ANSWER

The correct interpretation of this ECG includes normal sinus rhythm with left atrial enlargement and a left bundle branch block (LBBB). Normal sinus rhythm is evidenced by a P wave associated with each QRS complex with a consistent PR interval.

Left atrial enlargement is evidenced by a P-wave duration ≥ 120 ms in lead II, a notched P wave in the limb leads with a peak duration ≥ 4 ms, and a terminal P-wave negativity in lead V₁ with a duration ≥ 4 ms and a depth ≥ 1 mm.

An LBBB is illustrated by the QRS duration ≥ 120 ms, a dominant S wave in lead V₁, broad monophasic R waves in the lateral leads (including I, aVL, V₅, and V₆), and R-wave peak times of > 60 ms in leads V₅ and V₆.

Further work-up revealed elevated left end-diastolic filling pressures, volume overload, and pulmonary edema consistent with diastolic heart failure. Given the unclear etiology of the LBBB, cardiac catheterization was performed. It revealed no significant coronary artery disease.

ANSWER

The correct interpretation of this ECG includes normal sinus rhythm with left atrial enlargement and a left bundle branch block (LBBB). Normal sinus rhythm is evidenced by a P wave associated with each QRS complex with a consistent PR interval.

Left atrial enlargement is evidenced by a P-wave duration ≥ 120 ms in lead II, a notched P wave in the limb leads with a peak duration ≥ 4 ms, and a terminal P-wave negativity in lead V₁ with a duration ≥ 4 ms and a depth ≥ 1 mm.

An LBBB is illustrated by the QRS duration ≥ 120 ms, a dominant S wave in lead V₁, broad monophasic R waves in the lateral leads (including I, aVL, V₅, and V₆), and R-wave peak times of > 60 ms in leads V₅ and V₆.

Further work-up revealed elevated left end-diastolic filling pressures, volume overload, and pulmonary edema consistent with diastolic heart failure. Given the unclear etiology of the LBBB, cardiac catheterization was performed. It revealed no significant coronary artery disease.

ANSWER

The correct interpretation of this ECG includes normal sinus rhythm with left atrial enlargement and a left bundle branch block (LBBB). Normal sinus rhythm is evidenced by a P wave associated with each QRS complex with a consistent PR interval.

Left atrial enlargement is evidenced by a P-wave duration ≥ 120 ms in lead II, a notched P wave in the limb leads with a peak duration ≥ 4 ms, and a terminal P-wave negativity in lead V₁ with a duration ≥ 4 ms and a depth ≥ 1 mm.

An LBBB is illustrated by the QRS duration ≥ 120 ms, a dominant S wave in lead V₁, broad monophasic R waves in the lateral leads (including I, aVL, V₅, and V₆), and R-wave peak times of > 60 ms in leads V₅ and V₆.

Further work-up revealed elevated left end-diastolic filling pressures, volume overload, and pulmonary edema consistent with diastolic heart failure. Given the unclear etiology of the LBBB, cardiac catheterization was performed. It revealed no significant coronary artery disease.

ANSWER

The correct answer is trichotillomania (choice “c”). See Discussion for more information.

Alopecia mucinosa (choice “a”) is a rare cause of focal hair loss that can occur in children. However, it usually presents with papules or plaques, unlike the smooth skin surface seen here.

Alopecia areata (choice “b”), common in children, typically entails complete hair loss in a given area—or, as hair regrows, with hairs of equal length. The uneven hairs seen in trichotillomania help a great deal in distinguishing it from alopecia areata.

Traction alopecia (choice “d”) is focal hair loss caused by chronic tension related to hairstyling. Most common in African-American women, and typically affecting the frontal periphery of the scalp, it is an unlikely explanation for hair loss in a 10-year-old boy.

DISCUSSION

Trichotillomania (TT) means, literally, “hair-pulling madness.” But in reality, there’s little actual plucking of hairs in this common condition. Instead, patients habitually manipulate hair by twirling and tugging, which weakens the shafts and follicles and renders them more susceptible to everyday wear and tear. In some cases, individual hairs speed through their growth phases and others break off in mid-shaft. All of this contributes to the classic “uneven” look of TT.

Patients with TT tend to be in the 4-to-17 age range, and most have issues with unresolved anxiety that manifest in part with manipulation of the hair. Officially considered an impulse control disorder, TT in most cases belongs to the psychiatrist’s domain.

In this case, it was enormously helpful to have corroboration from the patient and his mother regarding his role in creating and perpetuating the problem. Had that not been the case—or in the event of other doubts as to the correct diagnosis—biopsy could have been performed to rule out most of the other items in the differential, particularly alopecia areata.

Interestingly enough, studies have shown that the more sharply defined the area of hair loss, the more likely the patient is to admit his/her role in its creation. However, as is often the case with scientific research, contradictory findings have also been made.

TREATMENT

Treatment of TT is problematic, since no medications have proven to be completely helpful. Psychiatrists use a combination of medication, cognitive behavioral therapy, and other behavior modifications that are designed to overcome the habitual component of the problem. Most cases of TT resolve on their own, but in severe cases that persist for years, permanent hair loss can result.

In this case, there was enough insight and motivation on the part of the patient and his family to stop the offending behavior and allow the hair to regrow.

ANSWER

The correct answer is trichotillomania (choice “c”). See Discussion for more information.

Alopecia mucinosa (choice “a”) is a rare cause of focal hair loss that can occur in children. However, it usually presents with papules or plaques, unlike the smooth skin surface seen here.

Alopecia areata (choice “b”), common in children, typically entails complete hair loss in a given area—or, as hair regrows, with hairs of equal length. The uneven hairs seen in trichotillomania help a great deal in distinguishing it from alopecia areata.

Traction alopecia (choice “d”) is focal hair loss caused by chronic tension related to hairstyling. Most common in African-American women, and typically affecting the frontal periphery of the scalp, it is an unlikely explanation for hair loss in a 10-year-old boy.

DISCUSSION

Trichotillomania (TT) means, literally, “hair-pulling madness.” But in reality, there’s little actual plucking of hairs in this common condition. Instead, patients habitually manipulate hair by twirling and tugging, which weakens the shafts and follicles and renders them more susceptible to everyday wear and tear. In some cases, individual hairs speed through their growth phases and others break off in mid-shaft. All of this contributes to the classic “uneven” look of TT.

Patients with TT tend to be in the 4-to-17 age range, and most have issues with unresolved anxiety that manifest in part with manipulation of the hair. Officially considered an impulse control disorder, TT in most cases belongs to the psychiatrist’s domain.

In this case, it was enormously helpful to have corroboration from the patient and his mother regarding his role in creating and perpetuating the problem. Had that not been the case—or in the event of other doubts as to the correct diagnosis—biopsy could have been performed to rule out most of the other items in the differential, particularly alopecia areata.

Interestingly enough, studies have shown that the more sharply defined the area of hair loss, the more likely the patient is to admit his/her role in its creation. However, as is often the case with scientific research, contradictory findings have also been made.

TREATMENT

Treatment of TT is problematic, since no medications have proven to be completely helpful. Psychiatrists use a combination of medication, cognitive behavioral therapy, and other behavior modifications that are designed to overcome the habitual component of the problem. Most cases of TT resolve on their own, but in severe cases that persist for years, permanent hair loss can result.

In this case, there was enough insight and motivation on the part of the patient and his family to stop the offending behavior and allow the hair to regrow.

ANSWER

The correct answer is trichotillomania (choice “c”). See Discussion for more information.

Alopecia mucinosa (choice “a”) is a rare cause of focal hair loss that can occur in children. However, it usually presents with papules or plaques, unlike the smooth skin surface seen here.

Alopecia areata (choice “b”), common in children, typically entails complete hair loss in a given area—or, as hair regrows, with hairs of equal length. The uneven hairs seen in trichotillomania help a great deal in distinguishing it from alopecia areata.

Traction alopecia (choice “d”) is focal hair loss caused by chronic tension related to hairstyling. Most common in African-American women, and typically affecting the frontal periphery of the scalp, it is an unlikely explanation for hair loss in a 10-year-old boy.

DISCUSSION

Trichotillomania (TT) means, literally, “hair-pulling madness.” But in reality, there’s little actual plucking of hairs in this common condition. Instead, patients habitually manipulate hair by twirling and tugging, which weakens the shafts and follicles and renders them more susceptible to everyday wear and tear. In some cases, individual hairs speed through their growth phases and others break off in mid-shaft. All of this contributes to the classic “uneven” look of TT.

Patients with TT tend to be in the 4-to-17 age range, and most have issues with unresolved anxiety that manifest in part with manipulation of the hair. Officially considered an impulse control disorder, TT in most cases belongs to the psychiatrist’s domain.

In this case, it was enormously helpful to have corroboration from the patient and his mother regarding his role in creating and perpetuating the problem. Had that not been the case—or in the event of other doubts as to the correct diagnosis—biopsy could have been performed to rule out most of the other items in the differential, particularly alopecia areata.

Interestingly enough, studies have shown that the more sharply defined the area of hair loss, the more likely the patient is to admit his/her role in its creation. However, as is often the case with scientific research, contradictory findings have also been made.

TREATMENT

Treatment of TT is problematic, since no medications have proven to be completely helpful. Psychiatrists use a combination of medication, cognitive behavioral therapy, and other behavior modifications that are designed to overcome the habitual component of the problem. Most cases of TT resolve on their own, but in severe cases that persist for years, permanent hair loss can result.

In this case, there was enough insight and motivation on the part of the patient and his family to stop the offending behavior and allow the hair to regrow.

NEW ORLEANS – Lower doses of quizartinib reduced worrisome QT-interval prolongation events without a loss of efficacy in patients with FLT3-ITD–positive relapsed or refractory acute myeloid leukemia, a phase II study shows.

In a 76-patient study, grade 2 QT-interval prolongation (QTcF) of more than 480-500 msec occurred in two patients (5%) on oral quizartinib 30 mg/day and in five patients (14%) on 60 mg/day, with no differences between groups in QTcF events of more than 500 msec (5% vs. 3%).

In addition, an increase in QTcF from baseline of more than 60 msec was seen in 19% of patients on the 60-mg dose and in 3% of those on the 30-mg dose, Dr. Jorge Cortes reported at the annual meeting of the American Society of Hematology.

About a third of patients with acute myeloid leukemia (AML) will have FLT3 internal tandem duplications (FLT3-ITD), which are associated with early relapse and poor survival in AML. Quizartinib has shown the highest single-agent activity among FMS-like tyrosine kinase 3 (FLT3)-targeted agents in this population, according to Dr. Cortes.

At last year’s ASH meeting, investigators presented results from a phase II study in which the investigational agent elicited responses in both FLT3-positive and -negative relapsed/refractory AML. The unprecedented results at doses of 90, 135, and 200 mg were partially eclipsed, however, by respective 46%, 39%, and 92% increases in QTcF from baseline of more than 60 msec, noted Dr. Cortes, chair of the AML section, department of leukemia, University of Texas M.D. Anderson Cancer Center, Houston.

The current study randomized 76 patients to quizartinib 30 mg or 60 mg continuous daily dosing for primary AML or AML secondary to myelodysplastic syndrome that relapsed or was refractory to first-line salvage therapy or prior hematopoietic stem cell transplantation. The coprimary endpoints were rate of grade 2 QTc prolongation and the composite complete remission rate, which included complete remission (CR), CR with incomplete platelet recovery, and CR with incomplete hematologic recovery.

In all, 92% of patients had FLT3 internal tandem duplications, and 58 of 60 evaluable patients had intermediate or poor cytogenetic risk. Their mean age was 55 years. Two patients were randomized but not treated.

Treatment with the 30-mg and 60-mg doses resulted in a composite CR rate of 47%, Dr. Cortes said. The median duration of response was 4.1 weeks in the 30-mg group and 20 weeks in the 60-mg group.

Two patients (5%) on the 30-mg dose and 1 patient (3%) on the 60-mg dose achieved CR; 1 patient (3%) in the 60-mg group had a CR with incomplete platelet recovery; and 16 patients (42%) in each arm had a CR with incomplete hematologic recovery.

Partial responses were also seen in 5 patients (13%) in the 30-mg group and 9 (24%) in the 60-mg group.

