Peripheral Lung Tumors Research Articles

Implementation and Safety of a Single Fraction Peripheral Lung SBRT during the Global COVID-19 Pandemic, a Single Institution's Experience

Purpose/Objective(s)In response to the COVID-19 pandemic, a single fraction peripheral lung SBRT program was established to minimize potential COVID-19 exposures. This analysis aims to review clinical and treatment characteristics and associated toxicities in appropriately selected patients for this newly implemented technique.Materials/MethodsFrom May 2020 until Feb 2022, patients with peripheral lung tumors who met eligibility for 3400cGy in a single-fraction SBRT were treated at a tertiary academic cancer center. Patient, treatment, and toxicity parameters were retrospectively collected. Radiation dosimetric parameters were tabulated. Toxicities were quantified using CTCAE v5.0. Fisher's exact test was used to assess the differences in toxicities with clinical and dosimetric parameters. P-value < 0.05 was considered significant.Results23 patients were analyzed with a median age of 72 years (IRQ: 67-80) and 61% were females. 96% were smokers and 43% had COPD. All patients were ECOG ≤ 2. Majority of patients (96%) had early-stage primary lung cancer while 4% had pulmonary oligometastatic cancer. 39% of patients were treated on SABR-BRIDGE protocol while another 35% were medically inoperable and 26% refused surgery. A total of 23 peripheral lesions were treated with median greatest dimension of 1.7 cm (IQR: 1.4-2), ITV 4.9 cm3 (IQR: 3.6-8.4) and PTV 18.1 cm3 (IQR: 12.8-26). 87% had PTV within 1 cm form chest wall. After median follow-up of 6 months (IQR: 2-12), 52% of patients experienced grade ≤ 2 toxicities and no patients experienced ≥ grade 3. Radiation pneumonitis was the most common toxicity (35%; 5/8 with asymptomatic radiographic) followed by fatigue (30%) and chest wall pain (30%; 3/7 with grade 2). Two patients (9%) had rib fractures. Chest wall pain was significantly higher in patients with tumor diameter >1.5 cm (p = 0.02). No other significant difference was observed between clinical or dosimetric parameters and development of radiation pneumonitis or chest wall pain (p > 0.05). On the other hand, patients with ribs fractures were observed to have larger tumors (mean 3.2 vs. 1.7 cm), ITVs (mean 30 vs. 11 cm3), PTVs (mean 61 vs. 16 cm3), chest wall V30Gy (mean 4.8 vs. 0.4 cm3), and ribs V30Gy (mean 1.1 vs. 0.1 cm3). Only 1 patient had local failure after 12 months while another patient on SABR-BRIDGE underwent surgical resection after 6 months in which there were 20% viable tumor cells.ConclusionSingle fraction peripheral lung SBRT is a practical and safe option with no grade ≥ 3 toxicity. Our observed toxicities are within previously reported ranges. We observed that patients with rib fractures had larger tumors and higher V30Gy to chest wall and ribs. Careful patient selection and dosimetric efforts to limit high fall-off dose to chest wall and ribs may limit these toxicities.

