For the 87 patients who tested negative for ctHPV-DNA, none developed recurrence.

“In this study, we had accumulated enough follow-up data to see who was going to develop recurrence and who wasn’t,” said Gaorav Gupta, MD, PhD, assistant professor in the department of radiation oncology at UNC School of Medicine, in a press release. “That allowed us to determine that the test performs best if you look at two consecutively confirmed blood tests.”

Chera and team did acknowledge that heterogenous clinical factors (intensity of treatment, tobacco pack-years, use of chemotherapy) might have impacted the pattern and frequency of disease recurrence in this study. Other study limitations included the fact that the results for the ctHPV-DNA assay used in this study might not apply to alternative ctHPV-DNA assays.

Since there is no “gold standard” for surveillance imaging, the researchers chose the more stringent criterion of biopsy-proven recurrence to define a change in disease status. They added that a shorter interval between ctHPV-DNA testing (e.g., every 3 months) would more precisely define the extent of earlier detection.

Source Reference: Journal of Clinical Oncology 2020; DOI: 10.1200/JCO.19.02444

    Study Highlights and Explanation of Findings:

While imaging and image-guided procedures play important roles in the screening, diagnosis, and surveillance of cancer, serial monitoring for disease recurrence can be a costly, invasive, and cumbersome process.

“We developed a technology that enabled us to distinguish HPV DNA that came from a tumor from HPV that’s simply related to infection,” said Gupta.

“The way I see this working in the clinic is that if you have a negative test, we don’t do a fiberoptic exam, we don’t order any imaging,” said Chera. “If you have a patient whose surveillance test is positive, we would bring the patient back 2 or 3 months later and repeat the blood test. If it’s positive again, then we would do an in-depth physical examination; we would do a fiberoptic exam and order a total-body PET/CT scan. This test can help us better identify which patients we can omit imaging in and those patients we can do imaging in.”

The test very well could have value in the management of patients with other types of HPV-related cancers, he said. The researchers have already examined the rate of ctHPV-DNA clearance as a biomarker for response to treatment and a possible decision-making tool for treatment de-escalation.

The testing technology has been licensed to Naveris for commercial development, and multiple medical centers have already partnered with the company to conduct studies across a variety of HPV-related diseases, said Chera.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate Professor, Weill Cornell Medical College

References:
Chera BS, et al “Plasma circulating tumor HPV DNA for the surveillance of cancer recurrence in HPV-associated oropharyngeal cancer” J Clin Oncol 2020; DOI: 10.1200/JCO.19.02444.

Bankhead C “Blood Test Spot On for HPV Cancer Recurrence”, MedPage Today 2020-4-09.

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April, 2020|Oral Cancer News|

Which cancers have increased over the past decade?

Source: www.mdlinx.com
Author: Naveed Saleh, MD, MS, for MDLinx

The incidence of cancers at the level of the oral cavity and pharynx increased between 2007 and 2016, according to a recent report by researchers from the CDC published in Morbidity and Mortality Weekly Report. This rise occurred despite respective decreases in the incidence of cancers at various anatomic sites.

Cancers of the oral cavity and pharynx make up 3% of cancers diagnosed in the United States each year, with risk factors including tobacco use, HPV infection, and excessive alcohol intake.

“The overall increase appears to be driven by increases in cancers of the tonsil, base of tongue, oropharynx, and other cancers of the oral cavity and pharynx, which are HPV-associated, as well as by those of gum and anterior tongue,” wrote the authors.

Breaking down the numbers
On average, the incidence rates for cancers of the oral cavity and pharynx combined increased by 0.6% per year between 2007 and 2016, with specific increases as follows:
Oral cavity and pharynx (3.4%)
Base of tongue (1.8%)
Anterior tongue (1.8%)
Gum (1.9%)
Tonsil (2.4%)
Oropharynx (1.9%)

For the following cancers, however, incidence rates decreased:
Soft palate and uvula (−3.7%)
Hard palate (−0.9%)
Floor of mouth (−3.1%)
Lip (−2.7%)
Hypopharynx (−2.4%)
Nasopharynx (−1.3%)

Of note, the incidence of cheek and other mouth and salivary gland cancers remained unchanged.

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April, 2020|Oral Cancer News|

Novel intervention looks to improve timeliness, equity of head and neck cancer care delivery

Source: www.miragenews.com
Author: staff report, Medical University of South Carolina

Many factors go into surviving cancer.

