For the May podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights original reports on the prognostic significance of HPV status in postoperative squamous cell carcinoma of the head and neck, the contributions of caregivers in American Indian cancer patients, and the omission of dexamethasone from antiemetics treatment in breast cancer patients with hepatitis B infection or diabetes. He also describes how providers at a comprehensive cancer center devised a framework for implementing survivorship care planning, and, in keeping with the ‘how we do it’ theme, he discusses an article by 2 practicing on oncologists on managing and treating multiple myeloma. The line-up is rounded off with articles on the effects of exercise interventions during different treatments in patients with breast cancer, the approval of trabectedin for some forms of advanced soft tissue sarcoma, and a Case Report on a rare case of hypoglycemia induced by a classical gastro-intestinal stromal tumor.

Listen to the podcast below.

For the May podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights original reports on the prognostic significance of HPV status in postoperative squamous cell carcinoma of the head and neck, the contributions of caregivers in American Indian cancer patients, and the omission of dexamethasone from antiemetics treatment in breast cancer patients with hepatitis B infection or diabetes. He also describes how providers at a comprehensive cancer center devised a framework for implementing survivorship care planning, and, in keeping with the ‘how we do it’ theme, he discusses an article by 2 practicing on oncologists on managing and treating multiple myeloma. The line-up is rounded off with articles on the effects of exercise interventions during different treatments in patients with breast cancer, the approval of trabectedin for some forms of advanced soft tissue sarcoma, and a Case Report on a rare case of hypoglycemia induced by a classical gastro-intestinal stromal tumor.

Listen to the podcast below.

For the May podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights original reports on the prognostic significance of HPV status in postoperative squamous cell carcinoma of the head and neck, the contributions of caregivers in American Indian cancer patients, and the omission of dexamethasone from antiemetics treatment in breast cancer patients with hepatitis B infection or diabetes. He also describes how providers at a comprehensive cancer center devised a framework for implementing survivorship care planning, and, in keeping with the ‘how we do it’ theme, he discusses an article by 2 practicing on oncologists on managing and treating multiple myeloma. The line-up is rounded off with articles on the effects of exercise interventions during different treatments in patients with breast cancer, the approval of trabectedin for some forms of advanced soft tissue sarcoma, and a Case Report on a rare case of hypoglycemia induced by a classical gastro-intestinal stromal tumor.

Listen to the podcast below.

Stella Fitzgibbons, MD, FHM, was an engineer for several years after college. But there wasn’t enough working with people for her taste. So she moved into internal medicine. But then there was, how to put this, something lacking in office work.

“I realized how bored I was with office practice and how much more interesting were the problems at the hospital than outpatient ones,” Dr. Fitzgibbons says.

So she went to work in hospitals. She hasn’t left.

Dr. Fitzgibbons is a hospitalist and ED practitioner with Mint Physician Staffing, primarily in the Apollo Hospital System in The Woodlands, Texas. And the best part of the job for Dr. Fitzgibbons, one of eight new members of Team Hospitalist, the volunteer editorial advisory board of The Hospitalist newsmagazine, is easy to pick.

“Seeing sick people get better,” she says.

Question: Switching careers from engineering to medicine is a big step. What motivated that?

Answer: I wanted to see my efforts helping people I could actually see, and I thought—and still do—that medicine uses my talents better and is far more interesting.

Q: You say office practice became a bit boring. How so? What appealed about the inpatient setting?

A: An internist in the office only sees a tiny fraction of the interesting problems that our field covers. Rheumatoid arthritis is diagnosed by a rheumatologist, who then makes all the decisions. Abdominal pain gets sent to the hospital, where all the diagnostic tests are done.

Fortunately, my multispecialty group arranged for about a quarter of its internists [the youngest quarter in most cases] to manage hospital patients; I figured out pretty quickly that it was only there that I got to see pulmonary hypertension, congestive heart failure, and acute abdomens. Even night call was better at the hospital since office doctors only answered phone calls and never had a chance to do any real evaluation and treatment no matter how sick the caller was.

And a problem at the office was something that made me run behind that odious and impractical appointment schedule; at the hospital I was seeing real illnesses, not people who wanted a prescription med for their sore throat so they wouldn’t be bothered with it on their vacation.

Q: What is your biggest professional challenge?

A: EHRs.

Q: What is your biggest professional reward?

A: When a patient says, “Thanks for taking care of me, doctor.”

Q: What does teaching mean to you, and how has it been gratifying in your career?

A: Teaching means paying it forward, in gratitude to those who taught me, with the reward of seeing light bulbs go off behind the eyes of students and younger doctors who are eager to learn.

Q: When you aren’t working, what is important to you?

A: Family and music and church.

Q: Faith is obviously important to you. How does that help your work as a care provider?

A: I don’t think anybody goes around being religious all the time. But it sometimes makes all the difference knowing that a higher power is looking out for me and the patients.

Q: You’ve described mentoring as fun for you. What exactly do you mean by fun?

A: Mentoring is what we do. Patients, nurses—anybody we work with—need explanations and clarifications. About the third day of med school, docs in training realize that anybody who can help us understand and retain the huge stream of information directed at us is performing a necessary service. Throughout the training period, residents teach students, fellows teach residents, and attending faculty teach everybody. Doctors in training are bright people who want to learn both the facts and how to deal with patients’ side of things, and feeding their desires is very enjoyable.

Q: You’d like to see more physicians than MBAs in decision-making positions. Why? What real changes do you think that would effectuate?

A: Physicians and nurses were administrators for decades before insurance company penny-pinching and government regulations led hospitals to hire “bean counters” to replace them. It is a tremendous change for the worse, to have people making decisions for patients whose primary consideration is the bottom line.

Q: What’s next professionally?

A: Small-volume ERs, where I don’t have to do discharge planning while being harassed by insurance company reps.

Q: Where do you see yourself in 10 years?

A: Retired.

Q: If you weren’t a doctor, what would you be doing right now?

A: Law enforcement.

Q: Devices like iPhones and tablets can take away from patient face time. But they can also be valuable. How do you balance that? How do you encourage younger docs to do so, particularly when they’re much more used to having smartphones glued to their hands?

A: I use my iPhone when I’m with patients … but only when they can see the reason I need it to help them, such as looking up the side effects of a medication. Electronic health records can work on an iPad, but I hesitate to use them unless the patient knows just what I am doing, such as looking up results of a lab test that concerns them. Taking a computer on wheels into a patient’s room means that I spend part of the visit looking at a screen instead of at the patient, and I prefer to avoid it if at all possible.

Q: What’s the best book you’ve read recently? Why?

A: The House of Silk by Anthony Horowitz. Great continuation of the Holmes stories, with a seamless link to [Sir Arthur] Conan Doyle’s style.

Q: How many Apple products (phones, iPods, tablets, iTunes, etc.) do you interface with in a given week?

A: Three.

Q: What’s your favorite social network? Do you use it all for work or professional development?

A: Facebook. Heck no, it’s just fun.

Q: What’s next in your Netflix queue?

A: Last two episodes of Game of Thrones season 5.

Richard Quinn is a freelance writer in New Jersey.

Stella Fitzgibbons, MD, FHM, was an engineer for several years after college. But there wasn’t enough working with people for her taste. So she moved into internal medicine. But then there was, how to put this, something lacking in office work.

“I realized how bored I was with office practice and how much more interesting were the problems at the hospital than outpatient ones,” Dr. Fitzgibbons says.

So she went to work in hospitals. She hasn’t left.

Dr. Fitzgibbons is a hospitalist and ED practitioner with Mint Physician Staffing, primarily in the Apollo Hospital System in The Woodlands, Texas. And the best part of the job for Dr. Fitzgibbons, one of eight new members of Team Hospitalist, the volunteer editorial advisory board of The Hospitalist newsmagazine, is easy to pick.

“Seeing sick people get better,” she says.

Question: Switching careers from engineering to medicine is a big step. What motivated that?

Answer: I wanted to see my efforts helping people I could actually see, and I thought—and still do—that medicine uses my talents better and is far more interesting.

Q: You say office practice became a bit boring. How so? What appealed about the inpatient setting?

A: An internist in the office only sees a tiny fraction of the interesting problems that our field covers. Rheumatoid arthritis is diagnosed by a rheumatologist, who then makes all the decisions. Abdominal pain gets sent to the hospital, where all the diagnostic tests are done.

Fortunately, my multispecialty group arranged for about a quarter of its internists [the youngest quarter in most cases] to manage hospital patients; I figured out pretty quickly that it was only there that I got to see pulmonary hypertension, congestive heart failure, and acute abdomens. Even night call was better at the hospital since office doctors only answered phone calls and never had a chance to do any real evaluation and treatment no matter how sick the caller was.

And a problem at the office was something that made me run behind that odious and impractical appointment schedule; at the hospital I was seeing real illnesses, not people who wanted a prescription med for their sore throat so they wouldn’t be bothered with it on their vacation.

Q: What is your biggest professional challenge?

A: EHRs.

Q: What is your biggest professional reward?

A: When a patient says, “Thanks for taking care of me, doctor.”

Q: What does teaching mean to you, and how has it been gratifying in your career?

A: Teaching means paying it forward, in gratitude to those who taught me, with the reward of seeing light bulbs go off behind the eyes of students and younger doctors who are eager to learn.

Q: When you aren’t working, what is important to you?

A: Family and music and church.

Q: Faith is obviously important to you. How does that help your work as a care provider?

A: I don’t think anybody goes around being religious all the time. But it sometimes makes all the difference knowing that a higher power is looking out for me and the patients.

Q: You’ve described mentoring as fun for you. What exactly do you mean by fun?

A: Mentoring is what we do. Patients, nurses—anybody we work with—need explanations and clarifications. About the third day of med school, docs in training realize that anybody who can help us understand and retain the huge stream of information directed at us is performing a necessary service. Throughout the training period, residents teach students, fellows teach residents, and attending faculty teach everybody. Doctors in training are bright people who want to learn both the facts and how to deal with patients’ side of things, and feeding their desires is very enjoyable.

Q: You’d like to see more physicians than MBAs in decision-making positions. Why? What real changes do you think that would effectuate?

A: Physicians and nurses were administrators for decades before insurance company penny-pinching and government regulations led hospitals to hire “bean counters” to replace them. It is a tremendous change for the worse, to have people making decisions for patients whose primary consideration is the bottom line.

Q: What’s next professionally?

A: Small-volume ERs, where I don’t have to do discharge planning while being harassed by insurance company reps.

Q: Where do you see yourself in 10 years?

A: Retired.

Q: If you weren’t a doctor, what would you be doing right now?

A: Law enforcement.

Q: Devices like iPhones and tablets can take away from patient face time. But they can also be valuable. How do you balance that? How do you encourage younger docs to do so, particularly when they’re much more used to having smartphones glued to their hands?

A: I use my iPhone when I’m with patients … but only when they can see the reason I need it to help them, such as looking up the side effects of a medication. Electronic health records can work on an iPad, but I hesitate to use them unless the patient knows just what I am doing, such as looking up results of a lab test that concerns them. Taking a computer on wheels into a patient’s room means that I spend part of the visit looking at a screen instead of at the patient, and I prefer to avoid it if at all possible.

Q: What’s the best book you’ve read recently? Why?

A: The House of Silk by Anthony Horowitz. Great continuation of the Holmes stories, with a seamless link to [Sir Arthur] Conan Doyle’s style.

Q: How many Apple products (phones, iPods, tablets, iTunes, etc.) do you interface with in a given week?

A: Three.

Q: What’s your favorite social network? Do you use it all for work or professional development?

A: Facebook. Heck no, it’s just fun.

Q: What’s next in your Netflix queue?

A: Last two episodes of Game of Thrones season 5.

Richard Quinn is a freelance writer in New Jersey.

Stella Fitzgibbons, MD, FHM, was an engineer for several years after college. But there wasn’t enough working with people for her taste. So she moved into internal medicine. But then there was, how to put this, something lacking in office work.

“I realized how bored I was with office practice and how much more interesting were the problems at the hospital than outpatient ones,” Dr. Fitzgibbons says.

So she went to work in hospitals. She hasn’t left.

Dr. Fitzgibbons is a hospitalist and ED practitioner with Mint Physician Staffing, primarily in the Apollo Hospital System in The Woodlands, Texas. And the best part of the job for Dr. Fitzgibbons, one of eight new members of Team Hospitalist, the volunteer editorial advisory board of The Hospitalist newsmagazine, is easy to pick.

“Seeing sick people get better,” she says.

Question: Switching careers from engineering to medicine is a big step. What motivated that?

Answer: I wanted to see my efforts helping people I could actually see, and I thought—and still do—that medicine uses my talents better and is far more interesting.

Q: You say office practice became a bit boring. How so? What appealed about the inpatient setting?

A: An internist in the office only sees a tiny fraction of the interesting problems that our field covers. Rheumatoid arthritis is diagnosed by a rheumatologist, who then makes all the decisions. Abdominal pain gets sent to the hospital, where all the diagnostic tests are done.

Fortunately, my multispecialty group arranged for about a quarter of its internists [the youngest quarter in most cases] to manage hospital patients; I figured out pretty quickly that it was only there that I got to see pulmonary hypertension, congestive heart failure, and acute abdomens. Even night call was better at the hospital since office doctors only answered phone calls and never had a chance to do any real evaluation and treatment no matter how sick the caller was.

And a problem at the office was something that made me run behind that odious and impractical appointment schedule; at the hospital I was seeing real illnesses, not people who wanted a prescription med for their sore throat so they wouldn’t be bothered with it on their vacation.

Q: What is your biggest professional challenge?

A: EHRs.

Q: What is your biggest professional reward?

A: When a patient says, “Thanks for taking care of me, doctor.”

Q: What does teaching mean to you, and how has it been gratifying in your career?

A: Teaching means paying it forward, in gratitude to those who taught me, with the reward of seeing light bulbs go off behind the eyes of students and younger doctors who are eager to learn.

Q: When you aren’t working, what is important to you?

A: Family and music and church.

Q: Faith is obviously important to you. How does that help your work as a care provider?

A: I don’t think anybody goes around being religious all the time. But it sometimes makes all the difference knowing that a higher power is looking out for me and the patients.

