Adaptive radiotherapy in locally advanced esophageal cancer with atelectasis: a case report

BACKGROUND: To the best of our knowledge, no study has reported mediastinal shift accompanied with obstructive atelectasis due to bulky primary esophageal tumor components treated with adaptive radiotherapy and concurrent chemotherapy. CASE PRESENTATION: Here we report the case of a 65-year-old male patient diagnosed with locally advanced thoracic esophageal squamous cell cancer, clinical T4bN1M0, stage IVA. Bronchoscopy and computed tomography (CT) revealed an almost complete obstruction of the lumen of the left bronchus due to compression by bulky primary esophageal tumor components. On admission, the patient presented with dyspnea and decreased arterial oxygen saturation. Chest radiography and CT on admission revealed mediastinal shift with left atelectasis, as opposed to findings from the chest radiography performed 26 days before admission. Because of the patient's overall good condition, we recommended definitive chemoradiotherapy instead of palliative bronchial stent placement. After obtaining the patient's consent, chemoradiotherapy was initiated on the following day and it comprised three-dimensional conformal radiotherapy with 60 Gy in 30 fractions with concurrent administration of cisplatin and 5-fluorouracil. During chemoradiotherapy, tumor location was monitored with cone-beam CT and chest radiography. Chemoradiotherapy on day 8 revealed no evidence of the mediastinal shift. CT simulation was reperformed to adjust the radiotherapy fields to account for geometrical changes induced by the absence of the mediastinal shift. Subsequently, the mediastinal shift and bronchial obstruction did not recur during the course of chemoradiotherapy. The patient completed the planned radiotherapy with concurrent and adjuvant chemotherapy, and no non-hematological grade ≥ 3 adverse events were observed. Complete response was confirmed 7 months after initiating chemoradiotherapy. Currently, no disease recurrence, dysphagia, or respiratory symptoms have been reported at 13 months after initiating chemoradiotherapy. CONCLUSIONS: In this study, a bulky primary esophageal tumor caused mediastinal shift due to ipsilateral bronchial obstruction. The close follow-up for monitoring resolution of the mediastinal shift during the course of chemoradiotherapy enabled adequate dose delivery to targets, thus reflecting the geometrical changes induced by the absence of the mediastinal shift. Adaptive radiotherapy technique was crucial for favorable patient outcomes in this challenging clinical situation

Statistical deformation reconstruction using multi-organ shape features for pancreatic cancer localization

Respiratory motion and the associated deformations of abdominal organs and tumors are essential information in clinical applications. However, inter- and intra-patient multi-organ deformations are complex and have not been statistically formulated, whereas single organ deformations have been widely studied. In this paper, we introduce a multi-organ deformation library and its application to deformation reconstruction based on the shape features of multiple abdominal organs. Statistical multi-organ motion/deformation models of the stomach, liver, left and right kidneys, and duodenum were generated by shape matching their region labels defined on four-dimensional computed tomography images. A total of 250 volumes were measured from 25 pancreatic cancer patients. This paper also proposes a per-region-based deformation learning using the non-linear kernel model to predict the displacement of pancreatic cancer for adaptive radiotherapy. The experimental results show that the proposed concept estimates deformations better than general per-patient-based learning models and achieves a clinically acceptable estimation error with a mean distance of 1.2 ± 0.7 mm and a Hausdorff distance of 4.2 ± 2.3 mm throughout the respiratory motion

Pharmacological inhibition of sodium-calcium exchange activates NADPH oxidase and induces infection-independent NETotic cell death

In addition to its function of innate immunity against invading pathogens, neutrophil extracellular traps (NETs) promote thrombosis, autoimmune disease, and cancer metastasis; therefore, unnecessary exposure to the triggers of infection-independent NET generation should be avoided. We herein show that inhibition of forward-mode Na⁺/Ca²⁺ exchange by amiloride analogs, 5-(N-ethyl-N-isopropyl)amiloride (EIPA) and 5-(N-Methyl-N-isobutyl)amiloride (MIA), triggers NETotic cell death independently of infectious stimuli. Isolated human neutrophils treated with EIPA and MIA undergo NETotic cell death by an increase of intracellular Ca²⁺ following activation of NADPH oxidase and the resultant upregulation of intracellular ROS. EIPA- and MIA-mediated intracellular Ca²⁺ increase is attributed to the competitive binding of EIPA and MIA against Na⁺ to Na⁺/Ca²⁺ exchanger 1 (NCX1). These results demonstrate a new mechanism of infection-independent NET generation and implicate NCX1 as a physiologic regulator of intracellular calcium balance and NETotic cell death

Dosimetric comparison among dynamic conformal arc therapy, coplanar and non-coplanar volumetric modulated arc therapy for single brain metastasis

