• adaptive radiation therapy
• automated contouring
• cone-beam computed tomography
• deformable image registration (dir)
• lung cancer
• propagation
• treatment planning system

• EPID dosimetry
• adaptive radiotherapy
• lung
• secondary dose calculation
• synthetic CT

• Humans
• Radiotherapy Planning, Computer-Assisted/methods
• Lung Neoplasms/radiotherapy
• Lung Neoplasms/diagnostic imaging
• Cone-Beam Computed Tomography/methods
• Radiotherapy Dosage
• Quality Assurance, Health Care/standards
• Phantoms, Imaging
• Feasibility Studies
• Radiotherapy, Intensity-Modulated/methods
• Image Processing, Computer-Assisted/methods
• Radiotherapy, Image-Guided/methods
• Organs at Risk/radiation effects
• Algorithms

• University of Würzburg
• University of Würzburg

• GTV changes
• Radiomic biomarker
• Radiotherapy
• Small-cell lung cancer
• Tumor volume

• Humans
• Carcinoma, Non-Small-Cell Lung/pathology
• Lung Neoplasms/pathology
• Prognosis
• Tumor Burden
• Small Cell Lung Carcinoma/radiotherapy
• Radiotherapy Dosage
• Retrospective Studies

• Universitätsklinikum Münster (8918)

• adaptive radiotherapy
• deformable image registration
• dose accumulation
• quality assurance

• Humans
• Uncertainty
• Algorithms
• Neoplasms
• Software
• Radiotherapy, Intensity-Modulated
• Radiotherapy Planning, Computer-Assisted/methods
• Image Processing, Computer-Assisted/methods
• Radiotherapy Dosage

• R01 EB028324 NIBIB NIH HHS
• National Institute of Biomedical Imaging and Bioengineering, NIH

• Adaptive radiation therapy
• Isoeffective organ at risk sparing
• Isotoxic dose-escalation
• stage III NSCLC

• MR-guided radiotherapy
• Mr-linac
• adaptive fractionation
• adaptive radiotherapy
• inter-fraction motion

• ART
• NSCLC
• how
• when
• who

• adaptive therapy
• carbon ion therapy
• locally advanced non-small cell lung cancer

• Carcinoma, Non-Small-Cell Lung/diagnostic imaging
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Heavy Ion Radiotherapy
• Humans
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/pathology
• Lung Neoplasms/radiotherapy
• Organs at Risk
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy, Intensity-Modulated/methods

• SHDC12019X25 Shanghai Shen Kang Hospital Development Center Clinical Science and Technology Innovation Project
• 201940334 Shanghai Municipal Health Commission Funds

Hybrid magnetic resonance (MR)-Linac systems have recently been introduced into clinical practice. The systems allow online adaption of the treatment plan with the aim of compensating for interfractional anatomical changes. The aim of this study was to evaluate the dose volume histogram (DVH)-based dosimetric benefits of online adaptive MR-guided radiotherapy (oMRgRT) across different tumor entities and to investigate which subgroup of plans improved the most from adaption.

Fifty patients treated with oMRgRT for five different tumor entities (liver, lung, multiple abdominal lymph nodes, pancreas, and prostate) were included in this retrospective analysis. Various target volume (gross tumor volume GTV, clinical target volume CTV, and planning target volume PTV) and organs at risk (OAR) related DVH parameters were compared between the dose distributions before and after plan adaption.

All subgroups clearly benefited from online plan adaption in terms of improved PTV coverage. For the liver, lung and abdominal lymph nodes cases, a consistent improvement in GTV coverage was found, while many fractions of the prostate subgroup showed acceptable CTV coverage even before plan adaption. The largest median improvements in GTV near-minimum dose (D_98%) were found for the liver (6.3%, p < 0.001), lung (3.9%, p < 0.001), and abdominal lymph nodes (6.8%, p < 0.001) subgroups. Regarding OAR sparing, the largest median OAR dose reduction during plan adaption was found for the pancreas subgroup (-87.0%). However, in the pancreas subgroup an optimal GTV coverage was not always achieved because sparing of OARs was prioritized.

