Impact of Medical Operability and Total Metastatic Ablation on Outcomes After SABR for Oligometastases.

PURPOSE: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites. METHODS AND MATERIALS: Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database. We retrospectively compared overall survival (OS) and progression-free survival (PFS) for medically operable or inoperable patients and patients undergoing total or subtotal metastatic ablation. Secondary endpoints were patterns of failure, high-grade treatment toxic effects (Common Terminology Criteria for Adverse Events version 4.0), and freedom from systemic therapy. The threshold dose per fraction considered ablative was 8 Gy. RESULTS: A total of 401 patients with 530 treated oligometastases were included, with a median follow-up of 3 years. Three hundred and two and 99 patients had metachronous and synchronous presentations of oligometastatic disease, respectively. Common histologies included prostate (24%), lung (18%), gastrointestinal (19%), and breast (11%). More than 90% of doses delivered were Biologically Effective Dose [BED10]≥60 Gy. Cumulative incidence at 5 years of local-only failure was 6%, local and distant 2%, and distant-only 58%. The 3- and 5-year OS [95% confidence intervals {CIs}] were 68% [62-73] and 54% [47-61], and PFS was 20% [15-25] and 14% [10-20]. The 3- and 5-year freedom from systemic therapy [95% CIs] were 40% [34-46] and 31% [24-37], respectively. Seventy-six patients were inoperable and 325 were operable. Operability status was not prognostic for OS (adjusted hazard ratio [HR], 1.0; 95% CI, 0.6-1.7; P = .9) or for PFS (adjusted HR, 1.1; 95% CI, 0.8-1.6; P = .5). Total metastatic ablation was prognostic for OS (adjusted HR, 0.8; 95% CI, 0.4-0.9; P = .032) and for PFS (adjusted HR, 0.6; 95% CI, 0.4-0.8; P = .003). CONCLUSIONS: Medical operability was not prognostic in patients with oligometastatic disease treated with SABR. Total metastatic ablation was associated with superior OS and PFS compared with subtotal metastatic ablation. Our data support ablation of all sites of oligometastases wherever feasible.

Controversies in the role of radiotherapy in pleural mesothelioma.

Malignant pleural mesothelioma is an uncommon thoracic cancer with a relatively poor outcome, which has only seen modest improvements when compared to non-small cell lung cancer. The mainstays of treatment have been surgery and systemic therapy, with radiation reserved for palliation or as an adjunct. However, there is re-emergent interest in the use of radiotherapy in the treatment of mesothelioma, given recent technical advances in radiotherapy delivery which permit increased treatment accuracy. This overview article reviews the radiobiology of the mesothelioma and whether or not mesothelioma is an inherently radioresistant cancer and the potential impact that hypofractionation may have on different histological subtypes in mesothelioma. This overview also considers the role of radiation in palliation, as adjunct to surgical resection and as adjunct to pleural tract procedures. In particular we review the growing evidence that pleural tract or port site adjuvant radiotherapy provides no clinical benefit. This overview will also consider potential emerging therapeutic strategies such as pre-operative short course hypofractionated radiotherapy. The role of novel radiotherapy techniques such as stereotactic ablative radiotherapy, image guided radiotherapy, proton therapy and the potential role of radiotherapy as an immune stimulating agent in combination of immunotherapy, will also be discussed. Finally, given the many unanswered questions, this review discusses some of the emerging and ongoing clinical trials of radiotherapy in the treatment of mesothelioma.

Monitoring DNA Damage and Repair in Peripheral Blood Mononuclear Cells of Lung Cancer Radiotherapy Patients.

Thoracic radiotherapy (RT) is required for the curative management of inoperable lung cancer, however, treatment delivery is limited by normal tissue toxicity. Prior studies suggest that using radiation-induced DNA damage response (DDR) in peripheral blood mononuclear cells (PBMC) has potential to predict RT-associated toxicities. We collected PBMC from 38 patients enrolled on a prospective clinical trial who received definitive fractionated RT for non-small cell lung cancer. DDR was measured by automated counting of nuclear γ-H2AX foci in immunofluorescence images. Analysis of samples collected before, during and after RT demonstrated the induction of DNA damage in PBMC collected shortly after RT commenced, however, this damage repaired later. Radiation dose to the tumour and lung contributed to the in vivo induction of γ-H2AX foci. Aliquots of PBMC collected before treatment were also irradiated ex vivo, and γ-H2AX kinetics were analyzed. A trend for increasing of fraction of irreparable DNA damage in patients with higher toxicity grades was revealed. Slow DNA repair in three patients was associated with a combined dysphagia/cough toxicity and was confirmed by elevated in vivo RT-generated irreparable DNA damage. These results warrant inclusion of an assessment of DDR in PBMC in a panel of predictive biomarkers that would identify patients at a higher risk of toxicity.

Evaluation of an artificial intelligence clinical trial matching system in Australian lung cancer patients.

OBJECTIVE: The objective of this technical study was to evaluate the performance of an artificial intelligence (AI)-based system for clinical trials matching for a cohort of lung cancer patients in an Australian cancer hospital. METHODS: A lung cancer cohort was derived from clinical data from patients attending an Australian cancer hospital. Ten phases I-III clinical trials registered on clinicaltrials.gov and open to lung cancer patients at this institution were utilized for assessments. The trial matching system performance was compared to a gold standard established by clinician consensus for trial eligibility. RESULTS: The study included 102 lung cancer patients. The trial matching system evaluated 7252 patient attributes (per patient median 74, range 53-100) against 11 467 individual trial eligibility criteria (per trial median 597, range 243-4132). Median time for the system to run a query and return results was 15.5 s (range 7.2-37.8). In establishing the gold standard, clinician interrater agreement was high (Cohen's kappa 0.70-1.00). On a per-patient basis, the performance of the trial matching system for eligibility was as follows: accuracy, 91.6%; recall (sensitivity), 83.3%; precision (positive predictive value), 76.5%; negative predictive value, 95.7%; and specificity, 93.8%. DISCUSSION AND CONCLUSION: The AI-based clinical trial matching system allows efficient and reliable screening of cancer patients for clinical trials with 95.7% accuracy for exclusion and 91.6% accuracy for overall eligibility assessment; however, clinician input and oversight are still required. The automated system demonstrates promise as a clinical decision support tool to prescreen a large patient cohort to identify subjects suitable for further assessment.

PET-detected pneumonitis following curative-intent chemoradiation in non-small cell lung cancer (NSCLC): recognizing patterns and assessing the impact on the predictive ability of FDG-PET/CT response assessment.

PURPOSE: Inflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS). METHODS: Retrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1-5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural; B) diffuse (involving more than a segment); and C) peripheral (diffusely surrounding a photopenic region). RESULTS: Follow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days; interquartile range, 79-93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.6-2.5; p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7; 95% CI, 1.2-2.2; p < 0.001). CONCLUSION: PET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.

Radiation Therapy Modulates DNA Repair Efficiency in Peripheral Blood Mononuclear Cells of Patients With Non-Small Cell Lung Cancer.

PURPOSE: There is growing interest in developing individually tailored cancer radiation therapy (RT), wherein patients with high intrinsic radiosensitivity are identified before commencing treatment, to minimize severe adverse reactions. In a previous retrospective study of severely radiosensitive RT patients, we established a functional assay with a high predictive capability. The assay involves ex vivo irradiation of peripheral blood mononuclear cells and analysis of DNA repair using the γ-H2AX assay. It is unknown whether RS is a fixed phenomenon or is modulated under different conditions. We now report the impact of RT on the apparent radiosensitivity, as reflected by the assay. METHODS AND MATERIALS: Peripheral blood mononuclear cells of 11 patients with non-small cell lung cancer were collected before, during, and after RT. Quantitative parameters derived from the nonlinear regression analysis of γ-H2AX foci were applied to examine the cellular radiation response. RESULTS: Although the repair rate and foci yield remained constant during and after RT, the "unrepairable" component of γ-H2AX foci decreased over the course of treatment in 7 patients, signifying a generally enhanced DNA repair capacity. Interestingly, enhanced repair capacity tended to be associated with a poorer response to RT. CONCLUSIONS: Although generalization of these results into normal and tumor tissues warrants further investigation, the findings of this study have important implications in future strategies for identifying radiosensitive individuals before exposure to RT. We can anticipate that the threshold values that will discriminate radiosensitive patients in a future prospective trial will differ from those established in the retrospective study.

What 18F-FDG PET Response-Assessment Method Best Predicts Survival After Curative-Intent Chemoradiation in Non-Small Cell Lung Cancer: EORTC, PERCIST, Peter Mac Criteria, or Deauville Criteria?

The optimal methodology for defining response with 18F-FDG PET after curative-intent chemoradiation for non-small cell lung cancer (NSCLC) is unknown. We compared survival outcomes according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC), PERCIST 1.0, the Peter Mac metabolic visual criteria, and the Deauville criteria, respectively. Methods: Three prospective trials of chemoradiation for NSCLC, involving baseline and posttreatment 18F-FDG PET/CT imaging, were conducted between 2004 and 2016. Responses were categorized as complete metabolic response (CMR), partial metabolic response, stable metabolic disease, or progressive metabolic disease. Cox proportional-hazards models and log-rank tests assessed the impact of each response on overall survival (OS). Results: Eighty-seven patients underwent 18F-FDG PET/CT before and after radical chemoradiation for NSCLC. Follow-up 18F-FDG PET/CT scans were performed at a median of 89 d (interquartile range, 79-93 d) after radiotherapy. Median follow-up and OS after PET response imaging were 49 and 28 mo, respectively. Interobserver agreements for EORTC, PERCIST, Peter Mac, and Deauville had κ values of 0.76, 0.76, 0.87, and 0.84, respectively. All 4 response criteria were significantly associated with OS. Peter Mac and Deauville showed better fit than EORTC and PERCIST and distinguished better between CMR and non-CMR. Conclusion: All 4 response criteria were highly predictive of OS, but visual criteria showed greater interobserver agreement and stronger discrimination between CMR and non-CMR, highlighting the importance of visual assessment to recognize radiation pneumonitis, changes in lung configuration, and patterns of response.

Systematic Endobronchial Ultrasound-guided Mediastinal Staging Versus Positron Emission Tomography for Comprehensive Mediastinal Staging in NSCLC Before Radical Radiotherapy of Non-small Cell Lung Cancer: A Pilot Study.

Despite known limitations of positron emission tomography (PET) for mediastinal staging of non-small cell lung cancer (NSCLC), radiation treatment fields are generally based on PET-identified disease extent. However, no studies have examined the accuracy of FDG-PET/CT on a per-node basis in patients being considered for curative-intent radiotherapy in NSCLC.In a prospective trial, patients with NSCLC being considered for definitive thoracic radiotherapy (± systemic chemotherapy) underwent minimally invasive systematic mediastinal evaluation with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) following noninvasive staging with integrated PET-CT.Thirty patients underwent EBUS-TBNA, with TBNA performed from a mean 2.5 lymph node (LN) stations per patient (median 3, range 1-5). Discordant findings between PET-CT and EBUS-TBNA were observed in 10 patients (33%, 95% CI 19%-51%). PET-occult LN metastases were demonstrated by EBUS in 4 patients, whereas a lesser extent of mediastinal involvement, compared with FDG-PET, was demonstrated by EBUS in 6 patients, including 2 patients downstaged from cN3 to pN2. LNs upstaged by EBUS were significantly smaller than nodes downstaged by EBUS, 7.5 mm (range 7-9) versus 12 mm (range 6-21), P = 0.005.A significant proportion of patients considered for definitive radiotherapy (+/-chemotherapy) undergoing systematic mediastinal evaluation with EBUS-TBNA in this study have an extent of mediastinal NSCLC involvement discordant with that indicated by PET-CT. Systematic EBUS-TBNA may aid in defining the extent of mediastinal involvement in NSCLC patients undergoing radiotherapy. Systematic EBUS-TBNA has the potential to contribute significantly to radiotherapy planning and delivery, by either identifying occult nodal metastases, or demonstrating FDG-avid LNs to be disease-free.

Ga-68 MAA Perfusion 4D-PET/CT Scanning Allows for Functional Lung Avoidance Using Conformal Radiation Therapy Planning.

