The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to b... more The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to bone marrow metastases, which are common in the natural history of neuroblastoma. In vitro and preliminary clinical studies have implied improved efficacy of I-125 relative to I-131 in certain clinical situations, although areas of uncertainty remain regarding intratumoral dosimetry. This prompted our study using human neuroblastoma multicellular spheroids as a model of metastasis. 3D dose calculations were made using voxel-based Medical Internal Radiation Dosimetry (MIRD) and dose-point-kernel (DPK) techniques. Dose distributions for I-131 and I-125 labeled mIBG were calculated for spheroids (metastases) of various sizes from 0.01 cm to 3 cm diameter, and the relative dose delivered to the tumors was compared for the same limiting dose to the bone marrow. Based on the same data, arguments were advanced based upon the principles of tumor control probability (TCP) to emphasize the potentia...
It has been recognized that flocculation performance can be related to the mixing process. This p... more It has been recognized that flocculation performance can be related to the mixing process. This process has traditionally been described by vessel average parameters such as the root-mean square velocity gradient G¯, which may not represent local mixing conditions within a vessel, particularly in the impeller vicinity. The analysis of turbulence in the flocculator allows a more refined specification of flow, energy, and dissipation, which have long been known to be important to the flocculation process. Presented is a study to characterize hydrodynamic conditions in the impeller zone of an upflow solids-contacting clarifier using a laser Doppler anemometer. Results were analyzed based on an analogy of the impeller-generated flow to a swirling radial jet. It was found that mean and fluctuating velocities scaled on the tip speed of the impeller. Use of the swirling radial jet analogy also allowed the scaling of local dissipation rates. Results compared favorably to other impeller studies and true radial jet...
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans f... more Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Materials and Methods-IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results-Compared with IMRT, median lung volumes exposed to 5,10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%,5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%,5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index CI=1.99) and greater irradiation of the heart (heart-V40=41.8%) compared with the IMRT plan(CI=1.55, heart-V40=35.7%) or the three-beam proton plan (CI=1.46, heart-V40=27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas-filling. Conclusions-Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.
International Journal of Radiation Oncology*Biology*Physics, 2008
Materials/Methods: Real-time tracking of the position of a gold marker surgically embedded in the... more Materials/Methods: Real-time tracking of the position of a gold marker surgically embedded in the lung was performed using the RTRT system at Hokkaido University Hospital. Measurements were carried out prior to the first radiation therapy session of each patient. The marker motion was determined for 4 setup , with and without the SBF. Population for this study consisted of 18 patients at various cancer stages. Patient data were classified based on the location of the marker. Histograms of the displacement of the marker positions relative to its median were constructed for the x-axis (medio-lateral), yaxis (cranio-caudal) and z-axis (dorso-ventral). The effect of the SBF on respiratory organ motion was evaluated by considering the displacement from the median position of the marker along each of the coordinate axes that included a cumulative frequency of 90% or greater of all recorded the marker positions. Smaller displacements of the gold marker indicated less organ motion. Results from measurements without the SBF were used as the benchmark. Results: Marker displacements confirmed that the range of respiratory organ motion is highest in the y-axis and least in the x-axis, regardless of whether the SBF is used or not. The range of motion along the coordinate axes of the markers in the upper right and left lobes of the lung were not influenced by the SBF. However, using it in combination with an abdominal press resulted in 1.4 mm reduction in the marker range of motion along the y-axis for the upper right lobe but increased by about 3mm for the upper left lobe. For markers placed in the lower right lobe, the range of motion along the x-axis was 1.4mm and 0.8mm shorter when an SBF and an SBF together with an abdominal press was used, respectively. The y-axis motion was reduced by as much as 4.4 mm with the SBF but only by 0.8 mm with the SBF plus abdominal press. This may have been brought about by the large deviation in the individual data for this set of patients. Motion along the z-axis was not significantly changed with the use of the SBF. No significant differences in the x-and z-axes motion between all setups for markers embedded in the lower left lobe. In the y-axis, using the SBF alone reduce the motion by 1 mm and by 2 mm when the body frame was used together with the abdominal press. Conclusions: The stereotactic body frame used together with an abdominal press may be useful in restricting respiratory organ motion during RTRT, particularly in the cranio-caudal direction.