These results compare favorably with composite CR rates of 47%, 45%, and 42% with the 90-, 135-, and 200-mg doses used in the earlier study, Dr. Cortes observed.

Median overall survival in the current study was 20.7 weeks in the lower-dose group and 25.4 weeks with the 60-mg dose.

Importantly, 34% of patients were successfully bridged to transplant, extending median survival to 31 weeks for those on 30 mg of quizartinib and to 28.1 weeks for those given 60 mg.

"This study demonstrates there is certainly sustained efficacy with these lower doses of quizartinib and a decreased QT signal at doses of 30 and 60 mg compared with the higher doses we’ve tested in the past," Dr. Cortes concluded.

Grade 3/4 adverse events were mainly anemia (39%) in the 30-mg group and febrile neutropenia (36%) in the 60-mg group. Three patients required dose reductions due to QTc prolongation.

A global phase III randomized study of quizartinib in FLT3-ITD–positive patients in first relapse is planned to start in early 2014, he said.

Development of quizartinib has been somewhat rocky, with Astellas Pharma announcing in March 2013 it was ending its collaboration with Ambit Biosciences to develop FLT3 inhibitors including quizartinib.

Dr. Cortes reported research funding from Astellas Pharma, Arog, Novartis, and Ambit Biosciences, which is developing quizartinib, and consulting for Astellas, Arog, and Ambit.

[email protected]

NEW ORLEANS – Lower doses of quizartinib reduced worrisome QT-interval prolongation events without a loss of efficacy in patients with FLT3-ITD–positive relapsed or refractory acute myeloid leukemia, a phase II study shows.

In a 76-patient study, grade 2 QT-interval prolongation (QTcF) of more than 480-500 msec occurred in two patients (5%) on oral quizartinib 30 mg/day and in five patients (14%) on 60 mg/day, with no differences between groups in QTcF events of more than 500 msec (5% vs. 3%).

In addition, an increase in QTcF from baseline of more than 60 msec was seen in 19% of patients on the 60-mg dose and in 3% of those on the 30-mg dose, Dr. Jorge Cortes reported at the annual meeting of the American Society of Hematology.

About a third of patients with acute myeloid leukemia (AML) will have FLT3 internal tandem duplications (FLT3-ITD), which are associated with early relapse and poor survival in AML. Quizartinib has shown the highest single-agent activity among FMS-like tyrosine kinase 3 (FLT3)-targeted agents in this population, according to Dr. Cortes.

At last year’s ASH meeting, investigators presented results from a phase II study in which the investigational agent elicited responses in both FLT3-positive and -negative relapsed/refractory AML. The unprecedented results at doses of 90, 135, and 200 mg were partially eclipsed, however, by respective 46%, 39%, and 92% increases in QTcF from baseline of more than 60 msec, noted Dr. Cortes, chair of the AML section, department of leukemia, University of Texas M.D. Anderson Cancer Center, Houston.

The current study randomized 76 patients to quizartinib 30 mg or 60 mg continuous daily dosing for primary AML or AML secondary to myelodysplastic syndrome that relapsed or was refractory to first-line salvage therapy or prior hematopoietic stem cell transplantation. The coprimary endpoints were rate of grade 2 QTc prolongation and the composite complete remission rate, which included complete remission (CR), CR with incomplete platelet recovery, and CR with incomplete hematologic recovery.

In all, 92% of patients had FLT3 internal tandem duplications, and 58 of 60 evaluable patients had intermediate or poor cytogenetic risk. Their mean age was 55 years. Two patients were randomized but not treated.

Treatment with the 30-mg and 60-mg doses resulted in a composite CR rate of 47%, Dr. Cortes said. The median duration of response was 4.1 weeks in the 30-mg group and 20 weeks in the 60-mg group.

Two patients (5%) on the 30-mg dose and 1 patient (3%) on the 60-mg dose achieved CR; 1 patient (3%) in the 60-mg group had a CR with incomplete platelet recovery; and 16 patients (42%) in each arm had a CR with incomplete hematologic recovery.

Partial responses were also seen in 5 patients (13%) in the 30-mg group and 9 (24%) in the 60-mg group.

These results compare favorably with composite CR rates of 47%, 45%, and 42% with the 90-, 135-, and 200-mg doses used in the earlier study, Dr. Cortes observed.

Median overall survival in the current study was 20.7 weeks in the lower-dose group and 25.4 weeks with the 60-mg dose.

Importantly, 34% of patients were successfully bridged to transplant, extending median survival to 31 weeks for those on 30 mg of quizartinib and to 28.1 weeks for those given 60 mg.

"This study demonstrates there is certainly sustained efficacy with these lower doses of quizartinib and a decreased QT signal at doses of 30 and 60 mg compared with the higher doses we’ve tested in the past," Dr. Cortes concluded.

Grade 3/4 adverse events were mainly anemia (39%) in the 30-mg group and febrile neutropenia (36%) in the 60-mg group. Three patients required dose reductions due to QTc prolongation.

A global phase III randomized study of quizartinib in FLT3-ITD–positive patients in first relapse is planned to start in early 2014, he said.

Development of quizartinib has been somewhat rocky, with Astellas Pharma announcing in March 2013 it was ending its collaboration with Ambit Biosciences to develop FLT3 inhibitors including quizartinib.

Dr. Cortes reported research funding from Astellas Pharma, Arog, Novartis, and Ambit Biosciences, which is developing quizartinib, and consulting for Astellas, Arog, and Ambit.

[email protected]

NEW ORLEANS – Lower doses of quizartinib reduced worrisome QT-interval prolongation events without a loss of efficacy in patients with FLT3-ITD–positive relapsed or refractory acute myeloid leukemia, a phase II study shows.

In a 76-patient study, grade 2 QT-interval prolongation (QTcF) of more than 480-500 msec occurred in two patients (5%) on oral quizartinib 30 mg/day and in five patients (14%) on 60 mg/day, with no differences between groups in QTcF events of more than 500 msec (5% vs. 3%).

In addition, an increase in QTcF from baseline of more than 60 msec was seen in 19% of patients on the 60-mg dose and in 3% of those on the 30-mg dose, Dr. Jorge Cortes reported at the annual meeting of the American Society of Hematology.

About a third of patients with acute myeloid leukemia (AML) will have FLT3 internal tandem duplications (FLT3-ITD), which are associated with early relapse and poor survival in AML. Quizartinib has shown the highest single-agent activity among FMS-like tyrosine kinase 3 (FLT3)-targeted agents in this population, according to Dr. Cortes.

At last year’s ASH meeting, investigators presented results from a phase II study in which the investigational agent elicited responses in both FLT3-positive and -negative relapsed/refractory AML. The unprecedented results at doses of 90, 135, and 200 mg were partially eclipsed, however, by respective 46%, 39%, and 92% increases in QTcF from baseline of more than 60 msec, noted Dr. Cortes, chair of the AML section, department of leukemia, University of Texas M.D. Anderson Cancer Center, Houston.

The current study randomized 76 patients to quizartinib 30 mg or 60 mg continuous daily dosing for primary AML or AML secondary to myelodysplastic syndrome that relapsed or was refractory to first-line salvage therapy or prior hematopoietic stem cell transplantation. The coprimary endpoints were rate of grade 2 QTc prolongation and the composite complete remission rate, which included complete remission (CR), CR with incomplete platelet recovery, and CR with incomplete hematologic recovery.

In all, 92% of patients had FLT3 internal tandem duplications, and 58 of 60 evaluable patients had intermediate or poor cytogenetic risk. Their mean age was 55 years. Two patients were randomized but not treated.

Treatment with the 30-mg and 60-mg doses resulted in a composite CR rate of 47%, Dr. Cortes said. The median duration of response was 4.1 weeks in the 30-mg group and 20 weeks in the 60-mg group.

Two patients (5%) on the 30-mg dose and 1 patient (3%) on the 60-mg dose achieved CR; 1 patient (3%) in the 60-mg group had a CR with incomplete platelet recovery; and 16 patients (42%) in each arm had a CR with incomplete hematologic recovery.

Partial responses were also seen in 5 patients (13%) in the 30-mg group and 9 (24%) in the 60-mg group.

These results compare favorably with composite CR rates of 47%, 45%, and 42% with the 90-, 135-, and 200-mg doses used in the earlier study, Dr. Cortes observed.

Median overall survival in the current study was 20.7 weeks in the lower-dose group and 25.4 weeks with the 60-mg dose.

Importantly, 34% of patients were successfully bridged to transplant, extending median survival to 31 weeks for those on 30 mg of quizartinib and to 28.1 weeks for those given 60 mg.

"This study demonstrates there is certainly sustained efficacy with these lower doses of quizartinib and a decreased QT signal at doses of 30 and 60 mg compared with the higher doses we’ve tested in the past," Dr. Cortes concluded.

Grade 3/4 adverse events were mainly anemia (39%) in the 30-mg group and febrile neutropenia (36%) in the 60-mg group. Three patients required dose reductions due to QTc prolongation.

A global phase III randomized study of quizartinib in FLT3-ITD–positive patients in first relapse is planned to start in early 2014, he said.

Development of quizartinib has been somewhat rocky, with Astellas Pharma announcing in March 2013 it was ending its collaboration with Ambit Biosciences to develop FLT3 inhibitors including quizartinib.

Dr. Cortes reported research funding from Astellas Pharma, Arog, Novartis, and Ambit Biosciences, which is developing quizartinib, and consulting for Astellas, Arog, and Ambit.

[email protected]

Cabozantinib in metastatic prostate cancer^1,2

Researchers tested cabozantinib, a tyrosine-kinase inhibitor (TKI) against MET and vascular endothelial growth factor receptor 2 (VEGF), in a large phase 2 randomized discontinuation trial in 9 tumor types. A subset of 171 patients with castrateresistant prostate cancer (CRPC) was reported in this study. Patients were treated on open label for 12 weeks, and then if stable, were randomized to receive the active drug or placebo. The trial was suspended early by the study oversight committee because: a) Cabozantinib was too toxic for the study to continue. b) The prostate-specific antigen (PSA) level fell in most of the treated patients. c) In the initial 121 patients, there was an unexpected improvement in bone scans and decrease in pain in the lead-in stage of the study. d) Unexpected rapid soft tissue progression. Bone scans improved in 78% of patients, and in 12% there was complete remission. After further analysis, the following were true except for: a) Cabozantinib interfered with technetium-99, and thus, the responses were not real, but rather an artifact. b) The PSA did not correlate with improvement in bone pain. c) Markers of bone formation and resorption showed improvement, and there was no correlation with prior bisphosphonate therapy. d) Bone scan improvement correlated with improvement in soft tissue disease. 

Key points

The results in patients with prostate cancer were so striking – 72% of patients had regression in soft tissue lesions, and 68% of evaluable patients had improvement on bone scan, including complete resolution in 12% – that the subset analysis was published as a rapid communication.1,2 Because of very high response rates (5% at 12 weeks) and symptomatic improvement in the initial 122 patients who were enrolled, random assignment was discontinued. Bone markers improved in concert with the radiologic and clinical improvement. Answers c, a

Cabozantinib in metastatic prostate cancer^1,2

Researchers tested cabozantinib, a tyrosine-kinase inhibitor (TKI) against MET and vascular endothelial growth factor receptor 2 (VEGF), in a large phase 2 randomized discontinuation trial in 9 tumor types. A subset of 171 patients with castrateresistant prostate cancer (CRPC) was reported in this study. Patients were treated on open label for 12 weeks, and then if stable, were randomized to receive the active drug or placebo. The trial was suspended early by the study oversight committee because: a) Cabozantinib was too toxic for the study to continue. b) The prostate-specific antigen (PSA) level fell in most of the treated patients. c) In the initial 121 patients, there was an unexpected improvement in bone scans and decrease in pain in the lead-in stage of the study. d) Unexpected rapid soft tissue progression. Bone scans improved in 78% of patients, and in 12% there was complete remission. After further analysis, the following were true except for: a) Cabozantinib interfered with technetium-99, and thus, the responses were not real, but rather an artifact. b) The PSA did not correlate with improvement in bone pain. c) Markers of bone formation and resorption showed improvement, and there was no correlation with prior bisphosphonate therapy. d) Bone scan improvement correlated with improvement in soft tissue disease. 

