Stereotactic body radiation therapy for multiple lung cancers in a patient with six primary cancers: a case report.

BACKGROUND: Surgery is the standard care for patients with early-stage lung cancer, and stereotactic body radiation therapy is an option for those who are medically inoperable or refuse surgery. Medical developments in diagnostic and therapeutic strategies would prolong prognosis of patients with cancer. The number of patients with multiple cancers has also increased. Duplex primary malignant neoplasms are the most common, and triple or more primary malignant neoplasms were extremely rare. This is the first case of sextuple primary malignant neoplasms with lung cancer. CASE PRESENTATION: We report a case of two courses of stereotactic body radiation therapy for an 88-year-old Japanese male patient with six primary cancers in five organs. Cancers were detected in the thyroid, prostate, esophagus, bladder, and lungs. He also had a history of angina pectoris and had undergone percutaneous coronary intervention. Although he was capable of undergoing surgery for lung cancers, he refused it because he had experienced many invasive treatments, such as surgeries and percutaneous coronary intervention. In January 2020, the first stereotactic body radiation therapy was performed for the adenocarcinoma in the right lung. In March 2022, the second stereotactic body radiation therapy was performed for the nodule of the left lung. Although he complained of mild dyspnea after the first stereotactic body radiation therapy, we did not use steroids because his peripheral oxygen saturation was within the normal range. He had pleural effusion, cardiac dilatation, and pericardial effusion 2 months after the second stereotactic body radiation therapy, which improved with the use of compression stockings. CONCLUSION: A total of 43 and 17 months have passed since the first and second stereotactic body radiation therapy, respectively, there is no local recurrence and the patient can walk independently. We safely performed stereotactic body radiation therapy twice for our older patient with metachronous early-stage lung cancers. If another new tumor is detected, stereotactic body radiation therapy would be a good treatment option for the functional preservation of organs.

Unifying gamma passing rates in patient-specific QA for VMAT lung cancer treatment based on data assimilation.

This study aimed to identify systematic errors in measurement-, calculation-, and prediction-based patient-specific quality assurance (PSQA) methods for volumetric modulated arc therapy (VMAT) on lung cancer and to standardize the gamma passing rate (GPR) by considering systematic errors during data assimilation. This study included 150 patients with lung cancer who underwent VMAT. VMAT plans were generated using a collapsed-cone algorithm. For measurement-based PSQA, ArcCHECK was employed. For calculation-based PSQA, Acuros XB was used to recalculate the plans. In prediction-based PSQA, GPR was forecasted using a previously developed GPR prediction model. The representative GPR value was estimated using the least-squares method from the three PSQA methods for each original plan. The unified GPR was computed by adjusting the original GPR to account for systematic errors. The range of limits of agreement (LoA) were assessed for the original and unified GPRs based on the representative GPR using Bland-Altman plots. For GPR (3%/2 mm), original GPRs were 94.4 ± 3.5%, 98.6 ± 2.2% and 93.3 ± 3.4% for measurement-, calculation-, and prediction-based PSQA methods and the representative GPR was 95.5 ± 2.0%. Unified GPRs were 95.3 ± 2.8%, 95.4 ± 3.5% and 95.4 ± 3.1% for measurement-, calculation-, and prediction-based PSQA methods, respectively. The range of LoA decreased from 12.8% for the original GPR to 9.5% for the unified GPR across all three PSQA methods. The study evaluated unified GPRs that corrected for systematic errors. Proposing unified criteria for PSQA can enhance safety regardless of the methods used.