Hollings Cancer Center researcher Evan Graboyes, M.D., specializes in head and neck cancer, a disease with poor survival prospects despite intense therapy with combinations of surgery, radiation and chemotherapy. While head and neck cancer only accounts for 4% of all cancer cases each year in the US, it has a high mortality rate. The American Cancer Society estimates that more than 14,000 patients died from this disease in the U.S. in 2019.

Overall, only 50% of head and neck cancer patients are alive at five years. Unfortunately, the mortality rate is even worse for African American head and neck cancer patients. That’s why researchers are looking for new strategies to improve patient survival and decrease racial disparities in outcomes for these patients.

Graboyes and MUSC Hollings Cancer Center researchers Chanita Hughes-Halbert, Ph.D., Katherine Sterba, Ph.D., Hong Li, Ph.D., and Graham Warren, M.D., Ph.D., have teamed up to develop and test a novel intervention to improve the timeliness, equity and quality of head and neck cancer care delivery, which they think might one day be the key to improving survival for these patients.

Funded by a $1.3 million 5-year grant from the National Cancer Institute, their study – Improving the Timeliness and Equity of Adjuvant Therapy Following Surgery for Head and Neck Cancer-started in September 2019 and built upon important research funded by grants from Hollings Cancer Center.

Graboyes explained that for patients with advanced head and neck cancer who are treated with surgery, national guidelines recommend that postoperative radiation therapy should start within six weeks of surgery.

“However, we know from our research that despite national guidelines, over half of the patients nationally don’t get radiation started in a timely fashion. Patients who have delays with radiation are more likely to die and have their cancer recur,” he said. “We are trying to find new ways to deliver timely head and neck cancer care. It’s an appealing way to help improve survival for this group.”

Innovative approach
The study is designed in three parts. The first part aims to identify the underlying reasons for why delays starting postoperative radiation are so common for this patient population. The researchers then developed a new multilevel health care delivery intervention called NDURE (Navigation for Disparities and Untimely Radiation thErapy), that specifically targets the barriers that lead to delays.

In the second part of the grant, the researchers will pilot the NDURE intervention in a small group of patients to make sure that it’s feasible and acceptable and refine the intervention based on participant feedback. In the third and final part of the study, they will compare NDURE to standard care in a randomized controlled trial to see whether NDURE is effective at decreasing treatment delays.

“This study interests me because it is clinically important. To help patients with head and neck cancer live longer, you don’t need to invent a new drug. All you need to do is get them the treatment they’re supposed to be getting. If we can find a way to deliver timely guideline-recommended care, it could have such a large impact on their survival,” he said

“It’s also a scientifically important study. Head and neck cancer treated with surgery followed by radiation is a great model system for us to understand how we deliver cancer care. Right now, we spend a lot of time and effort helping get people in to initiate cancer care. However, we understand a lot less about how cancer patients move through complicated treatment plans.”

Graboyes said South Carolina is primarily a rural state with some geographic barriers that present obstacles for patients to navigate. “Many of the patients will have surgery at a regional center like MUSC, then because radiation is five days a week for six weeks, they’ll get radiation at a different facility closer to where they live. We have to coordinate cancer care across health care systems, which presents some barriers that can lead to treatment delays.”

Graboyes emphasized that head and neck cancer is a major concern for the state of South Carolina and Hollings Cancer Center, a National Cancer Institute-Designated Cancer Center. The two major causes of head and neck cancer are smoking and human papillomavirus (HPV). The state’s population is affected by both, due to high rates of tobacco use and very low rates of HPV vaccination.

“As a result, Hollings has recognized this issue and has really invested a lot in the clinical enterprise of head and neck cancer because it’s such a problem in South Carolina.”

Hollings also has a strong cancer control program dedicated to reducing issues of health disparities and equity in the state, he explained.

“We think that NDURE, our intervention targeting the multilevel barriers to timely head and neck postoperative radiation, will be an effective way to help improve timely cancer care delivery for these patients, which will lead to higher rates of survival and low recurrence and decrease racial disparities and outcomes. That’s very exciting to our team.”

Did you know?
About 70% of cancers in the oropharynx (which includes the tonsils, soft palate and base of the tongue) are linked to HPV.

Dedicated to the mission of raising HPV vaccination rates for teens and young adults, Hollings Cancer Center has initiated a $700,000 three-year project. The Centers for Disease Control and Prevention recommends speaking with a doctor about the HPV vaccination. The HPV vaccine can prevent new infections with the types of HPV that most often cause oropharyngeal and other cancers.

