Optimizing SABR delivery for synchronous multiple lung tumors using volumetric-modulated arc therapy.

BACKGROUND: Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. MATERIAL AND METHODS: Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. RESULTS: Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gy of ≥6.5% (in 2Gy/fraction equivalent) (p = .007). CONCLUSION: Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions.

The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R): Real-World Data on Stage III Non-Small Cell Lung Cancer Patients Treated With Curative Chemoradiation.

INTRODUCTION: Chemoradiotherapy (CRT) is the standard of care in inoperable non-small-cell lung cancer (NSCLC) patients, favoring concurrent (cCRT) over sequential CRT (seqCRT), with adjuvant immunotherapy in responders. Elderly and frail NSCLC patients have generally been excluded from trials in the past. In elderly patients however, the higher treatment related morbidity of cCRT, may outweigh the possible lower tumor control of seqCRT. For elderly patients with locally advanced NSCLC real-world data is essential to be able to balance treatment toxicity and treatment outcome. The aim of this study is to analyze acute toxicity and 3-month mortality of curative chemoradiation (CRT) in patients with stage III NSCLC and to analyze whether cCRT for elderly stage III NSCLC patients is safe. METHODS: The Dutch Lung Cancer Audit-Radiotherapy (DLCA-R) is a national lung cancer audit that started in 2013 for patients treated with curative intent radiotherapy. All Dutch patients treated for stage III NSCLC between 2015 and 2018 with seqCRT or cCRT for (primary or recurrent) stage III lung cancer are included in this population-based study. Information was collected on patient, tumor- and treatment characteristics and the incidence and severity of acute non-hematological toxicity (CTCAE-4 version 4.03) and mortality within 3 months after the end of radiotherapy. To evaluate the association between prognostic factors and outcome (acute toxicity and mortality within 3 months), an univariable and multivariable analysis was performed. The definition of cCRT was:radiotherapy started within 30 days after the start of chemotherapy. RESULTS: Out of all 20 Dutch departments of radiation oncology, 19 centers participated in the registry. A total of 2942 NSCLC stage III patients were treated with CRT. Of these 67.2% (n = 1977) were treated with cCRT (median age 66 years) and 32.8% (n = 965) were treated with seqCRT (median age 69 years). Good performance status (WHO 0-1) was scored in 88.6% for patients treated with cCRT and in 71.0% in the patients treated with seqCRT. Acute nonhematological 3-month toxicity (CTCAE grade ≥3 or radiation pneumonitis grade ≥2) was scored in 21.9% of the patients treated with cCRT and in 17.7% of the patients treated with seqCRT. The univariable analysis for acute toxicity showed significantly increased toxicity for cCRT (P = .008), WHO ≥2 (P = .006), and TNM IIIC (P = .031). The multivariable analysis for acute toxicity was significant for cCRT (P = .015), WHO ≥2 (P = .001) and TNM IIIC (P = .016). The univariable analysis for 3-month mortality showed significance for seqCRT (P = .025), WHO ≥2 (P < .001), higher cumulative radiotherapy dose (P < .001), higher gross tumor volume total (P = .020) and male patients (p < .001). None of these variables reached significance in the multivariable analysis for 3-month mortality. CONCLUSION: In this national lung cancer audit of inoperable NSCLC patients, 3-month toxicity was significantly higher in patients treated with cCRT (21.9% vs. 17.7% for seqCRT) higher TNM stage IIIC, and poor performance (WHO≥2) patients.The 3-months mortality was not significantly different for tested parameters. Age was not a risk factor for acute toxicity, nor 3 months mortality.

Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer.

Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process.

Factors influencing multi-disciplinary tumor board recommendations in stage III non-small cell lung cancer.

