Real-world data on patterns and outcomes of radiation therapy for brain metastases in a population-based cohort of lung cancer patients in Victoria.

INTRODUCTION: We evaluated real-world data on the patterns and outcomes of radiotherapy (RT) for brain metastases (BM) in a population-based cohort of patients with lung cancer (LC) in Victoria. METHODS: The Victorian Radiotherapy Minimum Data set (VRMDS) and the Victorian Cancer Registry (VCR) were linked to identify patients with LC who underwent RT for BM between 2013 and 2016. We determined: (i) proportion of patients treated with stereotactic radiosurgery (SRS); (ii) overall survival (OS); and (iii) 30-day mortality (30M) following RT for BM. RESULTS: Of the 1001 patients included in the study, 193 (19%) had SRS. There was no significant increase in SRS use over time - from 18% in 2013 to 21% in 2016 (P-trend = 0.8). In multivariate analyses, increased age (P = 0.03) and treatment in regional centres (P < 0.001) were independently associated with lower likelihood of SRS treatment. The median OS following RT for BM was 3.6 months. Patients who had SRS had better OS than those who did not have SRS (median OS 8.9 months vs. 3 months, P < 0.01). SRS use, age, sex and year of treatment were independently associated with OS in multivariate analyses. A total of 184 (18%) patients died within 30 days of RT for BM, and the proportion was higher in older (P = 0.001) and male patients (P = 0.004). CONCLUSION: One-in-five LC patients who received RT for BM had SRS. The improved OS with SRS is likely confounded by patient selection. It is important to reduce 30M by better selecting patients who may not benefit from RT for BM.

A review of diffusion-weighted magnetic resonance imaging in head and neck cancer patients for treatment evaluation and prediction of radiation-induced xerostomia.

The incidence of head and neck cancers (HNC) is rising worldwide especially with HPV-related oropharynx squamous cell carcinoma. The standard of care for the majority of patients with locally advanced pharyngeal disease is curative-intent radiotherapy (RT) with or without concurrent chemotherapy. RT-related toxicities remain a concern due to the close proximity of critical structures to the tumour, with xerostomia inflicting the most quality-of-life burden. Thus, there is a paradigm shift towards research exploring the use of imaging biomarkers in predicting treatment outcomes. Diffusion-weighted imaging (DWI) is a functional MRI feature of interest, as it quantifies cellular changes through computation of apparent diffusion coefficient (ADC) values. DWI has been used in differentiating HNC lesions from benign tissues, and ADC analyses can be done to evaluate tumour responses to RT. It is also useful in healthy tissues to identify the heterogeneity and physiological changes of salivary glands to better understand the inter-individual differences in xerostomia severity. Additionally, DWI is utilised in irradiated salivary glands to produce ADC changes that correlate to clinical xerostomia. The implementation of DWI into multi-modal imaging can help form prognostic models that identify patients at risk of severe xerostomia, and thus guide timely interventions to mitigate these toxicities.

A clinical study comparing polymer and gold fiducials for prostate cancer radiotherapy.

Introduction: Image guidance with gold fiducials improves outcomes of prostate radiotherapy. However, gold produces artefact on CT imaging, interfering with contouring and verification. The purpose of this study was to compare polymer to standard gold fiducials using radiotherapy imaging modalities to assess the visibility and artefact. Methods: Twenty eight patients with locally advanced prostate cancer were enrolled, half had three polymer fiducials implanted into the prostate and half underwent insertion of gold fiducials. Patients were imaged with CT, T2 weighted MRI, cone-beam CT (CBCT) and planar KV images. Fiducials were scored for visibility and assessed for CT artefact in surrounding prostate tissue. The artefact was quantified from Hounsfield number histograms and separated into percentile ranges and proportion of voxels in HU normal tissue range of a 2cm sphere surrounding the fiducial. Results: Gold and polymer fiducials were sufficiently visible for CT and CBCT verification. The gold fiducials could be visualized well on KV planar imaging; however, the polymer markers were obscured by pelvic bones. Neither polymer nor gold fiducials could be visualized on MRI. The polymer fiducial produced less artefact than gold on CT, having less voxel spread for the HU percentile ranges and a greater proportion of voxels in the normal tissue range. Conclusions: Polymer fiducials are a more suitable fiducial than gold for CT/CBCT in prostate cancer radiotherapy, demonstrating minimal artefact and good visibility on CT. However, they were not well seen on MRI or KV imaging and thus not suitable for co-registration or planar KV verification.

