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KTE-C19 feasible in most young, high-risk ALL patients, study suggests
Photo by Bill Branson
SAN DIEGO—Trial results suggest treatment with the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 is feasible for most young patients with high-risk B-cell acute lymphoblastic leukemia (ALL).
Nearly all ALL patients in this trial were able to receive their assigned dose of KTE-C19 after a preparative chemotherapy regimen.
The complete response (CR) rate in these patients was 62%, and the rate of severe cytokine release syndrome (CRS) was low.
Daniel W. Lee III, MD, of the University of Virginia in Charlottesville, presented these results at the 2016 ASH Annual Meeting (abstract 218).
Dr Lee noted that CAR T cells have shown promise in early studies, but morbidity related to high-grade CRS and/or neurotoxicity could limit wide applicability of this treatment in patients with high disease burden. Among those who achieve CR to CD19 CAR T-cell therapy, nearly half of patients relapse in the first year.
At ASH, Dr Lee reported results of a non-randomized clinical trial of KTE-C19, a CD19 CAR T-cell therapy under development by Kite Pharmaceuticals. The company did not sponsor this study, although investigators reported relationships with Kite and other companies. The trial was sponsored by the National Cancer Institute.
The trial included 53 children and young adults with relapsed/refractory ALL (n=51) or diffuse large B-cell lymphoma (n=2). The patients’ median age was 13 (range, 4-30), and most were male (n=41).
Of the ALL patients, 11 had primary refractory disease, 5 had Ph-positive ALL, 3 had Down syndrome, 6 had central nervous system (CNS) disease (2 with CNS3, 4 with CNS2), and 2 had MLL-rearranged ALL. The median ALL disease burden was 27%.
The first 21 patients received a low-dose fludarabine/cyclophosphamide preparative regimen, and the subsequent 32 patients received an alternative intensified preparative regimen in an attempt to mitigate severe CRS risk and improve response.
Possible intensive preparative regimens included higher-dose fludarabine/cyclophosphamide, fludarabine/high-dose cytarabine/G-CSF, and ifosfamide/etoposide.
All 53 patients had peripheral blood cells collected, and 52 were infused with CAR T cells. One patient did not receive an infusion due to progressive fungal pneumonia, and 2 patients received less than their assigned dose.
Therefore, Dr Lee said KTE-C19 was feasible in 94% of patients.
Efficacy
The median follow-up was 18.7 months.
Dr Lee said KTE-C19 “produced robust responses in very high-risk ALL patients.” He noted, however, that the CR rate was lower among patients with high disease burden.
The CR rate among the ALL patients was 62%. Of the 31 patients who achieved a CR, 28 had a minimal residual disease (MRD)-negative remission.
The rate of MRD-negative CR was 100% among the 11 patients with primary refractory ALL, 100% among the 6 patients with CNS disease, 60% among the 5 patients with Ph+ ALL, and 67% among the 3 with Down syndrome. Neither of the 2 patients with MLL-rearranged ALL responded.
“Attempts to increase response rate by modifying the preparative regimen have not yet been successful,” Dr Lee pointed out.
However, he noted superior response and overall survival rates among patients who received a fludarabine/cyclophosphamide preparative regimen.
“Median overall survival in all enrolled patients is 13.3 months with fludarabine/cyclophosphamide prep versus 5.5 months with other regimens,” he said.
The overall survival rate for the ALL patients was 28%, and the median overall survival was 11.2 months.
For patients who achieved an MRD-negative remission, the leukemia-free survival (LFS) rate was 56%. The median LFS was not reached.
Dr Lee noted that hematopoietic stem cell transplant (HSCT) after KTE-C19 correlated with decreased relapse rates and led to superior LFS.
Of the 28 patients who achieved MRD-negative CR, 21 went on to HSCT after KTE-C19. The median time to HSCT after CAR T-cell dose was 54 days. (Ten of the 28 patients had HSCT before receiving KTE-C19.)
Nineteen (91%) of the patients who proceeded to HSCT after KTE-C19 did not relapse, compared to 1 (14%) of the patients who did not have a post-CAR T transplant.
The median LFS was 4.9 months among the MRD responders who did not proceed to HSCT and undefined among MRD responders with a transplant after KTE-C19.
The probability of survival was 65% beginning at 18 months among patients who underwent HSCT and 14% beginning at 9.8 months among patients without a post-KTE-C19 transplant.
CD19 escape remains a challenge, Dr Lee said. The risk may be diminished, but not eradicated, with HSCT.
Toxicity
“There was a low rate of CRS, which was successfully managed with a grade-driven algorithm,” Dr Lee noted.
Five patients (10%) had grade 3 CRS, and 2 (4%) had grade 4 CRS.
Other grade 3/4 adverse events that were considered at least possibly related to therapy included fever (38% grade 3), febrile neutropenia (23% grade
3), hypotension (9% grade 3, 4% grade 4), LV systolic dysfunction (9% grade 3), prolonged QTc (2% grade 3), dysphasia (2% grade 3), cardiac arrest (2% grade 4), multi-organ failure (2% grade 3), hypoxia (2% grade 3, 2% grade 4), and pulmonary embolism (2% grade 3).
“There were no severe or permanent neurologic toxicities,” Dr Lee said. “Intensive neuropsychological testing in 13 patients revealed no consistent treatment-related neurocognitive decline, and several patients improved following therapy.”
In all, there were 46 cases of neurotoxicity, including visual hallucination (8 grade 1, 17%), headache (1 grade 3 [2%], 3 grade 2 [6%]), confusion (2 grade 1, 4%),
dysphasia (1 grade 3, 2%), delirium (1 grade 3, 2%), seizure (1 grade 2, 1 grade 1 [2% each]), ataxia (1 grade 2, 2%), tremor (1 grade 2, 2%), dysesthesia (1 grade 2, 2%), and dysarthria (1 grade 1, 2%). 
Photo by Bill Branson
SAN DIEGO—Trial results suggest treatment with the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 is feasible for most young patients with high-risk B-cell acute lymphoblastic leukemia (ALL).
Nearly all ALL patients in this trial were able to receive their assigned dose of KTE-C19 after a preparative chemotherapy regimen.
The complete response (CR) rate in these patients was 62%, and the rate of severe cytokine release syndrome (CRS) was low.
