Radiotherapy In Lung Cancer Patients Research Articles

USP9X-mediated REV1 deubiquitination promotes lung cancer radioresistance via the action of REV1 as a Rad18 molecular scaffold for cystathionine γ-lyase.

Radioresistance is a key clinical constraint on the efficacy of radiotherapy in lung cancer patients. REV1 DNA directed polymerase (REV1) plays an important role in repairing DNA damage and maintaining genomic stability. However, its role in the resistance to radiotherapy in lung cancer is not clear. This study aims to clarify the role of REV1 in lung cancer radioresistance, identify the intrinsic mechanisms involved, and provide a theoretical basis for the clinical translation of this new target for lung cancer treatment. The effect of targeting REV1 on the radiosensitivity was verified by in vivo and in vitro experiments. RNA sequencing (RNA-seq) combined with nontargeted metabolomics analysis was used to explore the downstream targets of REV1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify the content of specific amino acids. The coimmunoprecipitation (co-IP) and GST pull-down assays were used to validate the interaction between proteins. A ubiquitination library screening system was constructed to investigate the regulatory proteins upstream of REV1. Targeting REV1 could enhance the radiosensitivity in vivo, while this effect was not obvious in vitro. RNA sequencing combined with nontargeted metabolomics revealed that the difference result was related to metabolism, and that the expression of glycine, serine, and threonine (Gly/Ser/Thr) metabolism signaling pathways was downregulated following REV1 knockdown. LC-MS/MS demonstrated that REV1 knockdown results in reduced levels of these three amino acids and that cystathionine γ-lyase (CTH) was the key to its function. REV1 enhances the interaction of CTH with the E3 ubiquitin ligase Rad18 and promotes ubiquitination degradation of CTH by Rad18. Screening of the ubiquitination compound library revealed that the ubiquitin-specific peptidase 9 X-linked (USP9X) is the upstream regulatory protein of REV1 by the ubiquitin-proteasome system, which remodels the intracellular Gly/Ser/Thr metabolism. USP9X mediates the deubiquitination of REV1, and aberrantly expressed REV1 acts as a scaffolding protein to assist Rad18 in interacting with CTH, promoting the ubiquitination and degradation of CTH and inducing remodeling of the Gly/Ser/Thr metabolism, which leads to radioresistance. A novel inhibitor of REV1, JH-RE-06, was shown to enhance lung cancer cell radiosensitivity, with good prospects for clinical translation.

Dose-Escalated vs. Conventional Hypofractionated Radiotherapy for Lung Cancer Patients in Predominantly Central Locations

Hypofractionated radiation therapy (HFRT) is an increasingly utilized treatment option for patients with lung cancers unamenable to stereotactic body radiotherapy (SBRT). Conventional HFRT (C-HFRT) is often prescribed to 60 Gy in 15 fractions, which has a lower biologically effective dose (BED10 of 84.0) than SBRT. We compared outcomes of patients treated with a dose-escalated HFRT regimen (DE-HFRT, 72 Gy in 18 fractions, BED10 of 100.8) to those treated with C-HFRT. We aimed to evaluate local control (LC), overall survival (OS), and grade 3+ toxicity between patients who received C-HFRT vs. DE-HFRT as we hypothesized DE-HFRT may be superior/equivalent to C-HFRT. A database was created of all patients at our institution who received either thoracic C-HFRT or DE-HFRT between 2013 and 2020. Baseline variables were compared by chi-square analysis and logistic regression. We analyzed the association between treatment regimens with LC and OS (log-rank test and Cox proportional hazards regression), as well as grade 3+ toxicity. A total of 107 patients were included, among whom 55 (51.4%) received C-HFRT and 52 (48.6%) received DE-HFRT. Median age was 73, 88.8% of patients had non-small cell lung cancer, 81.3% received lung-only treatment, and 52.3% had an ultra-central tumor location (within 1 cm of proximal tracheobronchial tree, esophagus, or heart). Patients with DE-HFRT were more likely to have lung-only treatment (92.3% vs. 70.9%, p = 0.005) and stage I disease (47.1% vs 24.1%, p = 0.01) than those with C-HFRT, but had a similar proportion of ultra-central tumors (57.1% vs. 54.9%, p = 0.82). Patients with DE-HFRT had a non-statistically significant trend towards higher LC (2-year 81.0% vs. 72.3%, 3-year 77.3% vs 52.3%, HR 0.53 [95% CI 0.26-1.09], p = 0.09) and OS (2-year 61.3% vs. 44.8%, 3-year 44.9% vs 33.9%, HR 0.68 [95% CI 0.41-1.11], p = 0.13) compared to those with C-HFRT. Similar findings were noted among those with lung-only treatment. Among those with ultra-central tumors, patients with DE-HFRT had statistically significantly higher LC (2-year 86.6% vs 71.2%, 3-year 86.6% vs 42.2%, HR 0.26 [95% CI 0.08-0.84] p = 0.02) and a non-statistically significant trend towards higher OS (2-year 63.8% vs 40.0%, 3-year 46.2% vs 31.1% HR 0.55 [95% CI 0.28-1.09] p = 0.09) compared to those with C-HFRT. There was no statistically significant difference in grade 3+ toxicities between DE-HFRT and C-HFRT (15.4% vs. 10.9%, OR 1.48 [95% CI 0.47-4.61], p = 0.49). We noted promising local control and overall survival for patients treated with 72 Gy in 18 fractions compared to 60 Gy in 15 fractions, especially among those with ultra-central tumors. Grade 3+ toxicities were not significantly higher for patients undergoing dose escalation. Hence, our findings suggest that DE-HFRT to the lung is a safe and effective treatment regimen for highly selected patients who cannot undergo SBRT.