Lung Tumor Motion and its Impact on Deep Learning Prediction of Local Recurrence

<h3>Purpose/Objective(s)</h3> In order for deep learning (DL) models to successfully predict local recurrence of lung tumors from image-based features, uncertainties of the model must be quantified. One potential source of uncertainty for the DL model is lung tumor motion. We aimed to evaluate the association of motion magnitude with the prediction accuracy of the DL model. We hypothesized that knowledge of motion will help quantify the uncertainties of prediction and guide the use of individualized risk predictions for lung radiotherapy. <h3>Materials/Methods</h3> Physician delineated gross tumor volume (GTV) of 19 patients were propagated to their corresponding 10 breathing phases of the 4DCT images using a commercial treatment planning system. A programming environment code was used to extract the contours and determine the centroid and volume bounded by the contours. Motion was determined from the displacement of the GTV centroid. The Euclidean distance was calculated and used as an aggregate measure of tumor motion magnitude. The 4DCT, free-breathing CT (FBCT) and maximum-intensity projection (MIP) images of the 18 patients were used as input to a pre-trained DL model. The 8-layer DL model was previously trained to predict local recurrence using FBCT images of 933 lung patients. Correlation between motion magnitude and prediction accuracy was calculated for 4DCT images in each respiratory phase, FBCT and MIP images. <h3>Results</h3> Tumor movement with a mean exertion of 1 cm [IQR: 0.72-1.53] was observed from the cohort with 47.4 % of patients subjected to abdominal compression, and 57.9% of patients had peripheral lung tumors. The standard deviation of DL scores obtained from each 4DCT image correlated with the magnitude of tumor motion (R² =0.45, p=0.005). Higher uncertainty in DL scores was attributed to the larger tumor motion. The average DL score obtained from the 10 phases of the 4DCT images of each patient was (i) highly associated with the DL scores obtained from the FBCT images (r = 0.99; p<0.0001), and (ii) closest to the DL score obtained with the end-inspiration images. In comparing the prediction performance across image acquisition types, MIP images yields a higher DL score compared to FBCT (<i>p</i><0.0001) or 4DCT images (<i>p</i> =<0.0001). <h3>Conclusion</h3> The impact of tumor motion on the range of DL scores for prediction of local recurrence was reported for the first time. Standard deviations of the DL scores increased with motion magnitude. However, when DL score was measured and averaged across the 10 phases of the 4DCT images, DL score correlated well with those obtained from the FBCT images. This preliminary finding suggests that despite the increased variation with larger motion, the DL score, when averaged across the sinusoidal breathing trajectory, correlates with the DL score obtained from the FBCT images that were used for treatment planning. However, caution should be exercised when using MIP images for local recurrence prediction since a higher DL score than the FBCT images used for planning will be observed.

Novel light delivery method for performing transbronchial photodynamic therapy ablation to treat peripheral lung cancer: A pilot study

BackgroundPhotodynamic therapy involves using a photosensitizer with l illumination and is recommended for treating early, centrally located lung cancers, but it is not a standard treatment for peripheral lung tumor.. We previously proposed a novel light delivery method, in which lipiodol is perfused into the bronchial tree to increase the scope of illumination via the fiber effect. Herein, we attempted this novel technique under electromagnetic bronchoscope guidance in a hybrid operation room where lipiodol facilitated light diffusion, and evaluated the effectiveness and feasibility of this technique for peripheral lung cancers. MethodsThis phase 0 pilot study included three patients with peripheral lung cancers (primary tumors ≤20-mm diameter). The photodynamic therapy was administered using Porfimer sodium as the photosensitizer, and an electromagnetic navigation bronchoscope in a hybrid operating room to guide the catheter to the tumor. This facilitated lipiodol infusion to encase the tumor and permit the transbronchial photodynamic therapy ablation. ResultsAdministering 630 nm 200 J/cm (400mW/500sec) energy through a 3-cm cylindrical diffusing laser fiber was safe; no significant acute complications were observed. Although the treatment outcome was unsatisfactory due to the low light dose, tumor pathology in one case revealed tumor necrosis, with no significant damage to the surrounding lung tissue. ConclusionsNovel light delivery transbronchial photodynamic therapy ablation for peripheral lung tumors is feasible and safe. Additional clinical trials may help determine the best illumination plan and light dose through multiple deliveries from multiple angles.

Current tendencies in diagnostics and treatment of peripheral benign lung tumors

The OBJECTIVE was to estimate clinical characteristics, diagnostic possibilities of computed tomography, minimally invasive methods of treatment of peripheral benign lung tumors.MATERIALS AND METHODS. Benign tumors were diagnosed in 311 (8.2 %) patients among 3789 people with bronchopulmonary neoplasms. A comparative assessment of the results of diagnostics and treatment of two groups of patients was carried out. The first group included 103 patients treated from 2003 to 2009, the second one – 128 patients treated from 2013–2020. 219 (94.8 %) patients were operated on. RESULTS. Benign lung tumors were more often detected at the age of 40-60 years – in 143 (61.9%) patients. The majority (184 patients, 79.6%) had no complaints. In 208 (90 %) patients, tumors were diagnosed during fluorography studies. In the second group, multispiral computed tomography revealed tumors less than 10 mm in size in 38 % of cases. The histological type of tumors was determined during intraoperative express histological test. In the second group, the number of thoracoscopies increased from 2.2 to 43 %, and – thoracotomies decreased from 94.5 to 52.3 %, the number of stapler resections of the lungs doubled, and the number of tumor enucleation decreased by half (p&lt;0.01). Thoracotomy was performed in case of deep tumor localization or large size of the tumor, it was impossible to find it endoscopically. Ten patients underwent lobectomy.CONCLUSION. Most peripheral benign lung tumors are asymptomatic. Computed tomography revealed tumors less than 1cm in size in 38 % of cases. To rule out malignancy, it is necessary to perform urgent surgery with an intraoperative express histological test. Thoracoscopy allows to remove surface peripheral tumors using the method of stapler resection.