With online plan adaptation, it was possible to achieve significant improvements in target volume coverage and OAR sparing for various tumor entities and account for interfractional anatomical changes.

• NSCLC
• prediction
• radiotherapy
• tumour changes

• Jacobian maps
• NSCLC
• radiotherapy
• tumor regression

The standard of care for stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by durvalumab. Although doses higher than 66 Gy are standard in our center, they were used in only 6.9% of patients in the PACIFIC trial. We report our experience with durvalumab after high-dose radiotherapy. The database of a tertiary hospital for patients with stage III NSCLC who were treated with CRT and adjuvant durvalumab was evaluated. Progression-free survival (PFS), overall survival (OS), and local-regional failure (LRF) were measured from the administration of durvalumab. Thirty-nine patients were included. All were treated with intensity-modulated radiation (mean dose 69.9 Gy); Median follow-up time was 20.4 months (range 1–35.4). At 12 months, PFS was 49%, OS 79%, and LRF 14%. Intrathoracic failure at first progression was demonstrated in 8 (21%) patients. Adverse events requiring corticosteroids occurred in 10(25.6%) patients: pneumonitis – 6 (15.4%), hepatitis – 2 (5.1%), and arthralgia and pericarditis – 1 (2.6%). One patient (2.6%) died of pneumonitis. The occurrence of pneumonitis was significantly associated with lung V5 (55% vs. 42%, p = .04) and V20 (28% vs. 19%, p = .01) and mean lung dose (14.8 Gy vs.11.6 Gy, p = .05). The similar 12-month PFS and OS rates of our cohort and the PACIFIC trial support the use of high-dose radiotherapy in patients with stage III NSCLC. Treatment-related mortality was similar to the PACIFIC results. The intrathoracic failure rate in our cohort was lower than that reported from the PACIFIC trial, suggesting that radiation dose escalation may improve local control.

• Chemoradiation
• dose escalation
• durvalumab
• immunotherapy
• non-small cell lung cancer

• Adaptive radiotherapy
• Cone-beam CT
• Lung cancer
• Re-calculation of radiation doses

• Adaptive Radiotherapy (ART)
• Intensity-modulated radiation therapy (IMRT)
• Non-small cell lung cancer (NSCLC)

During the last years, preclinical and clinical studies have emerged supporting the rationale to integrate radiotherapy and immunotherapy. Radiotherapy may enhance the effects of immunotherapy by improving tumor antigen release, antigen presentation, and T-cell infiltration. Recently, magnetic resonance guided radiotherapy (MRgRT) has become clinically available. Compared to conventional radiotherapy techniques, MRgRT firstly allows for daily on-table treatment adaptation, which enables both dose escalation for increasing tumor response and superior sparing of radiosensitive organs-at-risk for reducing toxicity. The current review focuses on the potential of combining MR-guided adaptive radiotherapy with immunotherapy by providing an overview on the current status of MRgRT, latest developments in preclinical and clinical radio-immunotherapy, and the unique opportunities and challenges for MR-guided radio-immunotherapy. MRgRT might especially assist in answering open questions in radio-immunotherapy regarding optimal radiation dose, fractionation, timing of immunotherapy, appropriate irradiation volumes, and response prediction.

• adaptive treatment
• immunotherapy
• magnetic resonance-guided radiotherapy
• preclinical
• radio-immunotherapy

To evaluate the potential of cone-beam-CT (CB-CT) guided adaptive radiotherapy (ART) for locally advanced non-small cell lung cancer (NSCLC) for sparing of surrounding organs-at-risk (OAR).

In 10 patients with locally advanced NSCLC, daily CB-CT imaging was acquired during radio- (n = 4) or radiochemotherapy (n = 6) for simulation of ART. Patients were treated with conventionally fractionated intensity-modulated radiotherapy (IMRT) with total doses of 60–66 Gy (pPlan) (311 fraction CB-CTs). OAR were segmented on every daily CB-CT and the tumor volumes were modified weekly depending on tumor changes. Doses actually delivered were recalculated on daily images (dPlan), and voxel-wise dose accumulation was performed using a deformable registration algorithm. For simulation of ART, treatment plans were adapted using the new contours and re-optimized weekly (aPlan).

CB-CT showed continuous tumor regression of 1.1 ± 0.4% per day, leading to a residual gross tumor volume (GTV) of 65.3 ± 13.4% after 6 weeks of radiotherapy (p = 0.005). Corresponding PTVs decreased to 83.7 ± 7.8% (p = 0.005). In the actually delivered plans (dPlan), both conformity (p = 0.005) and homogeneity (p = 0.059) indices were impaired compared to the initial plans (pPlan). This resulted in higher actual lung doses than planned: V_20Gy was 34.6 ± 6.8% instead of 32.8 ± 4.9% (p = 0.066), mean lung dose was 19.0 ± 3.1 Gy instead of 17.9 ± 2.5 Gy (p = 0.013). The generalized equivalent uniform dose (gEUD) of the lung was 18.9 ± 3.1 Gy instead of 17.8 ± 2.5 Gy (p = 0.013), leading to an increased lung normal tissue complication probability (NTCP) of 15.2 ± 13.9% instead of 9.6 ± 7.3% (p = 0.017). Weekly plan adaptation enabled decreased lung V_20Gy of 31.6 ± 6.2% (−3.0%, p = 0.007), decreased mean lung dose of 17.7 ± 2.9 Gy (−1.3 Gy, p = 0.005), and decreased lung gEUD of 17.6 ± 2.9 Gy (−1.3 Gy, p = 0.005). Thus, resulting lung NTCP was reduced to 10.0 ± 9.5% (−5.2%, p = 0.005). Target volume coverage represented by conformity and homogeneity indices could be improved by weekly plan adaptation (CI: p = 0.007, HI: p = 0.114) and reached levels of the initial plan (CI: p = 0.721, HI: p = 0.333).

IGRT with CB-CT detects continuous GTV and PTV changes. CB-CT-guided ART for locally advanced NSCLC is feasible and enables superior sparing of healthy lung at high levels of plan conformity.

• adaptive radiotherapy
• cone-beam computed tomography
• lung cancer
• non-small cell lung cancer
• normal tissue
• organs at risk
• pneumonitis
• quality assessment

This study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART).

Twenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test.

Patients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1%, range − 2.9-44.0%). The V₅₁ of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p = 0.452). Only 11.1% of patients had above 5% relative decrease in V₅₁ of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase < 5%) was observed in doses of total lung (mean dose, V₂₀ and V₃₀), esophagus (mean dose, maximum dose) and heart (mean dose, V₃₀ and V₄₀) in accumulated plans. Less than 30% of patients had above 5% relative increase of lung or heart doses. Patients with quick tumor regression or baseline obstructive pneumonitis showed more notable increase in doses to normal structures. Patients with baseline obstructive atelectasis showed notable decrease (10.3%) in dose coverage of PTV-GTV.

LANSCLC patients treated with HRT had sufficient tumor dose coverage and acceptable normal tissue dose deviation. ART should be applied in patients with quick tumor regression and baseline obstructive pneumonitis/atelectasis to spare more normal structures.

Supplementary information accompanies this paper at 10.1186/s12885-020-07617-3.

• Accumulation
• Deformable image registration
• Hypofractionated radiotherapy
• Non-small cell lung cancer

To analyze patterns of failure in patients with LA-NSCLC who received definitive chemoradiotherapy (CRT) and to build a nomogram for predicting the failure patterns in this population of patients.

Clinicopathological data of patients with LA-NSCLC who received definitive chemoradiotherapy and follow-up between 2013 and 2016 in our hospital were collected. The endpoint was the first failure after definitive chemoradiotherapy. With using elastic net regression and 5-fold nested cross-validation, the optimal model with better generalization ability was selected. Based on the selected model and corresponding features, a nomogram prediction model was built. This model was also validated by ROC curves, calibration curve and decision curve analysis (DCA).

With a median follow-up of 28 months, 100 patients experienced failure. There were 46 and 54 patients who experience local failure and distant failure, respectively. Predictive model including 9 factors (smoking, pathology, location, EGFR mutation, age, tumor diameter, clinical N stage, consolidation chemotherapy and radiation dose) was finally built with the best performance. The average area under the ROC curve (AUC) with 5-fold nested cross-validation was 0.719, which was better than any factors alone. The calibration curve revealed a satisfactory consistency between the predicted distant failure rates and the actual observations. DCA showed most of the threshold probabilities in this model were with good net benefits.

