Purpose
To predict radiation pneumonitis (RP) grade 2 or worse after lung stereotactic body radiation therapy (SBRT) using dose‐based radiomic (dosiomic) features.
Methods
This multi‐institutional ...study included 247 early‐stage nonsmall cell lung cancer patients who underwent SBRT with a prescribed dose of 48–70 Gy at an isocenter between June 2009 and March 2016. Ten dose–volume indices (DVIs) were used, including the mean lung dose, internal target volume size, and percentage of entire lung excluding the internal target volume receiving greater than x Gy (x = 5, 10, 15, 20, 25, 30, 35, and 40). A total of 6,808 dose‐segmented dosiomic features, such as shape, first order, and texture features, were extracted from the dose distribution. Patients were randomly partitioned into two groups: model training (70%) and test datasets (30%) over 100 times. Dosiomic features were converted to z‐scores (standardized values) with a mean of zero and a standard deviation (SD) of one to put different variables on the same scale. The feature dimension was reduced using the following methods: interfeature correlation based on Spearman’s correlation coefficients and feature importance based on a light gradient boosting machine (LightGBM) feature selection function. Three different models were developed using LightGBM as follows: (a) a model with ten DVIs (DVI model), (b) a model with the selected dosiomic features (dosiomic model), and (c) a model with ten DVIs and selected dosiomic features (hybrid model). Suitable hyperparameters were determined by searching the largest average area under the curve (AUC) value in the receiver operating characteristic curve (ROC–AUC) via stratified fivefold cross‐validation. Each of the final three models with the closest the ROC–AUC value to the average ROC–AUC value was applied to the test datasets. The classification performance was evaluated by calculating the ROC–AUC, AUC in the precision–recall curve (PR–AUC), accuracy, precision, recall, and f1‐score. The entire process was repeated 100 times with randomization, and 100 individual models were developed for each of the three models. Then the mean value and SD for the 100 random iterations were calculated for each performance metric.
Results
Thirty‐seven (15.0%) patients developed RP after SBRT. The ROC–AUC and PR–AUC values in the DVI, dosiomic, and hybrid models were 0.660 ± 0.054 and 0.272 ± 0.052, 0.837 ± 0.054 and 0.510 ± 0.115, and 0.846 ± 0.049 and 0.531 ± 0.116, respectively. For each performance metric, the dosiomic and hybrid models outperformed the DVI models (P < 0.05). Texture‐based dosiomic feature was confirmed as an effective indicator for predicting RP.
Conclusions
Our dose‐segmented dosiomic approach improved the prediction of the incidence of RP after SBRT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To develop a prediction model (PM) for target positioning using diaphragm waveforms extracted from CBCT projection images.
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 (PM
). 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 (W
) by adapting to the respiratory phase of the external surrogate. W
was used as the target positions (PM
). 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 W
were corrected based on the AS signal. The AS-corrected W
was used as the target positions (PM
). 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.
The 3D prediction error within 3 mm was 77.3% for PM
, which was 12.8% lower than that for PM
. Using the diaphragm waveforms, the percentage of errors within 3 mm improved by approximately 7% to 84.0%-85.3% for PM
in Scenarios C and D, respectively. Statistically significant differences were observed between the prediction errors of PM
and PM
.
PM
outperformed PM
, proving the efficacy of the AS signal-based correction. PM
would make it possible to predict target positions from 4D-CBCT images without gold markers.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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.
The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is ...not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women.
We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years.
We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI.
This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.