Conformity of Fine Needle Aspiration Biopsy (FNAB) and Core Needle Biopsy (CNB) in peripheral lung tumor patients: A cross-sectional study

BackgroundThe problem of establishing lung tumor diagnostics is a challenge for clinicians, especially pulmonologists, in determining a definitive diagnosis of a lung tumor. ObjectiveAnalyzing the conformity of anatomical pathology results between fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) materials in peripheral lung tumors. MethodsA cross-sectional study was conducted from July 2019 to December 2020 with 66 participants. Participants were examined for CNB and FNAB, in which the results of these examinations were compared for conformity. Statistical analysis used the Kappa test with p < 0.05. ResultMost participants' tumor size was >70 mm, with FNAB results showing malignant category (39.5%), non-malignant (40.0%), and undiagnosed (38.9%; p = 0.757). Meanwhile, CNB examination showed a tumor size of >70 mm that was categorized into malignant (40.4%) and non-malignant (33.3%; p = 0.510). Most tumors were located in the right superior lobe that had FNAB results in the malignant (39.5%), non-malignant (30.0%) and undiagnosed (27.8%; p = 0.306) categories. The CNB examination also showed that most tumors were located in the right superior lobe, which had resulted in the category of malignant (34.4%), non-malignant (26.7%), and undiagnosed (75.0%; p = 0.240). Conformity of anatomical pathology results from FNAB and CNB subject such as malignancy category of 35 participants (74.5%), non-malignancy of 7 participants (53.8%) and undiagnosed of 4 participants (16.7%) with an accuracy of 69.69% (Κ = 0.43; p = 0.001). ConclusionThere is a conformity between the anatomical pathology results from FNAB and CNB materials for the diagnosis of lung tumors. CNB showed better results in the detection of anatomical malignancy and specimen adequacy.

Diagnostic Value of Bronchoscopy for Peripheral Metastatic Lung Tumors.

Simple SummaryMetastatic lung tumors are relatively common, and their pathological diagnosis is crucial for determining the appropriate treatment strategy. Although bronchoscopy is one biopsy method, its role has not been established for peripheral metastatic lung tumors. The present study aimed to investigate the value of bronchoscopy, using radial endobronchial ultrasound for diagnosis. We analyzed 235 lesions consecutively, and the overall diagnostic yield was 76.6%, which was slightly higher than the reported cumulative sensitivity for general peripheral pulmonary lesions. There were no serious complications. The results demonstrated that bronchoscopy is a valuable technique for peripheral metastatic lung tumors that combines diagnostic accuracy and safety. Moreover, the higher diagnostic yield was associated with the large lesion size, inner location, and visibility on radiography. These findings should contribute to the selection of biopsy methods for metastatic lung tumors and improve the diagnostic yield.Although lungs are one of the most frequent sites of metastasis for malignant tumors, little has been reported about the value of bronchoscopy for lung metastases presenting with peripheral pulmonary lesions (PPLs). This retrospective cohort study investigated the diagnostic value of bronchoscopy for peripheral metastatic lung tumors. Consecutive patients who underwent diagnostic bronchoscopy with radial endobronchial ultrasound for PPLs and were finally diagnosed with metastatic lung tumors from April 2012 to March 2019 were included. We analyzed 235 PPLs, with a median size of 18.8 mm. The overall diagnostic yield was 76.6%. In a multivariable analysis, large lesion size (>20.0 mm vs. <20.0 mm: 87.6% vs. 67.7%, p = 0.043, OR = 2.26), inner location (inner 2/3 vs. outer 1/3: 84.8% vs. 69.1%, p = 0.004, OR = 2.79), and visibility on radiography (visible vs. invisible: 83.2% vs. 56.1%, p = 0.015, OR = 3.29) significantly affected the diagnostic yield. Although a positive bronchus sign tended to have a higher yield, no significant difference was observed (81.8% vs. 70.6%, p = 0.063). Only one case of lung abscess was observed, with no serious complications. In conclusion, bronchoscopy is a valuable technique for peripheral metastatic lung tumors, with good diagnostic accuracy and safety.