Clinicopathological factors could collaboratively predict failure patterns in patients with LA-NSCLC who are receiving definitive chemoradiotherapy. A nomogram was built and validated based on these factors, showing a potential predictive value in clinical practice.

• Failure
• Locally advanced non-small cell lung cancer
• Predictor
• Recurrence

• MR-guided radiation therapy
• magnetic resonance imaging
• radiation oncology
• radiation oncology imaging

• Humans
• Magnetic Resonance Imaging, Interventional/methods
• Neoplasms/diagnostic imaging
• Neoplasms/radiotherapy
• Radiotherapy, Image-Guided/methods

• 21993 Cancer Research UK
• A21993 Cancer Research UK

• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Chemoradiotherapy
• Female
• Humans
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/pathology
• Lung Neoplasms/radiotherapy
• Male
• Middle Aged
• Neoplasm Staging
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy, Image-Guided/methods
• Survival Rate
• Tomography, X-Ray Computed/methods

Robotic stabilization of a therapeutic radiation beam with respect to a dynamically moving tumor target can be accomplished either by moving the radiation source, the patient, or both. As the treatment beam is on during this process, the primary goal is to minimize exposure of normal tissue to radiation as much as possible when moving the target back to the desired position. Due to the complex mechanical structure of 6 degree-of-freedom (6DoF) robots, it is not intuitive as to what 6 dimensional (6D) correction trajectory is optimal in achieving such a goal. With proportional-integrative-derivative (PID) and other controls, the potential exists that the controller may generate a trajectory that is highly curved, slow, or suboptimal in that it leads to unnecessary exposure of healthy tissue to radiation. This work investigates a novel feedback planning method that takes into account a robot’s mechanical joint structure, patient safety tolerances, and other system constraints, and performs real-time optimization to search the entire 6D trajectory space in each time cycle so it can respond with an optimal 6D correction trajectory.

Computer simulations were created for two 6DoF robotic patient support systems: a Stewart-Gough platform for moving a patient’s head in frameless maskless stereotactic radiosurgery, and a linear accelerator treatment table for moving a patient in prostate cancer radiation therapy. Motion planning was formulated as an optimization problem and solved at real-time speeds using the L-BFGS algorithm. Three planning methods were investigated, moving the platform as fast as possible (platform-D), moving the target along a straight-line (target-S), and moving the target based on the fastest descent of position error (target-D). Both synthetic motion and prior recorded human motion were used as input data and output results were analyzed.

For randomly generated 6D step-like and sinusoidal synthetic input motion, target-D planning demonstrated the smallest net trajectory error in all cases. On average, optimal planning was found to have a 45% smaller target trajectory error than platform-D control, and a 44% smaller target trajectory error than target-S planning. For patient head motion compensation, only target-D planning was able to maintain a ≤0.5mm and ≤0.5deg clinical tolerance objective for 100% of the treatment time. For prostate motion, both target-S planning and target-D planning outperformed platform-D control.

A general 6D target trajectory optimization framework for robotic patient motion compensation systems was investigated. The method was found to be flexible as it allows control over various performance requirements such as mechanical limits, velocities, acceleration, or other system control objectives.

• Computer Simulation
• Computer Systems
• Head Movements
• Humans
• Male
• Motion
• Patient Positioning/methods
• Patient Positioning/statistics & numerical data
• Phantoms, Imaging
• Prostatic Neoplasms/radiotherapy
• Radiosurgery/methods
• Radiosurgery/statistics & numerical data
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy Planning, Computer-Assisted/statistics & numerical data
• Robotic Surgical Procedures/methods
• Robotic Surgical Procedures/statistics & numerical data
• Robotics/methods
• Robotics/statistics & numerical data

• R01 CA227124 NCI NIH HHS
• National Cancer Institute
• American Cancer Society

• automated treatment planning
• dose escalation
• pancreatic cancer
• personalized treatment
• stereotactic body radiotherapy

