Radiotherapy For Lung Tumors Research Articles

Multi-institutional phase II study on the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy for lung tumors

Background and purposeThis study aimed to evaluate the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) for lung tumors. Materials and methodsPatients with cStage I primary lung cancer or metastatic lung cancer with an expected range of respiratory motion of ≥10 mm were eligible for the study. The prescribed dose was 50 Gy in four fractions. A gimbal-mounted linac was used for DTT-SBRT delivery. The primary endpoint was local control at 2 years. ResultsForty-eight patients from four institutions were enrolled in this study. Forty-two patients had primary non-small-cell lung cancer, and six had metastatic lung tumors. DTT-SBRT was delivered for 47 lesions in 47 patients with a median treatment time of 28 min per fraction. The median respiratory motion during the treatment was 13.7 mm (range: 4.5–28.1 mm). The motion-encompassing method was applied for the one remaining patient due to the poor correlation between the abdominal wall and tumor movement. The median follow-up period was 32.3 months, and the local control at 2 years was 95.2% (lower limit of the one-sided 85% confidence interval [CI]: 90.3%). The overall survival and progression-free survival at 2 years were 79.2% (95% CI: 64.7%–88.2%) and 75.0% (95% CI: 60.2%–85.0%), respectively. Grade 3 toxicity was observed in one patient (2.1%) with radiation pneumonitis. Grade 4 or 5 toxicity was not observed. ConclusionDTT-SBRT achieved excellent local control with low incidences of severe toxicities in lung tumors with respiratory motion.

109 - Tumour location is important in selecting patients who may benefit from abdominal compression when receiving stereotactic radiotherapy for lung tumours

109 - Tumour location is important in selecting patients who may benefit from abdominal compression when receiving stereotactic radiotherapy for lung tumours

Four-Dimensional Computed Tomography-Based Correlation of Respiratory Motion of Lung Tumors With Implanted Fiducials and an External Surrogate

PurposeOur purpose was to assess the suitability of airway-implanted internal fiducial markers and an external surrogate of respiratory motion for motion management during radiation therapy of lung tumors. Methods and MaterialsWe analyzed 4-dimensional computed tomography scans acquired during radiation therapy simulation for 28 patients with lung tumors who had anchored fiducial markers bronchoscopically implanted inside small airways in or near the tumor in a prospective trial. We used a linear mixed model to build population-based correlative models of tumor and surrogate motion. The first 24 of the 28 patients were used to build correlative models, and 4 of the 28 consecutive patients were excluded and used as an internal validation cohort. Of the 24 patients from the model building cohort, all were used for the models based on the internal fiducial. The external surrogate was completely visualized in 11 patients from the model building cohort, so only those were used for the models based on the external surrogate. Furthermore, we determined the predicted residual error sum of squares for our correlative models, which may serve as benchmarks for future research. ResultsThe motion of the internal fiducials was significantly associated with the tumor motion in the anterior-posterior (P < .0001) and superior-inferior (SI) directions (P < .0001). We also observed a strong correlation of the external surrogate anterior-posterior motion to the tumor dominant SI motion (P < .0001). In the validation cohort, the internal fiducial SI motion was the only reliable predictor of lung tumor motion. ConclusionsThe internal fiducials appear to be more reliable predictors of lung tumor motion than the external surrogate. The suitability of such airway-implanted internal fiducial markers for advanced motion management techniques should be further investigated. Although the external surrogate seems to be less reliable, its wide availability and noninvasive application support its clinical utility, albeit the greater uncertainty will need to be compensated for.

