Publications by authors named "Corinne Faivre-Finn"

150 Publications

Stereotactic Radiation for Lung Cancer: A Practical Approach to Challenging Scenarios.

J Thorac Oncol 2021 Apr 23. Epub 2021 Apr 23.

Washington University School of Medicine, St Louis, MO, USA. Electronic address:

Stereotactic body radiation therapy (SBRT) is an effective and well-tolerated treatment for medically inoperable patients with early-stage non-small cell lung carcinoma (NSCLC). SBRT is a noninvasive treatment involving the delivery of ablative radiation doses with high precision over the course of a few treatments. Relative to conventionally fractionated radiation, SBRT achieves superior local control and survival. SBRT utilization has increased dramatically over the past 15 years and is currently considered the standard-of-care in cases of inoperable early-stage NSCLC. It is being increasingly applied to more complex patient populations at higher risk of treatment-related toxicity. In these more complex patients, there is an increasing need to balance patient and treatment factors in selecting the optimal patients for SBRT. Here we review several challenging clinical scenarios commonly encountered in thoracic multidisciplinary tumor boards.
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http://dx.doi.org/10.1016/j.jtho.2021.04.002DOI Listing
April 2021

Outcomes of curative-intent radiotherapy in non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).

Radiother Oncol 2021 Apr 23. Epub 2021 Apr 23.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Department Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. Electronic address:

Outcomes of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD n=587) and interstitial lung disease (ILD n=34) treated with curative-intent radiotherapy were retrospectively investigated. Presence of ILD but not decreased forced expiratory volume in 1-second correlated with poor overall survival. Increased breathlessness and oxygen requirements after radiotherapy were observed in severe/very severe COPD and ILD.
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http://dx.doi.org/10.1016/j.radonc.2021.04.014DOI Listing
April 2021

Optimising use of 4D-CT phase information for radiomics analysis in lung cancer patients treated with stereotactic body radiotherapy.

Phys Med Biol 2021 Apr 21. Epub 2021 Apr 21.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom., The University of Manchester, Manchester, Manchester, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.

Purpose: 4D-CT is routine imaging for lung cancer patients treated with stereotactic body radiotherapy. No studies have investigated optimal 4D phase selection for radiomics. We aim to determine how phase data should be used to identify prognostic biomarkers for distant failure, and test whether stability assessment is required. A phase selection approach will be developed to aid studies with different 4D protocols, and account for patient differences.

Methods: 186 features were extracted from the tumour and peritumour on all phases for 258 patients. Feature values were selected from phase features using four methods: A) mean across phases, B) median across phases, C) 50% phase, and D) the most stable phase (closest in value to two neighbours), coined personalised selection. Four levels of stability assessment were also analysed, with inclusion of: 1) all features, 2) stable features across all phases, 3) stable features across phase and neighbour phases, and 4) features averaged over neighbour phases. Clinical-radiomics models were built for twelve combinations of feature type and assessment method. Model performance was assessed by concordance index and fraction of new information from radiomic features.

Results: The most stable phase spanned the whole range but was most often near exhale. All radiomic signatures provided new information for distant failure prediction. The personalised model had the highest concordance index (0.77), and 58% of new information was provided by radiomic features when no stability assessment was performed.

Conclusion: The most stable phase varies per-patient and selecting this improves model performance compared to standard methods. We advise the single most stable phase should be determined by minimising feature differences to neighbour phases. Stability assessment over all phases decreases performance by excessively removing features. Instead, averaging of neighbour phases should be used when stability is of concern. The models suggest that higher peritumoural intensity predicts distant failure.
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http://dx.doi.org/10.1088/1361-6560/abfa34DOI Listing
April 2021

Initial Clinical Experience of MR-Guided Radiotherapy for Non-Small Cell Lung Cancer.

Front Oncol 2021 10;11:617681. Epub 2021 Mar 10.

Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.

Curative-intent radiotherapy plays an integral role in the treatment of lung cancer and therefore improving its therapeutic index is vital. MR guided radiotherapy (MRgRT) systems are the latest technological advance which may help with achieving this aim. The majority of MRgRT treatments delivered to date have been stereotactic body radiation therapy (SBRT) based and include the treatment of (ultra-) central tumors. However, there is a move to also implement MRgRT as curative-intent treatment for patients with inoperable locally advanced NSCLC. This paper presents the initial clinical experience of using the two commercially available systems to date: the ViewRay MRIdian and Elekta Unity. The challenges and potential solutions associated with MRgRT in lung cancer will also be highlighted.
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http://dx.doi.org/10.3389/fonc.2021.617681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988221PMC
March 2021

MRI and CBCT for lymph node identification and registration in patients with NSCLC undergoing radical radiotherapy.

