Wanet Marie, Delor Antoine, Hanin François-Xavier, Ghaye Benoît, Van Maanen Aline, Remouchamps Vincent, Clermont Christian, Goossens Samuel, Lee John Aldo, Janssens Guillaume, Bol Anne, Geets Xavier
Center of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Hippocrate, 54 Bte B1.54.07, 1200, Brussels, Belgium.
Department of Radiation Oncology, Cliniques universitaires Saint-Luc, 1200, Brussels, Belgium.
Strahlenther Onkol. 2017 Oct;193(10):812-822. doi: 10.1007/s00066-017-1168-z. Epub 2017 Jul 21.
The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity.
A total of 13 patients with stage II-III NSCLC were enrolled to receive a dose of 62.5 Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTV) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method.
The average dose to PTV reached 89.17 Gy for peripheral and 75 Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis.
These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.
本研究旨在评估个体化18F氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）引导下非小细胞肺癌（NSCLC）患者剂量递增加量放疗的可行性，并评估其对局部肿瘤控制和毒性的影响。
共纳入13例II-III期NSCLC患者，对基于CT的计划靶区（PTV；原发肿瘤和受累淋巴结）给予25次分割、总量62.5 Gy的剂量。使用调强放疗（IMRT）同步整合加量（SIB），在基于PET的个体化PTV（PTV）内增加分次剂量，直至达到预定的危及器官（OAR）阈值。随访期间通过重复FDG-PET/计算机断层扫描评估肿瘤反应。根据CTCAE标准（第4.0版）记录并分类急性和晚期毒性。采用Kaplan-Meier法确定局部无进展生存期。
外周肿瘤PTV的平均剂量达到89.17 Gy，中央肿瘤为75 Gy。中位随访29个月后，7例患者仍存活，6例死亡（4例因远处进展，2例因5级毒性）。2例患者出现局部进展并伴有进一步复发。1年和2年局部无进展生存率分别为76.9%和52.8%。观察到3例急性3级食管炎。2例中央型肿瘤患者出现晚期毒性并因严重咯血死亡。
这些结果表明，在IMRT治疗中基于FDG-PET进行非均匀和个体化的剂量递增是可行的。外周肿瘤患者达到的剂量高于中央肿瘤患者。该策略能够以可接受的毒性率实现良好的局部控制。然而，对于直接侵犯纵隔器官的中央型肿瘤，剂量递增必须谨慎进行，以避免严重的晚期毒性。