A Phase II Trial of Individualized Stereotactic Ablative Radiotherapy for Lung Tumors (iSABR)

Stereotactic ablative radiotherapy (SABR) is an effective treatment for lung tumors, but can result in toxicity such as chest wall pain and life-threatening damage to central lung structures. We hypothesized that while larger tumors require higher dose, small tumors up to 10cc in volume can be controlled with biologically effective dose < 100Gy. In this phase II single-arm trial, we tested the hypothesis that individualizing lung SABR dose and fractionation to tumor size, location, and histology would result in excellent local control with acceptable toxicity. The trial was conducted at two centers in the United States and Japan (NCT# redacted for blinded review).Patients in three groups were enrolled: initial diagnosis of non-small cell lung cancer (NSCLC), AJCC 7th edition stage T1-3 N0 M0 (group 1); new primary NSCLC with history of NSCLC, or multiple synchronously diagnosed NSCLCs (group 2); and lung metastases from NSCLC or another primary site (group 3). Up to four tumors could be treated with once-daily SABR. There were six dose/fractionation schedules used, depending on gross tumor volume (≤10cc, 10-30cc, > 30cc) and location (peripheral vs. central). Larger tumors received higher dose and central tumors generally received lower dose per fraction. Dose ranged from 25Gy in one fraction for 0-10cc peripheral tumors to 60Gy in 8 fractions for > 30cc central tumors. Colorectal cancer metastases were treated to higher dose, at least 50Gy in 4 fractions. The primary endpoint was per-group cumulative incidence of local recurrence at 1 year (recurrence of treated tumor within same lobe), with distant recurrence and death as competing risks. Treated tumor recurrence (recurrence with epicenter within 1cm of PTV) and toxicity were also analyzed.A total of 217 patients were enrolled from 2011-2018 (some patients were enrolled multiple times). Median age was 72, 59% were male, and 69% were current/former smokers. There were 240 treatment courses and 285 tumors treated (range 1-3 tumors per course). 211 tumors were peripheral and 74 were central. Tumor size distribution was: ≤10cc, 74%; 10-30cc, 19%; > 30cc, 7%. The most common dose was 25Gy in one fraction (158 tumors). Median follow-up was 30 months (range 2-95). Median overall survival was 57 months. Local recurrence data are currently being updated and will be presented at the meeting. The rate of grade 2 or higher pneumonitis was 16/217 (7%) and grade 3 or higher pneumonitis was 3/217 (1%). The rate of grade 2 or higher chest wall pain was 13/217 (6%). One patient had a grade 5 adverse event, developing pulmonary hemorrhage that was possibly related to radiotherapy, 17 months after treatment of a large central NSCLC.Individualized SABR to lung cancers resulted in excellent local control and favorable toxicity profile.

12\u202f\xd7\u20096\u202fGy stereotactic radiotherapy for lung tumors. Is there a\xa0difference in response between lung metastases and primary bronchial carcinoma?

PurposeThe aim of this study was to evaluate the safety and long-term tumor control after stereotactic radiotherapy (SRT) with 12 × 6 Gy of patients with primary bronchial carcinoma (BC) or with pulmonary metastases (MET) of various solid tumors. Local progression-free survival (LPFS), progression-free survival (PFS), overall survival (OS), and prognostic factors were compared.MethodsBetween May 2012 and January 2020, 168 patients with 206 pulmonary lesions (170 MET and 36 primary BC) were treated with 12 × 6 Gy (BED10 116 Gy). The irradiated pulmonary MET were from the following cancers: 47 (27.6%) head and neck, 37 (21.8%) rectum or colon, 30 (17.6%) bronchial, 13 (7.6%) malignant melanoma, 9 (5.3%) esophageal, 9 (5.3%) sarcoma, and 25 (14.8%) other.ResultsThe median follow-up was 16.26 months (range: 0.46–89.34) for BC and 19.18 months (0.89–91.11) for MET. Survival rates at 3 years were: OS 43% for BC and 35% for MET; LPFS BC 96% and MET 85%; PFS BC 35% and MET 29%. The most frequently observed grade 3 adverse events (AEs) were pneumonitis (5.9% BC, 4.8% MET), pulmonary fibrosis (2.9% BC, 4% MET), and pulmonary embolism (2.9% BC, 0.8% MET). The favorable prognostic effects on overall survival of patients with MET were female gender (log-rank: p < 0.001), no systemic progression (log-rank; p = 0.048, multivariate COX regression p = 0.039), and malignant melanoma histology (log-rank; p = 0.015, multivariate COX regression p = 0.020). For patients with BC, it was tumor location within the lower lobe (vs. upper lobe, log-rank p = 0.027). LPFS of patients with metastatic disease was beneficially influenced by female gender (log-rank: p = 0.049).ConclusionThe treatment concept of 12 × 6 Gy is associated with 96% local progression-free survival for BC and 85% for pulmonary metastases after 3 years. There was no difference in response after SRT of primary lung carcinoma or pulmonary metastases.