OBJECTIVES: Treatment patterns in patients with stage III non-small cell lung cancer (NSCLC) vary considerably between countries, for reasons that are not well understood. We studied factors influencing treatment decision-making at thoracic multidisciplinary tumor boards (MDT's) and outcome for patients treated between 2015-2017, at a regional network comprising 5 hospitals. MATERIALS AND METHODS: Details of all patients, including comorbidities, with stage III NSCLC were collected in an ethics-approved database. Weekly MDT's were conducted. The preferred radical intent treatments (RIT) for suitable patients were assumed to be concurrent chemoradiotherapy and/or surgery and other therapies were non-radical intent treatments (n-RIT). RESULTS: Of 197 patients identified, 95 % were discussed at an MDT. RIT were recommended in 61 % of patients, but only 48 % finally received RIT. The estimated median OS was significantly better for patients undergoing RIT (28.3 months, CI-95 % 17.3-39.3), versus those who did not (11.2 months, CI-95 % 8.0-14.3). Patient age ≥70 years and a WHO-PS ≥2 were the most important predictors of not recommending RIT. Deaths due to progressive lung cancer within 2 years were observed in 36, 26 and 29 % of patients who received RIT, sequential chemoradiotherapy or radical radiotherapy. Corresponding comorbidity related deaths within 2 years were 3, 12 and 38 %. CONCLUSION: A large number of patients who underwent MDT review were considered too old or not fit for RIT. More effective and better tolerated systemic treatments are required for patients presenting with stage III NSCLC.

The Impact of the Availability of Immunotherapy on Patterns of Care in Stage III NSCLC: A Dutch Multicenter Analysis.

INTRODUCTION: Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available. METHODS: Details of patients presenting with stage III NSCLC were retrospectively collected. Both CCRT and multimodality schemes incorporating planned surgery were defined as being radical-intent treatment (RIT). RESULTS: Of 855 eligible patients, most (95%) were discussed at a thoracic multidisciplinary tumor board, which recommended a RIT in 63% (n = 510). Only 52% (n = 424) of the patients finally received a RIT. Predictors for not recommending RIT were age greater than or equal to 70 years, WHO performance score greater than or equal to 2, Charlson comorbidity index greater than or equal to 2 (excluding age), forced expiratory volume in 1 second less than 80% of predicted value, N3 disease, and period of diagnosis. Between 2015 to 2017 and 2018 to 2019, the proportion of patients undergoing CCRT increased from 34% to 42% (p = 0.02) and use of sequential chemoradiotherapy declined (21%-16%, p = 0.05). Rates of early toxicity and 1-year mortality were comparable for both periods. After 2018, 57% of the patients who underwent CCRT (90 of 159) received adjuvant durvalumab. CONCLUSIONS: After publication of the PACIFIC trial, a significant increase was observed in the use of CCRT for patients with stage III NSCLC with rates of early toxicity and mortality being unchanged. Since 2018, 57% of the patients undergoing CCRT went on to receive adjuvant durvalumab. Nevertheless, approximately half of the patients were still considered unfit for a RIT.

Delivery of magnetic resonance-guided single-fraction stereotactic lung radiotherapy.

BACKGROUND AND PURPOSE: Single-fraction stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage lung cancer, but concerns remain about the accurate delivery of SABR in a single session. We evaluated the delivery of single-fraction lung SABR using magnetic resonance (MR)-guidance. MATERIALS AND METHODS: An MR-simulation was performed in 17 patients, seven of whom were found to be unsuitable, largely due to unreliable tracking of small tumors. Ten patients underwent single-fraction SABR to 34 Gy on a 0.35 T MR-linac system, with online plan adaptation. Gated breath-hold SABR was delivered using a planning target volume (PTV) margin of 5 mm, and a 3 mm gating window. Continuous MR-tracking of the gross tumor volume (GTVt) was performed in sagittal plane, with visual patient feedback provided using an in-room monitor. The real-time MR images were analyzed to determine precision and efficiency of gated delivery. RESULTS: All but one patient completed treatment in a single session. The median total in-room procedure was 120 min, with a median SABR delivery session of 39 min. Review of 7.4 h of cine-MR imaging revealed a mean GTVt coverage by the PTV during beam-on of 99.6%. Breath-hold patterns were variable, resulting in a mean duty cycle efficiency of 51%, but GTVt coverage was not influenced due to real-time MR-guidance. On-table adaptation improved PTV coverage, but had limited impact on GTV doses. CONCLUSIONS: Single-fraction gated SABR of lung tumors can be performed with high precision using MR-guidance. However, improvements are needed to ensure MR-tracking of small tumors, and to reduce treatment times.

