Impact of different respiratory gating methods on target delineation and a radiotherapy plan for solitary pulmonary tumors.

BACKGROUND AND PURPOSE: Respiratory movement has an important impact on the radiotherapy for lung tumor. Respiratory gating technology is helpful to improve the accuracy of target delineation. This study investigated the value of prospective and retrospective respiratory gating simulations in target delineation and radiotherapy plan design for solitary pulmonary tumors (SPTs) in radiotherapy. METHODS: The enrolled patients underwent CT simulation with three-dimensional (3D) CT non gating, prospective respiratory gating, and retrospective respiratory gating simulation. The target volumes were delineated on three sets of CT images, and radiotherapy plans were prepared accordingly. Tumor displacements and movement information obtained using the two respiratory gating approaches, as well as the target volumes and dosimetry parameters in the radiotherapy plan were compared. RESULTS: No significant difference was observed in tumor displacement measured using the two gating methods (p > 0.05). However, the internal gross tumor volumes (IGTVs), internal target volumes (ITVs), and planning target volumes (PTVs) based on the retrospective respiratory gating simulation were larger than those obtained using prospective gating (group A: pIGTV = 0.041, pITV = 0.003, pPTV = 0.008; group B: pIGTV = 0.025, pITV = 0.039, pPTV = 0.004). The two-gating PTVs were both smaller than those delineated on 3D non gating images (p < 0.001). V5Gy, V10Gy, V20Gy, V30Gy, and mean lung dose in the two gated radiotherapy plans were lower than those in the 3D non gating plan (p < 0.001); however, no significant difference was observed between the two gating plans (p > 0.05). CONCLUSIONS: The application of respiratory gating could reduce the target volume and the radiation dose that the normal lung tissue received. Compared to prospective respiratory gating, the retrospective gating provides more information about tumor movement in PTV.

Single-cell RNA sequencing reveals the multi-cellular ecosystem in different radiological components of pulmonary part-solid nodules.

BACKGROUND: Early-stage lung adenocarcinoma that radiologically manifests as part-solid nodules, consisting of both ground-glass and solid components, has distinctive growth patterns and prognosis. The characteristics of the tumour microenvironment and transcriptional features of the malignant cells of different radiological phenotypes remain poorly understood. METHODS: Twelve treatment-naive patients with radiological part-solid nodules were enrolled. After frozen pathology was confirmed as lung adenocarcinoma, two regions (ground-glass and solid) from each of the 12 part-solid nodules and 5 normal lung tissues from 5 of the12 patients were subjected to single-cell sequencing by 10x Genomics. We used Seurat v3.1.5 for data integration and analysis. RESULTS: We comprehensively dissected the multicellular ecosystem of the ground-glass and solid components of part-solid nodules at the single-cell resolution. In tumours, these components had comparable proportions of malignant cells. However, the angiogenesis, epithelial-to-mesenchymal transition, KRAS, p53, and cell-cycle signalling pathways were significantly up-regulated in malignant cells within solid components compared to those within ground-glass components. For the tumour microenvironment, the relative abundance of myeloid and NK cells tended to be higher in solid components than in ground-glass components. Slight subtype composition differences existed between the ground-glass and solid components. The T/NK cell subsets' cytotoxic function and the macrophages' pro-inflammation function were suppressed in solid components. Moreover, pericytes in solid components had a stronger communication related to angiogenesis promotion with endothelial cells and tumour cells. CONCLUSION: The cellular landscape of ground-glass components is significantly different from that of normal tissue and similar to that of solid components. However, transcriptional differences exist in the vital signalling pathways of malignant and immune cells within these components.

Comparison of different width detector on the gross tumor volume delineation of the solitary pulmonary lesion.

