Publications by authors named "Sweet Ping Ng"

55 Publications

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

Current State of Neoadjuvant Radiotherapy for Rectal Cancer.

Clin Colorectal Cancer 2021 Nov 4. Epub 2021 Nov 4.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Australia.

Colorectal cancer is the third most commonly diagnosed cancer, with rectal cancer accounting for 30% of cases. The current standard of care curative treatment for locally advanced rectal cancer is (chemo)radiotherapy followed by surgery and adjuvant chemotherapy. Although neoadjuvant radiotherapy has reduced the risk of local recurrence to less than 10%, the risk of distant metastasis remained high at 30% affecting patient survival. In addition, there is a recognition that there is heterogeneity in tumor biology and treatment response with good responders potentially suitable for treatment de-escalation. Therefore, new treatment sequencing and regimens were investigated. Here, we reviewed the evidence for current neoadjuvant treatment options in patients with locally advanced rectal adenocarcinoma, and highlight the new challenges in this new treatment landscape.
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http://dx.doi.org/10.1016/j.clcc.2021.10.008DOI Listing
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

Cascaded deep learning-based auto-segmentation for head and neck cancer patients: Organs at risk on T2-weighted magnetic resonance imaging.

Med Phys 2021 Dec 1;48(12):7757-7772. Epub 2021 Nov 1.

Department of Physical Science, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Purpose: To investigate multiple deep learning methods for automated segmentation (auto-segmentation) of the parotid glands, submandibular glands, and level II and level III lymph nodes on magnetic resonance imaging (MRI). Outlining radiosensitive organs on images used to assist radiation therapy (radiotherapy) of patients with head and neck cancer (HNC) is a time-consuming task, in which variability between observers may directly impact on patient treatment outcomes. Auto-segmentation on computed tomography imaging has been shown to result in significant time reductions and more consistent outlines of the organs at risk.

Methods: Three convolutional neural network (CNN)-based auto-segmentation architectures were developed using manual segmentations and T2-weighted MRI images provided from the American Association of Physicists in Medicine (AAPM) radiotherapy MRI auto-contouring (RT-MAC) challenge dataset (n = 31). Auto-segmentation performance was evaluated with segmentation similarity and surface distance metrics on the RT-MAC dataset with institutional manual segmentations (n = 10). The generalizability of the auto-segmentation methods was assessed on an institutional MRI dataset (n = 10).

Results: Auto-segmentation performance on the RT-MAC images with institutional segmentations was higher than previously reported MRI methods for the parotid glands (Dice: 0.860 ± 0.067, mean surface distance [MSD]: 1.33 ± 0.40 mm) and the first report of MRI performance for submandibular glands (Dice: 0.830 ± 0.032, MSD: 1.16 ± 0.47 mm). We demonstrate that high-resolution auto-segmentations with improved geometric accuracy can be generated for the parotid and submandibular glands by cascading a localizer CNN and a cropped high-resolution CNN. Improved MSDs were observed between automatic and manual segmentations of the submandibular glands when a low-resolution auto-segmentation was used as prior knowledge in the second-stage CNN. Reduced auto-segmentation performance was observed on our institutional MRI dataset when trained on external RT-MAC images; only the parotid gland auto-segmentations were considered clinically feasible for manual correction (Dice: 0.775 ± 0.105, MSD: 1.20 ± 0.60 mm).

Conclusions: This work demonstrates that CNNs are a suitable method to auto-segment the parotid and submandibular glands on MRI images of patients with HNC, and that cascaded CNNs can generate high-resolution segmentations with improved geometric accuracy. Deep learning methods may be suitable for auto-segmentation of the parotid glands on T2-weighted MRI images from different scanners, but further work is required to improve the performance and generalizability of these methods for auto-segmentation of the submandibular glands and lymph nodes.
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http://dx.doi.org/10.1002/mp.15290DOI Listing
December 2021

Radiomics feature stability of open-source software evaluated on apparent diffusion coefficient maps in head and neck cancer.

Sci Rep 2021 09 3;11(1):17633. Epub 2021 Sep 3.

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

Radiomics is a promising technique for discovering image based biomarkers of therapy response in cancer. Reproducibility of radiomics features is a known issue that is addressed by the image biomarker standardisation initiative (IBSI), but it remains challenging to interpret previously published radiomics signatures. This study investigates the reproducibility of radiomics features calculated with two widely used radiomics software packages (IBEX, MaZda) in comparison to an IBSI compliant software package (PyRadiomics). Intensity histogram, shape and textural features were extracted from 334 diffusion weighted magnetic resonance images of 59 head and neck cancer (HNC) patients from the PREDICT-HN observational radiotherapy study. Based on name and linear correlation, PyRadiomics shares 83 features with IBEX and 49 features with MaZda, a sub-set of well correlated features are considered reproducible (IBEX: 15 features, MaZda: 18 features). We explore the impact of including non-reproducible radiomics features in a HNC radiotherapy response model. It is possible to classify equivalent patient groups using radiomic features from either software, but only when restricting the model to reliable features using a correlation threshold method. This is relevant for clinical biomarker validation trials as it provides a framework to assess the reproducibility of reported radiomic signatures from existing trials.
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http://dx.doi.org/10.1038/s41598-021-96600-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417253PMC
September 2021

Patient-Reported Outcomes after Intensity-Modulated Proton Therapy for Oropharynx Cancer.

Int J Part Ther 2021 25;8(1):213-222. Epub 2021 Jun 25.

The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: To report patient-reported outcomes (PROs) derived from the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) tool, in patients with oropharynx cancer (OPC) treated with intensity-modulated proton therapy (IMPT) in the context of first-course irradiation.