Whole brain atlas-based diffusion kurtosis imaging parameters for the evaluation of multiple cognitive-related brain microstructure injuries after radiotherapy in lung cancer patients with brain metastasis.

Whole brain radiation therapy (WBRT) can cause cognitive dysfunctions in lung cancer patients with brain metastasis (BM). Diffusion kurtosis imaging (DKI) can detect brain microstructural alterations sensitivly. We aimed to identify the potential of DKI parameters for early radiation-induced brain injury and investigate the association between microstructure changes and neurocognitive function (NCF) decline. Lung cancer patients with BM (n=35) who underwent WBRT in a single center in Zhejiang, China, were consecutively and prospectively enrolled between June 24th, 2020 and December 22nd, 2021, and the median follow-up time was 6.0 months (3.6-6.6 months). DKI and T1-weighted (T1W) MRI scans were acquired prior to and following WBRT. Diffusivity-based (mean diffusivity, MD; fractional anisotropy, FA) and kurtosis-based (mean kurtosis, MK; axial kurtosis, AK) parameters were calculated within the automated anatomical labeling (AAL) atlas-based regions. Reliable change indices practice effects (RCI-PE) scores of the Mini-Mental State Examination (MMSE) were calculated to determine significant neurocognitive decline by a one-sample t-test from baseline to 2-6 months post-WBRT. To assess the subacute induced effects within the whole brain, percentage changes of DKI parameters were evaluated at 170 atlas-based regions by a one-sample t-test. Linear regression analyses were used to evaluate the association between DKI parameter changes and RCI-PE scores. Finally, the study included 19 patients in the longitudinal follow-up. RCI-PE scores declined at 2-6 months post-WBRT (mean RCI-PE =-0.842, 95% CI, -0.376 to -1.310; P=0.002). With the atlas-based analysis of subacute effects after post-WBRT, a total of 28 regions changed in at least one diffusion parameter, revealing region-wise microstructural alterations in the brain. Significant correlations of at least one diffusion parameters with RCI-PEs were observed in 9 regions, such as the right orbital part of the inferior frontal gyrus [right IFGorb, r(AK) =0.47, P=0.03] and left middle temporal gyrus [left MTG, r(MK) =-0.49, P=0.03]. DKI parameters can be used to detect early microstructure changes and represent important imaging predictors for cognitive decline. The reported 9 regions are more particularly vulnerable to neurocognitive radiation-induced impairment for lung cancer patients with BM, representing potential dose-avoidance targets for cognitive function preservation.

