Publications by authors named "Laura A Dawson"

196 Publications

Simulated dose painting of hypoxic sub-volumes in pancreatic cancer stereotactic body radiotherapy.

Phys Med Biol 2021 Sep 9;66(18). Epub 2021 Sep 9.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.

Dose painting of hypoxic tumour sub-volumes using positron-emission tomography (PET) has been shown to improve tumour controlin several sites, predominantly head and neck and lung cancers. Pancreatic cancer presents a more stringent challenge, given its proximity to critical gastro-intestinal organs-at-risk (OARs), anatomic motion, and impediments to reliable PET hypoxia quantification. A radiobiological model was developed to estimate clonogen survival fraction (SF), usingF-fluoroazomycin arabinoside PET (FAZA PET) images from ten patients with unresectable pancreatic ductal adenocarcinoma to quantify oxygen enhancement effects. For each patient, four simulated five-fraction stereotactic body radiotherapy (SBRT) plans were generated: (1) a standard SBRT plan aiming to cover the planning target volume with 40 Gy, (2) dose painting plans delivering escalated doses to a maximum of three FAZA-avid hypoxic sub-volumes, (3) dose painting plans with simulated spacer separating the duodenum and pancreatic head, and (4), plans with integrated boosts to geometric contractions of the gross tumour volume (GTV). All plans saturated at least one OAR dose limit. SF was calculated for each plan and sensitivity of SF to simulated hypoxia quantification errors was evaluated. Dose painting resulted in a 55% reduction in SF as compared to standard SBRT; 78% with spacer. Integrated boosts to hypoxia-blind geometric contractions resulted in a 41% reduction in SF. The reduction in SF for dose-painting plans persisted for all hypoxia quantification parameters studied, including registration and rigid motion errors that resulted in shifts and rotations of the GTV and hypoxic sub-volumes by as much as 1 cm and 10 degrees. Although proximity to OARs ultimately limited dose escalation, with estimated SFs (∼10) well above levels required to completely ablate a ∼10 cmtumour, dose painting robustly reduced clonogen survival when accounting for expected treatment and imaging uncertainties and thus, may improve local response and associated morbidity.
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http://dx.doi.org/10.1088/1361-6560/ac215cDOI Listing
September 2021

Current Understanding of Ablative Radiation Therapy in Hepatocellular Carcinoma.

J Hepatocell Carcinoma 2021 14;8:575-586. Epub 2021 Jun 14.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.

The role of ablative stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) has been evolving over the last few decades. SBRT has mostly been used in early stages of HCC, including few (≤ 3 in number) tumors, small tumours (< 3 cm in size), as well as larger tumours which are ineligible for other ablative modalities, mostly without vascular invasion. In early stage HCC, SBRT is used as a definitive treatment with curative intent or with intent to bridge to liver transplant. Retrospective and prospective institutional series document a high rate of local control (68-95% at 3 years) following SBRT. This coupled with a low risk of toxicity makes this non-invasive ablative treatment an attractive option for patients who are ineligible for other ablative treatments. Small randomized studies of ablative radiation have also shown non-inferiority of radiation as compared to radiofrequency ablation (RFA). Currently, SBRT is widely available as a safe and effective liver directed therapy, although there is a need for more studies providing higher level evidence. This review gives a brief overview of SBRT and the evidence for its use in HCC patients with ablative intent.
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http://dx.doi.org/10.2147/JHC.S284403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214025PMC
June 2021

Variability in Steroid Prophylaxis for Radiation-Induced Pain Flare: Practice of Canadian Radiation Oncologists.

J Palliat Med 2021 07;24(7):965-966

Allan and Ruth Kerbel Palliative Radiation Oncology Program, Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Ontario, Canada.

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http://dx.doi.org/10.1089/jpm.2020.0761DOI Listing
July 2021

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions.

Front Oncol 2021 11;11:628155. Epub 2021 May 11.

Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States.

Introduction: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC.

Methods: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications.