Radiother Oncol 2021 Mar 26;159:112-118. Epub 2021 Mar 26.

Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, UK; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.

Purpose: This study compared MRI to CBCT for the identification and registration of lymph nodes (LN) in patients with locally advanced (LA)-NSCLC, to assess the suitability of targeting LNs in future MR-image guided radiotherapy (MRgRT) workflows.

Method: Radiotherapy radiographers carried out Visual Grading Analysis (VGA) assessment of image quality, LN registration and graded their confidence in registration for each of the 24 LNs on CBCT and two MR sequences, MR1 (T2w Turbo Spin Echo) and MR2 (T1w DIXON water only image).

Results: Pre-registration image quality assessment revealed MR1 and MR2 as significantly superior to CBCT in terms of image quality (p ≤ 0.01). No significant differences were noted in interobserver variability for LN registration between CBCT, MR1 and MR2. Observers were more confident in their MR registrations compared to their CBCT based LN registrations (p ≤ 0.02).

Summary: Interobserver setup correction variability was not found to be significantly different between CBCT and MR. Image quality and registration confidence were found to be superior for MRI sequences. This is a promising step towards MR-guided radiotherapy for the treatment of LA-NSCLC.
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http://dx.doi.org/10.1016/j.radonc.2021.03.015DOI Listing
March 2021

Patient-reported outcomes with durvalumab by PD-L1 expression and prior chemoradiotherapy-related variables in unresectable stage III non-small-cell lung cancer.

Future Oncol 2021 Apr 15;17(10):1165-1184. Epub 2021 Feb 15.

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

We retrospectively investigated the impact of tumor PD-L1 expression and prior chemoradiotherapy (CRT)-related variables on patient-reported outcomes (PROs) from PACIFIC. PACIFIC was a Phase III study of durvalumab versus placebo after CRT in patients with unresectable, stage III non-small-cell lung cancer. If available, pre-CRT tumor tissue was tested for PD-L1 tumor-cell expression, scored at prespecified (25%) and (1%) cut-offs. PROs were assessed using EORTC QLQ C30/-LC13. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time across PD-L1 and CRT subgroups, with few clinically relevant differences between treatment arms. Time to deterioration was generally similar to the ITT population. Neither PD-L1 expression nor prior CRT-related variables influenced PROs with durvalumab therapy. NCT02125461 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-1102DOI Listing
April 2021

Safety of G-CSF with concurrent chemo-radiotherapy in limited-stage small cell lung cancer - Secondary analysis of the randomised phase 3 CONVERT trial.

Lung Cancer 2021 03 30;153:165-170. Epub 2021 Jan 30.

Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Sciences, University of Manchester, Manchester, UK.

Objectives: The use of granulocyte colony-stimulating factors (G-CSF) during concurrent chemo-radiotherapy (cCTRT) for small cell lung cancer is not recommended by the American Society of Clinical Oncology due to safety concerns. This secondary analysis explored the safety and the role of prophylactic G-CSF (proG-CSF) in the delivery of cCTRT.

Material And Methods: Secondary analysis of 487 patients treated as per protocol on the phase 3 CONVERT trial which randomized patients between once-daily RT or twice-daily.

Results: 180 of 487 eligible patients (37 %) received proG-CSF, 60 (33 %) as primary prophylaxis and 120 (67 %) as secondary prophylaxis following myelotoxic events. The regimen incidence of febrile neutropenia (FN) was 22 %. Its incidence in the proG-CSF group reduced significantly when proG-CSF was administered (22 % vs 10 %; OR 0.4; 95 %CI 0.2-0.7; p = 0.002). The rate of blood transfusion was higher in the proG-CSF group (51 % vs 31 %; OR 2.4; 95 %CI 1.6-3.5; p < 0.001). The incidence of severe thrombocytopenia was also higher is this group (28 % vs 15 %; OR 2.2; 95 %CI 1.4-3.5; p = 0.001). But this was significantly higher in those on secondary vs primary prophylaxis (34 % vs 15 %; OR 2.9; 95 %CI 1.3-7.4 p = 0.009) No differences observed in RT-related toxicity, treatment-related mortality or any survival outcomes. The optimal dose intensity (85 % or higher) of cisplatin was achieved in more patients within the proG-CSF group (75 % vs 67 %; OR 1.5; 95 %CI 0.9-2.3; p = 0.056).

Conclusion: There was no evidence that G-CSF directly caused myelotoxicity, instead most patients started G-CSF due to higher myelotoxicity risk. G-CSF maintained the planned dose intensity and there was no detrimental effect on survival. G-CSF may be considered as a supportive measure in this setting.
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http://dx.doi.org/10.1016/j.lungcan.2021.01.025DOI Listing
March 2021

Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial.

J Thorac Oncol 2021 May 19;16(5):860-867. Epub 2021 Jan 19.

