Publications by authors named "Richard Khor"

22 Publications

  • Page 1 of 1

Long-term clinical outcomes of lipiodol marking using standard gastroscopy for image-guided radiotherapy of upper gastrointestinal cancers.

World J Gastroenterol 2021 Nov;27(42):7387-7401

Department of Gastroenterology and Hepatology, Austin Health, Heidelberg 3084, Victoria, Australia.

Background: Image-guided radiotherapy (IGRT) has significantly improved the precision in which radiotherapy is delivered in cancer treatment. Typically, IGRT uses bony landmarks and key anatomical structures to locate the tumor. Recent studies have demonstrated the feasibility of peri-tumor fiducials in enabling even more accurate delineation of target and normal tissue. The use of gold coils as fiducials in gastrointestinal tumors has been extensively studied. However, placement requires expertise and specialized endoscopic ultrasound equipment. This article reports the long-term outcomes of using a standard gastroscopy to inject liquid fiducials for the treatment of oesophageal and gastric tumors with IGRT.

Aim: To assess the long-term outcomes of liquid fiducial-guided IGRT in a cohort of oesophageal and gastric cancer patients.

Methods: A retrospective cohort study of consecutive adults with Oesophagogastric cancers referred for liquid fiducial placement before definitive/neo-adjuvant or palliative IGRT between 2013 and 2021 at a tertiary hospital in Melbourne, Australia was conducted. Up to four liquid fiducials were inserted per patient, each injection consisting of 0.2-0.5mL of a 1:1 mixture of iodized oil (Lipiodol; Aspen Pharmacare) and n-butyl 2-cyanoacrylate (Histoacryl; B. Braun). A 23-gauge injector (Cook Medical) was used for the injection. All procedures were performed by or under the supervision of a gastroenterologist. Liquid fiducial-based IGRT (LF-IGRT) consisted of computer-assisted direct matching of the fiducial region on cone-beam computerised tomography at the time of radiotherapy. Patients received standard-IGRT (S-IGRT) if fiducial visibility was insufficient, consisting of bone match as a surrogate for tumor position. Radiotherapy was delivered to 54Gy in 30 fractions for curative patients and up to 45Gy in 15 fractions for palliative treatments.

Results: 52 patients were referred for liquid fiducial placement within the study period. A total of 51 patients underwent liquid fiducial implantation. Of these a total of 31 patients received radiotherapy. Among these, the median age was 77.4 years with a range between 57.5 and 88.8, and 64.5% were male. Twenty-seven out of the 31 patients were able to have LF-IGRT while four had S-IGRT. There were no complications after endoscopic implantation of liquid fiducials in our cohort. The cohort overall survival (OS) post-radiotherapy was 19 mo (range 0 to 87 mo). Whilst the progression-free survival (PFS) post-radiotherapy was 13 mo (range 0 to 74 mo). For those treated with curative intent, the median OS was 22.0 mo (range 0 to 87 mo) with a PFS median of 14.0 mo (range 0 to 74 mo). Grade 3 complication rate post-radiotherapy was 29%.

Conclusion: LF-IGRT is feasible in 87.1% of patients undergoing liquid fiducial placement through standard gastroscopy injection technique. Our cohort has an overall survival of 19 mo and PFS of 13 mo. Further studies are warranted to determine the long-term outcomes of liquid-fiducial based IGRT.
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http://dx.doi.org/10.3748/wjg.v27.i42.7387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611208PMC
November 2021

Recent Research on Combination of Radiotherapy with Targeted Therapy or Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Review for Radiation Oncologists.

Cancers (Basel) 2021 Nov 15;13(22). Epub 2021 Nov 15.

Oliver Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, VIC 3079, Australia.