Results: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed.

Conclusions: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.
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http://dx.doi.org/10.3389/fonc.2021.628155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144850PMC
May 2021

Locoregional Therapies for Colorectal Cancer Liver Metastases: Options Beyond Resection.

Am Soc Clin Oncol Educ Book 2021 Mar;41:133-146

Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD.

Colorectal cancer was the third most common malignancy worldwide in 2018, and most patients present with or develop distant metastases. Colorectal liver metastases are most commonly observed because of the vascular drainage of the colon and superior rectum. Current guidelines recommend surgical resection as first-line treatment; however, 80% to 90% of patients with colorectal liver metastases are ineligible for primary resection. For patients with unresectable disease, a multidisciplinary treatment approach is favored, incorporating systemic therapy and a toolbox of local ablative therapies. These treatments either aim at cytoreduction to enable a conversion to surgical resectability or control of disease progression and spread. Each of these treatments carries unique outcomes and risk profiles, thereby contributing to an individualized treatment strategy for patients with colorectal liver metastases. This review summarizes evidence on hepatic artery infusion, stereotactic body radiation therapy, thermal ablation, transarterial chemoembolization with drug-eluding beads, and transarterial radioembolization for treatment of colorectal liver metastases. Results of large-scale prospective and retrospective studies and international guidelines are discussed to provide detailed background on the current and prospective use of local ablative techniques in management of colorectal liver metastases.
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http://dx.doi.org/10.1200/EDBK_320519DOI Listing
March 2021

MRI evaluation of normal tissue deformation and breathing motion under an abdominal compression device.

J Appl Clin Med Phys 2021 Feb 15;22(2):90-97. Epub 2021 Jan 15.

Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.

Purpose: Abdominal compression can minimize breathing motion in stereotactic radiotherapy, though it may impact the positioning of dose-limiting normal tissues. This study quantified the reproducibility of abdominal normal tissues and respiratory motion with the use of an abdominal compression device using MR imaging.

Methods: Twenty healthy volunteers had repeat MR over 3 days under an abdominal compression plate device. Normal tissues were delineated on daily axial T2-weighted MR and compared on days 2 and 3 relative to day 1, after adjusting for baseline shifts relative to bony anatomy. Inter-fraction organ deformation was computed using deformable registration of axial T2 images. Deformation > 5 mm was assumed to be clinically relevant. Inter-fraction respiratory amplitude changes and intra-fraction baseline drifts during imaging were quantified on daily orthogonal cine-MR (70 s each), and changes > 3 mm were assumed to be relevant.

Results: On axial MR, the mean inter-fraction normal tissue deformation was > 5 mm for all organs (range 5.1-13.4 mm). Inter-fraction compression device misplacements > 5 mm and changes in stomach volume > 50% occurred at a rate of 93% and 38%, respectively, in one or more directions and were associated with larger adjacent organ deformation, in particular for the duodenum. On cine-MR, inter-fraction amplitude changes > 3 mm on day 2 and 3 relative to day 1 occurred at a rate of < 12.5% (mean superior-inferior change was 1.6 mm). Intra-fraction baseline drifts > 3 mm during any cine-MR acquisition occurred at a rate of 23% (mean superior-inferior changes was 2.4 mm).

Conclusions: Respiratory motion under abdominal compression is reproducible in most subjects within 3 mm. However, inter-fraction deformations greater than 5 mm in normal tissues were common and larger than inter- and intra-fraction respiratory changes. Deformations were driven mostly by variable stomach contents and device positioning. The magnitude of this motion may impact normal tissue dosimetry during stereotactic radiotherapy.
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http://dx.doi.org/10.1002/acm2.13165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882116PMC
February 2021

Stereotactic body radiation therapy for hepatocellular carcinoma with Macrovascular invasion.

Radiother Oncol 2021 03 5;156:120-126. Epub 2020 Dec 5.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada. Electronic address:

Background: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT).

Methods: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed.

Results: 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT.