International Journal of Radiation Oncology*Biology*Physics, 2011
Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesio... more Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.
World Health Organization Trial Registration Dataset. List of Fields in Trial Registration Databa... more World Health Organization Trial Registration Dataset. List of Fields in Trial Registration Database. (DOC 76 kb)
International Journal of Radiation Oncology*Biology*Physics, 2019
Purpose/Objective(s): Coronary artery calcium (CAC) is one of the strongest predictors of long-te... more Purpose/Objective(s): Coronary artery calcium (CAC) is one of the strongest predictors of long-term atherosclerotic coronary vascular disease in asymptomatic individuals, however the feasibility of quantitating this measurement from radiotherapy (RT) planning computed tomography (CT) scans is unknown. Since patients with non-small cell lung cancer (NSCLC) represent a distinctly high cardiovascular risk population, we sought to quantify CAC from RT planning CTs in NSCLC patients using a deep learning model. Materials/Methods: Retrospective analysis of non-contrast enhanced RT planning CTs from 464 consecutive locally-advanced NSCLC patients treated with thoracic RT. The CAC algorithm was previously trained on 693 independent cardiac-gated CT scans manually segmented by expert readers using three consecutive deep learning networks for segmentation and tested on three independent cohorts of 441, 664, and 398 scans. Plaques 1 cubic millimeter were volumetrically measured and multiplied by a maximum plaque density factor to generate an Agatson-like CAC Score. The model was used to calculate a CAC risk group for each planning CT, defined as CACZ0 (very low risk) versus CAC>0 (elevated risk). For patient factors, continuous covariates were evaluated using a Wilcoxon rank sum test whereas categorical covariates were compared using a Fisher exact test. Univariable Cox regression analysis was performed and Kaplan-Meier estimates of all-cause mortality were calculated. Results: After a median follow-up of 18 months, there were 353 deaths (2-year all-cause mortality, 52.2% [95% CI, 47.7-56.8%]). Of the 464 planning CTs, 35% (162/464) were CACZ0 and 65% (302/464) were CAC>0. Patients in the CAC>0 group were older (median age 67 vs. 60 years, P<.0001), more likely male (58% vs. 37%, P<.001), have an eversmoking history (95% vs. 84%, P<.001), and less likely treated with surgery (32% vs. 45%, PZ.003) or chemotherapy (91% vs. 97%, PZ.008). There was no difference in mean heart dose delivered between CAC>0 vs. CACZ0 (11.9 Gy vs. 11.5 Gy, PZ.83). CAC>0 was associated with an increased risk of all-cause mortality on univariable Cox regression (hazard ratio, 1.29 [95% CI, 1.03-1.62]; PZ.027). The 2-year all-cause mortality stratified by CAC group was 56.7% (95% CI, 51.1-62.3%) in CAC>0 vs. 47.1% (95% CI, 39.6-55.1%) in CACZ0 (log-rank PZ.0259). Conclusion: Coronary artery calcium was effectively measured from non-contrast RT planning CTs using an automated deep learning model. Elevated CAC, as predicted by the deep neural network, was associated with an increased risk of all-cause mortality on univariable analysis in locally-advanced NSCLC patients despite a high competing risk of lung cancer death. Deeper investigation of contributing and confounding variables in a comprehensive predictive model is warranted.
The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast c... more The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia. We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms. More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and pos...
