[Inter-rater Reliability and Cost in Pricing for Creating Dataset Focused on Mediolateral Oblique View in Mammography].

PURPOSE: The purpose of this study was to assess inter-rater reliability and workload for creating accurate training data in the clinical evaluation of mammographic positioning for deep learning. METHODS: A total of 107 mammographic images without lesions were labeled by two certified radiologic technologists in seven items: six clinical image evaluation criteria in positioning and breast tissue density. The kappa coefficient was calculated as an indicator of interrater reliability. Furthermore, the labeling cost per image was calculated based on labeling time and salary for the technologists. RESULTS: The kappa coefficients were 0.71 for inframammary fold, 0.43 for nipple in profile, 0.45 for great pectoral muscle, 0.10 for symmetrical images, and 0.61 for retromammary fat. No significant difference was found in the coefficients of spread of breast tissue. The cost per image was calculated at 11.0 yen. CONCLUSION: The inter-rater reliability for the inframammary fold, nipple in profile, great pectoral muscle, and retromammary fat ranged from "moderate" to "substantial." The reliability for symmetrical images was "slight," indicating the need for a consensus among evaluators during labeling. The labeling cost was equivalent to or higher than that of existing services.

Applying Artificial Neural Networks to Develop a Decision Support Tool for Tis-4N0M0 Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy.

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

CT Findings and Treatment Outcomes of Ground-Glass Opacity Predominant Lung Cancer After Stereotactic Body Radiotherapy.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been rapidly evolving and increasingly performed in patients with ground-glass opacity (GGO) predominant lung cancer (GGOp-LC). PURPOSE: To evaluate early-phase CT findings of GGOp-LC after SBRT. MATERIALS AND METHODS: Patients with GGOp-LC staged as cTis-2bN0M0 treated with SBRT were retrospectively identified. The CT images were analyzed using radiologists' interpretation and CT-density histograms. Long-term treatment outcomes were also assessed. RESULTS: This study evaluated 126 patients with 133 cases of GGOp-LC, comprising GGOp-LC with pure GGO (pureGGO-LC) (n = 31) and part-solid tumors (partsolid-LC) (n = 102). The median follow-up duration was 64.3 months (range, 10.8-178.9 months). Most GGOp-LC cases were interpreted as stable disease at 1 and 3 months after SBRT (96% [125/130] and 85% [62/73], respectively). However, the solid component was often interpreted as progressive disease (42% [34/82] and 60% [29/48], respectively). The GGO component was interpreted as denser in 47% (61/130) and 86% (63/73) of cases, respectively. For 25 evaluable pureGGO-LC cases at 3 months, the median tumor density values increased over time (P < .001). For 48 evaluable partsolid-LC cases at 3 months, the median areas of CT-density ≥ -160 HU increased over time (P < .001). The 5-year overall survival for GGOp-LC patients was 78.0%. No local or regional recurrence were observed. CONCLUSION: Clinical outcomes of SBRT for GGOp-LC were excellent, without local or regional recurrence. In the interpretation of early-phase follow-up CT scans of GGOp-LC after SBRT, it should be noted that most GGOp-LC remains stable disease, solid component increases in size, and GGO component is denser.

Hypofractionated radiotherapy for hepatocellular carcinomas adjacent to the gastrointestinal tract.

AIM: Decisions regarding therapeutic plans for inoperable patients with hepatocellular carcinoma (HCC) adjacent to the gastrointestinal (GI) tract are challenging because radiofrequency ablation has the potential risk of thermal injury. Moreover, the response rate of transcatheter arterial chemoembolization is relatively low and stereotactic body radiotherapy (SBRT) is believed to be too toxic. We have applied hypofractionated radiotherapy (HFRT) for such lesions. This study investigated the outcomes and toxicities of this treatment. METHODS: Among consecutive HCC patients treated with radiotherapy with curative intent at our institution between 2015 and 2019, we retrospectively extracted those outside of the indication for SBRT due to exceeding the constraint of the GI tract and who were treated using HFRT with a prescription dose of 42 Gy in 14 fractions and prophylactic proton pump inhibitor administration for 6 months. The oncological outcomes and toxicities were investigated. RESULTS: A total of 66 patients with 73 lesions were eligible. The median follow-up period was 24.0 months. The local recurrence, intrahepatic recurrence, liver-related death, and overall survival rates at 2 years were 11.3%, 50.6%, 15.9%, and 60.4%, respectively. Six (9.1%) patients experienced Child-Pugh score deterioration ≥2 within 6 months following treatment. Two and one patient developed grades 2 and 3 gastroduodenal bleeding, respectively. CONCLUSIONS: HFRT can achieve good local control in patients with HCC adjacent to the GI tract, with low GI toxicity incidence. Our study demonstrated that HFRT can be a potentially curative treatment option for lesions.

Stereotactic body radiotherapy for patients with non-small-cell lung cancer using RapidArc delivery and a steep dose gradient: prescription of 60% isodose line of maximum dose fitting to the planning target volume.

We retrospectively investigated outcomes, including pulmonary toxicities, of stereotactic body radiation therapy using RapidArc and a risk-adapted 60% isodose plan for early-stage non-small-cell lung cancer patients. We evaluated patients staged as cT1a-2bN0M0 between 2011 and 2017 and treated with a total dose of 40-60 Gy in five fractions to the 60% isodose line of the maximum dose encompassing the planning target volume with curative intent. Comorbidities and age were rated using an age-adjusted Charlson comorbidity index (AACCI). Factors associated with overall survival (OS) were investigated. A total of 237 patients with 250 lesions were eligible. The median follow-up was 28.0 months. The local recurrence rate at 3 years was 0.8%; none of the patients developed isolated local recurrence. OS, deaths from lung cancer, and deaths from intercurrent disease at 3 years were 72.7%, 8.2% and 19.1%, respectively. On multivariate analysis for correlating factors with OS, AACCI and maximal standardized uptake value on [18F]-fluorodeoxyglucose positron emission tomography/computed tomography remained significant. Grade ≥3 toxicities were limited to radiation pneumonitis in six (2.4%) patients (Grade 3 in four patients and Grade 5 in two patients). Among those, three patients had idiopathic interstitial pneumonia. The total dose was unrelated to the incidence of Grade ≥3 radiation pneumonitis (P = 0.69). Using the 60% isodose prescription and RapidArc, maximal local control was achieved with acceptable toxicities. Although the OS may depend on patient background, dose escalation aiming at higher local control can be beneficial for medically inoperable patients.

Clarithromycin mitigates radiation pneumonitis in patients with lung cancer treated with stereotactic body radiotherapy.

BACKGROUND: Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). METHODS: Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. RESULTS: Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3. CONCLUSIONS: CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be confirmed in prospective studies.

Stereotactic body radiotherapy for lung cancer patients with idiopathic interstitial pneumonias.

PURPOSE: To compare toxicity and survival after stereotactic body radiotherapy (SBRT) between lung cancer patients with or without idiopathic interstitial pneumonias (IIPs), and to investigate the potential value of SBRT for the patients. METHODS: Among lung cancer patients receiving SBRT between 2005 and 2016, we evaluated those treated with a total dose of 40-60Gy in five fractions with curative intent who either were staged as cT1-4N0M0 or experienced postoperative isolated local recurrence. We analyzed the incidence of radiation pneumonitis (RP) in all patients and local recurrence and overall survival (OS) in T1a-2a patients. RESULTS: A total of 508 patients were eligible, including 42 with IIPs. The median follow-up was 32.3 (6.0-120.9) months. Significantly more patients with IIPs had grade ≥3RP than did those without IIPs (12% vs. 3%, p=0.009). The 2-year local recurrence rate was low in both groups (3.4% vs. 5.6%, p=0.38). The 2-year OS rate was significantly lower in the patients with IIPs (42.2% vs. 80.9%, p<0.001), although death from lung cancer was comparable (p=0.74). CONCLUSION: SBRT achieved excellent local control with acceptable pulmonary toxicity in lung cancer patients with IIPs. SBRT can be a reasonable option for early lung cancer patients with IIPs.

Stereotactic body radiotherapy for operable early-stage non-small cell lung cancer.