PURPOSE: To explore the impact of different width detector on the volume and geometric position of gross tumor volume (GTV) of the solitary pulmonary lesion (SPL), as well as the impact on scanning time and radiation dose during the simulation. MATERIALS AND METHODS: Twenty-three patients with SPL underwent three-dimensional computed tomography (3DCT) simulation using different width detector, followed by four-dimensional computed tomography (4DCT) scans. GTV16 and GTV4 derived from different width detectors were compared with internal gross tumor volume (IGTV) generated from 4DCT on the volume and geometric position. Fourteen patients with lesions located in the upper lobe were defined as Group A and nine patients in the middle or lower lobe were defined as Group B. The scanning time and radiation dose during the simulation with the different width detector were compared as well. RESULTS: The volumes of IGTV, GTV16, and GTV4 in Group A were 13.86 ± 14.42 cm3, 11.88 ± 11.93 cm3, and 11.64 ± 12.88 cm3, respectively, and the corresponding volumes in Group B were 12.84 ± 11.48 cm3, 6.90 ± 6.63 cm3, and 7.22 ± 7.15 cm3, respectively. No difference was found between GTV16 and GTV4 in Groups A and B (PA = 0.11, PB = 0.86). Either GTV16 or GTV4 was smaller than IGTV (P16 = 0.001, P4 = 0.000). The comparison of the centroidal positions in x, y, and z directions for GTV16, GTV4, and IGTV showed no significant difference both in Groups A and B (Group A: Px = 0.19, Py = 0.14, Pz = 0.47. Group B: Px = 0.09, Py = 0.90, Pz = 0.90). The scanning time was shorter and radiation dose patient received was lower using 16 × 1.5 mm detector combination than 4 × 1.5 mm detector (P = 0.000). CONCLUSIONS: Different width detector had no impact on the volume and geometric position of GTV of SPL during 3DCT simulation. Using wide detector would save time and decrease radiation dose compared with the narrow one. 3DCT simulation using either 16 × 1.5 mm detector or 4 × 1.5 mm detector could not cover all tumor motion information that 4DCT offered under free breathing conditions.

[Localizating and Extracting Small Peripheral Nodules of Lung with Simulating 
Radiaotherapy Combining Methylene Blue Staining].

BACKGROUND: With the extensively application of HRCT (high resolution CT) and the popularization of early lung cancer screening, the proportion of small nodullar lung cancer to be operated increases rapidly. Identifying the focus lesions quickly and accurately in operation has shown to be a challenge. We carried out this research trying to make use of and evaluate a new method that localizaes and extracts small peripheral pulmonary nodules by way of simulating radiaotherapy combining methylene blue staining. METHODS: From February 2012 to January 2015, 97 patients with 100 peripheral pulmonary nodules ≤10 mm in size were simulated puncturing using a radiotherapy planning. When the anaesthesia came into use, methylene blue dye was injected to the virtually identified point corresponding to the surface point, according to the angle and depth previously computed by the radiotherapy planning. The video-assisted thoracoscopic surgery (VATS) wedge resections of the marked lesions were undertaken and the specimens were sent for frozen pathologic examination. The interval time from anesthesia-completing to puncture and injection, The interval time from methylene blue injection to identifying the stained area and the distances between the centre point of the stains and edge of coloured lesion were recorded. RESULTS: Our preoperative localization procedure was successful in 96 of 100 (96%) nodules. The interval time from anesthesia-completing to puncture and injection of methylene blue were (4.85±1.25) min. The interval time from methylene blue injection to identifying the stained area was (16.36±2.36) min. The distances between the centre point of the stains and edge of coloured lesion were (4.78±2.51) mm. No complication was observed in all participants. CONCLUSIONS: The new method of locating peripheral pulmonary nodules by simulating simulating radiaotherapy combining methylene blue staining has a high success rate and no complication for localizing small peripheral pulmonary lesions, avoiding the fear and pain of the patients untaken puncture without anaesthesia reducing radial damage.

The Fate of Residual Tumor Masses That Persist After Stereotactic Body Radiotherapy for Solitary Lung Nodules: Will They Recur?

BACKGROUND: After stereotactic body radiotherapy (SBRT) to the lung, radiation pneumonitis and fibrotic changes often develop, and the tumor shadow usually becomes indistinguishable from the fibrotic shadow. Occasionally, however, a residual mass in patients with no or mild radiation pneumonitis will be observed on serial computed tomography (CT) scans. The purpose of the present study was to evaluate the fate of such residual masses and, if possible, to determine the types of tumor at increased risk of local recurrence. PATIENTS AND METHODS: A total of 50 patients (underlying disease: primary lung cancer in 45, local recurrence in 2, and metastasis in 3) were selected because they had been followed up for > 2 years or until death and had observable CT changes and measurable tumor size for > 1 year, regardless of the influence of radiation pneumonitis. The patients' outcomes were compared according to various patient and tumor characteristics, including the presence and absence of emphysema, tumor size, and tumor shrinkage rate. The median follow-up period was 52 months. RESULTS: Of the 50 patients, only 8 developed local recurrence. The local control rate was 81% at 3 years and 73% at 5 years. The local control rates were similar between patients with a high tumor shrinkage rate and those with a low rate. The patients with emphysema exhibited a lower local control rate. CONCLUSION: The persistence of lung masses for > 1 year after SBRT is not necessarily indicative of an increased risk of local recurrence. A low tumor shrinkage rate also was not predictive of recurrence.