Daniel W. Lee III, MD, of the University of Virginia in Charlottesville, presented these results at the 2016 ASH Annual Meeting (abstract 218).
Dr Lee noted that CAR T cells have shown promise in early studies, but morbidity related to high-grade CRS and/or neurotoxicity could limit wide applicability of this treatment in patients with high disease burden. Among those who achieve CR to CD19 CAR T-cell therapy, nearly half of patients relapse in the first year.
At ASH, Dr Lee reported results of a non-randomized clinical trial of KTE-C19, a CD19 CAR T-cell therapy under development by Kite Pharmaceuticals. The company did not sponsor this study, although investigators reported relationships with Kite and other companies. The trial was sponsored by the National Cancer Institute.
The trial included 53 children and young adults with relapsed/refractory ALL (n=51) or diffuse large B-cell lymphoma (n=2). The patients’ median age was 13 (range, 4-30), and most were male (n=41).
Of the ALL patients, 11 had primary refractory disease, 5 had Ph-positive ALL, 3 had Down syndrome, 6 had central nervous system (CNS) disease (2 with CNS3, 4 with CNS2), and 2 had MLL-rearranged ALL. The median ALL disease burden was 27%.
The first 21 patients received a low-dose fludarabine/cyclophosphamide preparative regimen, and the subsequent 32 patients received an alternative intensified preparative regimen in an attempt to mitigate severe CRS risk and improve response.
Possible intensive preparative regimens included higher-dose fludarabine/cyclophosphamide, fludarabine/high-dose cytarabine/G-CSF, and ifosfamide/etoposide.
All 53 patients had peripheral blood cells collected, and 52 were infused with CAR T cells. One patient did not receive an infusion due to progressive fungal pneumonia, and 2 patients received less than their assigned dose.
Therefore, Dr Lee said KTE-C19 was feasible in 94% of patients.
Efficacy
The median follow-up was 18.7 months.
Dr Lee said KTE-C19 “produced robust responses in very high-risk ALL patients.” He noted, however, that the CR rate was lower among patients with high disease burden.
The CR rate among the ALL patients was 62%. Of the 31 patients who achieved a CR, 28 had a minimal residual disease (MRD)-negative remission.
The rate of MRD-negative CR was 100% among the 11 patients with primary refractory ALL, 100% among the 6 patients with CNS disease, 60% among the 5 patients with Ph+ ALL, and 67% among the 3 with Down syndrome. Neither of the 2 patients with MLL-rearranged ALL responded.
“Attempts to increase response rate by modifying the preparative regimen have not yet been successful,” Dr Lee pointed out.
However, he noted superior response and overall survival rates among patients who received a fludarabine/cyclophosphamide preparative regimen.
“Median overall survival in all enrolled patients is 13.3 months with fludarabine/cyclophosphamide prep versus 5.5 months with other regimens,” he said.
The overall survival rate for the ALL patients was 28%, and the median overall survival was 11.2 months.
For patients who achieved an MRD-negative remission, the leukemia-free survival (LFS) rate was 56%. The median LFS was not reached.
Dr Lee noted that hematopoietic stem cell transplant (HSCT) after KTE-C19 correlated with decreased relapse rates and led to superior LFS.
Of the 28 patients who achieved MRD-negative CR, 21 went on to HSCT after KTE-C19. The median time to HSCT after CAR T-cell dose was 54 days. (Ten of the 28 patients had HSCT before receiving KTE-C19.)
Nineteen (91%) of the patients who proceeded to HSCT after KTE-C19 did not relapse, compared to 1 (14%) of the patients who did not have a post-CAR T transplant.
The median LFS was 4.9 months among the MRD responders who did not proceed to HSCT and undefined among MRD responders with a transplant after KTE-C19.
The probability of survival was 65% beginning at 18 months among patients who underwent HSCT and 14% beginning at 9.8 months among patients without a post-KTE-C19 transplant.
CD19 escape remains a challenge, Dr Lee said. The risk may be diminished, but not eradicated, with HSCT.
Toxicity
“There was a low rate of CRS, which was successfully managed with a grade-driven algorithm,” Dr Lee noted.
Five patients (10%) had grade 3 CRS, and 2 (4%) had grade 4 CRS.
Other grade 3/4 adverse events that were considered at least possibly related to therapy included fever (38% grade 3), febrile neutropenia (23% grade
3), hypotension (9% grade 3, 4% grade 4), LV systolic dysfunction (9% grade 3), prolonged QTc (2% grade 3), dysphasia (2% grade 3), cardiac arrest (2% grade 4), multi-organ failure (2% grade 3), hypoxia (2% grade 3, 2% grade 4), and pulmonary embolism (2% grade 3).
“There were no severe or permanent neurologic toxicities,” Dr Lee said. “Intensive neuropsychological testing in 13 patients revealed no consistent treatment-related neurocognitive decline, and several patients improved following therapy.”
In all, there were 46 cases of neurotoxicity, including visual hallucination (8 grade 1, 17%), headache (1 grade 3 [2%], 3 grade 2 [6%]), confusion (2 grade 1, 4%),
dysphasia (1 grade 3, 2%), delirium (1 grade 3, 2%), seizure (1 grade 2, 1 grade 1 [2% each]), ataxia (1 grade 2, 2%), tremor (1 grade 2, 2%), dysesthesia (1 grade 2, 2%), and dysarthria (1 grade 1, 2%).
Photo by Bill Branson
SAN DIEGO—Trial results suggest treatment with the chimeric antigen receptor (CAR) T-cell therapy KTE-C19 is feasible for most young patients with high-risk B-cell acute lymphoblastic leukemia (ALL).
Nearly all ALL patients in this trial were able to receive their assigned dose of KTE-C19 after a preparative chemotherapy regimen.
The complete response (CR) rate in these patients was 62%, and the rate of severe cytokine release syndrome (CRS) was low.
Daniel W. Lee III, MD, of the University of Virginia in Charlottesville, presented these results at the 2016 ASH Annual Meeting (abstract 218).
Dr Lee noted that CAR T cells have shown promise in early studies, but morbidity related to high-grade CRS and/or neurotoxicity could limit wide applicability of this treatment in patients with high disease burden. Among those who achieve CR to CD19 CAR T-cell therapy, nearly half of patients relapse in the first year.