Clinical efficacy of ct-guided transthoracic needle biopsy of peripheral lung lesions

To evaluate the effectiveness of a step-by-step protocol for GT-guided transthoracic biopsy in verification of peripheral lung tumors. A retrospective analysis of the results of GT-guided transthoracic biopsies of focal lung neoplasms was performed between October 2019 and December 2020. The analysis included the results of 176 biopsies in 158 patients. Primary biopsy was informative in 139 (87.97%) out of 158 patients. There were 155 (88.07%) informative and 21 (11.93%) non-informative biopsies. Lung adenocarcinoma was diagnosed in 41 (25.95%) patients, squamous cell carcinoma in 35 (22.15%) patients, and small cell carcinoma in 9 (5.7%) patients. There were 17 (10.76%) patients with uninformative biopsy results. Sensitivity, specificity and accuracy were 86%, 95.5%, and 87.8%, respectively. PPV was 98.9%, NPV - 58.3%. Various complications occurred after 65 (36.93%) out of 176 biopsies (95% CI 30.15-44.27). Pneumothorax followed by pleural drainage was detected after 8 (4.55%) biopsies. Accuracy of a step-by-step protocol for transthoracic biopsy was 88% that is not inferior to similar results in large-scale studies devoted to specialized navigation systems.

Effect of abdominal compression on target movement and extension of the external boundary of peripheral lung tumours treated with stereotactic radiotherapy based on four-dimensional computed tomography

BackgroundThis study aimed to investigate the effect of abdominal compression on tumour motion and target volume and to determine suitable planning target volume (PTV) margins for patients treated with lung stereotactic body radiotherapy (SBRT) based on four-dimensional computed tomography (4DCT).MethodsTwenty-three patients diagnosed to have a peripheral pulmonary tumour were selected and divided into an all lesions group (group A), an upper middle lobe lesions group (group B), and a lower lobe lesions group (group C). Two 4DCT scans were performed in each patient, one with and one without abdominal compression. Cone beam computed tomography (CBCT) was performed before starting treatment. The gross target volumes (GTVs) were delineated and internal gross target volumes (IGTVs) were defined. IGTVs were generated using two methods: (1) the maximum intensity projections (MIPs) based on the 4DCT were reconstructed to form a single volume and defined as the IGTVMIP and (2) GTVs from all 10 phases were combined to form a single volume and defined as the IGTV10. A 5-mm, 4-mm, and 3-mm margin was added in all directions on the IGTVMIP and the volume was constructed as PTVMIP5mm, PTVMIP4mm, and PTVMIP3mm.ResultsThere was no significant difference in the amplitude of tumour motion in the left–right, anterior–posterior, or superior-inferior direction according to whether or not abdominal compression was applied (group A, p = 0.43, 0.27, and 0.29, respectively; group B, p = 0.46, 0.15, and 0.45; group C, p = 0.79, 0.86, and 0.37; Wilcoxon test). However, the median IGTVMIP without abdominal compression was 33.67% higher than that with compression (p = 0.00), and the median IGTV10 without compression was 16.08% higher than that with compression (p = 0.00). The median proportion of the degree of inclusion of the IGTVCBCT in PTVMIP5mm, PTVMIP4mm, and PTVMIP3mm ≥ 95% was 100%, 100%, and 83.33%, respectively.ConclusionsAbdominal compression was useful for reducing the size of the IGTVMIP and IGTV10 and for decreasing the PTV margins based on 4DCT. In IGTVMIP with abdominal compression, adding a 4-mm margin to account for respiration is feasible in SBRT based on 4DCT.

Influence of target dose heterogeneity on dose sparing of normal tissue in peripheral lung tumor stereotactic body radiation therapy

ObjectiveTo evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT).MethodsBased on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff.ResultsWhen MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively.ConclusionsFor peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.

The Conformity of Anatomical Pathology Results between Core-Needle Biopsy and Fine-Needle Aspirate Biopsy in Peripheral Lung Tumors

The Conformity of Anatomical Pathology Results between Core-Needle Biopsy and Fine-Needle Aspirate Biopsy in Peripheral Lung Tumors

Improving interinstitutional and intertechnology consistency of pulmonary SBRT by dose prescription to the mean internal target volume dose

PurposeDose, fractionation, normalization and the dose profile inside the target volume vary substantially in pulmonary stereotactic body radiotherapy (SBRT) between different institutions and SBRT technologies. Published planning studies have shown large variations of the mean dose in planning target volume (PTV) and gross tumor volume (GTV) or internal target volume (ITV) when dose prescription is performed to the PTV covering isodose. This planning study investigated whether dose prescription to the mean dose of the ITV improves consistency in pulmonary SBRT dose distributions.Materials and methodsThis was a multi-institutional planning study by the German Society of Radiation Oncology (DEGRO) working group Radiosurgery and Stereotactic Radiotherapy. CT images and structures of ITV, PTV and all relevant organs at risk (OAR) for two patients with early stage non-small cell lung cancer (NSCLC) were distributed to all participating institutions. Each institute created a treatment plan with the technique commonly used in the institute for lung SBRT. The specified dose fractionation was 3 × 21.5 Gy normalized to the mean ITV dose. Additional dose objectives for target volumes and OAR were provided.ResultsIn all, 52 plans from 25 institutions were included in this analysis: 8 robotic radiosurgery (RRS), 34 intensity-modulated (MOD), and 10 3D-conformal (3D) radiation therapy plans. The distribution of the mean dose in the PTV did not differ significantly between the two patients (median 56.9 Gy vs 56.6 Gy). There was only a small difference between the techniques, with RRS having the lowest mean PTV dose with a median of 55.9 Gy followed by MOD plans with 56.7 Gy and 3D plans with 57.4 Gy having the highest. For the different organs at risk no significant difference between the techniques could be found.ConclusionsThis planning study pointed out that multiparameter dose prescription including normalization on the mean ITV dose in combination with detailed objectives for the PTV and ITV achieve consistent dose distributions for peripheral lung tumors in combination with an ITV concept between different delivery techniques and across institutions.

Human Cadaveric Artificial Lung Tumor-Mimic Training Model.

Introduction: An important phase in surgical training is gaining experience in real human anatomical situations. When a cadaver is available it may complement the various artificial practice models. However, it is often necessary to supplement the characteristics of the cadavers with a simulation of a tumor. Our objective was to develop an easy-to-create, realistic artificial tumor-mimic model for peripheral lung tumor resection practice. Methods: In our work we injected barium sulphate enriched silicone suspension into 10 isolated, non-fixed lungs of human cadavers, through the puncture of the visceral pleura. Four lesions–apical, hilar and two peripheral–were created in each of ten specimens. After fixation CT scans were obtained and analyzed. The implanted tumor-mimics were examined after anatomical preparation and slicing. Also performed CT-guided percutaneous puncture was also performed to create the lesions in situ in two lungs of human cadavers. Results: Analyzing the CT data of 10 isolated lungs, out of 40 lesions, 34 were nodular (85.0%) and in the nodular group five were spiculated (12.5%). Satellite lesions were formed in two cases (5.0%). Relevant outflow into vessels or airway occurred in five lesions (12.5%). Reaching the surface of the lung occured in 11 lesions (27.5%). The tumor-mimics were elastic and adhered well to the surrounding tissue. The two lesions, implanted via percutaneous puncture, both were nodular and one also showed lobulated features. Conclusion: Our artificial tumor-mimics were easy to create, varied in shape and size, and with percutaneous implantation the lesions provide a model for teaching every step of a surgical procedure.

Cryobiopsy in Lung Cancer Diagnosis-A Literature Review.