Lung cancer.

(18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) plays a key role in the evaluation of undiagnosed lung nodules, when primary lung cancer is strongly suspected, or when it has already been diagnosed by other techniques. Although technical factors may compromise characterization of small or highly mobile lesions, lesions without apparent FDG uptake can generally be safely observed, whereas FDG-avid lung nodules almost always need further evaluation. FDG-PET/CT is now the primary staging imaging modality for patients with lung cancer who are being considered for curative therapy with either surgery or definitive radiation therapy.

Positron emission tomography in the diagnostic work-up of screening-detected lung nodules.

Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screening-detected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for ⩾2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules ⩾15 mm, better (sensitivity 98%) for solid nodules ⩾15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules ⩾15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used.

Imaging evaluation of the solitary pulmonary nodule: self-assessment module.

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging evaluation of the solitary pulmonary nodule.

Solitary pulmonary nodules: association between signal characteristics in dynamic contrast enhanced MRI and tumor angiogenesis.

PURPOSE: To estimate the association between signal characteristic of dynamic enhanced MRI using curve types and angiogenesis in solitary pulmonary nodules. MATERIALS AND METHODS: Thirty-six patients with a solitary pulmonary nodule (SPN) ranging in size from 6 to 37 mm (median 17 mm) underwent dynamic contrast enhanced MRI with a time interval of 10 s over a total period of 4 min. Resulting from the time-intensity curves four different enhancement curve profiles (A-D) were defined: type A with strong increase followed by early washout, type B with strong increase without washout, type C with slow increase and type D without relevant increase. Maximum peak (Pmax), slope of the first bolus transit (slope) and washout were calculated. Microvessel densities (MVD) were counted at the margins and at the center of the nodules. The mean MVD of each nodule was calculated. Enhancement characteristics were correlated with MVD grouped by diagnosis and by curve types. Curve types were correlated with the score of vascular endothelial growth factor (VEGF). RESULTS: The frequency of malignancy was 55% (20/36). Using curve types for differentiation between malignant and benign SPN, the sensitivity, specificity and accuracy were 100%, 75% and 89%, respectively. The correlation between Pmax and MVD(mean) for all nodules was moderate (r(s)=0.4, P=0.02). A relevant correlation was found between Pmax and MVD(margin) in curve type A (r(s)=0.63; P=0.04) and Pmax and MVD(mean) in curve type C (r(s)=0.86; P=0.006). No positive correlation was found between Pmax and MVD (mean, center and margin) in curve type B. No significant correlation was found for slope and washout. VEGF score correlated positively with curve types (r(s)=0.67; P<0.001). CONCLUSION: A relevant association between perfusion curve profiles and angiogenesis was found in malignant nodules having early washout and in benign lesion with a slow increase of enhancement. In cases of strong signal increase without washout additional factors for enhancement must be considered. The use of curve profiles could allow for the estimation of the extent of VEGF.

Significance and management of computed tomography detected pulmonary nodules: a report from the National Wilms Tumor Study Group.

PURPOSE: To define the optimal treatment for children with Wilms tumor who have pulmonary nodules identified on chest computed tomography (CT) scan, but have a negative chest radiograph, we evaluated the outcome of all such patients randomized or followed on National Wilms Tumor Study (NWTS)-3 and -4. PATIENTS AND METHODS: We estimated the event-free and overall survival percentages of 53 patients with favorable histology tumors and pulmonary densities identified only by CT scan (CT-only) who were treated as Stage IV with intensive doxorubicin-containing chemotherapy and whole-lung irradiation, and compared these to the event-free and overall survival percentages of 37 CT-only patients who were treated less aggressively based on the extent of locoregional disease with 2 or 3 drugs, and without whole-lung irradiation. RESULTS: The 4-year event-free and overall survival percentages of the 53 patients with CT-only nodules and favorable histology Wilms tumor who were treated as Stage IV were 89% and 91%, respectively. The 4-year event-free and overall survival percentages for the 37 patients with CT-only nodules and favorable histology who were treated according to the extent of locoregional disease were 80% and 85%, respectively. The differences observed between the 2 groups were not statistically significant. Among the patients who received whole-lung irradiation, there were fewer pulmonary relapses, but more deaths attributable to lung toxicity. CONCLUSIONS: The current data raise the possibility that children with Wilms tumor and CT-only pulmonary nodules who receive whole lung irradiation have fewer pulmonary relapses, but a greater number of deaths due to treatment toxicity. The role of whole lung irradiation in the treatment of this group of patients cannot be definitively determined based on the present data. Prolonged follow-up of this group of patients is necessary to accurately estimate the frequency of late, treatment-related mortality.