Materials And Methods: Patients with locally advanced OPC treated with radical IMPT between 2011 and 2018 were included in a prospective registry. FACT-HN scores were measured serially during and 24 months following IMPT. PRO changes in the FACT-HN scores over time were assessed with mixed-model analysis.

Results: Fifty-seven patients met inclusion criteria. Median age was 60 years (range, 41-84), and 91% had human papillomavirus-associated disease. In total, 28% received induction chemotherapy and 68% had concurrent chemotherapy. Compliance to FACT-HN questionnaire completion was 59%, 48%, and 42% at 6, 12, and 24 months after treatment, respectively. The mean FACT-General (G), FACT-Total, and FACT-Trial Outcome Index (TOI) score changes were statistically and clinically significant relative to baseline from week 3 of treatment up to week 2 after treatment. Nadir was reached at week 6 of treatment for all scores, with maximum scores dropping by 15%, 20%, and 39% compared to baseline for FACT-G, FACT-Total, and FACT-TOI, respectively. Subdomain scores of physical well-being, functional well-being, and head and neck additional concerns decreased from baseline during treatment and returned to baseline at week 4 after treatment.

Conclusions: IMPT was associated with a favorable PRO trajectory, characterized by an acute decline followed by rapid recovery to baseline. This study establishes the expected acute, subacute, and chronic trajectory of PROs for patients undergoing IMPT for OPC.
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http://dx.doi.org/10.14338/IJPT-20-00081.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270092PMC
June 2021

Computed Tomography Radiomics Kinetics as Early Imaging Correlates of Osteoradionecrosis in Oropharyngeal Cancer Patients.

Front Artif Intell 2021 9;4:618469. Epub 2021 Apr 9.

Department of Electrical and Computer Engineering, Rice University, Houston, TX, United States.

Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs. Control subvolumes with an area under curve (AUC) = 0.74 [95% confidence interval (C.I.): 0.61-0.90], significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e., at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN.
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http://dx.doi.org/10.3389/frai.2021.618469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063205PMC
April 2021

Vocal-cord Only vs. Complete Laryngeal radiation (VOCAL): a randomized multicentric Bayesian phase II trial.

BMC Cancer 2021 Apr 22;21(1):446. Epub 2021 Apr 22.

Radiation Oncology Department, Western University, London, Ontario, Canada.

Background: Radiotherapy, along with laser surgery, is considered a standard treatment option for patients with early glottic squamous cell cancer (SCC). Historically, patients have received complete larynx radiotherapy (CL-RT) due to fear of swallowing and respiratory laryngeal motion and this remains the standard approach in many academic institutions. Local control (LC) rates with CL-RT have been excellent, however this treatment can carry significant toxicities include adverse voice and swallowing outcomes, along with increased long-term risk of cerebrovascular morbidity. A recent retrospective study reported improved voice quality and similar local control outcomes with focused vocal cord radiotherapy (VC-RT) compared to CL-RT. There is currently no prospective evidence on the safety of VC-RT. The primary objective of this Bayesian Phase II trial is to compare the LC of VC-RT to that of CL-RT in patients with T1N0 glottic SCC.

Methods: One hundred and fifty-five patients with T1a-b N0 SCC of the true vocal cords that are n ot candidate or declined laser surgery, will be randomized in a 1:3 ratio the control arm (CL-RT) and the experimental arm (VC-RT). Randomisation will be stratified by tumor stage (T1a/T1b) and by site (each site will be allowed to select one preferred radiation dose regimen, to be used in both arms). CL-RT volumes will correspond to the conventional RT volumes, with the planning target volume extending from the top of thyroid cartilage lamina superiorly to the bottom of the cricoid inferiorly. VC-RT volumes will include the involved vocal cord(s) and a margin accounting for respiration and set-up uncertainty. The primary endpoint will be LC at 2-years, while secondary endpoints will include patient-reported outcomes (voice impairment, dysphagia and symptom burden), acute and late toxicity radiation-induced toxicity, overall survival, progression free survival, as well as an optional component of acoustic and objective measures of voice analysis using the Consensus Auditory-Perceptual Evaluation of Voice.

Discussion: This study would constitute the first prospective evidence on the efficacy and safety of VC-RT in early glottic cancer. If positive, this study would result in the adoption of VC-RT as standard approach in early glottic cancer.

Trial Registration: ClinicalTrials.gov Identifier: NCT03759431 Registration date: November 30, 2018.
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http://dx.doi.org/10.1186/s12885-021-08195-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061218PMC
April 2021

Role of Radiation Therapy in Gastric Cancer.

Ann Surg Oncol 2021 Aug 10;28(8):4151-4157. Epub 2021 Mar 10.

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

The only curative treatment for localised gastric cancer is surgical resection. However, survival outcomes post-surgery alone remain poor, particularly in those with node-positive disease with 5-year survival of approximately 30%. Therefore, additional perioperative treatment strategies such as radiotherapy and/or chemotherapy have been explored to improve survival outcomes. Early studies established the role of postoperative radiotherapy in improving locoregional control. However, there are now several adjuvant treatment options available, with many centres favouring perioperative chemotherapy. The delivery of radiotherapy in the postoperative setting can be challenging, thereby resulting in suboptimal patient compliance. Hence, the role of preoperative radiotherapy is currently being evaluated. This review focuses on and summarises the landmark clinical trials that have established the current role of radiation therapy in patients with resectable gastric and gastroesophageal adenocarcinoma, and highlights the potential for preoperative radiotherapy.
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http://dx.doi.org/10.1245/s10434-021-09639-yDOI Listing
August 2021

Radiation-Associated Lymphopenia and Outcomes of Patients with Unresectable Hepatocellular Carcinoma Treated with Radiotherapy.