Key points

The results in patients with prostate cancer were so striking – 72% of patients had regression in soft tissue lesions, and 68% of evaluable patients had improvement on bone scan, including complete resolution in 12% – that the subset analysis was published as a rapid communication.1,2 Because of very high response rates (5% at 12 weeks) and symptomatic improvement in the initial 122 patients who were enrolled, random assignment was discontinued. Bone markers improved in concert with the radiologic and clinical improvement. Answers c, a

Cabozantinib in metastatic prostate cancer^1,2

Researchers tested cabozantinib, a tyrosine-kinase inhibitor (TKI) against MET and vascular endothelial growth factor receptor 2 (VEGF), in a large phase 2 randomized discontinuation trial in 9 tumor types. A subset of 171 patients with castrateresistant prostate cancer (CRPC) was reported in this study. Patients were treated on open label for 12 weeks, and then if stable, were randomized to receive the active drug or placebo. The trial was suspended early by the study oversight committee because: a) Cabozantinib was too toxic for the study to continue. b) The prostate-specific antigen (PSA) level fell in most of the treated patients. c) In the initial 121 patients, there was an unexpected improvement in bone scans and decrease in pain in the lead-in stage of the study. d) Unexpected rapid soft tissue progression. Bone scans improved in 78% of patients, and in 12% there was complete remission. After further analysis, the following were true except for: a) Cabozantinib interfered with technetium-99, and thus, the responses were not real, but rather an artifact. b) The PSA did not correlate with improvement in bone pain. c) Markers of bone formation and resorption showed improvement, and there was no correlation with prior bisphosphonate therapy. d) Bone scan improvement correlated with improvement in soft tissue disease. 

Key points

The results in patients with prostate cancer were so striking – 72% of patients had regression in soft tissue lesions, and 68% of evaluable patients had improvement on bone scan, including complete resolution in 12% – that the subset analysis was published as a rapid communication.1,2 Because of very high response rates (5% at 12 weeks) and symptomatic improvement in the initial 122 patients who were enrolled, random assignment was discontinued. Bone markers improved in concert with the radiologic and clinical improvement. Answers c, a

Medical Education Library

A Best Practices Supplement to Skin & Allergy News®. This supplement was sponsored by Valeant Pharmaceuticals North America LLC.

• Introduction 
• Carac Cream (fluorouracil cream) 0.5%
• Zyclara (imiquimod) Cream 2.5% and 3.75%
• Summary
• IMPORTANT SAFETY INFORMATION

Faculty/Faculty Disclosure

Dr. Harper, MD
Clinical Associate Professor of Dermatology University of Alabama-Birmingham Dermatology and Skin Care Center of Birmingham, P.C.

Birmingham, Alabama

Dr. Harper reported that she is a consultant and speaker for Medicis Pharmaceutical Corporation, a division of Valeant Pharmaceuticals, and received compensation from Valeant for her assistance in developing the content of this article.

LINKS: Click Here for PDF.

Copyright © by Frontline Medical Communications Inc.

Medical Education Library

A Best Practices Supplement to Skin & Allergy News®. This supplement was sponsored by Valeant Pharmaceuticals North America LLC.

• Introduction 
• Carac Cream (fluorouracil cream) 0.5%
• Zyclara (imiquimod) Cream 2.5% and 3.75%
• Summary
• IMPORTANT SAFETY INFORMATION

Faculty/Faculty Disclosure

Dr. Harper, MD
Clinical Associate Professor of Dermatology University of Alabama-Birmingham Dermatology and Skin Care Center of Birmingham, P.C.

Birmingham, Alabama

Dr. Harper reported that she is a consultant and speaker for Medicis Pharmaceutical Corporation, a division of Valeant Pharmaceuticals, and received compensation from Valeant for her assistance in developing the content of this article.

LINKS: Click Here for PDF.

Copyright © by Frontline Medical Communications Inc.

Medical Education Library

A Best Practices Supplement to Skin & Allergy News®. This supplement was sponsored by Valeant Pharmaceuticals North America LLC.

• Introduction 
• Carac Cream (fluorouracil cream) 0.5%
• Zyclara (imiquimod) Cream 2.5% and 3.75%
• Summary
• IMPORTANT SAFETY INFORMATION

Faculty/Faculty Disclosure

Dr. Harper, MD
Clinical Associate Professor of Dermatology University of Alabama-Birmingham Dermatology and Skin Care Center of Birmingham, P.C.

Birmingham, Alabama

Dr. Harper reported that she is a consultant and speaker for Medicis Pharmaceutical Corporation, a division of Valeant Pharmaceuticals, and received compensation from Valeant for her assistance in developing the content of this article.

LINKS: Click Here for PDF.

Copyright © by Frontline Medical Communications Inc.

The code set of the 2014 Current Procedural Terminology (CPT), which took effect on January 1, includes several changes that affect all women’s health-care providers, including:

• a clarification of who should bill discharge-day management

• the addition of interprofessional telephone and Internet consultations

• new codes for image-guided fluid drainage

• new codes for fibroid embolization and laparoscopic ablation of fibroids.

There are also some new laboratory codes: one that captures the work of the noninvasive prenatal DNA test Harmony, and one to test for Trichomonas vaginalis. Finally, the code for anogenital examinations was revised to reflect current practice.

Medicare also has made some changes you should note, related to the levonorgestrel-releasing intrauterine system Skyla and billing for “incident to” services, and the type of provider who can order a fecal occult blood test. In addition, Medicare changes to some of the practice expense relative value units (RVUs) and geographic payment adjustor values will have an impact on some frequently used ObGyn services.

The changes to the CPT code set took effect January 1. Because of Health Insurance Portability and Accountability Act (HIPAA) requirements, insurers were required to accept new codes on that date.

CPT CODE CHANGES
Discharge-day management coding clarified
Codes 99238 and 99239 should be reported by the admitting provider for all services rendered on the date of discharge as long as the admission and discharge were not on the same date of service. Concurrent hospital services performed by the nonadmitting clinician on the date of discharge should be billed instead as a subsequent inpatient hospital encounter (codes 99231–99233).

Interprofessional phone and Web consultations now reimbursed
Most clinicians at one time or another end up giving advice to another health-care provider about the care of a patient he or she never sees and, up until 2014, there was no way to ask for reimbursement for this additional work. Starting on January 1, however, there were four new codes to allow a consultant clinician to report this work. These services, of a consulting physician who has specific specialty expertise, typically will be provided in complex or urgent situations where a timely face-to-face service with the patient may not be feasible.

The new codes are billed based on total documented cumulative time spent (to account for more than one telephone/Internet contact to complete the consultation request). The codes are for interprofessional telephone/Internet assessment and management service provided by a consultative physician including a verbal and written report to the patient’s treating/requesting physician or other qualified health-care professional, with varying time intervals for medical consultative discussion and review:

• 99446 5–10 minutes

• 99447 11–20 minutes

• 99448 21–30 minutes

• 99449 31 minutes or more

Like all new codes, these have some very specific requirements:

• The billing physician cannot have had a face-to-face encounter with the patient within the past 14 days. If the consultation leads to scheduling a face-to-face appointment or surgery within 14 days, these codes cannot be reported.

• If the consultation is to accept transfer of care or arrange for an immediate face-to-face encounter with the consulting physician, these codes should not be billed.

• The documentation must include a review of all pertinent medical records, studies, medications, etc., that may be required to render an opinion on how to proceed with care of the patient, and reviewing of any data is not reported separately.

• The patient either can be new to the consultant or can be established (with a new or an exacerbated problem).

• The majority of the service (more than 50%) must be devoted to the medical consultative verbal/Internet real-time discussion, and not be reported more than once within a 7-day interval.

• The request for advice by the qualified health-care professional must be documented in the patient’s medical record, including the reason for the request.

• There must be a verbal opinion report and written report from the consultant to the treating physician.

• The treating physician who asks for the telephone/Internet advice can report a prolonged services, non–face-to-face code if the time exceeds the typical time of a problem E/M service by 30 minutes to get credit for the discussion with the consultant.

CASE
As an example, Dr. Moody, Mary’s primary care physician, has ordered a computed tomography scan for her due to reports of sharp epigastric pain. A large mass in the area of the right ovary is detected. Dr. Moody phones Dr. Gerard, the patient’s ObGyn of record, for an opinion about additional testing for this mass. Mary was last seen by Dr. Gerard at her well-woman visit 8 months ago; there were no complaints reported or problems detected.

Dr. Gerard recommends that additional views of the mass be obtained and that a CA 125 test be performed due to Mary’s family history of ovarian cancer. He also recommends that Mary be sent for a consultation with a gynecologic oncologist as soon as possible. The total time spent on this consultation is 15 minutes, and Dr. Gerard reports Mary’s consultative session to her insurance company with CPT code 99447.

Image-guided drainage of a fluid collection
CPT code 10030 has been added to report image-guided drainage of a fluid collection using a catheter for areas just under the skin. This code would be used if the patient had an abscess, hematoma, seroma, lymphocele, or cyst that was drained percutaneously. For instance, this code could be reported for a hematoma located in the abdominal wall or just under the skin. The code bundles image guidance, but it can be reported more than once if there is more than one collection drained with a separate catheter.

CPT also has added additional codes for image-guided fluid collection drainage by catheter (eg, abscess, hematoma, seroma, lymphocele, cyst) of visceral, peritoneal, or retroperitoneal collections. The codes for these procedures are:

• 49405...; visceral (eg, kidney, liver, spleen, lung/mediastinum), percutaneous

• 49406...; peritoneal or retroperitoneal, percutaneous

• 49407...; peritoneal or retroperitoneal, transvaginal or transrectal

With the addition of these new codes, the old code 58823 has been eliminated.

Uterine fibroid treatment
There are two changes with regard to the treatment of uterine fibroids. First, CPT code 37210 (Uterine fibroid embolization [UFE, embolization of the uterine arteries to treat uterine fibroids, leiomyomata], percutaneous approach inclusive of vascular access, vessel selection, embolization, and all radiologic supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the procedure) has been eliminated and replaced by a more general code that will apply to any tumor or organ. This new code is 37243 (Vascular embolization or occlusion, inclusive of all radiological supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the intervention; for tumors, organ ischemia, or infarction).

Second, there is now a Category III code for the laparoscopic ablation of uterine fibroids: 0336T (Laparoscopy, surgical, ablation of uterine fibroid[s], including intraoperative ultrasound guidance and monitoring, radiofrequency). Clinical research has shown that radiofrequency ablation (RFA) is effective in treating fibroids, resolving associated symptoms in more than 80% of treated patients. Because RFA is not yet a standard of care, this Category III code must be reported in order for data on its use to be collected. Under CPT rules, you may not use an unlisted code in place of the Category III code for this procedure. If you are performing RFA, it may be considered experimental by some payers, but you can still make a case for payment with the submission of adequate documentation with the claim in the form of peer-reviewed articles and the patient’s circumstances that preclude more standard surgeries.

Anogenital examination coding
Code 99170 was revised to reflect current practice. The procedure is not always performed with a colposcope, but usually requires digital imaging for legal recoding and documentation. The revised code reads “anogenital examination, magnified, in childhood for suspected trauma, including image recording when performed.” Moderate sedation, if performed, may be billed separately using code 99143-99150.

LABORATORY CODE CHANGES
Cell-free DNA testing code added
As of January 1, there is a new code to report cell-free prenatal DNA testing to screen for fetal aneuploidy. This new code is 81507 (Fetal aneuploidy [trisomy 21, 18, and 13] DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy).

Related Article: Update on Obstetrics Jaimey Pauli, MD, and John T. Repke, MD (January 2014)

In addition, the code 84112, which used to be defined as “placental alpha microglobulin-1 (PAMG-1), cervicovaginal secretion, qualitative,” has been revised. The revision was done to make it clear that it can be ordered for other proteins that are tested in amniotic fluid. Code 84112 is now defined as follows: Evaluation of cervicovaginal fluid for specific amniotic fluid protein(s) (eg, placental alpha microglobulin-1 [PAMG-1], placental protein 12 [PP12], alpha-fetoprotein), qualitative, each specimen.

This test is normally ordered to determine whether the fetal membranes have ruptured, but this is not a Clinical Laboratory Improvement Amendments (CLIA) waived or Provider Performed Microscopy Procedures (PPMP) test. Therefore, only the laboratory with the applicable CLIA certificate can bill for it.

