Thomas Delaney | Harvard Medical School (original) (raw)
Papers by Thomas Delaney
Fuel and Energy Abstracts, 2011
Purpose/Objective(s): Chemotherapy is considered the treatment of choice for inoperable intracran... more Purpose/Objective(s): Chemotherapy is considered the treatment of choice for inoperable intracranial low-grade glioma (LGG) in young children. Children under the age of 5 years who receive radiation therapy (RT) risk significant cognitive effects and vasculopathy. Although older patients have fewer complications with RT, some would consider the use of chemotherapy to be appropriate regardless of age. We sought to determine if chemotherapy administered prior to RT reduced progression-free or overall survival. Materials/Methods: An IRB approved retrospective review was undertaken using the information from 180 children (median age 8.1 years, range, 1.2-20.0 years) with intracranial LGG irradiated at St. Jude Children's Research Hospital between 5/1986 and 8/2010. The cohort was characterized according to gender (female = 81), race (white = 148), pre-RT chemotherapy (n = 66), progression after RT (n = 46) and death (n = 18). Results: With a median follow-up of 8.8 years (range, 0.3-24.3 years) after RT for the survivors, the 10 year progression-free and overall survivals were 71% + 4% and 89% + 3%, respectively. The 10 year overall survival estimates were 85% + 5% for those treated with chemotherapy prior to RT vs. 92% + 3% for those treated with RT alone (p = 0.014). The impact of pre-RT chemotherapy was increased (p = 0.004) when age was included as a continuous variable in Cox regression analysis. Conclusions: The use of chemotherapy prior to RT reduced overall survival but did not impact progression-free survival. Chemotherapy plays an important role in delaying the use of definitive irradiation in young children; however, this benefit must be balanced against the negative impact of chemotherapy on overall survival after RT. Further investigation will focus on the impact of specific chemotherapy regimens and clinical features of these patients to specify the risks.
International journal of radiation oncology, biology, physics, 2015
Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcom... more Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended t...
Journal of the National Comprehensive Cancer Network: JNCCN
These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Ti... more These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.
Journal of the National Comprehensive Cancer Network: JNCCN
... MD,; John D. Pfeifer, MD, PhD,; Raphael E. Pollock, MD,; R. Lor Randall, MD,; Richard F. Ried... more ... MD,; John D. Pfeifer, MD, PhD,; Raphael E. Pollock, MD,; R. Lor Randall, MD,; Richard F. Riedel, MD,; Karen D. Schupak, MD,; Herbert S. Schwartz, MD,; Katherine Thornton, MD,; Margaret von Mehren, MD and; Jeffrey Wayne, MD. ...
Journal of the National Comprehensive Cancer Network: JNCCN
The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the man... more The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.
Cancer control : journal of the Moffitt Cancer Center
For patients with sarcomas, radiotherapy can be used as neoadjuvant, adjuvant, or primary local t... more For patients with sarcomas, radiotherapy can be used as neoadjuvant, adjuvant, or primary local therapy, depending on the site and type of sarcoma, the surgical approach, and the efficacy of chemotherapy. The authors review the current status of advanced technology radiation therapy in the management of bone and soft tissue sarcoma. Advances in radiotherapy have resulted in improved treatment for bone and soft tissue sarcomas. Intensity-modulated radiation therapy (IMRT) uses modifications in the intensity of the photon-beam from a linear accelerator across the irradiated fields to enhance dose conformation in three dimensions. For proton-beam radiation therapy, the nuclei of hydrogen atoms are accelerated in cyclotrons or synchrotrons, extracted, and transported to treatment rooms where the proton beam undergoes a series of modifications that conform the dose in a particular patient to the tumor target. Brachytherapy and intraoperative radiation therapy have generally been used to ...