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April, 2020|Oral Cancer News|

Home-based chemo skyrockets at one US center

Source: www.medscape.com
Author: Nick Mulcahy

In the fall of 2019, the University of Pennsylvania in Philadelphia started planning a pilot program of home-based chemotherapy for two treatment regimens (one via infusion and one via injection). Six months later, the Cancer Care at Home program had referred 40 patients.

The uptake within the university’s large regional health system was acceptable but not rapid, admitted Amy Laughlin, MD, a hematology-oncology fellow involved with the program.

Then COVID-19 arrived, along with related travel restrictions.

Suddenly, in a 4-week period (March 10 to April 7), an additional 135 patients had been referred ― a 300% increase from earlier. The list of chemotherapies delivered went from two to seven, with more coming.

“We’re not the pilot anymore ― we’re the standard of care,” Laughlin told Medscape Medical News.

“The impact [on patients] is amazing,” she said. “As long as you are selecting the right patients and right therapy, it is feasible and even preferable for a lot of patients.”

For example, patients with hormone-positive breast cancer who receive leuprolide (to shut down the ovaries and suppress estrogen production) ordinarily would have to visit a Penn facility for an injection every month, potentially for years. Now, a nurse can meet patients at home (or before the COVID-19 pandemic, even at their place of work) and administer the injection, saving the patient travel time and associated costs.

This home-based chemotherapy service does not appear to be offered elsewhere in the United States, and a major oncology organization ― the Community Oncology Alliance ― is opposed to the practice because of patient safety concerns.

The service is not offered at a sample of cancer centers queried by Medscape Medical News, including the Dana-Farber Cancer Institute in Boston, the Moffitt Cancer Center in Tampa, the Huntsman Cancer Institute in Salt Lake City, Utah, and Moores Cancer Center, the University of California, San Diego.

Opposition Because of Safety Concerns
On April 9, the Community Oncology Alliance (COA) issued a statement saying it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The COA warned that “many of the side effects caused by cancer treatment can have a rapid, unpredictable onset that places patients in incredible jeopardy and can even be life-threatening.”

In contrast, in a recent communication related to COVID-19, the National Comprehensive Cancer Network tacitly endorsed the concept, stating that a number of chemotherapies may potentially be administered at home, but it did not include guidelines for doing so.

The American Society of Clinical Oncology said that chemotherapy at home is “an issue [we] are monitoring closely,” according to a spokesperson.

What’s Involved
Criteria for home-based chemotherapy at Penn include use of anticancer therapies that a patient has previously tolerated and low toxicity (that can be readily managed in the home setting). In addition, patients must be capable of following a med chart.

The chemotherapy is reconstituted at a Penn facility in a Philadelphia suburb. A courier then delivers the drug to the patient’s home, where it is administered by an oncology-trained nurse. Drugs must be stable for at least a few hours to qualify for the program.

The Penn program started with two regimens: EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) for lymphoma, and leuprolide acetate injections for either breast or prostate cancer.

The two treatments are polar opposites in terms of complexity, common usage, and time required, which was intended, said Laughlin.

Time to deliver the chemo varies from a matter of minutes with leuprolide to more than 2 hours for rituximab, a lymphoma drug that may be added to EPOCH.

The current list of at-home chemo agents in the Penn program also includes bortezomib, lanreotide, zoledronic acid, and denosumab. Soon to come are rituximab and pembrolizumab for lung cancer and head and neck cancer.

Already Practiced in Some European Countries
Home-based chemotherapy dates from at least the 1980s in the medical literature and is practiced in some European countries.

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April, 2020|Oral Cancer News|

Gene variant makes head and neck cancer more aggressive

Source: www.futurity.org
Author: posted by National University of Singapore

A genetic variant in a gene called MET is responsible for more aggressive growth of head and neck cancer, and lung cancer, according to a new study.

A further probe into the finding reveals therapeutic strategies that could potentially target this genetic alteration and pave the way for better and more effective treatments.

The MET gene encodes for a cancer promoting protein that relays growth, survival, and transmission of signals in cancer cells, researchers say.

As reported in Nature Communications, researchers also identified a form of MET protein which showed ethnic preference with higher incidence among Asians, and associated with poorer prognosis in patients diagnosed with head and neck squamous cell carcinoma or lung squamous cell carcinoma.

Even though the MET variant does not seem to predispose someone to head and neck cancer or lung cancer, it leads to more aggressive growth of cancers that have already developed.