High-dose hypofractionated pencil beam scanning carbon ion radiotherapy for lung tumors: Dosimetric impact of different spot sizes and robustness to interfractional uncertainties.

The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors. CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions. Standard spots (SS) were compared to big spots (BS). Plans were recalculated on multiple 4DCTs acquired within 3 weeks from treatment simulation and rigidly registered with planning images using bone matching. Warped dose distributions were generated using deformable image registration and accumulated on the planning 4DCTs. Target coverage (D98%, D95% and V95%) and dose to lung were evaluated in the recalculated and accumulated dose distributions. Comparable target coverage was obtained with both spot sizes (p = 0.53 for D95%). The mean lung dose increased of 0.6 Gy(RBE) with BS (p = 0.0078), still respecting the dose constraint of a 4-fraction stereotactic treatment for the risk of radiation pneumonitis. Statistically significant differences were found in the recalculated and accumulated D95% (p = 0.048 and p = 0.024), with BS showing to be more robust. Using BS, the average degradations of the D98%, D95% and V95% in the accumulated doses were -2.7%, -1.6% and -1.5%. Gated 4DRRO was highly robust against setup and motion uncertainties. BS increased the dose to healthy tissues but were more robust than SS. The selected optimization settings guaranteed adequate target coverage during the simulated treatment course with acceptable risk of toxicity.

Abstract PO-067: The transactivation domain of TWIST1 is required for TWIST1-induced aggressiveness in non-small cell lung cancer

Abstract Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer mortality. Although therapeutic advances have been made, resistance to treatments remain high and the overall survival is still dismal. The high expression of the transcription factor TWIST1 strongly correlates with invasive and metastatic cancers, and is generally attributed to the epithelial-to-mesenchymal transition phenotype. We have demonstrated that TWIST1 can antagonize the induction of fail-safe programs as oncogene (KrasG12D)-induced senescence (OIS) in primary NSCLC tumor. OIS suppression by TWIST1 required increased global O-GlcNAcylation, which perhaps can also impact DNA repair and radiation response. As TWIST1 is essential for development, deciphering the critical domains and downstream transcriptional targets required for pro-tumorigenicity and radioresistance may allow the identification of new therapeutic strategies by targeting TWIST1. We created a transactivation-null TWIST1 mutant, by mutation of phenylalanine 191 to glycine, genetically engineered mouse model (GEMM) utilizing the tetracycline-inducible gene expression system. In these GEMMs, doxycycline treatment allows a concomitant induction of KrasG12D oncogene (R) with TWIST1 (T) or with TWIST1F191G mutant (F) expression, specifically in the lung epithelium directed by CCSP promoter-rtTA (C) transgene. CRT mice presented a more aggressive tumor progression and a shorter survival (median= 15.6 weeks) compared to CR (31 weeks). TWIST1F191G expression in CRF abrogates these effects (26.7 weeks) suggesting that the TWIST1 transactivation domain is required for TWIST1-dependent accelerated tumorigenesis. CRT mice, HBEC, and H460 cells overexpressing TWIST1 showed radiation resistance. A second KrasG12D lung tumor GEMM with induction of TWIST1 prior to 15Gy lung tumor irradiation showed lung tumor stasis compared to regression without TWIST1 expression. Histological analysis showed a strong expression of TWIST1 in CRT lungs while CRF showed a progressive loss over time suggesting that TWIST1F191G was non-functional and conferred no selective advantage. CRT mice also had lung tumors with higher proliferation (by Ki67), reduced apoptosis (by cleaved caspase3) and a decreased cell cycle arrest (by p16) compared to CR lung tumors. In comparison, CRF mice lung tumors did not show any change in cell death but showed increased p16 cell cycle arrest marker suggesting that the transactivation domain of TWIST1 is important for the suppression of OIS. We are exploring similar in vitro phenotypes using a primary immortalized HBEC cell lines co-transfected with HRasG12V oncogene and TWIST1 versus TWIST1 transactivation mutant. In future work, we are investigating the role of the TWIST1 transactivation domain in the induction of O-GlcNAcylation and the stabilization and/or activation of critical targets for OIS suppression and radiation resistance, with the goal of identifying new therapeutic targets and radiosensitizers. Citation Format: Audrey Lafargue, Hailun Wang, Sivarajan T. Chettiar, Rajendra P. Gajula, Caleb Smack, Ismaeel Siddiqui, Kekoa Taparra, Christine Lam, Francesca Carrieri, Katriana Nugent, Natasha Zachara, Phuoc T. Tran. The transactivation domain of TWIST1 is required for TWIST1-induced aggressiveness in non-small cell lung cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-067.