Journal of surgical oncology, 2014
Negative surgical margins are uncommon for spine sarcomas; hence, adjuvant radiotherapy (RT) may ... more Negative surgical margins are uncommon for spine sarcomas; hence, adjuvant radiotherapy (RT) may be recommended but tumor dose may be constrained by spinal cord, nerve, and viscera tolerance. Prospective Phase II clinical trial incorporating high dose RT. Eligible patients had primary or locally recurrent thoracic, lumbar, and/or sacral spine/paraspinal chordomas or sarcomas. Treatment included pre- and/or post-operative photon/proton RT ± radical resection. Fifty patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). RT dose was ≤72.0 GyRBE in 25 patients and 76.6-77.4 GyRBE in 25 patients. With 7.3-year median follow-up, the 5 and 8-year actuarial local control (LC) rates were 94% and 85% for primary tumors and 81% and 74% for the entire group. Local recurrence was less common for primary tumors, 4/36 (11%) versus 7/14 (50%) for recurrent tumors, P = 0.002. The 8-year actuarial risk of grade 3-4 late RT ...
Practical radiation oncology
Proper positioning of patients with extremity sarcoma tumors can be challenging. A surface imagin... more Proper positioning of patients with extremity sarcoma tumors can be challenging. A surface imaging technique was utilized to quantify the setup uncertainties for sarcoma patients and to assess whether surface imaging could improve the accuracy of patient positioning. Pretreatment and posttreatment 3-dimensional (3D) surface images were obtained for 16 patients and 236 treatments. Offline surface registration was performed to quantify interfraction and intrafraction setup errors, and the required planning target volume (PTV) margins were calculated. Setup differences were also assessed using root mean square (RMS) error analysis. For intrafraction variation, the mean 3D vector shift was 2.1 mm, and the systematic and random errors were 1.3 mm or less. When using a reference surface from the first fraction, the mean interfraction setup variation (3D vector shift) was 7.6 mm. Systematic and random errors were 3-4 mm in each direction. When using a computed tomographic based reference s...
Journal of surgical oncology, 2014
The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and su... more The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and surgery in extremity soft tissue sarcomas (STS) is unclear. We assessed the contribution of a boost to local control (LC), disease-free survival (DFS), and overall survival (OS). We identified 67 patients treated from 1987 to 2011 with pre-operative RT and surgery with positive margin(s). Select patients received a boost delivered as peri-operative Iridium-192 brachytherapy (BRT), intra-operative electrons (IORT), or post-operative external beam RT (EBRT). Ten patients received no RT boost, 10 received a BRT or IORT boost, and 47 received an EBRT boost. Five-year LC rates for no boost, BRT/IORT boost, and EBRT boost were 100%, 78%, and 71% (P = 0.5). On multivariate analysis, there were no significant predictors for LC. Variables associated with improved DFS rates were single positive margin (P = 0.007) and low tumor grade (P = 0.03). Tumor size <5 cm (P = 0.003), low grade (P = 0.001),...
International journal of radiation oncology, biology, physics, 2014
To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-P... more To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy...
Anticancer research, 2009
Chordomas are rare tumors of the axial skeleton for which surgical resection remains the most rel... more Chordomas are rare tumors of the axial skeleton for which surgical resection remains the most reliable means of cure. PI-103 is a inhibitor of PI3K/AKT and mTOR activation. This study aims to determine whether the PI3K/mTOR pathway was active in chordomas and whether their inhibition could lead to decreased proliferation and increased apoptosis. Thirteen human chordoma were tested for activation of the PI3K/mTOR pathway. The human chordoma cell line UCH-1 was treated with increasing doses of PI-103. Inhibition of AKT and mTOR was examined and assays assessing proliferation and apoptosis were performed. The chordoma specimen demonstrated activation of the PI3K/mTOR pathway. PI-103 inhibited the AKT and mTOR activation in the UCH-1 cell line. PI-103 inhibited proliferation and induced apoptosis in UCH-1. The PI3K/AKT and mTOR signaling pathway is constitutively activated in chordoma. PI-103 decreases proliferation and induces apoptosis in the UCH-1 via inhibition of the PI3K/mTOR path...