On the correction of respiratory motion-induced image reconstruction errors in positron-emission tomography-guided radiation therapy

Free breathing (FB) positron emission tomography (PET) images are routinely used in radiotherapy for lung cancer patients. Respiration-induced artifacts in these images compromise treatment response assessment and obstruct clinical implementation of dose painting and PET-guided radiotherapy. The purpose of this study is to develop a blurry image decomposition (BID) method to correct motion-induced image-reconstruction errors in FB-PETs. Assuming a blurry PET is represented as an average of multi-phase PETs. A four-dimensional computed-tomography image is deformably registered from the end-inhalation (EI) phase to other phases. With the registration-derived deformation maps, PETs at other phases can be deformed from a PET at the EI phase. To reconstruct the EI-PET, the difference between the blurry PET and the average of the deformed EI-PETs is minimized using a maximum-likelihood expectation-maximization algorithm. The developed method was evaluated with computational and physical phantoms as well as PET/CT images acquired from three patients. The BID method increased the signal-to-noise ratio from 1.88±1.05 to 10.5±3.3 and universal-quality index from 0.72±0.11 to 1.0 for the computational phantoms, and reduced the motion-induced error from 69.9% to 10.9% in the maximum of activity concentration and from 317.5% to 8.7% in the full width at half maximum of the physical PET-phantom. The BID-based corrections increased the maximum standardized-uptake values by 17.7±15.4% and reduced tumor volumes by 12.5±10.4% on average for the three patients. The proposed image-decomposition method reduces respiration-induced errors in PET images and holds potential to improve the quality of radiotherapy for thoracic and abdominal cancer patients.

Real-World Patterns and Decision Drivers of Radiotherapy for Lung Cancer Patients in Romania: RADIO-NET Study Results.

Radiotherapy (RT) plays a crucial role in all stages of lung cancer. Data on recent real-world RT patterns and main drivers of RT decisions in lung cancer in Romania is scarce; we aimed to address these knowledge gaps through this physician-led medical chart review in 16 RT centers across the country. Consecutive patients with lung cancer receiving RT as part of their disease management between May-October 2019 (pre-COVID-19 pandemic) were included. Descriptive statistics were generated for all variables. This cohort included 422 patients: median age 63 years, males 76%, stages I-II 6%, III 43%, IV 50%, mostly adeno- and squamous cell carcinoma (76%), ECOG 0-1 50% at the time of RT. Curative intent RT was used in 36% of cases, palliative RT in 64%. Delays were reported in 13% of patients, mostly due to machine breakdown (67%). Most acute reported RT toxicity was esophagitis (19%). Multiple disease-, patient-, physician- and context-related drivers counted in the decision-making process. This is the first detailed analysis of RT use in lung cancer in Romania. Palliative RT still dominates the landscape. Earlier diagnosis, coordinated multidisciplinary strategies, and the true impact of the multimodal treatments on survival are strongly needed to improve lung cancer outcomes.

Automatic segmentation of the gross target volume in radiotherapy for lung cancer using transresSEUnet 2.5D Network

ObjectiveThis paper intends to propose a method of using TransResSEUnet2.5D network for accurate automatic segmentation of the Gross Target Volume (GTV) in Radiotherapy for lung cancer.MethodsA total of 11,370 computed tomograms (CT), deriving from 137 cases, of lung cancer patients under radiotherapy developed by radiotherapists were used as the training set; 1642 CT images in 20 cases were used as the validation set, and 1685 CT images in 20 cases were used as the test set. The proposed network was tuned and trained to obtain the best segmentation model and its performance was measured by the Dice Similarity Coefficient (DSC) and with 95% Hausdorff distance (HD95). Lastly, as to demonstrate the accuracy of the automatic segmentation of the network proposed in this study, all possible mirrors of the input images were put into Unet2D, Unet2.5D, Unet3D, ResSEUnet3D, ResSEUnet2.5D, and TransResUnet2.5D, and their respective segmentation performances were compared and assessed.ResultsThe segmentation results of the test set showed that TransResSEUnet2.5D performed the best in the DSC (84.08 ± 0.04) %, HD95 (8.11 ± 3.43) mm and time (6.50 ± 1.31) s metrics compared to the other three networks.ConclusionsThe TransResSEUnet 2.5D proposed in this study can automatically segment the GTV of radiotherapy for lung cancer patients with more accuracy.

A traffic light protocol workflow for image-guided adaptive radiotherapy in lung cancer patients.

Image-guided radiotherapy using cone beam-CT (CBCT) images is used to evaluate patient anatomy and positioning before radiotherapy. In this study we analyzed and optimized a traffic light protocol (TLP) used in lung cancer patients to identify patients requiring treatment adaptation. First, CBCT review requests of 243 lung cancer patients were retrospectively analyzed and divided into 6 pre-defined categories. Frequencies and follow-up actions were scored. Based on these results, the TLP was optimized and evaluated in the same way on 230 patients treated in 2018. In the retrospective study, a total of 543 CBCT review requests were created during treatment in 193/243 patients due to changed anatomy of lung (24%), change of tumor volume (24%), review of match (18%), shift of the mediastinum (15%), shift of tumor (15%) and other (4%). The majority of requests (474, 87%) did not require further action. In 6% an adjustment of the match criteria sufficed; in 7% treatment plan adaptation was required. Plan adaptation was frequently seen in the categories changed anatomy of lung, change of tumor volume and shift of tumor outside the PTV. Shift of mediastinum outside PRV and shift of GTV outside CTV (but inside PTV) never required plan adaptation and were omitted to optimize the TLP, which reduced the CBCT review requests by 23%. The original TLP selected patients that required a treatment adaptation, but with a high false positive rate. The optimized TLP reduced the amount of CBCT review requests, while still correctly identifying patients requiring adaptation.

The prognostic value of 18F-FDG PET/CT taken immediately after completion of radiotherapy for lung cancer treated with concurrent chemoradiotherapy: A pilot study

PurposeThe prognostic value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) taken immediately after completion of radiotherapy in lung cancer patients is not well known. The purpose of this study is to assess the prognostic value of PET/CT taken immediately after completion of radiotherapy in lung cancer patients. Materials and methodsPatients with primary lung cancer planned to undergo concurrent chemoradiotherapy were enrolled. Patients underwent PET/CT scans at 3 time points: before radiotherapy, within 24hours of completing radiotherapy (im-PET/CT), and 2–9 months after radiotherapy (post-PET/CT). Maximum standardized uptake value (SUVmax) was obtained. A post-PET/CT-SUVmax cut-off of 2.5 was determined as radiotherapy success. ResultsNineteen patients were enrolled. im-PET/CT-SUVmax for patients in the high post-PET/CT-SUVmax group was significantly higher than that of the low group (P=0.004). Receiver operator curve analysis indicated that im-PET/CT-SUVmax of 4.35 was an optimal cut-off value to discriminate between the two groups. Multivariable analysis showed that a high im-PET/CT-SUVmax was significantly associated with a high post-PET/CT-SUVmax (P=0.003). ConclusionPET/CT-SUVmax taken immediately following radiotherapy was associated with that evaluated 2–9 months after radiotherapy.

PO-1270 Reduction of the acute pulmonary toxicity with a VMAT adaptive radiotherapy in lung cancer patients

PO-1270 Reduction of the acute pulmonary toxicity with a VMAT adaptive radiotherapy in lung cancer patients

Evaluation of the Treatment Field Deviations in Different Set-up Positions During Thoracic Radiotherapy in Lung Cancer Patients

Evaluation of the Treatment Field Deviations in Different Set-up Positions During Thoracic Radiotherapy in Lung Cancer Patients

OA02.01 Assessment of Patient-Reported Outcomes in Lung cancer Patients Treated with Thoracic Radiation

Patient reported outcomes is limited in Chinese lung cancer patients with radiation therapy (RT) to thorax. The purpose of this study is to investigate Patient Reported Outcome Measures (PROM) at baseline and end for RT in lung cancer patients receiving RT to thorax.

Programmed cell death 1 inhibitors with or without concurrent brain radiotherapy for lung cancer patients with brain metastases.