Clinical Outcomes of Stereotactic MR-Guided Adaptive Radiation Therapy for High-Risk Lung Tumors.

PURPOSE: Magnetic resonance (MR)-guided SABR was performed for patients with lung tumors in whom treatment delivery was challenging owing to tumor location, motion, or pulmonary comorbidity. Because stereotactic MR-guided adaptive radiation therapy (SMART) is a novel approach, we studied clinical outcomes in these high-risk lung tumors. METHODS AND MATERIALS: Fifty consecutive patients (54 lung tumors) underwent SMART between 2016 and 2018 for either a primary lung cancer (29 patients) or for lung metastases (21 patients). Eligible patients had risk factors that could predispose them to toxicity, including a central tumor location (n = 30), previous thoracic radiation therapy (n = 17), and interstitial lung disease (n = 7). A daily 17-second breath-hold MR scan was acquired in treatment position, and on-table plan adaptation was performed using the anatomy of the day. Gated SABR was delivered during repeated breath-holds under continuous MR guidance. RESULTS: All but 1 patient completed the planned SMART schedule. With daily plan adaptation, a biologically effective dose ≥100 Gy to 95% of the planning target volume was delivered in 50 tumors (93%). Median follow-up was 21.7 months (95% confidence interval, 19.9-28.1). Local control and overall and disease-free survival rates at 12 months were 95.6%, 88.0%, and 63.6%, respectively. Local failures developed in 4 patients: in 2 after reirradiation for a recurrent lung cancer and in 2 patients with a colorectal metastasis. Overall rates of any grade ≥2 and ≥3 toxicity were 30% and 8%, respectively. Commonest toxicities were grade ≥2 radiation pneumonitis (12%) and chest wall pain (8%). No grade 4 or 5 toxicities were observed. CONCLUSIONS: Use of MR-guided SABR resulted in low rates of high-grade toxicity and encouraging early local control in a cohort of high-risk lung tumors. Additional studies are needed to identify patients who are most likely to benefit from the SMART approach.

Stereotactic MR-guided adaptive radiation therapy for peripheral lung tumors.

BACKGROUND AND PURPOSE: We studied the benefits of using stereotactic MR-guided adaptive radiation therapy (SMART) for delivery of SABR in peripherally located lung tumors. METHODS AND MATERIALS: Twenty-three patients (25 peripheral lung tumors) underwent SMART in 3-8 fractions on an MR Linac or Cobalt-60 system. Before each fraction, a breath-hold MR scan was acquired, followed by on-table plan adaptation based on the anatomy-of-the-day. Breath-hold gated delivery was performed under continuous MR-guidance using an in-room monitor. Benefits of on-table adaptation were studied by comparing 112 «predicted¼ plans, which are the baseline plans recalculated on the anatomy-of-the-day, with the on-table reoptimized plans. RESULTS: The full SMART procedure took a median of 48 and 62 minutes on the MR Linac and Cobalt-60 system, respectively. Median SMART-PTVs were 9.5 cm3 (range, 3.1-55.6). In 14 patients who had undergone a free-breathing 4DCT, SMART-PTVs measured 53.7% (range, 31.9-75.0) of PTVs that would have been generated using a motion-encompassing internal target volume approach. On-table adaptation improved prescription dose coverage of the PTV from a median of 92.1% in predicted plans, to 95.0% in reoptimized ones, thereby increasing the proportion of fractions delivering ≥100 Gy (BED10Gy) to 95% of PTV, from 90.2% to 100.0%. CONCLUSION: Delivery of gated breath-hold SABR using MR-guidance resulted in significantly smaller target volumes than would have been the case with an ITV-based approach. Although on-table adaptation ensured delivery of ablative doses in all fractions, the dosimetric benefits were modest, suggesting that daily online plan adaptation may not benefit most patients with peripheral lung tumors.

Role of On-Table Plan Adaptation in MR-Guided Ablative Radiation Therapy for Central Lung Tumors.