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

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.

Exploratory models comparing ethiodized oil-glue and gold fiducials for bladder radiotherapy image-guidance.

BACKGROUND AND PURPOSE: Image-guidance with fiducials has been shown to improve pelvic radiotherapy outcome. However, bladder fiducials using ethiodized oil (EO) alone can disperse widely, and gold causes Computed Tomography scan (CT) metal artifacts. The study's purpose was to investigate the ability to deliver EO-tissue glue fiducials and compare them to gold for bladder radiotherapy image guidance. MATERIALS AND METHODS: A fluid-filled porcine bladder model was used to assess the ability to cystoscopically inject visible EO glue fiducials into the submucosa. We then transferred the bladders into a porcine pelvis for imaging and compared them to gold fiducials using CT, Cone Beam CT (CBCT), and kilovoltage (KV) planar views. A tissue-equivalent phantom was utilized to analyze the CT number Hounsfield Unit (HU) characteristics and artifacts of the glue and gold fiducials. Percentile ranges and normal tissue voxel percentages of the subsequent CT number voxel histogram from a 2 cm sphere surrounding the fiducial was used to characterize the artifact. RESULTS: We successfully delivered all EO glue fiducials into the porcine bladders as discrete fiducials. They were well seen on CT, CBCT, and KV imaging. The glue fiducials had lower CT number values, but less CT number spread of the voxel percentile ranges consistent with the diminished contrast and less artifact than gold. The glue fiducial types had similar CT number characteristics. CONCLUSION: This study has shown that EO glue fiducials can be delivered with online visualization qualities comparable to gold fiducials without metal-related artifacts.

A phantom study to contrast and compare polymer and gold fiducial markers in radiotherapy simulation imaging.

To assess visibility and artifact characteristics of polymer fiducials compared to standard gold fiducials for radiotherapy CT and MRI simulation. Three gold and three polymer fiducials were inserted into a CT and MRI tissue-equivalent phantom that approximated the prostate cancer radiotherapy configuration. The phantom and fiducials were imaged on CT and MRI. Images were assessed in terms of fiducial visibility and artifact. ImageJ was employed to quantify the pixel gray-scale of each fiducial and artifact. Fiducial gray-scale histograms and profiles were generated for analysis. Objective measurements of the contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and artifact index (AI) were calculated. The CT images showed that the gold fiducials are visually brighter, with greater contrast than the polymer. The higher peak values illustrate this in the line profiles. However, they produce bright radiating and dark shadowing artifacts. This is depicted by the greater width of line profiles and the disruption of phantom area profiles. Quantitatively this results in greater percentile ranges of the histograms. Furthermore, for CT, gold had a higher CNR than polymer, relative to the phantom. However, the gold CNR and SNR were degraded by the greater artifact and thus AI. Both fiducials were visible on MRI and had similar histograms and profiles that were also reflected in comparable CNR, SNR and AI. Polymer fiducials were well visualized in a phantom on CT and MR and produce less artifact than the gold fiducials. Polymer markers could enhance the quality and accuracy of radiotherapy co-registration and planning but require clinical confirmation.

Proximal seminal vesicle displacement and margins for prostate cancer radiotherapy.