PURPOSE: To analyze outcomes of stereotactic body radiotherapy (SBRT) for operable patients with early-stage non-small cell lung cancer (NSCLC) and to evaluate factors associated with outcomes. METHODS: We retrospectively analyzed operable patients with NSCLC, staged as cT1-2N0M0, treated with SBRT between 2006 and 2015. Both biopsy-proven and clinically diagnosed NSCLC were included. Local control and survival rates were calculated and compared between subsets of patients. We investigated factors associated with outcomes. RESULTS: We identified 88 operable patients among 661 patients with cT1-2N0M0 NSCLC. The median age was 79 years (range: 55-88). The median follow-up time after SBRT was 40 months (range: 4-121). Fifty-nine patients had been pathologically diagnosed and the other 29 had been clinically diagnosed as having NSCLC. Local control, cause-specific survival (CSS) and overall survival (OS) at 3 years were 91%, 97% and 90% for T1, and 100%, 82% and 74% for T2, respectively. The CSS and OS at 3 years were 100% and 100% for GGO and 83% and 59% for solid tumors, respectively (p=0.005). On univariate analysis, age and T stage were significantly associated with CSS, and age, the Charlson Comorbidity Index (CCI), and opacity were significantly associated with OS. On multivariate analysis, age and CCI were significantly associated with OS. As for toxicities, Grades 0, 1, 2 and 3 radiation pneumonitis occurred in 37.5%, 47.7%, 13.6% and 1.1% of patients, respectively. No Grade 4 or 5 radiation pneumonitis occurred, and no other toxicities of Grade 2 or above were observed. CONCLUSION: Outcomes of SBRT for operable early stage NSCLC were as good as previous SBRT and surgery studies. Further investigation for selecting good SBRT candidates is warranted in high-risk operable patients.

Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation.

BACKGROUND: Curative treatment options for patients with early stage hepatocellular carcinoma (HCC) include resection, liver transplantation, and percutaneous ablation therapy. However, even patients with solitary HCC are not always amenable to these treatments. The authors prospectively investigated the clinical outcomes of patients who received stereotactic body radiotherapy (SBRT) for solitary HCC. METHODS: A phase 2 study involving SBRT and optional transarterial chemoembolization (TACE) was conducted in patients with Child-Pugh grade A or B and underlying, solitary HCC (greatest tumor dimension, ≤4 cm) who were unsuitable candidates for resection and radiofrequency ablation. The prescription dose was 35 to 40 grays in 5 fractions. The primary endpoint was 3-year local tumor control. RESULTS: From 2007 to 2012, 101 patients were enrolled, and 90 were evaluable with a median follow-up of 41.7 months (range, 6.8-96.2 months). Thirty-two patients were treatment-naïve, 20 were treated for newly diagnosed intrahepatic failure, and 38 were treated for residual or recurrent HCC as salvage therapy. Thirty-two patients did not receive TACE, 48 received insufficient TACE, and 10 attained full lipiodol accumulation. The 3-year local control rate was 96.3%, the 3-year liver-related cause-specific survival rate was 72.5%, and the overall survival rate was 66.7%. Grade 3 laboratory abnormalities were observed in 6 patients, and 8 patients had Child-Pugh scores that worsened by 2 points. CONCLUSIONS: SBRT achieved high local control and overall survival with feasible toxicities for patients with solitary HCC, despite rather stringent conditions. SBRT can be effective against solitary HCC in treatment-naive, intrahepatic failure, residual disease, and recurrent settings, taking advantage of its distinctive characteristics. Cancer 2016;122:2041-9. © 2016 American Cancer Society.

Stereotactic body radiotherapy for T3 and T4N0M0 non-small cell lung cancer.

