Manjeet Chadha - Academia.edu (original) (raw)

Papers by Manjeet Chadha

Research paper thumbnail of Boron Neutron Capture Therapy of Glioblastoma Multiforme at Brookhaven National Laboratory: Results of the Phase I/II Trial

Neurosurgery, 1998

Introduction: Boron neutron capture therapy (BNCT) is a binary treatment that allows for the targ... more Introduction: Boron neutron capture therapy (BNCT) is a binary treatment that allows for the targeted irradiation of cancer cells. Significant advances in BNCT technology have occurred since the early clinical trials for glioblastoma multiforme in the United States (1951-1961). ...

Research paper thumbnail of Boron Neutron-Capture Therapy (BNCT) for Glioblastoma Multiforme (GBM) Using the Epithermal Neutron Beam at the Brookhaven National Laboratory

International Journal of Radiation OncologyBiologyPhysics, 1998

Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear r... more Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Research paper thumbnail of 2025 Boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM), using the epithermal neutron beam at the Brookhaven national laboratory

International Journal of Radiation Oncology*Biology*Physics, 1996

Research paper thumbnail of Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: Trial design and early clinical results

Journal of neuro- …, 1997

Jeffrey A. Coderre,1 Eric H. Elowitz,2 Manjeet Chadha,3 Richard Bergland,2 Jacek Capala,1 Darrel ... more Jeffrey A. Coderre,1 Eric H. Elowitz,2 Manjeet Chadha,3 Richard Bergland,2 Jacek Capala,1 Darrel D. Joel,1 Hungyuan B. Liu,1 Daniel N. Slatkin1 and Arjun D. Chanana1 1Medical Department Brookhaven National Laboratory, Upton, NY, 11973, USA; Departments of 2 ...

Research paper thumbnail of Abstract P3-01-03: Vitamin D levels at breast cancer diagnosis: Association with patient and tumor characteristics

Research paper thumbnail of Abstract P3-08-08: Vitamin D status at breast cancer diagnosis: correlation with patient and tumor characteristics

Research paper thumbnail of Correlation of Pathological Features of Ductal Carcinoma In Situ (DCIS) and Oncotype DCIS Score

International Journal of Radiation Oncology*Biology*Physics, 2014

Research paper thumbnail of Managing a small recurrence in the previously irradiated breast. Is there a second chance for breast conservation?

Oncology (Williston Park, N.Y.), 2009

Over the past 30 years, lumpectomy and radiation therapy (breast-conservation therapy, or BCT) ha... more Over the past 30 years, lumpectomy and radiation therapy (breast-conservation therapy, or BCT) has been the preferred treatment for early-stage breast cancer. With accumulating follow-up, we have an ever-expanding pool of patients with history of an irradiated intact breast. Routine use of every-6-month or annual screening in this population has identified an emerging clinical dilemma with respect to managing a small recurrence or a second primary tumor in the treated breast. Most women diagnosed with a second cancer in a previously irradiated breast are advised to undergo mastectomy. More recently, with an improved understanding of the patterns of in-breast failure, and with advances in the delivery of conformal radiation dose there is an opportunity to reevaluate treatment alternatives for managing a small in-breast recurrence. A limited number of publications have reported on patient outcomes after a second lumpectomy and radiation therapy for this clinical scenario. In this repo...

Research paper thumbnail of Pilot study evaluating nicotinamide in metastatic brain tumors treated with radiation

Nicotinamide (NAM) has been shown to be an effective radiosensitizer in animal studies, but to da... more Nicotinamide (NAM) has been shown to be an effective radiosensitizer in animal studies, but to date no clinical studies have substantiated this effect. Twenty-nine patients with brain metastases were randomized to receive NAM and external radiation therapy (RT) (n = 14) or irradiation alone (n = 15). NAM was started on day 1 at 3 g/day and continued until radiation was completed. The RT dose to the whole brain was 30 Gy in 10 fractions in 12-14 days. To evaluate response, a computed tomographic (CT) scan of the head was repeated 1 month post-treatment. Toxicity was graded from the skin, liver, and gastrointestinal tract. There were no toxicities observed at 39.0 g total dose of NAM. Median survival for the 29 patients, calculated by the Kaplan-Meier method, was 3.5 months for the NAM + RT group (14 patients) and 3.9 months for the RT alone group (1 5 patients). Eighteen patients were evaluable for 1 month tumor response by CT scan. Response rates were compared with Fisher's exact two-tailed test. There was no difference in complete response (CR) (P = 0.62) or CR + partial response (PR) (P = 1.000) between the two groups. Adjuvant NAM, given in doses of 3.0 g/day (39.0 g total dose) in the treatment of brain metastases, has shown no benefit in survival or response in this preliminary study.