At ASH, Dr Lee reported results of a non-randomized clinical trial of KTE-C19, a CD19 CAR T-cell therapy under development by Kite Pharmaceuticals. The company did not sponsor this study, although investigators reported relationships with Kite and other companies. The trial was sponsored by the National Cancer Institute.
The trial included 53 children and young adults with relapsed/refractory ALL (n=51) or diffuse large B-cell lymphoma (n=2). The patients’ median age was 13 (range, 4-30), and most were male (n=41).
Of the ALL patients, 11 had primary refractory disease, 5 had Ph-positive ALL, 3 had Down syndrome, 6 had central nervous system (CNS) disease (2 with CNS3, 4 with CNS2), and 2 had MLL-rearranged ALL. The median ALL disease burden was 27%.
The first 21 patients received a low-dose fludarabine/cyclophosphamide preparative regimen, and the subsequent 32 patients received an alternative intensified preparative regimen in an attempt to mitigate severe CRS risk and improve response.
Possible intensive preparative regimens included higher-dose fludarabine/cyclophosphamide, fludarabine/high-dose cytarabine/G-CSF, and ifosfamide/etoposide.
All 53 patients had peripheral blood cells collected, and 52 were infused with CAR T cells. One patient did not receive an infusion due to progressive fungal pneumonia, and 2 patients received less than their assigned dose.
Therefore, Dr Lee said KTE-C19 was feasible in 94% of patients.
Efficacy
The median follow-up was 18.7 months.
Dr Lee said KTE-C19 “produced robust responses in very high-risk ALL patients.” He noted, however, that the CR rate was lower among patients with high disease burden.
The CR rate among the ALL patients was 62%. Of the 31 patients who achieved a CR, 28 had a minimal residual disease (MRD)-negative remission.
The rate of MRD-negative CR was 100% among the 11 patients with primary refractory ALL, 100% among the 6 patients with CNS disease, 60% among the 5 patients with Ph+ ALL, and 67% among the 3 with Down syndrome. Neither of the 2 patients with MLL-rearranged ALL responded.
“Attempts to increase response rate by modifying the preparative regimen have not yet been successful,” Dr Lee pointed out.
However, he noted superior response and overall survival rates among patients who received a fludarabine/cyclophosphamide preparative regimen.
“Median overall survival in all enrolled patients is 13.3 months with fludarabine/cyclophosphamide prep versus 5.5 months with other regimens,” he said.
The overall survival rate for the ALL patients was 28%, and the median overall survival was 11.2 months.
For patients who achieved an MRD-negative remission, the leukemia-free survival (LFS) rate was 56%. The median LFS was not reached.
Dr Lee noted that hematopoietic stem cell transplant (HSCT) after KTE-C19 correlated with decreased relapse rates and led to superior LFS.
Of the 28 patients who achieved MRD-negative CR, 21 went on to HSCT after KTE-C19. The median time to HSCT after CAR T-cell dose was 54 days. (Ten of the 28 patients had HSCT before receiving KTE-C19.)
Nineteen (91%) of the patients who proceeded to HSCT after KTE-C19 did not relapse, compared to 1 (14%) of the patients who did not have a post-CAR T transplant.
The median LFS was 4.9 months among the MRD responders who did not proceed to HSCT and undefined among MRD responders with a transplant after KTE-C19.
The probability of survival was 65% beginning at 18 months among patients who underwent HSCT and 14% beginning at 9.8 months among patients without a post-KTE-C19 transplant.
CD19 escape remains a challenge, Dr Lee said. The risk may be diminished, but not eradicated, with HSCT.
Toxicity
“There was a low rate of CRS, which was successfully managed with a grade-driven algorithm,” Dr Lee noted.
Five patients (10%) had grade 3 CRS, and 2 (4%) had grade 4 CRS.
Other grade 3/4 adverse events that were considered at least possibly related to therapy included fever (38% grade 3), febrile neutropenia (23% grade
3), hypotension (9% grade 3, 4% grade 4), LV systolic dysfunction (9% grade 3), prolonged QTc (2% grade 3), dysphasia (2% grade 3), cardiac arrest (2% grade 4), multi-organ failure (2% grade 3), hypoxia (2% grade 3, 2% grade 4), and pulmonary embolism (2% grade 3).
“There were no severe or permanent neurologic toxicities,” Dr Lee said. “Intensive neuropsychological testing in 13 patients revealed no consistent treatment-related neurocognitive decline, and several patients improved following therapy.”
In all, there were 46 cases of neurotoxicity, including visual hallucination (8 grade 1, 17%), headache (1 grade 3 [2%], 3 grade 2 [6%]), confusion (2 grade 1, 4%),
dysphasia (1 grade 3, 2%), delirium (1 grade 3, 2%), seizure (1 grade 2, 1 grade 1 [2% each]), ataxia (1 grade 2, 2%), tremor (1 grade 2, 2%), dysesthesia (1 grade 2, 2%), and dysarthria (1 grade 1, 2%).
It’s working! (No it’s not! Yes it is!)
A man walks into a doctor’s office, snapping his fingers.
“Why are you snapping your fingers?” asks the doctor.
“To keep the elephants away,” says the man, still snapping his fingers.
“That’s ridiculous!” says the doctor. “There are no elephants within 3,000 miles of here!”
“You see,” says the man, still snapping. “It’s working!”
Even saying that sounds strange. Don’t we physicians apply the evidence-based fruits of science? What does the patient’s mind have to do with that?
Yesterday we saw Emma, who spent 5 years in Austria. On her back was perfectly circular purpura.
“Who does your cupping?” I asked her.
“My acupuncturist,” said Emma. “He does cupping too.”
“What’s it for?”
“Aches and pains, stress, that sort of thing.”
“Does it help?”
“It seems to,” said Emma. Sometimes, anyway.”
Later I asked my student what she thought Emma meant. “What did Emma see or feel to make her conclude that cupping was working, at least sometimes? Did she feel better Tuesday than Monday? What if she felt worse again Wednesday? Would that mean the treatment wasn’t working anymore? That it works some days and not others?”
If you think this line of analysis applies only to exotic forms of alternative medicine, consider how often we could ask the same questions about the medically approved treatments we prescribe every day.
Acne
• Henrietta, for whom I’d prescribed clindamycin in the morning and tretinoin at night. Her verdict? “I stopped the clindamycin because it didn’t work. But I love the tretinoin—it works great!”