Radiotherapy plays an important role of managing head and neck squamous cell carcinoma (HNSCC). Concurrent radiotherapy with radiosensitizing cisplastin chemotherapy is the standard of care (SOC) for non-operable locally advanced HNSCC. Cetuximab, a monoclonal antibody of epidermal growth factor receptor, was the most extensively studied targeted therapy as a chemo-sparing agent that was used concurrently with radiotherapy. Immunotherapy is used in the treatment of metastatic HNSCC. There is evidence to support the synergistic effect when combining radiotherapy with immunotherapy to potentiate anti-tumor immune response. There has been increasing interest to incorporate immune checkpoint inhibitor (ICI) with radiotherapy in the curative setting for HNSCC. In this review, we discuss the latest evidence that supports concurrent radiotherapy with cisplatin which remains the SOC for locally advanced HNSCC (LA-HNSCC). Cetuximab is suitable for patients who are not fit for cisplatin. We then summarize the clinical trials that incorporate ICI with radiotherapy for LA-HNSCC in concurrent, neoadjuvant, and adjuvant settings. We also discuss the potential of combining immunotherapy with radiotherapy as a treatment de-escalating strategy in HPV-associated oropharyngeal carcinoma. Finally, the pre-clinical and clinical evidence of the abscopal effect when combining stereotactic body radiotherapy with ICIs is presented.
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http://dx.doi.org/10.3390/cancers13225716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616456PMC
November 2021

Assessment and management of newly diagnosed classical Hodgkin lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance.

Intern Med J 2021 Dec 22;51(12):2119-2128. Epub 2021 Nov 22.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.

The management of Hodgkin lymphoma (HL) has undergone significant changes in recent years. Due to the predilection of HL to affect younger patients, balancing cure and treatment-related morbidity is a constant source of concern for physicians and patients alike. Positron emission tomography adapted therapy has been developed for both early and advanced stage HL to try and improve the outcome of treatment, while minimising toxicities. The aim of this review is to digest the plethora of studies recently conducted and provide some clear, evidence-based practice statements to simplify the management of HL.
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http://dx.doi.org/10.1111/imj.15503DOI Listing
December 2021

A Prospective Trial Demonstrating the Benefit of Personalized Selection Of Breath-Hold Technique for Upper-Abdominal Radiation Therapy Using the Active Breathing Coordinator.

Int J Radiat Oncol Biol Phys 2021 12 10;111(5):1289-1297. Epub 2021 Aug 10.

Radiation Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health. Heidelberg, Victoria, Australia; School of Molecular Sciences, La Trobe University, Melbourne, Australia; Olivia Newton John Cancer Research Institute, Melbourne, Australia. Electronic address:

Purpose: For upper abdominal tumors, our institutional-standard motion reduction method is the expiration breath-hold (EBH) technique, using Active Breathing Coordinator (ABC). However, an individual patient's breath-hold (BH) reproducibility (R) may be improved in deep inspiration or inspiration breath-hold (DIBH or IBH). This trial compared the tumor position R, stability (S), and breath-hold time (T) of 3 BH methods, using ABC, to personalize the selection of technique, by using a preplanning screening assessment.

Methods And Materials: We invited patients planned for upper abdominal radiation therapy (kidney, pancreas, liver, or adrenal gland) to participate in this prospective trial. We conducted ABC education with the study participants, who then attempted EBH, DIBH, and IBH in randomized order. During 5 consecutive BH's for each method, we acquire kV fluoroscopy images of the diaphragm. We personalized the BH technique selection according to a decision matrix. We analyzed the EBH and the personalized technique cohort mean R and S.

Results: Between May 2019 and March 2020, we recruited 19 participants. Median age of participants was 68 years (range 32-81). Tumor sites included kidney (n = 1), adrenal gland (n = 5) and liver (n = 14). We excluded 1 participant due to poor BH compliance, leaving 270 images from 18 participants for analysis. Mean T was 22.1, 23.9, and 24.2 seconds for EBH, DIBH, and IBH respectively. Screening selected EBH for 44% (n = 8), IBH for 39% (n = 7), and DIBH for 17% (n = 3) of participants. The mean R was superior at 0.92 mm (0.79 mm SD) for the personalized technique, compared with EBH of 1.79 mm (1.49 mm SD) (P = .016). Preplanned subset analysis of participants whose personalized technique was not EBH showed improved mean R of 0.63 mm (0.29 mm SD) compared with their EBH R of 2.2 mm (1.7 mm SD) (P = .011).

Conclusions: In 56% of participants, DIBH or IBH demonstrated superior R compared with EBH. Personalised BH screening can inform selection of an ABC BH method which provides optimal R with improved T for an individual's planning and treatment course.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.001DOI Listing
December 2021

Victoria (Australia) radiotherapy response to working through the first and second wave of COVID-19: Strategies and staffing.

J Med Imaging Radiat Oncol 2021 Jun 27;65(3):374-383. Epub 2021 Apr 27.

