Image-guidance triggered adaptive replanning of radiation therapy for locally advanced lung cancer: an evaluation of cases requiring plan adaptation.
- 作者列表："Appel S","Bar J","Alezra D","Ben-Ayun M","Rabin-Alezra T","Honig N","Katzman T","Chatterji S","Symon Z","Lawrence YR
OBJECTIVES:Anatomic changes may occur during chemoradiation treatment for lung cancers, requiring adaptive replanning. Here we characterize these cases. METHODS:We retrospectively studied lung cancer cases that underwent resimulation and adaptive replanning during 1/2016-3/2019. We compared first and second CT-simulation regarding tumor location, timing of change, tumor volume, anatomical alteration and change in simulation technique. We also compared dosimetric parameters between the plans, recorded local control, and overall survival outcomes. RESULTS:Out of 281 patients, 58 underwent replanning (20.6%). Histology included small cell (22.4%) and non-small cell (77.6%). Stage III was in 91.4%. Mean radiation dose of 59.4 Gray (Gy) (range 50-66Gy).Tumor location was peribronchial in 53.5%. Timing of replanning was in the first, second and final third of the treatment course in 26%, 43% and 31% respectively. Changes in gross tumor volume were observed in 74%; mean gross tumor volume was 276.7cc vs 192.7 cc (first vs second simulation, p = 0.001). Anatomical changes were identified in 35.4% including pleural fluid accumulation, atelectasis or pneumothorax alteration. Change in simulation technique was performed in 25.9%, including breath-hold or continuous positive airway pressure.Changes in dosimetric parameters when the same technique was used: lung V20Gy 26% (standard deviation, SD 7.6) vs 25.3% (SD 6.6) (p = 0.36), mean lung dose 15.1 Gy (SD 3.7) vs 14.7Gy (SD 3.3) (p = 0.23), heart V40Gy 10.2% (SD13) vs 7.2% (SD 9.8) (p = 0.037). When simulation technique changed: lung V20Gy 30.8% (SD 8.2) vs 27.3% (SD 8) (p = 0.012), mean lung dose 17.3 Gy (SD 4.4) vs 15.3 Gy (SD 3.8) (p = 0.007), heart V40Gy 11.1% (SD 14.7) vs 6.5% (SD 6.7) (p = 0.014).2 year local control was 60.7% (95% confidence interval, 34.5-79.2%), and median overall survival was 19.7 months. CONCLUSION:Adaptive replanning of radiation was performed in a fifth of locally advanced lung cancer patients. In most cases tumor volume decreased, or atelectasis resolved, causing mediastinal shifts, which, if unidentified and left uncorrected, may have led to local failure and increased toxicity. The heart V40Gy was reduced significantly in all cases, but significant reduction in lung doses was evident only if simulation technique was altered. ADVANCES IN KNOWLEDGE:In locally advanced lung cancer image-guidance with cone beam CT can detect significant mediastinal shifts and gross tumor volume changes that raise the need for adaptive replanning. Image guidance-triggered adaptive replanning should be added to the armament of advanced radiation treatment planning in locally advanced lung cancer.
目的: 肺癌放化疗治疗过程中可能发生解剖结构改变，需要适应性重新规划。这里我们描述这些病例。 方法: 我们回顾性研究了 1/2016-3/2019 期间接受再模拟和适应性再计划的肺癌病例。我们比较了第一和第二次 CT 模拟关于肿瘤位置、变化时间、肿瘤体积、解剖改变和模拟技术的变化。我们还比较了计划、记录的局部控制和总生存结局之间的剂量学参数。 结果: 在 281 例患者中，58 例接受了重新计划 (20.6%)。组织学包括小细胞 (22.4%) 和非小细胞 (77.6%)。第三阶段为 91.4%。平均辐射剂量为 59.4 Gray (Gy) (范围 50-66Gy)。53.5% 肿瘤位于支气管周围。重新计划的时间分别为 26% 、 43% 和 31% 疗程的第一、第二和最后三分之一。观察到 74% 的大体肿瘤体积变化; 平均大体肿瘤体积为 276.7cc vs 192.7 cc (第一次 vs 第二次模拟，p = 0.001)。35.4% 的解剖改变包括胸水积聚、肺不张或气胸改变。25.9% 进行了模拟技术的改变，包括屏气或持续气道正压。使用相同技术时剂量学参数的变化: 肺 V20Gy 26% (标准差，SD 7.6) vs 25.3% (SD 6.6) (p = 0.36), 平均肺剂量 15.1 gy (SD 3.7) vs 14。 7Gy(SD 3.3) (p = 0.23)，心脏 V40Gy 10.2% (SD13) vs 7.2% (SD 9.8) (p = 0.037)。当模拟技术改变时: 肺 V20Gy 30.8% (SD 8.2) vs 27.3% (SD 8) (p = 0.012)，平均肺剂量 17.3 gy (SD 4.4) vs 15.3 gy (SD 3.8) (p = 0.007)，心脏 V40Gy 11.1% (SD 14.7) vs 6.5% (SD 6.7)(P = 0.014).2 年局部对照为 60.7% (95% 置信区间，34.5-79.2%)，中位总生存期为 19.7 个月。 结论: 五分之一的局部晚期肺癌患者进行了放射适应性重新计划。在大多数情况下，肿瘤体积缩小，或肺不张消退，引起纵隔移位，如果不明而未矫正，可能导致局部失败和毒性增加。所有病例的心脏 V40Gy 均显著减少，但只有改变模拟技术，肺剂量才显著减少。 知识进步: 在局部晚期肺癌图像引导下，锥形束 CT 可以检测到显著的纵隔移位和肿瘤体积变化，增加了适应性重新规划的需要。在局部晚期肺癌的晚期放射治疗计划中，应加入图像引导触发的适应性重新计划。
METHODS:BACKGROUND:The objectives of this study are to assess the chest drainage volumes of patients undergoing anatomic resection of non-small cell lung carcinoma and to determine the safety and effectiveness of administering enoxaparin for thromboprophylaxis. METHODS:A total of 77 patients were included in the study. A study was conducted on the first group of 42 patients in which enoxaparin prophylaxis (enoxaparin, 40 mg) was subcutaneously injected once a day for a period of three days after the patients underwent anatomic pulmonary resection between March 2016 and March 2018. An enoxaparin-free group was identified and included 35 patients who received no enoxaparin prophylaxis after undergoing anatomic pulmonary resection between February 2013 and February 2016. We compared the changes in hemoglobin (Hb) levels, postoperative 3-day drainage volume, transfusion volume, pulmonary complications and length of stay between the two groups. RESULTS:No differences in postoperative Hb levels, chest drainage volume, transfusion volume, postoperative complications, and length of stay were observed between the two groups. Deep-vein thrombosis was noted in a patient in the enoxaparin-free group. No major bleeding was noted in either group. CONCLUSION:We found that for patients undergoing anatomic resection of primary lung cancer, the blood transfusion and chest drainage volumes did not differ, regardless of whether the patients were given enoxaparin. To the best of our knowledge, the impact of low-molecular-weight heparin on chest tube drainage volume for patients undergoing anatomic resection of non-small cell lung carcinoma has not been investigated before.
METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.
METHODS:BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS:Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS:Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION:Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02304809.