Since she was putting both creams on exactly the same area, what did Henrietta observe to lead her to this paradoxical conclusion?
• Janet has two pimples, yet she’s decided that minocycline doesn’t work. Her evidence? “I still get breakouts around my period.”
Eczema
• “Amcinonide worked amazingly but clobetasol didn’t work at all!”
• “I stopped the betamethasone. Calendula works better.”
• And of course: “Sure the cream helped, but the rash came back!”
Patients say things like this all day long. From a medical standpoint, active ingredients work better than inert vehicles. In theory, class 1 steroids are more effective than class 3 steroids.
Perhaps, but many of my patients don’t agree. Maybe their eczema has gone into remission, in which case anything will work. Even if so, there is no way I can prove that to them. So I usually don’t try.
Psoriasis
“Your psoriasis looks better.”
“No, it’s worse.”
“Why? It covers a lot less skin than it used to.”
“But now it’s coming in new places.”
One could go on. With my students, I often do. If they learn nothing else, I try to convey the essential difference between a person and a toaster. Which is this:
If you know how to fix a toaster, the toaster does not have to agree with you.
A person is another matter. Patients have minds to go with their parts. They pick up knowledge from places doctors have never been and make inferences doctors would never make. Then they act on this knowledge and those inferences by saying things like: “The morning cream didn’t work but the night cream did, so I stopped the morning cream.”
I therefore advise students to ask patients two questions first thing:
• What treatments are the patients actually using? Assuming that they are doing what the chart says you asked them to do can jam your foot so deep in your mouth that you’ll never get it out.
• How do the patients themselves think they’re doing? One man with a couple of pimples or scaly spots is thrilled. Another with the same pimples or spots is miserable. It’s helpful to find out which he is before making suggestions. (See foot in mouth, above.)
Emma, by the way, was unhappy that she couldn’t find a practitioner of craniosacral therapy (look it up) as proficient as the one she had in Austria.
I asked her how she judged proficiency but won’t bother you with her answer. I just referred her to a physician who practices both Eastern and Western medicine.
That worked for her.
Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected] .
A man walks into a doctor’s office, snapping his fingers.
“Why are you snapping your fingers?” asks the doctor.
“To keep the elephants away,” says the man, still snapping his fingers.
“That’s ridiculous!” says the doctor. “There are no elephants within 3,000 miles of here!”
“You see,” says the man, still snapping. “It’s working!”
Even saying that sounds strange. Don’t we physicians apply the evidence-based fruits of science? What does the patient’s mind have to do with that?
Yesterday we saw Emma, who spent 5 years in Austria. On her back was perfectly circular purpura.
“Who does your cupping?” I asked her.
“My acupuncturist,” said Emma. “He does cupping too.”
“What’s it for?”
“Aches and pains, stress, that sort of thing.”
“Does it help?”
“It seems to,” said Emma. Sometimes, anyway.”
Later I asked my student what she thought Emma meant. “What did Emma see or feel to make her conclude that cupping was working, at least sometimes? Did she feel better Tuesday than Monday? What if she felt worse again Wednesday? Would that mean the treatment wasn’t working anymore? That it works some days and not others?”
If you think this line of analysis applies only to exotic forms of alternative medicine, consider how often we could ask the same questions about the medically approved treatments we prescribe every day.
Acne
• Henrietta, for whom I’d prescribed clindamycin in the morning and tretinoin at night. Her verdict? “I stopped the clindamycin because it didn’t work. But I love the tretinoin—it works great!”
Since she was putting both creams on exactly the same area, what did Henrietta observe to lead her to this paradoxical conclusion?
• Janet has two pimples, yet she’s decided that minocycline doesn’t work. Her evidence? “I still get breakouts around my period.”
Eczema
• “Amcinonide worked amazingly but clobetasol didn’t work at all!”
• “I stopped the betamethasone. Calendula works better.”
• And of course: “Sure the cream helped, but the rash came back!”
Patients say things like this all day long. From a medical standpoint, active ingredients work better than inert vehicles. In theory, class 1 steroids are more effective than class 3 steroids.
Perhaps, but many of my patients don’t agree. Maybe their eczema has gone into remission, in which case anything will work. Even if so, there is no way I can prove that to them. So I usually don’t try.
Psoriasis
“Your psoriasis looks better.”
“No, it’s worse.”
“Why? It covers a lot less skin than it used to.”
“But now it’s coming in new places.”
One could go on. With my students, I often do. If they learn nothing else, I try to convey the essential difference between a person and a toaster. Which is this:
If you know how to fix a toaster, the toaster does not have to agree with you.
A person is another matter. Patients have minds to go with their parts. They pick up knowledge from places doctors have never been and make inferences doctors would never make. Then they act on this knowledge and those inferences by saying things like: “The morning cream didn’t work but the night cream did, so I stopped the morning cream.”
I therefore advise students to ask patients two questions first thing:
• What treatments are the patients actually using? Assuming that they are doing what the chart says you asked them to do can jam your foot so deep in your mouth that you’ll never get it out.
• How do the patients themselves think they’re doing? One man with a couple of pimples or scaly spots is thrilled. Another with the same pimples or spots is miserable. It’s helpful to find out which he is before making suggestions. (See foot in mouth, above.)
Emma, by the way, was unhappy that she couldn’t find a practitioner of craniosacral therapy (look it up) as proficient as the one she had in Austria.
I asked her how she judged proficiency but won’t bother you with her answer. I just referred her to a physician who practices both Eastern and Western medicine.
That worked for her.
Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected] .
A man walks into a doctor’s office, snapping his fingers.
“Why are you snapping your fingers?” asks the doctor.
“To keep the elephants away,” says the man, still snapping his fingers.
“That’s ridiculous!” says the doctor. “There are no elephants within 3,000 miles of here!”
“You see,” says the man, still snapping. “It’s working!”
Even saying that sounds strange. Don’t we physicians apply the evidence-based fruits of science? What does the patient’s mind have to do with that?
Yesterday we saw Emma, who spent 5 years in Austria. On her back was perfectly circular purpura.
“Who does your cupping?” I asked her.
“My acupuncturist,” said Emma. “He does cupping too.”
“What’s it for?”
“Aches and pains, stress, that sort of thing.”
“Does it help?”
“It seems to,” said Emma. Sometimes, anyway.”