Department of Radiation Oncology, ONJ Centre, Austin Hospital, Melbourne, Victoria, Australia.

Introduction: The COVID-19 pandemic demanded a rapid response within Radiation Oncology services to minimise the risk of infection to patients and workforce. This study aimed to assess whether the operational changes put in place to reduce infection risks were effective in engaging and supporting staff.

Methods: Our service's response saw staff and patients split into morning or afternoon shifts without overlap. Changes included extended clinic hours, modified treatment regimens, expanded online/electronic communication and remote working. Staff were invited to respond to an electronic questionnaire in September 2020, just after the peak of the second COVID-19 wave in Victoria. Responses captured demographic data, parental status, profession, happiness levels, fear of COVID-19 and e-communication efficacy.

Results: A 57% response rate was achieved. 69% of respondents were female; 40% were aged 45+ and 35% had school-aged children. Staff aged 45+ showed a significantly greater fear of COVID-19 than younger staff. 36% of respondents reported feeling nervous or anxious watching news reports about COVID-19. 92% of staff were happy with their work arrangements; staff with children were happier than staff without children with their shifts. Online chat/channels were reported as the preferred e-communication method between colleagues.

Conclusion: Staff provided predominantly positive feedback to the changes made in response to the pandemic, reporting high levels of happiness and willingness to continue with the changes implemented during COVID-19. The strategies adopted worked well and the overall high levels of staff satisfaction will allow our service to quickly pivot should further surges, or another pandemic, arise.
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http://dx.doi.org/10.1111/1754-9485.13186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207051PMC
June 2021

Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi-institutional patterns of practice review.

J Med Imaging Radiat Oncol 2021 Jun 22;65(3):365-373. Epub 2021 Apr 22.

Department of Cancer Services, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Introduction: Stereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.

Methods: This was a multi-institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated.

Results: Three hundred and seventeen patients were evaluated with a median age of 67 years (range, 32-90). Liver cirrhosis was present in 88.6%, baseline Child-Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10-280). 63.1% had early-stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced-stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED ) delivered was 85.5 Gy for early-stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100-120 Gy BED (32.8%).

Conclusion: SBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT.
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http://dx.doi.org/10.1111/1754-9485.13184DOI Listing
June 2021

Neoadjuvant radiotherapy for locally advanced and high-risk breast cancer.

J Med Imaging Radiat Oncol 2021 Jun 5;65(3):345-353. Epub 2021 Apr 5.

Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia.

Introduction: Neoadjuvant radiotherapy (NART) as part of a multi-modality approach for locally advanced breast cancer (LABC) requires further investigation. Importantly, this approach may allow for a single-staged surgical procedure, with mastectomy and immediate autologous reconstruction. Multiple other potential benefits of NART include improved pathological downstaging of breast disease, reduced overall treatment time, elimination of time period with breast tissue deficit and improved patient satisfaction.

Methods: This is a retrospective multi-institutional review of patients with LABC and high-risk breast disease undergoing NART. Eligible patients sequentially underwent neoadjuvant chemotherapy (NACT) with or without HER2-targeted therapy, NART, followed by mastectomy with immediate autologous breast reconstruction (BR) 4- to 6 weeks post-completion of radiotherapy. Patient and tumour characteristics were analysed using descriptive statistics. Surgical complications were assessed using the Clavien-Dindo Classification (Ann Surg 2004; 240: 205).

Results: From 3/2013 to 9/2019, 153 patients were treated with NART. The median age was 47 years (IQR 42-52), with median body mass index of 27. Eighteen patients experienced Grade 3 acute surgical complications. This included 13 Grade 3B breast-site events and 9 Grade 3B donor-site events, where further surgical intervention was required for management of wound infection, wound dehiscence, flap or mastectomy skin necrosis, haematoma and internal mammary venous anastomotic thrombosis. No autologous flap loss was observed.

Conclusion: Neoadjuvant radiotherapy facilitates a single-stage surgical procedure with mastectomy and immediate autologous BR, eliminating the delay to reconstructive surgery and thus shortening a woman's breast cancer journey. The findings of this review support the use of NART, with comparable rates of surgical complications to standard sequencing.
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http://dx.doi.org/10.1111/1754-9485.13180DOI Listing
June 2021

Choosing Wisely in radiation therapy for breast cancer: Time lag in adoption of hypofractionated radiation therapy in Victoria.