Optimizing the diagnosis of lung cancer represents a challenge, as well as a necessity, for improving the low survival of these patients. Flexible bronchoscopy with forceps biopsy is one of the key diagnostic procedures used for lung tumors. The small sample size and crush artifacts are several factors that can often limit access to a complete diagnosis, therefore leading to the need of repeating the bronchoscopy procedure or other invasive diagnostic methods. The bronchoscopic cryobiopsy is a recent technique that proved its utility in the diagnosis of both endobronchial and peripheral lung tumors. In comparison with conventional forceps biopsy, studies report a higher diagnostic yield and a superior quality of the collected samples for both the histopathological and the molecular diagnosis of lung cancer. This method shows promising results in sampling lung tissue, alone, or in conjunction with fluoroscopy or radial endobronchial ultrasound (r-EBUS). With a good safety and cost-benefit profile, this novel method has the potential to improve the diagnosis, and therefore the management of lung cancer patients. The objective of this narrative review is to provide a comprehensive review of the recent data regarding the advantages of cryobiopsy and r-EBUS in lung cancer diagnosis.

Patient individual phase gating for stereotactic radiation therapy of early stage non-small cell lung cancer (NSCLC)

Stereotactic body radiotherapy (SBRT) applies high doses and requires advanced techniques to spare surrounding tissue in the presence of organ motion. In this work patient individual phase gating is investigated. We studied peripheral and central primary lung tumors. The internal target volume (ITV) was defined including different numbers of phases picked from a 4D Computed tomography (CT) defining the gating window (gw). Planning target volume (PTV) reductions depending on the gw were analyzed. A treatment plan was calculated on a reference phase CT (rCT) and the dose for each breathing phase was calculated and accumulated on the rCT. We compared the dosimetric results with the dose calculated when all breathing phases were included for ITV definition. GWs including 1 to 10 breathing phases were analyzed. We found PTV reductions up to 38.4%. The mean reduction of the lung volume receiving 20 Gy due to gating was found to be 25.7% for peripheral tumors and 16.7% for central tumors. Gating considerably reduced esophageal doses. However, we found that simple reduction of the gw does not necessarily influence the dose in a clinically relevant range. Thus, we suggest a patient individual definition of the breathing phases included within the gw.

P05.13 Central vs Peripheral Thoracic Malignancies Treated with SBRT: Early Outcomes of a Prospective Quality of Life Study

Thoracic malignancies in close proximity to central mediastinal structures are known to have a higher rate of treatment-related toxicity following stereotactic body radiation therapy (SBRT). Intrinsic damage secondary to tumor invasion may contribute to this increased toxicity and could be identified by pretreatment quality of life metrics. The appropriate dose fractionation schedule as well as daily treatment schedule that may mitigate the aforementioned central toxicity remains nebulous. We reviewed patients on a prospective trial assessing quality of life before and after SBRT and stratified based on central versus peripheral anatomical location. In this single institutional study, patients were enrolled on a prospective quality of life trial approved by the local Institutional Review Board. All patients were evaluated by a multidisciplinary thoracic oncology team and were diagnosed with thoracic malignancy amenable to stereotactic body radiation therapy delivered in 5 or fewer treatment fractions on an every other day schedule. Central tumors were defined as those within 2 cm of central mediastinal structures including the proximal bronchial tree. Patients underwent pre-and post-treatment quality of life questionnaires including the prospectively validated EORTC Quality of Life Core questionnaire (QLQ-C30 version 3) and Supplemental Lung Cancer module questionnaire (QLQ-LC13). Baseline differences between groups were analyzed using the Mann-Whitney U and Chi-squared tests. Score comparisons for EORTC questionnaires pre- and post- SBRT were conducted using the Wilcoxon signed-rank test. All statistics were performed in SPSS, version 24. A total of 31 patients from February 2018 to February 2020 were enrolled with a median age of 70 (59-90) years. The majority of patients had an ECOG of 1 (n = 15) and the most common histology was adenocarcinoma (n = 17). A total of 13 patients were found to have central lung tumors. There were no significant pretreatment differences in age, performance status, gender or the predefined EORTC questionnaire-specific subcategorized functional, quality of life, or symptom domains between patients diagnosed with central versus peripheral tumors. Following SBRT, there were notable, statistically significant improvements in the Emotional functioning (EF) domain (pre- and post- treatment median: 61.5 and 91.7, respectively, z=-2.01, p=.044) and the Cognitive functioning (CF) domain (pre- and post- treatment median: 75.0 and 91.7, respectively z=-2.06, p=.039) in patients treated for central lung tumors. Similar improvements were not observed in patients treated for peripheral lung tumors. There were no significant changes in any other functional, symptom, or quality of life domain following treatment for either group. Pretreatment EORTC quality of life metrics did not demonstrate significant differences in patients diagnosed with central versus peripheral thoracic malignancies in our prospective cohort. However, patients with central lung tumors experienced significant improvements in their EF and CF domains following SBRT. These findings suggest patients with central lung tumors may experience greater psychological distress from their disease independent of self-reported physical symptom burden.

