Radiation-induced organizing pneumonia after stereotactic body radiotherapy for lung tumor

The aim of this retrospective study was to investigate characteristics of organizing pneumonia (OP) after stereotactic body radiotherapy (SBRT) for lung tumor. Between September 2010 and June 2014, patients who were diagnosed as Stage I lung cancer and treated with SBRT at our institution were included in this study. A total of 78 patients (47 males with a median age of 80 years) were analyzed. The median follow-up period was 23 months. Five patients (6.4%) developed OP at 6–18 months after SBRT. The cumulative incidence of OP was 4.3% (95% confidence interval [CI], 1.1–11.0) and 8.2% (95% CI, 2.9–17.0) at 1 and 2 years, respectively. Tumor location (superior and middle lobe vs inferior lobe) was shown to be a borderline significant factor for the occurrence of OP (P = 0.069). In the subgroup analysis of patients with a radiographic follow-up period at least 6 months, or who died within 6 months after SBRT, 7 of 72 patients (9.7%) developed Grade 2 or 3 radiation pneumonitis (G2/3 RP) at 2–4 months after SBRT. A statistically significant association between G2/3 RP in the subacute phase and OP was shown (P = 0.040). In two of the five patients who developed OP, the symptoms and radiographic change were improved rapidly by corticosteroid administration. One patient had relapsed OP after suspending the treatment and re-administration was required. Three patients with minor symptoms were managed without corticosteroid administration and OP resolved without any relapse. The radiation-induced OP should be considered as one of the late lung injuries after SBRT for lung tumors.     

Clinical results of stereotactic body radiotherapy for Stage I small-cell lung cancer: a single institutional experience

The purpose of this study was to evaluate the treatment outcomes of stereotactic body radiotherapy (SBRT) for Stage I small-cell lung cancer (SCLC). From April 2003 to September 2009, a total of eight patients with Stage I SCLC were treated with SBRT in our institution. In all patients, the lung tumors were proven as SCLC pathologically. The patients'' ages were 58–84 years (median: 74). The T-stage of the primary tumor was T1a in two, T1b in two and T2a in four patients. Six of the patients were inoperable because of poor cardiac and/or pulmonary function, and two patients refused surgery. SBRT was given using 7–8 non-coplanar beams with 48 Gy in four fractions. Six of the eight patients received 3–4 cycles of chemotherapy using carboplatin (CBDCA) + etoposide (VP-16) or cisplatin (CDDP) + irinotecan (CPT-11). The follow-up period for all patients was 6–60 months (median: 32). Six patients were still alive without any recurrence. One patient died from this disease and one died from another disease. The overall and disease-specific survival rate at three years was 72% and 86%, respectively. There were no patients with local progression of the lesion targeted by SBRT. Only one patient had nodal recurrence in the mediastinum at 12 months after treatment. The progression-free survival rate was 71%. No Grade 2 or higher SBRT-related toxicities were observed. SBRT plus chemotherapy could be an alternative to surgery with chemotherapy for inoperable patients with Stage I small-cell lung cancer. However, further investigation is needed using a large series of patients.     

The impact of abdominal compression on outcome in patients treated with stereotactic body radiotherapy for primary lung cancer

The aim of this study was to evaluate the impact of abdominal compression (AC) on outcome in patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer. We retrospectively reviewed data for 47 patients with histologically proven non-small cell lung cancer and lung tumour motion ≥8 mm treated with SBRT. Setup error was corrected based on bony structure. The differences in overall survival (OS), local control (LC) and disease-free survival (DFS) were evaluated to compare patients treated with AC (n = 22) and without AC (n = 25). The median follow-up was 42.6 months (range, 1.4–94.6 months). The differences in the 3-year OS, LC and DFS rate between the two groups were not statistically significant (P = 0.909, 0.209 and 0.639, respectively). However, the largest difference was observed in the LC rate, which was 82.5% (95% CI, 54.9–94.0%) for patients treated without AC and 65.4% (95% CI, 40.2–82.0%) for those treated with AC. After stratifying the patients into prognostic groups based on sex and T-stage, the LC difference increased in the group with an unfavourable prognosis. The present study suggests that AC might be associated with a worse LC rate after SBRT using a bony-structure-based set-up.     

Impact of low iodine density tumor area ratio on the local control of non-small cell lung cancer through stereotactic body radiotherapy

Lung cancer with low average iodine density measured via contrast-enhanced computed tomography (CT) using dual-energy CT technology has shown a reduced local control rate after stereotactic body radiotherapy (SBRT). The current study therefore investigated the relationship between low iodine density tumor area and its ratio and local recurrence after SBRT. Dual-energy CT was performed on the day before SBRT initiation, with a low iodine density tumor area being defined as that with an iodine density of <1.81 mg cm^–3. The low iodine density tumor area, the ratio between the low iodine density tumor area and the entire tumor, and the local recurrence rate were then determined. No correlation was observed between the low iodine density tumor area and the local recurrence rate. However, tumors with a large low iodine density tumor area ratio showed an increased local recurrence rate, with the prognostic accuracy almost similar to that in previous studies using average iodine densities. Our results therefore suggest that the low iodine density tumor area ratio was a useful prognostic index after SBRT, with an accuracy comparable with that of the average iodine density.     