J Hepatocell Carcinoma 2021 3;8:57-69. Epub 2021 Mar 3.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: The immune system plays a crucial role in cancer surveillance. Previous studies have shown that lymphopenia associated with radiotherapy (RT) portends a poor prognosis. We sought to differentiate the effects of proton and photon RT on changes in absolute lymphocyte count (ALC) for patients with hepatocellular carcinoma (HCC).

Patients And Methods: Patients with HCC treated with definitive RT from 2006 to 2016 were studied. Serial ALCs were graded according to CTCAE v4.0. Overall survival (OS), disease-free survival, and distant metastasis-free survival were analyzed using the Kaplan-Meier method. Univariable and multivariable Cox-proportional hazards analyses were used to identify predictors of OS. A cohort analysis matched for treatment volume was performed to investigate differences in ALC dynamics between photon and proton therapy.

Results: Of 143 patients identified, the median age was 66 (range, 19-90) years. The treatment modality was photon in 103 (72%) and proton in 40 (28%). Median follow-up was 17 months (95% confidence interval, 13-25 months). The median time to ALC nadir after initiation of RT was 17 days with a median relative decrease of 67%. Those who received proton RT had a higher median ALC nadir (0.41 vs 0.32 k/µL, p=0.002) and longer median OS (33 vs 13 months, p=0.002) than those who received photon RT. Matched cohort analyses revealed a larger low-dose liver volume in the photon group, which correlated with lower ALC. On multivariable Cox analysis, Grade 3 or higher lymphopenia prior to or after RT, portal venous tumor thrombus, larger planning target volumes, Child-Pugh (CP) Class B, and increased CP score after RT were associated with a higher risk of death, whereas the use of proton therapy was associated with lower risk.

Conclusion: Grade 3 or higher lymphopenia may be associated with poorer outcomes in patients receiving RT for HCC. Protons may mitigate lymphopenia compared with photons, potentially due to reduced dose exposure of sites of lymphopoiesis.
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http://dx.doi.org/10.2147/JHC.S282062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937383PMC
March 2021

Comparison of tumor delineation using dual energy computed tomography versus magnetic resonance imaging in head and neck cancer re-irradiation cases.

Phys Imaging Radiat Oncol 2020 Apr 29;14:1-5. Epub 2020 Apr 29.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0-0.91) for T1c. T1c MRI provided higher interobserver agreement for skull base sites and 60 kV DECT provided higher interobserver agreement for non-skull base sites.
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http://dx.doi.org/10.1016/j.phro.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807720PMC
April 2020

Patient Outcomes after Reirradiation of Small Skull Base Tumors using Stereotactic Body Radiotherapy, Intensity Modulated Radiotherapy, or Proton Therapy.

J Neurol Surg B Skull Base 2020 Dec 31;81(6):638-644. Epub 2019 Jul 31.

Department of Radiation Oncology, Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, Unites States.

 The aim of this study was to evaluate outcomes of patients who received reirradiation for small skull base tumors utilizing either intensity modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton radiotherapy (PRT).  Patients who received IMRT, SBRT or PRT reirradiation for recurrent or new small skull base tumors (< 60 cc) between April 2000 and July 2016 were identified. Those with < 3 months follow-up were excluded. Clinical outcomes and treatment toxicity were assessed. The Kaplan-Meier method was used to estimate the local control (LC), regional control (RC), distant control (DC), progression free survival (PFS), and overall survival (OS).  Of the 75 patients eligible, 30 (40%) received SBRT, 30 (40%) received IMRT, and 15 (20%) received PRT. The median retreatment volume was 28 cc. The median reirradiation dose was 66 Gy in 33 fractions for IMRT/PRT, and 45 Gy in 5 fractions for SBRT. The median time to reirradiation was 41 months. With a median follow-up of 24 months, the LC, RC, DC, PFS, and OS rates were 84%, 79%, 82%, 60%, and 87% at 1 year, and 75%, 72%, 80%, 49%, and 74% at 2 years. There was no difference in OS between radiation modalities. The 1- and 2-year late Grade 3 toxicity rates were 3% and 11% respectively..  Reirradiation of small skull base tumors utilizing IMRT, PRT, or SBRT provided good local tumor control and low rates of Grade 3 late toxicity. A prospective clinical trial is needed to guide selection of radiation treatment modalities.
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http://dx.doi.org/10.1055/s-0039-1694052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755504PMC
December 2020

Longitudinal characterization of the tumoral microbiome during radiotherapy in HPV-associated oropharynx cancer.

Clin Transl Radiat Oncol 2021 Jan 18;26:98-103. Epub 2020 Nov 18.

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

Purpose: To describe the baseline and serial tumor microbiome in HPV-associated oropharynx cancer (OPC) over the course of radiotherapy (RT).

Methods: Patients with newly diagnosed HPV-associated OPC treated with definitive radiotherapy +/- concurrent chemotherapy were enrolled in this prospective study. Using 16S rRNA gene sequencing, dynamic changes in the tumor site microbiome during RT were investigated. Surface tumor samples were obtained before RT and at week 1, 3 and 5 of RT. Radiological primary tumor response at mid-treatment was categorized as complete (CR) or partial (PR).

Results: Ten patients were enrolled, but 9 patients were included in the final analysis. Mean age was 62 years (range: 51-71). As per AJCC 8th Ed, 56%, 22% and 22% of patients had stage I, II and III, respectively. At 4-weeks, 6 patients had CR and 3 patients had PR; at follow-up imaging post treatment, all patients had CR. The baseline diversity of the tumoral versus buccal microbiome was not statistically different. For the entire cohort, alpha diversity was significantly decreased over the course of treatment (p = 0.04). There was a significant alteration in the bacterial community within the first week of radiation. Baseline tumor alpha diversity of patients with CR was significantly higher than those with PR (p = 0.03). While patients with CR had significant reduction in diversity over the course of radiation (p = 0.01), the diversity remained unchanged in patients with PR. Patients with history of smoking had significantly increased abundance of   (0.05) and lower abundance of  (p = 0.03) compared to never smokers.