Conclusions: SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.
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http://dx.doi.org/10.1016/j.radonc.2020.11.033DOI Listing
March 2021

Radiological tumor response and histopathological correlation of hepatocellular carcinoma treated with stereotactic body radiation therapy as a bridge to liver transplantation.

Abdom Radiol (NY) 2021 04 19;46(4):1572-1585. Epub 2020 Oct 19.

Joint Department of Medical Imaging, University Health Network/Mount Sinai Hospital/Women's College Hospital, 585 University Avenue, Toronto, ON, M5G 2N2, Canada.

Purpose: To assess the imaging findings of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) as a bridging therapy prior to liver transplantation (LT), with histopathological correlation at liver explant.

Methods: Our institutional review board approved this retrospective study. The study subjects included 25 HCC lesions in 23 patients (20 males; median age, 60 years; range 41-68 years) who underwent LT after SBRT for HCC as a bridge to LT in a single tertiary referral institution over a 12-year period. Target HCC lesions were assessed for imaging biomarkers on contrast-enhanced CT or MRI including change in HCC diameter and assessment of percentage necrosis. The radiologic response at pre-LT imaging was compared to explant pathology.

Results: There was a positive correlation between the tumor size (Spearman's ρ = 0.86; p < 0.001) and percentage necrosis (p < 0.001) on Pre-LT imaging and those on pathology. Partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST 1.1 were seen in 8 (32%), 15 (60%), and 2 (8%) lesions on pre-LT imaging, respectively. Of the 15 lesions with radiologic SD, 5/15 (33%) showed necrosis of more than 50% on post-SBRT imaging, while 9/15 (60%) showed necrosis of more than 50% at explant pathologic analysis, showing a tendency to underestimate the degree of tumor necrosis compared to pathology.

Conclusion: RECIST 1.1 radiologic response criteria may underestimate the response to treatment with SBRT, and radiologic estimation of percent tumor necrosis was more closely correlated with pathologic percent tumor necrosis.
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http://dx.doi.org/10.1007/s00261-020-02821-yDOI Listing
April 2021

Transplant Oncology in Primary and Metastatic Liver Tumors: Principles, Evidence, and Opportunities.

Ann Surg 2021 03;273(3):483-493

HPB Surgery and Liver Transplantation, Department of Oncology, University of Milan, Milan, Italy and Istituto Nazionale Tumori, Fondazione IRCCS, Milan, Italy.

Transplant oncology defines any application of transplant medicine and surgery aimed at improving cancer patients' survival and/or quality of life. In practice, liver transplantation for selected hepato-biliary cancers is the only solid organ transplant with demonstrated efficacy in curing cancer. Four are the proposed future contributions of transplant oncology in hepato-biliary cancer (4-e). (1) evolutionary approach to cancer care that includes liver transplantation; (2) elucidation of self and non-self recognition systems, by linking tumor and transplant immunology; (3) exploration of innovative endpoints both in clinical and experimental settings taking advantage from the access to the entire liver explant; (4) extension of surgical limitation in the multidisciplinary approach to hepato-biliary oncology. The aim of this review is to define the principles of transplant oncology that may be applied to hepato-biliary cancer treatment and research, attempting to balance current evidences with future opportunities.
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http://dx.doi.org/10.1097/SLA.0000000000004071DOI Listing
March 2021

Plasma metabolomic profiles in liver cancer patients following stereotactic body radiotherapy.

EBioMedicine 2020 Sep 3;59:102973. Epub 2020 Sep 3.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: Stereotactic body radiotherapy (SBRT) is an effective treatment for hepatocellular carcinoma (HCC). This study sought to identify differentially expressed plasma metabolites in HCC patients at baseline and early during SBRT, and to explore if changes in these metabolites early during SBRT may serve as biomarkers for radiation-induced liver injury and/or tumour response.