International Journal of Radiation Oncology*Biology*Physics, 2018
Purpose/Objective(s): Chartrounds (www.chartrounds.com) is a free web-based virtual conferencing ... more Purpose/Objective(s): Chartrounds (www.chartrounds.com) is a free web-based virtual conferencing platform for radiation oncologists to review cases with leading disease-site experts. Chartrounds was founded in the US in 2010, and in recent years the international member base has grown substantially. To respond to the increased interest in Chartrounds globally, 4 dedicated international Chartrounds sites were developed: Chartrounds India, Chartrounds Africa, Chartrounds Latin America, and Chartrounds China. Chartrounds India was the first site to launch in June 2017, and our initial experience with this initiative is reported here. Materials/Methods: The US Chartrounds platform was adapted to create Chartrounds India (ind.chartrounds.com). Through a partnership with the Association of Radiation Oncologists of India (AROI), India-based specialists were recruited, and the potential Chartrounds India audience was targeted through the AROI membership email list. The first Chartrounds India session commenced in June 2017, and one-hour disease site and/or technique focused sessions have continued on a weekly basis at a scheduled time since. In September 2017, a survey was sent to all Chartrounds India members to collect initial feedback. The same feedback questions from this initial survey were asked of participants after each subsequent session from October 2017 onward.
International Journal of Radiation Oncology*Biology*Physics, 2016
The current standard of care for unresectable locally advanced stage III non-small cell lung canc... more The current standard of care for unresectable locally advanced stage III non-small cell lung cancer (NSCLC) is chemoradiation therapy. However, there is no established consensus for the optimal chemotherapy regimen. We designed a phase I study of docetaxel and cisplatin (DC) chemotherapy with concurrent thoracic radiation therapy (RT) followed by consolidative DC for locally advanced NSCLC. The primary objective of this study is to determine optimal concurrent and consolidative DC doses, with secondary objectives to describe associated toxicities. Materials/Methods: Patients with histologically or cytologically proven and unresectable Stage IIIA or IIIB (dry) NSCLC were eligible for this single-institution research-ethics board approved study. In the concurrent cycles with thoracic RT, C was given every 3 weeks (fixed at 75mg/m 2) and D given weekly. The starting dose of D was 20mg/m 2 weekly escalated in cohorts of 3 to define the maximum tolerated dose. RT was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidative DC, which were dose escalated if concurrent chemoradiation therapy was tolerated. Evaluation for dose limiting toxicities was performed on a weekly basis during RT. Tumor response was characterized through the RECIST criteria. Actuarial outcomes of overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier analysis. Results: Between September 2004 and June 2014, 26 patients were enrolled. One patient did not receive protocol-specified treatment due to metastatic disease on baseline staging investigations. Of the eligible patients, 18 had stage IIIA and 7 had stage IIIB disease. The median OS of all patients was 33.6 months (95% CI 15.8-71.6). Median PFS was 17.0 months (95% CI 9.2-26.3) with median follow-up of 26.6 months (range 0.43-110.8). The majority of patients (19/26) completed both phases of treatment and most received concurrent D at 20mg/m 2 weekly. Eight patients tolerated dose escalation of posterior consolidative C or D. Twelve patients experienced grade 3 toxicities (5 esophagitis, 1 pneumonitis, 3 nausea, 1 leukopenia, and 2 neutropenia). Three patients had grade 4 neutropenia. No patients died due to early or late treatment toxicities. Complete response, partial response, and stable disease were observed in 1, 16, and 4 patients, respectively. Five patients underwent surgical resection, and 3 of 5 did not have evidence of residual disease. Conclusion: Cisplatin and docetaxel (DC) chemotherapy with concurrent radiation treatment followed by consolidative DC achieved promising results in the treatment of stage III NSCLC in light of reported outcomes from RTOG 0617 (standard arm median PFS 11.8, OS 28.7 months). However, treatment toxicities should be considered. The dose finding results of this study will inform the design of phase II/III trials.