Research paper thumbnail of Dose perturbation in the presence of vaginal cylinder with Ir-192 HDR source: A radiochromic film dosimetry study

Research paper thumbnail of Interstitial high dose rate (HDR) brachytherapy (BT) in patients with cancer (CA) of the head & neck (H&N)

International Journal of Radiation Oncology Biology Physics - INT J RADIAT ONCOL BIOL PHYS, 1993

Research paper thumbnail of Primary Systemic Therapy of Breast Cancer

The Oncologist, 2006

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to t... more Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer. The Oncologist 2006;11:574-589

Research paper thumbnail of Patterns of failure in carcinoma of the upper esophagus after alternating chemoradiotherapy

The American Journal of Surgery, 1994

Research paper thumbnail of Boron Neutron Capture Therapy for Glioblastoma Multiforme: Interim Results from the Phase I/II Dose-Escalation Studies

Neurosurgery, 1999

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the s... more OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the safety of boronophenylalanine (BPA)-fructose-mediated boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM). A secondary purpose is to assess the palliation of GBM by BNCT, if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gross total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused intravenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA infusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal radiation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weighted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 Gy-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder toxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GBM. No radiation-induced damage to normal brain tissue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor progression and the median survival time from diagnosis (from Kaplan-Meier curves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offered by a single session of BNCT is comparable to that provided by fractionated photon therapy. Additional studies with further escalation of radiation doses are in progress.

Research paper thumbnail of Computational dosimetry and treatment planning considerations for neutron capture therapy

Journal of Neuro-oncology, 2003

Specialized treatment planning software systems are generally required for neutron capture therap... more Specialized treatment planning software systems are generally required for neutron capture therapy (NCT) research and clinical applications. The standard simplifying approximations that work well for treatment planning computations in the case of many other modalities are usually not appropriate for application to neutron transport. One generally must obtain an explicit three-dimensional numerical solution of the governing transport equation, with energy-dependent neutron scattering completely taken into account. Treatment planning systems that have been successfully introduced for NCT applications over the past 15 years rely on the Monte Carlo stochastic simulation method for the necessary computations, primarily because of the geometric complexity of human anatomy. However, historically, there has also been interest in the application of deterministic methods, and there have been some practical developments in this area. Most recently, interest has turned toward the creation of treatment planning software that is not limited to any specific therapy modality, with NCT as only one of several applications. A key issue with NCT treatment planning has to do with boron quantification, and whether improved information concerning the spatial biodistribution of boron can be effectively used to improve the treatment planning process. Validation and benchmarking of computations for NCT are also of current developmental interest. Various institutions have their own procedures, but standard validation models are not yet in wide use.

Research paper thumbnail of Does Postmastectomy Radiation Therapy (PMRT) After Deep Inferior Epigastric Perforator Flap (DIEP) Reconstruction Increase Complications?

International Journal of Radiation Oncology*Biology*Physics, 2012

Research paper thumbnail of Early-Stage Breast Cancer Treated With 3-Week Accelerated Whole-Breast Radiation Therapy and Concomitant Boost

International Journal of Radiation Oncology*Biology*Physics, 2013

To report early outcomes of accelerated whole-breast radiation therapy with concomitant boost. Th... more To report early outcomes of accelerated whole-breast radiation therapy with concomitant boost. This is a prospective, institutional review board-approved study. Eligibility included stage TisN0, T1N0, and T2N0 breast cancer. Patients receiving adjuvant chemotherapy were ineligible. The whole breast received 40.5 Gy in 2.7-Gy fractions with a concomitant lumpectomy boost of 4.5 Gy in 0.3-Gy fractions. Total dose to the lumpectomy site was 45 Gy in 15 fractions over 19 days. Between October 2004 and December 2010, 160 patients were treated; stage distribution was as follows: TisN0, n = 63; T1N0, n = 88; and T2N0, n = 9. With a median follow-up of 3.5 years (range, 1.5-7.8 years) the 5-year overall survival and disease-free survival rates were 90% (95% confidence interval [CI] 0.84-0.94) and 97% (95% CI 0.93-0.99), respectively. Five-year local relapse-free survival was 99% (95% CI 0.96-0.99). Acute National Cancer Institute/Common Toxicity Criteria grade 1 and 2 skin toxicity was observed in 70% and 5%, respectively. Among the patients with ≥ 2-year follow-up no toxicity higher than grade 2 on the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic scale was observed. Review of the radiation therapy dose-volume histogram noted that ≥ 95% of the prescribed dose encompassed the lumpectomy target volume in >95% of plans. The median dose received by the heart D05 was 215 cGy, and median lung V20 was 7.6%. The prescribed accelerated schedule of whole-breast radiation therapy with concomitant boost can be administered, achieving acceptable dose distribution. With follow-up to date, the results are encouraging and suggest minimal side effects and excellent local control.