An Automated knowledge-based planning routine for stereotactic body radiotherapy of peripheral lung tumors via DCA-based volumetric modulated arc therapy.

PurposeTo develop a knowledge‐based planning (KBP) routine for stereotactic body radiotherapy (SBRT) of peripherally located early‐stage non‐small‐cell lung cancer (NSCLC) tumors via dynamic conformal arc (DCA)‐based volumetric modulated arc therapy (VMAT) using the commercially available RapidPlanTM software. This proposed technique potentially improves plan quality, reduces complexity, and minimizes interplay effect and small‐field dosimetry errors associated with treatment delivery.MethodsKBP model was developed and validated using 70 clinically treated high quality non‐coplanar VMAT lung SBRT plans for training and 20 independent plans for validation. All patients were treated with 54 Gy in three treatments. Additionally, a novel k‐DCA planning routine was deployed to create plans incorporating historical three‐dimensional‐conformal SBRT planning practices via DCA‐based approach prior to VMAT optimization in an automated planning engine. Conventional KBPs and k‐DCA plans were compared with clinically treated plans per RTOG‐0618 requirements for target conformity, tumor dose heterogeneity, intermediate dose fall‐off and organs‐at‐risk (OAR) sparing. Treatment planning time, treatment delivery efficiency, and accuracy were recorded.ResultsKBPs and k‐DCA plans were similar or better than clinical plans. Average planning target volume for validation was 22.4 ± 14.1 cc (7.1–62.3 cc). KBPs and k‐DCA plans provided similar conformity to clinical plans with average absolute differences of 0.01 and 0.01, respectively. Maximal doses to OAR were lowered in both KBPs and k‐DCA plans. KBPs increased monitor units (MU) on average 1316 (P < 0.001) while k‐DCA reduced total MU on average by 1114 (P < 0.001). This routine can create k‐DCA plan in less than 30 min. Independent Monte Carlo calculation demonstrated that k‐DCA plans showed better agreement with planned dose distribution.ConclusionA k‐DCA planning routine was developed in concurrence with a knowledge‐based approach for the treatment of peripherally located lung tumors. This method minimizes plan complexity associated with model‐based KBP techniques and improve plan quality and treatment planning efficiency.

Bronchoscopic treatments for early-stage peripheral lung cancer: Are we ready for prime time?

Lung cancer is the leading cause of cancer-related death worldwide and surgical lobectomy remains the preferred therapy for patients with early-stage NSCLC. Medical comorbidities and advanced age preclude resection in many patients and minimally invasive ablative therapies are needed for treatment. Stereotactic ablative radiation is established as an effective modality in this patient group, although may be contraindicated in some patients with prior radiation exposure, comorbidities or centrally positioned tumours. Percutaneous ablative methods are available, although are frequently associated with significant complications. Numerous endoscopic ablative techniques are under evaluation. With a more favourable safety profile and the ability to provide diagnosis and staging information potentially within a single procedure, there is a strong rationale for development of bronchoscopic ablative modalities. In the following article, the authors aim to explore the role bronchoscopic ablation may play in treatment of peripheral lung tumours, and to describe a pathway to establishing these modalities as part of routine care. The current status of several bronchoscopic ablative options is discussed in detail.

Bronchoscopic light delivery method for peripheral lung cancer photodynamic therapy.