Radiation oncology (London, England), Jan 27, 2017
A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR... more A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR) before surgery improves oncologic outcomes in patients with stage I non-small cell lung cancer (NSCLC). We report a mandated interim safety analysis for the first 10 patients who completed protocol treatment. Operable patients with biopsy-proven T1-2 N0 NSCLC were eligible. SABR was delivered using a risk-adapted fractionation (54Gy/3 fractions, 55/5 or 60/8). Surgical resection was planned 10 weeks later at a high-volume center (>200 lung cancer resections annually). Patients were imaged with dynamic positron emission tomography-computed tomography scans using (18)F-fludeoxyglucose ((18)F-FDG-PET CT) and dynamic contrast-enhanced CT before SABR and again before surgery. Toxicity was recorded using CTCAE version 4.0. Twelve patients were enrolled between 09/2014 and 09/2015. Two did not undergo surgery, due to patient or surgeon preference; neither patient has developed toxicity or ...
We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integ... more We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deter...
The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent che... more The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation...
Reports in the medical literature have described cases of extended survival of patients with non-... more Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population. A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm. Median survival was 7.8 months, and a...
ABSTRACT Management of patients who have disease relapse after completion of surgery and adjuvant... more ABSTRACT Management of patients who have disease relapse after completion of surgery and adjuvant chemo-radiation (CRT) is controversial.Some oncologists would advocate intensive therapeutic intervention due to promising experience on treatment for recurrence disease while others would recommend palliative support due to the concerns for poor patient outcome post disease recurrence.In Addition, it is not clear if patient outcome is improved post adjuvant CRT when patients at risk have resection margin involvement and if time interval to recurrence can affect patient survival post relapse.The present study was conducted to determine what factors will affect patient outcome at relapse after previous surgery and adjuvant CRT in high-risk esophageal cancer patientsThis clinical information may be useful in providing appropriate guidance for oncologists to manage esophageal cancer patients after disease relapse.
The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to b... more The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to bone marrow metastases, which are common in the natural history of neuroblastoma. In vitro and preliminary clinical studies have implied improved efficacy of I-125 relative to I-131 in certain clinical situations, although areas of uncertainty remain regarding intratumoral dosimetry. This prompted our study using human neuroblastoma multicellular spheroids as a model of metastasis. 3D dose calculations were made using voxel-based Medical Internal Radiation Dosimetry (MIRD) and dose-point-kernel (DPK) techniques. Dose distributions for I-131 and I-125 labeled mIBG were calculated for spheroids (metastases) of various sizes from 0.01 cm to 3 cm diameter, and the relative dose delivered to the tumors was compared for the same limiting dose to the bone marrow. Based on the same data, arguments were advanced based upon the principles of tumor control probability (TCP) to emphasize the potentia...
It has been recognized that flocculation performance can be related to the mixing process. This p... more It has been recognized that flocculation performance can be related to the mixing process. This process has traditionally been described by vessel average parameters such as the root-mean square velocity gradient G¯, which may not represent local mixing conditions within a vessel, particularly in the impeller vicinity. The analysis of turbulence in the flocculator allows a more refined specification of flow, energy, and dissipation, which have long been known to be important to the flocculation process. Presented is a study to characterize hydrodynamic conditions in the impeller zone of an upflow solids-contacting clarifier using a laser Doppler anemometer. Results were analyzed based on an analogy of the impeller-generated flow to a swirling radial jet. It was found that mean and fluctuating velocities scaled on the tip speed of the impeller. Use of the swirling radial jet analogy also allowed the scaling of local dissipation rates. Results compared favorably to other impeller studies and true radial jet...
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans f... more Purpose-To compare three-dimensional (3D) and 4D computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Materials and Methods-IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results-Compared with IMRT, median lung volumes exposed to 5,10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%,5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%,5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index CI=1.99) and greater irradiation of the heart (heart-V40=41.8%) compared with the IMRT plan(CI=1.55, heart-V40=35.7%) or the three-beam proton plan (CI=1.46, heart-V40=27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas-filling. Conclusions-Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.