There are now two code options for T vaginalis testing
To the existing code 87660 (direct probe technique) is added the new code 87661, T vaginalis, amplified probe technique.

Three new codes for the flu vaccine:

• 90673, Flublok (effective January 2013)

• 90686, Fluzone, preservative-free (effective December 2012)

• 90688, FluLaval (effective August 2013)

In addition, Medicare has deleted code G2033, which was used to report Flublok. It will now accept the CPT code 90673 for this influenza product.

Keep in mind that reporting the administration of the influenza vaccine is different for Medicare than private payers. Administration code G0008 and diagnosis code V04.81 would be reported in conjunction with the appropriate vaccine code for Medicare, while CPT instructs you to report 90471 instead for the administration.

MEDICARE CODING CHANGES
Skyla. The new code is J7301, levonorgestrel-releasing intrauterine contraceptive, 13.5 mg. This replaces the temporary code Q0090, which was added by Medicare on July 1, 2013.

Related Article: 5 IUD myths dispelled Anne A. Moore, DNP, APN (September 2013)

More providers can order fecal occult blood tests. To expand access to screening fecal occult blood testing, Medicare has revised the rules on who can order these tests. Effective January 1, 2014, not only a physician but also the billing physician’s assistant (PA), certified nurse specialist (CNS), or nurse practitioner (NP) can order the test. But as before January 1, the physician, PA, CNS, or NP is responsible for using the results of the screening test in the overall management of the patient’s medical care.

“Incident to” providers must be state-licensed. Medicare recently became aware that it was being billed in several situations for ‘‘incident to’’ services that were provided by auxiliary personnel (rather than the physician or practitioner billing for the services) who did not meet the state standards for those services. For this reason, Medicare has revised the “incident to” rules to make it clear that the person who is assigned to provide the aspect of the service must be licensed within their state to provide the services performed.

SGR fate, and your reimbursement, unknown at this time
At the time this article was finalized, there was no information about the fate of the Medicare payment mechanism for 2014. If the sustained growth formula used to calculate the Medicare conversion factor for physician reimbursement is not fixed by Congress, the projected 2014 conversion factor will be $27.2006, a decrease from the current conversion factor of $34.023.
But even without concrete, final information on this complicating factor, changes to the geographic adjustment units (which in turn determine the payment allowance for physicians based on their practice location), as well as changes to the practice expense RVUs for such office procedures as urodynamic testing, may spell decreased payments in 2014 from Medicare or payers who use Medicare as the basis for reimbursement.
Some states will fare better than others. The geographic payment cost index for all but a handful of states will be adjusted downward. The good news is that if you practice in Alabama, Alaska, Colorado, Connecticut, Delaware, Louisiana, Minnesota, New Hampshire, New Mexico, New York, Virginia, certain areas of California (San Francisco, Los Angeles, Marin County), and the Washington DC area, your geographic factors will increase. This increase may offset any decrease in the RVUs.
ObGyn reimbursements hardest hit by decreased RVUs. The RVUs for 2014 for the technical component of all the urodynamic testing codes will be reduced by 6% to 40%, with the biggest hit coming to codes 51726-51727 (complex cystometrogram with urethral and voiding pressure studies). In-office procedures such as endometrial ablation, endometrial cryoablation, and hysteroscopic sterilization will see around an 8% decrease to the practice expense RVUs. This same reduction will be noticed in the technical-component reimbursement for gynecologic and obstetric ultrasounds, with the notable exception that the RVUs were increased for umbilical artery Doppler.
The final result for increased or decreased payments via the relative value system will therefore depend on your practice location, and whether you are billing the technical component only for many of these procedures (and, of course, the final outcome of the SGR). WE WANT TO HEAR FROM YOU!
Drop us a line and let us know what you think about current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected]

The code set of the 2014 Current Procedural Terminology (CPT), which took effect on January 1, includes several changes that affect all women’s health-care providers, including:

• a clarification of who should bill discharge-day management

• the addition of interprofessional telephone and Internet consultations

• new codes for image-guided fluid drainage

• new codes for fibroid embolization and laparoscopic ablation of fibroids.

There are also some new laboratory codes: one that captures the work of the noninvasive prenatal DNA test Harmony, and one to test for Trichomonas vaginalis. Finally, the code for anogenital examinations was revised to reflect current practice.

Medicare also has made some changes you should note, related to the levonorgestrel-releasing intrauterine system Skyla and billing for “incident to” services, and the type of provider who can order a fecal occult blood test. In addition, Medicare changes to some of the practice expense relative value units (RVUs) and geographic payment adjustor values will have an impact on some frequently used ObGyn services.

The changes to the CPT code set took effect January 1. Because of Health Insurance Portability and Accountability Act (HIPAA) requirements, insurers were required to accept new codes on that date.

CPT CODE CHANGES
Discharge-day management coding clarified
Codes 99238 and 99239 should be reported by the admitting provider for all services rendered on the date of discharge as long as the admission and discharge were not on the same date of service. Concurrent hospital services performed by the nonadmitting clinician on the date of discharge should be billed instead as a subsequent inpatient hospital encounter (codes 99231–99233).

Interprofessional phone and Web consultations now reimbursed
Most clinicians at one time or another end up giving advice to another health-care provider about the care of a patient he or she never sees and, up until 2014, there was no way to ask for reimbursement for this additional work. Starting on January 1, however, there were four new codes to allow a consultant clinician to report this work. These services, of a consulting physician who has specific specialty expertise, typically will be provided in complex or urgent situations where a timely face-to-face service with the patient may not be feasible.

The new codes are billed based on total documented cumulative time spent (to account for more than one telephone/Internet contact to complete the consultation request). The codes are for interprofessional telephone/Internet assessment and management service provided by a consultative physician including a verbal and written report to the patient’s treating/requesting physician or other qualified health-care professional, with varying time intervals for medical consultative discussion and review:

• 99446 5–10 minutes

• 99447 11–20 minutes

• 99448 21–30 minutes

• 99449 31 minutes or more

Like all new codes, these have some very specific requirements:

• The billing physician cannot have had a face-to-face encounter with the patient within the past 14 days. If the consultation leads to scheduling a face-to-face appointment or surgery within 14 days, these codes cannot be reported.

• If the consultation is to accept transfer of care or arrange for an immediate face-to-face encounter with the consulting physician, these codes should not be billed.

• The documentation must include a review of all pertinent medical records, studies, medications, etc., that may be required to render an opinion on how to proceed with care of the patient, and reviewing of any data is not reported separately.

• The patient either can be new to the consultant or can be established (with a new or an exacerbated problem).

• The majority of the service (more than 50%) must be devoted to the medical consultative verbal/Internet real-time discussion, and not be reported more than once within a 7-day interval.

• The request for advice by the qualified health-care professional must be documented in the patient’s medical record, including the reason for the request.

• There must be a verbal opinion report and written report from the consultant to the treating physician.

• The treating physician who asks for the telephone/Internet advice can report a prolonged services, non–face-to-face code if the time exceeds the typical time of a problem E/M service by 30 minutes to get credit for the discussion with the consultant.

CASE
As an example, Dr. Moody, Mary’s primary care physician, has ordered a computed tomography scan for her due to reports of sharp epigastric pain. A large mass in the area of the right ovary is detected. Dr. Moody phones Dr. Gerard, the patient’s ObGyn of record, for an opinion about additional testing for this mass. Mary was last seen by Dr. Gerard at her well-woman visit 8 months ago; there were no complaints reported or problems detected.

Dr. Gerard recommends that additional views of the mass be obtained and that a CA 125 test be performed due to Mary’s family history of ovarian cancer. He also recommends that Mary be sent for a consultation with a gynecologic oncologist as soon as possible. The total time spent on this consultation is 15 minutes, and Dr. Gerard reports Mary’s consultative session to her insurance company with CPT code 99447.

Image-guided drainage of a fluid collection
CPT code 10030 has been added to report image-guided drainage of a fluid collection using a catheter for areas just under the skin. This code would be used if the patient had an abscess, hematoma, seroma, lymphocele, or cyst that was drained percutaneously. For instance, this code could be reported for a hematoma located in the abdominal wall or just under the skin. The code bundles image guidance, but it can be reported more than once if there is more than one collection drained with a separate catheter.

CPT also has added additional codes for image-guided fluid collection drainage by catheter (eg, abscess, hematoma, seroma, lymphocele, cyst) of visceral, peritoneal, or retroperitoneal collections. The codes for these procedures are:

• 49405...; visceral (eg, kidney, liver, spleen, lung/mediastinum), percutaneous

• 49406...; peritoneal or retroperitoneal, percutaneous

• 49407...; peritoneal or retroperitoneal, transvaginal or transrectal

With the addition of these new codes, the old code 58823 has been eliminated.

Uterine fibroid treatment
There are two changes with regard to the treatment of uterine fibroids. First, CPT code 37210 (Uterine fibroid embolization [UFE, embolization of the uterine arteries to treat uterine fibroids, leiomyomata], percutaneous approach inclusive of vascular access, vessel selection, embolization, and all radiologic supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the procedure) has been eliminated and replaced by a more general code that will apply to any tumor or organ. This new code is 37243 (Vascular embolization or occlusion, inclusive of all radiological supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the intervention; for tumors, organ ischemia, or infarction).

Second, there is now a Category III code for the laparoscopic ablation of uterine fibroids: 0336T (Laparoscopy, surgical, ablation of uterine fibroid[s], including intraoperative ultrasound guidance and monitoring, radiofrequency). Clinical research has shown that radiofrequency ablation (RFA) is effective in treating fibroids, resolving associated symptoms in more than 80% of treated patients. Because RFA is not yet a standard of care, this Category III code must be reported in order for data on its use to be collected. Under CPT rules, you may not use an unlisted code in place of the Category III code for this procedure. If you are performing RFA, it may be considered experimental by some payers, but you can still make a case for payment with the submission of adequate documentation with the claim in the form of peer-reviewed articles and the patient’s circumstances that preclude more standard surgeries.

Anogenital examination coding
Code 99170 was revised to reflect current practice. The procedure is not always performed with a colposcope, but usually requires digital imaging for legal recoding and documentation. The revised code reads “anogenital examination, magnified, in childhood for suspected trauma, including image recording when performed.” Moderate sedation, if performed, may be billed separately using code 99143-99150.

LABORATORY CODE CHANGES
Cell-free DNA testing code added
As of January 1, there is a new code to report cell-free prenatal DNA testing to screen for fetal aneuploidy. This new code is 81507 (Fetal aneuploidy [trisomy 21, 18, and 13] DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy).

Related Article: Update on Obstetrics Jaimey Pauli, MD, and John T. Repke, MD (January 2014)

In addition, the code 84112, which used to be defined as “placental alpha microglobulin-1 (PAMG-1), cervicovaginal secretion, qualitative,” has been revised. The revision was done to make it clear that it can be ordered for other proteins that are tested in amniotic fluid. Code 84112 is now defined as follows: Evaluation of cervicovaginal fluid for specific amniotic fluid protein(s) (eg, placental alpha microglobulin-1 [PAMG-1], placental protein 12 [PP12], alpha-fetoprotein), qualitative, each specimen.

This test is normally ordered to determine whether the fetal membranes have ruptured, but this is not a Clinical Laboratory Improvement Amendments (CLIA) waived or Provider Performed Microscopy Procedures (PPMP) test. Therefore, only the laboratory with the applicable CLIA certificate can bill for it.

There are now two code options for T vaginalis testing
To the existing code 87660 (direct probe technique) is added the new code 87661, T vaginalis, amplified probe technique.

Three new codes for the flu vaccine:

• 90673, Flublok (effective January 2013)

• 90686, Fluzone, preservative-free (effective December 2012)

• 90688, FluLaval (effective August 2013)

In addition, Medicare has deleted code G2033, which was used to report Flublok. It will now accept the CPT code 90673 for this influenza product.

Keep in mind that reporting the administration of the influenza vaccine is different for Medicare than private payers. Administration code G0008 and diagnosis code V04.81 would be reported in conjunction with the appropriate vaccine code for Medicare, while CPT instructs you to report 90471 instead for the administration.