Later I asked my student what she thought Emma meant. “What did Emma see or feel to make her conclude that cupping was working, at least sometimes? Did she feel better Tuesday than Monday? What if she felt worse again Wednesday? Would that mean the treatment wasn’t working anymore? That it works some days and not others?”
If you think this line of analysis applies only to exotic forms of alternative medicine, consider how often we could ask the same questions about the medically approved treatments we prescribe every day.
Acne
• Henrietta, for whom I’d prescribed clindamycin in the morning and tretinoin at night. Her verdict? “I stopped the clindamycin because it didn’t work. But I love the tretinoin—it works great!”
Since she was putting both creams on exactly the same area, what did Henrietta observe to lead her to this paradoxical conclusion?
• Janet has two pimples, yet she’s decided that minocycline doesn’t work. Her evidence? “I still get breakouts around my period.”
Eczema
• “Amcinonide worked amazingly but clobetasol didn’t work at all!”
• “I stopped the betamethasone. Calendula works better.”
• And of course: “Sure the cream helped, but the rash came back!”
Patients say things like this all day long. From a medical standpoint, active ingredients work better than inert vehicles. In theory, class 1 steroids are more effective than class 3 steroids.
Perhaps, but many of my patients don’t agree. Maybe their eczema has gone into remission, in which case anything will work. Even if so, there is no way I can prove that to them. So I usually don’t try.
Psoriasis
“Your psoriasis looks better.”
“No, it’s worse.”
“Why? It covers a lot less skin than it used to.”
“But now it’s coming in new places.”
One could go on. With my students, I often do. If they learn nothing else, I try to convey the essential difference between a person and a toaster. Which is this:
If you know how to fix a toaster, the toaster does not have to agree with you.
A person is another matter. Patients have minds to go with their parts. They pick up knowledge from places doctors have never been and make inferences doctors would never make. Then they act on this knowledge and those inferences by saying things like: “The morning cream didn’t work but the night cream did, so I stopped the morning cream.”
I therefore advise students to ask patients two questions first thing:
• What treatments are the patients actually using? Assuming that they are doing what the chart says you asked them to do can jam your foot so deep in your mouth that you’ll never get it out.
• How do the patients themselves think they’re doing? One man with a couple of pimples or scaly spots is thrilled. Another with the same pimples or spots is miserable. It’s helpful to find out which he is before making suggestions. (See foot in mouth, above.)
Emma, by the way, was unhappy that she couldn’t find a practitioner of craniosacral therapy (look it up) as proficient as the one she had in Austria.
I asked her how she judged proficiency but won’t bother you with her answer. I just referred her to a physician who practices both Eastern and Western medicine.
That worked for her.
Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected] .
FOUND IN TRANSLATION Minimal nomenclature and maximum sensitivity complicate MRD measures
In hematologic malignancies, there is a deep and direct connection between each individual patient, that patient’s symptoms, the visible cells that cause the disease, and the direct measurements and assessments of those cells. The totality of these factors helps to determine the diagnosis and treatment plan. As a butterfly needle often is sufficient for obtaining a diagnostic tumor biopsy, it is not surprising that these same diagnostic techniques are now standardly being used to monitor disease response.
The techniques differ in their limits of detection, however. With sequencing depths able to reliably detect variant allele frequencies of less than 10%, even when patients’ overt leukemia may no longer be detectable, clinicians may be left to ponder what to do with persistent “preleukemic” or “rising clones.”1-3
These patients, now more appropriately stratified for risk of recurrence, are in desperate need of better care algorithms. Standard MRD assessment by flow cytometric analysis is able to detect less than 1 x 10-4 cells. While it can be applied to most patients, its sensitivity will likely be surpassed by new and emerging genomic assays. Real time quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) require a leukemia-specific abnormality but have the potential for far greater sensitivity with deeper sequencing techniques.
Long-term follow up data in acute promyelocytic leukemia (APL) provides the illustrative example where morphologic remission is not durable in the setting of a persistent PML-RARa transcript and therapeutic goals for PCR negativity irrespective of morphology are standard. Pathologic fusion proteins are ideal for marker-driven therapy, but are found in only about 50% of patients, mainly those with APL and Philadelphia chromosome-positive leukemias.
With driver mutations identified in the majority of patients, we can be hopeful that NGS negativity may be a useful clinical endpoint. In work presented at ASH 2016 by Bartlomiej M Getta, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues, patients with concordant MRD positivity by flow cytometry and NGS had inferior outcomes, even after allogeneic transplant, compared to patients with MRD positivity on one assay but not both.5 Nonetheless, caution should be taken in early adoption of NGS as a independent marker of MRD status for two main reasons: 1) False positives and lack of standardization make current interpretation difficult. 2) The presence of “preleukemic” clones remains enigmatic – and no matter the nomenclature used, can a DNMT3A or IDH-mutant clone really be deemed “clonal hematopoiesis of indeterminate potential” when a patient has already had clonal transformation?
Conversely, not all patients reported in the work by Klco2 and Getta ultimately relapse. Thus, while it would be preferred to clear all mutant clones, as a therapeutic goal this likely would subject many patients to unnecessary toxicity. One half of the patients reported by Getta were disease free at a year with concordant flow and NGS positive MRD while patients with NGS positivity alone had outcomes equivalent to those of MRD-negative patients, highlighting that certain persistent clones in NGS-only, MRD-positive patients might be amenable to immunotherapy, either with checkpoint inhibitors or allogeneic transplant. Insight into which clones remain quiescent and which are more sinister will require more investigation, but there does seem to be an additive role to NGS-positivity, whereby all MRD is not created equal and the precision and clinical utility of MRD status will likely take on nuanced nomenclature.
References
1. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science Translational Medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012).
2. Klco, J. M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811-22. doi: 10.1001/jama.2015.9643.
3. Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016;127:893-7. doi: 10.1182/blood-2015-10-677021 (2016).
4. Lane, A. A. et al. Results from Ongoing Phase II Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD), Abstract 215, ASH 2016.
5. Getta, B. M. et al. Multicolor Flow Cytometry and Multi-Gene Next Generation Sequencing Are Complimentary and Highly Predictive for Relapse in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant, Abstract 834, ASH 2016.
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, New York, where he is a clinical instructor, on the staff of the leukemia service, and a clinical researcher in The Ross Levine Lab. Contact Dr. Viny at [email protected].