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Introduction: In the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53-0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42-65; p < 0.0001; February 13, 2017) with manageable safety. Here, we report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized.

Methods: Patients with WHO performance status of 0 or 1 (and any tumor programmed death-ligand 1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg) or placebo, administered every 2 weeks (≤12 months), stratified by age, sex, and smoking history. OS and PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS and PFS rates were estimated by the Kaplan-Meier method.

Results: Overall, 709 of 713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of March 20, 2020 (median follow-up = 34.2 months; range: 0.2-64.9), updated OS (HR = 0.71; 95% CI: 0.57-0.88) and PFS (HR = 0.55; 95% CI: 0.44-0.67) remained consistent with the primary analyses. The median OS for durvalumab was reached (47.5 mo; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively.

Conclusion: These updated exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab after chemoradiotherapy. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression-free (placebo, 19.5%).
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http://dx.doi.org/10.1016/j.jtho.2020.12.015DOI Listing
May 2021

Small-cell lung cancer.

Nat Rev Dis Primers 2021 01 14;7(1). Epub 2021 Jan 14.

Department of Pediatrics, Stanford University, Stanford, CA, USA.

Small-cell lung cancer (SCLC) represents about 15% of all lung cancers and is marked by an exceptionally high proliferative rate, strong predilection for early metastasis and poor prognosis. SCLC is strongly associated with exposure to tobacco carcinogens. Most patients have metastatic disease at diagnosis, with only one-third having earlier-stage disease that is amenable to potentially curative multimodality therapy. Genomic profiling of SCLC reveals extensive chromosomal rearrangements and a high mutation burden, almost always including functional inactivation of the tumour suppressor genes TP53 and RB1. Analyses of both human SCLC and murine models have defined subtypes of disease based on the relative expression of dominant transcriptional regulators and have also revealed substantial intratumoural heterogeneity. Aspects of this heterogeneity have been implicated in tumour evolution, metastasis and acquired therapeutic resistance. Although clinical progress in SCLC treatment has been notoriously slow, a better understanding of the biology of disease has uncovered novel vulnerabilities that might be amenable to targeted therapeutic approaches. The recent introduction of immune checkpoint blockade into the treatment of patients with SCLC is offering new hope, with a small subset of patients deriving prolonged benefit. Strategies to direct targeted therapies to those patients who are most likely to respond and to extend the durable benefit of effective antitumour immunity to a greater fraction of patients are urgently needed and are now being actively explored.
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http://dx.doi.org/10.1038/s41572-020-00235-0DOI Listing
January 2021

Automated gross tumor volume contour generation for large-scale analysis of early-stage lung cancer patients planned with 4D-CT.

Med Phys 2021 Feb 30;48(2):724-732. Epub 2020 Dec 30.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.

Purpose: Patients with early-stage lung cancer undergoing stereotactic ablative radiotherapy receive four-dimensional computed tomography (4D-CT) for treatment planning. Often, an internal gross target volume (iGTV), which approximates the motion envelope of a tumor over the breathing cycle, is delineated without defining a gross tumor volume (GTV). However, the GTV volume and shape are important parameters for prognostic and dose modelling, and there is interest in radiomic features extracted from the GTV and surrounding tissue. We demonstrate and validate a method to generate the GTV from an iGTV contour to aid retrospective analysis on routine data.

Method: It is possible to reconstruct the geometry of a tumor with knowledge of tumor motion and the motion envelope formed during respiration. To demonstrate this, the tumor motion path was estimated with local rigid registration, and the iGTV positioned incrementally at stations along the reverse path. It is shown that the tumor volume is the largest set common to the intersection of the iGTV at these positions, hence can be derived. This was implemented for 521 lung lesions on 4D-CT. Eleven patients with a GTV delineation performed by a radiation oncologist on a reference phase (50%) were used for validation. The generated GTV was compared to that delineated by the expert using distance-to-agreement (DTA), volume, and distance between centres of mass. An overall success rate was determined by detecting registration inaccuracy and performing a quality check on the routine iGTV. For successfully generated contours, GTV volume was compared to iGTV volume in a prognostic model for overall survival.

Results: For the validation dataset, DTA mean (0.79 - 1.55 mm) and standard deviation (0.68 - 1.51 mm) were comparable to expected observer variation. Difference in volume was < 5 cm , and average difference in position was 1.21 mm. Deviations in shape and position were mainly caused by observer differences in iGTV and GTV interpretation as opposed to algorithm performance. For the complete dataset, an acceptable contour was generated for 94% of patients using statistical and visual assessment to detect failures. Generated GTV volumes improved prognostic model performance over iGTV volumes.