胰腺癌三维适形放射治疗与γ射线体部立体定向放射治疗加量疗效分析

目的:回顾性分析61例胰腺癌患者行常规三维适形放射治疗、随后缩野行放射治疗加量或γ射线体部立体定向放射治疗加量的疗效差异。方法:将61例胰腺癌患者按治疗方法分为三维适形放疗加量治疗组21例(三维-CRT组)和γ射线体部立体定向放疗加量治疗(SBRT加量组)40例。对61例胰腺癌患者先行常规三维适形放疗(胰腺病灶+腹膜后淋巴结引流区域,TD40 Gy/20 Fx)后重新扫描;其中三维-CRT组针对胰腺病灶及腹膜后肿大淋巴结放射治疗加量至TD46~50 Gy;SBRT加量组使用γ射线体部立体定向放射治疗加量治疗追加14~16 Gy,共7~8次。结果:两组总中位生存时间为11.3个月,1年总生存率为44.95%。单因素分析显示,卡氏评分(KPS)≥90分、接受过化疗及女性患者疗效更佳,其中位生存时间差异有统计学意义(x2=8.992,x2=4.056,x2=3.953;P<0.05)。三维-CRT组与SBRT加量组的中位生存时间分别为7.5个月和13.0个月,两组治疗相关急性和后期副反应无差异。结论:适形放射治疗加γ射线立体定向放射治疗加量对于局部晚期胰腺癌患者而言耐受性好,有提高患者生存期的趋势。放射治疗前KPS评分高、放射治疗联合化疗以及女性患者可能获得更好的疗效。     

Dosimetry analyses comparing high-dose-rate brachytherapy,administered as monotherapy for localized prostate cancer,with stereotactic body radiation therapy simulated using CyberKnife

The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm³ for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm³ (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted.     

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.     

Survival outcomes after stereotactic body radiotherapy for 79 Japanese patients with hepatocellular carcinoma

Stereotactic body radiotherapy (SBRT) is a relatively new treatment for liver tumor. Outcomes of SBRT for liver tumors unsuitable for ablation or surgical resection were evaluated.A total of 79 patients treated with SBRT for primary hepatocellular carcinoma (HCC) between 2004 and 2012 in six Japanese institutions were studied retrospectively. Patients treated with SBRT preceded by trans-arterial chemoembolization were eligible. Their median age was 73 years, 76% were males, and their Child–Pugh scores were Grades A (85%) and B (11%) before SBRT. The median biologically effective dose (α/β = 10 Gy) was 96.3 Gy.The median follow-up time was 21.0 months for surviving patients. The 2-year overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival were 53%, 40% and 76%, respectively. Sex and serum PIVKA-II values were significant predictive factors for OS. Hypovascular or hypervascular types of HCC, sex and clinical stage were significant predictive factors for PFS. The 2-year PFS was 66% in Stage I vs 18% in Stages II–III. Multivariate analysis indicated that clinical stage was the only significant predictive factor for PFS. No Grade 3 laboratory toxicities in the acute, sub-acute, and chronic phases were observed.PFS after SBRT for liver tumor was satisfactory, especially for Stage I HCC, even though these patients were unsuitable for resection and ablation. SBRT is safe and might be an alternative to resection and ablation.     

Impact of pre-treatment C-reactive protein level and skeletal muscle mass on outcomes after stereotactic body radiotherapy for T1N0M0 non-small cell lung cancer: a supplementary analysis of the Japan Clinical Oncology Group study JCOG0403

This study aimed to evaluate the impact of pretreatment C-reactive protein (CRP) and skeletal muscle mass (SMM) on outcomes after stereotactic body radiotherapy (SBRT) for T1N0M0 non-small cell lung cancer (NSCLC) as a supplementary analysis of JCOG0403. Patients were divided into high and low CRP groups with a threshold value of 0.3 mg/dL. The paraspinous musculature area at the level of the 12th thoracic vertebra was measured on simulation computed tomography (CT). When the area was lower than the sex-specific median, the patient was classified into the low SMM group. Toxicities, overall survival (OS) and cumulative incidence of cause-specific death were compared between the groups. Sixty operable and 92 inoperable patients were included. In the operable cohort, OS significantly differed between the CRP groups (log-rank test p = 0.009; 58.8% and 83.6% at three years for high and low CRP, respectively). This difference in OS was mainly attributed to the difference in lung cancer deaths (Gray’s test p = 0.070; 29.4% and 7.1% at three years, respectively). No impact of SMM on OS was observed. The incidence of Grade 3–4 toxicities tended to be higher in the low SMM group (16.7% vs 0%, Fisher’s exact test p = 0.052). In the inoperable cohort, no significant impact on OS was observed for either CRP or SMM. The toxicity incidence was also not different between the CRP and SMM groups. The present study suggests that pretreatment CRP level may provide prognostic information in operable patients receiving SBRT for early-stage NSCLC.     

