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We aimed to evaluate the impact of systemic autoimmune diseases (SADs) on treatment outcomes and radiation toxicities following stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC). We queried an institution-based database on patients with SADs treated with SBRT for lung cancer between 2001 and 2016 (SAD group). Each patient was matched to three controls without SADs. The primary outcomes of interest were the overall survival (OS) and local control rate (LCR). The secondary outcomes were radiation toxicities of grades ≥2 (≥G2). Twelve patients with SADs were matched to 36 controls. The median follow-up duration was 3.6 years. There was a significant intergroup difference in the OS (hazard ratio [HR]: 4.11, 95% confidence incidence [CI]: 1.82–9.27, p < 0.001) and LCR (HR: 15.97, 95% CI: 2.89–88.29, p < 0.001). However, there were no significant intergroup differences in the odds of acute (odds ratio [OR]: 0.38, 95% CI: 0.02–8.91, p = 0.550) and late (OR: 2.20, 95% CI: 0.32–15.10, p = 0.422) ≥G2 radiation pneumonitis. No other ≥G2 toxicities were identified. In conclusion, although radiation toxicities are not enhanced by SADs, SADs are risk factors of poor prognosis following SBRT for stage I NSCLC.

The aims of this study were to evaluate the clinical impact of curative-intent subsequent treatment on overall prognosis in lenvatinib-treated hepatocellular carcinoma (HCC) patients.Eighty-three consecutive patients with intrahepatic target nodules who received lenvatinib were reviewed. The clinical impact of curative-intent subsequent treatments was investigated through analysis of overall survival (OS) according to pathological deterioration stratified by mALBI grade.In patients with mALBI grade 1 and 2a liver function, R0 resection and lenvatinib-transarterial chemoembolization (lenvatinib-TACE) sequential therapy resulted in significantly better OS compared with other, non-curative-intent subsequent therapy and lack of additional treatment (median OS, 37.6 vs 29.0 months and 17.1 vs 8.9 months, respectively; P 0.001). Multivariate analysis confirmed that use of R0 resection and lenvatinib-TACE sequential therapy were associated with better OS (hazard ratio [HR], 0.021; P 0.001 and 0.108; P 0.001) compared with other, non-curative-intent subsequent treatment (HR 0.256; P = 0.010). In contrast, in patients with mALBI grade 2b liver function, multivariate analysis confirmed higher treatment efficacy for non-curative-intent subsequent treatment with respect to OS (HR 0.041; P 0.001) compared with R0 resection and lenvatinib-TACE sequential therapy (HR 0.057; P = 0.027 and 0.063; P = 0.001).Curative-intent subsequent treatment is more useful for HCC patients with better liver function (mALBI grade 1 and 2a) and intrahepatic target nodules who have received lenvatini b-based treatment.

Background: The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). Methods: Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. Results: Heterogeneous enhancement patterns (Type-3 and -4), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (Type-2) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (p = 0.313). Because of significantly worse PPS, overall survival of Type-4 tumor was poor compared to Type-2 or -3 tumors (p = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01–0.71; p = 0.023), while Type-4 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06–8.05; p = 0.039). Conclusion: Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component

We aimed to assess the predictive value of the modified Glasgow prognostic score (mGPS) in patients with non-small cell lung cancer (NSCLC) who underwent stereotactic body radiation therapy (SBRT). We retrospectively reviewed the records of 207 patients, with a median age of 79 years. The pretreatment mGPS was calculated and categorized as high (mGPS = 1–2) or low (mGPS = 0). The median follow-up duration was 40.7 months. The five-year overall survival (OS), progression-free survival (PFS) and time to progression (TTP) rates were 44.3%, 36% and 54.4%, respectively. Multivariate analysis revealed that mGPS was independently predictive of OS (hazard ratio [HR] 1.67; 95% confidence interval 1.14–2.44: P = 0.009), PFS (HR 1.58; 1.10–2.28: P = 0.014) and TTP (HR 1.66; 1.03–2.68: P = 0.039). Patients who had high mGPS showed significantly worse OS (33.3 vs 64.5 months, P = 0.003) and worse PFS (23.8 vs 39 months, P = 0.008) than those who had low mGPS. The data showed a trend that patients with high mGPS suffered earlier progression compared to those with low mGPS (54.3 vs 88.1 months, P = 0.149). We confirmed that mGPS is independently predictive of prognosis in NSCLC patients treated with SBRT.

Purpose: To evaluate the safety and efficacy of stereotactic body radiation therapy for primary lesion of renal cell carcinoma with long-term and regular follow-up of tumor size and renal function. Methods: This prospective study included 13 patients treated with stereotactic body radiation therapy for primary lesion of stage I renal cell carcinoma between August 2007 and June 2016 in our institution. Diagnosis of renal cell carcinoma was made by 2 radiologists using computed tomography or magnetic resonance imaging. A dosage of 60 Gy in 10 fractions or 70 Gy in 10 fractions was prescribed. The higher dose was selected if dose constraints were satisfied. Tumor response on imaging examination, local progression-free rate, overall survival, and toxicity were assessed. Results: The mean follow-up period was 48.3 months (range: 11-108 months). The tumors showed very slow but continuous response during long-term follow-up. Three cases (23.1%) showed transient progression during the short follow-up. The mean duration until the day on which partial response was confirmed among the partial or complete response cases was 22.6 months (95% confidence interval, 15.3-30.0 months). Local progression-free rate was 92.3% for 3 years and overall survival rate 91.7% for 2 years and 71.3% for 3 years. Twelve cases (92.3%) had impaired renal function at baseline. Renal function decreased slowly and mildly in most of the cases, but 2 cases of solitary kidney showed grade 4 or 5 renal dysfunction. Conclusion: All renal tumors decreased in size slowly but continuously for years after stereotactic body radiation therapy. Renal cancer can be treated radically with stereotactic body radiation therapy as a radiosensitive tumor, but careful attention should be given in cases with solitary kidney.

Purpose To investigate prognostic and risk factors for recurrence after stereotactic body radiation therapy (SBRT) in patients with stage I non-small cell lung carcinoma (NSCLC), focusing on dual time point [18]F-fluorodeoxyglucose positron emission tomography (FDG PET). Materials and methods We prospectively evaluated 57 patients with stage I NSCLC (45 T1N0M0 and 12 T2N0M0) who had undergone pretreatment FDG-PET/CT and were subsequently treated with SBRT. All patients received a whole-body PET/CT scan at 60 min and a whole-lung at 120 min after the injection. The maximum standardized uptake value (SUV) and retention index (RI) of the lesions were calculated. Local recurrence, regional lymph node metastasis, distant metastasis, and the recurrence pattern were evaluated. Cox proportional hazard regression analyses were performed to evaluate prognostic factors or risk factors of recurrence. Results During the median follow-up period of 27 months, local recurrence, regional lymph node metastasis, and distant metastasis were seen in 17 (30%), 12 (21%), and 17 (30%) of the 57 patients, respectively. The 3-year overall survival rate was 63.4%. SUV max did not affect any recurrence, DFS, OS, or CSS. RI significantly predicted higher distant metastasis (HR 47.546, p = 0.026). In contrast, RI tended to predict lower local recurrence (HR 0.175, p = 0.246) and regional lymph node metastasis (HR 0.109, p = 0.115). Conclusions SUV max at staging FDG-PET does not predict any recurrence, DFS, OS or CSS. In contrast, higher RI predicts higher distant metastasis and tended to predict lower local or regional lymph node metastasis.

Stereotactic body radiotherapy (SBRT) for oligometastases represents a recent trend in radiation oncology. While abundant data are available regarding the use of SBRT for the treatment of lung or liver oligometastases from various retrospective series and prospective trials, relatively little information has been accumulated for the treatment of oligometastases at sites other than the lungs and liver, particularly for sequential oligometastases in multiple organs. Oligometastases with primary lesions controlled is called “oligo-recurrence.” We describe herein the case of a lung cancer patient who developed repeated oligo-recurrence at multiple sites that were each controlled by radical radiotherapy and achieved long-term survival and discuss the merits of locally aggressive radiotherapy for this type of disease condition with reviewing the literature. Although further investigation should be undertaken to clarify the benefits, objectives, and methods of SBRT for the treatment of oligometastases, we believe utilization of SBRT may be worthwhile for patients with remote metastases who hope for treatment to acquire better local control and possible longer survival.

Pretreatment pulmonary interstitial change (PIC) has been indicated as a risk factor of severe radiation pneumonitis (RP) following stereotactic body radiation therapy (SBRT) for early-stage lung cancer, but details of its true effect remain unclear. This study aims to evaluate treatment outcomes of SBRT for stage I non-small cell lung cancer in patients with PIC. A total of 242 patients are included in this study (88% male). The median age is 77 years (range, 55&ndash, 92 years). A total dose of 40&ndash, 70 Gy is administered in 4 to 10 fractions during a 4-to-25 day period. One, two, and three-year overall survival (OS) rates are 82.1%, 57.1%, and 42.6%, respectively. Fatal RP is identified in 6.9% of all patients. The percent vital capacity &lt, 70%, mean percentage normal lung volume receiving more than 20 Gy (&gt, 10%), performance status of 2&ndash, 4, presence of squamous cell carcinoma, clinical T2 stage, regular use of steroid before SBRT, and percentage predicting forced expiratory volume in one second (&lt, 70%) are associated with worse prognoses for OS. Our results indicate that fatal RP frequently occurs after SBRT for stage I lung cancer in patients with PIC.

