Jody Kaplan - Academia.edu (original) (raw)
Papers by Jody Kaplan
The Harvard-MIT BNCT Program
Springer eBooks, 2001
The clinical use of BNCT originated in Boston largely through the efforts of Dr. William Sweet at... more The clinical use of BNCT originated in Boston largely through the efforts of Dr. William Sweet at the Massachusetts General Hospital and his collaborators at the Brookhaven National Laboratory (BNL) and the Massachusetts Institute of Technology (MIT). The early clinical trials were for patients with primary brain tumors but were unsuccessful largely due to the poor biodistribution of 10B and thermal neutron beams that had limited penetration into tissue. Clinical and basic researchers recognized there would have to be a dramatic improvement in the amount of 10B delivered to a tumor as well as an improvement in the biodistribution, i.e., an increase in the tumor to normal tissue ratio, before clinical studies could be resumed. In addition, nuclear engineers and physicists realized epithermal beams needed to be developed that would obviate many of the physical limitations inherent in the thermal beams that had previously been used. The culmination of this multifaceted preclinical work in biology, physics, 10B quantification, treatment planning, and epithermal beam design was in September 1994 when the first human subject was irradiaied with epithcrmal nculton BNCT at the MIT Nuclear Reaclor Laboratory. This subject was irradiated to the plantar surface of the foot following the administration of oral p-boronophenylalanine (BPA); two weeks later another patient wiih glioblastoma received a single field of epithermal neutron irradiation al BNL, with iniravenously adminisiered BPA-fructose as a 10B carrier. Since then a number of clinical trials that are primarily phase I in natute have been conducted or are currently in progress at both insiitutions with epithermal neutton beams.1 Over 60 subjects have been irradiaied. the majority to the cranium for glioblasioma multiforme and in addition, 4 subjects have been irradiaied to 5 sites at MIT for melanoma of the extremity.
A critical examination of the results from the phase I clinical trial of cranial neutron capture therapy at Harvard-MIT: normal tissue reaction and initial tumor response
International Journal of Radiation Oncology Biology Physics, Oct 1, 2002
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in
A critical examination of the results from the phase I clinical trial of cranial neutron capture therapy at Harvard-MIT: normal tissue reaction and initial tumor response
International Journal of Radiation Oncology*Biology*Physics, 2002
Applied Radiation and Isotopes, 2004
A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a... more A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m 2 body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBE Gy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBE Gy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBE Gy (median 57.8 RBE Gy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBE Gy. r
The Harvard-MIT BNCT Program
Frontiers in Neutron Capture Therapy, 2001
Journal of Neuro-oncology, 2003
A phase i trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase i trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The l~ carrier, L-p-boronophenylalanine-fi'uctose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg-~ over 1 h (10 subjects), 300 mg kg 1 over 1.5 h (two subjects), or 350 mg kg-~ over 1.5-2 h (10 subjects). The pharmacokinetic profile of l~ in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evatuable subjects had a measurable reduction in enhanced tumor volume following NCT.
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10 B carrier, l-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg −1 over 1 h (10 subjects), 300 mg kg −1 over 1.5 h (two subjects), or 350 mg kg −1 over 1.5-2 h (10 subjects). The pharmacokinetic profile of 10 B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24–78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10B carrier, L-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg−1 over 1 h (10 subjects), 300 mg kg−1 over 1.5 h (two subjects), or 350 mg kg−1 over 1.5–2 h (10 subjects). The pharmacokinetic profile of 10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.
The Harvard-MIT BNCT Program
Springer eBooks, 2001
The clinical use of BNCT originated in Boston largely through the efforts of Dr. William Sweet at... more The clinical use of BNCT originated in Boston largely through the efforts of Dr. William Sweet at the Massachusetts General Hospital and his collaborators at the Brookhaven National Laboratory (BNL) and the Massachusetts Institute of Technology (MIT). The early clinical trials were for patients with primary brain tumors but were unsuccessful largely due to the poor biodistribution of 10B and thermal neutron beams that had limited penetration into tissue. Clinical and basic researchers recognized there would have to be a dramatic improvement in the amount of 10B delivered to a tumor as well as an improvement in the biodistribution, i.e., an increase in the tumor to normal tissue ratio, before clinical studies could be resumed. In addition, nuclear engineers and physicists realized epithermal beams needed to be developed that would obviate many of the physical limitations inherent in the thermal beams that had previously been used. The culmination of this multifaceted preclinical work in biology, physics, 10B quantification, treatment planning, and epithermal beam design was in September 1994 when the first human subject was irradiaied with epithcrmal nculton BNCT at the MIT Nuclear Reaclor Laboratory. This subject was irradiated to the plantar surface of the foot following the administration of oral p-boronophenylalanine (BPA); two weeks later another patient wiih glioblastoma received a single field of epithermal neutron irradiation al BNL, with iniravenously adminisiered BPA-fructose as a 10B carrier. Since then a number of clinical trials that are primarily phase I in natute have been conducted or are currently in progress at both insiitutions with epithermal neutton beams.1 Over 60 subjects have been irradiaied. the majority to the cranium for glioblasioma multiforme and in addition, 4 subjects have been irradiaied to 5 sites at MIT for melanoma of the extremity.
A critical examination of the results from the phase I clinical trial of cranial neutron capture therapy at Harvard-MIT: normal tissue reaction and initial tumor response
International Journal of Radiation Oncology Biology Physics, Oct 1, 2002
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in
A critical examination of the results from the phase I clinical trial of cranial neutron capture therapy at Harvard-MIT: normal tissue reaction and initial tumor response
International Journal of Radiation Oncology*Biology*Physics, 2002
Applied Radiation and Isotopes, 2004
A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a... more A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m 2 body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBE Gy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBE Gy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBE Gy (median 57.8 RBE Gy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBE Gy. r
The Harvard-MIT BNCT Program
Frontiers in Neutron Capture Therapy, 2001
Journal of Neuro-oncology, 2003
A phase i trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase i trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The l~ carrier, L-p-boronophenylalanine-fi'uctose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg-~ over 1 h (10 subjects), 300 mg kg 1 over 1.5 h (two subjects), or 350 mg kg-~ over 1.5-2 h (10 subjects). The pharmacokinetic profile of l~ in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evatuable subjects had a measurable reduction in enhanced tumor volume following NCT.
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10 B carrier, l-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg −1 over 1 h (10 subjects), 300 mg kg −1 over 1.5 h (two subjects), or 350 mg kg −1 over 1.5-2 h (10 subjects). The pharmacokinetic profile of 10 B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.
Journal of Neuro-oncology, 2003
A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT)... more A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24–78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10B carrier, L-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg−1 over 1 h (10 subjects), 300 mg kg−1 over 1.5 h (two subjects), or 350 mg kg−1 over 1.5–2 h (10 subjects). The pharmacokinetic profile of 10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.