Q: You’ve described mentoring as fun for you. What exactly do you mean by fun?

A: Mentoring is what we do. Patients, nurses—anybody we work with—need explanations and clarifications. About the third day of med school, docs in training realize that anybody who can help us understand and retain the huge stream of information directed at us is performing a necessary service. Throughout the training period, residents teach students, fellows teach residents, and attending faculty teach everybody. Doctors in training are bright people who want to learn both the facts and how to deal with patients’ side of things, and feeding their desires is very enjoyable.

Q: You’d like to see more physicians than MBAs in decision-making positions. Why? What real changes do you think that would effectuate?

A: Physicians and nurses were administrators for decades before insurance company penny-pinching and government regulations led hospitals to hire “bean counters” to replace them. It is a tremendous change for the worse, to have people making decisions for patients whose primary consideration is the bottom line.

Q: What’s next professionally?

A: Small-volume ERs, where I don’t have to do discharge planning while being harassed by insurance company reps.

Q: Where do you see yourself in 10 years?

A: Retired.

Q: If you weren’t a doctor, what would you be doing right now?

A: Law enforcement.

Q: Devices like iPhones and tablets can take away from patient face time. But they can also be valuable. How do you balance that? How do you encourage younger docs to do so, particularly when they’re much more used to having smartphones glued to their hands?

A: I use my iPhone when I’m with patients … but only when they can see the reason I need it to help them, such as looking up the side effects of a medication. Electronic health records can work on an iPad, but I hesitate to use them unless the patient knows just what I am doing, such as looking up results of a lab test that concerns them. Taking a computer on wheels into a patient’s room means that I spend part of the visit looking at a screen instead of at the patient, and I prefer to avoid it if at all possible.

Q: What’s the best book you’ve read recently? Why?

A: The House of Silk by Anthony Horowitz. Great continuation of the Holmes stories, with a seamless link to [Sir Arthur] Conan Doyle’s style.

Q: How many Apple products (phones, iPods, tablets, iTunes, etc.) do you interface with in a given week?

A: Three.

Q: What’s your favorite social network? Do you use it all for work or professional development?

A: Facebook. Heck no, it’s just fun.

Q: What’s next in your Netflix queue?

A: Last two episodes of Game of Thrones season 5.

Richard Quinn is a freelance writer in New Jersey.

Drugs in vials

Photo by Bill Branson

A report assessing the value of newer multiple myeloma (MM) treatments “dangerously oversimplifies” a complex issue and could limit patients’ access to treatment, according to the International Myeloma Foundation (IMF).

The report, which was drafted by the Institute for Clinical and Economic Review (ICER), is scheduled to be discussed at the inaugural meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) in St. Louis, Missouri, on May 26.

The main conclusion of ICER’s report was that newer second- and third-line treatment regimens for MM appear to confer clinical benefits, but the estimated cost-effectiveness of these regimens exceeds commonly cited thresholds.

For example, ICER said that, based on the available data, there was “moderate certainty” that carfilzomib (CFZ), ixazomib (IX), or elotuzumab (ELO) given in combination with lenalidomide and dexamethasone (LEN+DEX) can provide an incremental or better net health benefit for second-line, third-line, or subsequent therapy in adults with relapsed/refractory MM, relative to LEN+DEX alone.

However, the estimated cost-effectiveness, compared to LEN+DEX, was $200,000 per quality-adjusted life year (QALY) gained for CFZ+LEN+DEX, $428,000 for ELO+LEN+DEX, and $434,000 for IX+LEN+DEX. All of these exceed commonly cited thresholds of $50,000 to $150,000 per QALY.

ICER said achieving levels of value more closely aligned with patient benefit would require substantial discounts from the list price in many cases. In other cases, there is no realistic price for the newest agents that would achieve these thresholds.

IMF’s response

IMF said ICER’s report has a few flaws—namely, the absence of many newer MM drugs and combinations, the use of inaccurate data, and an underestimation of QALYs.

Furthermore, IMF said it is concerned that, if ICER's recommendations were to be adopted by the Centers for Medicare & Medicaid Services, patients might be required to “fail first” before other, possibly more effective drugs would be an option.

“We believe that the IMF’s research body, the International Myeloma Working Group (IMWG), will produce superior patient-centered and research-supported guidelines to effectively impact drug costs at our annual summit in June,” said IMF Chairman Brian Durie.

IMWG plans to focus on healthcare cost containment in a special session at the 2016 IMWG Summit, which is scheduled to take place June 7-9 in Copenhagen, Denmark.

IMF said the guidelines resulting from this session should be available in about 2 months. And they will spell out primary and secondary recommendations that allow for individualized therapy choices based on unique features of the disease, patient and/or physician preference, and local and/or regional access issues.

Drugs in vials

Photo by Bill Branson

A report assessing the value of newer multiple myeloma (MM) treatments “dangerously oversimplifies” a complex issue and could limit patients’ access to treatment, according to the International Myeloma Foundation (IMF).

The report, which was drafted by the Institute for Clinical and Economic Review (ICER), is scheduled to be discussed at the inaugural meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) in St. Louis, Missouri, on May 26.

The main conclusion of ICER’s report was that newer second- and third-line treatment regimens for MM appear to confer clinical benefits, but the estimated cost-effectiveness of these regimens exceeds commonly cited thresholds.

For example, ICER said that, based on the available data, there was “moderate certainty” that carfilzomib (CFZ), ixazomib (IX), or elotuzumab (ELO) given in combination with lenalidomide and dexamethasone (LEN+DEX) can provide an incremental or better net health benefit for second-line, third-line, or subsequent therapy in adults with relapsed/refractory MM, relative to LEN+DEX alone.

However, the estimated cost-effectiveness, compared to LEN+DEX, was $200,000 per quality-adjusted life year (QALY) gained for CFZ+LEN+DEX, $428,000 for ELO+LEN+DEX, and $434,000 for IX+LEN+DEX. All of these exceed commonly cited thresholds of $50,000 to $150,000 per QALY.

ICER said achieving levels of value more closely aligned with patient benefit would require substantial discounts from the list price in many cases. In other cases, there is no realistic price for the newest agents that would achieve these thresholds.

IMF’s response

IMF said ICER’s report has a few flaws—namely, the absence of many newer MM drugs and combinations, the use of inaccurate data, and an underestimation of QALYs.

Furthermore, IMF said it is concerned that, if ICER's recommendations were to be adopted by the Centers for Medicare & Medicaid Services, patients might be required to “fail first” before other, possibly more effective drugs would be an option.

“We believe that the IMF’s research body, the International Myeloma Working Group (IMWG), will produce superior patient-centered and research-supported guidelines to effectively impact drug costs at our annual summit in June,” said IMF Chairman Brian Durie.

IMWG plans to focus on healthcare cost containment in a special session at the 2016 IMWG Summit, which is scheduled to take place June 7-9 in Copenhagen, Denmark.

IMF said the guidelines resulting from this session should be available in about 2 months. And they will spell out primary and secondary recommendations that allow for individualized therapy choices based on unique features of the disease, patient and/or physician preference, and local and/or regional access issues.