Conclusions: The tumor microbiome of HPV-associated OPC exhibits reduced alpha diversity and altered taxa abundance over the course of radiotherapy. The baseline bacterial profiles of smokers vs. non-smokers were inherently different. Baseline tumor alpha diversity of patients with CR was higher than patients with PR, suggesting that the microbiome deserves further investigation as a biomarker of radiation response.
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http://dx.doi.org/10.1016/j.ctro.2020.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749292PMC
January 2021

Patterns of Failure After Intensity Modulated Radiation Therapy in Head and Neck Squamous Cell Carcinoma of Unknown Primary: Implication of Elective Nodal and Mucosal Dose Coverage.

Adv Radiat Oncol 2020 Sep-Oct;5(5):929-935. Epub 2020 May 15.

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

Purpose: We evaluated the geometric and dosimetric-based distribution of mucosal and nodal recurrences in patients with metastatic head and neck squamous cell carcinoma to cervical lymph nodes of unknown primary after intensity modulated radiation therapy using validated typology-indicative taxonomy.

Methods And Materials: We reviewed the data of 260 patients who were irradiated between 2000 and 2015 and had a median follow-up time for surviving patients of 61 months. The mucosal and nodal recurrences were manually delineated on computed tomography images demonstrating the recurrences. The images were overlaid on the treatment plan using deformable image registration. The locations of the recurrences were determined relative to the original planning target volumes and doses using centroid-based approaches. Subsequently, the pattern of failures were classified into 5 types based on combined spatial and dosimetric criteria: A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose). For patients with type A failure with simultaneous nontype A lesions, the overall pattern of failures was defined as type A.

Results: Thirty-two patients had mucosal or nodal recurrences. The most common clinical nodal stage was N2b (66%). Preradiation therapy neck dissections were performed in 6 patients. The median dose delivered to clinical tumor volume 1 was 66 Gy. The majority (84%) had total/partial pharyngeal mucosa elective irradiation. Twenty-three patients had nodal recurrences, 8 had mucosal recurrences, and 1 had both nodal and mucosal recurrences. Twenty-one patients (91%) had type A nodal failure, and 7 of the mucosal failures (89%) were type C.

Conclusions: The majority of nodal recurrences occurred within the high-dose area, demanding the need for identification of radioresistant areas within malignant nodes. Future studies should focus on either dose escalation of high-risk volumes or novel radiosensitizers.
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http://dx.doi.org/10.1016/j.adro.2020.04.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557124PMC
May 2020

Results of phase II trial of intensified neoadjuvant treatment with interdigitating radiotherapy and chemotherapy with oxaliplatin, 5-fluorouracil and folinic acid in patients with locally advanced rectal cancer (PROARCT trial).

Radiother Oncol 2021 02 14;155:27-32. Epub 2020 Oct 14.

Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. Electronic address:

Background And Purpose: The chemotherapy exposure during chemoradiotherapy for rectal cancer is adequate for radiosensitization but suboptimal for treatment of distant micrometastasis. This study aimed to determine tolerability, dose intensity, response, and toxicity of a novel intensified neoadjuvant treatment approach.

Materials And Methods: Eligible patients were MRI-staged T3-4NxM0 rectal adenocarcinoma. Treatment consisted of FOLFOX chemotherapy given in weeks 1, 6, and 11 with pelvic radiotherapy (25.2 Gy in 3 weeks in 1.8 Gy/fraction with oxaliplatin and 5-FU continuous infusion) given in weeks 3-5, and weeks 8-10. Surgery was performed 4-6 weeks later. The primary endpoint was tolerability defined as the percentage of patients who were able to complete the planned treatment course. Survival rates were estimated using the Kaplan-Meier method.

Results: Median age of the 40 patients was 61.5 years. Rectal MRI-stage was T3 in 88%. Overall, 95% completed the regimen. All patients received 50.4 Gy. Relative dose intensity (≥75%) was 92% and 98% for oxaliplatin and 5-FU, respectively. High grade toxicities included neutropenia (25% grade 3; 7.5% grade 4) and diarrhoea (10%). Pathologic CR rate was 20%. Median follow-up was 54 months. The 5-year overall survival, freedom from relapse, locoregional control, and freedom from distant metastasis of the cohort was 82%, 72%, 97% and 72%.

Conclusions: Delivery of intensified neoadjuvant treatment with interdigitating chemotherapy and radiotherapy is feasible with no increase in acute perioperative complications. A larger prospective study is required to further evaluate the potential survival benefit of this design.
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http://dx.doi.org/10.1016/j.radonc.2020.10.012DOI Listing
February 2021

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with oropharyngeal cancer treated with radiotherapy.

Br J Cancer 2021 02 14;124(3):628-633. Epub 2020 Oct 14.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer.

Methods: Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median.

Results: Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis.

Conclusions: Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.
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http://dx.doi.org/10.1038/s41416-020-01106-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851392PMC
February 2021

COVID-19-An Opportunity for Optimizing Surveillance Protocols During and Beyond the Pandemic: HPV-Associated Oropharyngeal Cancer as an Example of Response-Based Local Surveillance.

Int J Radiat Oncol Biol Phys 2020 Oct;108(2):400-403

GenesisCare Radiation Oncology, Division Radiation Oncology, St. Vincent's Hospital, Melbourne, Victoria, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, Victoria, Australia.