In hematologic malignancies, there is a deep and direct connection between each individual patient, that patient’s symptoms, the visible cells that cause the disease, and the direct measurements and assessments of those cells. The totality of these factors helps to determine the diagnosis and treatment plan. As a butterfly needle often is sufficient for obtaining a diagnostic tumor biopsy, it is not surprising that these same diagnostic techniques are now standardly being used to monitor disease response.
The techniques differ in their limits of detection, however. With sequencing depths able to reliably detect variant allele frequencies of less than 10%, even when patients’ overt leukemia may no longer be detectable, clinicians may be left to ponder what to do with persistent “preleukemic” or “rising clones.”1-3
These patients, now more appropriately stratified for risk of recurrence, are in desperate need of better care algorithms. Standard MRD assessment by flow cytometric analysis is able to detect less than 1 x 10-4 cells. While it can be applied to most patients, its sensitivity will likely be surpassed by new and emerging genomic assays. Real time quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) require a leukemia-specific abnormality but have the potential for far greater sensitivity with deeper sequencing techniques.
Long-term follow up data in acute promyelocytic leukemia (APL) provides the illustrative example where morphologic remission is not durable in the setting of a persistent PML-RARa transcript and therapeutic goals for PCR negativity irrespective of morphology are standard. Pathologic fusion proteins are ideal for marker-driven therapy, but are found in only about 50% of patients, mainly those with APL and Philadelphia chromosome-positive leukemias.
With driver mutations identified in the majority of patients, we can be hopeful that NGS negativity may be a useful clinical endpoint. In work presented at ASH 2016 by Bartlomiej M Getta, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues, patients with concordant MRD positivity by flow cytometry and NGS had inferior outcomes, even after allogeneic transplant, compared to patients with MRD positivity on one assay but not both.5 Nonetheless, caution should be taken in early adoption of NGS as a independent marker of MRD status for two main reasons: 1) False positives and lack of standardization make current interpretation difficult. 2) The presence of “preleukemic” clones remains enigmatic – and no matter the nomenclature used, can a DNMT3A or IDH-mutant clone really be deemed “clonal hematopoiesis of indeterminate potential” when a patient has already had clonal transformation?
Conversely, not all patients reported in the work by Klco2 and Getta ultimately relapse. Thus, while it would be preferred to clear all mutant clones, as a therapeutic goal this likely would subject many patients to unnecessary toxicity. One half of the patients reported by Getta were disease free at a year with concordant flow and NGS positive MRD while patients with NGS positivity alone had outcomes equivalent to those of MRD-negative patients, highlighting that certain persistent clones in NGS-only, MRD-positive patients might be amenable to immunotherapy, either with checkpoint inhibitors or allogeneic transplant. Insight into which clones remain quiescent and which are more sinister will require more investigation, but there does seem to be an additive role to NGS-positivity, whereby all MRD is not created equal and the precision and clinical utility of MRD status will likely take on nuanced nomenclature.
References
1. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science Translational Medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012).
2. Klco, J. M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811-22. doi: 10.1001/jama.2015.9643.
3. Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016;127:893-7. doi: 10.1182/blood-2015-10-677021 (2016).
4. Lane, A. A. et al. Results from Ongoing Phase II Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD), Abstract 215, ASH 2016.
5. Getta, B. M. et al. Multicolor Flow Cytometry and Multi-Gene Next Generation Sequencing Are Complimentary and Highly Predictive for Relapse in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant, Abstract 834, ASH 2016.
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, New York, where he is a clinical instructor, on the staff of the leukemia service, and a clinical researcher in The Ross Levine Lab. Contact Dr. Viny at [email protected].
In hematologic malignancies, there is a deep and direct connection between each individual patient, that patient’s symptoms, the visible cells that cause the disease, and the direct measurements and assessments of those cells. The totality of these factors helps to determine the diagnosis and treatment plan. As a butterfly needle often is sufficient for obtaining a diagnostic tumor biopsy, it is not surprising that these same diagnostic techniques are now standardly being used to monitor disease response.
The techniques differ in their limits of detection, however. With sequencing depths able to reliably detect variant allele frequencies of less than 10%, even when patients’ overt leukemia may no longer be detectable, clinicians may be left to ponder what to do with persistent “preleukemic” or “rising clones.”1-3
These patients, now more appropriately stratified for risk of recurrence, are in desperate need of better care algorithms. Standard MRD assessment by flow cytometric analysis is able to detect less than 1 x 10-4 cells. While it can be applied to most patients, its sensitivity will likely be surpassed by new and emerging genomic assays. Real time quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) require a leukemia-specific abnormality but have the potential for far greater sensitivity with deeper sequencing techniques.
Long-term follow up data in acute promyelocytic leukemia (APL) provides the illustrative example where morphologic remission is not durable in the setting of a persistent PML-RARa transcript and therapeutic goals for PCR negativity irrespective of morphology are standard. Pathologic fusion proteins are ideal for marker-driven therapy, but are found in only about 50% of patients, mainly those with APL and Philadelphia chromosome-positive leukemias.
With driver mutations identified in the majority of patients, we can be hopeful that NGS negativity may be a useful clinical endpoint. In work presented at ASH 2016 by Bartlomiej M Getta, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues, patients with concordant MRD positivity by flow cytometry and NGS had inferior outcomes, even after allogeneic transplant, compared to patients with MRD positivity on one assay but not both.5 Nonetheless, caution should be taken in early adoption of NGS as a independent marker of MRD status for two main reasons: 1) False positives and lack of standardization make current interpretation difficult. 2) The presence of “preleukemic” clones remains enigmatic – and no matter the nomenclature used, can a DNMT3A or IDH-mutant clone really be deemed “clonal hematopoiesis of indeterminate potential” when a patient has already had clonal transformation?
Conversely, not all patients reported in the work by Klco2 and Getta ultimately relapse. Thus, while it would be preferred to clear all mutant clones, as a therapeutic goal this likely would subject many patients to unnecessary toxicity. One half of the patients reported by Getta were disease free at a year with concordant flow and NGS positive MRD while patients with NGS positivity alone had outcomes equivalent to those of MRD-negative patients, highlighting that certain persistent clones in NGS-only, MRD-positive patients might be amenable to immunotherapy, either with checkpoint inhibitors or allogeneic transplant. Insight into which clones remain quiescent and which are more sinister will require more investigation, but there does seem to be an additive role to NGS-positivity, whereby all MRD is not created equal and the precision and clinical utility of MRD status will likely take on nuanced nomenclature.
