- Email: [email protected]
EP-1171: Repeat CT imaging and adaptive planning during radiotherapy for locally advanced lung cancer
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ESTRO 33, 2014
Results: Between May 2009 and March 2013 44 patients were treated at our Institution. Patients characteristics: IIIA(N2)/IIIB 25/19; m/f 29/15; adeno/squamous/NOS 29/10/5; age: median 62 (range 37-69). Acute Esophageal toxicity Grade 1- 2 occurred in all patients. No grade 3 toxicity occurred. Only one patient had asymptomatic pneumonia a month after the end of concurrent treatment requiring hospitalization. The median follow up was 24 months (range 4-48). Four patients had only locoregional progression and eight patients had local and systemic disease progression. The overall survival at 1, 2, 3 years was 70%, 45%, 35% respectively. Conclusions: Concurrent chemo-radiotherapy using VMAT proved to be a safe and advantageous treatment modality for locally advanced NSCLC with good toxicity profile. Clinical outcomes were satisfactory and comparable to the literature data. EP-1169 WHO performance score and hand grip strength in lung cancer: The influence on survival K.M. Smits1, G. Nalbantov1, C. Oberije1, R.M.A. Houben1, J.M.J. Paulissen1, R. Wanders1, E.G.C. Troost1, P. Lambin1 1 GROW-School for Oncology and Developmental Biology Maastricht University Medical Center, Department of Radiation Oncology (MAASTRO), Maastricht, The Netherlands Purpose/Objective: To quantify general well-being and daily living activities of cancer patients, several performance status scoring systems have been developed. The World Health Organisation (WHO) performance status is often used due to its simplicity and is regarded a good prognostic predictor. However, it remains a subjective measurement and the addition of an objective tool might improve outcome prediction for individual patients. In this study, we assessed the association between hand grip strength (HGS) at baseline and during (chemo)radiotherapy (RT), and overall survival (OS) in patients with nonsmall cell lung cancer (NSCLC). Materials and Methods: Analyses were done using data of 392 stage I-IIIB NSCLC patients that were treated with RT alone or combined with chemotherapy in the period 2006-2011. HGS was measured at two time points (baseline and halfway through RT). OS was defined as time from first visit to our clinic until death or end of follow-up (October 2013). Kaplan-Meier curves and log-rank tests, and Cox proportional hazards models were used to assess the influence of HGS on survival. In multivariate analyses we added variables from a previously validated model in NSCLC (sex, WHO performance status, forced expiratory volume in 1 second, number of positive mediastinal/hilar lymph node stations and gross tumor volume). Models were compared using the -log likelihood and Harrel’s c-statistic. Results: Baseline HGS did not differ from HGS during RT. Median survival in the population was 19 months (18 months for males, 21 for females), at the end of follow-up 72% of the patients had deceased. HGS was strongly correlated with age (p<0.0001) and WHO performance score in both men and women (p=0.0001 and p=0.035, respectively).As expected, patients with a low WHO performance score had a superior OS (Figure1A, p<0.0001). However, male patients with a high HGS at baseline or during RT also had a superior OS (p=0.030 and 0.009, respectively) (Figure 1B and C).Although male patients with WHO score≥2 and low HGS appeared to have the lowest median OS, subgroups were small and differences were not statistically significant (Table 1). Moreover, multivariate Cox regression did not show an additional prognostic value of HGS as compared to the published baseline model(Table 1). For female patients, no influence of HGS on survival was observed.