Quantitative analysis of interstitial lung abnormalities on computed tomography to predict symptomatic radiation pneumonitis after lung stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: Symptomatic radiation pneumonitis (SRP) is a complication of thoracic stereotactic body radiotherapy (SBRT). As visual assessments pose limitations, artificial intelligence-based quantitative computed tomography image analysis software (AIQCT) may help predict SRP risk. We aimed to evaluate high-resolution computed tomography (HRCT) images with AIQCT to develop a predictive model for SRP. MATERIALS AND METHODS: AIQCT automatically labelled HRCT images of patients treated with SBRT for stage I lung cancer according to lung parenchymal pattern. Quantitative data including the volume and mean dose (Dmean) were obtained for reticulation + honeycombing (Ret + HC), consolidation + ground-glass opacities, bronchi (Br), and normal lungs (NL). After associations between AIQCT's quantified metrics and SRP were investigated, we developed a predictive model using recursive partitioning analysis (RPA) for the training cohort and assessed its reproducibility with the testing cohort. RESULTS: Overall, 26 of 207 patients developed SRP. There were significant between-group differences in the Ret + HC, Br-volume, and NL-Dmean in patients with and without SRP. RPA identified the following risk groups: NL-Dmean ≥ 6.6 Gy (high-risk, n = 8), NL-Dmean < 6.6 Gy and Br-volume ≥ 2.5 % (intermediate-risk, n = 13), and NL-Dmean < 6.6 Gy and Br-volume < 2.5 % (low-risk, n = 133). The incidences of SRP in these groups within the training cohort were 62.5, 38.4, and 7.5 %; and in the testing cohort 50.0, 27.3, and 5.0 %, respectively. CONCLUSION: AIQCT identified CT features associated with SRP. A predictive model for SRP was proposed based on AI-detected Br-volume and the NL-Dmean.

Validation of the Lung-Mol Graded Prognostic Assessment (GPA) System for the Prognosis of Patients Receiving Radiotherapy for Brain Metastasis From Non-small Cell Lung Cancer.

PURPOSE: The Lung-mol graded prognostic assessment (GPA) system predicts the prognosis of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) separately for adenocarcinoma and non-adenocarcinoma. This study aimed to validate the Lung-molGPA system using a cohort of patients in our institution who received radiotherapy for BM. MATERIALS AND METHODS: Three hundred and thirty-nine patients with NSCLC who received their first course of radiotherapy for BM were included in the analysis. Among them, 65 received their second course of radiotherapy for BM. Data on sex, age, Karnofsky performance status (KPS), extracranial metastases (ECM), number of BM, histological type, and gene mutations were collected according to the Lung-molGPA system. We examined the validity of the scores assigned to the factors included in the Lung-molGPA system, separately for adenocarcinoma and non-adenocarcinoma. In addition, we validated the Lung-molGPA system to predict survival during both the first and second courses of radiotherapy. RESULTS: The factors in the Lung-molGPA were significantly associated with survival, except for age in non-adenocarcinoma with marginal significance. Regarding discrimination ability, the C-indices were 0.65 and 0.69 for adenocarcinoma and non-adenocarcinoma, respectively, in the first course of radiotherapy for BM, while those in the second course were 0.62 and 0.74, respectively. Survival prediction by Lung-molGPA was almost consistent with actual survival in the first course of radiotherapy, except for the score of 0-1.0 in both histologies and 2.5-3.0 in non-adenocarcinoma. In the second course of radiotherapy, median survival could be predicted for some patients with adenocarcinoma. CONCLUSIONS: Our study confirms the validity of Lung-molGPA for the estimation of median survival based on patient characteristics at the time of initiation of radiotherapy for patients in the first course of radiotherapy and shows that it may be applicable to patients with adenocarcinoma in the second course of radiotherapy.

Protocol of a phase II study to evaluate the efficacy and safety of deep-inspiration breath-hold daily online adaptive radiotherapy for centrally located lung tumours (PUDDING study).

BACKGROUND: Centrally located lung tumours present a challenge because of their tendency to exhibit symptoms such as airway obstruction, atelectasis, and bleeding. Surgical resection of these tumours often requires sacrificing the lungs, making definitive radiotherapy the preferred alternative to avoid pneumonectomy. However, the proximity of these tumours to mediastinal organs at risk increases the potential for severe adverse events. To mitigate this risk, we propose a dual-method approach: deep inspiration breath-hold (DIBH) radiotherapy combined with adaptive radiotherapy. The aim of this single-centre, single-arm phase II study is to investigate the efficacy and safety of DIBH daily online adaptive radiotherapy. METHODS: Patients diagnosed with centrally located lung tumours according to the International Association for the Study of Lung Cancer recommendations, are enrolled and subjected to DIBH daily online adaptive radiotherapy. The primary endpoint is the one-year cumulative incidence of grade 3 or more severe adverse events, as classified by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). DISCUSSION: Delivering definitive radiotherapy for centrally located lung tumours presents a dilemma between ensuring optimal dose coverage for the planning target volume and the associated increased risk of adverse events. DIBH provides measurable dosimetric benefits by increasing the normal lung volume and distancing the tumour from critical mediastinal organs at risk, leading to reduced toxicity. DIBH adaptive radiotherapy has been proposed as an adjunct treatment option for abdominal and pelvic cancers. If the application of DIBH adaptive radiotherapy to centrally located lung tumours proves successful, this approach could shape future phase III trials and offer novel perspectives in lung tumour radiotherapy. TRIAL REGISTRATION: Registered at the Japan Registry of Clinical Trials (jRCT; https://jrct.niph.go.jp/ ); registration number: jRCT1052230085 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1052230085 ).

Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

Dosimetric verification of four dose calculation algorithms for spine stereotactic body radiotherapy.

The applications of Type B [anisotropic analytical algorithm (AAA) and collapsed cone (CC)] and Type C [Acuros XB (AXB) and photon Monte Carlo (PMC)] dose calculation algorithms in spine stereotactic body radiotherapy (SBRT) were evaluated. Water- and bone-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. Subsequently, 48 consecutive patients with clinical spine SBRT plans were evaluated. All treatment plans were created using AXB in Eclipse. The prescription dose was 24 Gy in two fractions at a 10 MV FFF on TrueBeam. The doses were then recalculated with AAA, CC and PMC while maintaining the AXB-calculated monitor units and beam arrangement. The dose index values obtained using the four dose calculation algorithms were then compared. The AXB and PMC dose distributions agreed with the bone-equivalent phantom measurements (within ±2.0%); the AAA and CC values were higher than those in the bone-equivalent phantom region. For the spine SBRT plans, PMC, AAA and CC were overestimated compared with AXB in terms of the near minimum and maximum doses of the target and organ at risk, respectively; the mean dose difference was within 4.2%, which is equivalent with within 1 Gy. The phantom study showed that the results from AXB and PMC agreed with the measurements within ±2.0%. However, the mean dose difference ranged from 0.5 to 1 Gy in the spine SBRT planning study when the dose calculation algorithms changed. Users should incorporate a clinical introduction that includes an awareness of these differences.

Development and evaluation of a novel water-based pigment marker for radiation therapy skin marking.

Skin marks are widely used in external radiation therapy to ensure the accuracy of the irradiation position. However, conventional skin markers contain harmful substance, so we developed an alternative skin marker. The purpose of this study was to investigate the feasibility of using a novel water-based pigment marker comprising safe materials commonly used in cosmetics for clinical radiation therapy. We investigated various properties of the marker, namely marker longevity, color variety, line visibility, ink bleeding, and line durability, and improved the marker in response to the feel when drawing or being drawn on. The durability of the ink was evaluated by simultaneously applying the new marker and oil-based pen and comparing the period until the marks faded and became invisible. In clinical trial, we applied marks on the skin of 56 patients over three months to observe symptoms and visible changes in the skin. There were no complications of discomfort or pain, owing to the improvements in the marker tip. The marks drawn on the arms of volunteers with the new marker and the oil-based pen remained visible for a mean of 7.2 days and 3.6 days, respectively (P value < 0.001). The percentages of participants with no symptoms and no visible changes were 100%, respectively. We developed an alternative skin marker that complies with current regulatory standards by excluding crystal violet. The newly developed marker has features suitable for clinical use, such as resistance to smudging and water, marker tip shape and texture, and color variations.

Real-World Results of Stereotactic Body Radiotherapy for 399 Medically Operable Patients with Stage I Histology-Proven Non-Small Cell Lung Cancer.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

Development of a prediction model for target positioning by using diaphragm waveforms extracted from CBCT projection images.

PURPOSE: To develop a prediction model (PM) for target positioning using diaphragm waveforms extracted from CBCT projection images. METHODS: Nineteen patients with lung cancer underwent orthogonal rotational kV x-ray imaging lasting 70 s. IR markers placed on their abdominal surfaces and an implanted gold marker located nearest to the tumor were considered as external surrogates and the target, respectively. Four different types of regression-based PM were trained using surrogate motions and target positions for the first 60 s, as follows: Scenario A: Based on the clinical scenario, 3D target positions extracted from projection images were used as they were (PMCL ). Scenario B: The short-arc 4D-CBCT waveform exhibiting eight target positions was obtained by averaging the target positions in Scenario A. The waveform was repeated for 60 s (W4D-CBCT ) by adapting to the respiratory phase of the external surrogate. W4D-CBCT was used as the target positions (PM4D-CBCT ). Scenario C: The Amsterdam Shroud (AS) signal, which depicted the diaphragm motion in the superior-inferior direction was extracted from the orthogonal projection images. The amplitude and phase of W4D-CBCT were corrected based on the AS signal. The AS-corrected W4D-CBCT was used as the target positions (PMAS-4D-CBCT ). Scenario D: The AS signal was extracted from single projection images. Other processes were the same as in Scenario C. The prediction errors were calculated for the remaining 10 s. RESULTS: The 3D prediction error within 3 mm was 77.3% for PM4D-CBCT , which was 12.8% lower than that for PMCL . Using the diaphragm waveforms, the percentage of errors within 3 mm improved by approximately 7% to 84.0%-85.3% for PMAS-4D-CBCT in Scenarios C and D, respectively. Statistically significant differences were observed between the prediction errors of PM4D-CBCT and PMAS-4D-CBCT . CONCLUSION: PMAS-4D-CBCT outperformed PM4D-CBCT , proving the efficacy of the AS signal-based correction. PMAS-4D-CBCT would make it possible to predict target positions from 4D-CBCT images without gold markers.

Comparative Analysis of Photon Stereotactic Radiotherapy and Carbon-Ion Radiotherapy for Elderly Patients with Stage I Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study.

The emergence of an aging society and technological advances have made radiotherapy, especially stereotactic body radiotherapy (SBRT), a common alternative to surgery for elderly patients with early stage non-small-cell lung cancer (NSCLC). Carbon-ion radiotherapy (CIRT) is also an attractive treatment option with potentially lower toxicity for elderly patients with comorbidities. We compared the clinical outcomes of the two modalities using Japanese multicenter data. SBRT (n = 420) and single-fraction CIRT (n = 70) data for patients with stage I NSCLC from 20 centers were retrospectively analyzed. Contiguous patients ≥ 80 years of age were enrolled, and overall survival (OS), disease-specific survival (DSS), local control (LC), and adverse event rates were compared. The median age was 83 years in both groups and the median follow-up periods were 28.5 and 42.7 months for SBRT and CIRT, respectively. The 3-year OS, DSS, and LC rates were 76.0% vs. 72.3% (p = 0.21), 87.5% vs. 81.6% (p = 0.46), and 79.2% vs. 78.2% (p = 0.87), respectively, for the SBRT vs. CIRT groups. Regarding toxicity, 2.9% of the SBRT group developed grade ≥ 3 radiation pneumonitis, whereas none of the CIRT group developed grade ≥ 2 radiation pneumonitis. SBRT and CIRT in elderly patients showed similar survival and LC rates, although CIRT was associated with less severe radiation pneumonitis.

Dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors using a gimbal-mounted linac: A multi-institutional phase II study.

Background and purpose: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. Materials and methods: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. Results: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. Conclusion: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Brief Overview.

Stereotactic body radiotherapy (SBRT), a type of external beam radiotherapy, yields local control of hepatocellular carcinoma (HCC) at rates as high as 90%. SBRT has been recognized as an alternative therapy for patients for whom standard modalities such as surgery (resection or transplantation) or ablation are deemed unsuitable. SBRT has the potential to improve the prognosis of HCC, as it can be used as an adjunct to other treatment modalities. The assessment of post-SBRT images of the treated tumor and surrounding normal liver tissue requires special attention. Future research is warranted to determine how best to use SBRT versus other therapies and how to combine them.

Recurrence patterns and progression-free survival after chemoradiotherapy with or without consolidation durvalumab for stage III non-small cell lung cancer.

Chemoradiotherapy followed by consolidation durvalumab (CCRT+D) improves survival in patients with stage III non-small-cell lung cancer (NSCLC). We compared recurrence patterns and survival in the CCRT+D and CCRT cohorts. We conducted a multicenter, retrospective study in Japan. Patients who received CCRT for stage III NSCLC were included in this study. Of 178 eligible patients, 136 were in the CCRT+D and 42 were in the CCRT cohorts. Locoregional recurrence (LR), LR plus distant metastases (DM), and DM were observed in 20.6%, 8.8%, 27.9% of the CCRT+D, and 26.2%, 16.7% and 33.3% of the CCRT cohorts, respectively. In-field recurrence was the most common LR pattern in both cohorts. Squamous cell carcinoma and PD-L1 expression < 1%, and female sex and EGFR mutations were significantly associated with an increased risk of LR and DM. In patients with any risk factors for LR, the incidence of LR was similar in the CCRT+D and CCRT (39.5% vs 45.5%). The 24 month progression-free survival (PFS) and overall survival (OS) were 40.3% and 69.4% in the CCRT+D and 24.7% and 61.0% in the CCRT cohorts, respectively. Poor performance status and no consolidation durvalumab were significantly associated with shorter PFS. There was a significant difference in PFS between the CCRT+D and CCRT in the propensity score-matched cohort (HR = 0.51, P = 0.005). In conclusion, consolidation durvalumab decreased both LR and DM, and significantly improved PFS. However, in-field recurrence was still a major problem, as well as DM.