Journal of the National Comprehensive Cancer Network : JNCCN, 2014
Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointes... more Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.
Journal of Clinical Oncology, 2015
We performed a multi-institutional prospective phase II trial to assess late toxicities in patien... more We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in-field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P &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;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;lt; .001). The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.
Practical Radiation Oncology, 2012
PURPOSE: Dose-volume histograms (DVH) are the most common tool used in the appraisal of the quali... more PURPOSE: Dose-volume histograms (DVH) are the most common tool used in the appraisal of the quality of a clinical treatment plan. However, when delivery uncertainties are present, the DVH may not always accurately describe the dose distribution actually delivered to the patient. We present a method, based on DVH formalism, to visualize the variability in the expected dosimetric outcome of a treatment plan. METHOD: For a case of chordoma of the cervical spine, we compared two intensity-modulated proton therapy plans. Treatment Plan A was optimized based on dosimetric objectives alone (i.e., desired target coverage, normal tissue tolerance). Plan B was created employing a published probabilistic optimization method that considered the uncertainties in patient set-up and proton range in tissue. Dose distributions and DVH for both plans were calculated for the nominal delivery scenario, as well as for scenarios representing deviations from the nominal set-up, and a systematic error in the estimate of range in tissue. The histograms from various scenarios were combined to create DVH-bands to illustrate possible deviations from the nominal plan for the expected magnitude of set-up and range errors. RESULTS: In the nominal scenario, the DVH from Plan A showed superior dose coverage, higher dose homogeneity within the target, and improved sparing of the adjacent critical structure. However, when the dose distributions and DVH from plans A and B were recalculated for different error scenarios (e.g., proton range underestimation by 3 mm), the plan quality, reflected by DVH, deteriorated significantly for Plan A, while Plan B was only minimally affected. In the DVH-band representation, Plan A produced wider bands, reflecting its higher vulnerability to delivery errors, and uncertainty in the dosimetric outcome. CONCLUSIONS: The results illustrate that comparison of DVH for the nominal scenario alone does not provide any information about the relative sensitivity of dosimetric outcome to delivery uncertainties. Thus, such comparison may be misleading, and may result in the selection of an inferior plan for delivery to a patient. A better-informed decision can be made, if additional information about possible dosimetric variability is presented, e.g., in the form of DVH bands.
Biological and Medical Physics, Biomedical Engineering, 2011
ABSTRACT The Francis H. Burr Proton Therapy Center (FHBPTC) is one of the first hospital-based pr... more ABSTRACT The Francis H. Burr Proton Therapy Center (FHBPTC) is one of the first hospital-based proton therapy (PT) facilities. Its development was the natural evolution of several decades of PT experience of the Massachusetts General Hospital treating patients at the Harvard Cyclotron Laboratory. The operations of the FHBPTC reflect the combined missions of patient care, clinical and physics research, technological developments, and education. This chapter will discuss aspects of the history, evolution, and performance of this unique PT center.
Fuel and Energy Abstracts, 2010
Fuel and Energy Abstracts, 2010
European journal of cancer (Oxford, England : 1990), 2014
Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Pro... more Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9)....
Practical Radiation Oncology, 2014
Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors.... more Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors. Methods and materials: Fifteen patients were enrolled in a prospective institutional review boardapproved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectable biopsyproven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤ 6 cm. Patients received 15 fractions to a total dose of 45-75 GyE [gray equivalent] using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring based system. Results: Of the 15 patients enrolled in this clinical trial, 11 had HCC, 3 had ICC, and 1 had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients had 3 lesions. Toxicities were grade 3 bilirubinemia-2, grade 3 gastrointestinal bleed-1, and grade 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-, 2-, and 3-year overall survivals are 53%, 40%, and 33%, respectively. Progression-free survivals are 40%, 33%, and 27% at 1, 2, and 3 years, respectively. Practical Radiation Oncology (2013) xx, xxx-xxx Conclusions: Respiratory-gated proton beam therapy for liver tumors is feasible. Phase 2 studies for primary liver tumors and metastatic tumors are underway.