MEDICARE CODING CHANGES
Skyla. The new code is J7301, levonorgestrel-releasing intrauterine contraceptive, 13.5 mg. This replaces the temporary code Q0090, which was added by Medicare on July 1, 2013.

Related Article: 5 IUD myths dispelled Anne A. Moore, DNP, APN (September 2013)

More providers can order fecal occult blood tests. To expand access to screening fecal occult blood testing, Medicare has revised the rules on who can order these tests. Effective January 1, 2014, not only a physician but also the billing physician’s assistant (PA), certified nurse specialist (CNS), or nurse practitioner (NP) can order the test. But as before January 1, the physician, PA, CNS, or NP is responsible for using the results of the screening test in the overall management of the patient’s medical care.

“Incident to” providers must be state-licensed. Medicare recently became aware that it was being billed in several situations for ‘‘incident to’’ services that were provided by auxiliary personnel (rather than the physician or practitioner billing for the services) who did not meet the state standards for those services. For this reason, Medicare has revised the “incident to” rules to make it clear that the person who is assigned to provide the aspect of the service must be licensed within their state to provide the services performed.

SGR fate, and your reimbursement, unknown at this time
At the time this article was finalized, there was no information about the fate of the Medicare payment mechanism for 2014. If the sustained growth formula used to calculate the Medicare conversion factor for physician reimbursement is not fixed by Congress, the projected 2014 conversion factor will be $27.2006, a decrease from the current conversion factor of $34.023.
But even without concrete, final information on this complicating factor, changes to the geographic adjustment units (which in turn determine the payment allowance for physicians based on their practice location), as well as changes to the practice expense RVUs for such office procedures as urodynamic testing, may spell decreased payments in 2014 from Medicare or payers who use Medicare as the basis for reimbursement.
Some states will fare better than others. The geographic payment cost index for all but a handful of states will be adjusted downward. The good news is that if you practice in Alabama, Alaska, Colorado, Connecticut, Delaware, Louisiana, Minnesota, New Hampshire, New Mexico, New York, Virginia, certain areas of California (San Francisco, Los Angeles, Marin County), and the Washington DC area, your geographic factors will increase. This increase may offset any decrease in the RVUs.
ObGyn reimbursements hardest hit by decreased RVUs. The RVUs for 2014 for the technical component of all the urodynamic testing codes will be reduced by 6% to 40%, with the biggest hit coming to codes 51726-51727 (complex cystometrogram with urethral and voiding pressure studies). In-office procedures such as endometrial ablation, endometrial cryoablation, and hysteroscopic sterilization will see around an 8% decrease to the practice expense RVUs. This same reduction will be noticed in the technical-component reimbursement for gynecologic and obstetric ultrasounds, with the notable exception that the RVUs were increased for umbilical artery Doppler.
The final result for increased or decreased payments via the relative value system will therefore depend on your practice location, and whether you are billing the technical component only for many of these procedures (and, of course, the final outcome of the SGR). WE WANT TO HEAR FROM YOU!
Drop us a line and let us know what you think about current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected]

The code set of the 2014 Current Procedural Terminology (CPT), which took effect on January 1, includes several changes that affect all women’s health-care providers, including:

• a clarification of who should bill discharge-day management

• the addition of interprofessional telephone and Internet consultations

• new codes for image-guided fluid drainage

• new codes for fibroid embolization and laparoscopic ablation of fibroids.

There are also some new laboratory codes: one that captures the work of the noninvasive prenatal DNA test Harmony, and one to test for Trichomonas vaginalis. Finally, the code for anogenital examinations was revised to reflect current practice.

Medicare also has made some changes you should note, related to the levonorgestrel-releasing intrauterine system Skyla and billing for “incident to” services, and the type of provider who can order a fecal occult blood test. In addition, Medicare changes to some of the practice expense relative value units (RVUs) and geographic payment adjustor values will have an impact on some frequently used ObGyn services.

The changes to the CPT code set took effect January 1. Because of Health Insurance Portability and Accountability Act (HIPAA) requirements, insurers were required to accept new codes on that date.

CPT CODE CHANGES
Discharge-day management coding clarified
Codes 99238 and 99239 should be reported by the admitting provider for all services rendered on the date of discharge as long as the admission and discharge were not on the same date of service. Concurrent hospital services performed by the nonadmitting clinician on the date of discharge should be billed instead as a subsequent inpatient hospital encounter (codes 99231–99233).

Interprofessional phone and Web consultations now reimbursed
Most clinicians at one time or another end up giving advice to another health-care provider about the care of a patient he or she never sees and, up until 2014, there was no way to ask for reimbursement for this additional work. Starting on January 1, however, there were four new codes to allow a consultant clinician to report this work. These services, of a consulting physician who has specific specialty expertise, typically will be provided in complex or urgent situations where a timely face-to-face service with the patient may not be feasible.

The new codes are billed based on total documented cumulative time spent (to account for more than one telephone/Internet contact to complete the consultation request). The codes are for interprofessional telephone/Internet assessment and management service provided by a consultative physician including a verbal and written report to the patient’s treating/requesting physician or other qualified health-care professional, with varying time intervals for medical consultative discussion and review:

• 99446 5–10 minutes

• 99447 11–20 minutes

• 99448 21–30 minutes

• 99449 31 minutes or more

Like all new codes, these have some very specific requirements:

• The billing physician cannot have had a face-to-face encounter with the patient within the past 14 days. If the consultation leads to scheduling a face-to-face appointment or surgery within 14 days, these codes cannot be reported.

• If the consultation is to accept transfer of care or arrange for an immediate face-to-face encounter with the consulting physician, these codes should not be billed.

• The documentation must include a review of all pertinent medical records, studies, medications, etc., that may be required to render an opinion on how to proceed with care of the patient, and reviewing of any data is not reported separately.

• The patient either can be new to the consultant or can be established (with a new or an exacerbated problem).

• The majority of the service (more than 50%) must be devoted to the medical consultative verbal/Internet real-time discussion, and not be reported more than once within a 7-day interval.

• The request for advice by the qualified health-care professional must be documented in the patient’s medical record, including the reason for the request.

• There must be a verbal opinion report and written report from the consultant to the treating physician.

• The treating physician who asks for the telephone/Internet advice can report a prolonged services, non–face-to-face code if the time exceeds the typical time of a problem E/M service by 30 minutes to get credit for the discussion with the consultant.

CASE
As an example, Dr. Moody, Mary’s primary care physician, has ordered a computed tomography scan for her due to reports of sharp epigastric pain. A large mass in the area of the right ovary is detected. Dr. Moody phones Dr. Gerard, the patient’s ObGyn of record, for an opinion about additional testing for this mass. Mary was last seen by Dr. Gerard at her well-woman visit 8 months ago; there were no complaints reported or problems detected.

Dr. Gerard recommends that additional views of the mass be obtained and that a CA 125 test be performed due to Mary’s family history of ovarian cancer. He also recommends that Mary be sent for a consultation with a gynecologic oncologist as soon as possible. The total time spent on this consultation is 15 minutes, and Dr. Gerard reports Mary’s consultative session to her insurance company with CPT code 99447.

Image-guided drainage of a fluid collection
CPT code 10030 has been added to report image-guided drainage of a fluid collection using a catheter for areas just under the skin. This code would be used if the patient had an abscess, hematoma, seroma, lymphocele, or cyst that was drained percutaneously. For instance, this code could be reported for a hematoma located in the abdominal wall or just under the skin. The code bundles image guidance, but it can be reported more than once if there is more than one collection drained with a separate catheter.

CPT also has added additional codes for image-guided fluid collection drainage by catheter (eg, abscess, hematoma, seroma, lymphocele, cyst) of visceral, peritoneal, or retroperitoneal collections. The codes for these procedures are:

• 49405...; visceral (eg, kidney, liver, spleen, lung/mediastinum), percutaneous

• 49406...; peritoneal or retroperitoneal, percutaneous

• 49407...; peritoneal or retroperitoneal, transvaginal or transrectal

With the addition of these new codes, the old code 58823 has been eliminated.

Uterine fibroid treatment
There are two changes with regard to the treatment of uterine fibroids. First, CPT code 37210 (Uterine fibroid embolization [UFE, embolization of the uterine arteries to treat uterine fibroids, leiomyomata], percutaneous approach inclusive of vascular access, vessel selection, embolization, and all radiologic supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the procedure) has been eliminated and replaced by a more general code that will apply to any tumor or organ. This new code is 37243 (Vascular embolization or occlusion, inclusive of all radiological supervision and interpretation, intraprocedural roadmapping, and imaging guidance necessary to complete the intervention; for tumors, organ ischemia, or infarction).

Second, there is now a Category III code for the laparoscopic ablation of uterine fibroids: 0336T (Laparoscopy, surgical, ablation of uterine fibroid[s], including intraoperative ultrasound guidance and monitoring, radiofrequency). Clinical research has shown that radiofrequency ablation (RFA) is effective in treating fibroids, resolving associated symptoms in more than 80% of treated patients. Because RFA is not yet a standard of care, this Category III code must be reported in order for data on its use to be collected. Under CPT rules, you may not use an unlisted code in place of the Category III code for this procedure. If you are performing RFA, it may be considered experimental by some payers, but you can still make a case for payment with the submission of adequate documentation with the claim in the form of peer-reviewed articles and the patient’s circumstances that preclude more standard surgeries.

Anogenital examination coding
Code 99170 was revised to reflect current practice. The procedure is not always performed with a colposcope, but usually requires digital imaging for legal recoding and documentation. The revised code reads “anogenital examination, magnified, in childhood for suspected trauma, including image recording when performed.” Moderate sedation, if performed, may be billed separately using code 99143-99150.

LABORATORY CODE CHANGES
Cell-free DNA testing code added
As of January 1, there is a new code to report cell-free prenatal DNA testing to screen for fetal aneuploidy. This new code is 81507 (Fetal aneuploidy [trisomy 21, 18, and 13] DNA sequence analysis of selected regions using maternal plasma, algorithm reported as a risk score for each trisomy).

Related Article: Update on Obstetrics Jaimey Pauli, MD, and John T. Repke, MD (January 2014)

In addition, the code 84112, which used to be defined as “placental alpha microglobulin-1 (PAMG-1), cervicovaginal secretion, qualitative,” has been revised. The revision was done to make it clear that it can be ordered for other proteins that are tested in amniotic fluid. Code 84112 is now defined as follows: Evaluation of cervicovaginal fluid for specific amniotic fluid protein(s) (eg, placental alpha microglobulin-1 [PAMG-1], placental protein 12 [PP12], alpha-fetoprotein), qualitative, each specimen.

This test is normally ordered to determine whether the fetal membranes have ruptured, but this is not a Clinical Laboratory Improvement Amendments (CLIA) waived or Provider Performed Microscopy Procedures (PPMP) test. Therefore, only the laboratory with the applicable CLIA certificate can bill for it.

There are now two code options for T vaginalis testing
To the existing code 87660 (direct probe technique) is added the new code 87661, T vaginalis, amplified probe technique.

Three new codes for the flu vaccine:

• 90673, Flublok (effective January 2013)

• 90686, Fluzone, preservative-free (effective December 2012)

• 90688, FluLaval (effective August 2013)

In addition, Medicare has deleted code G2033, which was used to report Flublok. It will now accept the CPT code 90673 for this influenza product.

Keep in mind that reporting the administration of the influenza vaccine is different for Medicare than private payers. Administration code G0008 and diagnosis code V04.81 would be reported in conjunction with the appropriate vaccine code for Medicare, while CPT instructs you to report 90471 instead for the administration.

MEDICARE CODING CHANGES
Skyla. The new code is J7301, levonorgestrel-releasing intrauterine contraceptive, 13.5 mg. This replaces the temporary code Q0090, which was added by Medicare on July 1, 2013.

Related Article: 5 IUD myths dispelled Anne A. Moore, DNP, APN (September 2013)

More providers can order fecal occult blood tests. To expand access to screening fecal occult blood testing, Medicare has revised the rules on who can order these tests. Effective January 1, 2014, not only a physician but also the billing physician’s assistant (PA), certified nurse specialist (CNS), or nurse practitioner (NP) can order the test. But as before January 1, the physician, PA, CNS, or NP is responsible for using the results of the screening test in the overall management of the patient’s medical care.