Abstract Purpose To quantify the accuracy of extracted target motion trajectories in dual-source four-dimensional cone-beam computed tomography (4D-CBCT) by comparison with the actual ...three-dimensional (3D) target motion acquired simultaneously during 4D-CBCT scan. Materials and methods 4D-CBCT scans were performed for 19 different sinusoidal-like patterns and 13 lung cancer patients with implanted markers. Internal (In) or external (Ex) surrogates with amplitude (Amp)- or phase (Ph)-based sorting were used for the reconstructions. The targets were a pseudo-tumor and implanted marker for the phantom and clinical studies, respectively. The accuracy was evaluated by determining the maximum error (MaxEi ) between the 3D target position extracted from 4D-CBCT and the actual 3D target position detected by fluoroscopy in each i th phase (0 ⩽ i ⩽ 7). Results Median peak-to-peak target displacements in the superior–inferior (SI) direction were 20.6 and 20.6 mm in the phantom and clinical studies, respectively. In the phantom and clinical studies, the maximum of median MaxEi s in the SI direction was 4.6 and 9.2 mm in the In_Ph reconstruction. In the clinical study, the maximum of median MaxEi s was observed during the end-inhalation phase among all reconstruction approaches. Conclusions This study showed the magnitude of underestimation toward the inferior direction of target motion in clinical 4D-CBCT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Background and Purpose There is no early predictor of treatment response after lung stereotactic body radiotherapy (SBRT). We conducted this pilot study to evaluate whether serial diffusion ...weighted magnetic resonance imaging (DW-MRI) or positron emission tomography (PET) could predict response after SBRT. Material and Methods Early stage non-small cell lung cancer patients who received SBRT were eligible. DW-MRI and PET were undertaken pretreatment and every 3 months after SBRT in the first year. Patients with <1 year of follow-up were excluded from the analysis. The apparent diffusion coefficient (ADC) value and maximum standardized uptake value (SUVmax) of tumors were measured and compared between groups with or without local recurrence (LR). Results Fifteen patients were enrolled and the data of 14 patients were analyzed. The median ADC value was significantly lower in patients with LR (n = 3) than in those without LR (n = 11) at 3 and 6 months (1.11 vs. 1.54 and 0.98 vs. 1.69 ×10−3 mm2 /s; p = 0.039 and 0.012, respectively) while there was no significant difference pretreatment and at 9 and 12 months after treatment. No significant difference was observed in the SUVmax at any time point. Conclusions DW-MRI could be an early predictor of treatment response after lung SBRT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This pilot study evaluated the safety and efficacy of a dose escalation method with steep dose gradients using stereotactic body radiotherapy for peripheral lung tumors. The rate of grade 2 or higher ...radiation pneumonitis within 1 year was almost 10%. This dose escalation method was safe and effective for peripheral lung tumors and may obtain excellent local control rates.
This pilot study aimed to evaluate the safety and efficacy of a dose escalation method for the treatment of peripheral lung tumors by administrating steep dose gradients in the target volumes via stereotactic body radiotherapy (SBRT).
Patients with peripheral lung tumors were enrolled onto this study and treated with SBRT using a total dose of 70 Gy in 4 fractions at target isocenter, covering the planning target volume surface with 70% of the isodose. The primary end point was the rate of grade 2 or higher radiation pneumonitis (RP) within 1 year.
A total of 35 patients were enrolled onto this study between September 2014 and January 2016. Thirty-two patients with primary lung cancers and 3 patients with lung metastases were treated with SBRT. Grade 2 RP was observed in 4 patients within 1 year. No severe RP (grade 3 or higher) was observed within the follow-up period. The median follow-up period was 21.2 months (range, 4.2-31.7 months). Local recurrence was observed in a single patient with lung metastasis. No local recurrence was observed within the follow-up period in the 32 patients with primary lung cancer. The local control and overall survival rates at 2 years were 95.7% (95% confidence interval, 72.9-99.4) and 85.2% (95% confidence interval, 67.8-93.6), respectively.
This dose escalation method with steep dose gradients using SBRT for peripheral lung tumors was safe in the subacute phases. These results also suggest that this method can obtain excellent local control rates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Systemic inflammation and poor nutritional status have a negative effect on the outcomes of cancer. Here, we analyzed the effects of the pretreatment inflammatory and nutritional status on ...clinical outcomes of locally advanced non-small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. We retrospectively reviewed 89 patients with locally advanced NSCLC treated with chemoradiotherapy between July 2006 and June 2013. Serum C-reactive protein (CRP) was assessed as an inflammatory marker, and serum albumin, body mass index (BMI) and skeletal mass index were assessed as nutritional status markers. The relationships between these markers and overall survival (OS) were assessed. The median OS was 24.6 months 95% confidence interval (CI): 19.4–39.3 months. During follow-up, 58 patients (65%) had disease recurrence and 52 patients (58%) died. In multivariate Cox hazard analysis, CRP levels and BMI approached but did not achieve a significant association with OS (P = 0.062 and 0.094, respectively). Recursive partitioning analysis identified three prognostic groups based on hazard similarity (CRP-BMI scores): 0 = CRP < 0.3 mg/dl, 1 = CRP ≥ 0.3 mg/dl and BMI ≥ 18.5 kg/m2, and 2 = CRP ≥ 0.3 mg/dl and BMI < 18.5 kg/m2. The CRP-BMI score was significantly associated with OS (P = 0.023). Patients with scores of 0, 1 and 2 had median OS of 39.3, 24.5 and 14.5 months, respectively, and the scores also predicted the probability of receiving salvage treatment after recurrence. The CRP-BMI score is thus a simple and useful prognostic marker of clinical outcome for patients with locally advanced NSCLC treated with chemoradiotherapy.
Background:
Concurrent chemoradiotherapy (CCRT) with tri-weekly high-dose cisplatin (HDC) is considered the standard regimen. However, due to significant toxicity, various weekly low-dose schedules ...have been increasingly used. We investigated the tolerability and survival of patients with head and neck squamous cell carcinoma (HNSCC) who underwent CCRT with low-dose weekly cisplatin (LDC) for Japanese population.
Methods:
A retrospective review was conducted among patients with HNSCC who were treated with CCRT/LDC in our institute. Ninety-five patients who met the criteria were enrolled in this study. We evaluated the cycle and cumulative cisplatin dose, completion rate of radiotherapy, adverse events, and survival outcome.
Results:
The mean cycles and cumulative cisplatin dose were 4.7 cycles and 187 mg/m2. All patients completed planned dose of radiation without prolonged breaks. Leucopoenia was the most frequent dose-limiting factor and 44% patients developed grade 3 or 4 toxicity. The 2-year overall survival and recurrence-free survival were 93% and 74%, respectively. The significant differences of survival outcomes between the patients with total cisplatin dose (⩾200 mg and <200 mg) or among age distribution (35-55, 56-75, and ⩾76) were not observed.
Conclusions:
Concurrent chemoradiotherapy/LDC can be safely administered with acceptable toxicity and survival outcome even if the patients with higher age, lower eGFR, and so on.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Abstract
The aim of this study was to assess the impact of fractional dose and the number of arcs on interplay effects when volumetric modulated arc therapy (VMAT) is used to treat lung tumors with ...large respiratory motions. A three (fractional dose of 4, 7.5 or 12.5 Gy) by two (number of arcs, one or two) VMAT plan was created for 10 lung cancer cases. The median 3D tumor motion was 17.9 mm (range: 8.2–27.2 mm). Ten phase-specific subplans were generated by calculating the dose on each respiratory phase computed tomography (CT) scan using temporally assigned VMAT arcs. We performed temporal assignment of VMAT arcs using respiratory information obtained from infrared markers placed on the abdomens of the patients during CT simulations. Each phase-specific dose distribution was deformed onto exhale phase CT scans using contour-based deformable image registration, and a 4D plan was created by dose accumulation. The gross tumor volume dose of each 4D plan (4D GTV dose) was compared with the internal target volume dose of the original plan (3D ITV dose). The near-minimum 4D GTV dose (D99%) was higher than the near-minimum 3D internal target volume (ITV) dose, whereas the near-maximum 4D GTV dose (D1%) was lower than the near-maximum 3D ITV dose. However, the difference was negligible, and thus the 4D GTV dose corresponded well with the 3D ITV dose, regardless of the fractional dose and number of arcs. Therefore, interplay effects were negligible in VMAT-based stereotactic body radiation therapy for lung tumors with large respiratory motions.
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