International Journal of Radiation Oncology*Biology*Physics, 2014
We report toxicity, efficacy, and tissue and circulating Purpose: To evaluate the safety, efficac... more We report toxicity, efficacy, and tissue and circulating Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients.
Fuel and Energy Abstracts, 2011
Purpose/Objective(s): Chemotherapy is considered the treatment of choice for inoperable intracran... more Purpose/Objective(s): Chemotherapy is considered the treatment of choice for inoperable intracranial low-grade glioma (LGG) in young children. Children under the age of 5 years who receive radiation therapy (RT) risk significant cognitive effects and vasculopathy. Although older patients have fewer complications with RT, some would consider the use of chemotherapy to be appropriate regardless of age. We sought to determine if chemotherapy administered prior to RT reduced progression-free or overall survival. Materials/Methods: An IRB approved retrospective review was undertaken using the information from 180 children (median age 8.1 years, range, 1.2-20.0 years) with intracranial LGG irradiated at St. Jude Children's Research Hospital between 5/1986 and 8/2010. The cohort was characterized according to gender (female = 81), race (white = 148), pre-RT chemotherapy (n = 66), progression after RT (n = 46) and death (n = 18). Results: With a median follow-up of 8.8 years (range, 0.3-24.3 years) after RT for the survivors, the 10 year progression-free and overall survivals were 71% + 4% and 89% + 3%, respectively. The 10 year overall survival estimates were 85% + 5% for those treated with chemotherapy prior to RT vs. 92% + 3% for those treated with RT alone (p = 0.014). The impact of pre-RT chemotherapy was increased (p = 0.004) when age was included as a continuous variable in Cox regression analysis. Conclusions: The use of chemotherapy prior to RT reduced overall survival but did not impact progression-free survival. Chemotherapy plays an important role in delaying the use of definitive irradiation in young children; however, this benefit must be balanced against the negative impact of chemotherapy on overall survival after RT. Further investigation will focus on the impact of specific chemotherapy regimens and clinical features of these patients to specify the risks.
International journal of radiation oncology, biology, physics, 2015
Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcom... more Evidence for external beam radiation therapy (RT) as part of treatment for retroperitoneal sarcoma (RPS) is limited. Preoperative RT is the subject of a current randomized trial, but the results will not be available for many years. In the meantime, many practitioners use preoperative RT for RPS, and although this approach is used in practice, there are no radiation treatment guidelines. An international expert panel was convened to develop consensus treatment guidelines for preoperative RT for RPS. An expert panel of 15 academic radiation oncologists who specialize in the treatment of sarcoma was assembled. A systematic review of reports related to RT for RPS, RT for extremity sarcoma, and RT-related toxicities for organs at risk was performed. Due to the paucity of high-quality published data on the subject of RT for RPS, consensus recommendations were based largely on expert opinion derived from clinical experience and extrapolation of relevant published reports. It is intended t...
Journal of the National Comprehensive Cancer Network: JNCCN
These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Ti... more These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.
Journal of the National Comprehensive Cancer Network: JNCCN
... MD,; John D. Pfeifer, MD, PhD,; Raphael E. Pollock, MD,; R. Lor Randall, MD,; Richard F. Ried... more ... MD,; John D. Pfeifer, MD, PhD,; Raphael E. Pollock, MD,; R. Lor Randall, MD,; Richard F. Riedel, MD,; Karen D. Schupak, MD,; Herbert S. Schwartz, MD,; Katherine Thornton, MD,; Margaret von Mehren, MD and; Jeffrey Wayne, MD. ...
Journal of the National Comprehensive Cancer Network: JNCCN
The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the man... more The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.