Unlike other MET mutants, existing MET-blocking drugs do not seem to inhibit this genetic variant, prompting researchers to conduct further investigation on the mechanism behind the genetic alteration.

The team found that the single amino-acid change in the MET receptor from the genetic alteration leads to preferential strong binding to another cancer promoting protein, HER2. Both proteins then work together to drive cancer aggression and allow the cancer cells to survive therapies that involve MET-blocking drugs.

“The mechanism of this MET variant is novel and unreported. This finding contributes to the growing evidence of the role of genetic variants in affecting clinical outcome, and underscores the importance of diving deep into our genetic inheritance in cancer research,” says Kong Li Ren of the Cancer Science Institute (CSI) Singapore at NUS, who initiated the study.

Knowledge of this unique mechanism also allowed researchers to identify several HER2 inhibitors capable of blocking cancer progression the genetic alteration caused.

“Our study represents a conceptual advancement to cancer research, as we have shown that it is possible to block the activity of a cancer-driving gene by administrating a targeted therapy directed not against the mutant protein in question, but rather, a corresponding protein with which it binds to,” says Goh Boon Cher, deputy director and senior principal investigator at CSI Singapore.

“The remarkable anti-tumor responses observed in our experimental models, coupled with the availability of FDA-approved HER2 inhibitors, also presents a huge opportunity for clinicians to improve disease outcome of this genetic alteration via precision medicine.”

The research team is now translating the findings to a clinical trial where patients tested positive for this MET variant gene are treated with suitable medications that have shown effectiveness in the laboratory.

Additional coauthors are from the National University Cancer Institute, the National Cancer Centre Singapore, and the Bioinformatics Institute at the Agency for Science, Technology and Research, Singapore.

Source: National University of Singapore

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April, 2020|Oral Cancer News|

John Prine, Who Chronicled the Human Condition in Song, Dies at 73

Source: The New York Times
Date: April 7th, 2020
Author: William Grimes

 

John Prine, the raspy-voiced country-folk singer whose ingenious lyrics to songs by turns poignant, angry and comic made him a favorite of Bob Dylan, Kris Kristofferson and others, died on Tuesday in Nashville. He was 73.

The cause was complications of the coronavirus, his family said.

Mr. Prine underwent cancer surgery in 1998 to remove a tumor in his neck identified as squamous cell cancer, which had damaged his vocal cords. In 2013, he had part of one lung removed to treat lung cancer. He had been hospitalized since late last month.

Mr. Prine was a relative unknown in 1970 when Mr. Kristofferson heard him play one night at a small Chicago club called the Fifth Peg, dragged there by the singer-songwriter Steve Goodman. Mr. Kristofferson was performing in Chicago at the time at the Quiet Knight. At the Fifth Peg, Mr. Prine treated him to a brief after-hours performance of material that, Mr. Kristofferson later wrote, “was unlike anything I’d heard before.”

A few weeks later, when Mr. Prine was in New York, Mr. Kristofferson invited him onstage at the Bitter End in Greenwich Village, where he was appearing with Carly Simon, and introduced him to the audience.

“No way somebody this young can be writing so heavy,” he said. “John Prine is so good, we may have to break his thumbs.”

The record executive Jerry Wexler, who was in the audience, signed Mr. Prine to a contract with Atlantic Records the next day.

Music writers at the time were eager to crown a successor to Mr. Dylan, and Mr. Prine, with his nasal, sandpapery voice and literate way with a song, came ready to order. His debut album, called simply “John Prine” and released in 1971, included songs that became his signatures. Some gained wider fame after being recorded by other artists.

They included “Sam Stone,” about a drug-addicted war veteran (with the unforgettable refrain “There’s a hole in Daddy’s arm where all the money goes”); “Hello in There,” a heart-rending evocation of old age and loneliness; and “Angel From Montgomery,” the hard-luck lament of a middle-aged woman dreaming about a better life, later made famous by Bonnie Raitt.

“He’s a true folk singer in the best folk tradition, cutting right to the heart of things, as pure and simple as rain,” Ms. Raitt told Rolling Stone in 1992.

Mr. Dylan, listing his favorite songwriters in a 2009 interview, put Mr. Prine front and center. “Prine’s stuff is pure Proustian existentialism,” he said. “Midwestern mind trips to the nth degree. And he writes beautiful songs.”

John Prine was born on Oct. 10, 1946, in Maywood, Ill., a working-class suburb of Chicago, to William and Verna (Hamm) Prine. His father, a tool-and-die maker at the American Can Company, and his mother had moved from the coal town of Paradise, Ky., in the 1930s.