Conclusions: Our results suggest that a high HGS at baseline or during RT is associated with superior survival outcomes in male NSCLC patients treated with (chemo)radiotherapy. However, the prognostic influence of HGS is strongly correlated with WHO performance score, and incorporation of HGS in the multivariate model does not seem to have additional prognostic value. Nevertheless, in patients with WHO performance status ≥ 2, HGS might be an easy and low-cost prognostic marker to identify patients with very poor survival outcomes; this observation merits further research. EP-1170 Role of postoperative radiotherapy after adjuvant chemotherapy in pN2 NSCLC: A propensity score matching analysis B.H. Kim1, H.J. Kim1, H.G. Wu1, C.H. Kang2, Y.T. Kim2, S.H. Lee3 1 Seoul National University Hospital, Radiation Oncology, Seoul, Korea Republic of 2 Seoul National University Hospital, Thoracic Surgery, Seoul, Korea Republic of 3 Seoul National University Hospital, Internal Medicine, Seoul, Korea Republic of Purpose/Objective: To evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 non-small cell lung cancer (pN2 NSCLC). Materials and Methods: We performed a retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy between 2000 and 2011. Among 219 patients, 41 received PORT additionally. Propensity scores for PORT receipt were calculated for each patient and used for matching to compare the outcome of patients who did and did not receive PORT after controlling for selection bias. 111 patients in non-PORT group and 38 patients in PORT group were matched. Clinical and pathologic characteristics were well-balanced between two groups, which standardized differences of all covariates were less than 5%. Median 4 cycles of adjuvant chemotherapy was administered sequentially with PORT. PORT was delivered using conventional (n=13) or threedimensional conformal technique (n=25) with median dose of 54 Gy (range, 50-56). Results: The median follow-up duration was 48 months. PORT resulted in a significantly lower crude loco-regional relapse, before (39.9% vs. 22.0%, p = 0.032) and after (43.2% vs. 23.7%, p =0.032) propensity score matching. In the matched cohort, PORT was associated with improved loco-regional control rate (LRC) (5yr LRC 63.7% vs.48.6%, p = 0.036), but not distant metastasis-free survival, disease-free survival (DFS) and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5yr DFS 43.2% vs. 16.6%, p = 0.037) and squamous cell carcinoma histology (5yr DFS 70.1% vs. 23.3%, p = 0.011). Grade 3 radiation pneumonitis and esophagitis was seen in only one patient (2.6%), respectively. Conclusions: Even in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC, without severe toxicity. Furthermore, our data suggest that some subgroups appear to benefit from PORT in terms of DFS as well as LRC. Individualized strategies based on risk factors may be effective. EP-1171 Repeat CT imaging and adaptive planning during radiotherapy for locally advanced lung cancer E. Kucukmorkoc1, H. Acar1, A. Altinok1, H. Sertkaya1, A. Omurca1, S. Aydemir1, H. Caglar1 1 Medipol University Hospital, Radiation Oncology, Bagcilar - Istanbul, Turkey Purpose/Objective: Many patients with lung cancer have tumor changes like shrinkage, improvement in atelectasis or mediastinal replacement during radiotherapy. The aim of this study was to determine the dosimetric effects of repeated CT scanning and adaptive planning during
ESTRO 33, 2014
S45
intensity modulated radiotherapy (IMRT) on both normal tissues and target volumes. Materials and Methods: Nine patients treated with concurrent chemoradiation were included within the study. The initial IMRT planning (IMRTinitial) was done on the primary CT and 4DCT scan using the ITV technique. The dose was prescribed to 66 Gy in 33 fractions. After the initiation of the study weekly cone beam CT (CBCT) images were obtained before treatment. The volumes were evaluated by the treating physician in terms of target volume changes or mediastinal replacement. When adequate change was distinguished on the CBCT images an adaptive CT (CTadapt) was obtained and the volumes were recontoured by the same physician and replanned by the same physicist (IMRT adapt). Changes in lymphatic disease were not taken into account. A hybrid IMRT plan was generated to the anatomy of the CTadapt (IMRThybrid) to observe the changes occurred in critical organs such as lung, spinal cord, heart and esophagus. The dose volume histograms of the IMRTinitial versus IMRThybrid plans and IMRThybrid versus IMRT adapt were compared using paired samples t-test. Results: The median PTV volumes on initial and adaptive planning CT scans were significantly different (741 vs 414 cc; p<0.001). Significant changes were observed in lung doses between IMRTinitial and IMRThybrid (V5, 50% vs 55%; V20, 22% vs 27%; MLD 13Gy vs 15Gy; p<0.05) but these doses were significantly compensated with IMRTadapt (V5, 40%; V20, 18%; MLD, 10Gy; p<0.05). The PTV coverage significantly changed in 1 patient with mediastinal replacement. No changes were observed in other tissues. Conclusions: Repeat CT imaging and replanning during the course of IMRT for selected patients with lung cancer may help to identify dosimetric changes and to ensure safe doses to critical structures such as lung. With the implementation of adaptive treatments dose escalation may be possible in the future for improvements in clinical outcome without significant increase in toxicity. The anatomic changes seen throughout the treatment may increase the lung doses when replanning is not performed. EP-1172 Metabolic metrics in repeated FDG-PET scans show early treatment response for NSCLC patients S. Carvalho1, R. Leijenaar1, E. Rios Velazquez2, W. Van Elmpt1, C. Oberije1, E. Troost1, A. Dekker1, H. Aerts2, P. Lambin1 1 (MAASTRO), GROW – School for Oncology and Developmental Biology Maastricht University Medical Center (MUMC+), Department of Radiation Oncology, Maastricht, The Netherlands 2 Dana-Farber Cancer Institute, Department of Radiation Oncology and Radiology, Boston, USA
Results: Results for the made tests are displayed on the table. Although percentage differences of metabolic features were statistically significant in the Cox analysis, their hazard ratios reveal a nearly negligible impact on survival prediction is (HR≈1). A percentage change of the SUV threshold that encloses 70, 80 and 90% of the GTV showed a statistically significant decrease for 2-years survivors as opposed to an increase for non-survivors. The percentage difference in tumor volume above 70%SUV showed a statistical significance in splitting the two groups,with an associated decrease for survivors. For higher thresholds (80 and 90%),however, only a trend but no statistical significance was found. Similar results were also observed for relative portions of GTV above higher SUV thresholds (70% – 90%). The percentage changes in maximum mean and peak SUV were found to be significantly associated with 2-year overall survival, with a common trend of higher decrease for survivors. The percentage change in GTV showed no statistical significance between the two groups, and neither did percentage differences of possible surrogates for Metabolic Tumor Volume (MTV) based on relative (50%) and absolute (2.5 and 3) SUV thresholds.However, the percentage change of MTV defined for volume above an SUV of 4 provided a clear and significant distinction between groups.
Purpose/Objective: Non-small cell lung cancer (NSCLC) represents 80% of lung cancer incidences. Most NSCLC patients are treated with (chemo)radiotherapy,and early assessment of therapeutic response is of major importance to improve treatment outcomes. In this study we investigated the prognostic value of metabolic features of FDG-PET described by intensity-volume histograms (analogous to dose-volume histograms) acquired before and one week after (chemo)radiotherapy.We compared these metrics with commonly used predictors. We hypothesize that changes in metabolic features during the first week of (chemo)radiotherapy can be used for early response assessment. Materials and Methods: Thirty NSCLC patients (stages I-IV) underwent an FDG-PET scan before and one week after radiotherapy. Gross tumor volume (GTV) was delineated by an experienced radiation oncologist on both subsequent scans. Percentage changes of commonly used metrics (mean, maximum and peak SUV – the mean SUV inside a 1cm3 sphere centered on the maximum uptake voxel) and more complex SUV descriptors were analyzed. Univariable Cox regression was performed for overall survival assessment. Wilcoxon signed rank test was performed for 2-year overall survival (from start of radiotherapy) as outcome. A significance level of 0.05 was used.
Conclusions: We can report on the evolution of metabolic metrics based on PET images, measured as early as after the first week of radiotherapy,as being statistically significant for overall survival assessment. Further validation of these results in an extended cohort should follow these preliminary results. EP-1173 Study of offline setup error adaptive correction during radiotherapy for NSCLC based on online CBCT data L. Kong1, H. Li1, J. Cheng2, W. Huang1, B. Li1 1 Shandong Cancer Hospital and Institute, Sixth Department of Radiation Oncology, Jinan, China 2 The Second Hospital of Shandong University, Cancer Centre, Jinan, China Purpose/Objective: To investigate the systematical variations of setup errors during radiotherapy for NSCLC by analysis the online setup verification data using kilovoltage cone beam computed tomography (kV CBCT) of several fractions in a row. Then, to investigate the feasibility of using several CBCT scans to presume and correct systematic setup error for irradiation of NSCLC.
ESTRO 33, 2014
Results: Between May 2009 and March 2013 44 patients were treated at our Institution. Patients characteristics: IIIA(N2)/IIIB 25/19; m/f 29/15; adeno/squamous/NOS 29/10/5; age: median 62 (range 37-69). Acute Esophageal toxicity Grade 1- 2 occurred in all patients. No grade 3 toxicity occurred. Only one patient had asymptomatic pneumonia a month after the end of concurrent treatment requiring hospitalization. The median follow up was 24 months (range 4-48). Four patients had only locoregional progression and eight patients had local and systemic disease progression. The overall survival at 1, 2, 3 years was 70%, 45%, 35% respectively. Conclusions: Concurrent chemo-radiotherapy using VMAT proved to be a safe and advantageous treatment modality for locally advanced NSCLC with good toxicity profile. Clinical outcomes were satisfactory and comparable to the literature data. EP-1169 WHO performance score and hand grip strength in lung cancer: The influence on survival K.M. Smits1, G. Nalbantov1, C. Oberije1, R.M.A. Houben1, J.M.J. Paulissen1, R. Wanders1, E.G.C. Troost1, P. Lambin1 1 GROW-School for Oncology and Developmental Biology Maastricht University Medical Center, Department of Radiation Oncology (MAASTRO), Maastricht, The Netherlands Purpose/Objective: To quantify general well-being and daily living activities of cancer patients, several performance status scoring systems have been developed. The World Health Organisation (WHO) performance status is often used due to its simplicity and is regarded a good prognostic predictor. However, it remains a subjective measurement and the addition of an objective tool might improve outcome prediction for individual patients. In this study, we assessed the association between hand grip strength (HGS) at baseline and during (chemo)radiotherapy (RT), and overall survival (OS) in patients with nonsmall cell lung cancer (NSCLC). Materials and Methods: Analyses were done using data of 392 stage I-IIIB NSCLC patients that were treated with RT alone or combined with chemotherapy in the period 2006-2011. HGS was measured at two time points (baseline and halfway through RT). OS was defined as time from first visit to our clinic until death or end of follow-up (October 2013). Kaplan-Meier curves and log-rank tests, and Cox proportional hazards models were used to assess the influence of HGS on survival. In multivariate analyses we added variables from a previously validated model in NSCLC (sex, WHO performance status, forced expiratory volume in 1 second, number of positive mediastinal/hilar lymph node stations and gross tumor volume). Models were compared using the -log likelihood and Harrel’s c-statistic. Results: Baseline HGS did not differ from HGS during RT. Median survival in the population was 19 months (18 months for males, 21 for females), at the end of follow-up 72% of the patients had deceased. HGS was strongly correlated with age (p<0.0001) and WHO performance score in both men and women (p=0.0001 and p=0.035, respectively).As expected, patients with a low WHO performance score had a superior OS (Figure1A, p<0.0001). However, male patients with a high HGS at baseline or during RT also had a superior OS (p=0.030 and 0.009, respectively) (Figure 1B and C).Although male patients with WHO score≥2 and low HGS appeared to have the lowest median OS, subgroups were small and differences were not statistically significant (Table 1). Moreover, multivariate Cox regression did not show an additional prognostic value of HGS as compared to the published baseline model(Table 1). For female patients, no influence of HGS on survival was observed.
Conclusions: Our results suggest that a high HGS at baseline or during RT is associated with superior survival outcomes in male NSCLC patients treated with (chemo)radiotherapy. However, the prognostic influence of HGS is strongly correlated with WHO performance score, and incorporation of HGS in the multivariate model does not seem to have additional prognostic value. Nevertheless, in patients with WHO performance status ≥ 2, HGS might be an easy and low-cost prognostic marker to identify patients with very poor survival outcomes; this observation merits further research. EP-1170 Role of postoperative radiotherapy after adjuvant chemotherapy in pN2 NSCLC: A propensity score matching analysis B.H. Kim1, H.J. Kim1, H.G. Wu1, C.H. Kang2, Y.T. Kim2, S.H. Lee3 1 Seoul National University Hospital, Radiation Oncology, Seoul, Korea Republic of 2 Seoul National University Hospital, Thoracic Surgery, Seoul, Korea Republic of 3 Seoul National University Hospital, Internal Medicine, Seoul, Korea Republic of Purpose/Objective: To evaluate the role of postoperative radiotherapy (PORT) in the setting of adjuvant chemotherapy for pathological stage N2 non-small cell lung cancer (pN2 NSCLC). Materials and Methods: We performed a retrospective review of 219 consecutive pN2 NSCLC patients who underwent curative surgery followed by adjuvant chemotherapy between 2000 and 2011. Among 219 patients, 41 received PORT additionally. Propensity scores for PORT receipt were calculated for each patient and used for matching to compare the outcome of patients who did and did not receive PORT after controlling for selection bias. 111 patients in non-PORT group and 38 patients in PORT group were matched. Clinical and pathologic characteristics were well-balanced between two groups, which standardized differences of all covariates were less than 5%. Median 4 cycles of adjuvant chemotherapy was administered sequentially with PORT. PORT was delivered using conventional (n=13) or threedimensional conformal technique (n=25) with median dose of 54 Gy (range, 50-56). Results: The median follow-up duration was 48 months. PORT resulted in a significantly lower crude loco-regional relapse, before (39.9% vs. 22.0%, p = 0.032) and after (43.2% vs. 23.7%, p =0.032) propensity score matching. In the matched cohort, PORT was associated with improved loco-regional control rate (LRC) (5yr LRC 63.7% vs.48.6%, p = 0.036), but not distant metastasis-free survival, disease-free survival (DFS) and overall survival. An exploratory subgroup analysis suggested a potential DFS benefit of PORT in patients with multiple station mediastinal lymph node metastases (5yr DFS 43.2% vs. 16.6%, p = 0.037) and squamous cell carcinoma histology (5yr DFS 70.1% vs. 23.3%, p = 0.011). Grade 3 radiation pneumonitis and esophagitis was seen in only one patient (2.6%), respectively. Conclusions: Even in the setting of adjuvant chemotherapy, PORT significantly increased LRC for patients with curatively resected pN2 NSCLC, without severe toxicity. Furthermore, our data suggest that some subgroups appear to benefit from PORT in terms of DFS as well as LRC. Individualized strategies based on risk factors may be effective. EP-1171 Repeat CT imaging and adaptive planning during radiotherapy for locally advanced lung cancer E. Kucukmorkoc1, H. Acar1, A. Altinok1, H. Sertkaya1, A. Omurca1, S. Aydemir1, H. Caglar1 1 Medipol University Hospital, Radiation Oncology, Bagcilar - Istanbul, Turkey Purpose/Objective: Many patients with lung cancer have tumor changes like shrinkage, improvement in atelectasis or mediastinal replacement during radiotherapy. The aim of this study was to determine the dosimetric effects of repeated CT scanning and adaptive planning during
ESTRO 33, 2014
S45
intensity modulated radiotherapy (IMRT) on both normal tissues and target volumes. Materials and Methods: Nine patients treated with concurrent chemoradiation were included within the study. The initial IMRT planning (IMRTinitial) was done on the primary CT and 4DCT scan using the ITV technique. The dose was prescribed to 66 Gy in 33 fractions. After the initiation of the study weekly cone beam CT (CBCT) images were obtained before treatment. The volumes were evaluated by the treating physician in terms of target volume changes or mediastinal replacement. When adequate change was distinguished on the CBCT images an adaptive CT (CTadapt) was obtained and the volumes were recontoured by the same physician and replanned by the same physicist (IMRT adapt). Changes in lymphatic disease were not taken into account. A hybrid IMRT plan was generated to the anatomy of the CTadapt (IMRThybrid) to observe the changes occurred in critical organs such as lung, spinal cord, heart and esophagus. The dose volume histograms of the IMRTinitial versus