Significance of stereotactic body radiotherapy in older patients with early stage non-small cell lung cancer

Objectives

Our aim was to investigate long-term treatment outcomes in older patients with early stage non-small cell lung cancer (NSCLC) and the presence or absence of therapeutic benefits, using the G8 screening tool.

Co-morbidity index predicts for mortality after stereotactic body radiotherapy for medically inoperable early-stage non-small cell lung cancer

Purpose

To determine the prognostic role of co-morbidity in medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).

Methods and materials

Between 2000 and 2007, 88 consecutive early-stage medically inoperable NSCLC patients were treated by linac-based SBRT. The dose was either 45 Gy or 67.5 Gy in three fractions prescribed to the isocenter. Baseline co-morbidities were retrospectively retrieved by consultation of a formal electronic registry of diagnoses as well as patients’ charts. The age-adjusted Charlson Co-morbidity Index (CCI) was scored for each patient and subjected to univariate and multivariate analysis.

Results

With a median follow-up of 44 months, the actuarial local control rate at 4 years was 89% while the median overall survival was 22 months. The median age-adjusted CCI score was 5. The age-adjusted CCI was a significant predictor of overall survival on both univariate (p = 0.002) and multivariate analysis (p = 0.011). Patients with an age-adjusted CCI score of 3 or less had a median survival of 41 months versus only 11 months for those scoring 6 or more.

Conclusion

The number and seriousness of co-morbidities predict overall survival in medically inoperable early-stage NSCLC treated with SBRT. Because the determination of medical operability is frequently based on both objective measures and subjective clinical judgment, it is recommended that co-morbidity be formally indexed in all studies examining the outcomes of SBRT.     

非小细胞肺癌放射治疗的剂量分割研究进展

放疗是局限晚期非小细胞肺癌患者的主要治疗手段,改变不同的剂量分割方式是提高放疗疗效的手段之一.不同的剂量分割方式有不同的优缺点,当然也适用于不同的患者.我们将对非小细胞肺癌放射治疗不同的剂量分割方式作一综述.     

非小细胞肺癌寡转移的立体定向放射治疗研究

非小细胞肺癌(Non-small cell lung cancer,NSCLC)是除小细胞肺癌以外所有类型的肺癌,脑、骨、肝及肾上腺为最常见的远处转移部位。在NSCLC远处转移患者中,并非都是多发的、广泛的,有近7%的患者表现为肺外孤立性转移。这种特殊形式的晚期肿瘤转移状态称之为NSCLC寡转移。寡转移的治疗以局部治疗为主,局部治疗主要措施包括立体定向放疗、手术切除、射频消融等。本文主要探讨立体定向放射治疗(Stereotactic radiotherapy,SRT)对NSCLC在常见远处转移脏器寡转移的作用。     

A new index comparable to BED for evaluating the biological efficacy of hypofractionated radiotherapy schemes on early stage non-small cell lung cancer: Analysis of data from the literature

Background and purpose

Hypofractionated radiotherapy has been the principal curative treatment option for early stage NSCLC patients who are medically inoperable or those who refuse surgery and achieved favorable clinical outcomes. Evidence demonstrated that the linear quadratic model widely used in normally fractionated radiotherapy cannot work well to fit outcome data by use of BED to predict the effect of hypofractionation schemes. New models and the related metrics need to be developed to quantify the effect of high-dose ablative regimens for early stage NSCLC.

Patients and methods

Trials using hypofractionated radiotherapy without chemotherapy to treat early stage (T₁ or T₂N₀M₀) primary NSCLC and providing information on patient numbers, age, T stage and local control rates were eligible. The endpoint was local relapse and the covariates analyzed were total radiotherapy dose, dose per fraction or combinations of the two parameters, treatment duration, T stage and median age of patients within the trial. The model used was a multivariate logistic regression.

Results

19 trials were included (767 patients) in which 90 patients suffered local relapse. Only total dose×dose per fraction (D × d) and stage T had statistically significant effect on local control. Smaller T stage (p = 0.000) and increasing D × d (p = 0.006) were associated with improved probability of local control. In contrast, BED₁₀ had no significant impact on local control, which probably indicated that D × d might be a more effective metric than BED₁₀ to predict tumor control rate and assess the efficacy of the large dose fractionation schemes for early stage NSCLC.

Conclusions

BED was not an ideal metric to estimate the effect of the schemes of high-dose ablative radiotherapy for early stage NSCLC, and total dose×fraction dose could be considered as a comparable index, though the result need to be further validated.     