INTRODUCTION: Guidelines recommend that the proximal seminal vesicles (PrSV) should be included in the clinical target volume for locally advanced prostate cancer patients undergoing radiotherapy. Verification and margins for the prostate may not necessarily account for PrSV displacement. The purpose was to determine the inter-fraction displacement of the PrSV relative to the prostate during radiotherapy. METHODS: Fiducials were inserted into the prostate, and right and left PrSV (RSV and LSV) in 30 prostate cancer patients. Correctional shifts for the prostate, right and left PrSV and pelvic bones were determined from each patient's 39 daily orthogonal portal images relative to reference digitally reconstructed radiographs. RESULTS: There was a significant displacement of the RSV relative to the prostate in all directions: on average 0.38 mm (95% confidence interval (CI) 0.26 to 0.50) to the left, 0.80-0.81 mm (CI 0.68 to 0.93) superiorly and 1.51 mm (CI 1.36 to 1.65) posteriorly. The LSV was significantly displaced superiorly to the prostate 1.09-1.13 mm (CI 0.97 to 1.25) and posteriorly 1.81 mm (CI 1.67 to 1.96), but not laterally (mean 0.06, CI -0.06 to 0.18). The calculated PTV margins (left-right, superior-inferior, posterior-anterior) were 4.9, 5.3-5.6 and 4.8 mm for the prostate, 5.2, 7.1-8.0 and 9.7 mm for the RSV, and 7.2, 7.5-7.6 and 8.6 mm for the LSV. CONCLUSION: There is a significant displacement of the PrSV relative to the prostate during radiotherapy. Greater margins are recommended for the PrSV compared to the prostate.

Clinical and dosimetric risk stratification for patients at high-risk of feeding tube use during definitive IMRT for head and neck cancer.

INTRODUCTION: To identify organs to which dose limitation using intensity modulated radiotherapy (IMRT) can potentially modify the incidence and duration of feeding tube use, during and immediately following therapy for head and neck cancer. MATERIALS AND METHODS: One hundred and fourteen patients treated with definitive IMRT (± concurrent chemotherapy) head and neck mucosal cancers were included. Patients received a prophylactic feeding tube and followed up by a dietician for at least eight weeks post-radiotherapy. Salivary and swallowing organs were delineated for each patient. Tumour and dosimetric variables were recorded for all patients and analysed for incidence and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Multivariate analysis showed T-classification ≥3 and level II lymphadenopathy as independent significant predictors of incidence and duration of feeding tube use in oral cavity, pharyngeal and supraglottic primaries. Mean dose deposited in the cervical oesophagus over 36Gy further increased the incidence and duration of feeding tube use. Mean dose deposited in the base of tongue and superior pharyngeal constrictor muscles affected incidence and duration of feeding tube use, respectively. DISCUSSION: In patients treated with definitive IMRT, T-classification and Level II lymphadenopathy, combined with a mean cervical oesophagus dose over 36Gy can a stratify patients into eight distinct risk groups for using feeding tubes for at least 25% of their dietary requirements.

The changing landscape of head and neck cancer radiotherapy patients: is high-risk, prolonged feeding tube use indicative of on-treatment weight loss?

INTRODUCTION: Precision radiotherapy relies heavily on optimal weight management. Our group previously developed a risk stratification model for patients at risk of prolonged feeding tube (FT) intervention. The study objective was to assess on-treatment weight loss according to stratified risk of prolonged FT use. METHODS: One hundred and one (n = 101) definitive head and neck radiotherapy patients were included in this study. Patients were stratified into high risk (HRi: T-classification ≥ 3 with level 2 Nodal disease), high-intermediate risk (HIRi: T-classification ≥ 3 without level 2 Nodes) and low-intermediate risk (LIRi: T-classification < 3 with level 2 Nodes) of prolonged FT use. Demographic variables and on-treatment weight loss were evaluated according to risk status. RESULTS: Oropharyngeal carcinoma (OPC) was present in a larger proportion in the LIRi cohort (HRi: 71%, HIRi: 52%, LIRi: 81%, P = 0.008). LIRi patients were more likely to have human papilloma virus (HPV)-associated disease (88%, P = 0.001). Never/minimal smoking (P = 0.003), good performance status (P < 0.001), healthy BMI (P = 0.050) and no pre-existing dysphagia (P < 0.001) were predominant within the LIRi prognostic group. LIRi patients lost significantly more weight in total (HRi = 4.8% vs. LIRi = 8.2%, P = 0.002; HIRi = 5.2% vs. LIRi = 8.2%, P = 0.006) and when using a FT (HRi = 4.6% vs. LIRi = 8.8%, P < 0.001; HIRi = 5.3% vs. LIRi = 8.8%, P = 0.002). CONCLUSIONS: Patients identified as low-intermediate risk of prolonged, ≥25% FT use report significantly increased weight loss compared with patients at higher risk of FT use. This cohort is typical of the increasing number of patients presenting with HPV-associated OPC. Results of this study suggest we should closely observe such patients throughout treatment, to ensure optimal weight maintenance, facilitating precision radiotherapy.

Contemporary practice patterns of stereotactic radiosurgery for brain metastasis: A review of published Australian literature.

There has been a shift in the management of brain metastasis (BM), with increasing use of stereotactic radiosurgery (SRS) and delaying/avoiding whole-brain radiotherapy (WBRT), given the concern regarding the long-term neurocognitive effect and quality of life impact of WBRT. It is, however, unclear as to the contemporary practice pattern and outcomes of SRS in Australia. We conducted a literature search in PubMed and MEDLINE using a series of keywords: 'stereotactic', 'radiosurgery' and 'brain metastases', limiting to Australian studies, which report on clinical outcomes following SRS. Eight studies - one randomized trial and seven retrospective cohort studies - were identified and included in this review. A total of 856 patients were included, with the most common primary tumour types being melanoma, lung cancer and breast cancer. Approximately half of the patients had solitary BM, while 7% had 10 or more BM lesions. SRS is not routinely given in combination with WBRT. The 6-month intracranial control and 1-year intracranial control following SRS were reported in the range of 67-87% and 48-82%, respectively, whereas the 1-year overall survival and 2-year overall survival were reported in the range of 37-60% and 20-36%, respectively. There are limited data reported on SRS-related toxicities in all included studies. Overall, despite increasing use of SRS for BM, there is a low number of published Australian series in the literature. There is a potential role for establishing an Australian clinical quality registry or collaborative consortium for SRS in BM, to allow for systematic prospective data collection, and benchmarking of quality and outcomes of SRS.

Fiducial markers: can the urologist do better?

INTRODUCTION: Radiotherapy to the bladder has a risk of toxicity to pelvic structures, which can be reduced by using fiducial markers for targeting. Injectable contrast offers an alternative marker to gold seeds, which may fall out or exacerbate scarring. Combining contrast agents with tissue glue can minimize dispersion through tissue, enhancing its utility. We evaluated combinations of contrast agents and tissue glue using porcine bladder, for feasibility and utility as fiducial markers to aid image-guided radiotherapy. METHODS: Different contrast agents (Lipiodol ultra or Urografin) were combined with different tissue glues (Histoacryl, Tisseal or Glubran2). The mixtures were endoscopically injected into porcine bladder submucosa to identify the area of interest with multiple fiducial markers. The porcine bladders were imaged within a phantom porcine pelvis using standard radiation therapy imaging modalities. The feasibility as an injectable fiducial marker and visibility of each fiducial marker on imaging were scored as binary outcomes by two proceduralists and two radiation therapists, respectively. RESULTS: Lipiodol-glue combinations were successfully administered as multiple fiducials that were evident on CT and CBCT. Lipiodol with Histoacryl or Glubran2 was visible on kV imaging. The Lipiodol Glubran2 combination was deemed subjectively easiest to use at delivery, and a better fiducial on KV imaging. CONCLUSION: This study demonstrates the feasibility of mixing contrast medium Lipiodol with Histoacryl or Glubran2 tissue glue, which, injected endoscopically, provides discrete and visible fiducial markers to aid image-guided radiotherapy. Although promising, further study is required to assess the durability of these markers through a course of radiotherapy.