Data focusing on the synergistic effect of programmed cell death 1 (PD-1) inhibitors and brain radiotherapy for brain metastases (BMs) in lung cancer is scarce. A total of 60 lung cancer patients receiving PD-1 inhibitors with or without brain radiotherapy were identified in this retrospective study. The primary endpoints were intracranial progression-free survival (iPFS), extracranial progression-free survival (PFS), and overall survival (OS) among three groups. Twenty-one patients received PD-1 inhibitors and concurrent brain radiotherapy, 20 patients were treated with PD-1 inhibitors and non-concurrent brain radiotherapy, and the other 19 patients were treated with PD-1 inhibitors alone. Patients in the concurrent group achieved a higher intracranial objective response rate (iORR, 61.1% vs. 29.4% vs. 25.0%) and a higher intracranial disease control rate (iDCR, 83.3% vs. 58.8% vs. 56.3%) compared with those in the non-concurrent group and PD-1 inhibitors alone group. The median iPFS was significantly longer in the concurrent group than the non-concurrent group and the PD-1 inhibitors alone group (9.8, 5.7, and 4.8 months, P=0.039, respectively). The median PFS were 9.2, 5.7 and 4.6 months (P=0.347) in the concurrent group, non-concurrent group and PD-1 inhibitors alone group. And the median OS were not reached, 12.1 and 6.9 months (P=0.206), respectively. Multivariate analysis revealed that the lack of concurrent brain radiotherapy was independently associated with a shorter iPFS. PD-1 inhibitors with concurrent brain radiotherapy achieved a higher iORR, iDCR, and iPFS in lung cancer patients with treated or newly diagnosed BMs.

PO-1198 Changes in radical radiotherapy for lung cancer patients in the UK during the COVID-19 pandemic.

PO-1198 Changes in radical radiotherapy for lung cancer patients in the UK during the COVID-19 pandemic.

Geometric and Dosimetric Changes in Tumor and Lung Tissue During Radiotherapy for Lung Cancer With Atelectasis.

Background and PurposeThis article retrospectively characterized the geometric and dosimetric changes in target and normal tissues during radiotherapy for lung cancer patients with atelectasis.Materials and MethodsA total of 270 cone beam computed tomography (CBCT) scans of 18 lung patients with atelectasis were collected. The degree and time of resolution or expansion of the atelectasis were recorded. The geometric, dosimetric, and biological changes in the target and lung tissue were also quantified.ResultsThere were two patients with expansion, four patients with complete regression, six patients with partial regression, and six patients with no change. The time of resolution or expansion varied. The tumor volume increased by 3.8% in the first seven fractions, then decreased from the 9th fraction, and by 33.4% at the last CBCT. In the LR direction, the average center of mass (COM), boundaries of the tumors gradually shifted mediastinally. In the AP direction, the COM of the tumors was shifted slightly in the posterior direction and then gradually shifted to the anterior direction; the boundaries of the tumors all moved mediastinally. In the SI direction, the COM of the tumors on the right side of the body was substantially shifted toward the head direction. The boundaries of the tumors varied greatly. D2, D98, Dmean, V95, V107, and TCP of the PTV were reduced during radiotherapy and were reduced to their lowest values during the last two fractions. The volume of the ipsilateral lung tended to increase gradually. The V5, V10, V20, V30, V40, and NTCP of the total lung gradually increased with the fraction.ConclusionsFor most patients, regression of the atelectasis occurred, and the volume of the ipsilateral lung tended to increase while the tumor volume decreased, and the COM and boundary of the tumors shifted toward mediastinum, which caused an insufficient dose to the target and an overdose to the lungs. Regression or expansion may occur for any fraction, and it is therefore recommended that CBCT be performed at least every other day.

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study.

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P < 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size.

A method for predictive modeling of tumor regression for lung adaptive radiotherapy.

The purpose of this work is to create a decision support methodology to predict when patients undergoing radiotherapy treatment for locally advanced lung cancer would potentially benefit from adaptive radiotherapy. The proposed methodology seeks to eliminate the manual subjective review by developing an automated statistical learning model to predict when tumor regression would trigger implementation of adaptive radiotherapy based on quantified anatomic changes observed in individual patients on-treatment cone beam computed tomographies (CTs). This proposed process seeks to improve the efficacy and efficiency of both the existing manual and automated adaptive review processes for locally advanced stage III lung cancer. A predictive algorithm was developed as a decision support tool to determine the potential utility of mid-treatment adaptive radiotherapy based on anatomic changes observed on 1158 daily CBCT images across 43 patients. The anatomic changes on each axial slice within specified regions-of-interest were quantified into a single value utilizing imaging similarity criteria comparing the daily CBCT to the initial simulation CT. The range of the quantified metrics for each fraction across all axial slices are reduced to specified quantiles, which are used as the predictive input to train a logistic regression algorithm. A "ground-truth" of the need for adaptive radiotherapy based on tumor regression was evaluated systematically on each of the daily CBCTs and used as the classifier in the logistic regression algorithm. Accuracy of the predictive model was assessed utilizing both a tenfold cross validation and an independent validation dataset, with the sensitivity, specificity, and fractional accuracy compared to the ground-truth. The sensitivity and specificity for the individual daily fractions ranged from 87.9%-94.3% and 91.9%-98.6% for a probability threshold of 0.2-0.5, respectively. The corresponding average treatment fraction difference between the model predictions and assessed ART "ground-truth" ranged from -2.25 to -0.07 fractions, with the model predictions consistently predicting the potential need for ART earlier in the treatment course. By initially utilizing a lower probability threshold, the higher sensitivity minimizes the chance of false negative by alerting the clinician to review a higher number of questionable cases. The proposed methodology accurately predicted the first fraction at which individual patients may benefit from ART based on quantified anatomic changes observed in the on-treatment volumetric imaging. The generalizability of the proposed method has potential to expand to additional modes of adaptive radiotherapy for lung cancer patients with observed underlying anatomic changes.