Comparison of accelerated hypofractionation and stereotactic body radiotherapy for Stage 1 and node negative Stage 2 non-small cell lung cancer (NSCLC)

Purpose

Stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy (AHRT) have favorable local control (LC) relative to conventional fractionation in the treatment of stage I non-small cell lung cancer (NSCLC). We report the results of our single institution experience with the treatment of early stage NSCLC with SBRT or AHRT in cases where SBRT was felt to be suboptimal.

Methods

One hundred and sixty patients with Stage 1 and node negative Stage 2 NSCLC were treated with SBRT or AHRT from 2003 to 2011. Median follow-up was 29.4 and 19 months (mo), respectively. The median dose was 54 Gy in 3 fractions (fx) (SBRT) and 70.2 Gy in 26 fx (AHRT). Acute and late toxicities (tox) were graded (G) per CTCAE v4. Time to local (LF), regional (RF) and distant (DF) failure were estimated using the Kaplan–Meier method. The impact of patient and tumor related factors on LF were estimated by multivariate Cox proportional hazard model.

Results

Three-year LC rates were 87.7% (SBRT) and 71.7% (AHRT). The 3-year freedom from DF was 73.3% and 68.1%. Median OS was 38.4 (95% CI 29.7–51.6) and 35 (95% CI 22–48.3) mo. No G3 or 4 tox were observed. At 1 year, 30% and 50% of complications resolved, while (5–6%) had persistent chest wall pain.Multivariate analysis demonstrated that increasing dose per fraction and tumor size (>5.5 vs. 4 cm) in the AHRT and SBRT group were found to be associated with a reduced (HR 0.33 95% CI 0.13–0.84, p = 0.021) and increased (HR: 6.372 95% CI 1.23–32.92, p = 0.027) hazard for local failure respectively.

Conclusions

Our results compare favorably with other reports of treatment for early stage NSCLC. AHRT patients had comparable LC despite increased size and central disease. Toxicity was limited and overall survival, regional and distant recurrences were similar between groups.     

早期非小细胞肺癌立体定向放疗的相关研究

目前临床上确诊的早期非小细胞肺癌患者中,约20%因自身原因不能手术。立体定向放射治疗具有治疗时间短、治疗相关性损伤轻及肿瘤局控率高的优势,当前国际上已经将其作为早期不能手术非小细胞肺癌的一线治疗方案。在早期能手术非小细胞肺癌的治疗中,立体定向放疗也达到了令人鼓舞的治疗效果,但也存在部分亟待解决的问题。本文将对立体定向放射治疗在早期非小细胞肺癌治疗中的剂量分割、临床适应症及放疗损伤进行综述。     

Current status of stereotactic body radiotherapy for lung cancer

Stereotactic radiotherapy (SRT) for extracranial tumors has been recently performed to treat lung and liver cancers, and has subsequently been named stereotactic body radiotherapy (SBRT). The advantages of hypofractionated radiotherapy for treating lung tumors are a shortened treatment course that requires fewer trips to the clinic than a conventional program, and the adoption of a smaller irradiated volume allowed by greater setup precision. This treatment is possible because the lung and liver are considered parallel organs at risk. The preliminary clinical results, mostly reported on lung cancer, have been very promising, including a local control rate of more than 90%, and a relatively low complication rate. The final results of a few clinical trials are awaited. SBRT may be useful for the treatment of stage I lung tumors.     

Impact of low skeletal muscle mass on non-lung cancer mortality after stereotactic body radiotherapy for patients with stage I non-small cell lung cancer

Purpose

The purpose of the present study was to retrospectively evaluate impact of pre-treatment skeletal muscle mass (SMM) on overall survival and non-lung cancer mortality after stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC).

Dose-response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy

Purpose

To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT).

Materials and methods

A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n = 21) or pulmonary metastases (n = 54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n = 29) or three fractions of 12.5 Gy to 65% (n = 40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/β ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ? grade II SWOG were fitted using NTCP models.

Results

Eleven patients developed RP grade II. With an average MLD of 10.3 ± 5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5 ± 4.3 Gy and 9.9 ± 5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V_2.5-V₅₀) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses.

Conclusions

The MLD and V_2.5-V₅₀ of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.     