BACKGROUND: Ga-68-macroaggregated albumin ((68)Ga-perfusion) positron emission tomography/computed tomography (PET/CT) is a novel imaging technique for the assessment of functional lung volumes. The purpose of this study was to use this imaging technique for functional adaptation of definitive radiotherapy plans in patients with non-small cell lung cancer (NSCLC). METHODS: This was a prospective clinical trial of patients with NSCLC who received definitive 3-dimensional (3D) conformal radiotherapy to 60 Gy in 30 fx and underwent pretreatment respiratory-gated (4-dimensional [4D]) perfusion PET/CT. The "perfused" lung volume was defined as all lung parenchyma taking up radiotracer, and the "well-perfused" lung volume was contoured using a visually adapted threshold of 30% maximum standardized uptake value (SUV max). Alternate 3D conformal plans were subsequently created and optimized to avoid perfused and well-perfused lung volumes. Functional dose volumetrics were compared using mean lung dose (MLD), V5 (volume receiving 5 Gy or more), V10, V20, V30, V40, V50, and V60 parameters. RESULTS: Fourteen consecutive patients had alternate radiotherapy plans created based on functional lung volumes. When considering the original treatment plan, the dose to perfused and well-perfused functional lung volumes was similar to that of the conventional anatomical lung volumes with an average MLD of 12.15, 12.67, and 12.11 Gy, respectively. Plans optimized for well-perfused lung improved functional V30, V40, V50, and V60 metrics (all P values <.05). The functional MLD of well-perfused lung was improved by a median of 0.86 Gy, P < .01. However, plans optimized for perfused lung only showed significant improvement in the functional V60 dose parameter (median 1.00%, P = .04) but at a detriment of a worse functional V5 (median 3.33%, P = .05). CONCLUSIONS: This study demonstrates proof of principle that 4D-perfusion PET/CT may enable functional lung avoidance during treatment planning of patients with NSCLC. Radiotherapy plans adapted to well-perfused but not perfused functional lung volumes allow for reduction in dose to functional lung using 3D conformal radiotherapy.

Spleen Volume Variation in Patients with Locally Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemo-Radiotherapy.

There is renewed interest in the immune regulatory role of the spleen in oncology. To date, very few studies have examined macroscopic variations of splenic volume in the setting of cancer, prior to or during therapy, especially in humans. Changes in splenic volume may be associated with changes in splenic function. The purpose of this study was to investigate variations in spleen volume in NSCLC patients during chemo-radiotherapy. Sixty patients with stage I-IIIB NSCLC underwent radiotherapy (60 Gy/30 fractions) for six weeks with concomitant carboplatin/paclitaxel (Ca/P; n = 32) or cisplatin/etoposide (Ci/E; n = 28). A baseline PET/CT scan was performed within 2 weeks prior to treatment and during Weeks 2 and 4 of chemo-radiotherapy. Spleen volume was measured by contouring all CT slices. Significant macroscopic changes in splenic volume occurred early after the commencement of treatment. A significant decrease in spleen volume was observed for 66% of Ca/P and 79% of Ci/E patients between baseline and Week 2. Spleen volume was decreased by 14.2% for Ca/P (p<0.001) and 19.3% for Ci/E (p<0.001) patients. By Week 4, spleen volume was still significantly decreased for Ca/P patients compared to baseline, while for Ci/E patients, spleen volume returned to above baseline levels. This is the first report demonstrating macroscopic changes in the spleen in NSCLC patients undergoing radical chemo-radiotherapy that can be visualized by non-invasive imaging.

Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung.

PURPOSE: To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT). METHODS AND MATERIALS: In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC). RESULTS: A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment. CONCLUSIONS: Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.

Accuracy and Utility of Deformable Image Registration in (68)Ga 4D PET/CT Assessment of Pulmonary Perfusion Changes During and After Lung Radiation Therapy.

PURPOSE: Measuring changes in lung perfusion resulting from radiation therapy dose requires registration of the functional imaging to the radiation therapy treatment planning scan. This study investigates registration accuracy and utility for positron emission tomography (PET)/computed tomography (CT) perfusion imaging in radiation therapy for non-small cell lung cancer. METHODS: (68)Ga 4-dimensional PET/CT ventilation-perfusion imaging was performed before, during, and after radiation therapy for 5 patients. Rigid registration and deformable image registration (DIR) using B-splines and Demons algorithms was performed with the CT data to obtain a deformation map between the functional images and planning CT. Contour propagation accuracy and correspondence of anatomic features were used to assess registration accuracy. Wilcoxon signed-rank test was used to determine statistical significance. Changes in lung perfusion resulting from radiation therapy dose were calculated for each registration method for each patient and averaged over all patients. RESULTS: With B-splines/Demons DIR, median distance to agreement between lung contours reduced modestly by 0.9/1.1 mm, 1.3/1.6 mm, and 1.3/1.6 mm for pretreatment, midtreatment, and posttreatment (P < .01 for all), and median Dice score between lung contours improved by 0.04/0.04, 0.05/0.05, and 0.05/0.05 for pretreatment, midtreatment, and posttreatment (P < .001 for all). Distance between anatomic features reduced with DIR by median 2.5 mm and 2.8 for pretreatment and midtreatment time points, respectively (P = .001) and 1.4 mm for posttreatment (P > .2). Poorer posttreatment results were likely caused by posttreatment pneumonitis and tumor regression. Up to 80% standardized uptake value loss in perfusion scans was observed. There was limited change in the loss in lung perfusion between registration methods; however, Demons resulted in larger interpatient variation compared with rigid and B-splines registration. CONCLUSIONS: DIR accuracy in the data sets studied was variable depending on anatomic changes resulting from radiation therapy; caution must be exercised when using DIR in regions of low contrast or radiation pneumonitis. Lung perfusion reduces with increasing radiation therapy dose; however, DIR did not translate into significant changes in dose-response assessment.

Dosimetric Consequences of 3D Versus 4D PET/CT for Target Delineation of Lung Stereotactic Radiotherapy.

INTRODUCTION: Lung tumor delineation is frequently performed using 3D positron emission tomography (PET)/computed tomography (CT), particularly in the radiotherapy treatment planning position, by generating an internal target volume (ITV) from the slow acquisition PET. We investigate the dosimetric consequences of stereotactic ablative body radiotherapy (SABR) planning on 3D PET/CT in comparison with gated (4D) PET/CT. METHODS: In a prospective clinical trial, patients with lung metastases were prescribed 26 Gy single-fraction SABR to the covering isodose. Contemporaneous 3D PET/CT and 4D PET/CT was performed in the same patient position. An ITV was generated from each data set, with the planning target volume (PTV) being a 5-mm isotropic expansion. Dosimetric parameters from the SABR plan derived using the 3D volumes were evaluated against the same plan applied to 4D volumes. RESULTS: Ten lung targets were evaluated. All 3D plans were successfully optimized to cover 99% of the PTV by the 26 Gy prescription. In all cases, the calculated dose delivered to the 4D target was less than the expected dose to the PTV based on 3D planning. Coverage of the 4D-PTV by the prescription isodose ranged from 74.48% to 98.58% (mean of 90.05%). The minimum dose to the 4D-ITV derived by the 3D treatment plan (mean = 93.11%) was significantly lower than the expected dose to ITV based on 3D PET/CT calculation (mean = 111.28%), p < 0.01. In all but one case, the planned prescription dose did not cover the 4D-PET/CT derived ITV. CONCLUSIONS: Target delineation using 3D PET/CT without additional respiratory compensation techniques results in significant target underdosing in the context of SABR.

High-resolution pulmonary ventilation and perfusion PET/CT allows for functionally adapted intensity modulated radiotherapy in lung cancer.

BACKGROUND AND PURPOSE: To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation/perfusion (V/Q) PET/CT. MATERIALS AND METHODS: In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters. RESULTS: The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values<0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively. CONCLUSION: IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality.

Respiratory-gated (4D) FDG-PET detects tumour and normal lung response after stereotactic radiotherapy for pulmonary metastases.

BACKGROUND: Response assessment after stereotactic ablative body radiotherapy (SABR) in lung can be confounded by radiation-induced inflammation, fibrosis and subsequent alteration of tumour motion. The purpose of this prospective pilot study was to evaluate the utility of four-dimensional (4D) FDG-PET/CT for post-SABR tumour and normal lung response assessment in pulmonary oligometastases. MATERIAL AND METHODS: Patients enrolled from February 2010 to December 2011 in this prospective ethics approved study had 1-2 pulmonary metastases on staging FDG-PET. Serial contemporaneous 3D and 4D FDG-PET/CT scans were performed at baseline, 14 days and 70 days after a single fraction of 26 Gy SABR. Tumour response was evaluated in 3D and 4D using SUVmax, RECIST and PERCIST criteria. Normal lung radiotoxicity was evaluated using SUVmean within 0-2 Gy, 2-5 Gy, 5-10 Gy, 10-20 Gy and 20 + Gy isodose volumes. RESULTS: In total, 17 patients were enrolled of which seven were ineligible due to interval progression from staging PET to baseline 4D-PET. The mean time between scans was 62 days. At a median follow-up of 16 months, 10 patients with 13 metastases received SABR, with no patient having local progression. The vector of tumour motion was larger in patients with discordant 3D and 4D PET PERCIST response (p < 0.01), with a mean (± SEM) motion of 10.5 mm (± 0.96 mm) versus 6.14 mm (± 0.81 mm) in those patients with concordant 3D and 4D response. Surrounding normal lung FDG uptake at 70 days was strongly correlated to delivered radiation dose (r(2) = 0.99, p < 0.01), with significant elevations across all dose levels (p ≤ 0.05), except the < 2 Gy volume (p = 0.30). CONCLUSIONS: We demonstrate high rates of interval progression between staging PET scans in patients with oligometastases. We found that tumour response on conventional 3D PET is not concordant with 4D PET for tumours with large motion. Normal lung metabolic uptake is strongly dose dependent after SABR, a novel finding that should be further validated.

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

OBJECTIVES: To assess the tolerability and survival outcome of curative radiotherapy in patients over the age of 85 years. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of all patients aged over 85 years who received radiotherapy as part of curative treatment for any cancer (excluding insignificant skin cancers) at the Peter MacCallum Cancer Centre between 1 January 2000 and 1 January 2010. MAIN OUTCOME MEASURES: Poor treatment tolerability (defined as hospital admission during radiotherapy, treatment break, or early treatment cessation); predictors for poor treatment tolerability, overall survival and cancer-specific survival. RESULTS: 327 treatment courses met eligibility criteria. The median age of patients was 87 years. The most common treatment sites were pelvis (30%), head and neck (25%), and breast (18%). The Eastern Cooperative Oncology Group performance status (ECOG PS) score was 0 or 1 for 70% of patients. Overall, 79% of patients completed the prescribed treatment without poor treatment tolerability, and 95% of patients completed all treatment. Only unfavourable ECOG PS score (odds ratio [OR], 1.80; P = 0.005) and increasing age (OR, 1.18; P = 0.018) predicted poor treatment tolerability. ECOG PS score predicted overall survival (hazard ratio, 1.53; P = 0.001). CONCLUSION: Age should not be the sole discriminator in decisions to prescribe aggressive loco-regional radiotherapy. ECOG PS score predicts for treatment tolerability, and also overall survival. The risk of cancer death was higher than non-cancer death for more than 5 years after treatment.

Multimodality guidance for accurate bronchoscopic insertion of fiducial markers.

INTRODUCTION: Fiducial markers act as visible surrogates of tumor position during image-guided radiotherapy. Marker placement has been attempted percutaneously but is associated with high rates of pneumothorax and chest drain placement. METHODS: Patients undergoing radical radiation treatment for non-small-cell lung cancer underwent bronchoscopic implantation of gold fiducials using radial probe endobronchial ultrasound (EBUS) with virtual bronchoscopy and fluoroscopic guidance to achieve tumor localization and placement within/adjacent to peripheral lung tumors. For tumors not localized using radial EBUS, fiducial placement was achieved by electromagnetic navigation to the vicinity of the tumor. RESULTS: Eighteen fiducials were placed to mark 16 lesions in 15 patients. In nine patients (60%), fiducials were implanted at the time of diagnostic bronchoscopy. No procedural complications occurred. EBUS localization allowed marker implantation within the target lesion in 12 cases. In four lesions, electromagnetic navigation bronchoscopy-guided implantation achieved a median fiducial-lesion distance of 6 mm (mean 12 mm). No marker migration occurred after the implantation of two-band markers; however, early migration was observed in two of eight (25%) of the smaller linear fiducials. No migration during the course of radiation therapy was observed. CONCLUSION: Fiducial marker placement is easily and safely performed bronchoscopically, including at the time of diagnostic bronchoscopy. Marker geometry appears important in stability of bronchoscopically inserted fiducials. Future studies are required to confirm the optimal marker size, geometry, and spatial relationship with the target lesion.