BackgroundTrans-bronchoscope treatment for early stage small peripheral lung cancer, such as photodynamic therapy (PDT), has been investigated. However, despite the efficacy of PDT, light delivery issues limit its application. A method of administering mineral oil with a high refractive index (RI) was previously proposed to enhance light delivery in branched or bent anatomic structures. Lipiodol has a high RI and an exhaustive history of use as a contrast medium for bronchography. We aimed to determine whether the use of lipiodol, like mineral oil, could enhance the illumination effect and therapeutic range of PDT for peripheral lung tumors.MethodsWe injected lipiodol into a pig lung model, guided by a bronchoscope under fluorescent surveillance, to simulate future treatment in humans, and then illuminated with PDT laser fiber to the lipiodol-infused lung to test the technique feasibility in a pig orally administered 20 mg/kg of 5-aminolevulinicc acid (5-ALA) 2 hours before treatment. We also attempted to determine the maximal tolerable light dose in this pilot study for the future studies in human.ResultsWe successfully injected lipiodol into peripheral lungs by this technique. The pig could tolerate up to a total of 40 mL of lipiodol and 800 J of red light, without severe acute fetal injury in a non-cancerous lung.ConclusionsThe technique of injecting lipiodol using bronchoscopy under fluorescent guidance was feasible in a pig model. We can apply the guide sheath through bronchoscopy under fluoroscope inspection. Lipiodol can be used as a light diffuser for the peripheral lung tumor PDT model. No severe lethal acute lung injury was caused by this PDT model under careful manipulation. Additional studies evaluating the dose correlation of the photosensitizer and light are needed.

Evidence for Expanding Invasive Mediastinal Staging for Peripheral T1 Lung Tumors

Guidelines recommend invasive mediastinal staging for patients with non-small cell lung cancer and a "central" tumor. However, there is no consensus definition for central location. As such, the decision to perform invasive staging largely remains on an empirical foundation. Should patients with peripheral T1 lung tumors undergo invasive mediastinal staging? All participants with a screen-detected cancer with a solid component between 8 and 30mm were identified from the National Lung Screening Trial. After translation of CT data, cancer location was identified and the X, Y, Z coordinates were determined as well as distance from the main carina. A multivariable logistic regression model was constructed to evaluate for predictors associated with lymph node metastasis. Three hundred thirty-two participants were identified, of which 69 had lymph node involvement (20.8%). Of those with lymph node metastasis, 39.1%were N2. There was no difference in rate of lymph node metastasis based on tumor size (OR, 1.03; P= .248). There was also no statistical difference in rate of lymph node metastasis based on location, either by distance from the carina (OR, 0.99; P= .156) or tumor coordinates (X: P= .180; Y: P= .311; Z: P= .292). When adjusted for age, sex, histology, and smoking history, there was no change in the magnitude of the risk, and tests of significance were not altered. Our data indicate a high rate of N2 metastasis among T1 tumors and no significant relationship between tumor diameter or location. This suggests that patients with small, peripheral lung cancers may benefit from invasive mediastinal staging.

Stereotactic body radiotherapy and systemic dose chemotherapy for locally advanced lung cancer, single-arm phase II study.

e21081 Background: The outcomes for locally advanced non-small cell lung cancer (NSCLC) are overall poor. This is a single arm phase 2 study (Clinical trials.gov NCT02568033) evaluating the role of stereotactic body radiosurgery (SBRT) along with full dose systemic chemotherapy in the treatment of unresectable stage 2 and stage 3 NSCLC. Methods: patients were treated with SBRT to all sites of gross disease. Dosing consisted of 60 Gy in 3 fractions for peripheral lung tumors, 50 Gy in 5 fractions for central lung tumors, and 40-50 Gy in 5 fractions for hilar and mediastinal lymph nodes. Chemotherapy was histology dependent and consisted of 4 cycles, there was a 7 days break between chemotherapy and SBRT. Quality of life was measured using FACT-L. Results: Twenty two patients were enrolled and analyzed. 17 (77 %) were stage III and 19 (86%) had lymph node involvement. Median follow-up for all patients was 23.1 months. Median overall survival is 27.2 months. Overall survival at one year was 82% and overall survival at two years was 53%. Two year regional failure rate 19%. Two year distant failure rate 47.2%. Quality of life scores at one year were available for 12 patients and were unchanged compared to baseline. Acute toxicity grade 3 or greater was seen in 6 patients and late toxicity grade 3 or higher was seen in 2 patients. Conclusions: A combination of SBRT and full dose chemotherapy appears to be a safe and effective treatment for locally advanced NSCLC and warrants further investigation. Clinical trial information: NCT02568033 .