J Med Imaging Radiat Oncol 2021 Apr 16;65(2):224-232. Epub 2021 Feb 16.

Department of Radiation Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia.

Introduction: To evaluate the adoption of hypofractionated radiotherapy (HFRT) for breast cancer (BC) in Victoria, Australia.

Methods: This is a population-based cohort of women with BC who had breast RT as captured in the Victorian Radiotherapy Minimum Data Set between 2012 and 2017. We defined HFRT as < 25 fractions of RT. The pattern of HFRT use over time was evaluated with the Cochrane-Armitage test for trend. Factors associated with HFRT were identified using multivariable logistic regression.

Results: 12,717 women were included in the study. Overall, 6,653 (52%) patients had HFRT. HFRT use increased from 35% in 2012 to 66% in 2017 (P-trend < 0.001). Older women were more likely to have HFRT (74% for women aged ≥ 70 years vs. 27% for women aged < 50 years; P < 0.001). Women who had nodal irradiation were less likely to have HFRT compared with those who did not (13% vs. 57%; P < 0.001). HFRT use was more common in public than private institutions (57% vs. 46%, P < 0.001), and in metropolitan than regional centres (54% vs. 46%, P < 0.001). In multivariable analyses, the progressive increase in HFRT use over time was independent of other covariates - women treated in 2017 were 7.3 times (95% CI = 6.3-8.6, P < 0.001) more likely to be treated with HFRT than in 2012. Age at RT, nodal irradiation, area of residence and institutional type and locations were all independently associated with HFRT use.

Conclusion: This large Australian contemporary population-based study demonstrates increasing use of HFRT for BC. However, large sociodemographic and institutional provider-related variations in practice still exist.
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http://dx.doi.org/10.1111/1754-9485.13155DOI Listing
April 2021

Protocol of a study investigating breath-hold techniques for upper-abdominal radiation therapy (BURDIE): addressing the challenge of a moving target.

Radiat Oncol 2020 Oct 30;15(1):250. Epub 2020 Oct 30.

Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Wellington Rd, Clayton, VIC, 3800, Australia.

Background: Radiation therapy to upper abdominal sites is technically challenging due to motion of tumors and surrounding organs resulting from normal respiration. Breath-hold, using an Active Breathing Coordinator is one strategy used to reduce motion in these tumor sites. Though widely used, no studies have prospectively compared the different breath-hold techniques (inspiration, deep-inspiration and expiration) using ABC in the same patient cohort.

Methods: Patients planned for radiation therapy to upper abdominal tumors are invited to participate in this prospective study. Participants attempt three breath hold techniques: inspiration, deep-inspiration and expiration breath-hold, in random order. kV fluoroscopy images of the dome of diaphragm are taken of five consecutive breath-holds in each technique. Reproducibility and stability of tumour position are measured, and used to select the technique with which to proceed to planning and treatment. Reproducibility at planning and each treatment fraction is measured, along with breath hold time, treatment efficiency and patient experience.

Discussion: The screening method was validated after the first three participants. This screening process may be able to select the best breath-hold technique for an individual, which may lead to improved reproducibility. The screening process is being piloted as a prospective clinical trial.

Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR): 12618001691235. Registered 12th October 2018. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376109&isReview=true .
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http://dx.doi.org/10.1186/s13014-020-01688-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602358PMC
October 2020

Prognostic performance of qSOFA in oncology patients admitted to the emergency department with suspected infection.

Asia Pac J Clin Oncol 2021 Feb 20;17(1):94-100. Epub 2020 Oct 20.

Department of Radiation Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia.

Aim: We aimed to test the performance of the quick Sequential Organ Failure Assessment score (qSOFA) in predicting the outcomes of oncology patients admitted to the emergency department (ED) with suspected infection.

Methods: Retrospective cohort analysis of all oncology patients presenting to the ED of a tertiary hospital with suspected infection from 1 December 2014 to 1 June 2017. Patients were identified by cross-linkage of ED and Oncology electronic health records. The primary outcome was in-hospital mortality and/or ICU stay ≥ 3 days.