Mr. Prine later wrote a ruefully bitter song titled “Paradise,” in which he sang:

The coal company came with the world’s largest shovel
And they tortured the timber and stripped all the land
Well, they dug for their coal till the land was forsaken
Then they wrote it all down as the progress of man

John grew up in a country music-loving family. He learned guitar as a young teenager from his grandfather and brother and began writing songs.

After graduating from high school, he worked for the Post Office for two years before being drafted into the Army, which sent him to West Germany in charge of the motor pool at his base. After being discharged, he resumed his mail route, in and around his hometown, composing songs in his head.

“I always likened the mail route to a library with no books,” he wrote on his website. “I passed the time each day making up these little ditties.”

Reluctantly, he took the stage for the first time at an open-mic night at the Fifth Peg, where his performance of “Hello in There” and “Angel From Montgomery” met with profound silence from the audience. “They just sat there,” Mr. Prine wrote. “They didn’t even applaud, they just looked at me.”

Then the clapping began. “It was like I found out all of a sudden that I could communicate deep feelings and emotions,” he wrote. “And to find that out all at once was amazing.”

Not long after, Roger Ebert, the film critic for The Chicago Sun-Times, wandered into the club while Mr. Prine was performing. He liked what he heard and wrote Mr. Prine’s first review, under the headline “Singing Mailman Who Delivers a Powerful Message in a Few Words.”

“He appears onstage with such modesty he almost seems to be backing into the spotlight,” Mr. Ebert wrote. “He sings rather quietly, and his guitar work is good, but he doesn’t show off. He starts slow. But after a song or two, even the drunks in the room begin to listen to his lyrics. And then he has you.”

Mr. Prine had a particular gift for offbeat humor, reflected in songs like “Jesus, the Missing Years,” “Some Humans Ain’t Human,” “Sabu Visits the Twin Cities Alone” and the antiwar screed “Your Flag Decal Won’t Get You Into Heaven Anymore.”

“I guess what I always found funny was the human condition,” he told the British newspaper The Daily Telegraph in 2013. “There is a certain comedy and pathos to trouble and accidents.”

After recording several albums for Atlantic and Asylum, he started his own label, Oh Boy Records, in 1984. He never had a hit record, but he commanded a loyal audience that ensured steady if modest sales for his albums and a durable concert career.

In 1992, his album “The Missing Years,” with guest appearances by Bruce Springsteen, Tom Petty and other artists, won a Grammy Award for best contemporary folk recording. He received a second Grammy in the same category in 2006 for the album “Fair and Square.”

Mr. Prine, who lived in Nashville, was divorced twice. He is survived by his wife, Fiona Whelan Prine, a native of Ireland whom he married in 1996; three sons, Jody, Jack and Tommy; two brothers, Dave and Billy; and three grandchildren. In 2017, Mr. Prine published “John Prine Beyond Words,” a collection of lyrics, guitar chords, commentary and photographs from his own archive.

In 2019, he was inducted into the Songwriters Hall of Fame, and his album “Tree of Forgiveness” was nominated for a Grammy, for best Americana album. It was his 19th album and his first of original material in more than a decade. (The award went to Brandi Carlile, for “By the Way, I Forgive You.”)

Mr. Prine went on tour in 2018 to promote “Tree of Forgiveness,” and after a two-night stand at the Ryman Auditorium in Nashville — known there as the mother church of country music — Margaret Renkl, a contributing opinion writer for The New York Times, wrote, under the headline “American Oracle”:

“The mother church of country music, where the seats are scratched-up pews and the windows are stained glass, is the place where the new John Prine — older now, scarred by cancer surgeries, his voice deeper and full of gravel — is most clearly still the old John Prine: mischievous, delighting in tomfoolery, but also worried about the world.”

In December, he was chosen to receive a 2020 Grammy for lifetime achievement.

As a songwriter, Mr. Prine was prolific and quick. In the early days, he would sometimes dash off a song while driving to a club.

“Sometimes, the best ones come together at the exact same time, and it takes about as long to write it as it does to sing it,” he told the poet Ted Kooser in an interview at the Library of Congress in 2005. “They come along like a dream or something, and you just got to hurry up and respond to it, because if you mess around, the song is liable to pass you by.”

Featured Image by Chad Batka of the New York Times

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April, 2020|Oral Cancer News|

Blood Test Spot On for HPV Cancer Recurrence

Source: MedPage Today
Date: April 1st, 2020
Author: Charles Bankhead

 

A blood test for tumor-associated human papillomavirus (HPV)-DNA had near-perfect accuracy for identifying oropharyngeal cancer patients at high risk of recurrence after treatment, a prospective study showed.