18F-FDG Metabolic Tumor Volume: Association with Short- and Long-Term Feeding Tube Use in Head and Neck IMRT.

The purpose of this study was to investigate whether the metabolic tumor volume (MTV) of head and neck primary tumors may be a significant prognostic factor for feeding tube (FT) use and FT dependence. Seventy-nine patients with evaluable primary tumors, pre-therapy FDG-PET scans, treated with definitive intensity-modulated radiotherapy (IMRT) (± concurrent chemotherapy) for head and neck mucosal cancers were included. MTV was quantified and recorded for the primary lesion using a minimum standardized uptake value (SUV) threshold of 2.0. Patients were recommended prophylactic FT and followed up by a dietician for at least eight weeks of post-radiotherapy. Associations between MTV, dose to swallowing organs at risk, FT use, and FT dependence were analyzed. MTV was positively correlated with gross tumor volume (GTV) (r = 0.7357; p < 0.0001). MTVs larger than 17 cc were associated with higher rates of FT use (87.8% vs. 69.5%, p = 0.0067) and FT dependence at six weeks (76.7% vs. 41.7%, p = 0.0024) and six months (25.0% vs. 8.7%, p = 0.0088). Increasing MTV was associated with increasing mean dose to the oral cavity (p = < 0.0001), tongue base (p = 0.0009), and superior (SPCM) (p = 0.0001) and middle pharyngeal constrictor muscles (MPCM) (p = 0.0005). Increasing MTV was associated with increasing maximum dose to oral cavity (p = 0.0028), tongue base (p = 0.0056), SPCM (p = 0.0037), and MPCM (p = 0.0085). Pre-treatment MTV is a reproducible parameter that can be generated at or prior to a pre-treatment Multidisciplinary Tumor Board and may expedite decisions regarding placement of prophylactic FTs. Prospective evaluation in larger series is required to determine whether MTV is a more useful prognostic variable for FT use than clinical T-classification.

Clinical correlates of severe thrombocytopenia from temozolomide in glioblastoma patients.

BACKGROUND/AIM: This study was conducted retrospectively to evaluate rates of thrombocytopenia and their clinical impact during chemo-radiotherapy for glioblastomas and to elucidate associated clinical factors. METHODS: A total of 64 patients who received temozolomide chemotherapy at our institution was included; 35 patients received full-dose chemo-radiotherapy as per the STUPP protocol (Group A), and 9 patients received abbreviated radiotherapy with concurrent chemotherapy (Group B). Twenty patients received temozolomide alone with an intended 12 cycles of therapy for first relapse at least 6 months after completion of adjuvant chemotherapy (Group C). RESULTS: In Group A, 27 of 35 (77%) patients completed the chemo-radiotherapy phase; 14% had grade 3-4 thrombocytopenia leading to discontinuation. Of 27 patients, 16 (59%) completed adjuvant chemotherapy. There were no grade 3-4 thrombocytopenias, but 4% discontinued due to grade 2 thrombocytopenias. In Group B, four of nine (45%) patients completed the chemo-radiotherapy phase; 11% had grade 3-4 thrombocytopenias and discontinued treatment. Three of four (75%) patients completed adjuvant chemotherapy. Of these, 75% had grade 3-4 thrombocytopenias, but none discontinued. Finally, in Group C, 8 of 20 (40%) patients completed, with 10% discontinuing due to thrombocytopenias and the rest due to disease progression. In exploratory analyses, being female increased the risk of myelosuppresion, and there was a trend noticed in patients having a higher body surface area. CONCLUSION: Our toxicity data were within range of the literature. We identified the group of patients that have increased thrombocytopenia risk. Larger pooled retrospective series and prospective studies are required.

