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Introduction: To find the optimal dose prescription strategy for liver SBRT, this study investigated the tradeoffs between achievable target dose and healthy liver dose for a range of isotoxic uniform and non-uniform prescription level strategies. Material and methods: Nine patients received ten liver SBRT courses with intrafraction motion monitoring during treatment. After treatment, five VMAT treatment plans were made for each treatment course. The PTV margin was 5 mm (left-right, anterior-posterior) and 10 mm (cranio-caudal). All plans had a mean CTV dose of 56.25 Gy in three fractions, while the PTV was covered by 50%, 67%, 67 s% (steep dose gradient outside CTV), 80%, and 95% of this dose, respectively. The 50%, 67 s%, 80%, and 95% plans were then renormalized to be isotoxic with the standard 67% plan according to a Lyman-Kutcher-Burman normal tissue complication probability model for radiation induced liver disease. The CTV D98 and mean dose of the iso-toxic plans were calculated both without and with the observed intrafraction motion, using a validated method for motion-including dose reconstruction. Results: Under isotoxic conditions, the average [range] mean CTV dose per fraction decreased gradually from 21.2 [20.5-22.7] Gy to 15.5 [15.0-16.6] Gy and the D98 dose per fraction decreased from 20.4 [19.7-21.7] Gy to 15.0 [14.5-15.5] Gy, as the prescription level to the PTV rim was increased from 50% to 95%. With inclusion of target motion the mean CTV dose was 20.5 [16.5-22.5] Gy (50% PTV rim dose) and 15.4 [13.9-16.7] Gy (95% rim dose) while D98 was 17.8 [7.4-20.6] Gy (50% rim dose) and 14.6 [8.8-15.7] Gy (95% rim dose). Conclusion: Requirements of a uniform PTV dose come at the price of excess normal tissue dose. A non-uniform PTV dose allows increased CTV mean dose at the cost of robustness toward intrafraction motion. The increase in planned CTV dose by non-uniform prescription outbalanced the dose deterioration caused by motion.

Background: While the introduction of checkpoint inhibitors (CPIs) as standard of care treatment for various tumor types has led to considerable improvements in clinical outcome, the majority of patients still fail to respond. Preclinical data suggest that stereotactic body radiotherapy (SBRT) could work synergistically with CPIs by acting as an in situ cancer vaccine, thus potentially increasing response rates and prolonging disease control. Though SBRT administered concurrently with CPIs has been shown to be safe, evidence of its efficacy from large randomized trials is still lacking. The aim of this multicenter randomized phase II trial is to assess whether SBRT administered concurrently with CPIs could prolong progression-free survival as compared to standard of care in patients with advanced solid tumors. Methods/design: Ninety-eight patients with locally advanced or metastatic disease will be randomized in a 1:1 fashion to receive CPI treatment combined with SBRT (Arm A) or CPI monotherapy (Arm B). Randomization will be stratified according to tumor histology (melanoma, renal, urothelial, head and neck squamous cell or non-small cell lung carcinoma) and disease burden (≤ or > 3 cancer lesions). The recommended SBRT dose is 24Gy in 3 fractions, which will be administered to a maximum of 3 lesions and is to be completed prior to the second or third CPI cycle (depending on CPI treatment schedule). The study’s primary endpoint is progression-free survival as per iRECIST. Secondary endpoints include overall survival, objective response, local control, quality of life and toxicity. Translational analyses will be performed using blood, fecal and tissue samples. Discussion: The CHEERS trial will provide further insights into the clinical and immunological impact of SBRT when combined with CPIs in patients with advanced solid tumors. Furthermore, study results will inform the design of future immuno-radiotherapy trials. Trial registration: Clinicaltrials.gov identifier: NCT03511391. Registered 17 April 2018., SCOPUS: ar.j, info:eu-repo/semantics/published