In the delivery of stereotactic radiosurgery (SRS) by linear accelerator (LINAC), dynamic conformal arc therapy (DCAT) with non-coplanar beams is conventionally used. However, volumetric modulated arc therapy (VMAT) can improve target conformity, thereby decreasing the dose to organs at risk by inversed planning methods, but few studies have directly compared DCAT and VMAT with and without non-coplanar beams in patients with single brain metastasis. We therefore conducted a planning study to compare the dose distribution in DCAT, VMAT using only a coplanar arc (CoVMAT) and VMAT with non-coplanar arcs (NcVMAT) in the treatment of single brain metastasis. DCAT, CoVMAT and NcVMAT plans were created for 15 patients. The three modalities were compared in terms of target conformity, target coverage, the dose to normal brain tissue, monitor units (MUs) and beam-on time. Both conformity indices (RTOG-CI and IP-CI) as well as the D98% of the gross target volume (GTV) were significantly better in the NcVMAT plans than in the DCAT plans. Comparisons of the doses to normal brain tissue revealed that the V20Gy, V15Gy, V12Gy, V10Gy and V5Gy were significantly smaller in the NcVMAT plans than in the plans based on the other two modalities. The MUs of the DCAT and NcVMAT plans were larger than those of the CoVMAT plans, and the beam-on time was longer in the NcVMAT and CoVMAT plans than in the DCAT plans. Compared to the CoVMAT and DCAT plans, NcVMAT plans significantly improved target conformity and reduced the doses to normal brain tissue at V20Gy, V15Gy, V12Gy, V10Gy and V5Gy

Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy

[Background] The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT. [Methods] Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39–44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed. [Results] The median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions. [Conclusions] Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases

Vulnerabilities of radiomic features to respiratory motion on four‐dimensional computed tomography‐based average intensity projection images: A phantom study

[Purpose] To evaluate the influence of respiratory motion on the robustness of radiomic features on four-dimensional computed tomography (4DCT)-based average intensity projection (AIP) images by employing an anthropomorphic chest phantom. [Methods] Three spherical objects (φ30 mm), namely, acrylic (100 Hounsfield unit [HU], homogeneous), rubber (−140 HU, homogeneous), and cork (−630 HU, heterogeneous), were moved with motion amplitudes of 0, 1, 2.5, 4, 6, 8, and 10 mm in the phantom, and 4DCT scans were repeated at four different locations. Thereafter, the AIP images were generated considering the average of the 10 respiratory phases of the 4DCT images. Further, the targets were manually delineated on the AIP images in the lung window setting. A total of 851 radiomic features, including 107 unfiltered features and 744 wavelet filter-based features, were extracted from the region of interest for each material. The feature robustness among the different target motion amplitude (ε) was evaluated by normalizing the feature variability of the target motion relative to the variability of data from 573 patients with early-stage non-small cell lung cancer. The features with absolute ε values ≤0.5 were considered highly robust to target motions. [Results] The percentage of robust unfiltered and wavelet filter-based features with a motion amplitude of 1 mm was greater than 83.2% and 93.4%, respectively; however, the percentage decreased by more than 24.3% and 17.6%, respectively, for motion amplitudes greater than 2.5 mm. The movement of cork had a small effect on the feature robustness compared to that of acrylic and rubber, regardless of the target motion amplitudes. [Conclusions] Our phantom study demonstrated that target motion amplitudes ≤1 mm led to the robustness of radiomic features on the 4DCT-based AIP images of thoracic regions. The frequency components and directions of the wavelet filters may be essential factors in 4DCT-based radiomic analysis

Lack of an association between marital status and survival in patients receiving stereotactic body radiotherapy for early-stage non-small-cell lung cancer

Marital status has been proposed as a promising prognostic factor in many malignancies, including non-small-cell lung cancer (NSCLC). However, its prognostic value is still unclear for individual non-surgical treatments for stage I NSCLC. This study investigated the prognostic value of marital status in patients with early-stage NSCLC treated with stereotactic body radiotherapy (SBRT). Patients with early-stage NSCLC treated with SBRT between January 2003 and March 2014 at our institute were enrolled, and marital status at the time of SBRT was investigated. Propensity score matching (PSM) was applied to reduce potential selection bias between the married and unmarried groups. Two hundred and forty patients (median age 77 years; 152 married, 87 unmarried) were analyzed. The unmarried included higher proportions of the elderly, women, never smokers, and those with decreased pulmonary function compared to the married. PSM identified 53 matched pairs of married and unmarried patients, with no significant difference in patient background parameters. The 5-year overall survival (OS) was 52.8% and 46.9% in the married and unmarried groups, respectively (P = 0.26). There was no significant difference in NSCLC death or non-NSCLC death between the two groups (P = 0.88 and 0.30, respectively). There was no significant difference in OS between married and unmarried male patients (n = 85, 5-year OS, 52.6% vs. 46.0%; P = 0.42) and between married and unmarried female patients (n = 21, 54.5% vs. 50.0%; P = 0.44). In conclusion, marital status was not associated with OS in patients receiving SBRT for early-stage NSCLC