Cancer control : journal of the Moffitt Cancer Center
For patients with sarcomas, radiotherapy can be used as neoadjuvant, adjuvant, or primary local t... more For patients with sarcomas, radiotherapy can be used as neoadjuvant, adjuvant, or primary local therapy, depending on the site and type of sarcoma, the surgical approach, and the efficacy of chemotherapy. The authors review the current status of advanced technology radiation therapy in the management of bone and soft tissue sarcoma. Advances in radiotherapy have resulted in improved treatment for bone and soft tissue sarcomas. Intensity-modulated radiation therapy (IMRT) uses modifications in the intensity of the photon-beam from a linear accelerator across the irradiated fields to enhance dose conformation in three dimensions. For proton-beam radiation therapy, the nuclei of hydrogen atoms are accelerated in cyclotrons or synchrotrons, extracted, and transported to treatment rooms where the proton beam undergoes a series of modifications that conform the dose in a particular patient to the tumor target. Brachytherapy and intraoperative radiation therapy have generally been used to ...
Journal of surgical oncology, 2014
Negative surgical margins are uncommon for spine sarcomas; hence, adjuvant radiotherapy (RT) may ... more Negative surgical margins are uncommon for spine sarcomas; hence, adjuvant radiotherapy (RT) may be recommended but tumor dose may be constrained by spinal cord, nerve, and viscera tolerance. Prospective Phase II clinical trial incorporating high dose RT. Eligible patients had primary or locally recurrent thoracic, lumbar, and/or sacral spine/paraspinal chordomas or sarcomas. Treatment included pre- and/or post-operative photon/proton RT ± radical resection. Fifty patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). RT dose was ≤72.0 GyRBE in 25 patients and 76.6-77.4 GyRBE in 25 patients. With 7.3-year median follow-up, the 5 and 8-year actuarial local control (LC) rates were 94% and 85% for primary tumors and 81% and 74% for the entire group. Local recurrence was less common for primary tumors, 4/36 (11%) versus 7/14 (50%) for recurrent tumors, P = 0.002. The 8-year actuarial risk of grade 3-4 late RT ...
Practical radiation oncology
Proper positioning of patients with extremity sarcoma tumors can be challenging. A surface imagin... more Proper positioning of patients with extremity sarcoma tumors can be challenging. A surface imaging technique was utilized to quantify the setup uncertainties for sarcoma patients and to assess whether surface imaging could improve the accuracy of patient positioning. Pretreatment and posttreatment 3-dimensional (3D) surface images were obtained for 16 patients and 236 treatments. Offline surface registration was performed to quantify interfraction and intrafraction setup errors, and the required planning target volume (PTV) margins were calculated. Setup differences were also assessed using root mean square (RMS) error analysis. For intrafraction variation, the mean 3D vector shift was 2.1 mm, and the systematic and random errors were 1.3 mm or less. When using a reference surface from the first fraction, the mean interfraction setup variation (3D vector shift) was 7.6 mm. Systematic and random errors were 3-4 mm in each direction. When using a computed tomographic based reference s...
Journal of surgical oncology, 2014
The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and su... more The role of a radiation therapy (RT) boost for positive margins following pre-operative RT and surgery in extremity soft tissue sarcomas (STS) is unclear. We assessed the contribution of a boost to local control (LC), disease-free survival (DFS), and overall survival (OS). We identified 67 patients treated from 1987 to 2011 with pre-operative RT and surgery with positive margin(s). Select patients received a boost delivered as peri-operative Iridium-192 brachytherapy (BRT), intra-operative electrons (IORT), or post-operative external beam RT (EBRT). Ten patients received no RT boost, 10 received a BRT or IORT boost, and 47 received an EBRT boost. Five-year LC rates for no boost, BRT/IORT boost, and EBRT boost were 100%, 78%, and 71% (P = 0.5). On multivariate analysis, there were no significant predictors for LC. Variables associated with improved DFS rates were single positive margin (P = 0.007) and low tumor grade (P = 0.03). Tumor size <5 cm (P = 0.003), low grade (P = 0.001),...