Dosimetric considerations in radiation therapy of coin lesions of the lung.

PURPOSE: The dose distribution in small lung lesions (coin lesions) is determined by the combined effects of reduced attenuation and electronic disequilibrium. The magnitude of the dose delivered also depends on the algorithm used to correct for reduced lung density. These effects are investigated experimentally and computationally for 10 MV photons. METHODS AND MATERIALS: Using a polystyrene miniphantom embedded in cork or cedar, thermoluminescent dosimetry and film dosimetry was performed to investigate interface effects and the central dose per monitor unit (MU). Three frequently applied calculation techniques--no density correction, ratio of tissue maximum ratios (TMRs), and the Batho correction--were also used to calculate the dose per MU. The measurements and calculations were compared with a one-dimensional phenomenological theory with parameters taken from the literature. RESULTS: The measurements at the entrance surface and center of the miniphantom agreed well with the predictions of the phenomenological theory. The interface regions are usually thin enough (2-3 mm) to be clinically unimportant for 10 MV. Depending on the algorithm used to correct for decreased lung density, the lesion dose may be larger or smaller than the prescribed dose by as much as 20% in extreme cases. A clinical example is presented. CONCLUSIONS: In comparing clinical results of treatments of small lung lesions, it is important to be aware of the density correction used.

The value and limitations of 201Tl scintigraphy in the evaluation of lung lesions and post-therapy follow-up of primary lung carcinoma.

In this study 201Tl planar scintigraphy and single photon emission computed tomography (SPECT) were performed in 92 patients with solitary lung lesions in order to distinguish malignant versus benign and metastatic masses and to evaluate the radiotherapy response of 15 primary lung carcinomas. Semiquantitative and quantitative analyses were carried out and the results were compared with histopathological diagnosis. The overall sensitivity, specificity and accuracy of semiquantitative analysis were 56, 71 and 58%, and quantitative evaluations were 88.8, 100 and 92%, respectively. Retention indexes (RI) derived from the early and delayed images were 2.9 +/- 1.3 for primary lung carcinomas, -2.78 +/- 0.9 for benign conditions and -2.3 +/- 1.5 for metastatic pulmonary lesions. 201Tl scintigraphy seems to be a sensitive modality for differentiating malignancies from benign conditions since the difference between those two pathologies is significant. However, this procedure has a limited value in distinguishing metastatic pulmonary lesions from benign pathologies, and in tissue characterization of primary lung carcinomas. On the other hand, a good correlation was observed between 201Tl lung scintigraphy and clinical diagnostic examination during postradiotherapy follow-up of inoperable pulmonary neoplasia.

Choice of procedure for surgical treatment of non-small cell lung cancer.

Asymptomatic coin lesions without specific patterns of benign calcifications can and should have a diagnosis established. Surgical diagnosis can be accomplished with very low morbidity. Accurate staging of lung cancer requires tissue confirmation of mediastinal node status either by thorough sampling or by complete node dissection. Complete resection with lobectomy is the preferred treatment providing better results than lesser resections. Segmental or wedge resections and internal radiotherapy are appropriate for patients unable to tolerate lobectomy. Video assisted thoracoscopy may prove useful in wedge excision for patients with poor pulmonary reserve.

Small cell lung cancer presenting as a solitary pulmonary nodule.

Small cell lung cancer (SCLC) rarely presents radiographically as a solitary pulmonary nodule (SPN). Twenty-five patients with this feature were identified among 408 individuals with SCLC at McGill University (Montreal, Quebec) from 1979 through 1984. Of these, 15 (60%) were confirmed on pathologic review as SCLC (ten intermediate cell, four oat cell, one indeterminate). Pathologic review of a control group comprising 24 other limited-disease patients who were long-term survivors (greater than 20 months) confirmed 20 (84%) as SCLC (eight intermediate cell, 12 oat cell). Ten of the 15 patients with SPN were resected whereas five had chemotherapy and/or radiotherapy as primary treatment. Postoperative chemotherapy was administered to most of the resected patients. The median survival of the 15 patients with SPN was 24 months, a significantly longer survival than the other patients with SCLC. This improved prognosis in patients with SPN may be due to smaller initial tumor burden or to a fundamental biologic difference between SPN and other forms of SCLC.