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.

Efficacy and Safety of External-beam Radiation Therapy for Unresectable Primary or Local Recurrent Cholangiocarcinoma.

BACKGROUND/AIM: Treatment options for unresectable cholangiocarcinoma are limited. The aim of the study was to evaluate the clinical outcomes of definitive external-beam radiation therapy (EBRT) for patients with unresectable cholangiocarcinoma. PATIENTS AND METHODS: Patients with unresectable primary cholangiocarcinoma, or local recurrent cholangiocarcinoma after primary surgery, without distant metastasis who received definitive EBRT (≥45 Gy) between January 2006 and December 2020 at our Institution were analyzed retrospectively. EBRT was basically performed using conventional fractionation (1.8-2 Gy per fraction). Prophylactic nodal irradiation was not performed. RESULTS: A total of 21 consecutive patients were analyzed: 7 primary and 14 recurrent cases. The median age was 70 (range=38-85) years at initiation of EBRT. A median dose of 54 (range=45-60) Gy comprising 1.8 (range=1.8-3) Gy per fraction was administered to the primary/recurrent local tumor site. The median follow-up period was 21.6 months. The 2-year overall survival, cause-specific survival, progression-free survival, and local recurrence-free rates were 35.7, 35.7, 16.1, and 32.7%, respectively. Long-term local control (>2 years after EBRT) was achieved in 19.0%. Grade 3 toxicities related to EBRT were observed in 4.8% (duodenum hemorrhage). No grade 4 or higher toxicities were observed. CONCLUSION: Definitive EBRT for unresectable cholangiocarcinoma was feasible and achieved long-term local control in a subset of patients. As the avoidance of local recurrence may lead to the benefits of prolonging biliary patency and subsequently alleviating the need for an invasive procedure for biliary drainage, EBRT could be one sustainable therapeutic option for patients with unresectable cholangiocarcinoma.

Propensity score-based analysis of stereotactic body radiotherapy, lobectomy and sublobar resection for stage I non-small cell lung cancer.

We applied two propensity score-based analyses to simultaneously compare three treatment modalities-stereotactic body radiotherapy (SBRT), lobectomy, or sublobar resection (SLR)-for stage I non-small cell lung cancer (NSCLC), with the aim of clarifying the average treatment effect (ATE) and formulating a risk-adapted approach to treatment selection. A retrospective review of 823 patients aged ≥65 years who underwent SBRT, lobectomy, or SLR for stage I NSCLC was conducted. The following two analyses using machine learning-based propensity scores were performed: (i) propensity score weighting (PSW) to assess the ATE in the entire cohort, and (ii) propensity score subclassification (PSS) to evaluate treatment effects of subgroups. PSW showed no significant difference in the 5-year overall survival (OS) between SBRT and SLR (60.0% vs 61.2%; P = 0.70) and significant difference between SBRT and lobectomy (60.0% vs 77.6%; P = 0.026). Local (LR) and distant recurrence (DR) rates were significantly lower in lobectomy than in SBRT, whereas there was no significant difference between SBRT and SLR. PSS identified four subgroups with different patient characteristics: lobectomy-oriented (5-year cumulative incidences of non-lung cancer death, 7.5%), SLR-oriented (14.2%), SBRT-oriented (23.8%) and treatment-neutral subgroups (16.1%). Each subgroup showed different survival trends regarding the three treatments. The ATE of SBRT was not significantly different from that of SLR, but it was inferior to lobectomy. Four subgroups with different risks of non-lung cancer death and different survival trends for each treatment were identified. These would help decision-making for patients with stage I NSCLC.

Usefulness of pro-gastrin-releasing peptide as a predictor of the incidence of brain metastasis and effect of prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer.

Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan-Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.