Flattening filter free stereotactic body radiation therapy for lung tumors: outcomes and predictive factors.

BackgroundStereotactic body radiation therapy (SBRT) using flattening filter free (FFF) has been commonly used, however, its outcomes and predictive factors in lung tumors are limiting. Thus, we aim to assess the clinical outcomes of this approach and identify factors associated with outcomes in patients with early stage non-small cell lung cancer (NSCLC) and oligometastatic/oligoprogressive lung tumor (OLT).MethodsPatients who underwent lung SBRT with FFF were retrospectively reviewed. All patients were delivered using volumetric modulated arc therapy (VMAT) technique. The primary outcome was local control (LC). The secondary outcomes were overall survival (OS) and toxicities. We assessed the association between LC and various factors in OLT.ResultsFrom February 2014 to July 2019, ninety-four patients and 129 lesions with median follow-up time of 30 months were included in the analysis. Twenty-six patients with 26 lesions were early NSCLC, while 68 patients with 103 lesions were OLT, 41.7% of which were from colorectal cancers (CRC) and 18.5% were from primary lung cancers. Two-year LC was 88.9% and 85.7% for early NSCLC and OLT, respectively. Two-year OS was significantly higher for early NSCLC than OLT (83.3% vs. 68.7%, P=0.035). In the multivariate analysis for OLT, CRC origin (hazard ratio, HR 10.59, 95% CI: 2.29–48.95, P=0.003) and gross tumor volume (GTV) mean BED10 ≤147 Gy (HR 5.16, 95% CI: 1.13–23.59, P=0.034) were significantly associated with higher local failure (LF). Most of the acute grade 1–2 toxicities were radiation pneumonitis (26.5%). No grade 3–5 event was observed.ConclusionsThis study confirmed the clinical efficacy and safety of lung SBRT using FFF-technique. Our findings support the role of using a high BED10 regimen to achieve good LC for OLT and the potential role for dose escalation for primary CRC.

Clinical Practice and Workflow of Radiation Therapy for Lung Tumors at the University of Tokyo Hospital

Clinical Practice and Workflow of Radiation Therapy for Lung Tumors at the University of Tokyo Hospital

Evaluation of Dose Distribution in Lung Tumor Radiotherapy with Boron Neutron Capture Therapy

Introduction: Boron neutron capture therapy (BNCT) is recommended to treat glioblastoma. It is well known that neutrons are more effective treatment than photons to treat hypoxic tumors due to interaction with the nucleus and production of heavy particles. Objective: To evaluate the suitability of BNCT for treating lung cancer, neutron dose distributions was calculated in lung tumor volume and in peripheral organs at risk (OARs).Materials and Methods: Dose distribution to treat lung cancer was calculated by MCNPX code. An elliptical tumor with volume of 27cm3 was centered in the left lung of ORNL phantom and was irradiated with a rectangular field of neutron. Recommended neutron spectrums of MIT and CNEA-MEC were used as a neutron source. The tumor was loaded with different concentrations of Boron 0, 10, 30 and 60 ppm to evaluate the delivered dose to OARs. Results: neutron absorbed dose rate in the tumor was 2.2×10-3, 2.6×10-3, 3.4×10-3 and 4.7×10-3 Gy/s for boron concentrations of 0, 10, 30 and 60 ppm, respectively in MIT. Moreover, the similar results in CNEA-MEC was 1.2×10-3, 1.6×10-3, 2.5×10-3 and 3.7×10-3 Gy/s. Among all, heart absorbed the maximum neutron dose rate of 1.7×10-4 and 1.6×10-4 Gy/s in MIT and CNEA, respectively. For all energy’s bins of spectrums, the neutrons flux is decreased as it penetrates the lung. Conclusion: The implemented model was successful in calculating the dose to organs using BNCT. An Increase in boron concentrations in tumor results in an increase in the absorbed doses while dose uniformity deteriorates. Results showed that the MIT source is well suited to treat deep lung tumors while maintaining the OARs’ dose within the threshold dose.

Determination of reproducibility of end-exhaled breath-holding in stereotactic body radiation therapy.

ABSTRACTMethods to evaluate the positional reproducibility of breath-hold irradiation mostly require manual operation. The purpose of this study is to propose a method to determine the reproducibility of breath-hold irradiation of lung tumors between fractions using non-artificial methods. This study included 13 patients who underwent terminal exhaled breath-hold irradiation for primary and metastatic lung cancer. All subjects received a prescribed dose of 60 Gy/8 fractions. The contours of the gross tumor volume (GTV) were extracted by threshold processing using treatment-planning computed tomography (CT) and cone-beam CT (CBCT), which was done just before the beginning of the treatment. The method proposed in this study evaluates the dice similarity coefficient (DSC) and Hausdorff distance (HD) by comparing two volumes, the GTVCTS (GTV obtained from treatment-planning CT) and GTVCBCT (GTV obtained from CBCT). The reference contours for DSC and HD are represented by GTVCTS. The results demonstrated good visual agreement for cases with a DSC of ~0.7. However, apparent misalignment occurred when the DSC was <0.5. HD was >2 mm in 3 out of 13 cases, and when the DSC was ~0.7, the HD was ~1 mm. In addition, cases with greater HD also demonstrated more significant variability. It was found that the DSC and HD evaluation methods for the positional reproducibility of breath-hold irradiation proposed in this study are straightforward and can be performed without the involvement of humans. Our study is of extreme significance in the field of radiation studies.

Biologically effective dose and overall survival in stereotactic body radiotherapy for lung tumors

Stereotactic body radiotherapy (SBRT) delivers precise concentric radiation to a tumor. It is well established that local control depends on the biologically effective dose (BED) delivered, with BED10 of ≥100 as a significant predictor of local control. The aim of this study was to evaluate factors associated with overall survival (OS) in inoperable lung cancer cases treated with SBRT. From 2013 to 2016, 22 patients with inoperable lung cancer treated with SBRT who could be followed up until their time of death were retrospectively enrolled. Data on sex, age, dose (Gray), number of fractions, BED (α/β = 10), pathology, tumor location, performance status, and background lung disease were collected. The median total dose at the isocenter was 50 Gy, and median BED was 120 Gy. OS was compared in groups with BED of ≥120 Gy (“high-BED”; n = 15) and BED of <120 Gy (“low-BED,” n = 7). Overall, 1‑year OS was 48%. In the univariate analysis, the number of fractions, BED, and pathology were significantly associated with OS. The high-BED group showed better OS, with 1‑ and 2‑year OS of 64% and 21%, respectively, compared with 25% and 0%, respectively, for the low-BED group (p = 0.04). No adverse event of grade 3 or higher occurred. For these inoperable lung cancer cases treated with SBRT, BED was significantly associated with OS. The poor OS rate observed in this case series might be associated with the fact that all the tumors were inoperable.

Dose deviations induced by respiratory motion for radiotherapy of lung tumors: Impact of CT reconstruction, plan complexity, and fraction size.

A thorax phantom was used to assess radiotherapy dose deviations induced by respiratory motion of the target volume. Both intensity modulated and static, non‐modulated treatment plans were planned on CT scans of the phantom. The plans were optimized using various CT reconstructions, to investigate whether they had an impact on robustness to target motion during delivery. During irradiation, the target was programmed to simulate respiration‐induced motion of a lung tumor, using both patient‐specific and sinusoidal motion patterns in three dimensions. Dose was measured in the center of the target using an ion chamber. Differences between reference measurements with a stationary target and dynamic measurements were assessed. Possible correlations between plan complexity metrics and measured dose deviations were investigated. The maximum observed motion‐induced dose differences were 7.8% and 4.5% for single 2 Gy and 15 Gy fractions, respectively. The measurements performed with the largest target motion amplitude in the superior–inferior direction yielded the largest dosimetric deviations. For 2 Gy fractionation schemes, the summed dose deviation after 33 fractions is likely to be less than 2%. Measured motion‐induced dose deviations were significantly larger for one CT reconstruction compared to all the others. Static, non‐modulated plans showed superior robustness to target motion during delivery. Moderate correlations between the modulation complexity score applied to VMAT (MCSv) and measured dose deviations were found for 15 Gy SBRT treatment plans. Correlations between other plan complexity metrics and measured dose deviations were not found.

Investigation of 4D dose in volumetric modulated arc therapy-based stereotactic body radiation therapy: does fractional dose or number of arcs matter?

The aim of this study was to assess the impact of fractional dose and the number of arcs on interplay effects when volumetric modulated arc therapy (VMAT) is used to treat lung tumors with large respiratory motions. A three (fractional dose of 4, 7.5 or 12.5 Gy) by two (number of arcs, one or two) VMAT plan was created for 10 lung cancer cases. The median 3D tumor motion was 17.9 mm (range: 8.2–27.2 mm). Ten phase-specific subplans were generated by calculating the dose on each respiratory phase computed tomography (CT) scan using temporally assigned VMAT arcs. We performed temporal assignment of VMAT arcs using respiratory information obtained from infrared markers placed on the abdomens of the patients during CT simulations. Each phase-specific dose distribution was deformed onto exhale phase CT scans using contour-based deformable image registration, and a 4D plan was created by dose accumulation. The gross tumor volume dose of each 4D plan (4D GTV dose) was compared with the internal target volume dose of the original plan (3D ITV dose). The near-minimum 4D GTV dose (D99%) was higher than the near-minimum 3D internal target volume (ITV) dose, whereas the near-maximum 4D GTV dose (D1%) was lower than the near-maximum 3D ITV dose. However, the difference was negligible, and thus the 4D GTV dose corresponded well with the 3D ITV dose, regardless of the fractional dose and number of arcs. Therefore, interplay effects were negligible in VMAT-based stereotactic body radiation therapy for lung tumors with large respiratory motions.

A Beam-Angle-Selection Method to Improve Inter-Fraction Motion Robustness for Lung Tumor Irradiation With Passive Proton Scattering.