Results: A total of 1655 patients were included in this study--1267 (76.6%) with solid tumor and 388 (23.4%) with hematological malignancies. At presentation, 495 patients had chemotherapy, and 140 had radiotherapy within the preceding 6 months. Four hundred patients received chemotherapy and/or radiotherapy in the previous 4 weeks. Overall, 371 (22.4%) patients had qSOFA ≥ 2. Such patients had a higher likelihood of respiratory infections compared to patients with a qSOFA < 2 (43.9% vs 29%) and were more likely to be admitted to ICU or require mechanical ventilation. In-hospital mortality or in-hospital mortality and/or ICU stay ≥ 3 days were 17.3% and 21%, for qSOFA ≥ 2 patients versus 4.7% and 6.9% for qSOFA < 2 patients (P < .001). qSOFA ≥ 2 had a negative predictive value of 95% for in-hospital mortality and 93% for in-hospital mortality or ICU stay ≥ 3 days.

Conclusion: Among oncology patients presenting to the ED with suspected infection, a qSOFA ≥ 2 is associated with a threefold risk of hospital mortality/prolonged ICU stay. Its absence helps identify low-risk patients.
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http://dx.doi.org/10.1111/ajco.13422DOI Listing
February 2021

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

Extracting tumour prognostic factors from a diverse electronic record dataset in genito-urinary oncology.

Int J Med Inform 2019 01 23;121:53-57. Epub 2018 Oct 23.

Austin Health, Department of Radiation Oncology, Melbourne, Australia; Department of Cancer Medicine, Latrobe University, Melbourne, Australia.

Objectives: To implement a system for unsupervised extraction of tumor stage and prognostic data in patients with genitourinary cancers using clinicopathological and radiology text.

Methods: A corpus of 1054 electronic notes (clinician notes, radiology reports and pathology reports) was annotated for tumor stage, prostate specific antigen (PSA) and Gleason grade. Annotations from five clinicians were reconciled to form a gold standard dataset. A training dataset of 386 documents was sequestered. The Medtex algorithm was adapted using the training dataset.

Results: Adapted Medtex equaled or exceeded human performance in most annotations, except for implicit M stage (F-measure of 0.69 vs 0.84) and PSA (0.92 vs 0.96). Overall Medtex performed with an F-measure of 0.86 compared to human annotations of 0.92. There was significant inter-observer variability when comparing human annotators to the gold standard.

Conclusions: The Medtex algorithm performed similarly to human annotators for extracting stage and prognostic data from varied clinical texts.
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http://dx.doi.org/10.1016/j.ijmedinf.2018.10.008DOI Listing
January 2019

qSOFA as predictor of mortality and prolonged ICU admission in Emergency Department patients with suspected infection.

J Crit Care 2018 12 21;48:118-123. Epub 2018 Aug 21.

Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia; Data Analytics Research and Evaluation (DARE) Center, Melbourne University and Austin Hospital, Melbourne, Australia; School of Medicine, The University of Melbourne, Parkville, Melbourne, Victoria, Australia; Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. Electronic address:

Purpose: We assessed the quick Sequential Organ Failure Assessment (qSOFA) score as a predictor of in-hospital mortality or prolonged ICU stay in Emergency Department (ED) patients with suspected infection.

Patients And Methods: We measured qSOFA in a cohort of 11,205 ED patients with suspected infection. The primary outcome was in-hospital mortality and/or ICU stay ≥3 days.

Results: The qSOFA score was positive in 2429 (21.7%) patients. In-hospital mortality, and in-hospital mortality or ICU stay ≥3 days were 12.8% and 17.2% respectively for qSOFA positive patients vs 2.2% and 4.2% for qSOFA negative patients (p < .0001). For the prediction of in-hospital mortality, a positive qSOFA had a positive predictive value (PPV) of 13% (95% CI, 11-14) and a negative predictive value (NPV) of 98% (95% CI, 97-98). For the prediction of in-hospital mortality or ICU stay ≥3 days, the PPV and NPV of a positive qSOFA were 17% (95% CI, 16-19) and 96 (95% CI, 95-96), respectively.

Conclusion: Among ED patients with suspected infection, a positive qSOFA identified those at much greater risk of mortality and longer ICU stay.
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http://dx.doi.org/10.1016/j.jcrc.2018.08.022DOI Listing
December 2018

Outcome of patients with early-stage follicular lymphoma staged with F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and treated with radiotherapy alone.

Eur J Nucl Med Mol Imaging 2019 01 7;46(1):80-86. Epub 2018 Aug 7.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Purpose/objective(s): To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone.

Materials/methods: Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan-Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks.