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http://dx.doi.org/10.1016/j.ijrobp.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462789PMC
October 2020

Correlation of Circulating Tumor Cell Measurements with 3D Quantitative Tumor Characterization to Predict Clinical Outcomes in Cancer.

Methods Mol Biol 2021 ;2174:135-141

UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.

Head and neck squamous cell carcinoma (HNSCC) is a deadly disease which in many cases is managed with a combination of radiation and chemotherapy. Unfortunately, the ability to monitor treatment response in real time is limited. Thus, truly individualized therapy remains an unrealized goal. We have previously investigated the possibility of combining advanced imaging using magnetic resonance imaging (MRI) combined with the analysis of circulating tumor cells to classify response in HNSCC as part of a prospective trial (PREDICT-HN). An adaption of the methodology from that trial is described herein in hopes of allowing for recapitulation and further development of this exciting methodology.
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http://dx.doi.org/10.1007/978-1-0716-0759-6_9DOI Listing
April 2021

Simultaneously spatial and temporal Higher-Order Total Variations for noise suppression and motion reduction in DCE and IVIM.

Proc SPIE Int Soc Opt Eng 2020 Feb 10;11313. Epub 2020 Mar 10.

University of Texas, MD Anderson Cancer Cente, Houston, TX 77030.

In many applications based on kinetic evaluation analysis and model fitting, quantitative mapping retrieved on data series from modalites such as MRI is completed on a voxel-by-voxel basis, where motion and low signal to noise ratio (SNR) would considerably degenerate the reliability of estimations. The coherence of image series in space and time can be used as prior knowledge to mitigate this occurrence. In this study, spatial and temporal higher-order total variations (HOTVs) are applied on a data series of MRI signal (e.g. dynamic contrast-enhanced (DCE) MRI and intravoxel incoherent motion (IVIM) MRI) to exploit the coherence of signal in space and time to minimize the variabilities caused by motion as well as improving quality of images with low SNR while retaining the physical details of original data properly. Simultaneously applying spatial and temporal HOTVs on images is non-trivial in implementation since it is a non-smooth optimization problem with multiple regularizers. Therefore, we use the proximal gradient method as well as a primal-dual split proximal mechanism to address the problem properly. In addition to increase the reliability of quantitative parametric map estimations, this preprocessing procedure can be included into many existing map estimation algorithms and pipelines effortlessly. We demonstrate our method on the parametric maps estimation for DCE MRI and IVIM MRI.
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http://dx.doi.org/10.1117/12.2549625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401327PMC
February 2020

Conventionally fractionated large volume head and neck re-irradiation using multileaf collimator-based robotic technique: A feasibility study.

Clin Transl Radiat Oncol 2020 Sep 2;24:102-110. Epub 2020 Jul 2.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Purpose: To report on the feasibility and performance of conventionally fractionated multileaf collimator (MLC)-based robotic stereotactic body re-irradiation of the head and neck region using MLC-based Cyberknife (CK) technology.

Methods: Patients treated for recurrent or second primary head and neck cancer (HNC) with curative proton therapy to a target volume > 30 cm between 2011 and 2015 were included. MLC-based CK plans were generated using the CK M6 InCise2 MLC system. Dose statistics from MLC-based CK plans were compared to proton beam therapy (PBT) plans according to the following metrics: target coverage, target homogeneity index, gradient index, Paddick conformity index (CI), prescription isodose volume (PIV), treatment time (tTime) for one fraction as well as doses to organs at risk (OAR). Wilcoxon signed-rank test was used to compare dose metrics.

Results: Eight patients were included; the tumor sites included: salivary glands, pharynx (oropharynx, hypopharynx and retropharynx) and sinonasal cavities. Five of 8 patients were treated with multifield optimisation intensity modulated proton therapy, 3 were treated with passive scattering proton therapy. Median dose was 67 Gy (range 60-70) in 32 fractions (range 30-35). The median high-dose planning target volume (PTV) was 45.4 cm (range 2.4 - 130.2 cm) and the median elective PTV was 91.9 cm (range 61.2 - 269.7 cm). Overall, the mean target coverage (mean 98.3% vs. 96.2% for CK vs. PBT, respectively), maximum dose to PTV (mean 111% vs. 111%, p = 0.2) and mean dose to PTV (mean 104% vs. 104%) were similar across modalities. Highly conformal plans were achieved with both modalities, but mean CI was better with PBT (0.5 vs. 0.6 for CK vs. PBT, p = 0.04). Homogeneity and gradient indexes were similar between the 2 modalities; mean tTime with PBT and CK was 17 vs. 18 min, respectively (p = 0.7). Case-based study revealed that CK and PBT plans allowed for excellent sparing of OAR, with some clinical scenarios associated with better performance of CK while others with better performance of PBT.

Conclusion: Our study has demonstrated the dosimetric performance of large volume head and neck re-irradiation using MLC-based CK in various clinical scenarios. While conformity was generally better achieved with PBT, MLC-based CK allowed for high dose gradient leading to rapid dose drop-off and sparing of OAR. Conventionally fractionated MLC-based CK could be a competitive alternative in large volume head and neck re-irradiation that deserves further investigation in the clinical setting.
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http://dx.doi.org/10.1016/j.ctro.2020.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372092PMC
September 2020

Head and neck cancer patient images for determining auto-segmentation accuracy in T2-weighted magnetic resonance imaging through expert manual segmentations.

Med Phys 2020 Jun;47(5):2317-2322

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA.

Purpose: The use of magnetic resonance imaging (MRI) in radiotherapy treatment planning has rapidly increased due to its ability to evaluate patient's anatomy without the use of ionizing radiation and due to its high soft tissue contrast. For these reasons, MRI has become the modality of choice for longitudinal and adaptive treatment studies. Automatic segmentation could offer many benefits for these studies. In this work, we describe a T2-weighted MRI dataset of head and neck cancer patients that can be used to evaluate the accuracy of head and neck normal tissue auto-segmentation systems through comparisons to available expert manual segmentations.