Anaplastic Transformation of Follicular Thyroid Carcinoma in Pulmonary Metastasis With Gradually Progressive Intra-tumoral Cavitation: A Case Report

Anaplastic transformation of differentiated thyroid cancer is rare but clinically important because of the dismal prognosis after anaplastic transformation. Therefore, cases and findings of anaplastic transformation must be accumulated, which could ultimately lead to an earlier diagnosis and an improved prognosis. Here, we present a case of anaplastic transformation of follicular thyroid carcinoma (FTC) in a pulmonary metastatic lesion associated with gradually progressive tumor cavitation. The patient with FTC was diagnosed with multiple lung metastases three years after surgery for the primary tumor and metastatic neck lymph nodes. Annual treatment with radioactive iodine resulted in disease stability for 10 years. However, one lung metastasis in the left lower lobe gradually enlarged and was associated with intra-tumoral cavitation. The growing lung nodule was resected and pathologically diagnosed as an anaplastic transformation of FTC. Fourteen months after diagnosis, the patient died of pneumothorax caused by pleural dissemination despite multiple treatment interventions. This case highlights pulmonary metastasis with progressive cavitary lesions as a potential early sign of the anaplastic transformation of differentiated thyroid cancer

Feasibility study of deep learning-based markerless real-time lung tumor tracking with orthogonal X-ray projection images

[Purpose] The feasibility of a deep learning-based markerless real-time tumor tracking (RTTT) method was retrospectively studied with orthogonal kV X-ray images and clinical tracking records acquired during lung cancer treatment. [Methods] Ten patients with lung cancer treated with marker-implanted RTTT were included. The prescription dose was 50 Gy in four fractions, using seven- to nine-port non-coplanar static beams. This corresponds to 14–18 X-ray tube angles for an orthogonal X-ray imaging system rotating with the gantry. All patients underwent 10 respiratory phases four-dimensional computed tomography. After a data augmentation approach, for each X-ray tube angle of a patient, 2250 digitally reconstructed radiograph (DRR) images with gross tumor volume (GTV) contour labeled were obtained. These images were adopted to train the patient and X-ray tube angle-specific GTV contour prediction model. During the testing, the model trained with DRR images predicted GTV contour on X-ray projection images acquired during treatment. The predicted three-dimensional (3D) positions of the GTV were calculated based on the centroids of the contours in the orthogonal images. The 3D positions of GTV determined by the marker-implanted RTTT during the treatment were considered as the ground truth. The 3D deviations between the prediction and the ground truth were calculated to evaluate the performance of the model. [Results] The median GTV volume and motion range were 7.42 (range, 1.18–25.74) cm³ and 22 (range, 11–28) mm, respectively. In total, 8993 3D position comparisons were included. The mean calculation time was 85 ms per image. The overall median value of the 3D deviation was 2.27 (interquartile range: 1.66–2.95) mm. The probability of the 3D deviation smaller than 5 mm was 93.6%. [Conclusions] The evaluation results and calculation efficiency show the proposed deep learning-based markerless RTTT method may be feasible for patients with lung cancer

Potential utility of cone‐beam CT‐guided adaptive radiotherapy under end‐exhalation breath‐hold conditions for pancreatic cancer

[Purpose] The purpose of this study was to demonstrate the potential utility of cone-beam computed tomography (CBCT)-guided online adaptive radiotherapy (ART) under end-exhalation breath-hold (EE-BH) conditions for pancreatic cancer (PC). [Methods] Eleven PC patients who underwent 15-fraction volumetric-modulated arc therapy under EE-BH conditions were included. Planning CT images and daily 165 CBCT images were imported into a dedicated treatment planning system. The prescription dose was set to 48 Gy in 15 fractions. The reference plan was automatically generated along with predefined clinical goals. After segmentation was completed on CBCT images, two different plans were generated: One was an adapted (ADP) plan in which re-optimization was performed on the anatomy of the day, and the other was a scheduled (SCH) plan, which was the same as the reference plan. The dose distributions calculated using the synthetic CT created from both planning CT and CBCT were compared between the two plans. Independent calculation-based quality assurance was also performed for the ADP plans, with a gamma passing rate of 3%/3 mm. [Results] All clinical goals were successfully achieved during the reference plan generation. Of the 165 sessions, gross tumor volume D98% and clinical target volume D98% were higher in 100 (60.1%) and 122 (74.0%) ADP fractions. In each fraction, the V3 Gy < 1 cm³ of the stomach and duodenum was violated in 47 (28.5%) and 48 (29.1%), respectively, of the SCH fractions, whereas no violations were observed in the ADP fractions. There were statistically significant differences in the dose–volume indices between the SCH and ADP fractions (p < 0.05). The gamma passing rates were above 95% in all ADP fractions. [Conclusions] The CBCT-guided online ART under EE-BH conditions successfully reduced the dose to the stomach and duodenum while maintaining target coverage