To evaluate the outcomes and feasibility of stereotactic body radiotherapy (SBRT) for cT3 and cT4N0M0 non-small cell lung cancer (NSCLC), 25 patients with localized primary NSCLC diagnosed as cT3 or cT4N0M0, given SBRT between May 2005 and July 2013, were analyzed. All patients had inoperable tumors. The major reasons for tumors being unresectable were insufficient respiratory function for curative resection, advanced age (>80 years old) or technically inoperable due to invasion into critical organs. The median patient age was 79 years (range; 60-86). The median follow-up duration was 25 months (range: 5-100 months). The 2-year overall survival rates for T3 and T4 were 57% and 69%, respectively. The 2-year local control rates for T3 and T4 were 91% and 68%, respectively. As for toxicities, Grade 0-1, Grade 2 and Grade 3 radiation pneumonitis occurred in 23, 1 and 1 patient, respectively. No other acute or symptomatic late toxicities were reported. Thirteen patients who had no local, mediastinal or intrapulmonary progression at one year after SBRT underwent pulmonary function testing. The median variation in pre-SBRT and post-SBRT forced expiratory volume in 1 s (FEV1) values was -0.1 (-0.8-0.8). This variation was not statistically significant (P = 0.56). Forced vital capacity (FVC), vital capacity (VC), %VC and %FEV1 also showed no significant differences. SBRT for cT3 and cT4N0M0 NSCLC was both effective and feasible. Considering the favorable survival and low morbidity rate, SBRT is a potential treatment option for cT3 and cT4N0M0 NSCLC.

Stereotactic body radiotherapy for patients with oligometastases from colorectal cancer: risk-adapted dose prescription with a maximum dose of 83-100 Gy in five fractions.

We previously reported that the local control of pulmonary metastases from colorectal cancer (CRC) following stereotactic body radiotherapy (SBRT) with moderate prescription dose was relatively worse. We investigated the treatment outcomes and toxicities of patients with oligometastases from CRC treated by SBRT using risk-adapted, very high- and convergent-dose regimens. Among patients referred for SBRT from August 2011 to January 2015, those patients were extracted who had liver or pulmonary metastases from CRC, and they were treated with a total dose of 50-60 Gy in five fractions prescribed to the 60% isodose line of the maximum dose covering the surface of the planning target volume. Concurrent administration of chemotherapy was not admitted during SBRT, while neoadjuvant or adjuvant chemotherapy was allowed. A total of 21 patients (12 liver, 9 lung) with 28 oligometastases were evaluated. The median follow-up duration was 27.5 months (range: 6.5-43.3 months). Four patients were treated with SBRT as a series of initial treatments, and 17 patients were treated after recurrent oligometastases. The local control rates at 1 and 2 years from the start of SBRT were 100%. The disease-free and actuarial overall survival rates were 62% and 55%, and 79% and 79%, respectively. No severe toxicities (≥grade 3) occurred during follow-up. The outcomes following high-dose SBRT were excellent. This treatment can provide an alternative to the surgical resection of oligometastases from CRC. Prospective studies are needed to validate the effectiveness of SBRT.

Stereotactic body radiotherapy for chronic obstructive pulmonary disease patients undergoing or eligible for long-term domiciliary oxygen therapy.

A major cause of death in patients undergoing long-term domiciliary oxygen therapy (LTOT) is lung cancer progression. In our institution, we actively perform stereotactic body radiotherapy (SBRT) on patients with early-stage non-small-cell lung cancer undergoing LTOT. In this study, we retrospectively analyzed the treatment efficacy and safety of SBRT for patients with T1-3N0M0 non-small-cell lung cancer who had been prescribed LTOT for treatment of chronic obstructive pulmonary disease (COPD). A total of 24 patients were studied. Their median age was 74 years (range, 63-87 years). The median duration from the start of LTOT to SBRT was 23 months (range, 0-85 months). Four of the 24 patients underwent lobectomy due to lung cancer. The median follow-up duration was 29 months (range, 5-79 months). One patient had a local recurrence. The median survival time was 30 months. The 3-year overall survival was 49%. In 6 of the 24 patients (25%), COPD presented with interstitial pneumonia. The 3-year overall survival for patients with COPD without interstitial pneumonia was significantly better than that for patients with both COPD and interstitial pneumonia (67% and 0%, respectively; P < 0.0001). Grade 5 radiation pneumonitis occurred in one patient (4%) with COPD with interstitial pneumonia. SBRT was tolerated by patients with early-stage non-small-cell lung cancer undergoing LTOT. SBRT should be considered for patients undergoing LTOT. However, clinicians should consider the risk of severe radiation pneumonitis in patients with interstitial pneumonia.

Toxicities of organs at risk in the mediastinal and hilar regions following stereotactic body radiotherapy for centrally located lung tumors.