References
1. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science Translational Medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012).
2. Klco, J. M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811-22. doi: 10.1001/jama.2015.9643.
3. Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016;127:893-7. doi: 10.1182/blood-2015-10-677021 (2016).
4. Lane, A. A. et al. Results from Ongoing Phase II Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD), Abstract 215, ASH 2016.
5. Getta, B. M. et al. Multicolor Flow Cytometry and Multi-Gene Next Generation Sequencing Are Complimentary and Highly Predictive for Relapse in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant, Abstract 834, ASH 2016.
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, New York, where he is a clinical instructor, on the staff of the leukemia service, and a clinical researcher in The Ross Levine Lab. Contact Dr. Viny at [email protected].
Pembrolizumab is the first immune checkpoint inhibitor to receive approval for head and neck cancer
The first immune checkpoint inhibitor was approved for the treatment of head and neck cancer approved in August 2016. Pembrolizumab, which targets the programmed cell death 1 (PD-1) protein, is designed to reinstate the anti-tumor immune response to kill cancer cells and was approved for the treatment of recurrent or metastatic disease that progressed during or after platinum-containing chemotherapy.
Click on the PDF icon at the top of this introduction to read the full article.
The first immune checkpoint inhibitor was approved for the treatment of head and neck cancer approved in August 2016. Pembrolizumab, which targets the programmed cell death 1 (PD-1) protein, is designed to reinstate the anti-tumor immune response to kill cancer cells and was approved for the treatment of recurrent or metastatic disease that progressed during or after platinum-containing chemotherapy.
Click on the PDF icon at the top of this introduction to read the full article.
The first immune checkpoint inhibitor was approved for the treatment of head and neck cancer approved in August 2016. Pembrolizumab, which targets the programmed cell death 1 (PD-1) protein, is designed to reinstate the anti-tumor immune response to kill cancer cells and was approved for the treatment of recurrent or metastatic disease that progressed during or after platinum-containing chemotherapy.
Click on the PDF icon at the top of this introduction to read the full article.
Confirmation CT prevents unnecessary pulmonary nodule bronchoscopy
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
It’s probably a good idea to do a repeat CT the morning of a scheduled bronchoscopy to make sure the pulmonary nodule is still there, according to investigators from Johns Hopkins University, Baltimore.
From Jan. 2015 to June 2016, 116 patients there were scheduled for navigational bronchoscopy to diagnose pulmonary lesions found on screening CTs. Eight (6.9%) – four men, four women, with an average age of 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellations of their procedure. The number needed to screen to prevent one unnecessary procedure was 15. For canceled cases, the average time from screening CT to scheduled bronchoscopy was 53 days; for patients who underwent a bronchoscopy, it was 50 days (Ann Am Thorac Soc. 2016 Dec;13[12]:2223-8).
It can take months to schedule a bronchoscopy after a pulmonary nodule is found on CT screening. Once in a while, the investigators and others have found, even suspicious nodules resolve on their own, and patients end up having a bronchoscopy they don’t need.
“If there is a significant delay from the initial imaging, practitioners should consider repeat studies before proceeding with the scheduled procedure ... Same-day imaging may decrease unnecessary procedural risk ... The optimal time that should be allowed to pass is difficult to ascertain,” said investigators led by Roy Semaan, MD, of the division of pulmonary and critical care medicine at Hopkins.
The team used a newer version of electromagnetic navigation bronchoscopy (Veran Medical Technologies, St. Louis), which requires expiratory and inspiratory CTs the morning of the procedure so software can build a virtual airway model to localize the nodule.
In addition to nodule resolution, same-day CTs might identify disease progression that alters the diagnostic plan of care.
“The most obvious risk associated with repeat CT imaging is the increased radiation exposure to the patient. Patients in our study who received inspiratory and expiratory CT scans ... had a mean exposure of 9.485 mSv, which is not “negligible, but one-time doses at this range are generally considered to be low risk for contributing to the future development of a malignancy,” the team said.
The extra cost of a same-day noncontrast chest CT – about $300, the authors said – is more than offset if it cancels “an unnecessary procedure with its associated risks,” they said.
Dr. Semaan had no disclosures. Three investigators reported grants and personal fees from Veran.
Key clinical point:
Major finding: Of 116 patients, eight (6.9%) – four men, four women, average age 50 years – had a decrease in size or resolution of their lesion on confirmatory CT, leading to cancellation of their procedure.
Data source: Prospective series from Johns Hopkins University.
Disclosures: Three investigators reported grants and personal fees from Veran.
Pancreatic cancer: a therapeutic challenge yet to be met
Although there are numerous hard-to-treat tumor types, pancreatic cancer, which most commonly presents as pancreatic ductal adenocarcinoma (PDA) is particularly notorious and arguably the most challenging and deadly of all cancers. It is currently ranked as the fourth most common cause of cancer-related mortality, and looks set to move up to the number 2 slot within the next 15 years.1 Here, we discuss the evolution of much-needed novel treatment strategies.
Click on the PDF icon at the top of this introduction to read the full article.
Although there are numerous hard-to-treat tumor types, pancreatic cancer, which most commonly presents as pancreatic ductal adenocarcinoma (PDA) is particularly notorious and arguably the most challenging and deadly of all cancers. It is currently ranked as the fourth most common cause of cancer-related mortality, and looks set to move up to the number 2 slot within the next 15 years.1 Here, we discuss the evolution of much-needed novel treatment strategies.
Click on the PDF icon at the top of this introduction to read the full article.
Although there are numerous hard-to-treat tumor types, pancreatic cancer, which most commonly presents as pancreatic ductal adenocarcinoma (PDA) is particularly notorious and arguably the most challenging and deadly of all cancers. It is currently ranked as the fourth most common cause of cancer-related mortality, and looks set to move up to the number 2 slot within the next 15 years.1 Here, we discuss the evolution of much-needed novel treatment strategies.
Click on the PDF icon at the top of this introduction to read the full article.
Unicentric Castleman disease disguised as a pancreatic neoplasm
Castleman disease or angiofollicular lymph node hyperplasia is an uncommon cause of an incidental abdominal mass found on imaging. The etiology of Castleman disease is relatively unknown, however, it is thought to be primarily associated with an oversecretion of interleukin-6. The oversecretion of this pro-inflammatory cytokine leads to lymph node hyperplasia. Castleman disease can be classified into 2 categories: unicentric or multicentric. Most cases of unicentric Castleman disease are asymptomatic and are found on routine imaging. It is found predominately in middle-aged persons of equal sex and is managed primarily by surgical resection. We present here a case of a peripancreatic mass diagnosed by surgical excision as Castleman disease, hyaline vascular type.
Click on the PDF icon at the top of this introduction to read the full article.
Castleman disease or angiofollicular lymph node hyperplasia is an uncommon cause of an incidental abdominal mass found on imaging. The etiology of Castleman disease is relatively unknown, however, it is thought to be primarily associated with an oversecretion of interleukin-6. The oversecretion of this pro-inflammatory cytokine leads to lymph node hyperplasia. Castleman disease can be classified into 2 categories: unicentric or multicentric. Most cases of unicentric Castleman disease are asymptomatic and are found on routine imaging. It is found predominately in middle-aged persons of equal sex and is managed primarily by surgical resection. We present here a case of a peripancreatic mass diagnosed by surgical excision as Castleman disease, hyaline vascular type.
Click on the PDF icon at the top of this introduction to read the full article.
Castleman disease or angiofollicular lymph node hyperplasia is an uncommon cause of an incidental abdominal mass found on imaging. The etiology of Castleman disease is relatively unknown, however, it is thought to be primarily associated with an oversecretion of interleukin-6. The oversecretion of this pro-inflammatory cytokine leads to lymph node hyperplasia. Castleman disease can be classified into 2 categories: unicentric or multicentric. Most cases of unicentric Castleman disease are asymptomatic and are found on routine imaging. It is found predominately in middle-aged persons of equal sex and is managed primarily by surgical resection. We present here a case of a peripancreatic mass diagnosed by surgical excision as Castleman disease, hyaline vascular type.
Click on the PDF icon at the top of this introduction to read the full article.
Paraneoplastic Isaacs syndrome leading to diagnosis of small-cell lung cancer
Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm.
Click on the PDF icon at the top of this introduction to read the full article.
Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm.
Click on the PDF icon at the top of this introduction to read the full article.
Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm.
Click on the PDF icon at the top of this introduction to read the full article.
Quality of life after surgery for pleural malignant mesothelioma – methodological considerations
Background There is a dearth of literature on patient quality of life (QoL) after treatment for malignant pleural mesothelioma (MPM).
Objectives To review the literature on QoL after surgery for MPM and assess differences in quality of life between patients who have extrapleural pneumonectomy (EPP) and those who have pleurectomy and decortication (P-D).
Methods We retrieved and reviewed original research studies on quality of life after mesothelioma surgery. They had been published from January 1990 through June 2016, and included 15 articles and 12 datasets for a total of 523 patients.
Results QoL data was available for 102 EPP patients and 296 P-D patients. Two studies directly compared QoL outcomes between the 2 techniques. Symptoms, lung function parameters, and physical and social functioning were still compromised 6 months after surgery. However, P-D patients fared better than did EPP patients across QoL measures.
Limitations The amount of available literature is small, and the studies are heterogeneous.
Conclusions QoL is better for a longer period of time in patients who undergo P-D, compared with those who have EPP. Given the need for multimodality therapy for MPM and the aggressive nature of the disease, QoL outcomes should be strongly considered when choosing type of surgery for mesothelioma.
Click on the PDF icon at the top of this introduction to read the full article.
Background There is a dearth of literature on patient quality of life (QoL) after treatment for malignant pleural mesothelioma (MPM).
Objectives To review the literature on QoL after surgery for MPM and assess differences in quality of life between patients who have extrapleural pneumonectomy (EPP) and those who have pleurectomy and decortication (P-D).
Methods We retrieved and reviewed original research studies on quality of life after mesothelioma surgery. They had been published from January 1990 through June 2016, and included 15 articles and 12 datasets for a total of 523 patients.
Results QoL data was available for 102 EPP patients and 296 P-D patients. Two studies directly compared QoL outcomes between the 2 techniques. Symptoms, lung function parameters, and physical and social functioning were still compromised 6 months after surgery. However, P-D patients fared better than did EPP patients across QoL measures.
Limitations The amount of available literature is small, and the studies are heterogeneous.
Conclusions QoL is better for a longer period of time in patients who undergo P-D, compared with those who have EPP. Given the need for multimodality therapy for MPM and the aggressive nature of the disease, QoL outcomes should be strongly considered when choosing type of surgery for mesothelioma.
Click on the PDF icon at the top of this introduction to read the full article.
Background There is a dearth of literature on patient quality of life (QoL) after treatment for malignant pleural mesothelioma (MPM).
Objectives To review the literature on QoL after surgery for MPM and assess differences in quality of life between patients who have extrapleural pneumonectomy (EPP) and those who have pleurectomy and decortication (P-D).
Methods We retrieved and reviewed original research studies on quality of life after mesothelioma surgery. They had been published from January 1990 through June 2016, and included 15 articles and 12 datasets for a total of 523 patients.
Results QoL data was available for 102 EPP patients and 296 P-D patients. Two studies directly compared QoL outcomes between the 2 techniques. Symptoms, lung function parameters, and physical and social functioning were still compromised 6 months after surgery. However, P-D patients fared better than did EPP patients across QoL measures.
Limitations The amount of available literature is small, and the studies are heterogeneous.
Conclusions QoL is better for a longer period of time in patients who undergo P-D, compared with those who have EPP. Given the need for multimodality therapy for MPM and the aggressive nature of the disease, QoL outcomes should be strongly considered when choosing type of surgery for mesothelioma.
Click on the PDF icon at the top of this introduction to read the full article.
Social support needs among patients with advanced breast cancer: sensitivity trumps substance
Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.
Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.
Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).
Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.
Limitations Very small sample limits the ability to generalize findings.
Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.
Funding Peers for Progress
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Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.
Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.
Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).
Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.
Limitations Very small sample limits the ability to generalize findings.
Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.
Funding Peers for Progress
Click on the PDF icon at the top of this introduction to read the full article.
Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.
Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.
Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).
Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.
Limitations Very small sample limits the ability to generalize findings.
Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.
Funding Peers for Progress
Click on the PDF icon at the top of this introduction to read the full article.