Overall, 28 patients tested positive for circulating tumor (ct) HPV-DNA, including 16 patients who had two consecutive positive tests. All but one of the 16 patients subsequently had biopsy-proven disease recurrence. No patient who had only negative tests developed recurrent disease.

The findings have clear and immediate implications for clinical practice, including earlier initiation of salvage therapy for patients with recurrent disease, reported Bhisham S. Chera, MD, of the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and colleagues in the Journal of Clinical Oncology.

“With regard to how this is applicable to clinical practice, I think it improves the effectiveness, it improves the efficiency, and it reduces the cost and financial toxicity to patients,” Chera told MedPage Today. “This blood test’s performance is really good: Negative predictive value (NPV) 100%, two consecutive positive tests, 94% positive predictive value (PPV). This performs better than any physical examination, PET/CT, or fiberoptic re-examination in identifying cancer recurrence. Right now, I think this is the best surveillance tool we have.”

The findings extended those of a previous report, which showed that a persistently negative ctHPV-DNA test ruled out disease recurrence.

HPV infection accounts for a majority of new cases of oropharyngeal cancer in the U.S. After years of rapid increases in prevalence and incidence, oropharyngeal squamous cell carcinoma (OPSCC) has become the most common HPV-associated cancer, surpassing HPV-associated cervical cancer.

In general, HPV-positive OPSCC has a favorable prognosis as compared with HPV-negative disease, which has supported efforts to de-intensify treatment regimens to reduce exposure to potentially toxic therapies. Nonetheless, as many as a fourth of patiens will develop recurrences, the authors noted.

Most recurrences occur within the first 2 years after treatment, but some patients remain at risk of recurrence for as long as 5 years, or even longer in rare cases. Salvage therapy for recurrent HPV-positive OPSCC leads to better outcomes as compared with salvage therapy for recurrent HPV-negative disease.

PET/CT imaging 3 months after definitive treatment is standard for response assessment in many cases, the authors continued. National Comprehensive Cancer Network guidelines recommend surveillance visits at increasing time intervals through 5 years. During the visits, patients often undergo fiberoptic nasopharyngolaryngoscopy, although a recent report showed that routine surveillance rarely identifies recurrent disease.

A blood-based surveillance test based on detection of ctHPV-DNA offers potential for early detection of recurrent disease and has precedents in bladder, breast, and colorectal cancer. Chera and colleagues prospectively evaluated a ctHPV-DNA liquid biopsy in 115 patients who had completed definitive chemoradiotherapy for HPV-positive OPSCC. Each patient had PET/CT imaging 3 months after finishing treatment. Investigators tested patients for ctHPV-DNA at 6- to 9-month intervals.

During a median follow-up of 23 months, 28 patients tested positive for ctHPV-DNA, including 16 patients who had two consecutive positive tests. Also during follow-up, 15 patients developed biopsy-proven recurrence of OPSCC; all 15 had two consecutive positive tests for ctHPV-DNA. The median time from ctHPV-DNA positivity to recurrence was 3.9 months.

Consecutive positive tests had a PPV of 94%. The previous report from the study showed that a negative test had a NPV of 100%.

“The way I see this working in the clinic is that if you have a negative test, we don’t do a fiberoptic exam, we don’t order any imaging,” said Chera. “If you have a patient whose surveillance test is positive, we would bring the patient back 2 or 3 months later and repeat the blood test. If it’s positive again, then we would do an in-depth physical examination; we would do a fiberoptic exam and order a total-body PET/CT scan. This test can help us better identify which patients we can omit imaging in and those patients we can do imaging in.”

The test very well could have value in the management of patients with other types of HPV-related cancers, he said. Investigators have already examined the rate of ctHPV-DNA clearance as a biomarker for response to treatment and a possible decision-making tool for treatment de-escalation.

The testing technology has been licensed to Naveris for commercial development, and multiple medical centers have already partnered with the company to conduct studies across a variety of HPV-related diseases, said Chera.

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April, 2020|Oral Cancer News|

Guidelines developed for head and neck care during COVID-19

Source: www.physiciansweekly.com
Author: posted by Physicians Weekly

In a special article published online March 31 in JAMA Otolaryngology-Head & Neck Surgery, guidelines are presented for head and neck physical examination and associated procedures during the coronavirus disease 2019 (COVID-19) pandemic.