To retrospectively determine findings at gadoxetic acid-enhanced magnetic resonance (MR) imaging in hypervascular pseudolesions that were observed at computed tomography (CT) during hepatic arteriography, with special focus on distinguishing these pseudolesions from hypervascular hepatocellular carcinomas (HCCs).The institute ethics committee deemed study approval unnecessary. The study population comprised 80 patients (55 men, 25 women) with chronic liver disease who underwent CT during hepatic arteriography and arterial portography, gadoxetic acid-enhanced MR imaging, and follow-up dynamic contrast material-enhanced CT. The diagnosis of 104 pseudolesions and 123 HCCs was confirmed by means of histopathologic or multimodality evaluation. Two radiologists assessed the MR imaging findings of HCCs and pseudolesions in consensus, including the signal intensities (SIs) of the lesions on T2-weighted, diffusion-weighted (DW), and contrast-enhanced hepatocyte-phase images. The findings of nodular pseudolesions and HCCs were compared with the Fisher exact test. Additionally, the hepatocyte-phase SI ratio (ratio of lesion SI to liver SI) for HCCs and pseudolesions was compared by means of the Mann-Whitney U test.There were 62 wedge-shaped, 32 nodular, and 10 linear pseudolesions. On gadoxetic acid-enhanced hepatocyte-phase MR images, 15% of pseudolesions (16 of 104) were hypointense compared with surrounding liver tissue. The mean hepatocyte-phase SI ratio of HCCs (0.65 +/- 0.14 [standard deviation]) was significantly lower (P.01) than that of the nodular pseudolesions (0.95 +/- 0.11). The optimal cutoff value of hepatocyte-phase SI ratio for distinguishing between HCC and nodular pseudolesion was 0.84. No nodular pseudolesions were visible on DW images.Gadoxetic acid-enhanced hepatocyte-phase MR imaging and DW imaging could be used to distinguish hypervascular pseudolesions from hypervascular HCCs; a hepatocyte-phase SI ratio below 0.84 and visibility on DW images were findings specific for HCCs rather than pseudolesions.

Purpose: To clarify the factors that predict enhancement of the liver parenchyma in hepatocyte-phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging. Materials and Methods: Gd-EOB-DTPA–enhanced hepatocyte-phase MR images of 198 patients with chronic liver diseases (Child-Pugh class A in 112 patients, class B in 74 patients, and class C in 12 patients) were retrospectively analyzed. The hepatocyte-phase images were obtained using fat-suppressed T1-weighted gradient-echo images with a 3D acquisition sequence 10 min and 20 min after IV administration of Gd-EOB-DTPA (0.025 mmol/kg body weight). The quantitative liver–spleen contrast ratio (Q-LSC) was calculated using the signal intensities of the liver and spleen. Serum albumin levels, total bilirubin levels, prothrombin activity, and the results of indocyanine green clearance tests (ICGs) were recorded and correlated with the Q-LSC. Logistic regression analysis was performed to analyze which factors predict sufficient liver enhancement using a Q-LSC of 1.5 as a cutoff value. Results: Only ICGs and Child-Pugh classifications showed a statistically significant correlation with the Q-LSC. Logistic regression analysis showed that ICGs were the only factors that accurately predicted liver enhancement on hepatocyte-phase images. Conclusion: ICGs were found to be predictors of sufficient liver enhancement on hepatocyte-phase images. J. Magn. Reson. Imaging 2009;30:1042–1046. © 2009 Wiley-Liss, Inc.

Purpose To elucidate whether a contrast agent dilution method (dilution method), in which gadoxetate disodium (Gd-EOB-DTPA) is diluted with saline, is useful for good-quality arterial-phase images. Materials and Methods In this study we observed 494 hypervascular hepatocellular carcinomas (HCCs) in 327 patients with chronic liver disease. Three Gd-EOB-DTPA injection methods were adopted for comparison: 1) test injection method (undiluted Gd-EOB-DTPA and modified scan delay), in which a test dose of 0.5 mL of Gd-EOB-DTPA was injected to determine scan delay; 2) conventional method (undiluted Gd-EOB-DTPA and fixed scan delay); and (3) dilution method (diluted Gd-EOB-DTPA and fixed scan delay), in which Gd-EOB-DTPA was diluted to 20 mL with saline. Lesion-liver contrast was calculated. Image quality and lesion detectability were evaluated by two radiologists blinded to the injection methods. Results The lesion-liver contrast of the dilution method was significantly higher than that of the other two methods. Lesion detectability of the conventional method (64%) was significantly lower than that of the other two methods (contrast agent dilution method, 95%; test injection method, 93%). The image quality of the contrast agent dilution method was significantly better than that of the other two methods. Conclusion The dilution method contributed to improved image quality, high lesion-liver contrast, and high lesion detectability in the arterial-phase images of GD-EOB-DTPA-enhanced MRI. J. Magn. Reson. Imaging 2009;30:849–854. © 2009 Wiley-Liss, Inc.

Aim: To examine if it is possible to shorten the examination time of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB)-enhanced MRI by omitting hepatocyte-phase images of 20-min delay time (Im-20) for detecting focal liver lesions. Materials and methods: Four hundred ninety-five malignant focal liver lesions observed on Im-20 in 265 patients were included. The hepatocyte phase was obtained 10 min (Im-10) and 20 min (Im-20) after Gd-EOB injection. Liver enhancement was evaluated using a 4-point scale [excellent/good/poor/non-diagnostic; visual liver-spleen contrast (V-LSC)] and a quantitative liver–spleen contrast ratio (Q-LSC). Two radiologists evaluated lesion conspicuity for assessing the sensitivity of lesion detection. As Im-20 was used as the standard of reference for the lesions, Im-20 artificially had 100% sensitivity. Results: The results showed that although sensitivities and Q-LSC significantly increased from Im-10 to Im-20 (sensitivity/mean Q-LSC: Im-5, 81%/1.4 Im-10, 96%/1.7: Im-20, 100%/1.9), the sensitivity of Im-10 achieved 100% (the same as Im-20) in patients with good/excellent V-LSC or Q-LSC of more than 1.5. On Im-10, 202 patients (77%) were assigned as having good/excellent V-LSC (78%), and 161 (61%) were assigned as having Q-LSC of more than 1.5. Conclusion: We concluded that Im-20 can be omitted in at least 61% of the patients.

Background Treatment of primary renal cell carcinoma using radiotherapy with curative intent is rare, because renal cell carcinoma is generally regarded as a radiation-resistant tumor. Recently, stereotactic body radiation therapy has been radically applied for cancers in various organs including renal cell carcinoma. However, there were few reports describing pathological changes of renal cell carcinoma post stereotactic body radiation therapy. This is the first report we are aware of documenting late histological effects of stereotactic body radiation therapy on renal cell carcinoma and surrounding normal tissue. Case presentation A right renal tumor was identified in a Japanese 70-year-old man on follow-up computed tomography for his chronic hepatitis. T1N0M0 renal cell carcinoma was clinically diagnosed as the tumor was 3 cm in diameter and well-enhanced with intravenously infused contrast material in the arterial phase on computed tomography. No metastases in regional lymph nodes or distant sites were evident. Stereotactic body radiation therapy was selected as an alternative therapy to surgery because of his poor liver function. A total dose of 60 Gy in 10 fractions over 12 days was delivered using a 10-megavolt X-ray. The renal tumor gradually decreased in size and partial response had been achieved at 2 years after completing stereotactic body radiation therapy. Hepatocellular carcinoma was identified during follow-up in the patient and he died of progression of hepatocellular carcinoma with hepatic failure 2.5 years after completing stereotactic body radiation therapy. Autopsy was done and it showed almost complete necrosis of tumor tissues with a small amount of viable renal carcinoma cells. These pathological findings suggested marked effects of stereotactic body radiation therapy on clear cell renal cell carcinoma. Conclusion Our case demonstrates a good pathological response with small foci of remnant viable cancer cells after stereotactic body radiation therapy of 60Gy in 10 fractions for small renal cell carcinoma. Although further experiences and longer follow-up are mandatory to conclude the optimal treatment schedule and efficacy of stereotactic body radiation therapy for renal cell carcinoma, stereotactic body radiation therapy may represent a novel less-invasive option for the treatment of primary renal cell carcinoma.