PURPOSE: As patients with centrally located lung tumors are at increased risk of toxicity with stereotactic ablative radiation therapy (SABR), we performed stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for such patients. We retrospectively analyzed the benefits of daily on-table plan adaptation. METHODS AND MATERIALS: Twenty-five patients with central lung tumors underwent a total of 182 fractions of video-assisted, respiration-gated SMART on the MRIdian (ViewRay, Inc). Risk-adapted fractionation was used to deliver 60 Gy in 8 fractions (n = 20) or 55 Gy in 5 fractions (n = 5). For each fraction, daily MR-guided setup and on-table plan reoptimization, based on planning target volume (PTV) coverage and organ-at-risk (OAR) constraints, was performed. Gated breath-hold delivery was performed under continuous MR guidance. Benefits of daily plan reoptimization were studied by comparing 168 "predicted" plans, which are the calculated baseline plans on the anatomy of the day, with the reoptimized treatment plans. RESULTS: The reoptimized plan was chosen for treatment in 92% of fractions. On-table plan adaptation improved PTV coverage in 61% of fractions by achieving superior coverage by the prescription dose (V100%) and a higher median dose (D50%). Mean increase in PTV V100% was 4.6% (P < .01) with a median of 91.2% and 95.0% in predicted and reoptimized plans, respectively. The benefits of on-table adaptation persisted in an analysis restricted to fractions in which the PTV change was ≤1 cm3 compared with baseline. On-table plan adaptation reduced the number of OAR planning constraint violations (P < .05). Maximum OAR doses remained mostly stable, with on-table reoptimization avoiding excessive OAR doses in selected cases. CONCLUSIONS: On-table plan reoptimization during breath-hold MR-guided SABR for central lung tumors improves target coverage while avoiding excessive OAR doses. The SMART approach may widen the therapeutic window of SABR in high-risk patients with central lung tumors.

A Prospective Single-Arm Phase 2 Study of Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy for Prostate Cancer: Early Toxicity Results.

PURPOSE: Use of stereotactic body radiation therapy (SBRT) is increasing in patients with localized prostate cancer, but concerns about early and late gastrointestinal (GI) and genitourinary (GU) toxicity exist after moderately or extremely hypofractionated radiation therapy schemes. Magnetic resonance guided radiation therapy (MRgRT) was clinically introduced in 2014. MrgRT allows for SBRT delivery with smaller uncertainty margins and permits daily adaptive planning. A phase 2 study in patients with localized prostate cancer was performed to study early GI and GU toxicity after SBRT using MRgRT. METHODS AND MATERIALS: One hundred one patients with clinical stage T1-3bN0M0 prostate cancer were enrolled in this prospective phase 2 study. All but 4 patients had intermediate- or high-risk prostate cancer, and 82.2% received adjuvant hormonal treatment. MRgRT was delivered in 5 fractions of 7.25 Gy to the target volume using daily plan adaptation with simultaneous relative sparing of the urethra to a dose of 6.5 Gy per fraction. Early toxicity was studied using both clinician- (Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group) and patient-reported outcome measurements (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, Quality of Life Questionnaire PR25, and International Prostate Symptom Scoring). RESULTS: The maximum cumulative grade ≥2 early GU and GI toxicity measured by any symptom at any study time point was 23.8% and 5.0%, respectively. No early grade 3 GI toxicity was observed. Early grade 3 GU toxicity was 0% and 5.9% according to the Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group and scoring systems, respectively, as a result of different grading of radiation cystitis. The low incidence of early GI toxicity was confirmed by patient-reported outcome data. GU grade ≥2 toxicity peaked to 19.8% at the end of MRgRT, followed by a return to the baseline average score at 3-month follow-up. CONCLUSIONS: This prospective study of MRgRT in patients with localized prostate cancer observed a low incidence of early GI and GU toxicity, both in clinician- and patient-reported outcome measurements.

An in-silico quality assurance study of contouring target volumes in thoracic tumors within a cooperative group setting.

INTRODUCTION: Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee's multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a "dry run" for trial implementation. METHODS: CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV).Six board-certified thoracic radiation oncologists were designated as the 'Experts' for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants' contours were then compared with Experts' STAPLE contours. RESULTS: When compared to the Experts' STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans. CONCLUSIONS: High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.

Impact of audio-coaching on the position of lung tumors.

PURPOSE: Respiration-induced organ motion is a major source of positional, or geometric, uncertainty in thoracic radiotherapy. Interventions to mitigate the impact of motion include audio-coached respiration-gated radiotherapy (RGRT). To assess the impact of coaching on average tumor position during gating, we analyzed four-dimensional computed tomography (4DCT) scans performed both with and without audio-coaching. METHODS AND MATERIALS: Our RGRT protocol requires that an audio-coached 4DCT scan is performed when the initial free-breathing 4DCT indicates a potential benefit with gating. We retrospectively analyzed 22 such paired scans in patients with well-circumscribed tumors. Changes in lung volume and position of internal target volumes (ITV) generated in three consecutive respiratory phases at both end-inspiration and end-expiration were analyzed. RESULTS: Audio-coaching increased end-inspiration lung volumes by a mean of 10.2% (range, -13% to +43%) when compared with free breathing (p = 0.001). The mean three-dimensional displacement of the center of ITV was 3.6 mm (SD, 2.5; range, 0.3-9.6mm), mainly caused by displacement in the craniocaudal direction. Displacement of ITV caused by coaching was more than 5 mm in 5 patients, all of whom were in the subgroup of 9 patients showing total tumor motion of 10 mm or more during both coached and uncoached breathing. Comparable ITV displacements were observed at end-expiration phases of the 4DCT. CONCLUSIONS: Differences in ITV position exceeding 5 mm between coached and uncoached 4DCT scans were detected in up to 56% of mobile tumors. Both end-inspiration and end-expiration RGRT were susceptible to displacements. This indicates that the method of audio-coaching should remain unchanged throughout the course of treatment.

Analysis of reproducibility of respiration-triggered gated radiotherapy for lung tumors.

PURPOSE: Respiration-gated radiotherapy (RGRT) can decrease the toxicity of chemo-radiotherapy (CT-RT) by allowing use of smaller treatment fields. RGRT requires a predictable relationship between tumor position and external surrogate, which must be verified during treatment. Time-integrated electronic portal imaging (TI-EPI) identifies mean intra-fractional positions of moving structures, and was used to study reproducibility of anatomy during RGRT for lung tumors. MATERIALS AND METHODS: TI-EPIs were acquired using an amorphous silicon-based electronic portal imaging system (EPID, aS500) in continuous image acquisition mode in 11 patients treated with audio-coached RGRT at end-inspiration. The Varian Real-time Position Management (RPM) system was used for 4DCT imaging and RGRT delivery. All TI-EPI portals were co-registered to corresponding digitally reconstructed radiographs (DRR) of the planning 4DCT using the spinal column. Displacements in tumor position or that of an adjacent bronchus during RGRT was measured relative to the reference structure on the DRR. RESULTS: Vertebra-matched portals revealed systematic (Sigma) and random (sigma) errors of 1.8 and 1.3mm in medial-lateral direction and 1.7 and 1.7 mm in cranial-caudal direction, indicating a reproducible tumor/bronchus position during the RPM-triggered gates. CONCLUSIONS: RGRT delivery at end-inspiration can achieve reproducible internal anatomy in 'gated' fields delivered with audio-coaching.

Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cancer.

INTRODUCTION: We defined "ultracentral" lung tumors as centrally located non-small cell lung cancers with planning target volumes overlapping the trachea or main bronchi. Increased toxicity has been reported after both conventional and stereotactic radiotherapy for such lesions. We studied outcomes after 12 fractions of 5 Gy (BED10 = 90 Gy, heterogeneous dose distribution) to ultracentral tumors in patients unfit for surgery or conventional chemoradiotherapy. METHODS: Clinical outcomes and dosimetric details were analyzed in 47 consecutive patients with single primary or recurrent ultracentral non-small cell lung cancer treated between 2010 and 2015. Those irradiated previously or with metastasis to sites other than the brain and adrenal glands were excluded. Treatments were delivered using volumetric modulated arc therapy. RESULTS: The median age was 77.5 years, 49% of patients had a World Health Organization performance score of 2 or higher, and the median planning target volume was 104.5cm(3) (range 17.7-508.5). At a median follow-up of 29.3 months, median overall survival was 15.9 months, and 3-year survival was 20.1%. No isolated local recurrences were observed. Grade 3 or higher toxicity was recorded in 38% of patients, with 21% scored as having a "possible" (n = 2) or "likely" (n = 8) treatment-related death between 5.2 and 18.2 months after treatment. Fatal pulmonary hemorrhage was observed in 15% of patients. CONCLUSIONS: Unfit patients with ultracentral tumors who were treated using this scheme had a high local control and a median survival of 15.9 months. Despite manifestation of rates of a fatal lung bleeding comparable to those seen with conventional radiotherapy for endobronchial tumors, the overall rate of G5 toxicity is of potential concern. Additional work is needed to identify tumor and treatment factors related to hemorrhage.

Diagnostic challenges in survivors of early stage lung cancer.

OBJECTIVES: Survivors of early stage non-small cell lung cancer (NSCLC) are at risk of developing disease recurrence, as well as new lung tumors. Distinguishing metastatic disease from a second primary lung tumor (SPLC) is important, but can pose diagnostic challenges in what are often frail patients. MATERIALS AND METHODS: We highlight three long-term survivors of early stage NSCLC who developed multiple new lung lesions on long-term follow-up after undergoing an initial stereotactic ablative radiotherapy procedure. RESULTS: New radiological lesions were always evaluated by a multidisciplinary tumor board in order to determine the optimal diagnostic procedure and treatment. When identical histological types were identified, array comparative genomic hybridization (CGH) was used to differentiate between metastases and a second primary tumor. When a tissue diagnosis is not possible, a validated calculator of tumor probability can be used to calculate the likelihood of malignancy. All patients underwent multiple episodes of curative radiotherapy. CONCLUSION: These long-term survivors of early stage NSCLC highlight the importance of radiological follow-up, and describe approaches for guiding diagnostic and therapeutic management.

Parenchymal lung changes on computed tomography after stereotactic radiotherapy using high dose rate flattening filter free beams.

Flattening filter free (FFF) beams allow fast delivery of stereotactic radiotherapy. To evaluate biological effects of FFF in lung, we compared parenchymal changes after FFF and non-FFF stereotactic volumetric modulated arc therapy. Standardized multi-observer consensus evaluation of follow-up CT scans revealed no major differences between FFF and non-FFF.

High-risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.

BACKGROUND AND PURPOSE: Early detection of local recurrences following stereotactic ablative radiotherapy (SABR) for lung cancer may allow for curative salvage treatment, but recurrence can be difficult to distinguish from fibrosis. We studied the clinical performance of CT imaging high-risk features (HRFs) for detecting local recurrence. MATERIALS AND METHODS: Patients treated with SABR for early stage lung cancer between 2003 and 2012 who developed pathology-proven local recurrence (n=12) were matched 1:2 to patients without recurrences (n=24), based on baseline factors. Serial CT images were assessed by blinded radiation oncologists. Previously reported HRFs were (1) enlarging opacity at primary site; (2) sequential enlarging opacity; (3) enlarging opacity after 12-months; (4) bulging margin; (5) loss of linear margin and (6) air bronchogram loss. RESULTS: All HRFs were significantly associated with local recurrence (p<0.01), and one new HRF was identified: cranio-caudal growth (p<0.001). The best individual predictor of local recurrence was opacity enlargement after 12-months (100% sensitivity, 83% specificity, p<0.001). The odds of recurrence increased 4-fold for each additional HRF detected. The presence of ≥3 HRFs was highly sensitive and specific for recurrence (both >90%). CONCLUSION: The systematic assessment of post-SABR CT images for HRFs enables the accurate prediction of local recurrence.

Feasibility of using anatomical surrogates for predicting the position of lung tumours.

We studied the use of internal anatomical surrogates (carina and diaphragm) for the purpose of predicting the 3D position of lung tumours in 41 patients, in whom repeat 4DCT scans were available. Despite using two surrogates, significant prediction errors were observed, which varied depending on tumour position, baseline tumour motion and respiratory phase.

Variations in target volume definition for postoperative radiotherapy in stage III non-small-cell lung cancer: analysis of an international contouring study.

PURPOSE: Postoperative radiotherapy (PORT) in patients with completely resected non-small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). METHODS AND MATERIALS: Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM-based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. RESULTS: Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V(20) values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. CONCLUSION: Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study.