International journal of radiation oncology, biology, physics, 2014
To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-P... more To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm(3)) to potentially allow an intensity modulated proton therapy...
Anticancer research, 2009
Chordomas are rare tumors of the axial skeleton for which surgical resection remains the most rel... more Chordomas are rare tumors of the axial skeleton for which surgical resection remains the most reliable means of cure. PI-103 is a inhibitor of PI3K/AKT and mTOR activation. This study aims to determine whether the PI3K/mTOR pathway was active in chordomas and whether their inhibition could lead to decreased proliferation and increased apoptosis. Thirteen human chordoma were tested for activation of the PI3K/mTOR pathway. The human chordoma cell line UCH-1 was treated with increasing doses of PI-103. Inhibition of AKT and mTOR was examined and assays assessing proliferation and apoptosis were performed. The chordoma specimen demonstrated activation of the PI3K/mTOR pathway. PI-103 inhibited the AKT and mTOR activation in the UCH-1 cell line. PI-103 inhibited proliferation and induced apoptosis in UCH-1. The PI3K/AKT and mTOR signaling pathway is constitutively activated in chordoma. PI-103 decreases proliferation and induces apoptosis in the UCH-1 via inhibition of the PI3K/mTOR path...
Journal of the National Comprehensive Cancer Network : JNCCN, 2014
Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointes... more Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.
Journal of Clinical Oncology, 2015
We performed a multi-institutional prospective phase II trial to assess late toxicities in patien... more We performed a multi-institutional prospective phase II trial to assess late toxicities in patients with extremity soft tissue sarcoma (STS) treated with preoperative image-guided radiation therapy (IGRT) to a reduced target volume. Patients with extremity STS received IGRT with (cohort A) or without (cohort B) chemotherapy followed by limb-sparing resection. Daily pretreatment images were coregistered with digitally reconstructed radiographs so that the patient position could be adjusted before each treatment. All patients received IGRT to reduced tumor volumes according to strict protocol guidelines. Late toxicities were assessed at 2 years. In all, 98 patients were accrued (cohort A, 12; cohort B, 86). Cohort A was closed prematurely because of poor accrual and is not reported. Seventy-nine eligible patients from cohort B form the basis of this report. At a median follow-up of 3.6 years, five patients did not have surgery because of disease progression. There were five local treatment failures, all of which were in-field. Of the 57 patients assessed for late toxicities at 2 years, 10.5% experienced at least one grade ≥ 2 toxicity as compared with 37% of patients in the National Cancer Institute of Canada SR2 (CAN-NCIC-SR2: Phase III Randomized Study of Pre- vs Postoperative Radiotherapy in Curable Extremity Soft Tissue Sarcoma) trial receiving preoperative radiation therapy without IGRT (P &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;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;lt; .001). The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.