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

BACKGROUND: The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. METHODS: One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. CONCLUSION: In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use.

Prostate cancer post-prostatectomy radiotherapy: CT vs MRI for vesico-urethral anastomosis target delineation.

BACKGROUND: Vesico-urethral anastomosis (VUA) is critical to the clinical target volume (CTV) in post-prostatectomy radiotherapy (PPRT), as it is the commonest site of recurrence. Typically, this is performed on a CT alone but guidelines recommend MRI. OBJECTIVE: To evaluate the VUA spatial differences between CT (ctVUA) and MRI (mrVUA) and analyse its impact on the CT defined CTV (ctCTV) as recommended by published guidelines. MATERIALS AND METHODS: We identified 34 patients with a co-registered simulation CT and T2 weighted MRI. The VUA was located on CT and MRI whilst blinded to the opposing scan. The differences were analysed using Wilcoxon's Signed Rank Test. The mrVUA coverage was investigated using three ctCTV margins of 5mm, 8mm and 12mm. RESULTS: Median age was 63years with 59% having pT3a disease and median Gleason score of 7. The mrVUA was coincident with the ctVUA in 12% and inferior in 88%. Median difference was 5mm (0-10mm) (P<0.0001). Only a ctCTV margin of 12mm would have encompassed all mrVUAs. A ctCTV margin of 8mm and 5mm resulted in 12% and 38% cases where the VUA was excluded from the ctCTV. CONCLUSIONS: MRI is important for the accurate delineation of VUA for PPRT.

High-dose palliative radiotherapy for malignant pleural mesothelioma.

INTRODUCTION: High-dose radiotherapy to the hemithorax for patients with malignant pleural mesothelioma is a controversial treatment. Between 2003 and 2013 our institution had a policy of giving hemithoracic radiotherapy to at least 45 Gy. This retrospective study reports survival, progression and toxicity associated with this policy. METHODS: Seventy-one patients with pleural mesothelioma were irradiated with doses of 45-60 Gy. Conformal radiotherapy (3D-CRT) to the lower hemithorax was used for 17 and intensity-modulated radiotherapy (IMRT) to the whole hemithorax for 54 patients. All patients have been followed up for at least 2 years from commencement of radiotherapy. RESULTS: Sixty-four patients (90%) completed planned radiotherapy and seven stopped early, usually due to progressive disease. Median overall survival was 9.5 months (95% CI: 7.7-12.4) and median progression-free survival was 4.9 months (95% CI: 4.4-5.8). Eighty-seven per cent of patients progressed or died within 2 years: 25% in-field, 49% outside the RT field and 13% died without progression. Severe toxicity (grade 3-5) was observed in 53% of 3D-CRT and 78% of IMRT patients, most commonly pulmonary fibrosis 27%, radiation dermatitis 18%, dyspnoea 11%, GGT increased 11%, pneumonitis 10%, pleuritic pain 8% and fatigue 8%. There were two, possibly three, treatment-related deaths. CONCLUSION: High-dose radiotherapy to the hemithorax caused significant toxicity to most patients with no improvement in survival. Lower doses of radiotherapy to limited volumes may be useful for palliative purposes.

RADBIOMOD: A simple program for utilising biological modelling in radiotherapy plan evaluation.