Conclusion: A method to generate a GTV from an iGTV and 4D-CT dataset was developed. This method facilitates data analysis of patients with early-stage lung cancer treated in the routine setting, that is, data mining, prognostic modeling, and radiomics. Generation failure detection removes the need for visual assessment of all contours, reducing a time-consuming aspect of big-data analysis. Favorable prognostic performance of generated GTV volumes over iGTV ones demonstrates opportunities to use this methodology for future study.
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http://dx.doi.org/10.1002/mp.14644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986204PMC
February 2021

Impact of prior chemoradiotherapy-related variables on outcomes with durvalumab in unresectable Stage III NSCLC (PACIFIC).

Lung Cancer 2021 01 26;151:30-38. Epub 2020 Nov 26.

H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

Introduction: The PACIFIC trial demonstrated that durvalumab significantly improved progression-free and overall survival (PFS/OS), versus placebo, in patients with Stage III NSCLC and stable or responding disease following concurrent, platinum-based chemoradiotherapy (CRT). A range of CT and RT regimens were permitted, and used, in the trial. We report post-hoc, exploratory analyses of clinical outcomes from PACIFIC according to CRT-related variables.

Methods: Patients were randomized 2:1 (1-42 days post-CRT) to up to 12 months durvalumab (10 mg/kg intravenously every 2 weeks) or placebo. Efficacy and safety were analyzed in patient subgroups defined by the following baseline variables: platinum-based CT (cisplatin/carboplatin); vinorelbine, etoposide, or taxane-based CT (all yes/no); total RT dose (<60 Gy/60-66 Gy/>66 Gy); time from last RT dose to randomization (<14 days/≥14 days); and use of pre-CRT induction CT (yes/no). Treatment effects for time-to-event endpoints were estimated by hazard ratios (HRs) from unstratified Cox-proportional-hazards models.

Results: Overall, 713 patients were randomized, of whom 709 received treatment in either the durvalumab (n/N = 473/476) or placebo arms (n/N = 236/237). Durvalumab improved PFS, versus placebo, across all subgroups (median follow up, 14.5 months; HR range, 0.34-0.63). Durvalumab improved OS across most subgroups (median follow up, 25.2 months; HR range, 0.35-0.86); however, the 95 % confidence interval (CI) of the estimated treatment effect crossed one for the subgroups of patients who received induction CT (HR, 0.78 [95 % CI, 0.51-1.20]); carboplatin (0.86 [0.60-1.23]); vinorelbine (0.79 [0.49-1.27]); and taxane-based CT (0.73 [0.51-1.04]); and patients who were randomized ≥14 days post-RT (0.81 [0.62-1.06]). Safety was broadly similar across the CRT subgroups.

Conclusion: Durvalumab prolonged PFS and OS irrespective of treatment variables related to prior CRT to which patients with Stage III NSCLC had previously stabilized or responded. Limited patient numbers and imbalances in baseline factors in each subgroup preclude robust conclusions.
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http://dx.doi.org/10.1016/j.lungcan.2020.11.024DOI Listing
January 2021

Cardiac Toxicity of Thoracic Radiotherapy: Existing Evidence and Future Directions.

J Thorac Oncol 2021 02 3;16(2):216-227. Epub 2020 Dec 3.

Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; The Christie NHS Foundation Trust, Manchester, United Kingdom.

The impact of radiotherapy on the heart has become an area of interest in recent years. Many different cardiac dose-volume constraints have been associated with cardiac toxicity and survival; however, no consistent constraint has been found. Many patients undergoing treatment for lung cancer have risk factors for cardiovascular disease or known cardiac comorbidities; however, there is little evidence on the effects of radiotherapy on the heart in these patients. We aim to provide a summary of the existing literature on cardiac toxicity of lung cancer radiotherapy, propose strategies to avoid and manage cardiac toxicity, and suggest avenues for future research.
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http://dx.doi.org/10.1016/j.jtho.2020.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870458PMC
February 2021

Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study.

Int J Radiat Oncol Biol Phys 2021 Apr 21;109(5):1341-1348. Epub 2020 Nov 21.

The Christie NHS Foundation Trust Wilmslow Road, Manchester, United Kingdom; Department of Radiotherapy Related Research, University of Manchester, Manchester, United Kingdom. Electronic address:

Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification.

Methods And Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues).

Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1).

Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.
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http://dx.doi.org/10.1016/j.ijrobp.2020.11.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955281PMC
April 2021

Role of radiotherapy in the management of brain metastases of NSCLC - Decision criteria in clinical routine.

Radiother Oncol 2021 01 11;154:269-273. Epub 2020 Nov 11.

Department of Radiation Oncology, Kantonsspital St. Gallen, Switzerland; Department of Radiation Oncology, University of Bern, Switzerland.