“Incident to” providers must be state-licensed. Medicare recently became aware that it was being billed in several situations for ‘‘incident to’’ services that were provided by auxiliary personnel (rather than the physician or practitioner billing for the services) who did not meet the state standards for those services. For this reason, Medicare has revised the “incident to” rules to make it clear that the person who is assigned to provide the aspect of the service must be licensed within their state to provide the services performed.

SGR fate, and your reimbursement, unknown at this time
At the time this article was finalized, there was no information about the fate of the Medicare payment mechanism for 2014. If the sustained growth formula used to calculate the Medicare conversion factor for physician reimbursement is not fixed by Congress, the projected 2014 conversion factor will be $27.2006, a decrease from the current conversion factor of $34.023.
But even without concrete, final information on this complicating factor, changes to the geographic adjustment units (which in turn determine the payment allowance for physicians based on their practice location), as well as changes to the practice expense RVUs for such office procedures as urodynamic testing, may spell decreased payments in 2014 from Medicare or payers who use Medicare as the basis for reimbursement.
Some states will fare better than others. The geographic payment cost index for all but a handful of states will be adjusted downward. The good news is that if you practice in Alabama, Alaska, Colorado, Connecticut, Delaware, Louisiana, Minnesota, New Hampshire, New Mexico, New York, Virginia, certain areas of California (San Francisco, Los Angeles, Marin County), and the Washington DC area, your geographic factors will increase. This increase may offset any decrease in the RVUs.
ObGyn reimbursements hardest hit by decreased RVUs. The RVUs for 2014 for the technical component of all the urodynamic testing codes will be reduced by 6% to 40%, with the biggest hit coming to codes 51726-51727 (complex cystometrogram with urethral and voiding pressure studies). In-office procedures such as endometrial ablation, endometrial cryoablation, and hysteroscopic sterilization will see around an 8% decrease to the practice expense RVUs. This same reduction will be noticed in the technical-component reimbursement for gynecologic and obstetric ultrasounds, with the notable exception that the RVUs were increased for umbilical artery Doppler.
The final result for increased or decreased payments via the relative value system will therefore depend on your practice location, and whether you are billing the technical component only for many of these procedures (and, of course, the final outcome of the SGR). WE WANT TO HEAR FROM YOU!
Drop us a line and let us know what you think about current articles, which topics you'd like to see covered in future issues, and what challenges you face in daily practice. Tell us what you think by emailing us at: [email protected]

Background

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that received approval from the Food and Drug Administration in 1991 as part of adjuvant chemotherapy regimens for colorectal cancer. The addition of levamisole to 5-flouroruacil (5-FU) was first evaluated by the North Central Cancer Treatment Group in a 3-arm clinical trial that found that 5-FUlevamisole for 12 months was superior to either surgery alone or surgery followed by levamisole alone (recurrence rate was reduced by 40% and the death rate by 33% in Dukes’ C colon cancer).1 A subsequent trial intergroup trial randomized patients with Dukes’ B2 and C colon cancer to surgery alone or 1 year of adjuvant levamisole or 5FUlevamisole and confirmed the efficacy of 5FUlevamisole with respect to disease free survival and overall survival.2 As a result, adjuvant chemotherapy became the standard for stage III colon cancer as reported by an National Cancer Institute consensus development panel.3 Subsequently, primarily because of toxicity reasons, leucovorin replaced levamisole in most adjuvant chemotheraoy regimens for stage III colorectal cancer. Clinical toxicity of levamisole was noted as early as 1976 when several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978, presenting primarily as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. In the early 1990s, levamisole became unavailable for human use in the United States due to toxicity concerns. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy. Recently, several persons have developed a novel syndrome characterized by necrotic noses and ears, leg ulcers, agranulocytosis, thrombovasculopathy, and positive antineutrophil cytoplasmic antibodies (ANCAs) as a result of the drug cocaine being adulterated with levamisole. We describe the drug below.

Background

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that received approval from the Food and Drug Administration in 1991 as part of adjuvant chemotherapy regimens for colorectal cancer. The addition of levamisole to 5-flouroruacil (5-FU) was first evaluated by the North Central Cancer Treatment Group in a 3-arm clinical trial that found that 5-FUlevamisole for 12 months was superior to either surgery alone or surgery followed by levamisole alone (recurrence rate was reduced by 40% and the death rate by 33% in Dukes’ C colon cancer).1 A subsequent trial intergroup trial randomized patients with Dukes’ B2 and C colon cancer to surgery alone or 1 year of adjuvant levamisole or 5FUlevamisole and confirmed the efficacy of 5FUlevamisole with respect to disease free survival and overall survival.2 As a result, adjuvant chemotherapy became the standard for stage III colon cancer as reported by an National Cancer Institute consensus development panel.3 Subsequently, primarily because of toxicity reasons, leucovorin replaced levamisole in most adjuvant chemotheraoy regimens for stage III colorectal cancer. Clinical toxicity of levamisole was noted as early as 1976 when several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978, presenting primarily as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. In the early 1990s, levamisole became unavailable for human use in the United States due to toxicity concerns. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy. Recently, several persons have developed a novel syndrome characterized by necrotic noses and ears, leg ulcers, agranulocytosis, thrombovasculopathy, and positive antineutrophil cytoplasmic antibodies (ANCAs) as a result of the drug cocaine being adulterated with levamisole. We describe the drug below.

Background

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that received approval from the Food and Drug Administration in 1991 as part of adjuvant chemotherapy regimens for colorectal cancer. The addition of levamisole to 5-flouroruacil (5-FU) was first evaluated by the North Central Cancer Treatment Group in a 3-arm clinical trial that found that 5-FUlevamisole for 12 months was superior to either surgery alone or surgery followed by levamisole alone (recurrence rate was reduced by 40% and the death rate by 33% in Dukes’ C colon cancer).1 A subsequent trial intergroup trial randomized patients with Dukes’ B2 and C colon cancer to surgery alone or 1 year of adjuvant levamisole or 5FUlevamisole and confirmed the efficacy of 5FUlevamisole with respect to disease free survival and overall survival.2 As a result, adjuvant chemotherapy became the standard for stage III colon cancer as reported by an National Cancer Institute consensus development panel.3 Subsequently, primarily because of toxicity reasons, leucovorin replaced levamisole in most adjuvant chemotheraoy regimens for stage III colorectal cancer. Clinical toxicity of levamisole was noted as early as 1976 when several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978, presenting primarily as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. In the early 1990s, levamisole became unavailable for human use in the United States due to toxicity concerns. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy. Recently, several persons have developed a novel syndrome characterized by necrotic noses and ears, leg ulcers, agranulocytosis, thrombovasculopathy, and positive antineutrophil cytoplasmic antibodies (ANCAs) as a result of the drug cocaine being adulterated with levamisole. We describe the drug below.

NEW ORLEANS – Modified T cells continue to show their mettle against treatment-refractory leukemias, based on study results presented at the annual meeting of the American Society of Hematology.

Among children and young adults with heavily pretreated relapsed or refractory acute lymphoblastic leukemia (ALL), chimeric antigen receptor (CAR) T cells targeted against the CD19 receptor produced complete responses in 10 of 16 patients, including 3 patients with primary, treatment-refractory ALL who had never previously been in remission, reported Dr. Daniel W. Lee III of the National Cancer Institute in Bethesda, Md.

"We were able to clear CNS [central nervous system] leukemia using CAR-T cells alone," Dr. Lee said.

In a second study, CD19-targeted T cells induced molecular remissions in adults with B-lineage ALL refractory to chemotherapy, said Dr. Marco L. Davila from the cellular therapeutics center at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City.

The immunotherapy produced a complete response (CR) in 12 of 16 patients, and a complete molecular response (CRm) in 12.

Dr. Davila commented that CAR-T cell therapy appears to be a good therapeutic choice for relapsed/refractory B-ALL.

"Especially in light of the data that we see in indolent lymphomas, where the response rates have not been nearly as great, I would speculate that there may be something about this disease that makes it particularly well suited to the second-generation CAR-T cell therapy," he said.

In both studies, therapy with CAR-T cells served as a bridge to stem cell transplantation for several patients.

Different CAR-T flavors

Each research team used its own variation on CAR-T cell therapy. The NCI investigators collected peripheral blood mononuclear cells (PBMCs) from patients via apheresis and used a gamma retrovirus to introduce into effector cells a genetic sequence targeting the CD19 receptor on malignant cells. The NCI version also uses CD28 costimulatory signaling to boost cell-killing effects.

The patients are conditioned with fludarabine and cyclophosphamide, and the treated T-cells are reinfused into the patients 11 days after harvesting.

In the phase I study, 15 patients with relapsed or refractory ALL and 1 with diffuse large B-cell lymphoma were treated. Eight of the patients had undergone at least one hematopoietic stem cell transplant, and all had received total body irradiation. Four had previously received another form of immunotherapy. The patients had to have been at least 100 days post transplant, with no graft-vs.-host disease.

T-cell expansion and transduction was feasible in this heavily pretreated population. All but two patients had an adequate or good expression of CAR-T cells. These patients were treated nonetheless, and one went on to have a minimal-residual disease (MRD) negative response, Dr. Lee noted.

In all, 10 of the patients had complete responses: All of these patients had ALL, and three had never previously achieved a remission. The patient with non-Hodgkin’s lymphoma did not have a significant treatment response.

Of eight patients who were negative for MRD after therapy, six went on to have stem cell transplants, with no unexpected toxicities.

As in other CAR-T cell studies, the chief toxicities seen included grade 4 neutropenia lasting longer than 2 weeks in nine patients, and the cytokine-release syndrome in four patients (grade 3 in two patients and grade 4 in two patients). One patient with the cytokine-release syndrome had cardiac arrest but was successfully resuscitated.

The cytokine-release syndrome was found to be associated with interleukin-6 (IL-6) and could be ameliorated with the IL-6 blocking agent tocilizumab (Actemra). The severity of cytokine-release syndrome did not correlate with tumor burden, the researchers noted.

MSKCC Study

Dr. Davila and his colleagues used a slightly different CAR-T cell construction, also with CD28 costimulation, to treat B-ALL in adults who either had refractory or relapsed disease (MRD-positive) or who were in their first complete remission. Patients who were positive for the Philadelphia chromosome (Ph+) and those who had extramedullary disease, CNS leukemia, or were in relapse after allogeneic stem cell transplant were all eligible.

He presented data on 16 patients with B-ALL with long-term follow-up: 14 patients had a complete response, with an average time to complete response of 24.5 days.

Seven patients in the MSKCC study have gone on to allogeneic stem cell transplants; three patients in complete remission were not eligible for transplant because of medical contraindications, and one additional patient was being evaluated for transplant. There have been no post-transplant relapses to date, with the longest follow-up out to 2 years, Dr. Davila said.

As in the NCI study, the cytokine-release syndrome was a common toxicity. The investigators initially tried to manage it with steroids but found that it came at the cost of lymphotoxicity that caused a marked decline in serum T-cells. They subsequently switched to tocilizumab, which was effective at treating the syndrome without lymphotoxicity.

Dr. Lee’s study was supported by the National Cancer Institute and St. Baldrick’s Foundation. He discussed off-label use of CAR-T cells. Dr. Lee reported having no conflicts of interest. Dr. Davila’s study was supported by MSKCC. He reported having no conflicts of interest.

NEW ORLEANS – Modified T cells continue to show their mettle against treatment-refractory leukemias, based on study results presented at the annual meeting of the American Society of Hematology.

Among children and young adults with heavily pretreated relapsed or refractory acute lymphoblastic leukemia (ALL), chimeric antigen receptor (CAR) T cells targeted against the CD19 receptor produced complete responses in 10 of 16 patients, including 3 patients with primary, treatment-refractory ALL who had never previously been in remission, reported Dr. Daniel W. Lee III of the National Cancer Institute in Bethesda, Md.

"We were able to clear CNS [central nervous system] leukemia using CAR-T cells alone," Dr. Lee said.

In a second study, CD19-targeted T cells induced molecular remissions in adults with B-lineage ALL refractory to chemotherapy, said Dr. Marco L. Davila from the cellular therapeutics center at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City.

The immunotherapy produced a complete response (CR) in 12 of 16 patients, and a complete molecular response (CRm) in 12.

Dr. Davila commented that CAR-T cell therapy appears to be a good therapeutic choice for relapsed/refractory B-ALL.