Acquisition And Validation Methods: T2-weighted MRI images were acquired for 55 head and neck cancer patients. These scans were collected after radiotherapy computed tomography (CT) simulation scans using a thermoplastic mask to replicate patient treatment position. All scans were acquired on a single 1.5 T Siemens MAGNETOM Aera MRI with two large four-channel flex phased-array coils. The scans covered the region encompassing the nasopharynx region cranially and supraclavicular lymph node region caudally, when possible, in the superior-inferior direction. Manual contours were created for the left/right submandibular gland, left/right parotids, left/right lymph node level II, and left/right lymph node level III. These contours underwent quality assurance to ensure adherence to predefined guidelines, and were corrected if edits were necessary.

Data Format And Usage Notes: The T2-weighted images and RTSTRUCT files are available in DICOM format. The regions of interest are named based on AAPM's Task Group 263 nomenclature recommendations (Glnd_Submand_L, Glnd_Submand_R, LN_Neck_II_L, Parotid_L, Parotid_R, LN_Neck_II_R, LN_Neck_III_L, LN_Neck_III_R). This dataset is available on The Cancer Imaging Archive (TCIA) by the National Cancer Institute under the collection "AAPM RT-MAC Grand Challenge 2019" (https://doi.org/10.7937/tcia.2019.bcfjqfqb).

Potential Applications: This dataset provides head and neck patient MRI scans to evaluate auto-segmentation systems on T2-weighted images. Additional anatomies could be provided at a later time to enhance the existing library of contours.
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http://dx.doi.org/10.1002/mp.13942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322982PMC
June 2020

Patient-reported quality of life and toxicity in unilateral and bilateral radiotherapy for early-stage human papillomavirus associated tonsillar carcinoma.

Clin Transl Radiat Oncol 2020 Mar 30;21:85-90. Epub 2020 Jan 30.

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

Purpose: The purpose of this study was to compare self-reported health-related quality of life (QoL) and symptom burden in early stage tonsillar carcinoma patients treated with unilateral (URT) and bilateral radiotherapy (BRT).

Methods And Materials: This is a secondary analysis of a larger study assessing patient reported outcomes in human papillomavirus (HPV) oropharyngeal cancer (OPC) patients. Recruited patients were ≥12 months from completion of radiotherapy. This analysis included only patients with T1-2, N1-2b tonsil cancer and excluded patients with base of tongue involvement or recurrent disease. QoL and patient reported toxicity was measured using the EORTC QLQ-C30 module and the MDASI-HN.

Results: Patients were enrolled from November 2018 to May 2019. Of the 136 patients recruited to the main study, 43 were eligible for this substudy (22 URT, 21 BRT), with a median age and follow up of 58.2 and 3.0 years respectively. The two groups were balanced with respect to patient, tumor and treatment factors with the exception of higher rates of T2 disease (27% v 71%,  = 0.006) and more extensive GTV nodal volumes (11.0 v 25.5cc,  = 0.006) in the BRT group.BRT patients had lower global health status/QoL (84 v 69,  = 0.0005) and social functioning scores (93 vs 78,  = 0.033) on the EORTC QLQ-C30, and higher symptom severity (0.6 vs. 2.0,  = 0.001) and symptom interference scores (0.8 vs. 2.0,  = 0.010) on the MDASI-HN. Four of the six largest differences observed on MDASI-HN items were attributable to radiotherapy technique (dry mouth, mucous, difficulty swallowing/chewing and taste), with corresponding dose differences to the respective organs (contralateral parotid, oral cavity and pharyngeal constrictors). In every instance, severity of symptoms was worse on average for patients treated with BRT.

Conclusions: In the highly conformal radiotherapy era, BRT in early HPV tonsillar cancer survivors has an enduring impact on long-term QoL and toxicity.
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http://dx.doi.org/10.1016/j.ctro.2020.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013120PMC
March 2020

Automatic registration of 2D MR cine images for swallowing motion estimation.

PLoS One 2020 11;15(2):e0228652. Epub 2020 Feb 11.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.

Purpose: To automate the estimation of swallowing motion from 2D MR cine images using deformable registration for future applications of personalized margin reduction in head and neck radiotherapy and outcome assessment of radiation-associated dysphagia.

Methods: Twenty-one patients with serial 2D FSPGR-MR cine scans of the head and neck conducted through the course of definitive radiotherapy for oropharyngeal cancer. Included patients had at least one cine scan before, during, or after radiotherapy, with a total of 52 cine scans. Contours of 7 swallowing related regions-of-interest (ROIs), including pharyngeal constrictor, epiglottis, base of tongue, geniohyoid, hyoid, soft palate, and larynx, were manually delineated from consecutive frames of the cine scan covering at least one swallowing cycle. We applied a modified thin-plate-spline robust-point-matching algorithm to register the point sets of each ROI automatically over frames. The deformation vector fields from the registration were then used to estimate the motion during swallowing for each ROI. Registration errors were estimated by comparing the deformed contours with the manual contours.

Results: On average 22 frames of each cine scan were contoured. The registration for one cine scan (7 ROIs over 22 frames) on average took roughly 22 minutes. A number of 8018 registrations were successfully batch processed without human interaction after the contours were drawn. The average registration error for all ROIs and all patients was 0.36 mm (range: 0.06 mm- 2.06 mm). Larynx had the average largest motion in superior direction of all structures under consideration (range: 0.0 mm- 58.7 mm). Geniohyoid had the smallest overall motion of all ROIs under consideration and the superior-inferior motion was larger than the anterior-posterior motion for all ROIs.