Research paper thumbnail of Frequency of Breast Conserving Therapy Following an Ipsilateral Local Relapse in Patients With Ductal Carcinoma In Situ (DCIS) Treated With Lumpectomy (L) ± Radiation Therapy (RT)

International Journal of Radiation Oncology*Biology*Physics, 2013

Research paper thumbnail of Evaluating a Role for Oncotype Dx Breast Cancer Assay in the Management of Ductal Carcinoma In Situ

International Journal of Radiation Oncology*Biology*Physics, 2013

Research paper thumbnail of Three-Week Accelerated Radiation Therapy (ART) Schedule With a Concomitant In-Field Boost as Treatment for Early Stage Breast Cancer

International Journal of Radiation Oncology*Biology*Physics, 2007

Research paper thumbnail of Boron Neutron Capture Therapy of Glioblastoma Multiforme at Brookhaven National Laboratory: Results of the Phase I/II Trial

Neurosurgery, 1998

Introduction: Boron neutron capture therapy (BNCT) is a binary treatment that allows for the targ... more Introduction: Boron neutron capture therapy (BNCT) is a binary treatment that allows for the targeted irradiation of cancer cells. Significant advances in BNCT technology have occurred since the early clinical trials for glioblastoma multiforme in the United States (1951-1961). ...

Research paper thumbnail of Boron Neutron-Capture Therapy (BNCT) for Glioblastoma Multiforme (GBM) Using the Epithermal Neutron Beam at the Brookhaven National Laboratory

International Journal of Radiation OncologyBiologyPhysics, 1998

Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear r... more Boron neutron-capture therapy (BNCT) is a binary form of radiation therapy based on the nuclear reactions that occur when boron (10B) is exposed to thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial were to study the feasibility and safety of single-fraction BNCT in patients with GBM. The trial design required (a) a BPA biodistribution study performed at the time of craniotomy; and (b) BNCT within approximately 4 weeks of the biodistribution study. From September 1994 to July 1995, 10 patients were treated. For biodistribution, patients received a 2-hour intravenous (i.v.) infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after infusion, and multiple tissue samples collected during surgical debulking were analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood 10B concentrations measured before and during treatment were used to calculate the time of reactor irradiation that would deliver the prescribed dose. 10B concentrations in specimens of scalp and tumor were higher than in blood by factors of approximately 1.5 and approximately 3.5, respectively. The 10B concentration in the normal brain was < or = that in the blood; however, for purposes of estimating radiation doses to normal brain endothelium, it was always assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy-Eq), which is the sum of the various physical dose components multiplied to appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy-Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to 16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in-field alopecia. No CNS toxicity attributed to BNCT was observed. The median time to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The median time to local disease progression was longer in patients who received a higher tumor dose. The median survival time from diagnosis was 13.5 months. It is feasible to safely deliver a single fraction of BPA-based BNCT. At the dose prescribed, the patients did not experience any morbidity. To further evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a minimum target volume dose of 17 Gy-Eq is in progress.

Research paper thumbnail of 2025 Boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM), using the epithermal neutron beam at the Brookhaven national laboratory

International Journal of Radiation Oncology*Biology*Physics, 1996

Research paper thumbnail of Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: Trial design and early clinical results

Journal of neuro- …, 1997

Jeffrey A. Coderre,1 Eric H. Elowitz,2 Manjeet Chadha,3 Richard Bergland,2 Jacek Capala,1 Darrel ... more Jeffrey A. Coderre,1 Eric H. Elowitz,2 Manjeet Chadha,3 Richard Bergland,2 Jacek Capala,1 Darrel D. Joel,1 Hungyuan B. Liu,1 Daniel N. Slatkin1 and Arjun D. Chanana1 1Medical Department Brookhaven National Laboratory, Upton, NY, 11973, USA; Departments of 2 ...