PURPOSE: Radiotherapy plan evaluation is currently performed by assessing physical parameters, which has many limitations. Biological modelling can potentially allow plan evaluation that is more reflective of clinical outcomes, however further research is required into this field before it can be used clinically. METHODS: A simple program, RADBIOMOD, has been developed using Visual Basic for Applications (VBA) for Microsoft Excel that incorporates multiple different biological models for radiotherapy plan evaluation, including modified Poisson tumour control probability (TCP), modified Zaider-Minerbo TCP, Lyman-Kutcher-Burman normal tissue complication probability (NTCP), equivalent uniform dose (EUD), EUD-based TCP, EUD-based NTCP, and uncomplicated tumour control probability (UTCP). RADBIOMOD was compared to existing biological modelling calculators for 15 sample cases. RESULTS: Comparing RADBIOMOD to the existing biological modelling calculators, all models tested had mean absolute errors and root mean square errors less than 1%. CONCLUSIONS: RADBIOMOD produces results that are non-significantly different from existing biological modelling calculators for the models tested. It is hoped that this freely available, user-friendly program will aid future research into biological modelling.

Comparison of [(11)C]choline Positron Emission Tomography With T2- and Diffusion-Weighted Magnetic Resonance Imaging for Delineating Malignant Intraprostatic Lesions.

PURPOSE: The purpose of this study was to compare the accuracy of [(11)C]choline positron emission tomography (CHOL-PET) with that of the combination of T2-weighted and diffusion-weighted (T2W/DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET. METHODS AND MATERIALS: This study included 21 patients who underwent CHOL-PET and T2W/DW MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), and sensitivity and specificity values. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models. RESULTS: The best automatic contouring method, 60% of the maximum SUV (SUV60) , had similar correlations (DSC: 0.59) with the manual PET contours (DSC: 0.52, P=.127) and significantly better correlations than the manual MRI contours (DSC: 0.37, P<.001). The sensitivity and specificity values were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET. CONCLUSIONS: CHOL-PET is superior to the combination of T2W/DW MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies but may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict how well CHOL-PET delineates IPLs.

Dose-volume response in acute dysphagia toxicity: Validating QUANTEC recommendations into clinical practice for head and neck radiotherapy.

PURPOSE: To determine the validity of QUANTEC recommendations in predicting acute dysphagia using intensity-modulated head and neck radiotherapy. MATERIAL AND METHODS: Seventy-six consecutive patients with locally advanced squamous cell carcinoma (SCC) of the head and neck +/- systemic therapy were analyzed. Multiple dose parameters for the larynx (V50Gy, Dmean and Dmax) were recorded. Acute dysphagia toxicity was prospectively scored in all treatment weeks (week 1-6 or 1-7) using CTCAEv3 by three blinded investigators. QUANTEC larynx recommendations (V50Gy < 27%, Dmean < 44 Gy, Dmean < 40 Gy, Dmax < 66 Gy) were used to group the cohort (i.e. V50Gy < 27% vs. V50Gy > 27%). The proportion of patients with Grade 3 dysphagia was compared within each group. RESULTS: There was a significant reduction in the incidence of grade 3 toxicity in the V50Gy < or > 27% group at week 5 (14.3% vs. 45.2%, p = 0.01) and 6 (25.9% vs. 65.9%, p < 0.01). A significant reduction at week 5 (14.7% vs. 50.0, p = 0.02) and 6 (32.4% vs. 67.6%, p = 0.01) was seen in Dmean < 44 Gy when compared to Dmean > 44 Gy. Dmean < 40 Gy also delivered a significant reduction at week 5 (5.6% vs. 42.3%, p < 0.01) and week 6 (23.5% vs. 59.3%, p = 0.01). A significant toxicity reduction at treatment week 6 (28.0% vs. 63.0%, p = 0 < 01) was seen from Dmax < 66 Gy to Dmax > 66 Gy. V50Gy > 27% (p < 0.01), Dmean > 40 Gy (p = 0.01) and Dmax > 66 Gy (p < 0.01) were also predictors of Grade 3 dysphagia when analyzed with multiple clinical risk factors. CONCLUSIONS: QUANTEC late toxicity recommendations for dose to larynx during IMRT are a useful predictor for acute dysphagia toxicity in this patient cohort. Furthermore, this included chemoradiotherapy regimes and post-operative radiotherapy patients, allowing for prophylactic implementation of supportive care measures.