In terms of dose distribution, protons are more sensitive to range variations than photons due to their unique properties. The aim of this study was to develop a method to identify patient-specific robust proton beam angles for lung tumor irradiation by investigating the association between water equivalent thickness (WET) variation and inter-fraction motion-induced target dose degradation. Using 3-dimensional computed tomography (3D-CT) images, the impact of WET variations on the target dose coverage of a series of coplanar proton beams was evaluated for 4 patients with lung cancer. Using ray tracing, WET maps, or WET baseline, were estimated for the internal target volume (ITV) at every 5° gantry interval in the axial plane. After calculating the WET baseline, the planning CT was shifted 5 mm in each anterior-posterior (AP), superior-inferior (SI), and left-right (LR) direction, yielding a total of 6 shifted CTs, and differential WET maps between the planning CT and each shifted CT were calculated. Target dose differences were associated with the average WET change between the original planning CT and the shifted CTs for all 360° gantry rotation beams. Target and OAR dose metrics in the ΔWET-guided plans were compared with those of the clinical plans. The WET variation maps showed areas of both high and low WET variations, with overall similar patterns yet individual differences reflecting tumor position differences. For all 4 patients investigated in this study, the coplanar plans demonstrated a strong correlation between WET changes and ITV dose reductions. Target dose coverage was more stable with the ΔWET-guided plan while OAR doses were comparable to the clinical plan. The WET variation maps have been used in this pilot study to identify proton beam angles that are either sensitive or robust to WET changes in proton passive scattering. This work demonstrates the feasibility of using WET variation maps to assist the planner in inter-fraction motion-robust proton beam angle selection.

EP1.17-24 Biologically Effective Dose Was Associated with Overall Survival in Stereotactic Body Radiotherapy for Lung Tumors

EP1.17-24 Biologically Effective Dose Was Associated with Overall Survival in Stereotactic Body Radiotherapy for Lung Tumors

Lung Cancer Radiotherapy: Can Breathing Movement Evaluation be Improved By More Than One 4D-CT?

A recent national survey showed that a significant number of radiation oncologists resorted to more than one 4D-CT scans before lung cancer treatment planning. To our best knowledge, only two studies investigated whether only one 4D-CT was sufficient to evaluate breathing-induced motion of pulmonary tumors. However, the results were limited by the number of patients (10 to 26), and the old-generation scan machines. The present study was carried out to update the available data. The aim of the study was to assess the benefit of processing more than one 4D-CT in lung cancer patients as well as the immediate impact on patient’s quality of life. Data about all consecutive patients undergoing a curative radiotherapy for lung tumor (primary or metastases) were prospectively collected between April and July 2017. Patients had several 4D-CTs within a maximum of seven days but not on the same day. The ITV was contoured on each 4D-CT. The center of mass (used as a surrogate of the tumor position) was defined as the position of the barycenter of the tumor and was collected on each phase along with its standard deviation. The peak to peak tumor motion (distance between extreme tumor positions within one breathing cycle) and the three-dimensional tumor motion (left-right, supero-inferior and antero-posterior direction) were assessed. Patient’s self-reported quality of life was collected. 24 patients had two 4D-CT and were included. Mean age was 63 (range: 18-83). Contrast agent infusion was performed in 5 patients (20.8%). Abdominal compression was applied to 10 patients (41.7%) The mean volume of ITV was 125 cm3 (SD± 71,9 cm3). Between the repeated 4D-CTs, the ITV volume did not significantly vary (mean ITV variation: 8% i.e. 9 cm3, p=0.06). A variation of the ITV≥10% was observed in 9 patients (37.5%). The maximum variation of ITV volume between repeated 4D-CTs was 24.6%. The maximal mean peak to peak tumor motion in the prominent direction (i.e. possibly combining motions in the three different directions) was 1,79 ± 1,09 cm. Between 4D-CT, a relevant variation (≥2mm) was observed only in three patients. No variation reached 3mm, whatever the considered direction. The position of the center of mass did not significantly vary between repeated 4D-CTs (p=0.06). The mean three-dimensional tumor motion was 2,36 ± 1,33 cm (range : -3,04 cm to +1,92 cm). The mean tumor motion was higher at the first 4D-CT than at the second (p=0.035). Between repeated 4D-CTs, 4 patients (16%) had a mean tumor motion>5mm, with a 9mm motion in 2 patients (8%). Repeated 4D-CTs had no impact on patient’s quality of life. The repetition of 4D-CT did not highlight variations in tumor movement for most patients. However in 16% of patients, the second 4D-CT revealed an extra tumor motion that exceeded the standard additional margins used in SBRT. Although a second 4D-CT does not seem useful in normo-fractionnated radiotherapy given the usual margins, it seems essential for an accurate definition of ITV in SBRT.