后程X线立体定向放射治疗局部晚期非小细胞肺癌的研究

目的探讨后程大分割X线立体定向放射治疗在局部晚期非小细胞肺癌放射治疗中的作用。方法106例初治局部晚期(Ⅲa、Ⅲb期)非小细胞肺癌病例随机分为单纯常规放射治疗组(CRT)和后程立体定向放射治疗组(LCHSRT),完成治疗并且资料完整者共91例,CRT组43例,LCHSRT组48例。CRT组常规剂量分割大野对穿照射至43.5Gy后对原发肿瘤和转移淋巴结缩野加量至65.2Gy。LCHSRT组常规剂量分割大野对穿照射至44.4Gy后对原发肿瘤和转移淋巴结行大分割立体定向放射治疗,LCHSRT照射方式为圆形准直器非共面弧形照射,计划靶区体积边缘处方剂量4～7Gy/次,隔日1次,总剂量(22.8±5.5)Gy。结果CRT组和LCHSRT组放射性肺炎的发生率分别为11.6%和14.6%。放射治疗结束后3个月CT检查CRT与LCHSRT组局部肿瘤全消率分别为30.2%和63.5%(P<0.01);1年局部控制率分别为62.0%和86.5%(P>0.05);1年生存率分别为55.8%和79.2%(P<0.05)。两组急慢性放射性肺损伤差异均无显著性意义(χ2值分别为0.68和2.90,P值均>0.05)。结论圆形准直器非共面弧形照射后程大分割立体定向放射治疗提高了局部晚期非小细胞肺癌的局部肿瘤全消率和局部控制率,但其适形性和靶区内剂量均匀性不够理想,而且当照射剂量≥25Gy时放射性肺纤维化发生率明显增加。     

Stereotactic Ablative Radiotherapy for stage I histologically proven non-small cell lung cancer: An Italian multicenter observational study

Objectives

Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials.

Materials and Methods

We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3–8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival).

Results

Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS).

Conclusion

The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB).     

Double-scattered proton-based stereotactic body radiotherapy for stage I lung cancer: A dosimetric comparison with photon-based stereotactic body radiotherapy

Purpose

Stereotactic body radiotherapy (SBRT) has gained popularity in the treatment of early-stage non-small-cell lung cancer (NSCLC) because of its ability to deliver conformal radiation doses to small targets. However, photon-based SBRT (xSBRT) is associated with significant grade 3+ toxicities. In this study, we compare xSBRT treatment plans with proton-based SBRT (pSBRT) to determine whether dose to normal structures could be reduced if SBRT was delivered with protons.

Materials and methods

Eight patients with medically inoperable, peripherally located stage I NSCLC were treated with xSBRT to 48 Gy in 4 12-Gy fractions. These patients were retrospectively re-planned using the same treatment volumes with 3-dimensional conformal double-scatter proton therapy. A Wilcoxon paired test compared dosimetric parameters between the plans for each patient.

Results

Compared with xSBRT there was a dosimetric improvement with pSBRT for these volumes: lung V5 (median difference [MD] = 10.4%, p = 0.01); V10 (MD = 6.4%, p = 0.01); V20 (MD = 2.1%, p = 0.01); V40 (MD = 1.5%, p = 0.05); and mean lung dose (MD = 2.17 Gy, p = 0.01). There were also benefits (p = <0.05) in D0.1cm3 and D5cm3 with pSBRT to the heart, esophagus, and bronchus.

Conclusions

In a dosimetric comparison between photon and proton-based SBRT, protons resulted in lower doses to critical organs at risk and a smaller volume of non-targeted normal lung exposed to radiation (V5, V10, V20, and V40). The clinical significance and relevance of these dosimetric improvements remain unknown.     

Matched-pair comparisons of stereotactic body radiotherapy (SBRT) versus surgery for the treatment of early stage non-small cell lung cancer: A systematic review and meta-analysis

Purpose

A population-based matched-pair comparison was performed to compare the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC).

Methods

All the eligible studies were searched by PubMed, Medline, Embase, and the Cochrane Library. The meta-analysis was performed to compare odds ratios (OR) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local control (LC), and distant control (DC).

Results

Six studies containing 864 matched patients were included in the meta-analysis. The surgery was associated with a better long-term OS in patients with early-stage NSCLC. The pooled OR and 95% confidence interval (CI) for 1-year, 3-year OS were 1.31 [0.90, 1.91] and 1.82 [1.38, 2.40], respectively. However, the difference in 1-year and 3-year CSS, DFS, LC and DC was not significant.

Conclusions

This systematic review found a superior 3-year OS after surgery compared with SBRT, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials.