Long-Term Outcomes of Ablative Carbon-Ion Radiotherapy for Central Non-Small Cell Lung Cancer: A Single-Center, Retrospective Study.

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006-2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments.

Safety and Efficacy of Single-Fraction Carbon-Ion Radiotherapy for Early-Stage Lung Cancer with Interstitial Pneumonia.

Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer. The study included 50 consecutive patients treated between April 2013 and September 2022, whose clinical stage of lung cancer (UICC 7th edition) was 1A:1B:2A:2B = 32:13:4:1. Of these, 32 (64%) showed usual interstitial pneumonia patterns. With a median follow-up of 23.5 months, the 3-year overall survival (OS), cause-specific survival, and local control rates were 45.0, 75.4, and 77.8%, respectively. The median lung V5 and V20 were 10.0 and 5.2%, respectively (mean lung dose, 2.6 Gy). The lung dose, especially lung V20, showed a strong association with OS (p = 0.0012). Grade ≥ 2 pneumonia was present in six patients (13%), including two (4%) with suspected grade 5. CIRT can provide a relatively safe and curative treatment for patients with IP-complicated lung cancer. However, IP increases the risk of severe radiation pneumonitis, and further studies are required to assess the appropriate indications.

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.

Long-term outcomes of high dose carbon-ion radiation therapy for unresectable upper cervical (C1-2) chordoma.

BACKGROUND: Chordoma is a rare, locally invasive neoplasm of the axial skeleton. Complete resection is often difficult, especially for the upper-cervical (C1-2) spine. We evaluated the efficacy and safety of carbon-ion radiotherapy (CIRT) for unresectable C1-2 chordoma. METHODS: Patients with C1-2 chordoma treated with definitive CIRT (60.8 Gy [RBE] in 16 fractions) were retrospectively analyzed. We evaluated OS, LC, PFS, and toxicity. RESULTS: Nineteen eligible patients all completed the planned course of CIRT. With the median follow-up 68 months (range: 29-144), median OS was 126 months (range: 36-NA). Five-year OS, LC, and PFS were 68.4% (95% CI, 42.8%-84.4%), 75.2% (46.1%-90.0%), and 64.1% (36.3%-82.3%), respectively. Regarding acute toxicity of grade ≥3, there was only one grade 3 mucositis. Late toxicity included radiation-induced myelitis (grade 3 in 1 patient; 5.3%), and compression fractures (n = 5; 26.3%). CONCLUSIONS: High-dose CIRT is a promising treatment option for unresectable upper cervical chordoma.

Linear accelerator-based stereotactic body radiation therapy in the treatment of oligometastatic disease.

The present study reports the clinical outcomes of hypofractionated stereotactic body radiation therapy (SBRT) for oligometastasis (OM) originating from various tumors. Between February 2012 and April 2017, 40 patients with unresectable OM were treated with SBRT. Of these patients, 92% showed a solitary nodal metastasis and the rest had up to three metastases. The dose prescription was 50 Gy in 10 fractions with three-dimensional conformal techniques or volumetric intensity-modulated arc therapy. Median follow-up was 14 months. Of the 40 patients, none showed local progression at the site of SBRT, but 20 patients showed tumor growth at distant sites during follow-up. The 2- and 3-year overall survival rates were 45.1 and 36.1%, respectively. The 2- and 3-year progression-free survival rates were 35.4 and 26.5%, respectively. The interval between diagnosis and detection of OM (<2 vs. >2 years) and primary tumor site (esophagus vs. others) emerged as significant variables affecting survival. Grade 3 subacute and grade 4 chronic toxicities were observed in 1 and 2 patients, respectively. SBRT of 50 Gy in 10 fractions for OM from various primary tumors was shown to lead to good clinical outcomes from the viewpoints of local control and toxicity frequency. However, additional studies are required to identify the patient groups likely to receive maximal benefits from such treatment.

Salvage stereotactic body radiotherapy for post-operative oligo-recurrence of non-small cell lung cancer: A single-institution analysis of 59 patients.

A standard treatment for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgery, and subsequently develop local failure or intrathoracic oligo-recurrence, has not yet been established. The present study aimed to assess the feasibility of stereotactic body radiotherapy (SBRT) for this subgroup of patients. Consequently, a retrospective analysis was conducted of patients with NSCLC recurrence who were treated with SBRT, and previously underwent curative surgical resection between October 2011 and October 2016. Post-SBRT survival [overall survival (OS); progression-free survival (PFS); and local control (LC)] and toxicity were analyzed. Prognostic factors for OS were identified using univariate and multivariate analysis. A total of 52 patients and 59 tumors were analyzed. The median follow-up time was 25 months (35 months for surviving patients), and median OS following salvage SBRT was 32 months. The 1- and 3-year OS rates were 84.4 and 67.8%, respectively. 1- and 3-year PFS rates were 80.8 and 58.7%, respectively. Only 4 patients (7.7%) developed local failure. Median LC was 71 months and 1- and 3-year LC rate were 97.9 and 94.9%, respectively. A total of 4 patients experienced grade 3 or higher adverse events (AEs) and two experienced grade 5 AEs (pneumonitis and hemoptysis). Central tumor location and the possibility of re-operation were independent prognostic factors for OS. The present study indicated that post-operative salvage SBRT is a promising therapeutic option for patients with NSCLC with locoregional or intrathoracic oligo-recurrence. We regard toxicity was also acceptable. However, further research is required on the appropriate selection of subjects, and stratification of the analysis by certain risk factors would increase the accuracy of the conclusions.

Stereotactic body radiotherapy (SBRT) for oligo-metastatic liver metastases from breast cancer, as an effective and safe alternative to surgery: a review.

The liver is a common organ of metastases from most solid malignancies, including breast cancer, and breast cancer with liver metastases (BCLM) has a poor prognosis despite advances in systemic therapies. It has become widely recognized that local treatments for oligometastases with curative intent could improve disease control and survival outcomes under certain conditions. Regarding local therapy for BCLM, surgical resection had been the first choice though its indications were quite limited. Recently, an increasing number of prospective trials on stereotactic body radiation therapy (SBRT) for liver metastases (LMs) were published, reporting excellent tumor control with less toxicity. According to these reports, breast cancer origin is a favorable prognostic factor in SBRT for liver metastasis. Further research on patient selection and optimal dose fractionation will establish SBRT as a safe and feasible alternative treatment for resection and ablation in selected patients with BCLM. This review intends to provide evidence on the background and methods of focal radiation therapy for LMs, especially BCLM, and describes the current and future role of SBRT in the treatment of BCLM.

Standardization of imaging features for radiomics analysis.

Radiomics has the potential to provide tumor characteristics with noninvasive and repeatable way. The purpose of this paper is to evaluate the standardization effect of imaging features for radiomics analysis. For this purpose, we prepared two CT databases ; one includes 40 non-small cell lung cancer (NSCLC) patients for whom tumor biopsies was performed before stereotactic body radiation therapy in The University of Tokyo Hospital, and the other includes 29 early-stage NSCLC datasets from the Cancer Imaging Archive. The former was used as the training data, whereas the later was used as the test data in the evaluation of the prediction model. In total, 476 imaging features were extracted from each data. Then, both training and test data were standardized as the min-max normalization, the z-score normalization, and the whitening from the principle component analysis. All of standardization strategies improved the accuracy for the histology prediction. The area under the receiver observed characteristics curve was 0.725, 0.789, and 0.785 in above standardizations, respectively. Radiomics analysis has shown that robust features have a high prognostic power in predicting early-stage NSCLC histology subtypes. The performance was able to be improved by standardizing the data in the feature space. J. Med. Invest. 66 : 35-37, February, 2019.

Stereotactic body radiotherapy for centrally-located lung tumors with 56 Gy in seven fractions: A retrospective study.

Stereotactic body radiotherapy (SBRT) for centrally-located lung tumors remains a challenge because of the increased risk of treatment-related adverse events (AEs), and uncertainty around prescribing the optimal dose. The present study reported the results of central tumor SBRT with 56 Gy in 7 fractions (fr) at the University of Tokyo Hospital. A total of 35 cases that underwent SBRT with or without volumetric-modulated arc therapy consisting of 56 Gy/7 fr for central lung lesions between 2010 and 2016 at the University of Tokyo Hospital were reveiwed. A central lesion was defined as a tumor within 2 cm of the proximal bronchial tree (RTOG 0236 definition) or within 2 cm in all directions of any critical mediastinal structure. Local control (LC), overall survival (OS), and AEs were investigated. The Kaplan-Meier method was used to estimate LC and OS. AEs were scored per the Common Terminology Criteria for Adverse Events Version 4.0. Thirty-five patients with 36 central lung lesions were included. Fifteen lesions were primary non-small cell lung cancer (NSCLC), 13 were recurrences of NSCLC, and 8 had oligo-recurrences from other primaries. Median tumor diameter was 29 mm. Eighteen patients had had prior surgery. At a median follow-up of 13.1 months for all patients and 18.3 months in surviving patients, 22 patients had died, ten due to primary disease (4 NSCLC), while three were treatment-related. The 1- and 2-year OS were 57.3 and 40.4%, respectively, and median OS was 15.7 months. Local recurrence occurred in only two lesions. 1- and 2-year LC rates were both 96%. Nine patients experienced grade ≥3 toxicity, representing 26% of the cohort. Two of these were grade 5, one pneumonitis and one hemoptysis. Considering the background of the subject, tumor control of our central SBRT is promising, especially in primary NSCLC. However, the safety of SBRT to central lung cancer remains controversial.

Flattening filter-free technique in volumetric modulated arc therapy for lung stereotactic body radiotherapy: A clinical comparison with the flattening filter technique.

The present study sought to evaluate the impact of the flattening filter-free (FFF) technique in volumetric modulated arc therapy for lung stereotactic body radiotherapy. Its clinical safety and availability were compared with the flattening filter (FF) method. The cases of 65 patients who underwent lung volumetric modulated arc therapy-stereotactic body radiotherapy (VMAT-SBRT) using FF or FFF techniques were reviewed. A total of 55 Gy/4 fractions (fr) was prescribed for peripheral lesions or 56 Gy/7 fr for central lesions. The total monitor units (MU), treatment time, dose to tumors, dose to organs at risk, tumor control (local control rate, overall survival, progression-free survival) and adverse events between cases treated with FF and cases treated with the FFF technique were compared. A total of 35 patients were treated with conventional FF techniques prior to November 2014 and 30 patients were treated with FFF techniques after this date. It was revealed that the beam-on time was significantly shortened by the FFF technique (P<0.01). Other factors were similar for FFF and FF plans in respect to conformity (P=0.95), homogeneity (P=0.20) and other dosimetric values, including total MU and planning target volume/internal target volume coverage. The median follow-up period was 18 months (range, 2-35). One-year local control rates were 97.1 and 90.0% in the FF group and FFF groups, respectively (P=0.33). Grade 3 pneumonitis was observed in 5.8% of FF patients and 3.4% of FFF patients (P=1.00). No other adverse events ≥grade 3 were observed. The results of the study suggest that VMAT-SBRT using the FFF technique shortens the treatment time for lung SBRT while maintaining a high local control rate with low toxicity.

Classification of early stage non-small cell lung cancers on computed tomographic images into histological types using radiomic features: interobserver delineation variability analysis.

Radiomics, which involves the extraction of large numbers of quantitative features from medical images, has attracted attention in cancer research. In radiomics analysis, tumor segmentation is a crucial step. In this study, we evaluated the potential application of radiomics for predicting the histology of early stage non-small cell lung cancer (NSCLC) by analyzing interobserver variability in tumor delineation. Forty patient datasets were included in this study, 21 involving adenocarcinomas and 19 involving squamous cell carcinomas. All patients underwent stereotactic body radiotherapy treatment. In total, 476 features were extracted from each dataset, representing treatment planning, computed tomography images, and gross tumor volume (GTV). The definition of GTV can significantly affect the histology prediction. Therefore, in the present study, the effect of interobserver tumor delineation variability on radiomic features was evaluated by preparing 4 volumes of interest (VOIs) for each patient, as follows: the original GTV (which was delineated at treatment planning); two GTVs delineated retrospectively by radiation oncologists; and a semi-automatic GTV contoured by a medical physicist. Radiomic features extracted from each VOI were then analyzed using a naïve Bayesian model. Area-under-the-curve (AUC) analysis showed that interobserver variability in delineation is a significant factor in radiomics performance. Nevertheless, with 8 selected features, AUC values averaged over the VOIs were high (0.725 ± 0.070). The present study indicated that radiomics has potential for predicting early stage NSCLC histology despite variability in delineation. The high prediction accuracy implies that noninvasive histology evaluation by radiomics is a promising clinical application.

Examination of the predictive factors of the response to whole brain radiotherapy for brain metastases from lung cancer using MRI.

Previous studies have been conducted on the prognostic factors for overall survival in patients with brain metastases (BMs) following whole brain radiotherapy (WBRT). However, there have been a small number of studies regarding the prognostic factors for the response of tumor to WBRT. The aim of the present study was to identify the predictive factors for the response to WBRT from the point of view of reduction of tumor using magnetic resonance imaging. A retrospective analysis of 62 patients with BMs from primary lung cancer treated with WBRT was undertaken. The effects of the following factors on the response to WBRT were evaluated: Age; sex; performance status; lactate dehydrogenase; pathology; existence of extracranial metastases; activity of extracranial disease; chemo-history; chest radiotherapy history; treatment term; γ-knife radiotherapy; diffusion weighted image signal intensity; tumor diameter; extent of edema and the edema/tumor (E/T) ratio. The association between the reduction of tumors and clinical factors was evaluated using logistic regression analysis. P<0.05 was considered to indicate a statistically significant difference. The overall response ratio of this cohort was 54.8%. In the univariate analysis, the response of tumors was associated with the presence of small cell lung carcinoma (SCLC; P=0.0007), an E/T ratio of ≥1.5 (P=0.048), and a median tumor diameter of <20 mm (P=0.014). In the multivariate analysis, the presence of SCLC [P=0.001; odds ratio (OR), 17.152), an E/T ratio of ≥1.5 (P=0.019; OR, 9.526), and the presence of extracranial metastases (P=0.031; OR, 4.875) were revealed to be independent predictive factors for the reduction of tumor. The following 3 factors were significantly associated with the response of tumors to WBRT: The presence of SCLC; an E/T ratio of ≥1.5; and the presence of extracranial metastases. The E/T ratio is a novel index that provides a simple and easy predictive method for use in a clinical setting.

Contribution of metals to brain MR signal intensity: review articles.

Various metals are essential nutrients in humans, and metal shortages lead to a variety of deficiency diseases. Metal concentration abnormalities may cause metal deposition in the brain, and magnetic resonance imaging (MRI) is the most potent and sensitive technique now available for detecting metal deposition given the difficulties associated with performing brain tissue biopsy. However, the brain contains many kinds of metals that affect the signal intensity of MRI, which has led to numerous misunderstandings in the history of metal analysis. We reviewed the history of brain metal analysis with histologic findings. Typically, manganese overload causes high signal intensity on T1-weighted images (T1WI) in the globus pallidus, iron overload causes low signal intensity in the globus pallidus on T2-weighted images, and gadolinium deposition causes high signal intensity in the dentate nucleus, globus pallidus, and pulvinar of thalamus on T1WI. However, because nonparamagnetic materials and other coexisting metals also affect the signal intensity of brain MRI, the quantitative analysis of metal concentrations is difficult. Thus, when analyzing metal deposition using MRI, caution should be exercised when interpreting the validity and reliability of the obtained data.

Qualitative Analysis of Preoperative High-Resolution Computed Tomography: Risk Factors for Pulmonary Complications After Major Lung Resection.

BACKGROUND: Postoperative pulmonary complications after major lung resection are strongly associated with mortality. Qualitative findings of emphysema, bronchiectasis, and bronchial wall thickening on high-resolution computed tomography (HRCT) are indicators of chronic obstructive pulmonary disease and may serve as risk factors for pulmonary complications. METHODS: The subjects were 347 consecutive patients who underwent single lobectomy for pulmonary malignancy from May 2010 to December 2014. Correlations of pulmonary complications with preoperative clinical factors and HRCT findings were retrospectively examined using multivariate logistic regression analysis to compare the predictive ability for pulmonary complications using clinical variables that were reported to be risk factors. RESULTS: Patients who had pulmonary complications were more frequently male (p < 0.001), with a greater smoking history (p < 0.001), lower rate of steroid use (p < 0.001), more frequent emphysema on HRCT (p < 0.001), more frequent bronchiectasis on HRCT (p = 0.002), more frequent bronchial wall thickening on HRCT (p < 0.001), and higher rate of extended resection (p = 0.006). In multivariate analysis, HRCT findings (odds ratio [OR] 12.01, 95% confidence interval [CI]: 5.582 to 25.83, p < 0.001) and extended resection (OR 7.726, 95% CI: 1.678 to 35.57, p = 0.009) were independent risk factors for pulmonary complications. After matching of risk factors between patients with and without pulmonary complication, emphysema (OR 3.394, 95% CI: 1.781 to 6.469, p < 0.001) and bronchial wall thickening (OR 6.250, 95% CI: 2.414 to 16.18, p < 0.001) were independently associated with pulmonary complications in the model with better performance. CONCLUSIONS: Qualitative findings on HRCT are independent risk factors for pulmonary complications after lobectomy. Preoperative HRCT may be useful to predict pulmonary complications.