"Especially in light of the data that we see in indolent lymphomas, where the response rates have not been nearly as great, I would speculate that there may be something about this disease that makes it particularly well suited to the second-generation CAR-T cell therapy," he said.

In both studies, therapy with CAR-T cells served as a bridge to stem cell transplantation for several patients.

Different CAR-T flavors

Each research team used its own variation on CAR-T cell therapy. The NCI investigators collected peripheral blood mononuclear cells (PBMCs) from patients via apheresis and used a gamma retrovirus to introduce into effector cells a genetic sequence targeting the CD19 receptor on malignant cells. The NCI version also uses CD28 costimulatory signaling to boost cell-killing effects.

The patients are conditioned with fludarabine and cyclophosphamide, and the treated T-cells are reinfused into the patients 11 days after harvesting.

In the phase I study, 15 patients with relapsed or refractory ALL and 1 with diffuse large B-cell lymphoma were treated. Eight of the patients had undergone at least one hematopoietic stem cell transplant, and all had received total body irradiation. Four had previously received another form of immunotherapy. The patients had to have been at least 100 days post transplant, with no graft-vs.-host disease.

T-cell expansion and transduction was feasible in this heavily pretreated population. All but two patients had an adequate or good expression of CAR-T cells. These patients were treated nonetheless, and one went on to have a minimal-residual disease (MRD) negative response, Dr. Lee noted.

In all, 10 of the patients had complete responses: All of these patients had ALL, and three had never previously achieved a remission. The patient with non-Hodgkin’s lymphoma did not have a significant treatment response.

Of eight patients who were negative for MRD after therapy, six went on to have stem cell transplants, with no unexpected toxicities.

As in other CAR-T cell studies, the chief toxicities seen included grade 4 neutropenia lasting longer than 2 weeks in nine patients, and the cytokine-release syndrome in four patients (grade 3 in two patients and grade 4 in two patients). One patient with the cytokine-release syndrome had cardiac arrest but was successfully resuscitated.

The cytokine-release syndrome was found to be associated with interleukin-6 (IL-6) and could be ameliorated with the IL-6 blocking agent tocilizumab (Actemra). The severity of cytokine-release syndrome did not correlate with tumor burden, the researchers noted.

MSKCC Study

Dr. Davila and his colleagues used a slightly different CAR-T cell construction, also with CD28 costimulation, to treat B-ALL in adults who either had refractory or relapsed disease (MRD-positive) or who were in their first complete remission. Patients who were positive for the Philadelphia chromosome (Ph+) and those who had extramedullary disease, CNS leukemia, or were in relapse after allogeneic stem cell transplant were all eligible.

He presented data on 16 patients with B-ALL with long-term follow-up: 14 patients had a complete response, with an average time to complete response of 24.5 days.

Seven patients in the MSKCC study have gone on to allogeneic stem cell transplants; three patients in complete remission were not eligible for transplant because of medical contraindications, and one additional patient was being evaluated for transplant. There have been no post-transplant relapses to date, with the longest follow-up out to 2 years, Dr. Davila said.

As in the NCI study, the cytokine-release syndrome was a common toxicity. The investigators initially tried to manage it with steroids but found that it came at the cost of lymphotoxicity that caused a marked decline in serum T-cells. They subsequently switched to tocilizumab, which was effective at treating the syndrome without lymphotoxicity.

Dr. Lee’s study was supported by the National Cancer Institute and St. Baldrick’s Foundation. He discussed off-label use of CAR-T cells. Dr. Lee reported having no conflicts of interest. Dr. Davila’s study was supported by MSKCC. He reported having no conflicts of interest.

NEW ORLEANS – Modified T cells continue to show their mettle against treatment-refractory leukemias, based on study results presented at the annual meeting of the American Society of Hematology.

Among children and young adults with heavily pretreated relapsed or refractory acute lymphoblastic leukemia (ALL), chimeric antigen receptor (CAR) T cells targeted against the CD19 receptor produced complete responses in 10 of 16 patients, including 3 patients with primary, treatment-refractory ALL who had never previously been in remission, reported Dr. Daniel W. Lee III of the National Cancer Institute in Bethesda, Md.

"We were able to clear CNS [central nervous system] leukemia using CAR-T cells alone," Dr. Lee said.

In a second study, CD19-targeted T cells induced molecular remissions in adults with B-lineage ALL refractory to chemotherapy, said Dr. Marco L. Davila from the cellular therapeutics center at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City.

The immunotherapy produced a complete response (CR) in 12 of 16 patients, and a complete molecular response (CRm) in 12.

Dr. Davila commented that CAR-T cell therapy appears to be a good therapeutic choice for relapsed/refractory B-ALL.

"Especially in light of the data that we see in indolent lymphomas, where the response rates have not been nearly as great, I would speculate that there may be something about this disease that makes it particularly well suited to the second-generation CAR-T cell therapy," he said.

In both studies, therapy with CAR-T cells served as a bridge to stem cell transplantation for several patients.

Different CAR-T flavors

Each research team used its own variation on CAR-T cell therapy. The NCI investigators collected peripheral blood mononuclear cells (PBMCs) from patients via apheresis and used a gamma retrovirus to introduce into effector cells a genetic sequence targeting the CD19 receptor on malignant cells. The NCI version also uses CD28 costimulatory signaling to boost cell-killing effects.

The patients are conditioned with fludarabine and cyclophosphamide, and the treated T-cells are reinfused into the patients 11 days after harvesting.

In the phase I study, 15 patients with relapsed or refractory ALL and 1 with diffuse large B-cell lymphoma were treated. Eight of the patients had undergone at least one hematopoietic stem cell transplant, and all had received total body irradiation. Four had previously received another form of immunotherapy. The patients had to have been at least 100 days post transplant, with no graft-vs.-host disease.

T-cell expansion and transduction was feasible in this heavily pretreated population. All but two patients had an adequate or good expression of CAR-T cells. These patients were treated nonetheless, and one went on to have a minimal-residual disease (MRD) negative response, Dr. Lee noted.

In all, 10 of the patients had complete responses: All of these patients had ALL, and three had never previously achieved a remission. The patient with non-Hodgkin’s lymphoma did not have a significant treatment response.

Of eight patients who were negative for MRD after therapy, six went on to have stem cell transplants, with no unexpected toxicities.

As in other CAR-T cell studies, the chief toxicities seen included grade 4 neutropenia lasting longer than 2 weeks in nine patients, and the cytokine-release syndrome in four patients (grade 3 in two patients and grade 4 in two patients). One patient with the cytokine-release syndrome had cardiac arrest but was successfully resuscitated.

The cytokine-release syndrome was found to be associated with interleukin-6 (IL-6) and could be ameliorated with the IL-6 blocking agent tocilizumab (Actemra). The severity of cytokine-release syndrome did not correlate with tumor burden, the researchers noted.

MSKCC Study

Dr. Davila and his colleagues used a slightly different CAR-T cell construction, also with CD28 costimulation, to treat B-ALL in adults who either had refractory or relapsed disease (MRD-positive) or who were in their first complete remission. Patients who were positive for the Philadelphia chromosome (Ph+) and those who had extramedullary disease, CNS leukemia, or were in relapse after allogeneic stem cell transplant were all eligible.

He presented data on 16 patients with B-ALL with long-term follow-up: 14 patients had a complete response, with an average time to complete response of 24.5 days.

Seven patients in the MSKCC study have gone on to allogeneic stem cell transplants; three patients in complete remission were not eligible for transplant because of medical contraindications, and one additional patient was being evaluated for transplant. There have been no post-transplant relapses to date, with the longest follow-up out to 2 years, Dr. Davila said.

As in the NCI study, the cytokine-release syndrome was a common toxicity. The investigators initially tried to manage it with steroids but found that it came at the cost of lymphotoxicity that caused a marked decline in serum T-cells. They subsequently switched to tocilizumab, which was effective at treating the syndrome without lymphotoxicity.

Dr. Lee’s study was supported by the National Cancer Institute and St. Baldrick’s Foundation. He discussed off-label use of CAR-T cells. Dr. Lee reported having no conflicts of interest. Dr. Davila’s study was supported by MSKCC. He reported having no conflicts of interest.

Monoclonal antibodies
Credit: Linda Bartlett

NEW ORLEANS—Brentuximab vedotin has demonstrated “compelling” antitumor activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

The investigators were also surprised

to find that the activity of this anti-CD30 monoclonal antibody

conjugate did not seem to

correlate with a patient’s level of CD30 expression.

In fact, some of

the patients with the weakest CD30 expression had the best responses to

the drug.

Eric Jacobsen, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues presented these results at the 2013 ASH Annual Meeting as abstract 848.

Thus far, the researchers have enrolled 62 patients with B-cell lymphomas, including 44 with DLBCL, on this phase 2 study.

Sixty-five percent of patients had primary refractory disease, 76% were refractory to their most recent prior therapy, and 23% had never responded to any treatment.

However, 40% of the 43 evaluable DLBCL patients had an objective response to brentuximab vedotin. The median response duration was 36 weeks, and some responses lasted more than 8 months.

Seven patients had complete remissions, and 10 had partial remissions. In the other B-cell lymphoma patients, 22 had an objective response.

The researchers called this compelling antitumor activity in a highly refractory population.

“[Brentuximab vedotin] was more active than many expected,” Dr Jacobsen said. “In my opinion, these results are encouraging enough to take the drug forward in diffuse large B-cell lymphoma.”

The researchers said the drug’s safety profile was consistent with previous results. Six patients stopped treatment due to adverse events, including 2 who developed peripheral neuropathy. 

Treatment-emergent adverse events included fatigue (40%), nausea (37%), neutropenia (37%), fever (32%), diarrhea (31%), peripheral sensory neuropathy (26%), vomiting (23%), anemia (21%), and constipation (21%).

Role of CD30

Brentuximab vedotin is a monoclonal antibody that binds to CD30. This molecule’s expression varies, but researchers have estimated that CD30 is present in a quarter to a third of B-cell non-Hodgkin lymphoma cells.

In this study, some of the patients’ lymphoma cells strongly expressed CD30. But, in other patients, the investigators were unable to detect any CD30 expression at all. And the patients’ level of CD30 expression bore no relationship to how they responded to the drug.

“In fact, although the trend was not statistically significant, there was almost an inverse correlation,” Dr Jacobsen said. “Some patients with the weakest CD30 expression had the most positive responses.”

One possible explanation for this is that the drug bound to another target, but preclinical tests suggested this was not the case. Other possibilities are that brentuximab vedotin binds more effectively to CD30 than the antibody used to detect CD30 in the lab or that different cells have differing abilities to ingest brentuximab once the antibody binds to the cell.

There is no clear answer from the study, Dr Jacobsen said, but lab tests are ongoing. He and his colleagues are beginning to evaluate the drug’s activity in a cohort of patients whose lymphomas have no measurable CD30 expression.

This study was supported by Seattle Genetics.

Monoclonal antibodies
Credit: Linda Bartlett

NEW ORLEANS—Brentuximab vedotin has demonstrated “compelling” antitumor activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

The investigators were also surprised

to find that the activity of this anti-CD30 monoclonal antibody

conjugate did not seem to

correlate with a patient’s level of CD30 expression.

In fact, some of

the patients with the weakest CD30 expression had the best responses to

the drug.

Eric Jacobsen, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues presented these results at the 2013 ASH Annual Meeting as abstract 848.

Thus far, the researchers have enrolled 62 patients with B-cell lymphomas, including 44 with DLBCL, on this phase 2 study.

Sixty-five percent of patients had primary refractory disease, 76% were refractory to their most recent prior therapy, and 23% had never responded to any treatment.

However, 40% of the 43 evaluable DLBCL patients had an objective response to brentuximab vedotin. The median response duration was 36 weeks, and some responses lasted more than 8 months.

Seven patients had complete remissions, and 10 had partial remissions. In the other B-cell lymphoma patients, 22 had an objective response.

The researchers called this compelling antitumor activity in a highly refractory population.

“[Brentuximab vedotin] was more active than many expected,” Dr Jacobsen said. “In my opinion, these results are encouraging enough to take the drug forward in diffuse large B-cell lymphoma.”