Comparison of Rapid to Standard Volumetric Modulated Arc Therapy for Palliative Radiotherapy in Lung Cancer Patients.

Patients with incurable lung cancer often present with debilitating symptoms that require urgent palliative radiotherapy. Volumetric modulated arc therapy (VMAT) provides several dosimetric advantages compared to basic non-conformal techniques, but involves complex planning resulting in a slower turn-around time for treatment. A simplified planning technique known as ‘rapid VMAT’ was developed with an aim to deliver palliative treatment to patients within 48 hours. The purpose of this study was to prospectively compare the dosimetric quality of rapid VMAT plans to standard VMAT plans. Fourteen consecutive rapid VMAT cases were re-planned de novo as per standard VMAT planning guidelines. Planning target volume (PTV) and organs at risk (OARs) were then compared. PTV coverage and dose to OARs including the spinal canal, lung, heart, and esophagus were similar between rapid and standard VMAT. Each plan was ready for treatment within 48 hours of the CT simulation. This study describes an expedited process for which palliative radiotherapy can be delivered to lung tumors with a similar robust quality that is provided for curative intent VMAT radiotherapy plans.

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

BackgroundThe 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.MethodsFor 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.ResultsIn 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.ConclusionThis 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.

The association between IDO activity and clinical prognosis in patients with early stage non-small cell lung cancer after stereotactic body radiotherapy.

e21054 Background: Immunity affects the efficacy of radiotherapy of lung cancer patients. Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that converts tryptophan (T) into heparin (K), which can promote immune suppression and assist tumor cells in immune evasion. The purpose of this study was to quantitatively analyze the immune activity of IDO in serum before and after SBRT, and to explore the changes in immune activity of IDO mediated by SBRT and its relationship with patient's survival. Methods: High-performance liquid chromatography and mass spectrometry were used to determine serum K and T in 30 patients with early non-small cell lung cancer before and after SBRT treatment. K: T stands for IDO activity. The Kaplan-Meier method and log-rank test were used to evaluate the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Cox proportional hazards model was used for univariate and multivariate analyses. Results: The median follow-up time was 37.4 months. The median PFS was 37.5 (95% CI, 31.0-44.0) months. The median survival was not reached. In all patients, lower post/pre kynurenine ratio correlated significantly with better PFS (HR = 0.31, 95% CI = 0.11-0.90, P = 0.032). The lower K: T ratio at post-RT received longer OS (HR = 0.27, 95% CI = 0.079-0.95, P = 0.042). In multivariate analysis, smoking &lt; 30 packs / year (P = 0.030), higher BED (P &lt; 0.001), and lower post/pre kynurenine (P = 0.043) were associated with better PFS. Lower K: T ratio post-RT (P = 0.040) and higher BED (P &lt; 0.001) were significantly associated with better OS. Conclusions: SBRT could alter IDO-mediated antitumor immune activity. The lower level of post/pre kynurenine ratio was significantly related with better PFS. The lower K: T ratio at post-RT was related with better OS. This study shows that IDO is a potentially valuable biomarker for monitoring the immune status and predicting survival in early NSCLC patients after SBRT.

Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement

BackgroundThe 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. MethodsFor 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. ResultsIn 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. ConclusionThis 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.