Drugs in vials

Photo by Bill Branson

A report assessing the value of newer multiple myeloma (MM) treatments “dangerously oversimplifies” a complex issue and could limit patients’ access to treatment, according to the International Myeloma Foundation (IMF).

The report, which was drafted by the Institute for Clinical and Economic Review (ICER), is scheduled to be discussed at the inaugural meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) in St. Louis, Missouri, on May 26.

The main conclusion of ICER’s report was that newer second- and third-line treatment regimens for MM appear to confer clinical benefits, but the estimated cost-effectiveness of these regimens exceeds commonly cited thresholds.

For example, ICER said that, based on the available data, there was “moderate certainty” that carfilzomib (CFZ), ixazomib (IX), or elotuzumab (ELO) given in combination with lenalidomide and dexamethasone (LEN+DEX) can provide an incremental or better net health benefit for second-line, third-line, or subsequent therapy in adults with relapsed/refractory MM, relative to LEN+DEX alone.

However, the estimated cost-effectiveness, compared to LEN+DEX, was $200,000 per quality-adjusted life year (QALY) gained for CFZ+LEN+DEX, $428,000 for ELO+LEN+DEX, and $434,000 for IX+LEN+DEX. All of these exceed commonly cited thresholds of $50,000 to $150,000 per QALY.

ICER said achieving levels of value more closely aligned with patient benefit would require substantial discounts from the list price in many cases. In other cases, there is no realistic price for the newest agents that would achieve these thresholds.

IMF’s response

IMF said ICER’s report has a few flaws—namely, the absence of many newer MM drugs and combinations, the use of inaccurate data, and an underestimation of QALYs.

Furthermore, IMF said it is concerned that, if ICER's recommendations were to be adopted by the Centers for Medicare & Medicaid Services, patients might be required to “fail first” before other, possibly more effective drugs would be an option.

“We believe that the IMF’s research body, the International Myeloma Working Group (IMWG), will produce superior patient-centered and research-supported guidelines to effectively impact drug costs at our annual summit in June,” said IMF Chairman Brian Durie.

IMWG plans to focus on healthcare cost containment in a special session at the 2016 IMWG Summit, which is scheduled to take place June 7-9 in Copenhagen, Denmark.

IMF said the guidelines resulting from this session should be available in about 2 months. And they will spell out primary and secondary recommendations that allow for individualized therapy choices based on unique features of the disease, patient and/or physician preference, and local and/or regional access issues.

K.C. Nicolaou, PhD

Photo courtesy of Jeff Fitlow

and Rice University

Researchers say they have streamlined synthesis of delta12-prostaglandin J3, a molecule that has been shown to kill leukemia cells.

Total synthesis of the molecule now requires only 6 steps from commercially available starting materials.

The researchers say this work sets the stage for large-scale synthesis of the molecule—a lipid found in nearly all animal tissues—and related compounds that can be produced as potential anticancer agents.

K.C. Nicolaou, PhD, of Rice University in Houston, Texas, and his colleagues described the work in Chemistry - A European Journal.

The prostaglandin the researchers synthesized had been isolated in 2011 as a secondary metabolite formed from eicosapentaenoic acid, which is found primarily in fish oil.

The team reported the first total synthesis of the molecule in 2014. That allowed them to confirm its structure.

Now, the researchers have established techniques to develop related disease-fighting compounds and ramp up bulk production if necessary.

Several such prostaglandin derivatives under consideration as preclinical drug candidates were detailed in a second paper published in the Journal of the American Chemical Society.

That publication described the synthesis of dozens of prostaglandin derivatives that were tested against a range of cancer cells by the National Cancer Institute.

One such derivative, macrolactone 11, is currently under evaluation as a preclinical drug candidate. Related compounds macrolactone 33 and 44 showed evidence of even higher potency against leukemia, lung cancer, colon cancer, melanoma, renal, and prostate cancer.

“The macrolactones are very good—better than the natural product—and now we’re following this lead to optimize the potency while minimizing toxicity,” Dr Nicolaou said. “It’s a balancing act.”

In addition, he and his colleagues are developing other drug candidates based on prostaglandin.

“In the process, we’ve developed a lot of nice chemistry, and we know a lot more about the biology of this compound,” Dr Nicolaou said. “We’ve advanced organic synthesis in general and also enriched the knowledge about how these kinds of molecules behave. We hope the papers provide some ideas and leads and inspiration for others to follow.”

K.C. Nicolaou, PhD

Photo courtesy of Jeff Fitlow

and Rice University

Researchers say they have streamlined synthesis of delta12-prostaglandin J3, a molecule that has been shown to kill leukemia cells.

Total synthesis of the molecule now requires only 6 steps from commercially available starting materials.

The researchers say this work sets the stage for large-scale synthesis of the molecule—a lipid found in nearly all animal tissues—and related compounds that can be produced as potential anticancer agents.

K.C. Nicolaou, PhD, of Rice University in Houston, Texas, and his colleagues described the work in Chemistry - A European Journal.

The prostaglandin the researchers synthesized had been isolated in 2011 as a secondary metabolite formed from eicosapentaenoic acid, which is found primarily in fish oil.

The team reported the first total synthesis of the molecule in 2014. That allowed them to confirm its structure.

Now, the researchers have established techniques to develop related disease-fighting compounds and ramp up bulk production if necessary.

Several such prostaglandin derivatives under consideration as preclinical drug candidates were detailed in a second paper published in the Journal of the American Chemical Society.

That publication described the synthesis of dozens of prostaglandin derivatives that were tested against a range of cancer cells by the National Cancer Institute.

One such derivative, macrolactone 11, is currently under evaluation as a preclinical drug candidate. Related compounds macrolactone 33 and 44 showed evidence of even higher potency against leukemia, lung cancer, colon cancer, melanoma, renal, and prostate cancer.

“The macrolactones are very good—better than the natural product—and now we’re following this lead to optimize the potency while minimizing toxicity,” Dr Nicolaou said. “It’s a balancing act.”

In addition, he and his colleagues are developing other drug candidates based on prostaglandin.

“In the process, we’ve developed a lot of nice chemistry, and we know a lot more about the biology of this compound,” Dr Nicolaou said. “We’ve advanced organic synthesis in general and also enriched the knowledge about how these kinds of molecules behave. We hope the papers provide some ideas and leads and inspiration for others to follow.”

K.C. Nicolaou, PhD

Photo courtesy of Jeff Fitlow

and Rice University

Researchers say they have streamlined synthesis of delta12-prostaglandin J3, a molecule that has been shown to kill leukemia cells.

Total synthesis of the molecule now requires only 6 steps from commercially available starting materials.

The researchers say this work sets the stage for large-scale synthesis of the molecule—a lipid found in nearly all animal tissues—and related compounds that can be produced as potential anticancer agents.

K.C. Nicolaou, PhD, of Rice University in Houston, Texas, and his colleagues described the work in Chemistry - A European Journal.

The prostaglandin the researchers synthesized had been isolated in 2011 as a secondary metabolite formed from eicosapentaenoic acid, which is found primarily in fish oil.

The team reported the first total synthesis of the molecule in 2014. That allowed them to confirm its structure.

Now, the researchers have established techniques to develop related disease-fighting compounds and ramp up bulk production if necessary.