Methods: Forty-seven HCC patients were treated with SBRT on previously published prospective trials. Plasma samples were collected at baseline and after one to two fractions of SBRT, and analysed by GC/MS and LC/MS for untargeted and targeted metabolomics profiling, respectively.

Findings: Sixty-nine metabolites at baseline and 62 metabolites after one to two fractions of SBRT were differentially expressed, and strongly separated the Child Pugh (CP) B from the CP A HCC patients. These metabolites are associated with oxidative stress and alterations in hepatic cellular metabolism. Differential upregulation of serine, alanine, taurine, and lipid metabolites early during SBRT from baseline was noted in the HCC patients who demonstrated the greatest increase in CP scores at three months post SBRT, suggesting that high protein and lipid turnover early during SBRT may portend increased clinical liver toxicity. Twenty annotated metabolites including fatty acids, glycerophospholipids, and acylcarnitines were differentially upregulated early during SBRT from baseline and separated patients with complete/partial response from those with stable disease at three months post SBRT.

Interpretation: Dysregulation of amino acid and lipid metabolism detected early during SBRT are associated with subsequent clinical liver injury and tumour response in HCC.
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http://dx.doi.org/10.1016/j.ebiom.2020.102973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484529PMC
September 2020

Association of pro-inflammatory soluble cytokine receptors early during hepatocellular carcinoma stereotactic radiotherapy with liver toxicity.

NPJ Precis Oncol 2020 14;4:17. Epub 2020 Jul 14.

Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON Canada.

Plasma levels of soluble factors early during hepatocellular carcinoma (HCC) stereotactic body radiotherapy (SBRT) were evaluated in relation to radiation liver injury, tumor response, and risk of early death. No significant differences were found in baseline plasma levels of AFP, CXCL1, and HGF amongst HCC patients with different Child Pugh scores. Higher levels of sTNFRII ( < 0.001), and lower levels of sCD40L ( < 0.001) and CXCL1 ( = 0.01) following one to two fractions of SBRT were noted in patients who developed liver toxicity vs. those who did not. High circulating levels of AFP (HR 2.16,  = 0.04), sTNFRII (HR 2.27,  = 0.01), and sIL-6R (HR 1.99,  = 0.03) early during SBRT were associated with increased risk of death 3 months post treatment. Plasma levels of the studied factors early during SBRT were not associated with tumor response. A pro-inflammatory systemic environment is associated with development of liver toxicity and increased risk of early death following SBRT.
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http://dx.doi.org/10.1038/s41698-020-0124-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360781PMC
July 2020

Efficacy and safety of radiotherapy for primary liver cancer.

Chin Clin Oncol 2021 Feb 11;10(1). Epub 2020 Jun 11.

Radiation Medicine Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.

Primary liver cancer includes hepatocellular carcinoma (HCC, 75-85%) and intrahepatic cholangiocarcinoma (10-15%). The vast majority of patients with primary HCC are not candidates for surgical treatment. Surgical resection, liver transplantation and percutaneous puncture are effective potentially curable treatments for patients with early stage liver cancer. Radiation therapy is a non-surgical alternative treatment that has generally been used to treat patients with advanced liver cancer, although it's use in the potentially curative setting is increasing. Radiotherapy is a non-invasive local treatment which works through ionizing radiation. This review summarizes the efficacy and safety of commonly used radiotherapy methods, and reviews three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiation therapy (IMRT), stereotactic body radiotherapy (SBRT), volume-modulated arc therapy (VMAT), and internal radiation therapies, for primary liver cancer (in particular for HCC).
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http://dx.doi.org/10.21037/cco-20-89DOI Listing
February 2021

Epidemiology of liver metastases.

Cancer Epidemiol 2020 08 17;67:101760. Epub 2020 Jun 17.

Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA; Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA. Electronic address:

Aims: The objectives of this study were to (1) characterize the epidemiology of liver metastases at the time of primary cancer diagnosis (synchronous liver metastases), (2) characterize the incidence trends of synchronous liver metastases from 2010-2015 and (3) assess survival of patients with synchronous liver metastases.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 was queried to obtain cases of patients with liver metastases at the time of primary cancer diagnosis. The primary cancers with an incidence rate of liver metastasis >0.1 are presented in this analysis.

