Organ Donors with Malignant Gliomas: An Update 2 of 2

[Guest guest]

Organ Donors with Malignant Gliomas: An Update 2 of 2

Conclusions

Transplantation of organs from donors with cancer in general and gliomas in

specific always carry an additional risk, that of cancer transmission. For

any individual transplant candidate at the 'top of the list', the option of

receiving the next organ from a donor without cancer may be most prudent in

all but the most urgent of circumstances. However, the increasingly critical

organ shortage demands that we as a community reassess our thresholds for

acceptable risk, particularly as there are candidates that are not at the

'top of the list' whose lives would be saved by transplantation. We have

outlined the clinical presentation, the natural history, and, most

importantly, the recent developments in the understanding of glioma biology

to provide a modern context for reconsideration of tumor transmission risk.

Historically, the infrequent metastasis of gliomas has been attributed to

the natural history of the tumor and the blood-brain barrier. Identified

risk factors for tumor transmission have been GBM histology and therapeutic

interventions such as craniotomy or ventricular shunting, presumably

secondary to disruption of the blood-brain barrier. However, clinically, we

now recognize that radiographic contrast enhancement signifies loss of

blood-brain barrier integrity and that major craniotomy is widely prevalent

as it is first line therapy for glioma. Biologically, we now understand that

the migratory pattern of glioma growth and metastasis recapitulates the

developmental program of glial precursors that does not include travel

outside of the CNS. The occurrence of glioma metastases, however, may

correlate with hyperactivity of critical signaling pathways. We hypothesize

that the molecular signature of a GBM tumor may simultaneously stratify risk

of metastatic potential and suggest efficacious pharmacologic antitumor

strategies. While data to substantiate these intriguing and exciting

hypotheses remain a promising horizon, we are faced today with a critical

and compelling organ shortage. As members of the transplant community, we

simply can no longer afford to refuse the organs of donors with glioma

without thoughtful consideration. While case reports and registry data have

certainly documented transmission of gliomas with resultant morbidity and

even mortality, the loss of quality and quantity of life by those on the

waiting list remains a staggering and sobering reality.

[Guest guest]

Organ Donors with Malignant Gliomas: An Update 2 of 2

Conclusions

Transplantation of organs from donors with cancer in general and gliomas in

specific always carry an additional risk, that of cancer transmission. For

any individual transplant candidate at the 'top of the list', the option of

receiving the next organ from a donor without cancer may be most prudent in

all but the most urgent of circumstances. However, the increasingly critical

organ shortage demands that we as a community reassess our thresholds for

acceptable risk, particularly as there are candidates that are not at the

'top of the list' whose lives would be saved by transplantation. We have

outlined the clinical presentation, the natural history, and, most

importantly, the recent developments in the understanding of glioma biology

to provide a modern context for reconsideration of tumor transmission risk.

Historically, the infrequent metastasis of gliomas has been attributed to

the natural history of the tumor and the blood-brain barrier. Identified

risk factors for tumor transmission have been GBM histology and therapeutic

interventions such as craniotomy or ventricular shunting, presumably

secondary to disruption of the blood-brain barrier. However, clinically, we

now recognize that radiographic contrast enhancement signifies loss of

blood-brain barrier integrity and that major craniotomy is widely prevalent

as it is first line therapy for glioma. Biologically, we now understand that

the migratory pattern of glioma growth and metastasis recapitulates the

developmental program of glial precursors that does not include travel

outside of the CNS. The occurrence of glioma metastases, however, may

correlate with hyperactivity of critical signaling pathways. We hypothesize

that the molecular signature of a GBM tumor may simultaneously stratify risk

of metastatic potential and suggest efficacious pharmacologic antitumor

strategies. While data to substantiate these intriguing and exciting

hypotheses remain a promising horizon, we are faced today with a critical

and compelling organ shortage. As members of the transplant community, we

simply can no longer afford to refuse the organs of donors with glioma

without thoughtful consideration. While case reports and registry data have

certainly documented transmission of gliomas with resultant morbidity and

even mortality, the loss of quality and quantity of life by those on the

waiting list remains a staggering and sobering reality.

[Guest guest]

Organ Donors with Malignant Gliomas: An Update 2 of 2

Conclusions

Transplantation of organs from donors with cancer in general and gliomas in

specific always carry an additional risk, that of cancer transmission. For

any individual transplant candidate at the 'top of the list', the option of

receiving the next organ from a donor without cancer may be most prudent in

all but the most urgent of circumstances. However, the increasingly critical

organ shortage demands that we as a community reassess our thresholds for

acceptable risk, particularly as there are candidates that are not at the

'top of the list' whose lives would be saved by transplantation. We have

outlined the clinical presentation, the natural history, and, most

importantly, the recent developments in the understanding of glioma biology

to provide a modern context for reconsideration of tumor transmission risk.

Historically, the infrequent metastasis of gliomas has been attributed to

the natural history of the tumor and the blood-brain barrier. Identified

risk factors for tumor transmission have been GBM histology and therapeutic

interventions such as craniotomy or ventricular shunting, presumably

secondary to disruption of the blood-brain barrier. However, clinically, we

now recognize that radiographic contrast enhancement signifies loss of

blood-brain barrier integrity and that major craniotomy is widely prevalent

as it is first line therapy for glioma. Biologically, we now understand that

the migratory pattern of glioma growth and metastasis recapitulates the

developmental program of glial precursors that does not include travel

outside of the CNS. The occurrence of glioma metastases, however, may

correlate with hyperactivity of critical signaling pathways. We hypothesize

that the molecular signature of a GBM tumor may simultaneously stratify risk

of metastatic potential and suggest efficacious pharmacologic antitumor

strategies. While data to substantiate these intriguing and exciting

hypotheses remain a promising horizon, we are faced today with a critical

and compelling organ shortage. As members of the transplant community, we

simply can no longer afford to refuse the organs of donors with glioma

without thoughtful consideration. While case reports and registry data have

certainly documented transmission of gliomas with resultant morbidity and

even mortality, the loss of quality and quantity of life by those on the

waiting list remains a staggering and sobering reality.

[Guest guest]

Organ Donors with Malignant Gliomas: An Update 2 of 2

Conclusions

Transplantation of organs from donors with cancer in general and gliomas in

specific always carry an additional risk, that of cancer transmission. For

any individual transplant candidate at the 'top of the list', the option of

receiving the next organ from a donor without cancer may be most prudent in

all but the most urgent of circumstances. However, the increasingly critical

organ shortage demands that we as a community reassess our thresholds for

acceptable risk, particularly as there are candidates that are not at the

'top of the list' whose lives would be saved by transplantation. We have

outlined the clinical presentation, the natural history, and, most

importantly, the recent developments in the understanding of glioma biology

to provide a modern context for reconsideration of tumor transmission risk.

Historically, the infrequent metastasis of gliomas has been attributed to

the natural history of the tumor and the blood-brain barrier. Identified

risk factors for tumor transmission have been GBM histology and therapeutic

interventions such as craniotomy or ventricular shunting, presumably

secondary to disruption of the blood-brain barrier. However, clinically, we

now recognize that radiographic contrast enhancement signifies loss of

blood-brain barrier integrity and that major craniotomy is widely prevalent

as it is first line therapy for glioma. Biologically, we now understand that

the migratory pattern of glioma growth and metastasis recapitulates the

developmental program of glial precursors that does not include travel

outside of the CNS. The occurrence of glioma metastases, however, may

correlate with hyperactivity of critical signaling pathways. We hypothesize

that the molecular signature of a GBM tumor may simultaneously stratify risk

of metastatic potential and suggest efficacious pharmacologic antitumor

strategies. While data to substantiate these intriguing and exciting

hypotheses remain a promising horizon, we are faced today with a critical

and compelling organ shortage. As members of the transplant community, we

simply can no longer afford to refuse the organs of donors with glioma

without thoughtful consideration. While case reports and registry data have

certainly documented transmission of gliomas with resultant morbidity and

even mortality, the loss of quality and quantity of life by those on the

waiting list remains a staggering and sobering reality.