Purpose: Thoracic reirradiation for non-small cell lung cancer with curative intent is potentially associated with severe toxicity. There are limited prospective data on the best method to deliver this treatment. We sought to develop expert consensus guidance on the safe practice of treating non-small cell lung cancer with radiation therapy in the setting of prior thoracic irradiation.Methods and Materials: Twenty-one thoracic radiation oncologists were invited to participate in an international Delphi consensus process. Guideline statements were developed and refined during 4 rounds on the definition of reirradiation, selection of appropriate patients, pretreatment assessments, planning of radiation therapy, and cumulative dose constraints. Consensus was achieved once >75% of respondents agreed with a statement. Statements that did not reach consensus in the initial survey rounds were revised based on respondents' comments and re-presented in subsequent rounds.Results: Fifteen radiation oncologists participated in the 4 surveys between September 2019 and March 2020. The first 3 rounds had a 100% response rate, and the final round was completed by 93% of participants. Thirty-three out of 77 statements across all rounds achieved consensus. Key recommendations are as follows: (1) appropriate patients should have a good performance status and can have locally relapsed disease or second primary cancers, and there are no absolute lung function values that preclude reirradiation; (2) a full diagnostic workup should be performed in patients with suspected local recurrence and; (3) any reirradiation should be delivered using optimal image guidance and highly conformal techniques. In addition, consensus cumulative dose for the organs at risk in the thorax are described.Conclusions: These consensus statements provide practical guidance on appropriate patient selection for reirradiation, appropriate radiation therapy techniques, and cumulative dose constraints. (C) 2021 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.

Preclinical and early clinical evidence suggest that radical radiotherapy of oligometastatic disease in non-small cell lung cancer (NSCLC) patients can impact outcomes with relatively limited toxicity. Whilst data from phase 2 randomized trials suggesting an improved overall survival (OS) with this treatment is promising, it has also illustrated the heterogeneity in this patient population and treatment. Oligometastatic disease in itself comprises a broad spectrum of patients, in terms of tumor load and location, stage of the disease and treatment history. This real-life variety in patient characteristics is often reflected in studies to a certain extent, hinting to the fact that all might benefit from radical radiotherapy to limited metastatic disease, yet leaving the question unanswered as to whom the ideal candidate is. Furthermore, differences between and within studies with regards to treatment modality, timing, radiation technique, and radiation dose are substantial. Also, preclinical and early clinical trials suggest that radiotherapy can work synergistically with checkpoint inhibitors by acting as an in situ cancer vaccine, therefore the combination of these two treatments in oligometastatic patients might entail the largest benefit. Ongoing randomized controlled phase 3 trials and prospective registry trials will further elucidate the true extent of benefit of this local treatment strategy and aid in identifying the ideal patient population and therapy. The current narrative review summarizes the clinical evidence on radiotherapy for oligometastatic NSCLC and highlights the remaining unknowns.

It is not clear as to which is the best treatment among surgery and stereotactic radiotherapy (SBRT) for lung oligometastases. A systematic review of literature with a priori selection criteria was conducted on articles on the treatment of pulmonary metastases with surgery or SBRT. Only original articles with a population of patients of more than 50 were selected. After final selection, 61 articles on surgical treatment and 18 on SBRT were included. No difference was encountered in short-term survival between pulmonary metastasectomy and SBRT. In the long-term surgery seems to guarantee better survival rates. Mortality and morbidity after treatment are 0–4.7% and 0–23% for surgery, and 0–2% and 4–31% for SBRT. Surgical metastasectomy remains the treatment of choice for pulmonary oligometastases., Lay abstract Patients with metastatic cancer with a limited number of deposits may benefit from surgical removal or irradiation of tumor nodules in addiction to chemotherapy. Surgical resection has been demonstrated to improve survival and, in some cases, can be curative. Stereotactic radiotherapy is emerging as a less invasive alternative to surgery, but settings and implications of the two treatments are profoundly different. The two techniques show similar results in the short-term, with lower complications rates for radiotherapy, while in the long-term surgery seems to guarantee higher survival rates.

BACKGROUND: The role of prophylactic cranial irradiation (PCI) and thoracic radiotherapy (TRT) is unclear in resected small cell lung cancer (SCLC).METHODS: Thirteen European radiotherapy experts on SCLC were asked to describe their strategies on PCI and TRT for patients with resected SCLC. The treatment strategies were converted into decision trees and analyzed for consensus and discrepancies.RESULTS: For patients with resected SCLC and positive lymph nodes most experts recommend prophylactic cranial irradiation and thoracic radiotherapy. For elderly patients with resected node negative SCLC, most experts do not recommend thoracic radiotherapy or prophylactic cranial irradiation.CONCLUSION: PCI and TRT are considered in patients with resected SCLC and these treatments should be discussed with the patient in the context of shared decision-making.