Since head and neck examinations are considered high risk in patients with suspected or confirmed COVID-19, Babak Givi, M.D., from NYU Langone Health in New York City, and colleagues developed recommendations for health care workers based on review of the literature and communication with physicians with firsthand knowledge of safety procedures during the COVID-19 pandemic.

The authors note that nonurgent appointments should be postponed to limit infection of patients or health care workers. This may include postponing appointments for patients with benign disease and for those undergoing routine surveillance after treatment for head and neck cancer. Patients should be queried by telephone about new or concerning signs or symptoms that may indicate recurrence and/or pending issues, as well as symptoms suggestive of COVID-19. In-person clinic visits should be offered to those at risk for significant negative outcomes without evaluation. To maintain relationships with patients and support assessments that can be made without in-person examinations, the use of telephone, video, or telemedicine visits should be considered. In-person examinations should be limited to patients who need a thorough head and neck examination. Detailed guidelines are provided for physical examinations and associated procedures.

“By following carefully planned routines and procedures, we will be able to provide excellent care and help protect the safety and health of our colleagues,” the authors write.

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April, 2020|Oral Cancer News|

New blood test can detect wide range of cancers, now available to at risk individuals in clinical study at Dana-Farber

Source: www.dana-farber.org
Author: news release

In a study involving thousands of participants, a new blood test detected more than 50 types of cancer as well as their location within the body with a high degree of accuracy, according to an international team of researchers led by Dana-Farber Cancer Institute and the Mayo Clinic.

The results, published online today by the Annals of Oncology, indicate that the test – which identified some particularly dangerous cancers that lack standard approaches to screening – can play a key role in early detection of cancer. Early detection can often be critical to successful treatment.

Developed by GRAIL, Inc., of Menlo Park, Calif., the test uses next-generation sequencing to analyze the arrangement of chemical units called methyl groups on the DNA of cancer cells. Adhering to specific sections of DNA, methyl groups help control whether genes are active or inactive. In cancer cells, the placement of methyl groups, or methylation pattern, is often markedly different from that of normal cells – to the extent that abnormal methylation patterns are even more characteristic of cancer cells than genetic mutations are. When tumor cells die, their DNA, with methyl groups firmly attached, empties into the blood, where it can be analyzed by the new test.

“Our previous work indicated that methylation-based tests outperform traditional DNA-sequencing approaches to detecting multiple forms of cancer in blood samples,” said Dana-Farber’s Geoffrey Oxnard, MD, co-lead author of the study with Minetta Liu, MD, of the Mayo Clinic. “The results of this study suggest that such assays could be a feasible way of screening people for a wide variety of cancers.”

In the study, investigators used the test to analyze cell-free DNA (DNA from normal and cancerous cells that had entered the bloodstream upon the cells’ death) in 6,689 blood samples, including 2,482 from people diagnosed with cancer and 4,207 from people without cancer. The samples from patients with cancer represented more than 50 cancer types, including breast, colorectal, esophageal, gallbladder, bladder, gastric, ovarian, head and neck, lung, lymphoid leukemia, multiple myeloma, and pancreatic cancer.

The overall specificity of the test was 99.3%, meaning that only 0.7% of the results incorrectly indicated that cancer was present. The sensitivity of the assay for 12 cancers that account for nearly two-thirds of U.S. cancer deaths was 67.3%, meaning the test could find the cancer two-thirds of the time but a third of the time the test returned a negative result. Within this group, the sensitivity was 39% for patients with stage I cancer, 69% for those with stage II, 83% for those with stage III, and 92% for those with stage IV. The stage I-III sensitivity across all 50 cancer types was 43.9%. When cancer was detected, the test correctly identified the organ or tissue where the cancer originated in more than 90% of cases – critical information for determining how the disease is diagnosed and managed.

“Our results show that this approach to testing cell-free DNA in blood can detect a broad range of cancer types at virtually any stage of the disease, with specificity and sensitivity approaching the level needed for population-level screening,” Oxnard observed. “The test can be an important part of clinical trials for early cancer detection.”

The study was funded by GRAIL, Inc. As part of further validation research, Dana-Farber has joined a multi-center clinical trial of the test. The PATHFINDER study intends to enroll about 6,200 participants across the U.S. Participants in the study will have the results of the test communicated to them.

Dana-Farber researchers are aiming to enroll hundreds of individuals, mainly cancer survivors and other people who are at elevated cancer risk. Enrollment is limited to individuals who receive care through the Partners HealthCare system.