International Journal of Radiation Oncology*Biology*Physics, 2008
Materials/Methods: Real-time tracking of the position of a gold marker surgically embedded in the... more Materials/Methods: Real-time tracking of the position of a gold marker surgically embedded in the lung was performed using the RTRT system at Hokkaido University Hospital. Measurements were carried out prior to the first radiation therapy session of each patient. The marker motion was determined for 4 setup , with and without the SBF. Population for this study consisted of 18 patients at various cancer stages. Patient data were classified based on the location of the marker. Histograms of the displacement of the marker positions relative to its median were constructed for the x-axis (medio-lateral), yaxis (cranio-caudal) and z-axis (dorso-ventral). The effect of the SBF on respiratory organ motion was evaluated by considering the displacement from the median position of the marker along each of the coordinate axes that included a cumulative frequency of 90% or greater of all recorded the marker positions. Smaller displacements of the gold marker indicated less organ motion. Results from measurements without the SBF were used as the benchmark. Results: Marker displacements confirmed that the range of respiratory organ motion is highest in the y-axis and least in the x-axis, regardless of whether the SBF is used or not. The range of motion along the coordinate axes of the markers in the upper right and left lobes of the lung were not influenced by the SBF. However, using it in combination with an abdominal press resulted in 1.4 mm reduction in the marker range of motion along the y-axis for the upper right lobe but increased by about 3mm for the upper left lobe. For markers placed in the lower right lobe, the range of motion along the x-axis was 1.4mm and 0.8mm shorter when an SBF and an SBF together with an abdominal press was used, respectively. The y-axis motion was reduced by as much as 4.4 mm with the SBF but only by 0.8 mm with the SBF plus abdominal press. This may have been brought about by the large deviation in the individual data for this set of patients. Motion along the z-axis was not significantly changed with the use of the SBF. No significant differences in the x-and z-axes motion between all setups for markers embedded in the lower left lobe. In the y-axis, using the SBF alone reduce the motion by 1 mm and by 2 mm when the body frame was used together with the abdominal press. Conclusions: The stereotactic body frame used together with an abdominal press may be useful in restricting respiratory organ motion during RTRT, particularly in the cranio-caudal direction.
International Journal of Radiation Oncology*Biology*Physics, 2011
Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesio... more Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.
World Health Organization Trial Registration Dataset. List of Fields in Trial Registration Databa... more World Health Organization Trial Registration Dataset. List of Fields in Trial Registration Database. (DOC 76 kb)
International Journal of Radiation Oncology*Biology*Physics, 2019
Purpose/Objective(s): Coronary artery calcium (CAC) is one of the strongest predictors of long-te... more Purpose/Objective(s): Coronary artery calcium (CAC) is one of the strongest predictors of long-term atherosclerotic coronary vascular disease in asymptomatic individuals, however the feasibility of quantitating this measurement from radiotherapy (RT) planning computed tomography (CT) scans is unknown. Since patients with non-small cell lung cancer (NSCLC) represent a distinctly high cardiovascular risk population, we sought to quantify CAC from RT planning CTs in NSCLC patients using a deep learning model. Materials/Methods: Retrospective analysis of non-contrast enhanced RT planning CTs from 464 consecutive locally-advanced NSCLC patients treated with thoracic RT. The CAC algorithm