For patients presenting with limited metastatic disease burden, known as the oligometastatic state of disease, a more aggressive treatment approach targeting the new or progressive metastatic lesions might improve patient outcome, with no or only limited toxicity to be expected from the treatment. This review provides an overview of the existing evidence and on-going trials on oligometastatic disease and metastasis-directed therapy in the field of renal, bladder and prostate cancer. ispartof: ECANCERMEDICALSCIENCE vol:14 ispartof: location:England status: published

Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

Stereotactic ablative body radiotherapy (SABR) is popular because of the high rates of local control with low toxicity seen in lung cancer patients. In this study we compared clinically significant toxicity and overall survival for SABR and non-SABR definitive radiotherapy (conformal radiotherapy) patients. A PUBMED search of all human, English language articles on SABR and non-SABR radically treated early stage lung cancer patients was performed until June 2016. Results of these searches were filtered in accordance with a set of eligibility criteria and analyzed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eighty-seven SABR and 25 non-SABR articles were reviewed. There was no significant difference in pneumonitis rates between patients receiving SABR (11.4%; 95% confidence interval [CI], 9.7-13.3) and non-SABR treatment (14.4%; 95% CI, 10.6-18.8; P = .20). Esophagitis was the most common mediastinal toxicity reported with 15% of all non-SABR patients versus 1% of all SABR patients reporting developing Grade >= 2 toxicity. The proportion of patient surviving at 2 and 3 years was superior for SABR patients (P < .001). Treatment-related deaths were rare (approximately 1% for both treatments). Both radiotherapy approaches had low rates of pneumonitis, mediastinal toxicity, and treatment-related deaths. However, significant heterogeneity in the patient population and study regimens limit the power of direct comparison, showing that further high-quality studies are required to define the role of SABR in higher risk and operable patients. Crown Copyright (C) 2017 Published by Elsevier Inc. All rights reserved.

Historically, a simple approach centered on palliation was applicable to the majority of patients with metastatic spinal disease. With advances in diagnosis and treatment, a more complicated algorithm has devolved requiring a multidisciplinary approach with institutional commitment and support. We performed a database review including pertinent articles exploring the multidisciplinary management of spinal metastatic disease. The wide variation in clinical presentation and tumor response to treatment necessitates a multidisciplinary approach that integrates the diagnosis and treatment of the cancer, symptom management, and rehabilitation for optimal care of patients with spinal metastases. Advances in the field of radiology have led to earlier and more focused diagnosis of spinal metastasis and acts to guide therapy. Advances in surgical techniques, neurophysiologic monitoring, and anesthetic expertise have allowed surgeons to perform more extensive procedures leading to improved outcomes and reduced morbidity. Radiation oncology input that is essential as external beam radiation therapy can provide significant pain relief. Non-operative measures may include bisphosphonate infusions, management of complications (e.g. hypercalcemia of malignancy), monoclonal antibody infusions, and chemotherapy if indicated in the treatment of the primary malignancy. Input from psychology services is necessary to address the biopsychosocial ramifications of spinal metastasis. Allied health professionals in the form of physiotherapists, social workers, and dieticians also contribute in maximizing patients' quality of life and well-being.

Objectives: Insights regarding utilization and survival of surgery and radiotherapy (stereotactic body radiotherapy (SBRT) or conventional radiotherapy (RT)) are lacking for older patients with stage I and II non-small cell lung cancer (NSCLC) in clinical practice.Methods: Data from the Netherlands Cancer Registry were retrieved for patients >= 65 years with clinical stage I-II NSCLC in 2010-2015. Descriptive analyses, overall survival (OS), and cox regression were stratified for stage I (n = 8742) and II (n = 3439) and compared age groups (65-74 years vs >= 75 years).Results: Patients aged 65-74 underwent surgery significantly more often compared to those aged >= 75 (stage I 55% vs 27%; stage II: 65% vs 35%), and received SBRT less often (I: 29% vs 42%; II: 5% vs 11%), conventional RT less often (I: 6% vs 11%; II 10% vs 24%) and best supportive care alone less often (BSC, I: 8% vs 19%; II: 9% vs 25%). One-year OS was significantly higher in patients aged 65-74 compared to those aged >= 75 (I: 87% vs 78%; II: 74% vs 60%); as was five-year OS (I: 49% vs 31%; II: 36% vs 18%). After adjustment for gender, histology, stage, treatment, and comorbidity, hazard ratio (HR) of death was higher for patients aged >= 75 compared to those aged 65-74 (1: HR 1.3, 95% confidence interval (CI) 1.1-1.5; II: HR 1.3 95%CI 1.1-1.7).Conclusion: Patients aged >= 75 with stage I-II NSCLC had poorer OS, underwent surgery less often, and received SBRT, conventional RT, and BSC more often than patients aged 65-74, In both stages, one-year OS within age groups was similar for surgery and SBRT. However, long-term OS adjusted for prognostic factors was superior for surgery compared to SBRT and remained poorer for those aged >= 75. Prospective research should focus on predictive characteristics for treatment selection and patient-centered outcomes. (C) 2019 Elsevier Ltd. All rights reserved.

Objective: Stereotactic ablative radiotherapy (SABR) is being increasingly used as a non-invasive treatment for early-stage non-small cell lung cancer (NSCLC). A non-invasive method to estimate treatment outcomes in these patients would be valuable, especially since access to tissue specimens is often difficult in these cases., Methods: We developed a method to predict survival following SABR in NSCLC patients using analysis of quantitative image features on pre-treatment CT images. We developed a Cox Lasso model based on two-dimensional Riesz wavelet quantitative texture features on CT scans with the goal of separating patients based on survival., Results: The median log-rank p-value for 1000 cross-validations was 0.030. Our model was able to separate patients based upon predicted survival. When we added tumor size into the model, the p-value lost its significance, demonstrating that tumor size is not a key feature in the model but rather decreases significance likely due to the relatively small number of events in the dataset. Furthermore, running the model using Riesz features extracted either from the solid component of the tumor or from the ground glass opacity (GGO) component of the tumor maintained statistical significance. However, the p-value improved when combining features from the solid and the GGO components, demonstrating that there are important data that can be extracted from the entire tumor., Conclusions: The model predicting patient survival following SABR in NSCLC may be useful in future studies by enabling prediction of survival-based outcomes using radiomics features in CT images., Advances in knowledge: Quantitative image features from NSCLC nodules on CT images have been found to significantly separate patient populations based on overall survival (p = 0.04). In the long term, a non-invasive method to estimate treatment outcomes in patients undergoing SABR would be valuable, especially since access to tissue specimens is often difficult in these cases.

Background Stereotactic ablative radiotherapy (SABR) offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional therapies. However, optimal dose planning and delivery strategies are unelucidated and gastro-intestinal (GI) toxicity remains a key concern. Methods Patients with inoperable non-metastatic pancreatic cancer who received CyberKnife® SABR (18–36 Gy) in three fractions as primary, adjuvant, consolidation or re-treatment options were studied. Patient individualised planning and delivery variables were collected and their impact on patient outcome examined. Linear-quadratic (LQ) radiobiology modelling methods were applied to assess SABR parameters against a conventional fractionated radiotherapy schedule. Results In total 42 patients were included, 37 (88%) of whom had stage T4 disease. SABR was used > 6 months post-primary therapy to re-treat residual disease in 11 (26.2%) patients and relapsed disease in nine (21.4%) patients. SABR was an adjuvant to other primary therapy for 14 (33.3%) patients and was the sole primary therapy for eight (19.0%) patients. The mean (95% CI) planning target volume (PTV), prescription isodose, percentage cover, minimum dose to PTV and biological effective dose (BED) were 76.3(63.8–88.7) cc, 67.3(65.2–69.5)%, 96.6(95.5–97.7)%, 22.3(21.0–23.6) Gy and 50.3(47.7–53.0) Gy, respectively. Only 3/37 (8.1%) patients experienced Grade 3 acute toxicities. Two (4.8%) patients converted to resectable status and median freedom-from-local-progression (FFLP) and overall survival (OS) were 9.8 and 8.4 months, respectively. No late toxicity was experienced in 27/32 (84.4%) patients; however, four (12.5%) patients — of whom two had particularly large PTV, two had sub-optimal number of fiducials and three breached organ-at-risk (OAR) constraints—showed Grade 4 duodenal toxicities. Longer delivery time, extended treatment course and reduced percentage coverage additionally associated with late toxicity, likely reflecting parameters typically applied to riskier patients. Larger PTV size and longer treatment course associated with OS. Comparator regimen LQ modelling analysis indicated 50% of patients received minimum PTV doses less potent than a conventional radiotherapy regimen, indicating scope for dose escalation. Conclusion The results demonstrate the value of SABR for a range of indications in pancreatic cancer. Dose escalation to increase BED may improve FFLP and OS in inoperable, non-metastatic disease: however concomitant enhanced stringency for duodenal protection is critical, particularly for patients where SABR is more challenging.

Purpose Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on F-18-HX4 positron emission tomography (PET) imaging of NSCLC. Methods Positron emission tomography imaging data based on the hypoxia tracer F-18-HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO(2)) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy. Results Gross target volumes ranged between 6.2 and 859.6 cm(3), and the hypoxic fraction

For conventional radiotherapy treatment units, automated planning can significantly improve plan quality. For robotic radiosurgery, systems for automatic generation of clinically deliverable plans do not yet exist. For prostate stereotactic body radiation therapy (SBRT), few studies have systematically compared VMAT with robotic treatment.The multi-criteria autoplanning optimizer, developed at our institute, was coupled to the commercial treatment planning system of our robotic treatment unit, for fully automated generation of clinically deliverable plans (autoROBOT). The system was then validated by comparing autoROBOT plans with manually generated plans. Next, the autoROBOT system was used for systematic comparisons between autoROBOT plans and VMAT plans, that were also automatically generated (autoVMAT). CTV-PTV margins of 3 mm were used for autoROBOT (clinical routine) and autoVMAT plan generation. For autoVMAT, an extra plan was generated with 5 mm margin (often applied for VMAT). Plans were generated for a 4 × 9.5 Gy fractionation scheme.Compared to manual planning, autoROBOT improved rectum D[Formula: see text] (16%), V[Formula: see text] (75%) and D[Formula: see text] (41%), and bladder D[Formula: see text] (37%) (all p [Formula: see text] .002), with equal PTV coverage. In the autoROBOT and autoVMAT comparison, both with 3 mm margin, rectum doses were lower for autoROBOT by 5% for rectum D[Formula: see text] (p=.002), 33% for V[Formula: see text] (p=.001) and 4% for D[Formula: see text] (p=.05), with comparable PTV coverage and other OAR sparing. With 5 mm margin for VMAT, 18/20 plans had a PTV coverage lower than requested (95%) and all plans had higher rectum doses than autoROBOT (mean percentage differences of 13% for D[Formula: see text], 69% for V[Formula: see text] and 32% for D[Formula: see text] (all p.001)).The first system for fully automated generation of clinically deliverable robotic plans was built. Autoplanning did largely enhance robotic plan quality, compared to manual planning. Using autoplanning for both the robotic system and VMAT, superiority of non-coplanar robotic treatment compared to coplanar VMAT for prostate SBRT was demonstrated.

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/Ts), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed 0.14 (37.5% versus 11.1% for RCV 0.14. Diagnosis of >90% FPHs, NA

Introduction: Surgery is the standard treatment for early stage non-small-cell lung cancer (NSCLC). For medically inoperable patients, stereotactic ablative radiotherapy (SABR) has emerged as widely used standard treatment. The aim of this study was to analyze survival and patterns of tumor recurrence in patients with clinical stage I NSCLC treated with surgery or SABR.Methods: Clinical data from all subsequent fluoro-deoxyglucose positron emission tomography/computed tomography-based stage I NSCLC patients (cT1-T2aN0M0) treated with surgery or SABR at our center between 2007 and 2010 were collected. Primary end-points were overall survival and tumor recurrences/new primary lung tumors. Treatment groups were compared using multivariable Cox regression and competing risk analyses.Results: Three hundred-forty patients treated with surgery (n = 143) or SABR (n = 197) were included. Surgical patients were younger, had a better WHO performance status and less comorbidities. After adjustment for prognostic covariables, treatment did not influence overall survival (adjusted hazard ratio [HR], SABR versus surgery 1.07; 95% confidence interval [CI]: 0.74-1.54; p = 0.73). Local control and distant recurrence were equal, whereas locoregional recurrences were significantly more frequent after SABR compared with surgery (adjusted sub-HR 2.51; 95% CI: 1.10-5.70; p = 0.028). Nodal failure (HR: 2.16; 95% CI: 1.34-3.48) and distant metastases (HR: 2.12; 95% CI: 1.52-2.97), but not local failure (HR: 1.00; 95% CI: 0.53-1.89) predicted overall survival.Conclusions: In patients with fluoro-deoxyglucose positron emission tomography/computed tomography-based stage I NSCLC, SABR confers worse locoregional tumor control because of more nodal failures compared with surgery, stressing the need to improve mediastinal and hilar staging.

Summary Background The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. Methods Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a ( Findings 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0–47·3) for the SABR group and 35·4 months (18·9–40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85–100) in the SABR group compared with 79% (64–97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017–1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74–100) in the SABR group and 80% (65–97) in the surgery group (HR 0·69 [95% CI 0·21–2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3–4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). Interpretation SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. Funding Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

Background and purpose: Stereotactic ablative radiotherapy (SABR; or stereotactic body radiotherapy, SBRT) emerges as treatment option for pulmonary oligometastatic disease (OMD), but there are no studies comparing SABR with pulmonary metastasectomy (PME). We analysed consecutive patients referred via a university-hospital based multidisciplinary team.Material and methods: Patients were offered PME as first choice and SABR in case they were considered to be less suitable surgical candidates. Overall survival was the primary endpoint. Secondary endpoints were progression-free-survival, local control of treated metastases, and freedom-from-failure of a local-only treatment strategy without systemic therapy.Results: From 2007 until 2010, 110 patients were treated and analysed (PME, n = 68; SABR, n = 42). Median follow-up time was 43 months (minimally, 25). Estimated overall survival rates at one, three, and five years were 87%, 62%, and 41% for PME, and 98%, 60%, and 49% for SABR, respectively (logrank-test, p = 0.43). Local control at two years was 94% for SABR and 90% for PME. Progression-free survival was 17% at three years, but 43% of the patients still had not failed a local-only treatment strategy.Conclusions: Although SABR was second choice after PME, survival after PME was not better than after SABR. Prospective comparative studies are clearly required to define the role of both, SABR and PME in OMD. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

Background and purpose: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment.Material and methods: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK". Studies performing SRT during or within 30 days of targeted/immunotherapy, reporting severe (>= Grade 3) toxicity were included.Results: Concurrent treatment is mostly well tolerated in cranial SRT, but high rates of severe toxicity were observed for the combination with BRAF-inhibitors. The relatively scarce literature on extra cranial SRT shows a potential risk of increased toxicity when SRT is combined with EGFR-targeting tyrosine kinase inhibitors and bevacizumab, which was not observed for cranial SRT.Conclusions: This review gives a best -possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field. (C) 2016 The Author(s). Published by Elsevier Ltd.

BACKGROUND Despite technical developments in treatment delivery, radiation-induced lung toxicity (RILT) remains a crucial problem in thoracic radiotherapy. Clinically based RILT scores have their limitations, and more objective measures such as pulmonary functions tests (PFTs) might help to improve treatment strategies. PURPOSE To summarize the available evidence about the effect of dose to the lung in thoracic radiotherapy on forced expiratory volume in one second (FEV1) and diffusion capacity (DLCO) in patients with lung and esophageal cancer treated with curative intent. MATERIAL AND METHODS A systematic review following the PRISMA guidelines was performed, using MEDLINE and including clinical studies using (chemo)radiotherapy (CRT) or stereotactic ablative radiotherapy (SABR) for lung or CRT for esophageal cancer that reported both lung dose-volume histogram (DVH) parameters and changes in PFT results. Search terms included lung and esophageal neoplasms, respiratory function tests, and radiotherapy. RESULTS Fifteen studies met the inclusion criteria. Seven out of 13 studies on lung cancer reported significant declines (defined as a p value

Purpose: To investigate survival and local recurrence after stereotactic ablative radiotherapy (SABR) or threedimensional conformal radiotherapy (3D-CRT) administered for early-stage primary lung cancer and to investigate longitudinal changes of health-related quality of life (HRQOL) parameters after either treatment.Methods and Materials: Two prospective cohorts of inoperable patients with T1-2N0M0 primary lung tumors were analyzed. Patients received 70 Gy in 35 fractions with 3D-CRT or 60 Gy in three to eight fractions with SABR. Global quality of life (GQOL), physical functioning (PF), and patient-rated dyspnea were assessed using the respective dimensions of European Organization for Research and Treatment of Cancer Core Questionnaire-C30 and LC13. HRQOL was analyzed using multivariate linear mixed-effects modeling, survival and local control (LC) using the Kaplan-Meier method, Cox proportional hazards analysis, and Fine and Gray multivariate competing risk analysis as appropriate.Results: Overall survival (OS) was better after SABR compared with 3D-CRT with a HR of 2.6 (95% confidence interval [CI]: 1.5-4.8; p Conclusion: In this nonrandomized comparison of two prospective cohorts of medically inoperable patients with Stage I lung cancer, OS and LC were better after SABR. GQOL, PF, and patient-rated dyspnea were stable after SABR, whereas PF decreased after 3D-CRTapproaching clinical significance already at 1 year. (C) 2011 Elsevier Inc.

Purpose: To determine the accuracy of four-dimensional computed tomography (4D-CT) scanning techniques in institutions participating in a Phase III trial of surgery vs. stereotactic radiotherapy (SBRT) for lung cancer.Methods and Materials: All 9 centers performed a 4D-CT scan of a motion phantom (Quasar, Modus Medical Devices) in accordance with their in-house imaging protocol for SBRT. A cylindrical cedar wood insert with plastic spheres of 15 mm ((sic)15) and 30 mm ((sic)30) diameter was moved in a cosine-based pattern, with an extended period in the exhale position to mimic the actual breathing motion. A range of motion of R = 15 and R = 25 mm and breathing period of T = 3 and T = 6 s were used. Positional and volumetric imaging accuracy was analyzed using Pinnacle version 8.1 x at various breathing phases, including the mid-ventilation phase and maximal intensity projections of the spheres.Results: Imaging using eight CT scanners (Philips, Siemens, GE) and one positron emission tomography-CT scanner (Institution 3, Siemens) was investigated. The imaging protocols varied widely among the institutions. No strong correlation was found between the specific scan protocol parameters and the observed results. Deviations in the maximal intensity projection volumes averaged 1.9% (starting phase of the breathing cycle [(sic)]15, R = 15), 12.3% ((sic)15, R = 25), and -0.9% ((sic)30, R = 15). The end-expiration volume deviations (13.4%, (sic)15 and 2.5%, (sic)30), were, on average, smaller than the end-inspiration deviations (20.7%, (sic)15 and 4.5%, (sic)30), which, in turn, were smaller than the mid-ventilation deviations (32.6%, (sic)15 and 8.0%, (sic)30). A slightly larger variation in the mid-ventilation origin position was observed (mean, -0.2 mm; range, -3.6-4.2) than in the maximal intensity projection origin position (mean, -0.1 mm; range, -2.5-2.5). The range of motion was generally underestimated (mean, -1.5 mm; range, -5.5-1).Conclusions: Notable differences were seen in the 4D-CT imaging protocols for SBRT among centers. However, the observed deviations in target volumes were generally small. They were slightly larger for the mid-ventilation phases and smallest for the end-expiration phases. Steps to optimize and standardize the 4D-CT scanning protocols for SBRT are desirable. (c) 2011 Elsevier Inc.

Background A phase III multi-centre randomised trial (ROSEL) has been initiated to establish the role of stereotactic radiotherapy in patients with operable stage IA lung cancer. Due to rapid changes in radiotherapy technology and evolving techniques for image-guided delivery, guidelines had to be developed in order to ensure uniformity in implementation of stereotactic radiotherapy in this multi-centre study. Methods/Design A Quality Assurance Working Party was formed by radiation oncologists and clinical physicists from both academic as well as non-academic hospitals that had already implemented stereotactic radiotherapy for lung cancer. A literature survey was conducted and consensus meetings were held in which both the knowledge from the literature and clinical experience were pooled. In addition, a planning study was performed in 26 stage I patients, of which 22 were stage 1A, in order to develop and evaluate the planning guidelines. Plans were optimised according to parameters adopted from RTOG trials using both an algorithm with a simple homogeneity correction (Type A) and a more advanced algorithm (Type B). Dose conformity requirements were then formulated based on these results. Conclusion Based on current literature and expert experience, guidelines were formulated for this phase III study of stereotactic radiotherapy versus surgery. These guidelines can serve to facilitate the design of future multi-centre clinical trials of stereotactic radiotherapy in other patient groups and aid a more uniform implementation of this technique outside clinical trials.