Conclusion: We developed and validated a deformable registration framework to automate the estimation of swallowing motion from 2D MR cine scans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228652PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012439PMC
April 2020

Lymphopenia during radiotherapy in patients with oropharyngeal cancer.

Radiother Oncol 2020 04 10;145:95-100. Epub 2020 Jan 10.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address:

Purpose/objective: Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors such as esophageal, lung, cervical and pancreatic cancers. We aim to determine the effect of treatment-related lymphopenia during radiotherapy on outcomes of patients with oropharyngeal cancer.

Materials/methods: A retrospective analysis of all patients who completed definitive radiotherapy for oropharyngeal cancer at The University of Texas MD Anderson Cancer Center and had blood counts taken during radiotherapy from 2002 to 2013 were included. Patient, tumor and treatment characteristics, clinical outcomes and lymphocyte counts during radiotherapy were recorded. Lymphopenia was graded according to the CTCAE v4.0. Survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests.

Results: 850 patients were evaluated. The median age was 57 years. The majority of the cohort had p16/HPV-positive disease (71%), 8% had HPV-negative disease and 21% were unknown. The median radiation total dose was 70 Gy. 45% of patients had induction chemotherapy, and 87% had concurrent chemotherapy. 703 (83%) patients developed ≥grade 3 (G3) lymphopenia and 209 (25%) had grade 4 (G4) lymphopenia during radiotherapy. The median follow-up was 59 months; the 5-year overall survival rate was 81%. There were no significant differences in overall survival rates nor in disease control rates, in those who developed G3/G4 lymphopenia compared with those who did not. No significant effect of lymphopenia on survival was observed when analyzed according to p16/HPV status.

Conclusion: In this large cohort of patients with oropharyngeal cancer, the development of lymphopenia during radiotherapy did not impact outcomes.
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http://dx.doi.org/10.1016/j.radonc.2019.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502182PMC
April 2020

Australasian Gastrointestinal Trials Group (AGITG) and Trans-Tasman Radiation Oncology Group (TROG) Guidelines for Pancreatic Stereotactic Body Radiation Therapy (SBRT).

Pract Radiat Oncol 2020 May - Jun;10(3):e136-e146. Epub 2019 Nov 21.

Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia.

Purpose: Nonrandomized data exploring pancreas stereotactic body radiation therapy (SBRT) has demonstrated excellent local control rates and low toxicity. Before commencing a randomized trial investigating pancreas SBRT, standardization of prescription dose, dose constraints, simulation technique, and clinical target volume delineation are required.

Methods And Materials: Specialists in radiation oncology, medical oncology, hepatobiliary surgery, and gastroenterology attended 2 consecutive Australasian Gastrointestinal Trials Group workshops in 2017 and 2018. Sample cases were discussed during workshop contact with specifically invited international speakers highly experienced in pancreas SBRT. Furthermore, sample cases were contoured and planned between workshop contact to finalize dose constraints and clinical target volume delineation.

Results: Over 2 separate workshops, consensus was reached on dose and simulation technique. The working group recommended a dose prescription of 40 Gy in 5 fractions. Treatment delivery during end-expiratory breath hold with triple-phase contrast enhanced computed tomography was recommended. In addition, dose constraints, stepwise contouring guidelines, and an anatomic atlas for pancreatic SBRT were developed.

Conclusions: Pancreas SBRT is emerging as a promising treatment modality requiring prospective evaluation in randomized studies. This work attempts to standardize dose, simulation technique, and volume delineation to support the delivery of high quality SBRT in a multicenter study.
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http://dx.doi.org/10.1016/j.prro.2019.07.018DOI Listing
December 2020

Surveillance imaging for patients with head and neck cancer treated with definitive radiotherapy: A partially observed Markov decision process model.

Cancer 2020 02 14;126(4):749-756. Epub 2019 Nov 14.

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

Background: A possible surveillance model for patients with head and neck cancer (HNC) who received definitive radiotherapy was created using a partially observed Markov decision process. The goal of this model is to guide surveillance imaging policies after definitive radiotherapy.

Methods: The partially observed Markov decision process model was formulated to determine the optimal times to scan patients. Transition probabilities were computed using a data set of 1508 patients with HNC who received definitive radiotherapy between the years 2000 and 2010. Kernel density estimation was used to smooth the sample distributions. The reward function was derived using cost estimates from the literature. Additional model parameters were estimated using either data from the literature or clinical expertise.

Results: When considering all forms of relapse, the model showed that the optimal time between scans was longer than the time intervals used in the institutional guidelines. The optimal policy dictates that there should be less time between surveillance scans immediately after treatment compared with years after treatment. Comparable results also held when only locoregional relapses were considered as relapse events in the model. Simulation results for the inclusive relapse cases showed that <15% of patients experienced a relapse over a simulated 36-month surveillance program.

Conclusions: This model suggests that less frequent surveillance scan policies can maintain adequate information on relapse status for patients with HNC treated with radiotherapy. This model could potentially translate into a more cost-effective surveillance program for this group of patients.
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http://dx.doi.org/10.1002/cncr.32597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439665PMC
February 2020

Setup Management for Stereotactic Body Radiation Therapy of Patients With Pancreatic Cancer Treated via the Breath-Hold Technique.

Pract Radiat Oncol 2020 Jul - Aug;10(4):e280-e289. Epub 2019 Oct 25.

Johns Hopkins University School of Medicine, Baltimore, Maryland; MD Anderson Cancer Center, Houston, Texas.