Differences in rates of radiation-induced true and false rib fractures after stereotactic body radiation therapy for Stage I primary lung cancer

The purpose of this study was to analyze the dosimetry and investigate the clinical outcomes of radiation-induced rib fractures (RIRFs) after stereotactic body radiotherapy (SBRT). A total of 126 patients with Stage I primary lung cancer treated with SBRT, who had undergone follow-up computed tomography (CT) at least 12 months after SBRT and who had no previous overlapping radiation exposure were included in the study. We used the Mantel–Haenszel method and multiple logistic regression analysis to compare risk factors. We analyzed D(0.5 cm³) (minimum absolute dose received by a 0.5-cm³ volume) and identified each rib that received a biologically effective dose (BED) (BED3, using the linear–quadratic (LQ) formulation assuming an α/β = 3) of at least 50 Gy. Of the 126 patients, 46 (37%) suffered a total of 77 RIRFs. The median interval from SBRT to RIRF detection was 15 months (range, 3–56 months). The 3-year cumulative probabilities were 45% (95% CI, 34–56%) and 3% (95% CI, 0–6%), for Grades 1 and 2 RIRFs, respectively. Multivariate analysis showed that tumor location was a statistically significant risk factor for the development of Grade 1 RIRFs. Of the 77 RIRFs, 71 (92%) developed in the true ribs (ribs 1–7), and the remaining six developed in the false ribs (ribs 8–12). The BED3 associated with 10% and 50% probabilities of RIRF were 55 and 210 Gy to the true ribs and 240 and 260 Gy to the false ribs. We conclude that RIRFs develop more frequently in true ribs than in false ribs.     

呼吸运动对肺癌三维适形放疗肿瘤靶区影响的研究

目的：探索呼吸运动对肺癌三维适形放疗肿瘤靶区的几何中心和体积的影响,为肿瘤靶区的勾画提供参考依据。方法：27例病理证实的原发性非小细胞肺癌患者平静呼吸状态,行CT扫描,相同条件下行呼气末屏气扫描和吸气末屏气扫描。在治疗计划系统（TPS）中,分别勾画平静呼吸状态扫描图像和吸气末屏气状态扫描图像的肿瘤靶区,得到肿瘤靶区（GTV）及诊断图像的肿瘤靶区（GTVz）,将呼气末屏气扫描和吸气末屏气扫描图像进行融合,得到融合图像,勾画得到融合图像的肿瘤靶区（GTVf）,并进行比较。结果：肿瘤靶区几何中心在X、Y、Z方向移位的平均值,平静图像和诊断图像与融合图像相比分别为（0．34±0．21）、（0．21±0．27）、（0．84±0．42）cm和（0．36±0．24）、（0．28±0．31）、（0．91±0．43）cm。融合图像靶体积与平静图像靶体积、诊断图像靶体积相比,在肺的上、中、下部位分别增加37．29％、21．44％、44．82％和42．33％、25．39％、50．97％,差异都有统计学意义。平静图像靶区体积与诊断图像靶体积相比,在肺的上、中、下部位分别增加4．09％、4．28％、4．24％,差异有统计学意义。结论：呼吸运动引起肺癌肿瘤靶区中心坐标在X、Y、Z方向上发生不同程度的移位,同时伴随肿瘤靶区体积的改变,勾画肿瘤靶区时中应充分考虑这一点。     

Outcomes of SBRT for lung oligo-recurrence of non-small cell lung cancer: a retrospective analysis

The benefit of local ablative therapy (LAT) for oligo-recurrence has been investigated and integrated into the treatment framework. In recent decades, stereotactic body radiation therapy (SBRT) has been increasingly used to eliminate metastasis owing to its high rate of local control and low toxicity. This study aimed to investigate the outcomes of SBRT for patients with lung oligo-recurrence of non-small cell lung cancer (NSCLC) from our therapeutic center. Patients with lung oligo-recurrence of NSCLC treated with SBRT between December 2011 and October 2018 at Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) were reviewed. The characteristics, treatment-related outcomes, and toxicities of the patients were analyzed. Univariable and multivariable Cox regression were performed to identify the factors associated with survival. A total of 50 patients with lung oligo-recurrence of NSCLC were enrolled. The median follow-up period was 23.6 months. The 3-year local progression-free survival (LPFS), progression-free survival (PFS) and overall survival (OS) after SBRT were 80.2%, 21.9% and 45.3%, respectively. Patients in the subgroup with LAT to all residual diseases showed significantly improved OS and PFS. No treatment-related death occurred after SBRT. SBRT is a feasible option to treat patients with lung oligo-recurrence of NSCLC, with high rates of local control and low toxicity. LAT to all residual diseases was associated with better survival outcomes. Future prospective randomized clinical trials should evaluate SBRT strategies for such patients.     

Modified Glasgow Prognostic Score is predictive of prognosis for non-small cell lung cancer patients treated with stereotactic body radiation therapy: a retrospective study

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.     

头颈部肿瘤立体定向放射治疗中的质量保证

本文介绍了头颈部肿瘤立体定向放射治疗时各环节中的质量保证     

Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.