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April, 2020|Oral Cancer News|

Insurance coverage key to timely care in head and neck cancer cases

Source: www.eurekalert.org
Author: Medical University of South Carolina

A study published in the JAMA Otolaryngology-Head & Neck Surgery examines the effect of Medicaid expansion on head and neck cancer patients, finding that the expansions under the Affordable Care Act (ACA) were associated with improved access to care for these patients and selective Medicaid expansion may worsen existing regional disparities in terms of access to care and outcomes.

Medicaid expansion refers to a provision in the ACA that called for expansion of Medicaid eligibility to cover more low-income Americans. It was determined that each state would decide whether to participate in the expansion – accept federal funds – or not. As of 2020, 37 states including the District of Columbia accepted Medicaid expansion. South Carolina is one of 14 states that has not. As a result, there are gaps in coverage for adults who have incomes above Medicaid eligibility limits yet still below the poverty level, exacerbating challenges with access to care, which is vital in the early detection of cancer.

“We performed the study because delivering timely head and neck cancer care is critical for optimal outcomes,” said Evan Graboyes, M.D., a researcher at Hollings Cancer Center at the Medical University of South Carolina and senior author on the study. The surgeon at MUSC Health specializes in the treatment of head and neck cancers.

The team analyzed data from a national sample of nearly 91,000 adults with newly diagnosed head and neck cancer who were identified from the National Cancer Database. In this observational study, researchers examined the effect that Medicaid expansion, as part of the ACA, had on the patients’ stages of cancer at the time of diagnosis as well as treatment delays for these patients.

Medicaid expansions are known to increase the percentage of patients getting treatment who have localized (stages I or II) cancer at diagnosis for cancers such as colon and breast cancer that have screening tests. Graboyes said the researchers wanted to know the effect of Medicaid expansions on head and neck cancer, which lacks a screening test, he said.

The study showed in states that expanded Medicaid as part of the ACA, patients with head and neck cancer were more likely to be diagnosed with localized (stages I to II) cancer and initiate treatment in a timelier fashion than patients in nonexpansion states. Because of the strong association with a particular stage at diagnosis and the timely treatment that leads to survival for head and neck cancer, the study suggests that Medicaid expansion that offers insurance coverage may help to improve outcomes for these patients.

“I hope that the data we produce gets referenced and is used by policy makers in the future,” Graboyes said.

Helmneh Sineshaw, M.D., lead author on the study and a principal scientist at the American Cancer Society, said the study found that Medicaid expansion provided a huge benefit to those who didn’t have access to insurance, leading to earlier diagnosis and timely treatment.

“What we find is that patients, in states that expanded Medicaid, had a greater chance of being diagnosed early, whereas patients living in nonexpansion states were likely to be diagnosed in a more advanced stage,” Sineshaw said.

Graboyes said delays in the delivery of head and neck cancers are a key driver of suboptimal survival for patients with head and neck cancers and contribute to racial disparities in mortality. Head and neck cancers are rising in number and carry a high mortality rate, with black patients even more likely to die from it.

This study adds to a growing portfolio of other health disparity studies by Graboyes and colleagues, including:

A 5-year $1.2 million grant from the National Cancer Institute awarded in 2019 to decrease mortality and racial disparities in survival for head and neck cancer patients by developing innovative interventions to improve the timeliness, equity and quality of care delivery.

A 2018 study in JAMA Otolaryngology-Head & Neck Surgery that found that ensuring head and neck cancer patients receive postoperative radiotherapy within six weeks of their surgical procedure maximizes their chances of a cure.

Graboyes said more research is needed to understand more fully how changes in insurance coverage affects patients with head and neck cancer. Although there is a strong relationship between the patient’s stage at diagnosis and timely treatment, the current study does not address whether Medicaid expansion is associated with fewer recurrences or better survival since there has not been enough time since the implementation of Medicaid expansion to answer this question.

Another limitation of the current study is that it did not analyze how Medicaid expansion was associated with changes in the cost of treatment for head and neck cancer patients. More research is needed to understand the relative costs of expansion of Medicaid provisions as compared to the assumed cost savings of catching and treating head and neck cancers in a more localized stage (I to II) versus advanced stages (III to IV), he said.

“The study is an important first step in understanding how insurance coverage affects health care delivery for patients with head and neck cancer, particularly those who, due to lack of insurance coverage, are more likely to present with advanced disease and experience treatment delays.”

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April, 2020|Oral Cancer News|