Research paper thumbnail of Abstract P3-01-03: Vitamin D levels at breast cancer diagnosis: Association with patient and tumor characteristics

Research paper thumbnail of Abstract P3-08-08: Vitamin D status at breast cancer diagnosis: correlation with patient and tumor characteristics

Research paper thumbnail of Correlation of Pathological Features of Ductal Carcinoma In Situ (DCIS) and Oncotype DCIS Score

International Journal of Radiation Oncology*Biology*Physics, 2014

Research paper thumbnail of Managing a small recurrence in the previously irradiated breast. Is there a second chance for breast conservation?

Oncology (Williston Park, N.Y.), 2009

Over the past 30 years, lumpectomy and radiation therapy (breast-conservation therapy, or BCT) ha... more Over the past 30 years, lumpectomy and radiation therapy (breast-conservation therapy, or BCT) has been the preferred treatment for early-stage breast cancer. With accumulating follow-up, we have an ever-expanding pool of patients with history of an irradiated intact breast. Routine use of every-6-month or annual screening in this population has identified an emerging clinical dilemma with respect to managing a small recurrence or a second primary tumor in the treated breast. Most women diagnosed with a second cancer in a previously irradiated breast are advised to undergo mastectomy. More recently, with an improved understanding of the patterns of in-breast failure, and with advances in the delivery of conformal radiation dose there is an opportunity to reevaluate treatment alternatives for managing a small in-breast recurrence. A limited number of publications have reported on patient outcomes after a second lumpectomy and radiation therapy for this clinical scenario. In this repo...

Research paper thumbnail of Pilot study evaluating nicotinamide in metastatic brain tumors treated with radiation

Nicotinamide (NAM) has been shown to be an effective radiosensitizer in animal studies, but to da... more Nicotinamide (NAM) has been shown to be an effective radiosensitizer in animal studies, but to date no clinical studies have substantiated this effect. Twenty-nine patients with brain metastases were randomized to receive NAM and external radiation therapy (RT) (n = 14) or irradiation alone (n = 15). NAM was started on day 1 at 3 g/day and continued until radiation was completed. The RT dose to the whole brain was 30 Gy in 10 fractions in 12-14 days. To evaluate response, a computed tomographic (CT) scan of the head was repeated 1 month post-treatment. Toxicity was graded from the skin, liver, and gastrointestinal tract. There were no toxicities observed at 39.0 g total dose of NAM. Median survival for the 29 patients, calculated by the Kaplan-Meier method, was 3.5 months for the NAM + RT group (14 patients) and 3.9 months for the RT alone group (1 5 patients). Eighteen patients were evaluable for 1 month tumor response by CT scan. Response rates were compared with Fisher's exact two-tailed test. There was no difference in complete response (CR) (P = 0.62) or CR + partial response (PR) (P = 1.000) between the two groups. Adjuvant NAM, given in doses of 3.0 g/day (39.0 g total dose) in the treatment of brain metastases, has shown no benefit in survival or response in this preliminary study.

Research paper thumbnail of Dose perturbation in the presence of vaginal cylinder with Ir-192 HDR source: A radiochromic film dosimetry study

Research paper thumbnail of Interstitial high dose rate (HDR) brachytherapy (BT) in patients with cancer (CA) of the head & neck (H&N)

International Journal of Radiation Oncology Biology Physics - INT J RADIAT ONCOL BIOL PHYS, 1993

Research paper thumbnail of Primary Systemic Therapy of Breast Cancer

The Oncologist, 2006

Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to t... more Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer. The Oncologist 2006;11:574-589

Research paper thumbnail of Patterns of failure in carcinoma of the upper esophagus after alternating chemoradiotherapy

The American Journal of Surgery, 1994

Research paper thumbnail of Boron Neutron Capture Therapy for Glioblastoma Multiforme: Interim Results from the Phase I/II Dose-Escalation Studies

Neurosurgery, 1999

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the s... more OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the safety of boronophenylalanine (BPA)-fructose-mediated boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM). A secondary purpose is to assess the palliation of GBM by BNCT, if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gross total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused intravenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA infusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal radiation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weighted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 Gy-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder toxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GBM. No radiation-induced damage to normal brain tissue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor progression and the median survival time from diagnosis (from Kaplan-Meier curves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offered by a single session of BNCT is comparable to that provided by fractionated photon therapy. Additional studies with further escalation of radiation doses are in progress.

Research paper thumbnail of Computational dosimetry and treatment planning considerations for neutron capture therapy

Journal of Neuro-oncology, 2003

Specialized treatment planning software systems are generally required for neutron capture therap... more Specialized treatment planning software systems are generally required for neutron capture therapy (NCT) research and clinical applications. The standard simplifying approximations that work well for treatment planning computations in the case of many other modalities are usually not appropriate for application to neutron transport. One generally must obtain an explicit three-dimensional numerical solution of the governing transport equation, with energy-dependent neutron scattering completely taken into account. Treatment planning systems that have been successfully introduced for NCT applications over the past 15 years rely on the Monte Carlo stochastic simulation method for the necessary computations, primarily because of the geometric complexity of human anatomy. However, historically, there has also been interest in the application of deterministic methods, and there have been some practical developments in this area. Most recently, interest has turned toward the creation of treatment planning software that is not limited to any specific therapy modality, with NCT as only one of several applications. A key issue with NCT treatment planning has to do with boron quantification, and whether improved information concerning the spatial biodistribution of boron can be effectively used to improve the treatment planning process. Validation and benchmarking of computations for NCT are also of current developmental interest. Various institutions have their own procedures, but standard validation models are not yet in wide use.

Research paper thumbnail of Does Postmastectomy Radiation Therapy (PMRT) After Deep Inferior Epigastric Perforator Flap (DIEP) Reconstruction Increase Complications?

International Journal of Radiation Oncology*Biology*Physics, 2012

Research paper thumbnail of Early-Stage Breast Cancer Treated With 3-Week Accelerated Whole-Breast Radiation Therapy and Concomitant Boost

International Journal of Radiation Oncology*Biology*Physics, 2013

To report early outcomes of accelerated whole-breast radiation therapy with concomitant boost. Th... more To report early outcomes of accelerated whole-breast radiation therapy with concomitant boost. This is a prospective, institutional review board-approved study. Eligibility included stage TisN0, T1N0, and T2N0 breast cancer. Patients receiving adjuvant chemotherapy were ineligible. The whole breast received 40.5 Gy in 2.7-Gy fractions with a concomitant lumpectomy boost of 4.5 Gy in 0.3-Gy fractions. Total dose to the lumpectomy site was 45 Gy in 15 fractions over 19 days. Between October 2004 and December 2010, 160 patients were treated; stage distribution was as follows: TisN0, n = 63; T1N0, n = 88; and T2N0, n = 9. With a median follow-up of 3.5 years (range, 1.5-7.8 years) the 5-year overall survival and disease-free survival rates were 90% (95% confidence interval [CI] 0.84-0.94) and 97% (95% CI 0.93-0.99), respectively. Five-year local relapse-free survival was 99% (95% CI 0.96-0.99). Acute National Cancer Institute/Common Toxicity Criteria grade 1 and 2 skin toxicity was observed in 70% and 5%, respectively. Among the patients with ≥ 2-year follow-up no toxicity higher than grade 2 on the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic scale was observed. Review of the radiation therapy dose-volume histogram noted that ≥ 95% of the prescribed dose encompassed the lumpectomy target volume in >95% of plans. The median dose received by the heart D05 was 215 cGy, and median lung V20 was 7.6%. The prescribed accelerated schedule of whole-breast radiation therapy with concomitant boost can be administered, achieving acceptable dose distribution. With follow-up to date, the results are encouraging and suggest minimal side effects and excellent local control.

Research paper thumbnail of Frequency of Breast Conserving Therapy Following an Ipsilateral Local Relapse in Patients With Ductal Carcinoma In Situ (DCIS) Treated With Lumpectomy (L) ± Radiation Therapy (RT)

International Journal of Radiation Oncology*Biology*Physics, 2013

Research paper thumbnail of Evaluating a Role for Oncotype Dx Breast Cancer Assay in the Management of Ductal Carcinoma In Situ

International Journal of Radiation Oncology*Biology*Physics, 2013

Research paper thumbnail of Three-Week Accelerated Radiation Therapy (ART) Schedule With a Concomitant In-Field Boost as Treatment for Early Stage Breast Cancer

International Journal of Radiation Oncology*Biology*Physics, 2007