Purpose: Active Breathing Coordinator (Elekta AB, Crawley, UK) is a motion management strategy for radiation treatment. During setup, aligning the patient to the bony spine alone does not necessarily lead to an accurate alignment to soft tissue targets, and further adjustment is necessary. Determining a safe range of values for such adjustments is an important quality assurance measure and was the purpose of this study, with focus on stereotactic body radiation therapy in patients with pancreatic cancer.

Methods And Materials: The retrospective study included 19 previously treated patients. For each fraction, a free-breathing cone beam computed tomography scan was registered to a reference breath-hold computed tomography for alignment to the spine. Two perpendicular breath-hold kV projection images were then acquired and compared with corresponding reference digitally reconstructed radiographs for additional alignment with a surrogate fiducial marker. By comparing the breath-hold kV projection images from subsequent treatment fractions with those from the first fraction, we derived the 3-dimensional variability of the fiducial position with respect to the reference image.

Results: We observed intrafraction setup error to be within 2.0 mm. For interfraction, we observed average reproducibility of 1.7 ± 0.8 mm, 2.0 ± 1.4 mm, and 3.2 ± 2.5 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The average excursion values from free breathing spine to breath-hold fiducial alignment were 1.5 ± 1.4 mm, 2.0 ± 1.9 mm, and 3.0 ± 2.0 mm in the LR, AP and SI directions, respectively. The observed ranges of average excursions among all patients were 0.2 to 5.1 mm, 0.1 to 5. 9 mm, and 0.6 to 7.8 mm in the LR, AP, and SI directions, respectively.

Conclusions: This study demonstrates that intrafraction targeting errors can be within 2 mm, and interfraction shifts from free-breathing spine to Active Breathing Coordinator breath-hold target can be as high as 8 mm. Values that deviate significantly would need further investigation to rule out factors such as local progression, bowel gas, or fiducial shift before treatment.
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http://dx.doi.org/10.1016/j.prro.2019.10.012DOI Listing
March 2021

Risk of second primary malignancies in head and neck cancer patients treated with definitive radiotherapy.

NPJ Precis Oncol 2019 27;3:22. Epub 2019 Sep 27.

1Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA.

Second primary malignancy (SPM) may occur after index head and neck cancer (HNC) treatment. This study evaluated the prevalence and outcome of SPM in patients with HNC treated with definitive radiotherapy. Eligible patients include those with index mucosal HNC treated with definitive radiotherapy between 2000 and 2010. SPM was defined as an invasive cancer at a noncontiguous site diagnosed at least 6 months after completion of radiotherapy. Clinical data were collected, and the Kaplan-Meier method was used to estimate overall survival. In total, 1512 patients were studied. The majority of patients had index oropharyngeal cancer (86%). In all, 130 (9%) patients developed a SPM. The risk of SPM increased exponentially with time with 5-, 10-, and 15-year rates of 4, 10, and 25%. Half of SPMs were within the head and neck or thoracic regions. SPM rates were significantly higher ( < 0.0001) in current smokers and former smokers than never smokers with 5-, 10-, and 15-year risk being: never smoker (2, 4, 14%), former smokers with <10-pack year (5, 10, 23%), former smokers with ≥10-pack year (5, 14, 35%), and current smokers (6, 18, 32%). In total, 102 (78%) had subsequent curative-intent therapy. The 5-year overall survival from SPM was 44%. The majority of SPMs were in those with significant smoking history reflecting the same risk factor as for the index mucosal HNC. Nearly one in two patients with SPMs were salvaged underscoring the importance of regular surveillance for SPMs.
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http://dx.doi.org/10.1038/s41698-019-0097-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764977PMC
September 2019

Prospective quantitative quality assurance and deformation estimation of MRI-CT image registration in simulation of head and neck radiotherapy patients.

Clin Transl Radiat Oncol 2019 Sep 24;18:120-127. Epub 2019 Apr 24.

Department of Radiation Oncology, the University of Texas MD Anderson Cancer Center, The MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Background: MRI-guided radiotherapy planning (MRIgRT) may be superior to CT-guided planning in some instances owing to its improved soft tissue contrast. However, MR images do not communicate tissue electron density information necessary for dose calculation and therefore must either be co-registered to CT or algorithmically converted to synthetic CT. No robust quality assessment of commercially available MR-CT registration algorithms is yet available; thus we sought to quantify MR-CT registration formally.

Methods: Head and neck non-contrast CT and T2 MRI scans acquired with standard treatment immobilization techniques were prospectively acquired from 15 patients. Per scan, 35 anatomic regions of interest (ROIs) were manually segmented. MRIs were registered to CT rigidly (RIR) and by three commercially available deformable registration algorithms (DIR). Dice similarity coefficient (DSC), Hausdorff distance mean (HD mean) and Hausdorff distance max (HD max) metrics were calculated to assess concordance between MRI and CT segmentations. Each DIR algorithm was compared to DIR using the nonparametric Steel test with control for individual ROIs (n = 105 tests) and for all ROIs in aggregate (n = 3 tests). The influence of tissue type on registration fidelity was assessed using nonparametric Wilcoxon pairwise tests between ROIs grouped by tissue type (n = 12 tests). Bonferroni corrections were applied for multiple comparisons.

Results: No DIR algorithm improved the segmentation quality over RIR for any ROI nor all ROIs in aggregate (all p values >0.05). Muscle and gland ROIs were significantly more concordant than vessel and bone, but DIR remained non-different from RIR.

Conclusions: For MR-CT co-registration, our results question the utility and applicability of commercially available DIR over RIR alone. The poor overall performance also questions the feasibility of translating tissue electron density information to MRI by CT registration, rather than addressing this need with synthetic CT generation or bulk-density assignment.
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http://dx.doi.org/10.1016/j.ctro.2019.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630195PMC
September 2019
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