Background: Whole brain radiotherapy (WBRT) is a common treatment option for brain metastases secondary to non-small cell lung cancer (NSCLC). Data from the QUARTZ trial suggest that WBRT can be omitted in selected patients and treated with optimal supportive care alone. Nevertheless, WBRT is still widely used to treat brain metastases secondary to NSCLC. We analysed decision criteria influencing the selection for WBRT among European radiation oncology experts.

Methods: Twenty-two European radiation oncology experts in lung cancer as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) for previous projects and by the Advisory Committee on Radiation Oncology Practice (ACROP) for lung cancer were asked to describe their strategies in the management of brain metastases of NSCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies.

Results: Eight decision criteria (suitability for SRS, performance status, symptoms, eligibility for targeted therapy, extra-cranial tumour control, age, prognostic scores and "Zugzwang" (the compulsion to treat)) were identified. WBRT was recommended by a majority of the European experts for symptomatic patients not suitable for radiosurgery or fractionated stereotactic radiotherapy. There was also a tendency to use WBRT in the ALK/EGFR/ROS1 negative NSCLC setting.

Conclusion: Despite the results of the QUARTZ trial WBRT is still widely used among European radiation oncology experts.
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http://dx.doi.org/10.1016/j.radonc.2020.10.043DOI Listing
January 2021

Radiotherapy tumor volume for limited-stage small cell lung cancer: less is more.

Ann Transl Med 2020 Sep;8(17):1114

Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, The Christie NHS Foundation Trust, Manchester, UK.

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http://dx.doi.org/10.21037/atm.2020.04.45DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575968PMC
September 2020

CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer.

Clin Transl Radiat Oncol 2020 Nov 22;25:61-66. Epub 2020 Sep 22.

Newcastle University, Newcastle upon Tyne, England, UK.

Lung cancer is the leading cause of cancer mortality worldwide and most patients are unsuitable for 'gold standard' treatment, which is concurrent chemoradiotherapy. CONCORDE is a platform study seeking to establish the toxicity profiles of multiple novel radiosensitisers targeting DNA repair proteins in patients treated with sequential chemoradiotherapy. Time-to-event continual reassessment will facilitate efficient dose-finding.
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http://dx.doi.org/10.1016/j.ctro.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548952PMC
November 2020

Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy.

Phys Med 2020 Oct 7;78:173-178. Epub 2020 Oct 7.

Division of Cancer Science, University of Manchester, Manchester, UK; Radiotherapy Related Research, The Christie Foundation Trust, Manchester, UK.

Purpose: The aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health.

Methods: Vascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated.

Results: The volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status.

Conclusion: It was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.
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http://dx.doi.org/10.1016/j.ejmp.2020.09.010DOI Listing
October 2020

The MOMENTUM Study: An International Registry for the Evidence-Based Introduction of MR-Guided Adaptive Therapy.

Front Oncol 2020 7;10:1328. Epub 2020 Sep 7.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands.

MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT. In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305). The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.
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http://dx.doi.org/10.3389/fonc.2020.01328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505056PMC
September 2020

ESTRO ACROP guidelines for target volume definition in the thoracic radiation treatment of small cell lung cancer.

Radiother Oncol 2020 11 13;152:89-95. Epub 2020 Jul 13.

Department of Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany; Department of Radiation Oncology, University Hospital Freiburg, Germany.

Radiotherapy (RT) plays a major role in the treatment of small cell lung cancer (SCLC). Therefore, the ACROP committee was asked by ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)-radiotherapy (CRT), adjuvant RT for stages I-III SCLC and consolidation thoracic RT for stage IV disease. The aim of these guidelines is to standardise and optimise the process of RT treatment planning for clinical practice and prospective studies. The process for the development of the guidelines included the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing process within the committee. Firstly, we provide recommendations for both the imaging to be performed as part of the diagnostic work-up and for the RT planning process. Secondly, recommendations are made for target volume delineation including delineation of the primary gross tumour volume (GTV) and lymph node GTV and clinical tumour volume (CTV) expansion in the context of definitive and adjuvant RT. With regard to internal target volume (ITV) and planning target volume (PTV) definitions, we make recommendations about the management of geometric uncertainties and target motion. Finally, we provide our opinions on organ at risk (OAR) delineation and organisational issues to be considered.
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http://dx.doi.org/10.1016/j.radonc.2020.07.012DOI Listing
November 2020

Protecting the Heart: A Practical Approach to Account for the Full Extent of Heart Motion in Radiation Therapy Planning.

Int J Radiat Oncol Biol Phys 2020 11 4;108(4):1082-1090. Epub 2020 Jul 4.

Radiotherapy-Related Research, University of Manchester, Manchester, United Kingdom; The Christie NHS Trust, Manchester, United Kingdom.