Practical Radiation Oncology, 2012
PURPOSE: Dose-volume histograms (DVH) are the most common tool used in the appraisal of the quali... more PURPOSE: Dose-volume histograms (DVH) are the most common tool used in the appraisal of the quality of a clinical treatment plan. However, when delivery uncertainties are present, the DVH may not always accurately describe the dose distribution actually delivered to the patient. We present a method, based on DVH formalism, to visualize the variability in the expected dosimetric outcome of a treatment plan. METHOD: For a case of chordoma of the cervical spine, we compared two intensity-modulated proton therapy plans. Treatment Plan A was optimized based on dosimetric objectives alone (i.e., desired target coverage, normal tissue tolerance). Plan B was created employing a published probabilistic optimization method that considered the uncertainties in patient set-up and proton range in tissue. Dose distributions and DVH for both plans were calculated for the nominal delivery scenario, as well as for scenarios representing deviations from the nominal set-up, and a systematic error in the estimate of range in tissue. The histograms from various scenarios were combined to create DVH-bands to illustrate possible deviations from the nominal plan for the expected magnitude of set-up and range errors. RESULTS: In the nominal scenario, the DVH from Plan A showed superior dose coverage, higher dose homogeneity within the target, and improved sparing of the adjacent critical structure. However, when the dose distributions and DVH from plans A and B were recalculated for different error scenarios (e.g., proton range underestimation by 3 mm), the plan quality, reflected by DVH, deteriorated significantly for Plan A, while Plan B was only minimally affected. In the DVH-band representation, Plan A produced wider bands, reflecting its higher vulnerability to delivery errors, and uncertainty in the dosimetric outcome. CONCLUSIONS: The results illustrate that comparison of DVH for the nominal scenario alone does not provide any information about the relative sensitivity of dosimetric outcome to delivery uncertainties. Thus, such comparison may be misleading, and may result in the selection of an inferior plan for delivery to a patient. A better-informed decision can be made, if additional information about possible dosimetric variability is presented, e.g., in the form of DVH bands.
Biological and Medical Physics, Biomedical Engineering, 2011
ABSTRACT The Francis H. Burr Proton Therapy Center (FHBPTC) is one of the first hospital-based pr... more ABSTRACT The Francis H. Burr Proton Therapy Center (FHBPTC) is one of the first hospital-based proton therapy (PT) facilities. Its development was the natural evolution of several decades of PT experience of the Massachusetts General Hospital treating patients at the Harvard Cyclotron Laboratory. The operations of the FHBPTC reflect the combined missions of patient care, clinical and physics research, technological developments, and education. This chapter will discuss aspects of the history, evolution, and performance of this unique PT center.
Fuel and Energy Abstracts, 2010
Fuel and Energy Abstracts, 2010
European journal of cancer (Oxford, England : 1990), 2014
Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Pro... more Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9)....
Practical Radiation Oncology, 2014
Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors.... more Purpose: To evaluate the feasibility of a respiratory-gated proton beam therapy for liver tumors. Methods and materials: Fifteen patients were enrolled in a prospective institutional review boardapproved protocol. Eligibility criteria included Childs-Pugh A/B cirrhosis, unresectable biopsyproven hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), or metastatic disease (solid tumors only), 1-3 lesions, and tumor size of ≤ 6 cm. Patients received 15 fractions to a total dose of 45-75 GyE [gray equivalent] using respiratory-gated proton beam therapy. Gating was performed with an external respiratory position monitoring based system. Results: Of the 15 patients enrolled in this clinical trial, 11 had HCC, 3 had ICC, and 1 had metastasis from another primary. Ten patients had a single lesion, 3 patients had 2 lesions, and 2 patients had 3 lesions. Toxicities were grade 3 bilirubinemia-2, grade 3 gastrointestinal bleed-1, and grade 5 stomach perforation-1. One patient had a marginal recurrence, 3 had hepatic recurrences elsewhere in the liver, and 2 had extrahepatic recurrence. With a median follow-up for survivors of 69 months, 1-, 2-, and 3-year overall survivals are 53%, 40%, and 33%, respectively. Progression-free survivals are 40%, 33%, and 27% at 1, 2, and 3 years, respectively. Practical Radiation Oncology (2013) xx, xxx-xxx Conclusions: Respiratory-gated proton beam therapy for liver tumors is feasible. Phase 2 studies for primary liver tumors and metastatic tumors are underway.
International Journal of Radiation Oncology*Biology*Physics, 2014
We report toxicity, efficacy, and tissue and circulating Purpose: To evaluate the safety, efficac... more We report toxicity, efficacy, and tissue and circulating Purpose: To evaluate the safety, efficacy and biomarkers of short-course proton beam radiation and capecitabine, followed by pancreaticoduodenectomy in a phase 1/2 study in pancreatic ductal adenocarcinoma (PDAC) patients.