was previously trained on 693 independent cardiac-gated CT scans manually segmented by expert readers using three consecutive deep learning networks for segmentation and tested on three independent cohorts of 441, 664, and 398 scans. Plaques 1 cubic millimeter were volumetrically measured and multiplied by a maximum plaque density factor to generate an Agatson-like CAC Score. The model was used to calculate a CAC risk group for each planning CT, defined as CACZ0 (very low risk) versus CAC>0 (elevated risk). For patient factors, continuous covariates were evaluated using a Wilcoxon rank sum test whereas categorical covariates were compared using a Fisher exact test. Univariable Cox regression analysis was performed and Kaplan-Meier estimates of all-cause mortality were calculated. Results: After a median follow-up of 18 months, there were 353 deaths (2-year all-cause mortality, 52.2% [95% CI, 47.7-56.8%]). Of the 464 planning CTs, 35% (162/464) were CACZ0 and 65% (302/464) were CAC>0. Patients in the CAC>0 group were older (median age 67 vs. 60 years, P<.0001), more likely male (58% vs. 37%, P<.001), have an eversmoking history (95% vs. 84%, P<.001), and less likely treated with surgery (32% vs. 45%, PZ.003) or chemotherapy (91% vs. 97%, PZ.008). There was no difference in mean heart dose delivered between CAC>0 vs. CACZ0 (11.9 Gy vs. 11.5 Gy, PZ.83). CAC>0 was associated with an increased risk of all-cause mortality on univariable Cox regression (hazard ratio, 1.29 [95% CI, 1.03-1.62]; PZ.027). The 2-year all-cause mortality stratified by CAC group was 56.7% (95% CI, 51.1-62.3%) in CAC>0 vs. 47.1% (95% CI, 39.6-55.1%) in CACZ0 (log-rank PZ.0259). Conclusion: Coronary artery calcium was effectively measured from non-contrast RT planning CTs using an automated deep learning model. Elevated CAC, as predicted by the deep neural network, was associated with an increased risk of all-cause mortality on univariable analysis in locally-advanced NSCLC patients despite a high competing risk of lung cancer death. Deeper investigation of contributing and confounding variables in a comprehensive predictive model is warranted.
The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast c... more The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia. We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms. More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and pos...
International Journal of Radiation Oncology*Biology*Physics, 2018
Purpose/Objective(s): Chartrounds (www.chartrounds.com) is a free web-based virtual conferencing ... more Purpose/Objective(s): Chartrounds (www.chartrounds.com) is a free web-based virtual conferencing platform for radiation oncologists to review cases with leading disease-site experts. Chartrounds was founded in the US in 2010, and in recent years the international member base has grown substantially. To respond to the increased interest in Chartrounds globally, 4 dedicated international Chartrounds sites were developed: Chartrounds India, Chartrounds Africa, Chartrounds Latin America, and Chartrounds China. Chartrounds India was the first site to launch in June 2017, and our initial experience with this initiative is reported here. Materials/Methods: The US Chartrounds platform was adapted to create Chartrounds India (ind.chartrounds.com). Through a partnership with the Association of Radiation Oncologists of India (AROI), India-based specialists were recruited, and the potential Chartrounds India audience was targeted through the AROI membership email list. The first Chartrounds India session commenced in June 2017, and one-hour disease site and/or technique focused sessions have continued on a weekly basis at a scheduled time since. In September 2017, a survey was sent to all Chartrounds India members to collect initial feedback. The same feedback questions from this initial survey were asked of participants after each subsequent session from October 2017 onward.