INTRODUCTION: We investigated tolerable doses to organs at risk (OARs) in the mediastinum and pulmonary hilum following stereotactic body radiotherapy for centrally located lung tumors. METHODS: Between 2005 and 2012, 381 patients with lung tumors were treated with stereotactic body radiotherapy of 40 to 60 Gy in five fractions. From among these patients, we extracted those who received greater than 25 Gy irradiation to OARs and analyzed dosimetric factors in relation to grade 3 to 5 toxicities. RESULTS: In total, 398 OARs in 133 patients were analyzed, with a median follow-up of 33 (range, 3-87) months. The numbers receiving greater than 25 Gy irradiation to the aorta, vena cava, pulmonary artery, pulmonary vein, bronchus, trachea, heart, and esophagus were 72, 33, 73, 60, 55, 13, 69, and 23, respectively. The corresponding median Dmax 0.5 ml were 43.8, 32.0, 32.2, 29.1, 28.4, 28.7, 41.1, and 21.7 Gy. Of these patients, two developed grade 5 and one grade 3 hemoptysis, and two had grade 3 obstructive pneumonia. Two patients with grade 5 hemoptysis received high doses at the pulmonary artery and bronchus (59.2 and 54.4 Gy, and 61.3 and 59.6 Gy, respectively). No other grade 3 to 5 toxicities occurred. CONCLUSION: Therapeutic indications and dose-intensity should be carefully determined for patients with central tumors, especially when doses to the pulmonary artery and bronchus in the pulmonary hilum exceed 50 Gy. Tolerable doses for other OARs might, however, be higher than in this study, though longer follow-up is necessary to assess this possibility.

Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume.

We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. - (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ≥ Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose-volumetric analysis, the trial regimen of 60 Gy/5 fr. - (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. - (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0-27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. - (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. - (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. - (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity.

Stereotactic ablative body radiation therapy with dynamic conformal multiple arc therapy for liver tumors: optimal isodose line fitting to the planning target volume.

PURPOSE: To assess optimal relative prescribed dose values in stereotactic ablative body radiation therapy (SABR) using dynamic conformal multiple arc therapy (DCMAT) for liver tumors. METHODS AND MATERIALS: We generated SABR plans for 8 typical liver tumors that received SABR with 50 Gy in 5 fractions. The prescribed dose had previously been defined as 80% of the maximal dose ("80% isodose plan"). Alternatively, 20%-90% isodose plans were created to compare dosimetric factors. RESULTS: The mean liver volume values (%) that received >20 Gy (V20) and the mean liver dose were both the lowest with a 70% isodose plan and were the second lowest with a 60% isodose plan. The V20 dose was 5.19% lower (11.14%) with a 70% isodose plan and 4.51% lower (11.22%) with a 60% isodose plan compared with the value with an 80% isodose plan (11.75%). Mean planning target volume (PTV) dose increased as the % isodose decreased. The mean PTV dose was 10% higher (62.4 Gy) with a 70% isodose plan and 21% higher (68.9 Gy) with a 60% isodose plan compared with the value with an 80% isodose plan (56.8 Gy). CONCLUSIONS: During SABR treatment planning using DCMAT for liver tumors, target doses increased as the percentage isodose value decreased, which could result in better outcomes. In contrast, a 70% isodose plan had the lowest normal liver dose and a 60% isodose plan had the second lowest. An optimal percentage isodose level might be adjusted depending on tumor radiation sensitivity and liver function reserve. Further investigation is warranted to determine whether these dosimetric advantages result in improved outcomes.

Maximum standardized uptake value on FDG-PET is a strong predictor of overall and disease-free survival for non-small-cell lung cancer patients after stereotactic body radiotherapy.