Purpose: Emerging evidence suggests that the heart is more radiosensitive than previously assumed; therefore, accounting for heart motion in radiation therapy planning is becoming more critical. In this study, we determined how much heart delineations based on 3-dimensional (3D) computed tomography (CT), 4-dimensional (4D) average projection (AVG), and maximum intensity projection (MIP) images should be extended to represent the full extent of heart motion during 4D imaging acquisition.

Methods And Materials: The 3D and 4D CT scans of 10 lung cancer patients treated with stereotactic ablative radiation therapy were used. Median surfaces were derived from heart delineations of 3 observers on the 3D CT, AVG, MIP, and 25% exhale scans. Per patient, the 25% exhale contour was propagated on every phase of the 4D scan. The union of all 4D phase delineations (U4D) represented the full extent of heart motion during imaging acquisition. Surface distances from U4D to 3D, AVG, and MIP volumes were calculated. Distances in the most extreme surface points (1.5 cm most superoinferior, 10% most right/left/anteroposterior) were used to derive margins accounting only for systematic (delineation) errors.

Results: Heart delineations on the MIP were the closest to the full extent of motion, requiring only ≤2.5-mm margins. Delineations on the AVG and 3D scans required margins up to 3.4 and 7.1 mm, respectively. The largest margins were for the inferior, right, and anterior aspects for the delineations on the 3D, AVG, and MIP scans, respectively.

Conclusion: Delineations on 3D, AVG, or MIP scans required extensions for representing the heart's full extent of motion, with the MIP requiring the smallest margins. Research including daily imaging to determine the random components for the margins and dosimetric measurements to determine the relevance of creating a planning organ at risk volume of the heart is required.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.068DOI Listing
November 2020

SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection.

Eur Respir J 2020 11 12;56(5). Epub 2020 Nov 12.

Leeds Cancer Centre, St James's University Hospital, Leeds, UK.

Objectives: Stereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible.

Design And Methods: SABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates.

Results: Between July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3.

Conclusions: We conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.
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http://dx.doi.org/10.1183/13993003.00118-2020DOI Listing
November 2020

Practice Recommendations for Lung Cancer Radiotherapy During the COVID-19 Pandemic: An ESTRO-ASTRO Consensus Statement.

Int J Radiat Oncol Biol Phys 2020 07;107(4):631-640

Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria.

Background: The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic.

Methods: For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk-benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC.

Results: In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided.

Conclusion: This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.ijrobp.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836268PMC
July 2020

Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival.

Int J Radiat Oncol Biol Phys 2020 11 23;108(4):1073-1081. Epub 2020 Jun 23.

Division of Clinical Cancer Science, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Department of Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.

Purpose: For patients with lung cancer treated with radiation therapy, a dose to the heart is associated with excess mortality; however, it is often not feasible to spare the whole heart. Our aim is to define cardiac substructures and dose thresholds that optimally reduce early mortality.

Methods And Materials: Fourteen cardiac substructures were delineated on 5 template patients with representative anatomies. One thousand one hundred sixty-one patients with non-small cell lung cancer were registered nonrigidly to these 5 template anatomies, and their radiation therapy doses were mapped. Mean and maximum dose to each substructure were extracted, and the means were evaluated as input to prediction models. The cohort was bootstrapped into 2 variable reduction techniques: elastic net least absolute shrinkage and selection operator and the random survival forest model. Each method was optimized to extract variables contributing most to overall survival, and model coefficients were evaluated to select these substructures. The most important variables common to both models were selected and evaluated in multivariable Cox-proportional hazard models. A threshold dose was defined, and Kaplan-Meier survival curves plotted.

Results: Nine hundred seventy-eight patients remained after visual quality assurance of the registration. Ranking the model coefficients across the bootstraps selected the maximum dose to the right atrium, right coronary artery, and ascending aorta as the most important factors associated with survival. The maximum dose to the combined cardiac region showed significance in the multivariable model, a hazard ratio of 1.01/Gy, and P = .03 after accounting for tumor volume (P < .001), N stage (P < .01), and performance status (P = .01). The optimal threshold for the maximum dose, equivalent dose in 2-Gy fractions, was 23 Gy. Kaplan-Meier survival curves showed a significant split (log-rank P = .008).

Conclusions: The maximum dose to the combined cardiac region encompassing the right atrium, right coronary artery, and ascending aorta was found to have the greatest effect on patient survival. A maximum equivalent dose in 2-Gy fractions of 23 Gy was identified for consideration as a dose limit in future studies.
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http://dx.doi.org/10.1016/j.ijrobp.2020.06.031DOI Listing
November 2020

Radiomics as a personalized medicine tool in lung cancer: Separating the hope from the hype.

Lung Cancer 2020 08 2;146:197-208. Epub 2020 Jun 2.

Division of Cancer Sciences, University of Manchester, Manchester, UK.

Radiomics has become a popular image analysis method in the last few years. Its key hypothesis is that medical images harbor biological, prognostic and predictive information that is not revealed upon visual inspection. In contrast to previous work with a priori defined imaging biomarkers, radiomics instead calculates image features at scale and uses statistical methods to identify those most strongly associated to outcome. This builds on years of research into computer aided diagnosis and pattern recognition. While the potential of radiomics to aid personalized medicine is widely recognized, several technical limitations exist which hinder biomarker translation. Aspects of the radiomic workflow lack repeatability or reproducibility under particular circumstances, which is a key requirement for the translation of imaging biomarkers into clinical practice. One of the most commonly studied uses of radiomics is for personalized medicine applications in Non-Small Cell Lung Cancer (NSCLC). In this review, we summarize reported methodological limitations in CT based radiomic analyses together with suggested solutions. We then evaluate the current NSCLC radiomics literature to assess the risk associated with accepting the published conclusions with respect to these limitations. We review different complementary scoring systems and initiatives that can be used to critically appraise data from radiomics studies. Wider awareness should improve the quality of ongoing and future radiomics studies and advance their potential as clinically relevant biomarkers for personalized medicine in patients with NSCLC.
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http://dx.doi.org/10.1016/j.lungcan.2020.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383235PMC
August 2020

Radiotherapy-Related Lymphopenia Affects Overall Survival in Patients With Lung Cancer.

J Thorac Oncol 2020 10 14;15(10):1624-1635. Epub 2020 Jun 14.

Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom; Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.

Introduction: Lymphopenia after radiotherapy has an adverse effect on the patient's outcome. However, the relationship between radiotherapy dose delivery and lymphopenia is not fully understood. This work used image-based data mining to identify anatomical regions where the received dose is correlated with severe lymphopenia.

Methods: A total of 901 patients with lung cancer were analyzed. A Cox model was used to assess prognostic factors of overall survival (OS). Two matched groups were defined-patients with lymphopenia of grade 3 or higher and patients without lymphopenia of grade 3-based on tumor volume, baseline lymphocytes, and prescribed dose. Then, data mining was used to identify regions where dose correlates significantly with lymphopenia of grade 3 or higher. For this, dose matrices were aligned using registration of the computed tomography images to one reference patient. Mean dose distributions were obtained for the two groups, and organs of significance were detected. Dosimetric parameters from the identified organs that had the highest correlation with lymphocytes at nadir were selected. Multivariable analysis was conducted for lymphopenia of grade 3 or higher on the full lung cohort, and the model was tested on 305 patients with esophageal cancer.

Results: Adjusted Cox regression revealed that lymphopenia of grade 3 or higher is an independent factor of OS. The anatomical regions identified were the heart, lung, and thoracic vertebrae. Dosimetric parameters for lymphopenia included thoracic vertebrae V, mean lung dose, and mean heart dose, which were further validated in the esophageal cancer cohort.

Conclusions: We report that severe lymphopenia during radiotherapy is a poor prognostic factor for OS in patients with lung cancer and could be mitigated by minimizing thoracic vertebrae V, mean lung dose, and mean heart dose to limit the irradiation of stem cells and blood pool.
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http://dx.doi.org/10.1016/j.jtho.2020.06.008DOI Listing
October 2020

Reliability and prognostic value of radiomic features are highly dependent on choice of feature extraction platform.

Eur Radiol 2020 Nov 1;30(11):6241-6250. Epub 2020 Jun 1.

Division of Cancer Sciences, University of Manchester, Manchester, UK.

Objective: To investigate the effects of Image Biomarker Standardisation Initiative (IBSI) compliance, harmonisation of calculation settings and platform version on the statistical reliability of radiomic features and their corresponding ability to predict clinical outcome.

Methods: The statistical reliability of radiomic features was assessed retrospectively in three clinical datasets (patient numbers: 108 head and neck cancer, 37 small-cell lung cancer, 47 non-small-cell lung cancer). Features were calculated using four platforms (PyRadiomics, LIFEx, CERR and IBEX). PyRadiomics, LIFEx and CERR are IBSI-compliant, whereas IBEX is not. The effects of IBSI compliance, user-defined calculation settings and platform version were assessed by calculating intraclass correlation coefficients and confidence intervals. The influence of platform choice on the relationship between radiomic biomarkers and survival was evaluated using univariable cox regression in the largest dataset.