International Journal of Radiation Oncology*Biology*Physics, 2016
The current standard of care for unresectable locally advanced stage III non-small cell lung canc... more The current standard of care for unresectable locally advanced stage III non-small cell lung cancer (NSCLC) is chemoradiation therapy. However, there is no established consensus for the optimal chemotherapy regimen. We designed a phase I study of docetaxel and cisplatin (DC) chemotherapy with concurrent thoracic radiation therapy (RT) followed by consolidative DC for locally advanced NSCLC. The primary objective of this study is to determine optimal concurrent and consolidative DC doses, with secondary objectives to describe associated toxicities. Materials/Methods: Patients with histologically or cytologically proven and unresectable Stage IIIA or IIIB (dry) NSCLC were eligible for this single-institution research-ethics board approved study. In the concurrent cycles with thoracic RT, C was given every 3 weeks (fixed at 75mg/m 2) and D given weekly. The starting dose of D was 20mg/m 2 weekly escalated in cohorts of 3 to define the maximum tolerated dose. RT was prescribed to a dose of 60 Gy in 30 fractions. This was followed by 2 cycles of consolidative DC, which were dose escalated if concurrent chemoradiation therapy was tolerated. Evaluation for dose limiting toxicities was performed on a weekly basis during RT. Tumor response was characterized through the RECIST criteria. Actuarial outcomes of overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier analysis. Results: Between September 2004 and June 2014, 26 patients were enrolled. One patient did not receive protocol-specified treatment due to metastatic disease on baseline staging investigations. Of the eligible patients, 18 had stage IIIA and 7 had stage IIIB disease. The median OS of all patients was 33.6 months (95% CI 15.8-71.6). Median PFS was 17.0 months (95% CI 9.2-26.3) with median follow-up of 26.6 months (range 0.43-110.8). The majority of patients (19/26) completed both phases of treatment and most received concurrent D at 20mg/m 2 weekly. Eight patients tolerated dose escalation of posterior consolidative C or D. Twelve patients experienced grade 3 toxicities (5 esophagitis, 1 pneumonitis, 3 nausea, 1 leukopenia, and 2 neutropenia). Three patients had grade 4 neutropenia. No patients died due to early or late treatment toxicities. Complete response, partial response, and stable disease were observed in 1, 16, and 4 patients, respectively. Five patients underwent surgical resection, and 3 of 5 did not have evidence of residual disease. Conclusion: Cisplatin and docetaxel (DC) chemotherapy with concurrent radiation treatment followed by consolidative DC achieved promising results in the treatment of stage III NSCLC in light of reported outcomes from RTOG 0617 (standard arm median PFS 11.8, OS 28.7 months). However, treatment toxicities should be considered. The dose finding results of this study will inform the design of phase II/III trials.
Radiation oncology (London, England), Jan 27, 2017
A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR... more A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR) before surgery improves oncologic outcomes in patients with stage I non-small cell lung cancer (NSCLC). We report a mandated interim safety analysis for the first 10 patients who completed protocol treatment. Operable patients with biopsy-proven T1-2 N0 NSCLC were eligible. SABR was delivered using a risk-adapted fractionation (54Gy/3 fractions, 55/5 or 60/8). Surgical resection was planned 10 weeks later at a high-volume center (>200 lung cancer resections annually). Patients were imaged with dynamic positron emission tomography-computed tomography scans using (18)F-fludeoxyglucose ((18)F-FDG-PET CT) and dynamic contrast-enhanced CT before SABR and again before surgery. Toxicity was recorded using CTCAE version 4.0. Twelve patients were enrolled between 09/2014 and 09/2015. Two did not undergo surgery, due to patient or surgeon preference; neither patient has developed toxicity or ...
We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integ... more We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deter...
The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent che... more The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation...
Reports in the medical literature have described cases of extended survival of patients with non-... more Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population. A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm. Median survival was 7.8 months, and a...
ABSTRACT Management of patients who have disease relapse after completion of surgery and adjuvant... more ABSTRACT Management of patients who have disease relapse after completion of surgery and adjuvant chemo-radiation (CRT) is controversial.Some oncologists would advocate intensive therapeutic intervention due to promising experience on treatment for recurrence disease while others would recommend palliative support due to the concerns for poor patient outcome post disease recurrence.In Addition, it is not clear if patient outcome is improved post adjuvant CRT when patients at risk have resection margin involvement and if time interval to recurrence can affect patient survival post relapse.The present study was conducted to determine what factors will affect patient outcome at relapse after previous surgery and adjuvant CRT in high-risk esophageal cancer patientsThis clinical information may be useful in providing appropriate guidance for oncologists to manage esophageal cancer patients after disease relapse.
Uploads
Papers by Brian Yaremko