Results: Among 2.4 million cancer patients, 5.14 % of cancer patients presented with synchronous liver metastases. The most common primary site was breast cancers for younger women (ages 20-50), and colorectal cancers for younger men. As patients get older, a more heterogenous population of the top cancers with liver metastases emerges including esophageal, stomach, small intestine, melanoma, and bladder cancer in addition to the large proportion of lung, pancreatic, and colorectal cancers. The 1-year survival of all patients with liver metastases was 15.1 %, compared to 24.0 % in those with non-hepatic metastases. Regression analysis showed that the presence of liver metastasis was associated with reduced survival, particularly in patients with cancers of the testis, prostate, breast, and anus, and in those with melanoma.

Conclusions: The most common primary sites for patients with liver metastases varied based on age at diagnosis. Survival for patients with liver metastasis was significantly decreased as compared to patients without liver metastasis.
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http://dx.doi.org/10.1016/j.canep.2020.101760DOI Listing
August 2020

Hepatocellular Carcinoma in the COVID-19 Era: Primetime for Stereotactic Body Radiotherapy and a Lesson for the Future?

Oncologist 2020 08 23;25(8):e1249-e1250. Epub 2020 Jun 23.

Department of Radiation Oncology, University of Toronto, Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Center, Toronto, Canada.

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http://dx.doi.org/10.1634/theoncologist.2020-0416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307056PMC
August 2020

Management of primary hepatic malignancies during the COVID-19 pandemic: recommendations for risk mitigation from a multidisciplinary perspective.

Lancet Gastroenterol Hepatol 2020 08 6;5(8):765-775. Epub 2020 Jun 6.

UCL Cancer Institute, University College London, London, UK; Department of Medical Physics and Biomedical Engineering, University College London, London, UK.

Around the world, recommendations for cancer treatment are being adapted in real time in response to the pandemic of COVID-19. We, as a multidisciplinary team, reviewed the standard management options, according to the Barcelona Clinic Liver Cancer classification system, for hepatocellular carcinoma. We propose treatment recommendations related to COVID-19 for the different stages of hepatocellular carcinoma (ie, 0, A, B, and C), specifically in relation to surgery, locoregional therapies, and systemic therapy. We suggest potential strategies to modify risk during the pandemic and aid multidisciplinary treatment decision making. We also review the multidisciplinary management of intrahepatic cholangiocarcinoma as a potentially curable and incurable diagnosis in the setting of COVID-19.
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http://dx.doi.org/10.1016/S2468-1253(20)30182-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274990PMC
August 2020

Challenges in Reirradiation of Intrahepatic Tumors.

Semin Radiat Oncol 2020 Jul;30(3):242-252

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI. Electronic address:

Definitive reirradiation using a stereotactic technique is an effective local treatment option for both recurrent liver metastases and recurrent primary liver cancers. The tolerance of the liver, bile ducts, and surrounding gastrointestinal luminal organs must be respected to ensure safe retreatment. The risks associated with retreatment to these organs must be carefully balanced with the probability of clinical benefit. We present 2 cases for consideration of repeat irradiation along with the opinions of 4 experts, along with conclusions about recommendations.
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http://dx.doi.org/10.1016/j.semradonc.2020.02.004DOI Listing
July 2020

Long term outcomes of stereotactic body radiation therapy for hepatocellular carcinoma without macrovascular invasion.

Eur J Cancer 2020 07 24;134:41-51. Epub 2020 May 24.

Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address:

Background: Stereotactic Body Radiation Therapy (SBRT) is a non-invasive ablative treatment for hepatocellular carcinoma (HCC). This report aimed to address the limited availability of long-term outcomes after SBRT for HCC from North America.

Methods: Localized HCC patients without vascular invasion, who were ineligible for other liver-directed therapies and treated with SBRT at the University of Toronto or University of Michigan, were pooled to determine overall survival (OS), cumulative recurrence rates, and ≥ grade-3 toxicity. Multivariable analysis determined factors affecting OS and local recurrence rates.

Results: In 297 patients with 436 HCCs (42% > 3 cm), one-, three- and five-year OS was 77·3%, 39·0% and 24·1%, respectively. On Cox proportional hazards regression analysis, liver transplant after SBRT, Child-Pugh A liver function, alpha-fetoprotein ≤ 10 ng/ml, and Eastern Co-operative Oncology Group performance status 0 significantly improved OS (hazard ratio [HR] = 0·06, 95% confidence interval [CI- 0·02-0·25; p<0·001; HR = 0·42, 95% CI = 0·29-0·60, p<0·001; HR = 0·61, 95% CI- 0·44-0·83; p=0·002 and HR = 0·71, 95% CI = 0·51-0·97, p=0·034, respectively). Cumulative local recurrence was 6·3% (95% CI = 0.03-0.09) and 13·3% (95% CI = 0.06-0.21) at one and three years, respectively. Using Cox regression modelling, local control was significantly higher using breath-hold motion management and in HCC smaller than 3 cm (HR = 0.52, 95% CI = 0.58-0.98; p=0.042 and HR = 0.53, 95% CI = 0.26-0.98; p=0.042, respectively). Worsening of Child-Pugh score by ≥2 points three months after SBRT was seen in 15.9%.

Conclusions: SBRT confers high local control and long-term survival in a substantial proportion of HCC patients unsuitable for, or refractory to standard loco-regional treatments. Liver transplant should be considered if appropriate downsizing occurs after SBRT.
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http://dx.doi.org/10.1016/j.ejca.2020.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340168PMC
July 2020

ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy.

Am J Clin Oncol 2020 08;43(8):545-552

Department of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.

Aim/objectives/background: To standardize the practice of stereotactic body radiation therapy (SBRT), the American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) cooperatively developed the practice parameter for SBRT. SBRT is a treatment technique that delivers radiation dose to a well-defined extracranial target in 5 fractions or less and usually employs a higher dose per fraction than used in conventional radiation.

Methods: The ACR-ASTRO Practice Parameter for the Performance of Stereotactic Body Radiation Therapy was revised according to the process described on the ACR website ("The Process for Developing ACR Practice Parameters and Technical Standards," www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters of the ACR Commission on Radiation Oncology in collaboration with the ASTRO. Both societies then reviewed and approved the document.

Results: Given the complexities of SBRT, a separate document was created to develop a technical standard for the medical physics of SBRT (ACR-AAPM Technical Standard for Medical Physics Performance Monitoring of Stereotactic Body Radiation Therapy). Workflow, qualifications and responsibilities of personnel, specifications, documentation, quality control/safety/improvement, simulation/treatment, and follow-up were addressed in this practice parameter.

Conclusions: This practice parameter assists practitioners in providing safe and appropriate SBRT treatment and care for patients when clinically indicated. As technologies and techniques continue to evolve, this document will be reviewed, revised and renewed accordingly to a 5 year or sooner timeline specified by the ACR.
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http://dx.doi.org/10.1097/COC.0000000000000706DOI Listing
August 2020

Recommendations for the use of radiation therapy in managing patients with gastrointestinal malignancies in the era of COVID-19.

Radiother Oncol 2020 07 13;148:194-200. Epub 2020 Apr 13.

Department of Radiation Oncology, The Mount Sinai Hospital, New York, USA.

As of April 6, 2020, there are over 1,200,000 reported cases and 70,000 deaths worldwide due to COVID-19, the disease caused by the SARS-CoV-2 virus, and these numbers rise exponentially by the day [1]. According to the Centers for Disease Control (CDC), the most effective means of minimizing the spread of the virus is through reducing interactions between individuals [2]. We performed a review of the literature, as well as national and international treatment guidelines, seeking data in support of the RADS principle (Remote visits, Avoid radiation, Defer radiation, Shorten radiation) [3] as it applies to gastrointestinal cancers. The purpose of the present work is to guide radiation oncologists managing patients with gastrointestinal cancers during the COVID-19 crisis in order to maintain the safety of our patients, while minimizing the impact of the pandemic on cancer outcomes.
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http://dx.doi.org/10.1016/j.radonc.2020.04.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194719PMC
July 2020

Dose-Escalated Radiation Therapy for Pancreatic Cancer: A Simultaneous Integrated Boost Approach.

Pract Radiat Oncol 2020 Nov - Dec;10(6):e495-e507. Epub 2020 Feb 13.

Medical College of Wisconsin, Milwaukee, Wisconsin.

Purpose: To provide a detailed description of practical approaches to dose escalation in pancreatic cancer.

Methods And Materials: The current paper represents an international collaborative effort of radiation oncologists from the MR-linac consortium with expertise in pancreatic dose escalation.

Results: A 15-fraction hypofractionated intensity modulated radiation therapy (67.5 Gy in 15 fractions) and 5-fraction stereotactic body radiation therapy case (50 Gy in 5 fractions) are presented with information regarding patient selection, target volumes, organs at risk, dose constraints, and specific considerations regarding quality assurance. Additionally, we address barriers to dose escalation and briefly discuss future directions in dose escalation for pancreatic cancer, including particle therapy and magnetic resonance guided radiation therapy.

Conclusions: This article on dose escalation for pancreatic cancer may help to guide academic and community based physicians and to serve as a reference for future therapeutic trials.
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http://dx.doi.org/10.1016/j.prro.2020.01.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423616PMC
August 2021

Radiotherapy for HCC: Ready for prime time?

JHEP Rep 2019 Aug 21;1(2):131-137. Epub 2019 May 21.

Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, Ontario, Canada, M5G 2C1.

Stereotactic body radiation therapy (SBRT) has an evolving role in the management of hepatocellular carcinoma (HCC), largely due to recent advances in imaging technology. Often utilized in situations where other locoregional therapies are not feasible, SBRT has been demonstrated to be an effective treatment that confers high rates of durable local control. However, there is limited evidence to firmly establish its place in the treatment paradigm for HCC. In this article, we review the current evidence and highlight specific considerations in the multiple settings where SBRT may be used, including for primary HCC treatment and bridging/downstaging, as well as exploring the potential for SBRT in the treatment of extrahepatic oligo-metastatic HCC.
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http://dx.doi.org/10.1016/j.jhepr.2019.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001576PMC
August 2019

MRI-Based Upper Abdominal Organs-at-Risk Atlas for Radiation Oncology.

Int J Radiat Oncol Biol Phys 2020 03 14;106(4):743-753. Epub 2020 Jan 14.

Department of Radiation Oncology, University of Toronto, Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Electronic address:

Purpose: The purpose of our study was to provide a guide for identification and contouring of upper abdominal organs-at-risk (OARs) in the setting of online magnetic resonance imaging (MRI)-guided radiation treatment planning and delivery.

Methods And Materials: After a needs assessment survey, it was determined that an upper abdominal MRI-based atlas of normal OARs would be of benefit to radiation oncologists and radiation therapists. An anonymized diagnostic 1.5T MRI from a patient with typical upper abdominal anatomy was used for atlas development. Two MRI sequences were selected for contouring, a T1-weighted gadoxetic acid contrast-enhanced MRI acquired in the hepatobiliary phase and axial fast imaging with balanced steady-state precession. Two additional clinical MRI sequences from commercial online MRI-guided radiation therapy systems were selected for contouring and were included in the final atlas. Contours from each data set were completed and reviewed by radiation oncologists, along with a radiologist who specializes in upper abdominal imaging, to generate a consensus upper abdominal MRI-based OAR atlas.