Results: Median age was 57 years (range 24-83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123-607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30-36Gy in 15-24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25-6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15-18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79-100) for the whole cohort.

Conclusion: FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.
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http://dx.doi.org/10.1007/s00259-018-4112-2DOI Listing
January 2019

An abscopal effect may augment PD-1 inhibition in refractory classical Hodgkin lymphoma.

Leuk Lymphoma 2018 11 23;59(11):2749-2751. Epub 2018 Mar 23.

a Department of Haematology , Olivia Newton John Cancer and Wellness Centre, Austin Health , Heidelberg , Australia.

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http://dx.doi.org/10.1080/10428194.2018.1452217DOI Listing
November 2018

Patterns of health services utilization in the last two weeks of life among cancer patients: Experience in an Australian academic cancer center.

Asia Pac J Clin Oncol 2017 Dec 11;13(6):400-406. Epub 2017 Jul 11.

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.

Aim: To report the trend in end-of-life health services (HS) utilization among cancer patients treated in a large Australian academic cancer center over a 12-year period.

Methods: This is a retrospective study of cancer patients treated at the Peter MacCallum Cancer Centre (PMCC), who had documented death between January 2002 and December 2013. Using administrative and billing database, we report on the utilization of different categories of HS within two weeks of death: diagnostic investigations (pathology and radiology), inpatient and outpatient services, and potentially futile interventions (PFI, which include radiotherapy, chemotherapy and surgery).

Results: Of the 27 926 "active" cancer patients in the study (i.e. those with medical contact at PMCC in the last year of life), 6368 (23%) had documented HS utilization within two weeks of death. 11% and 9% had pathology and radiology investigations respectively, 14% had outpatient clinic appointments, and 7% had hospital admissions. There were 2654 patients (10%) who had PFI within two weeks of death - 2198 (8%) had radiotherapy, 287 (1%) chemotherapy and 267 (1%) surgery. We observed peak HS and PFI utilization in 2004, which then dropped to its lowest in 2009/2010.

Conclusion: Experience in an Australian cancer center suggests approximately one in four "active" cancer patients had HS utilization, and one in ten had PFI, within two weeks of death. The implementation of palliative care guidelines may reduce some of these potentially wasteful and futile interventions.
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http://dx.doi.org/10.1111/ajco.12701DOI Listing
December 2017

Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

Breast 2016 Jun 22;27:126-35. Epub 2016 Apr 22.

Epworth Radiation Oncology Research Centre, Epworth Richmond, 32 Erin St, Richmond VIC 3121, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques.
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http://dx.doi.org/10.1016/j.breast.2016.03.002DOI Listing
June 2016

Tolerability and outcomes of curative radiotherapy in patients aged 85 or more years.

Med J Aust 2015 Feb;202(3):153-5

Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Objectives: To assess the tolerability and survival outcome of curative radiotherapy in patients over the age of 85 years.

Design, Setting, And Participants: Retrospective analysis of all patients aged over 85 years who received radiotherapy as part of curative treatment for any cancer (excluding insignificant skin cancers) at the Peter MacCallum Cancer Centre between 1 January 2000 and 1 January 2010.

Main Outcome Measures: Poor treatment tolerability (defined as hospital admission during radiotherapy, treatment break, or early treatment cessation); predictors for poor treatment tolerability, overall survival and cancer-specific survival.

Results: 327 treatment courses met eligibility criteria. The median age of patients was 87 years. The most common treatment sites were pelvis (30%), head and neck (25%), and breast (18%). The Eastern Cooperative Oncology Group performance status (ECOG PS) score was 0 or 1 for 70% of patients. Overall, 79% of patients completed the prescribed treatment without poor treatment tolerability, and 95% of patients completed all treatment. Only unfavourable ECOG PS score (odds ratio [OR], 1.80; P = 0.005) and increasing age (OR, 1.18; P = 0.018) predicted poor treatment tolerability. ECOG PS score predicted overall survival (hazard ratio, 1.53; P = 0.001).

Conclusion: Age should not be the sole discriminator in decisions to prescribe aggressive loco-regional radiotherapy. ECOG PS score predicts for treatment tolerability, and also overall survival. The risk of cancer death was higher than non-cancer death for more than 5 years after treatment.
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http://dx.doi.org/10.5694/mja14.00441DOI Listing
February 2015

Contemporary issues in radiotherapy for clinically localized prostate cancer.