The researchers said the drug’s safety profile was consistent with previous results. Six patients stopped treatment due to adverse events, including 2 who developed peripheral neuropathy. 

Treatment-emergent adverse events included fatigue (40%), nausea (37%), neutropenia (37%), fever (32%), diarrhea (31%), peripheral sensory neuropathy (26%), vomiting (23%), anemia (21%), and constipation (21%).

Role of CD30

Brentuximab vedotin is a monoclonal antibody that binds to CD30. This molecule’s expression varies, but researchers have estimated that CD30 is present in a quarter to a third of B-cell non-Hodgkin lymphoma cells.

In this study, some of the patients’ lymphoma cells strongly expressed CD30. But, in other patients, the investigators were unable to detect any CD30 expression at all. And the patients’ level of CD30 expression bore no relationship to how they responded to the drug.

“In fact, although the trend was not statistically significant, there was almost an inverse correlation,” Dr Jacobsen said. “Some patients with the weakest CD30 expression had the most positive responses.”

One possible explanation for this is that the drug bound to another target, but preclinical tests suggested this was not the case. Other possibilities are that brentuximab vedotin binds more effectively to CD30 than the antibody used to detect CD30 in the lab or that different cells have differing abilities to ingest brentuximab once the antibody binds to the cell.

There is no clear answer from the study, Dr Jacobsen said, but lab tests are ongoing. He and his colleagues are beginning to evaluate the drug’s activity in a cohort of patients whose lymphomas have no measurable CD30 expression.

This study was supported by Seattle Genetics.

Monoclonal antibodies
Credit: Linda Bartlett

NEW ORLEANS—Brentuximab vedotin has demonstrated “compelling” antitumor activity in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

The investigators were also surprised

to find that the activity of this anti-CD30 monoclonal antibody

conjugate did not seem to

correlate with a patient’s level of CD30 expression.

In fact, some of

the patients with the weakest CD30 expression had the best responses to

the drug.

Eric Jacobsen, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues presented these results at the 2013 ASH Annual Meeting as abstract 848.

Thus far, the researchers have enrolled 62 patients with B-cell lymphomas, including 44 with DLBCL, on this phase 2 study.

Sixty-five percent of patients had primary refractory disease, 76% were refractory to their most recent prior therapy, and 23% had never responded to any treatment.

However, 40% of the 43 evaluable DLBCL patients had an objective response to brentuximab vedotin. The median response duration was 36 weeks, and some responses lasted more than 8 months.

Seven patients had complete remissions, and 10 had partial remissions. In the other B-cell lymphoma patients, 22 had an objective response.

The researchers called this compelling antitumor activity in a highly refractory population.

“[Brentuximab vedotin] was more active than many expected,” Dr Jacobsen said. “In my opinion, these results are encouraging enough to take the drug forward in diffuse large B-cell lymphoma.”

The researchers said the drug’s safety profile was consistent with previous results. Six patients stopped treatment due to adverse events, including 2 who developed peripheral neuropathy. 

Treatment-emergent adverse events included fatigue (40%), nausea (37%), neutropenia (37%), fever (32%), diarrhea (31%), peripheral sensory neuropathy (26%), vomiting (23%), anemia (21%), and constipation (21%).

Role of CD30

Brentuximab vedotin is a monoclonal antibody that binds to CD30. This molecule’s expression varies, but researchers have estimated that CD30 is present in a quarter to a third of B-cell non-Hodgkin lymphoma cells.

In this study, some of the patients’ lymphoma cells strongly expressed CD30. But, in other patients, the investigators were unable to detect any CD30 expression at all. And the patients’ level of CD30 expression bore no relationship to how they responded to the drug.

“In fact, although the trend was not statistically significant, there was almost an inverse correlation,” Dr Jacobsen said. “Some patients with the weakest CD30 expression had the most positive responses.”

One possible explanation for this is that the drug bound to another target, but preclinical tests suggested this was not the case. Other possibilities are that brentuximab vedotin binds more effectively to CD30 than the antibody used to detect CD30 in the lab or that different cells have differing abilities to ingest brentuximab once the antibody binds to the cell.

There is no clear answer from the study, Dr Jacobsen said, but lab tests are ongoing. He and his colleagues are beginning to evaluate the drug’s activity in a cohort of patients whose lymphomas have no measurable CD30 expression.

This study was supported by Seattle Genetics.

MELBOURNE – Corneal nerve fiber length, measured using corneal confocal microscopy, is significantly reduced in individuals with type 1 diabetes who go on to develop diabetic neuropathy at 3 years, according to data from the longitudinal LANDMark study.

Researchers found that corneal nerve fibre length was significantly lower at baseline in individuals who developed neuropathy than in those who did not over the 3-year follow up (13.3 vs. 17.4 mm/mm², respectively; P = 0.036).

Corneal nerve fiber length, which is a measure of amount of nerve tissue per unit area in the cornea, may be an useful, noninvasive adjunct to diabetic neuropathy screening, Nicola Pritchard, a researcher for the Institute of Health and Biomedical Innovation at Queensland University of Technology, Brisbane, suggested in her presentation of the results at the World Diabetes Congress.

"In animal models, we know that the dropout of nerves in the cornea actually does precede the dropout of nerves in the foot," Ms. Pritchard said in an interview.

"Our hope is that this technique will be useful to pick up very, very early signs of neuropathy, way before people are getting symptoms and before things develop to a stage where there’s damage," she said.

LANDMark (Longitudinal Assessment of Neuropathy in Diabetes Using Novel Ophthalmic Markers) is a 5-year observational study of 242 individuals with type 1 diabetes.

The 3-year analysis included data from 64 participants without baseline neuropathy, seven (11%) of whom had developed neuropathy by 3 years, as defined by the Toronto criteria.

Study participants undergo annual neuropathy assessments, including measurement of corneal nerve parameters using corneal confocal microscopy and measurements of corneal sensitivity using noncontact corneal esthesiometry.

The study showed that reduced peroneal conduction velocity and cold sensation and increased vibration threshold also were associated with development of diabetic neuropathy.

However, although corneal nerve fiber length was significantly reduced at baseline in individuals who developed neuropathy, compared with those who did not, at the 3-year mark there was no significant difference in corneal nerve fiber length between the two groups.

Ms. Pritchard said that it was unclear why the nerve fibre parameters improved over time, suggesting that perhaps the nerves were growing to fill in the gaps.

Nathan Efron, D.Sc., research leader of the LANDMark study, said corneal confocal microscopy had the potential to be a very simple screening technique for diabetic neuropathy that could be applied at the same time as patients come in for their annual fundus photographs.

"At the very least, it’s a viable alternative technique to the range of techniques neurologists and diabetic specialists already have at their disposal, but the potential advantage of this technique is that it might be a very early marker of diabetic neuropathy," said Dr. Efron, professor in the School of Optometry and Vision Science at Queensland University of Technology.

"We’re not there yet, but down the line, that’s where this all could come to, as long as we can get more firm data and validate it a bit better," he said.

There were no relevant conflicts of interest declared.

MELBOURNE – Corneal nerve fiber length, measured using corneal confocal microscopy, is significantly reduced in individuals with type 1 diabetes who go on to develop diabetic neuropathy at 3 years, according to data from the longitudinal LANDMark study.

Researchers found that corneal nerve fibre length was significantly lower at baseline in individuals who developed neuropathy than in those who did not over the 3-year follow up (13.3 vs. 17.4 mm/mm², respectively; P = 0.036).

Corneal nerve fiber length, which is a measure of amount of nerve tissue per unit area in the cornea, may be an useful, noninvasive adjunct to diabetic neuropathy screening, Nicola Pritchard, a researcher for the Institute of Health and Biomedical Innovation at Queensland University of Technology, Brisbane, suggested in her presentation of the results at the World Diabetes Congress.

"In animal models, we know that the dropout of nerves in the cornea actually does precede the dropout of nerves in the foot," Ms. Pritchard said in an interview.

"Our hope is that this technique will be useful to pick up very, very early signs of neuropathy, way before people are getting symptoms and before things develop to a stage where there’s damage," she said.

LANDMark (Longitudinal Assessment of Neuropathy in Diabetes Using Novel Ophthalmic Markers) is a 5-year observational study of 242 individuals with type 1 diabetes.

The 3-year analysis included data from 64 participants without baseline neuropathy, seven (11%) of whom had developed neuropathy by 3 years, as defined by the Toronto criteria.

Study participants undergo annual neuropathy assessments, including measurement of corneal nerve parameters using corneal confocal microscopy and measurements of corneal sensitivity using noncontact corneal esthesiometry.

The study showed that reduced peroneal conduction velocity and cold sensation and increased vibration threshold also were associated with development of diabetic neuropathy.

However, although corneal nerve fiber length was significantly reduced at baseline in individuals who developed neuropathy, compared with those who did not, at the 3-year mark there was no significant difference in corneal nerve fiber length between the two groups.

Ms. Pritchard said that it was unclear why the nerve fibre parameters improved over time, suggesting that perhaps the nerves were growing to fill in the gaps.

Nathan Efron, D.Sc., research leader of the LANDMark study, said corneal confocal microscopy had the potential to be a very simple screening technique for diabetic neuropathy that could be applied at the same time as patients come in for their annual fundus photographs.

"At the very least, it’s a viable alternative technique to the range of techniques neurologists and diabetic specialists already have at their disposal, but the potential advantage of this technique is that it might be a very early marker of diabetic neuropathy," said Dr. Efron, professor in the School of Optometry and Vision Science at Queensland University of Technology.

"We’re not there yet, but down the line, that’s where this all could come to, as long as we can get more firm data and validate it a bit better," he said.

There were no relevant conflicts of interest declared.

MELBOURNE – Corneal nerve fiber length, measured using corneal confocal microscopy, is significantly reduced in individuals with type 1 diabetes who go on to develop diabetic neuropathy at 3 years, according to data from the longitudinal LANDMark study.

Researchers found that corneal nerve fibre length was significantly lower at baseline in individuals who developed neuropathy than in those who did not over the 3-year follow up (13.3 vs. 17.4 mm/mm², respectively; P = 0.036).

Corneal nerve fiber length, which is a measure of amount of nerve tissue per unit area in the cornea, may be an useful, noninvasive adjunct to diabetic neuropathy screening, Nicola Pritchard, a researcher for the Institute of Health and Biomedical Innovation at Queensland University of Technology, Brisbane, suggested in her presentation of the results at the World Diabetes Congress.

"In animal models, we know that the dropout of nerves in the cornea actually does precede the dropout of nerves in the foot," Ms. Pritchard said in an interview.

"Our hope is that this technique will be useful to pick up very, very early signs of neuropathy, way before people are getting symptoms and before things develop to a stage where there’s damage," she said.

LANDMark (Longitudinal Assessment of Neuropathy in Diabetes Using Novel Ophthalmic Markers) is a 5-year observational study of 242 individuals with type 1 diabetes.

The 3-year analysis included data from 64 participants without baseline neuropathy, seven (11%) of whom had developed neuropathy by 3 years, as defined by the Toronto criteria.

Study participants undergo annual neuropathy assessments, including measurement of corneal nerve parameters using corneal confocal microscopy and measurements of corneal sensitivity using noncontact corneal esthesiometry.

The study showed that reduced peroneal conduction velocity and cold sensation and increased vibration threshold also were associated with development of diabetic neuropathy.

However, although corneal nerve fiber length was significantly reduced at baseline in individuals who developed neuropathy, compared with those who did not, at the 3-year mark there was no significant difference in corneal nerve fiber length between the two groups.

Ms. Pritchard said that it was unclear why the nerve fibre parameters improved over time, suggesting that perhaps the nerves were growing to fill in the gaps.

Nathan Efron, D.Sc., research leader of the LANDMark study, said corneal confocal microscopy had the potential to be a very simple screening technique for diabetic neuropathy that could be applied at the same time as patients come in for their annual fundus photographs.

"At the very least, it’s a viable alternative technique to the range of techniques neurologists and diabetic specialists already have at their disposal, but the potential advantage of this technique is that it might be a very early marker of diabetic neuropathy," said Dr. Efron, professor in the School of Optometry and Vision Science at Queensland University of Technology.

"We’re not there yet, but down the line, that’s where this all could come to, as long as we can get more firm data and validate it a bit better," he said.

There were no relevant conflicts of interest declared.