Purpose. Immune responses following stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) were examined from the point of view of lymphocyte subset counts and natural killer cell activity (NKA).Patients and Methods. Peripheral blood samples were collected from 62 patients at 4 time points between pretreatment and 4 weeks post-treatment for analysis of the change of total lymphocyte counts (TLC) and lymphocyte subset counts of CD3+, CD4+, CD8+, CD19+, CD56+, and NKA. In addition, the changes of lymphocyte subset counts were compared between patients with or without relapse. Further, the correlations between SBRT-related parameters and immune response were analyzed for the purpose of revealing the mechanisms of the immune response.Results. All lymphocyte subset counts and NKA at post-treatment and 1 week post-treatment were significantly lower than pre-treatment (P<0.01). No significant differences in the changes of lymphocyte subset counts were observed among patients with or without relapse. The volume of the vertebral body receiving radiation doses of 3 Gy or more (VV3) significantly correlated with the changes of nearly all lymphocyte subset counts.Conclusions. SBRT for stage I NSCLC induced significant immune suppression, and the decrease of lymphocyte subset counts may be associated with exposure of the vertebral bone marrow.

Background As stereotactic body radiotherapy (SBRT) is a highly dose-dense radiotherapy, adverse events of neighboring normal tissues are a major concern. This study thus aimed to clarify the frequency and degree of clinical symptoms in patients with rib fractures after SBRT for primary lung cancer and to reveal risk factors for rib fracture. Appropriate α/β ratios for discriminating between fracture and non-fracture groups were also investigated. Methods Between November 2001 and April 2009, 177 patients who had undergone SBRT were evaluated for clinical symptoms and underwent follow-up thin-section computed tomography (CT). The time of rib fracture appearance was also assessed. Cox proportional hazard modeling was performed to identify risk factors for rib fracture, using independent variables of age, sex, maximum tumor diameter, radiotherapeutic method and tumor-chest wall distance. Dosimetric details were analyzed for 26 patients with and 22 randomly-sampled patients without rib fracture. Biologically effective dose (BED) was calculated with a range of α/β ratios (1–10 Gy). Receiver operating characteristics analysis was used to define the most appropriate α/β ratio. Results Rib fracture was found on follow-up thin-section CT in 41 patients. The frequency of chest wall pain in patients with rib fracture was 34.1% (14/41), and was classified as Grade 1 or 2. Significant risk factors for rib fracture were smaller tumor-chest wall distance and female sex. Area under the curve was maximal for BED at an α/β ratio of 8 Gy. Conclusions Rib fracture is frequently seen on CT after SBRT for lung cancer. Small tumor-chest wall distance and female sex are risk factors for rib fracture. However, clinical symptoms are infrequent and generally mild. When using BED analysis, an α/β ratio of 8 Gy appears most effective for discriminating between fracture and non-fracture patients.

Background and purpose The aim of this study was to define the effects of voluntary anal contraction on prostate motion in an experimental setting. Materials and methods Thirty-eight patients (median age, 76years) with prostate cancer underwent thin-slice computed tomography (CT) in the vicinity of the prostate before and after active anal contraction. Three-dimensional displacement of the pelvis and prostate was measured. Results Mean (±standard deviation, SD) overall displacement of the prostate due to anal contraction was 0.3±1.4mm to the right, 9.3±7.8mm to the anterior, and 5±4mm to the cranial direction. Mean displacement of the pelvis was 0.5±1.8mm to the right, 4.1±7.1mm to the anterior, and 1±3mm to the cranial direction. Mean displacement of the prostate relative to the pelvis was 0.1±1.1mm to the left, 5.2±3.3mm to the anterior, and 4±4mm to the cranial direction. Conclusions Voluntary anal contraction within an experimental setting induces large prostate and bone motion, mainly in the anterior and cranial directions. The frequency and magnitude of actual anal contractions during radiotherapy for prostate cancer need to be determined.

and 779 cGy (SDZ 1012 cGy) in patients without ET (pZ 0.074). MPD per fraction was 727 cGy (SD Z 466) in patients with ET and 249 cGy (SD Z 255) in patients without ET (pZ 0.035). D5 cc per fraction was 482 cGy (SD Z 397) in patients with ETand 208 cGy in patients without ET (SDZ 265) p Z 0.1216). Table shows the characteristics of the RTOG dose constraints when used to predict toxicity in our patients. Conclusions: Lung SBRT is associated with a low rate of esophagitis but severe toxicity can occur at very high doses. Our study shows that higher maximum point dose and D5 cc are associated with esophageal toxicity. Respecting RTOG constraints has a high NPV for toxicity in our population.