• Automation
• Dose Fractionation, Radiation
• Humans
• Organs at Risk
• Pancreatic Neoplasms/radiotherapy
• Precision Medicine
• Radiometry
• Radiosurgery/methods
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/methods

• P30 CA008748 NCI NIH HHS

• Aged
• Aged, 80 and over
• Female
• Humans
• Lung/diagnostic imaging
• Lung/pathology
• Lung/physiopathology
• Lung/radiation effects
• Lung Neoplasms/radiotherapy
• Male
• Middle Aged
• Prospective Studies
• Pulmonary Ventilation
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted/methods
• Radiotherapy, Image-Guided/methods
• Tomography, X-Ray Computed/methods
• Tumor Burden

• K12 CA138464 NCI NIH HHS
• P30 CA093373 NCI NIH HHS

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Chemoradiotherapy
• Female
• Follow-Up Studies
• Humans
• Lung/radiation effects
• Lung Neoplasms/pathology
• Lung Neoplasms/radiotherapy
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasms/radiotherapy
• Positron-Emission Tomography
• Prognosis
• Radiation Dosage
• Tomography, X-Ray Computed
• Treatment Outcome

• Dose escalated chemoradiotherapy
• NSCLC
• Phase II
• Randomized
• Stage III

• Adaptive planning
• GTV changes
• Intensity-modulated radiation therapy
• Lung cancer
• Survival

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carboplatin/administration & dosage
• Carcinoma, Non-Small-Cell Lung/diagnostic imaging
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Carcinoma, Non-Small-Cell Lung/pathology
• Carcinoma, Non-Small-Cell Lung/radiotherapy
• Cisplatin/administration & dosage
• Disease-Free Survival
• Dose Fractionation, Radiation
• Female
• Humans
• Lung Neoplasms/diagnostic imaging
• Lung Neoplasms/drug therapy
• Lung Neoplasms/pathology
• Lung Neoplasms/radiotherapy
• Male
• Middle Aged
• Neoplasm Staging
• Radiotherapy, Intensity-Modulated
• Tomography, X-Ray Computed

• atelectasis
• deformable image registration
• deformation
• lung
• registration

• adaptive
• cat
• dog
• radiation therapy
• thymoma

and purpose: This retrospective study aimed to investigate the feasibility of shrinking field radiotherapy during chemoradiotherapy in non-small cell lung cancer (NSCLC).

Ninety-seven patients with stage III NSCLC who achieved a good response to chemoradiation were analyzed. Computed tomography was performed after 40-50 Gy dose radiation to evaluate curative effect. Patients in the shrinking field group underwent resimulation CT scans and shrinking field radiotherapy. Acute symptomatic irradiation-induced pneumonia (ASIP), progression patterns and survival were assessed.

Of the 97 patients who achieved response after a median total dose of 60 Gy, fifty patients received shrinking field radiotherapy. The incidence of acute symptomatic irradiation-induced pneumonia tended to be lower for the shrinking field group (18.0% vs. 23.4%, P = 0.51). The rate of disease progression was significantly higher in the non-shrinking than shrinking field group (95.7% vs. 66.0%, P < 0.001). Compared to the non-shrinking field group, the shrinking field group had similar overall survival (30.0 vs. 30.0 months, P = 0.58) but significantly better median progression-free survival (14.0 vs. 11.0 months, P = 0.006).

Shrinking field radiotherapy during chemoradiotherapy in stage III non-small cell lung cancer seems safe with acceptable toxicities and relapse, and potentially spares normal tissues and enables dose escalation. Prospective trials are warranted.

• adaptive radiotherapy
• chemoradiation therapy
• dose escalation
• lung cancer

• Adaptive radiotherapy
• Chemoradiation
• Intrathoracic changes
• Locally advanced
• NSCLC

• 4D imaging
• computed tomography
• cone beam computed tomography lung

To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V₅, V₁₀, V₁₅, V₂₀, V₂₅, V₃₀ and the mean dose of total lung, V₁₀, V₂₀, V₃₀, V₄₀, V₅₀, V₆₀ and the mean dose of heart, V₃₅, V₄₀, V₅₀, V_55, V₆₀, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC.