Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

W. Uyterlinde



Author of

  • +

    E02 - Radiation Toxicity (ID 2)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
    • +

      E02.2 - Radiation Esophagitis (ID 378)

      14:25 - 14:45  |  Author(s): W. Uyterlinde

      • Abstract
      • Presentation
      • Slides

      Abstract
      Introduction The improved survival in locally advanced non-small cell lung cancer (NSCLC) patients treated with concurrent chemo-radiation (CCRT) comes at a price of increased esophagus toxicity. Acute esophagus toxicity (AET) occurs within 3 months after CCRT and late esophagus toxicity (LET) consists of symptoms persisting or occurring >3 months after treatment. AET is treated with dietary changes, proton pump inhibitors, analgesics, promotility agents, intravenous fluids, and/or nasogastric- or gastrostomy tube insertion. Patients who develop stenosis, perforation or fistula are categorized as severe LET (grade 3-5). Patients with stenosis are treated by dilatation. Some patients will develop a fistula, which can be treated with intraluminal stenting. However the prognosis for patients with a fistula is grim. Estimation of the probability and severity of radiation esophagitis after CCRT treatment is crucial. This allows the individual prescription of tumor doses. Several prediction models have been reported to estimate the risk of AET based on the planned dose distributions. Currently used models to predict acute esophageal toxicity (AET) in lung cancer patients after Intensity Modulated Radiotherapy (IMRT) and concurrent chemotherapy were derived from patients treated with 3D-conformal-radiotherapy (3DCRT). These models first reduce the dose-volume histograms to a single parameter like the volume of esophagus receiving more than a certain threshold dose (V~x~). In a large multi-institutional study on 1082 patients treated with 3DCRT, or IMRT concurrent with chemotherapy, the high-dose volumes were the most important predictors for radiation esophagitis [ref 1]. The V60 emerged as the best predictor for both moderate and severe esophagus toxicity. A low-risk subgroup was identified with a very low V60 of <0.07%, an intermediate-risk subgroup with a V60 of 0.07%-16.99%, and a high-risk subgroup with a V60 of ≥17%. Severe LET seriously affects the patients’ quality of life or even leads to death. For LET predicting models are lacking. With improved survival in patients treated with CCRT, it is important and feasible to analyze LET. This abstract is a summary from a series of studies conducted at NKI on esophagus toxicity in a large NSCLC patient cohort. The patients were all treated with hypofractionated radiotherapy, 66 Gy in 24 fractions, and concurrent daily low dose cisplatin. The following items were investigated: 1) Comparison of AET incidence in patients treated with 3DCRT and CCRT to sequential chemoradiation and RT only.¨ 2) Compare incidence of AET with 3DCRT to IMRT. 3) Analysis of prognostic factors for AET using IMRT. 4) Correlation of radiotherapy dose to the oesophagus wall and AET by means of post-RT 18FDG-PET scans acquired after CCRT. 5) Relations between severe LET and the clinical and dosimetric variables. Material and methods The dose-effect relation of AET (185 patients) [ref 3] and LET ≥grade 3 (171 patients) [ref 6] and dose-volume parameters of the esophagus after hypofractionated IMRT (66 Gy/24 fractions) and concurrent low dose cisplatin were investigated. The dose distributions were first converted to Normalized Total Doses to account for fractionation effects with an α/β-ratio of 10 Gy (AET) or 3 Gy (LET). Equivalent Uniform Dose (EUD) to the esophagus and the volume percentage receiving more than x Gy (Vx) were evaluated by Lyman-Kutcher-Burman model. The association between AET and severe LET (grade ≥3 RTOG/EORTC) was tested through Cox-proportional-hazards model Clinical parameters, onset and recovery times were analyzed as well. Results Acute Esophagus Toxicity -For NSCLC patients treated with 3DCRT and concurrent chemotherapy, the incidence of AET grade ≥ 2 was 27% and significantly higher compared to patients treated with sequential chemoradiation or radiotherapy only regimens [ref 2]. -The AET incidences were not significantly different between 3DCRT based and IMRT based CCRT patients. In order to illustrate the differences between 3DCRT and IMRT we show the Vx (α/β-ratio=10) in steps of 5 Gy derived from the AET study by Kwint et al, and also for 36 CCRT patients treated in the EORTC 08972 trial. From Figure 1 it can be appreciated that with IMRT the volume of esophagus receiving a dose from 5-40 Gy was significantly smaller, while at 70 Gy it was increased. Moreover, the LKB model based on the V50 was not significantly different between IMRT and 3DCRT [ref 3]. -A total of 22% NSCLC patients developed AET toxicity ≥ grade 3 after IMRT to 66 Gy in 24 fractions and concurrent daily low dose cisplatin. The V50 was identified as most accurate predictor of grade ≥ 3 AET [ref 3]. -The median time to AET grade 3 was 30 days, with a median duration of >80 days. Higher grade of AET was also associated with a lower recovery rate [ref 4]. -Post-CCRT esophageal FDG uptake on 18FDG-PET is associated with AET grade. SUV predictability of grade 2-3 AET was significantly improved by using the derived relation between RT dose and PETpost [ref 5]. Results Late Esophagus Toxicity A total of 6% patients developed LET ≥ grade 3 at a median follow-up of 33 months (95% CI 29~37) with a median overall survival of 24 months (95% CI 16~32) [ref 6]. The median onset time was 5 months (range 3~12). Patients with un-recovered AET had a significantly (p<0.001) higher risk of developing severe LET, compared to patients without AET or with a recovered AET. In the EUD; n=0.03 model, all severe LET patients had an NTD >70 Gy on the esophagus. In the EUD~n~-LKB model, the fitted values and 95% confidence intervals were TD~50=~76.1 Gy (73.2~78.6), m=0.03 (0.02~0.06) and n=0.03 (0~0.08). In the V~x~-LKB model, the fitted values and 95% CIs were Tx~50~=23.5% (16.4~46.6), m=0.44 (0.32~0.60) and x=76.7 Gy (74.7~77.5). Conclusions In routine clinical practice it is possible to provide insight in the probability and severity of esophagus toxicity for each individual lung cancer patient treated with CCRT. Both the maximum grade and the recovery rate of AET were significantly associated with severe LET. In clinical practice, NTD corrected esophagus EUD<70 Gy could be a dose constraint to minimize severe LET. AET was not changed with the use of IMRT.

      references
      1 Palma D. et al, Predicting Esophagitis after Chemoradiotherapy for Non-Small Cell Lung Cancer: An Individual Patient Data Meta-analysis. Int J Radiat Oncol Biol Phys. 2013 in press
      2 Belderbos J. et al, Acute esophageal toxicity in non-small cell lung cancer patients after high dose conformal radiotherapy. Radiother Oncol 2005;75:157-164
      3 Kwint M. et al, Acute esophagus toxicity in lung cancer patients after intensity modulated radiation therapy and concurrent chemotherapy. Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):e223-8
      4 Uyterlinde W. et al, Prognostic parameters for acute esophagus toxicity in Intensity Modulated Radiotherapy and concurrent chemotherapy for locally advanced non-small cell lung cancer. Radiother Oncol. 2013 Jun;107(3):392-7.
      5 Nijkamp J, et al. Relating acute esophagitis to radiotherapy dose using FDG-PET in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer. Radiother Oncol 2013 Jan;106(1):118-23
      6 Chen C. et al, Severe late esophagus toxicity in NSCLC patients treated with IMRT and concurrent chemotherapy. Radiotherapy & Oncology 2013 in press
      Figure 1

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    O14 - Radiotherapy - Toxicity and Clinical Trials (ID 105)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
    • +

      O14.02 - Vertebral fractures in NSCLC patients treated with IMRT and concurrent chemotherapy (ID 1880)

      10:40 - 10:50  |  Author(s): W. Uyterlinde

      • Abstract
      • Presentation
      • Slides

      Background
      Purpose To report on the incidence of vertebral fractures in locally advanced NSCLC patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. The RT dose to the vertebra was analyzed for its association with fractures.

      Methods
      Methods A total of 524 patients were treated between 2007 and 2011, with hypofractionated IMRT (66Gy/24fx) and concurrent daily low dose cisplatin. Planning and follow-up CT or MRI scans were retrospectively utilized to identify vertebral collapse by an experienced radiologist and a technician. Clinical and dosimetric parameters were retrospectively collected. Patients were excluded if they had no follow-up CT/MRI scan; had prior irradiation for thoracic or head and neck cancer; showed a vertebral fracture in the planning CT; or had vertebral collapse due to other causes. First, we reported the incidence of vertebral fractures. Afterwards, we analyzed the RT dose effect relationship using the maximum (Dmax) and mean (Dmean) dose to each vertebra. Dose-response was modeled using Cox model with patient as random effect. Data were analyzed using R, package “coxme”.

      Results
      Results Three hundred and thirty six patients were eligible for analysis. The median follow-up was 24 months The median age was 64 years (range 32-87); 40% of the patients female and 94% had a performance score (PS) 0-1. Twenty-eight (8%) patients developed ≥ 1 vertebral fracture; 22 had 1 vertebral fracture, 5 had 2 and 1 patient had 3 vertebral fractures. All fractures were located from the 6[th]-8[th] thoracic vertebra.The median onset time for the fracture was 7 months (range 2-26). The median age for the 28 fractured patients was 70 years (range 42-82); 61% were female, 89% had a PS of 0-1. The median Dmax was 40Gy (range 0-83) and 72Gy (range 42-83) for non-collapsed and fractured vertebrae, respectively. The median Dmean was 12Gy (range 0-65) and 51Gy (range 18-71) for non-collapsed and collapsed vertebras, respectively. Both Dmax and Dmean were significantly (p<0.001) associated with vertebral fractures.

      Conclusion
      Conclusion Vertebral fractures were retrospectively identified in 8% of NSCLC patients treated with IMRT and concurrent chemotherapy. The median onset time was 7 months. Both Dmax and Dmean of the vertebra were significantly associated with collapse in the collapsed population. A case-control study is in progress to analyze the dose-response relationship in the entire population and incorporate clinical variables, such as age, performance status and menopause status.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.