INTRODUCTION: The maximum standardized uptake value (SUVmax) on F-fluorodeoxyglucose positron emission tomography is a predictor for overall survival (OS) in non-small-cell lung cancer (NSCLC) after resection. We investigated the association between SUVmax and outcomes in NSCLC after stereotactic body radiotherapy. METHODS: Between 2005 and 2012, 283 patients with early NSCLC (T1a-2N0M0) were treated with stereotactic body radiotherapy; the total doses were 40 to 60 Gy in five fractions. Patients who underwent staging F-fluorodeoxyglucose positron emission tomography scans by a single scanner and were followed up for more than or who died within 6 months were eligible. The optimal threshold SUVmax was calculated for each outcome. Outcomes were analyzed using the Kaplan-Meier method and log-rank test. Prognostic significance was assessed by univariate and multivariate analyses. RESULTS: One hundred fifty-two patients were eligible. Median follow-up was 25.3 (range, 1.3-77.4) months. Local, regional, and distant recurrences, cancer-specific deaths, and deaths from other reasons occurred in 14, 11, 27, 21, and 31 patients, respectively. The optimal threshold SUVmax for local, regional, and distant recurrences, and disease-free survival (DFS), cancer-specific survival, and OS were 2.47 to 3.64. Outcomes of patients with SUVmax lower than each threshold were significantly better than those with higher SUVmax (all p<0.005): 3-year DFS rates were 93.0% versus 58.3% (p<0.001) and 3-year OS rates were 86.5% versus 42.2% (p<0.001), respectively. By multivariate analysis, higher SUVmax was a significantly worse predictor for DFS (p<0.01) and OS (p=0.04). CONCLUSIONS: SUVmax was a predictor for DFS and OS. A high SUVmax may be considered for intensive treatment to improve outcomes.

Salvage stereotactic ablative irradiation for isolated postsurgical local recurrence of lung cancer.

BACKGROUND: For isolated postsurgical local recurrences (IPSLR) of lung cancer, salvage resection is often unfeasible due to a high risk of morbidity and death. Stereotactic ablative body radiotherapy (SABR) provides excellent therapeutic effects, with mild toxicities, for patients with medically inoperable lung cancer. However, the outcomes of SABR for IPSLR have not been reported. METHODS: Patients with IPSLR who were treated with SABR between 2005 and 2012 were retrospectively identified. The prescribed doses were 40 to 60 Gy per 5 to 10 fractions. Treatment outcomes and toxicities were evaluated. RESULTS: We identified 23 patients with IPSLR, including 21 with bronchial stump or staple line recurrences and 2 with chest wall recurrences. During follow-up, IPSLR occurred at a median of 36.7 months (range, 5.0 to 190 months) after resection. All patients were N0 M0, and the T stages at recurrence were T1a, T1b, T2a, and T4 in 6, 5, 3, and 9 patients, respectively. The initial pathologic diagnoses were adenocarcinoma in 17 patients and squamous cell carcinoma in 6. At a median follow-up duration of 17.0 months (range, 6.0 to 89.6 months) after SABR, there were 2 local recurrences. Local control and overall survival rates at 1 and 2 years were 94.7% and 86.8% and 84.0% and 76.4%, respectively. Grade 3 to 5 radiation pneumonitis occurred in 1 patient each. Grade 3 temporary but repeated obstructive pneumonia occurred in 2 patients. CONCLUSIONS: SABR for IPSLR achieved high local control with limited toxicities. SABR may lead to a potential cure and should be considered as a salvage treatment option for IPSLR.

Stereotactic ablative body radiation therapy for octogenarians with non-small cell lung cancer.

PURPOSE: To retrospectively investigate treatment outcomes of stereotactic ablative body radiation therapy (SABR) for octogenarians with non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Between 2005 and 2012, 109 patients aged ≥80 years with T1-2N0M0 NSCLC were treated with SABR: 47 patients had histology-unproven lung cancer; 62 patients had pathologically proven NSCLC. The prescribed doses were either 50 Gy/5 fractions for peripheral tumors or 40 Gy/5 fractions for centrally located tumors. The treatment outcomes, toxicities, and the correlating factors for overall survival (OS) were evaluated. RESULTS: The median follow-up duration after SABR was 24.2 (range, 3.0-64.6) months. Only limited toxicities were observed, except for 1 grade 5 radiation pneumonitis. The 3-year local, regional, and distant metastasis-free survival rates were 82.3%, 90.1%, and 76.8%, respectively. The OS and lung cancer-specific survival rates were 53.7% and 70.8%, respectively. Multivariate analysis revealed that medically inoperable, low body mass index, high T stage, and high C-reactive protein were the predictors for short OS. The OS for the operable octogenarians was significantly better than that for inoperable (P<.01). CONCLUSIONS: Stereotactic ablative body radiation therapy for octogenarians was feasible, with excellent OS. Multivariate analysis revealed that operability was one of the predictors for OS. For medically operable octogenarians with early-stage NSCLC, SABR should be prospectively compared with resection.