Several such prostaglandin derivatives under consideration as preclinical drug candidates were detailed in a second paper published in the Journal of the American Chemical Society.

That publication described the synthesis of dozens of prostaglandin derivatives that were tested against a range of cancer cells by the National Cancer Institute.

One such derivative, macrolactone 11, is currently under evaluation as a preclinical drug candidate. Related compounds macrolactone 33 and 44 showed evidence of even higher potency against leukemia, lung cancer, colon cancer, melanoma, renal, and prostate cancer.

“The macrolactones are very good—better than the natural product—and now we’re following this lead to optimize the potency while minimizing toxicity,” Dr Nicolaou said. “It’s a balancing act.”

In addition, he and his colleagues are developing other drug candidates based on prostaglandin.

“In the process, we’ve developed a lot of nice chemistry, and we know a lot more about the biology of this compound,” Dr Nicolaou said. “We’ve advanced organic synthesis in general and also enriched the knowledge about how these kinds of molecules behave. We hope the papers provide some ideas and leads and inspiration for others to follow.”

Plasmodium sporozoite

Image courtesy of Ute Frevert

and Margaret Shear

A study published in PLOS Pathogens has revealed proteins that may be viable targets for malaria vaccines.

Investigators identified 42 proteins that can be found on the surface of Plasmodium falciparum sporozoites and could be targeted by vaccines.

However, the team also found evidence to suggest that 2 other surface proteins should not be targeted, as they may be able to evade the immune system.

“We used a method that we developed in a previous paper to identify which proteins of the malaria parasite, Plasmodium falciparum, might be visible to the human immune system on the outside of the parasite and therefore are good potential targets for the development of new malaria vaccines,” said study author Scott E. Lindner, PhD, of Pennsylvania State University in University Park.

“Current experimental malaria vaccines target single proteins and do not provide the level of protection necessary to prevent the spread of the disease. Our new list of potential vaccine targets will allow the development of more effective vaccines that target several proteins on the surface of the parasite.”

To identify these targets, Dr Lindner and his colleagues collected malaria sporozoites from the salivary glands of thousands of infected mosquitoes.

The investigators then marked proteins on the surface of the sporozoites with a chemical label that could not cross through the outer membrane of the parasite. The team identified and characterized the labeled proteins using mass spectrometry.

“We focused on the transmission stage of the parasite because, at this point in an infection, the number of parasites is low, and if we can design effective vaccines for this stage, we can stop the progress of the disease before it causes symptoms,” Dr Lindner said. “Once the parasites are in the liver, they can hide from our immune system by residing inside of liver cells.”

Based on multiple replications of their experiments, the investigators identified 42 proteins that are highly likely to be exposed on the surface of the parasite and are therefore potential targets for vaccines.

The team noted that many of the proteins they identified had been thought to be located exclusively on the inside of the parasite. They suggest that these proteins may become exposed as the parasite moves from the site of a mosquito bite toward the liver.

“Malaria is still one of the great global health issues today, with hundreds of millions of new infections and half a million deaths each year, most of which occur in children under the age of 5,” Dr Lindner said.

“The parasite quickly and efficiently develops resistance to the drugs that we use to treat the disease, so what’s really needed to make eradication of malaria possible is a better vaccine. Our research provides an experimentally validated list of protein targets that could be used to develop new, more effective malaria vaccines.”

The investigators also discovered that 2 surface proteins—CSP and TRAP—are glycosylated in sporozoites, which changes the way the proteins are recognized by the immune system.

The team believes this discovery will affect the way future vaccines are designed as well.

“Our goal was to identify proteins that are present on the surface of sporozoites in hopes of finding targets for new vaccines,” said study author Kristian E. Swearingen, PhD, of the Institute for Systems Biology in Seattle, Washington.

“In addition to the potential new targets we’ve found, we’re also excited about the discovery that 2 of the major sporozoite surface proteins are glycosylated. The presence of sugars on these proteins almost certainly affects the way they are recognized by antibodies, something that will need to be factored in for future vaccine efforts based on these proteins.”

Plasmodium sporozoite

Image courtesy of Ute Frevert

and Margaret Shear

A study published in PLOS Pathogens has revealed proteins that may be viable targets for malaria vaccines.

Investigators identified 42 proteins that can be found on the surface of Plasmodium falciparum sporozoites and could be targeted by vaccines.

However, the team also found evidence to suggest that 2 other surface proteins should not be targeted, as they may be able to evade the immune system.

“We used a method that we developed in a previous paper to identify which proteins of the malaria parasite, Plasmodium falciparum, might be visible to the human immune system on the outside of the parasite and therefore are good potential targets for the development of new malaria vaccines,” said study author Scott E. Lindner, PhD, of Pennsylvania State University in University Park.

“Current experimental malaria vaccines target single proteins and do not provide the level of protection necessary to prevent the spread of the disease. Our new list of potential vaccine targets will allow the development of more effective vaccines that target several proteins on the surface of the parasite.”

To identify these targets, Dr Lindner and his colleagues collected malaria sporozoites from the salivary glands of thousands of infected mosquitoes.

The investigators then marked proteins on the surface of the sporozoites with a chemical label that could not cross through the outer membrane of the parasite. The team identified and characterized the labeled proteins using mass spectrometry.

“We focused on the transmission stage of the parasite because, at this point in an infection, the number of parasites is low, and if we can design effective vaccines for this stage, we can stop the progress of the disease before it causes symptoms,” Dr Lindner said. “Once the parasites are in the liver, they can hide from our immune system by residing inside of liver cells.”

Based on multiple replications of their experiments, the investigators identified 42 proteins that are highly likely to be exposed on the surface of the parasite and are therefore potential targets for vaccines.

The team noted that many of the proteins they identified had been thought to be located exclusively on the inside of the parasite. They suggest that these proteins may become exposed as the parasite moves from the site of a mosquito bite toward the liver.

“Malaria is still one of the great global health issues today, with hundreds of millions of new infections and half a million deaths each year, most of which occur in children under the age of 5,” Dr Lindner said.

“The parasite quickly and efficiently develops resistance to the drugs that we use to treat the disease, so what’s really needed to make eradication of malaria possible is a better vaccine. Our research provides an experimentally validated list of protein targets that could be used to develop new, more effective malaria vaccines.”

The investigators also discovered that 2 surface proteins—CSP and TRAP—are glycosylated in sporozoites, which changes the way the proteins are recognized by the immune system.

The team believes this discovery will affect the way future vaccines are designed as well.

“Our goal was to identify proteins that are present on the surface of sporozoites in hopes of finding targets for new vaccines,” said study author Kristian E. Swearingen, PhD, of the Institute for Systems Biology in Seattle, Washington.

“In addition to the potential new targets we’ve found, we’re also excited about the discovery that 2 of the major sporozoite surface proteins are glycosylated. The presence of sugars on these proteins almost certainly affects the way they are recognized by antibodies, something that will need to be factored in for future vaccine efforts based on these proteins.”

Plasmodium sporozoite

Image courtesy of Ute Frevert

and Margaret Shear

A study published in PLOS Pathogens has revealed proteins that may be viable targets for malaria vaccines.

Investigators identified 42 proteins that can be found on the surface of Plasmodium falciparum sporozoites and could be targeted by vaccines.

However, the team also found evidence to suggest that 2 other surface proteins should not be targeted, as they may be able to evade the immune system.

“We used a method that we developed in a previous paper to identify which proteins of the malaria parasite, Plasmodium falciparum, might be visible to the human immune system on the outside of the parasite and therefore are good potential targets for the development of new malaria vaccines,” said study author Scott E. Lindner, PhD, of Pennsylvania State University in University Park.

“Current experimental malaria vaccines target single proteins and do not provide the level of protection necessary to prevent the spread of the disease. Our new list of potential vaccine targets will allow the development of more effective vaccines that target several proteins on the surface of the parasite.”

To identify these targets, Dr Lindner and his colleagues collected malaria sporozoites from the salivary glands of thousands of infected mosquitoes.

The investigators then marked proteins on the surface of the sporozoites with a chemical label that could not cross through the outer membrane of the parasite. The team identified and characterized the labeled proteins using mass spectrometry.

“We focused on the transmission stage of the parasite because, at this point in an infection, the number of parasites is low, and if we can design effective vaccines for this stage, we can stop the progress of the disease before it causes symptoms,” Dr Lindner said. “Once the parasites are in the liver, they can hide from our immune system by residing inside of liver cells.”

Based on multiple replications of their experiments, the investigators identified 42 proteins that are highly likely to be exposed on the surface of the parasite and are therefore potential targets for vaccines.

The team noted that many of the proteins they identified had been thought to be located exclusively on the inside of the parasite. They suggest that these proteins may become exposed as the parasite moves from the site of a mosquito bite toward the liver.

“Malaria is still one of the great global health issues today, with hundreds of millions of new infections and half a million deaths each year, most of which occur in children under the age of 5,” Dr Lindner said.

“The parasite quickly and efficiently develops resistance to the drugs that we use to treat the disease, so what’s really needed to make eradication of malaria possible is a better vaccine. Our research provides an experimentally validated list of protein targets that could be used to develop new, more effective malaria vaccines.”

The investigators also discovered that 2 surface proteins—CSP and TRAP—are glycosylated in sporozoites, which changes the way the proteins are recognized by the immune system.

The team believes this discovery will affect the way future vaccines are designed as well.

“Our goal was to identify proteins that are present on the surface of sporozoites in hopes of finding targets for new vaccines,” said study author Kristian E. Swearingen, PhD, of the Institute for Systems Biology in Seattle, Washington.

“In addition to the potential new targets we’ve found, we’re also excited about the discovery that 2 of the major sporozoite surface proteins are glycosylated. The presence of sugars on these proteins almost certainly affects the way they are recognized by antibodies, something that will need to be factored in for future vaccine efforts based on these proteins.”

Aspirin tablets

Photo by Sage Ross

Results of a retrospective study suggest that patients with low-risk essential thrombocythemia (ET) may benefit from a genotype-based approach to

antiplatelet therapy.

The study showed that, overall, neither CALR-mutated nor JAK2V617F-positive patients derived a significant benefit from treatment with low-dose aspirin.

JAK2V617F-positive patients had a somewhat lower risk of thrombosis while on the therapy than during observation.

But CALR-mutated patients had a significantly increased risk of major bleeding and no decrease in the risk of thrombosis while on antiplatelet therapy.

Carlos Besses, MD, PhD, of Hospital del Mar in Barcelona, Spain, and his colleagues reported these results in haematologica.

The researchers evaluated 433 patients with low-risk ET—271 with CALR mutations and 162 with JAK2V617F. In all, 353 patients received low-dose aspirin (81-100 mg/day), but the treatment was withdrawn in 50 patients (permanently in 46 of them).

Two hundred and thirty-one patients received cytoreductive therapy, including hydroxyurea (n=143), anagrelide (n=66), interferon (n=18), and busulfan (n=4).

The projected time from diagnosis to the start of cytoreductive therapy was significantly shorter in patients with CALR-mutated ET than in JAK2V617F-positive patients—a median of 5.0 years and 9.8 years, respectively (P=0.002). The most common reason for cytoreduction in CALR-mutated patients was extreme thrombocytosis.

Thrombosis

After 2215 person-years of follow-up free from cytoreduction, there were 25 arterial or venous thrombotic events.

Fourteen thrombotic events occurred while patients were receiving low-dose aspirin, and 11 occurred while patients were under observation only. The incidence rates were 10.7 and 12.1 events x 1000 person-years, respectively (P=0.7).

Among CALR-mutated patients, there were more thrombotic events during antiplatelet therapy than during observation—9.7 and 6.9 events x 1000 person-years, respectively (P=0.6).

Among JAK2V617F-positive patients, there were fewer thrombotic events during antiplatelet therapy than during observation, but the difference was not significant—11.6 and 21.1 events x 1000 person-years, respectively (P=0.3).

Coexistence of the JAK2V617F mutation and cardiovascular risk factors increased the risk of thrombosis, even after the researchers adjusted for treatment with low-dose aspirin. The incidence rate ratio (IRR) was 9.8 (P=0.02).

Bleeding

After 2215 person-years of follow-up free from cytoreduction, there were 17 major bleeding episodes.

Thirteen occurred while patients were on antiplatelet therapy, and 4 occurred while patients were on observation. The incidence rates were 9.9 and 4.6 events x 1000 person-years, respectively (P=0.2).

There was no significant difference in major bleeding episodes between the treatment groups for JAK2V617F-positive patients.

But CALR-mutated patients had a significantly higher rate of major bleeding while on antiplatelet therapy than on observation—12.9 and 1.8 events per 1000 person-years, respectively (P=0.03).

In CALR-mutated patients, antiplatelet therapy was associated with a tendency toward an increased risk of bleeding (IRR: 6.9, P=0.06), but extreme thrombocytosis was not (IRR: 2.7, P=0.1).

In JAK2V617F-positive patients, extreme thrombocytosis was associated with an increased risk of bleeding (IRR: 9.8, P=0.002), but antiplatelet therapy was not (IRR: 0.9, P=0.9).

Potential treatment recommendations

The researchers said this retrospective study suggests a genotype-based approach to antiplatelet therapy may be effective for patients with low-risk ET. However, this needs to be confirmed in prospective trials.

The failure of antiplatelet therapy to prevent thrombosis in CALR-mutated patients and their increased need for cytoreductive therapy suggest these patients require a different approach from that used in JAK2V617F-positive patients.

The researchers said the data suggest that patients with CALR-mutated ET who have a low risk of thrombosis and no symptoms should simply be observed. And CALR-mutated patients with symptoms or marked thrombocytosis should receive cytoreductive therapy, as it poses a lower risk of bleeding than antiplatelet therapy.

Patients with JAK2V617F-positive ET should receive antiplatelet therapy rather than undergoing observation, as antiplatelet therapy may reduce the risk of thrombosis in these patients and does not pose an increased risk of bleeding.

However, in JAK2V617F-positive patients with concomitant cardiovascular risk factors and/or leukocytosis, antiplatelet therapy may not be sufficient. These patients might be candidates for cytoreductive therapy, especially if they have marked thrombocytosis.

Aspirin tablets

Photo by Sage Ross

Results of a retrospective study suggest that patients with low-risk essential thrombocythemia (ET) may benefit from a genotype-based approach to

antiplatelet therapy.

The study showed that, overall, neither CALR-mutated nor JAK2V617F-positive patients derived a significant benefit from treatment with low-dose aspirin.

JAK2V617F-positive patients had a somewhat lower risk of thrombosis while on the therapy than during observation.

But CALR-mutated patients had a significantly increased risk of major bleeding and no decrease in the risk of thrombosis while on antiplatelet therapy.

Carlos Besses, MD, PhD, of Hospital del Mar in Barcelona, Spain, and his colleagues reported these results in haematologica.

The researchers evaluated 433 patients with low-risk ET—271 with CALR mutations and 162 with JAK2V617F. In all, 353 patients received low-dose aspirin (81-100 mg/day), but the treatment was withdrawn in 50 patients (permanently in 46 of them).

Two hundred and thirty-one patients received cytoreductive therapy, including hydroxyurea (n=143), anagrelide (n=66), interferon (n=18), and busulfan (n=4).

The projected time from diagnosis to the start of cytoreductive therapy was significantly shorter in patients with CALR-mutated ET than in JAK2V617F-positive patients—a median of 5.0 years and 9.8 years, respectively (P=0.002). The most common reason for cytoreduction in CALR-mutated patients was extreme thrombocytosis.

Thrombosis

After 2215 person-years of follow-up free from cytoreduction, there were 25 arterial or venous thrombotic events.

Fourteen thrombotic events occurred while patients were receiving low-dose aspirin, and 11 occurred while patients were under observation only. The incidence rates were 10.7 and 12.1 events x 1000 person-years, respectively (P=0.7).

Among CALR-mutated patients, there were more thrombotic events during antiplatelet therapy than during observation—9.7 and 6.9 events x 1000 person-years, respectively (P=0.6).

Among JAK2V617F-positive patients, there were fewer thrombotic events during antiplatelet therapy than during observation, but the difference was not significant—11.6 and 21.1 events x 1000 person-years, respectively (P=0.3).

Coexistence of the JAK2V617F mutation and cardiovascular risk factors increased the risk of thrombosis, even after the researchers adjusted for treatment with low-dose aspirin. The incidence rate ratio (IRR) was 9.8 (P=0.02).

Bleeding

After 2215 person-years of follow-up free from cytoreduction, there were 17 major bleeding episodes.

Thirteen occurred while patients were on antiplatelet therapy, and 4 occurred while patients were on observation. The incidence rates were 9.9 and 4.6 events x 1000 person-years, respectively (P=0.2).

There was no significant difference in major bleeding episodes between the treatment groups for JAK2V617F-positive patients.

But CALR-mutated patients had a significantly higher rate of major bleeding while on antiplatelet therapy than on observation—12.9 and 1.8 events per 1000 person-years, respectively (P=0.03).

In CALR-mutated patients, antiplatelet therapy was associated with a tendency toward an increased risk of bleeding (IRR: 6.9, P=0.06), but extreme thrombocytosis was not (IRR: 2.7, P=0.1).

In JAK2V617F-positive patients, extreme thrombocytosis was associated with an increased risk of bleeding (IRR: 9.8, P=0.002), but antiplatelet therapy was not (IRR: 0.9, P=0.9).

Potential treatment recommendations

The researchers said this retrospective study suggests a genotype-based approach to antiplatelet therapy may be effective for patients with low-risk ET. However, this needs to be confirmed in prospective trials.

The failure of antiplatelet therapy to prevent thrombosis in CALR-mutated patients and their increased need for cytoreductive therapy suggest these patients require a different approach from that used in JAK2V617F-positive patients.

The researchers said the data suggest that patients with CALR-mutated ET who have a low risk of thrombosis and no symptoms should simply be observed. And CALR-mutated patients with symptoms or marked thrombocytosis should receive cytoreductive therapy, as it poses a lower risk of bleeding than antiplatelet therapy.

Patients with JAK2V617F-positive ET should receive antiplatelet therapy rather than undergoing observation, as antiplatelet therapy may reduce the risk of thrombosis in these patients and does not pose an increased risk of bleeding.

However, in JAK2V617F-positive patients with concomitant cardiovascular risk factors and/or leukocytosis, antiplatelet therapy may not be sufficient. These patients might be candidates for cytoreductive therapy, especially if they have marked thrombocytosis.

Aspirin tablets

Photo by Sage Ross

Results of a retrospective study suggest that patients with low-risk essential thrombocythemia (ET) may benefit from a genotype-based approach to

antiplatelet therapy.

The study showed that, overall, neither CALR-mutated nor JAK2V617F-positive patients derived a significant benefit from treatment with low-dose aspirin.

JAK2V617F-positive patients had a somewhat lower risk of thrombosis while on the therapy than during observation.

But CALR-mutated patients had a significantly increased risk of major bleeding and no decrease in the risk of thrombosis while on antiplatelet therapy.

Carlos Besses, MD, PhD, of Hospital del Mar in Barcelona, Spain, and his colleagues reported these results in haematologica.

The researchers evaluated 433 patients with low-risk ET—271 with CALR mutations and 162 with JAK2V617F. In all, 353 patients received low-dose aspirin (81-100 mg/day), but the treatment was withdrawn in 50 patients (permanently in 46 of them).

Two hundred and thirty-one patients received cytoreductive therapy, including hydroxyurea (n=143), anagrelide (n=66), interferon (n=18), and busulfan (n=4).

The projected time from diagnosis to the start of cytoreductive therapy was significantly shorter in patients with CALR-mutated ET than in JAK2V617F-positive patients—a median of 5.0 years and 9.8 years, respectively (P=0.002). The most common reason for cytoreduction in CALR-mutated patients was extreme thrombocytosis.

Thrombosis

After 2215 person-years of follow-up free from cytoreduction, there were 25 arterial or venous thrombotic events.

Fourteen thrombotic events occurred while patients were receiving low-dose aspirin, and 11 occurred while patients were under observation only. The incidence rates were 10.7 and 12.1 events x 1000 person-years, respectively (P=0.7).

Among CALR-mutated patients, there were more thrombotic events during antiplatelet therapy than during observation—9.7 and 6.9 events x 1000 person-years, respectively (P=0.6).

Among JAK2V617F-positive patients, there were fewer thrombotic events during antiplatelet therapy than during observation, but the difference was not significant—11.6 and 21.1 events x 1000 person-years, respectively (P=0.3).

Coexistence of the JAK2V617F mutation and cardiovascular risk factors increased the risk of thrombosis, even after the researchers adjusted for treatment with low-dose aspirin. The incidence rate ratio (IRR) was 9.8 (P=0.02).

Bleeding

After 2215 person-years of follow-up free from cytoreduction, there were 17 major bleeding episodes.

Thirteen occurred while patients were on antiplatelet therapy, and 4 occurred while patients were on observation. The incidence rates were 9.9 and 4.6 events x 1000 person-years, respectively (P=0.2).

There was no significant difference in major bleeding episodes between the treatment groups for JAK2V617F-positive patients.

But CALR-mutated patients had a significantly higher rate of major bleeding while on antiplatelet therapy than on observation—12.9 and 1.8 events per 1000 person-years, respectively (P=0.03).

In CALR-mutated patients, antiplatelet therapy was associated with a tendency toward an increased risk of bleeding (IRR: 6.9, P=0.06), but extreme thrombocytosis was not (IRR: 2.7, P=0.1).

In JAK2V617F-positive patients, extreme thrombocytosis was associated with an increased risk of bleeding (IRR: 9.8, P=0.002), but antiplatelet therapy was not (IRR: 0.9, P=0.9).

Potential treatment recommendations

The researchers said this retrospective study suggests a genotype-based approach to antiplatelet therapy may be effective for patients with low-risk ET. However, this needs to be confirmed in prospective trials.

The failure of antiplatelet therapy to prevent thrombosis in CALR-mutated patients and their increased need for cytoreductive therapy suggest these patients require a different approach from that used in JAK2V617F-positive patients.

The researchers said the data suggest that patients with CALR-mutated ET who have a low risk of thrombosis and no symptoms should simply be observed. And CALR-mutated patients with symptoms or marked thrombocytosis should receive cytoreductive therapy, as it poses a lower risk of bleeding than antiplatelet therapy.

Patients with JAK2V617F-positive ET should receive antiplatelet therapy rather than undergoing observation, as antiplatelet therapy may reduce the risk of thrombosis in these patients and does not pose an increased risk of bleeding.

However, in JAK2V617F-positive patients with concomitant cardiovascular risk factors and/or leukocytosis, antiplatelet therapy may not be sufficient. These patients might be candidates for cytoreductive therapy, especially if they have marked thrombocytosis.

Multiple myeloma (MM) is a bone marrow- based malignancy of plasma cells that is diagnosed in over 30,000 patients annually in the United States. Despite the many recent advances in the treatment of MM, it remains an incurable disease. Thus, the need for the development of new effective therapies remains critical for these patients.

Smoldering MM
In general, it has not been shown that patients with smoldering MM (SMM) benefit from early treatment, but recent studies have identified a subset of patients who are at high-risk and may require therapy more quickly. Recent guidelines from the International Myeloma Working Group recommend immediate treatment of this subgroup of SMM.¹ However, although findings in a Spanish study suggested that early treatment of high-risk SMM patients with the immunomodulatory agent (IMiD) lenalidomide and dexamethasone improves overall survival (OS),² the design of that study limits its clinical applicability, and no other randomized trials have been completed to show the advantage of early therapy for these patients.

Specific drugs
The development of novel agents such as proteasome inhibitors (PIs), IMiDs, histone deacetylase inhibitors (HDACIs), and monoclonal antibodies (mAbs) in recent years has vastly changed the approach to the treatment of MM patients.

PIs that are cytotoxic to MM cells, such as bortezomib, have become a foundation for MM treatment over the past decade. However, patients develop drug resistance to bortezomib by acquiring gene mutations and through other mechanisms. In recent years, newer forms of PIs such as carfilzomib and the oral formulations ixazomib and oprozomib have been and are currently being developed.³ Preclinical studies have shown that resistance to one PI can be overcome with treatment with another PI.⁴

Click on the PDF icon at the top of this introduction to read the full article.

Multiple myeloma (MM) is a bone marrow- based malignancy of plasma cells that is diagnosed in over 30,000 patients annually in the United States. Despite the many recent advances in the treatment of MM, it remains an incurable disease. Thus, the need for the development of new effective therapies remains critical for these patients.

Smoldering MM
In general, it has not been shown that patients with smoldering MM (SMM) benefit from early treatment, but recent studies have identified a subset of patients who are at high-risk and may require therapy more quickly. Recent guidelines from the International Myeloma Working Group recommend immediate treatment of this subgroup of SMM.¹ However, although findings in a Spanish study suggested that early treatment of high-risk SMM patients with the immunomodulatory agent (IMiD) lenalidomide and dexamethasone improves overall survival (OS),² the design of that study limits its clinical applicability, and no other randomized trials have been completed to show the advantage of early therapy for these patients.

Specific drugs
The development of novel agents such as proteasome inhibitors (PIs), IMiDs, histone deacetylase inhibitors (HDACIs), and monoclonal antibodies (mAbs) in recent years has vastly changed the approach to the treatment of MM patients.

PIs that are cytotoxic to MM cells, such as bortezomib, have become a foundation for MM treatment over the past decade. However, patients develop drug resistance to bortezomib by acquiring gene mutations and through other mechanisms. In recent years, newer forms of PIs such as carfilzomib and the oral formulations ixazomib and oprozomib have been and are currently being developed.³ Preclinical studies have shown that resistance to one PI can be overcome with treatment with another PI.⁴

Click on the PDF icon at the top of this introduction to read the full article.

Multiple myeloma (MM) is a bone marrow- based malignancy of plasma cells that is diagnosed in over 30,000 patients annually in the United States. Despite the many recent advances in the treatment of MM, it remains an incurable disease. Thus, the need for the development of new effective therapies remains critical for these patients.

Smoldering MM
In general, it has not been shown that patients with smoldering MM (SMM) benefit from early treatment, but recent studies have identified a subset of patients who are at high-risk and may require therapy more quickly. Recent guidelines from the International Myeloma Working Group recommend immediate treatment of this subgroup of SMM.¹ However, although findings in a Spanish study suggested that early treatment of high-risk SMM patients with the immunomodulatory agent (IMiD) lenalidomide and dexamethasone improves overall survival (OS),² the design of that study limits its clinical applicability, and no other randomized trials have been completed to show the advantage of early therapy for these patients.

Specific drugs
The development of novel agents such as proteasome inhibitors (PIs), IMiDs, histone deacetylase inhibitors (HDACIs), and monoclonal antibodies (mAbs) in recent years has vastly changed the approach to the treatment of MM patients.

PIs that are cytotoxic to MM cells, such as bortezomib, have become a foundation for MM treatment over the past decade. However, patients develop drug resistance to bortezomib by acquiring gene mutations and through other mechanisms. In recent years, newer forms of PIs such as carfilzomib and the oral formulations ixazomib and oprozomib have been and are currently being developed.³ Preclinical studies have shown that resistance to one PI can be overcome with treatment with another PI.⁴

Click on the PDF icon at the top of this introduction to read the full article.

Background There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting.

Objective To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting.

Methods We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators.

Results Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; P = .010 and P = .018, respectively).

Limitations Retrospective, single-institution study; small patient cohort; short follow-up time

Conclusion The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.


Click on the PDF icon at the top of this introduction to read the full article.

Background There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting.

Objective To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting.

Methods We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators.

Results Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; P = .010 and P = .018, respectively).

Limitations Retrospective, single-institution study; small patient cohort; short follow-up time

Conclusion The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.


Click on the PDF icon at the top of this introduction to read the full article.

Background There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting.

Objective To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting.

Methods We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators.

Results Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV-positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; P = .010 and P = .018, respectively).

Limitations Retrospective, single-institution study; small patient cohort; short follow-up time

Conclusion The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De-escalation of postoperative treatment based on HPV status alone should be approached with caution.


Click on the PDF icon at the top of this introduction to read the full article.