Chest Magnetic Resonance Imaging Decreases Inter-observer Variability of Gross Target Volume for Lung Tumors.

Purpose: PET/CT is a standard medical imaging used in the delineation of gross tumor volume (GTV) in case of radiation therapy for lung tumors. However, PET/CT could present some limitations such as resolution and standardized uptake value threshold. Moreover, chest MRI has shown good potential in diagnosis for thoracic oncology. Therefore, we investigated the influence of chest MRI on inter-observer variability of GTV delineation.Methods and Materials: Five observers contoured the GTV on CT for 14 poorly defined lung tumors during three contouring phases based on true daily clinical routine and acquisition: CT phase, with only CT images; PET phase, with PET/CT; and MRI phase, with both PET/CT and MRI. Observers waited at least 1 week between each phases to decrease memory bias. Contours were compared using descriptive statistics of volume, coefficient of variation (COV), and Dice similarity coefficient (DSC).Results: MRI phase volumes (median 4.8 cm3) were significantly smaller than PET phase volumes (median 6.4 cm3, p = 0.015), but not different from CT phase volumes (median 5.7 cm3, p = 0.30). The mean COV was improved for the MRI phase (0.38) compared to the CT (0.58, p = 0.024) and PET (0.53, p = 0.060) phases. The mean DSC of the MRI phase (0.67) was superior to those of the CT and PET phases (0.56 and 0.60, respectively; p < 0.001 for both).Conclusions: The addition of chest MRI seems to decrease inter-observer variability of GTV delineation for poorly defined lung tumors compared to PET/CT alone and should be explored in further prospective studies.

Stereotactic Body Radiotherapy for Lung Tumors: Basic Principles and Clinical Results

Stereotactic Body Radiotherapy for Lung Tumors: Basic Principles and Clinical Results

Investigation of lung normal tissue doses in lung tumors radiation therapy using both gated and conventional radiotherapy

Introduction: In radiation therapy of lung tumors, respiratory motion causes target moving, so a larger margin is needed to cover the clinical target volume (CTV). With the margin increasing, a larger volume of normal tissue will be exposed to high-dose. In this study, dosimetric parameters of normal lung tissue were compared between gated and conventional radiotherapy (RT), using the NCAT digital phantom. Materials and Methods: Different series of CT images of sample patients were created, using the NCAT digital phantom and MATLAB software. Lesions with diameters of 3, 4 and 5cm were located in different positions of lung (left upper and lower lobes, right upper and lower lobes) in the CT images. Appropriate margins were applied to the CTVs depending on the radiation therapy technique and respiratory cycles. To evaluate the effect of diaphragm extension on the margins to CTV, different diaphragm motions were considered from 2 to 3.5 cm with 0.5 cm intervals. PCRT treatment planning system with Superposition computational algorithm was used to deliver a dose of 60Gy in 30 fractions to the PTVs. Totally, 36 treatment plans were evaluated for each RT technique and Mean lung dos (MLD) and V20 were calculated for both conventional and gated RT techniques. Results: A significant impact on MLD and V20 reduction was seen in lung normal tissue in gated RT up to 5Gy and 37%, respectively. Conclusion: In all cases, gated RT has a superior advantage compared to conventional RT, especially for the lesions that are near to the diaphragm.