Results: A normal OAR atlas was developed, including recommendations for contouring. The atlas and contouring guidance are described, and high-resolution MRI images and contours are displayed. OARs, such as the bile duct and biliary tree, which may be better seen on MRI than on computed tomography, are highlighted. The full DICOM/DICOM-RT MRI images from both the diagnostic and clinical online MRI-guided radiation therapy systems data sets have been made freely available, for educational purposes, at econtour.org.

Conclusions: This MRI contouring atlas for upper abdominal OARs should provide a useful reference for contouring and education. Its routine use may help to improve uniformity in contouring in radiation oncology planning and OAR dose calculation. Full DICOM/DICOM-RT images are available online and provide a valuable educational resource for upper abdominal MRI-based radiation therapy planning and delivery.
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http://dx.doi.org/10.1016/j.ijrobp.2019.12.003DOI Listing
March 2020

The transformation of radiation oncology using real-time magnetic resonance guidance: A review.

Eur J Cancer 2019 11 12;122:42-52. Epub 2019 Oct 12.

Medical College of Wisconsin, Department of Radiation Oncology, USA.

Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of RT. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a speciality focus in RT. Speciality implications, areas for physician education and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the speciality of radiation oncology that will occur with MRI-guided RT. The impacts on RT caused by MRI guidance include target identification, RT planning, quality assurance, treatment delivery, training, clinical workflow, tumour response assessment and treatment scheduling. In addition, entirely novel research areas that may be enabled by MRI guidance are identified for future investigation.
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http://dx.doi.org/10.1016/j.ejca.2019.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447225PMC
November 2019

Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma.

Cancer Res 2019 09;79(17):4326-4330

Department of Radiation Oncology, Pathology and Urology, Albert Einstein College of Medicine, Bronx, New York.

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-0803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330805PMC
September 2019

Radiation Therapy for Pancreatic Cancer: Executive Summary of an ASTRO Clinical Practice Guideline.

Pract Radiat Oncol 2019 Sep - Oct;9(5):322-332

Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.

Purpose: This guideline systematically reviews the evidence for treatment of pancreatic cancer with radiation in the adjuvant, neoadjuvant, definitive, and palliative settings and provides recommendations on indications and technical considerations.

Methods And Materials: The American Society for Radiation Oncology convened a task force to address 7 key questions focused on radiation therapy, including dose fractionation and treatment volumes, simulation and treatment planning, and prevention of radiation-associated toxicities. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.

Results: The guideline conditionally recommends conventionally fractionated or stereotactic body radiation for neoadjuvant and definitive therapy in certain patients and conventionally fractionated regimens for adjuvant therapy. The task force suggests a range of appropriate dose-fractionation schemes and provides recommendations on target volumes and sequencing of radiation and chemotherapy. Motion management, daily image guidance, use of contrast, and treatment with modulated techniques are all recommended. The task force supported prophylactic antiemetic medication, and patients may also benefit from medications to reduce acid secretion.

Conclusions: The role of radiation in the management of pancreatic cancer is evolving, with many ongoing areas of active investigation. Radiation therapy is likely to become even more important as new systemic therapies are developed and there is increased focus on controlling local disease. It is important that the nuances of available data are discussed with patients and families and that care be coordinated in a multidisciplinary fashion.
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http://dx.doi.org/10.1016/j.prro.2019.06.016DOI Listing
January 2020

In Regard to Sanford et al.

Int J Radiat Oncol Biol Phys 2019 09;105(1):230-231

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.

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http://dx.doi.org/10.1016/j.ijrobp.2019.03.009DOI Listing
September 2019

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases.

Pract Radiat Oncol 2019 Jul - Aug;9(4):e386-e393. Epub 2019 Feb 27.

Duke University Medical Center, Durham, North Carolina.

Purpose: This study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases.

Methods And Materials: Nonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT.

Results: A total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed.

Conclusions: Treatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting.
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http://dx.doi.org/10.1016/j.prro.2019.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592755PMC
December 2019
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