Reassessment of declines in pulmonary function ≥1 year after stereotactic body radiotherapy.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is standard care for patients with inoperable early-stage non-small cell lung cancer. However, clinicians may hesitate to use SBRT in patients with severe COPD because of potential negative effects on pulmonary function. We quantitatively analyzed long-term declines in pulmonary function after SBRT to ascertain lifelong tolerability to SBRT. METHODS: Between 2005 and 2010 at Ofuna Chuo Hospital, 292 patients with lung tumors were treated with SBRT. Among them, patients who underwent pulmonary function tests (PFTs) both pretreatment and at ≥1 year after SBRT were evaluated in this retrospective analysis. The decline ratio in FEV(1) and FVC was assessed (ie, ΔFEV(1)/preFEV(1) and ΔFVC/preFVC). Predictors were identified using univariate and multivariate analyses. RESULTS: The 141 eligible patients had follow-up PFTs at a median of 21.0 (range, 12.0-74.8) months after SBRT. Among groups with normal function, or mild to moderate or severe COPD, the median values for ΔFEV(1)/preFEV(1) were 7.9%, 7.9%, and 7.4%, respectively, and for ΔFVC/preFVC, 5.1%, 3.4%, and 0.5%, respectively. Low BMI was the only predictor for ΔFEV(1)/preFEV(1)> 10%. Low BMI, high lung volume receiving 20 Gy, and high pretreatment FVC were predictors for ΔFVC/preFVC > 10%. CONCLUSIONS: Declines in FEV(1) and FVC were small, but statistically significant in patients with normal function or mild to moderate COPD, but nonsignificant in patients with severe COPD. These declines were primarily due to physiologic aging. SBRT had a limited effect on decline in long-term pulmonary function and may be an acceptable alternative to surgery for patients with comorbid lung cancer and COPD.

Acceptable toxicity after stereotactic body radiation therapy for liver tumors adjacent to the central biliary system.

PURPOSE: To evaluate biliary toxicity after stereotactic body radiation therapy (SBRT) for liver tumors. METHODS AND MATERIALS: Among 297 consecutive patients with liver tumors treated with SBRT of 35 to 50 Gy in 5 fractions, patients who were irradiated with >20 Gy to the central biliary system (CBS), including the gallbladder, and had follow-up times >6 months were retrospectively analyzed. Toxicity profiles, such as clinical symptoms and laboratory and radiologic data especially for obstructive jaundice and biliary infection, were investigated in relation to the dose volume and length relationship for each biliary organ. RESULTS: Fifty patients with 55 tumors were irradiated with >20 Gy to the CBS. The median follow-up period was 18.2 months (range, 6.0-80.5 months). In the dose length analysis, 39, 34, 14, and 2 patients were irradiated with >20 Gy, >30 Gy, >40 Gy, and >50 Gy, respectively, to >1 cm of the biliary tract. Seven patients were irradiated with >20 Gy to >20% of the gallbladder. Only 2 patients experienced asymptomatic bile duct stenosis. One patient, metachronously treated twice with SBRT for tumors adjacent to each other, had a transient increase in hepatic and biliary enzymes 12 months after the second treatment. The high-dose area >80 Gy corresponded to the biliary stenosis region. The other patient experienced biliary stenosis 5 months after SBRT and had no laboratory changes. The biliary tract irradiated with >20 Gy was 7 mm and did not correspond to the bile duct stenosis region. No obstructive jaundice or biliary infection was found in any patient. CONCLUSIONS: SBRT for liver tumors adjacent to the CBS was feasible with minimal biliary toxicity. Only 1 patient had exceptional radiation-induced bile duct stenosis. For liver tumors adjacent to the CBS without other effective treatment options, SBRT at a dose of 40 Gy in 5 fractions is a safe treatment with regard to biliary toxicity.