Results: The reliability of radiomic features calculated by the different software platforms was only excellent (ICC > 0.9) for 4/17 radiomic features when comparing all four platforms. Reliability improved to ICC > 0.9 for 15/17 radiomic features when analysis was restricted to the three IBSI-compliant platforms. Failure to harmonise calculation settings resulted in poor reliability, even across the IBSI-compliant platforms. Software platform version also had a marked effect on feature reliability in CERR and LIFEx. Features identified as having significant relationship to survival varied between platforms, as did the direction of hazard ratios.

Conclusion: IBSI compliance, user-defined calculation settings and choice of platform version all influence the statistical reliability and corresponding performance of prognostic models in radiomics.

Key Points: • Reliability of radiomic features varies between feature calculation platforms and with choice of software version. • Image Biomarker Standardisation Initiative (IBSI) compliance improves reliability of radiomic features across platforms, but only when calculation settings are harmonised. • IBSI compliance, user-defined calculation settings and choice of platform version collectively affect the prognostic value of features.
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http://dx.doi.org/10.1007/s00330-020-06957-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553896PMC
November 2020

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

Eur Respir J 2020 06 11;55(6). Epub 2020 Jun 11.

Dept of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including and () for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
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http://dx.doi.org/10.1183/13993003.00953-2019DOI Listing
June 2020

ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma.

Eur J Cardiothorac Surg 2020 07;58(1):1-24

Unit of Thoracic Surgery, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy.

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
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http://dx.doi.org/10.1093/ejcts/ezaa158DOI Listing
July 2020

Once daily versus twice-daily radiotherapy in the management of limited disease small cell lung cancer - Decision criteria in routine practise.

Radiother Oncol 2020 09 22;150:26-29. Epub 2020 May 22.

Department of Radiation Oncology, Kantonsspital St. Gallen, Switzerland; Department of Radiation Oncology, University of Bern, Switzerland.

Background: In limited disease small cell lung cancer (LD-SCLC), the CONVERT trial has not demonstrated superiority of once-daily (QD) radiotherapy (66 Gy) over twice-daily (BID) radiotherapy (45 Gy). We explored the factors influencing the selection between QD and BID regimens.

Methods: Thirteen experienced European thoracic radiation oncologists as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) were asked to describe their strategies in the management of LD-SCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies.

Results: Logistic reasons, patients' performance status and radiotherapy dose constraints were the three major decision criteria used by most experts in decision making. The use of QD and BID regimens was balanced among European experts, but there was a trend towards the BID regimen for fit patients able to travel twice a day to the radiotherapy site.

Conclusion: BID and QD radiotherapy are both accepted regimens among experts and the decision is influenced by pragmatic factors such as availability of transportation.
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http://dx.doi.org/10.1016/j.radonc.2020.05.004DOI Listing
September 2020

Impact of small residual setup errors after image guidance on heart dose and survival in non-small cell lung cancer treated with curative-intent radiotherapy.

Radiother Oncol 2020 11 14;152:177-182. Epub 2020 Apr 14.

Manchester Cancer Research Centre, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, UK.

Background And Purpose: A recent study of NSCLC patients showed small residual setup errors (shifts) in the direction of the heart following image-guidance were significantly related to overall survival. This study of the dosimetric effects of these residual shifts investigates the hypothesis that observed survival differences were related to a change in heart dose.

Materials And Methods: Accumulated doses including shifts for each fraction were determined for 475 NSCLC patients. Planning CTs and corresponding dose distributions were deformed to a reference. Image-based data-mining techniques were then applied to the difference between the planned and accumulated dose (Δdose) to determine where Δdose relates to 1-year survival. The significance of Δdose in the identified region was assessed using multivariable Cox analysis. The cohort was then split into octiles, based upon planned dose to the region, and multivariable Cox analysis performed for each sub-cohort to explore the dose response relationship. The identified dose threshold for damage was then tested in an independent validation cohort of 1482 NSCLC patients from the same institution.

Results: Permutation testing identified a small region in the heart base where Δdose significantly correlated with 1-year survival. Δdose in this region showed no correlation with common clinical variables, and was significant in multivariable Cox regression (p < 0.001, hazard ratio 1.221/Gy), with increasing change in dose from plan resulting in greater risk of death. Octile analysis revealed Δdose to be significant only in the 7th octile, planning dose 16.2-23.4 Gy, suggesting a steep dose-effect relation for heart damage in this range. Taking 16.2 Gy as a conservative threshold dose, this result was successfully validated, with a significant difference being seen between patients with a region dose above or below 16.2 Gy.

Conclusions: This study suggests the relation between residual set-up errors and survival is explained by changes in cardiac dose, and identifies an area at the heart base where dose is correlated with survival. Our results suggest the dose threshold for cardiac damage is between 16.2 and 23.4 Gy in the base of the heart, which was validated in an independent cohort. However, the dose effect in other regions of the heart should also be investigated.
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http://dx.doi.org/10.1016/j.radonc.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707351PMC
November 2020