Hematol Oncol Clin North Am 2013 Dec 21;27(6):1137-62, vii. Epub 2013 Sep 21.

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Victoria 8006, Australia. Electronic address:

Radiotherapy is a valid curative alternative to surgery for prostate cancer. However, patient selection is critical to ensure patients obtain benefits from therapy delivered with curative intent. Dose-escalated radiation has been shown to improve patient outcomes, facilitated by development of robust image guidance and better target delineation imaging technologies. These concepts have also rekindled interest in hypofractionated radiotherapy in the forms of stereotactic body radiotherapy and brachytherapy. Postprostatectomy radiotherapy also improves long-term biochemical outcome in men at high risk of local recurrence.
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http://dx.doi.org/10.1016/j.hoc.2013.08.006DOI Listing
December 2013

Patterns of retreatment with radiotherapy in a large academic centre.

J Med Imaging Radiat Oncol 2013 Oct 9;57(5):610-6. Epub 2013 May 9.

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

Aims: To characterise retreatment rates with radiotherapy at a large multifacility academic radiotherapy centre and assess the effect of distance on retreatment rate.

Materials And Methods: Electronic administrative records were reviewed for patients receiving radiotherapy between 1998 and 2010 at regional and metropolitan facilities. Course-level data were reconstructed from electronic administrative databases. Intent of therapy, treatment dates and diagnosis were available for analysis. Retreatment characteristics were derived, including proportion of patients receiving retreatment, proportion of total radiotherapy prescriptions dedicated to retreatment and retreatment per treating facility. Travel distance for each patient to their treatment centre was estimated, and retreatment rates were reported as a function of increasing distance.

Results: A total of 48 200 patients were treated with 66 277 treatment courses during the study period. Retreatment courses constituted 25.2% of all courses prescribed. During the study period, 20.4% of all patients received at least one treatment course. Of these, the average number of retreatment courses prescribed was 1.84. Patients treated with radical intent had a retreatment rate of 13% compared with 45% for those treated initially with palliative intent. Retreatment rates in individual tumour sites ranged from 1.3 to 44.4%. The retreatment rate for those living less than 100 km from treatment facility was 24.8%, and 20.5% for those living more than 100 km from treatment centre (P < 0.001) CONCLUSION: Retreatment accounted for over one quarter of radiotherapy courses, with the rate influenced by casemix and follow-up duration. With increasing distance from treatment centre, a decrease in retreatment rate was observed.
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http://dx.doi.org/10.1111/1754-9485.12066DOI Listing
October 2013

Practical implementation of an existing smoking detection pipeline and reduced support vector machine training corpus requirements.

J Am Med Inform Assoc 2014 Jan-Feb;21(1):27-30. Epub 2013 Aug 6.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

This study aimed to reduce reliance on large training datasets in support vector machine (SVM)-based clinical text analysis by categorizing keyword features. An enhanced Mayo smoking status detection pipeline was deployed. We used a corpus of 709 annotated patient narratives. The pipeline was optimized for local data entry practice and lexicon. SVM classifier retraining used a grouped keyword approach for better efficiency. Accuracy, precision, and F-measure of the unaltered and optimized pipelines were evaluated using k-fold cross-validation. Initial accuracy of the clinical Text Analysis and Knowledge Extraction System (cTAKES) package was 0.69. Localization and keyword grouping improved system accuracy to 0.9 and 0.92, respectively. F-measures for current and past smoker classes improved from 0.43 to 0.81 and 0.71 to 0.91, respectively. Non-smoker and unknown-class F-measures were 0.96 and 0.98, respectively. Keyword grouping had no negative effect on performance, and decreased training time. Grouping keywords is a practical method to reduce training corpus size.
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http://dx.doi.org/10.1136/amiajnl-2013-002090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912731PMC
February 2014

Direct 2-arm comparison shows benefit of high-dose-rate brachytherapy boost vs external beam radiation therapy alone for prostate cancer.

Int J Radiat Oncol Biol Phys 2013 Mar 3;85(3):679-85. Epub 2012 Sep 3.

Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, and University of Melbourne, Melbourne, Australia.

Purpose: To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone.

Methods And Materials: From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRT was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed.

Results: Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed.

Conclusions: This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2012.07.006DOI Listing
March 2013
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