IMRThybrid plans and IMRThybrid versus IMRT adapt were compared using paired samples t-test. Results: The median PTV volumes on initial and adaptive planning CT scans were significantly different (741 vs 414 cc; p<0.001). Significant changes were observed in lung doses between IMRTinitial and IMRThybrid (V5, 50% vs 55%; V20, 22% vs 27%; MLD 13Gy vs 15Gy; p<0.05) but these doses were significantly compensated with IMRTadapt (V5, 40%; V20, 18%; MLD, 10Gy; p<0.05). The PTV coverage significantly changed in 1 patient with mediastinal replacement. No changes were observed in other tissues. Conclusions: Repeat CT imaging and replanning during the course of IMRT for selected patients with lung cancer may help to identify dosimetric changes and to ensure safe doses to critical structures such as lung. With the implementation of adaptive treatments dose escalation may be possible in the future for improvements in clinical outcome without significant increase in toxicity. The anatomic changes seen throughout the treatment may increase the lung doses when replanning is not performed. EP-1172 Metabolic metrics in repeated FDG-PET scans show early treatment response for NSCLC patients S. Carvalho1, R. Leijenaar1, E. Rios Velazquez2, W. Van Elmpt1, C. Oberije1, E. Troost1, A. Dekker1, H. Aerts2, P. Lambin1 1 (MAASTRO), GROW – School for Oncology and Developmental Biology Maastricht University Medical Center (MUMC+), Department of Radiation Oncology, Maastricht, The Netherlands 2 Dana-Farber Cancer Institute, Department of Radiation Oncology and Radiology, Boston, USA
Results: Results for the made tests are displayed on the table. Although percentage differences of metabolic features were statistically significant in the Cox analysis, their hazard ratios reveal a nearly negligible impact on survival prediction is (HR≈1). A percentage change of the SUV threshold that encloses 70, 80 and 90% of the GTV showed a statistically significant decrease for 2-years survivors as opposed to an increase for non-survivors. The percentage difference in tumor volume above 70%SUV showed a statistical significance in splitting the two groups,with an associated decrease for survivors. For higher thresholds (80 and 90%),however, only a trend but no statistical significance was found. Similar results were also observed for relative portions of GTV above higher SUV thresholds (70% – 90%). The percentage changes in maximum mean and peak SUV were found to be significantly associated with 2-year overall survival, with a common trend of higher decrease for survivors. The percentage change in GTV showed no statistical significance between the two groups, and neither did percentage differences of possible surrogates for Metabolic Tumor Volume (MTV) based on relative (50%) and absolute (2.5 and 3) SUV thresholds.However, the percentage change of MTV defined for volume above an SUV of 4 provided a clear and significant distinction between groups.
Purpose/Objective: Non-small cell lung cancer (NSCLC) represents 80% of lung cancer incidences. Most NSCLC patients are treated with (chemo)radiotherapy,and early assessment of therapeutic response is of major importance to improve treatment outcomes. In this study we investigated the prognostic value of metabolic features of FDG-PET described by intensity-volume histograms (analogous to dose-volume histograms) acquired before and one week after (chemo)radiotherapy.We compared these metrics with commonly used predictors. We hypothesize that changes in metabolic features during the first week of (chemo)radiotherapy can be used for early response assessment. Materials and Methods: Thirty NSCLC patients (stages I-IV) underwent an FDG-PET scan before and one week after radiotherapy. Gross tumor volume (GTV) was delineated by an experienced radiation oncologist on both subsequent scans. Percentage changes of commonly used metrics (mean, maximum and peak SUV – the mean SUV inside a 1cm3 sphere centered on the maximum uptake voxel) and more complex SUV descriptors were analyzed. Univariable Cox regression was performed for overall survival assessment. Wilcoxon signed rank test was performed for 2-year overall survival (from start of radiotherapy) as outcome. A significance level of 0.05 was used.
Conclusions: We can report on the evolution of metabolic metrics based on PET images, measured as early as after the first week of radiotherapy,as being statistically significant for overall survival assessment. Further validation of these results in an extended cohort should follow these preliminary results. EP-1173 Study of offline setup error adaptive correction during radiotherapy for NSCLC based on online CBCT data L. Kong1, H. Li1, J. Cheng2, W. Huang1, B. Li1 1 Shandong Cancer Hospital and Institute, Sixth Department of Radiation Oncology, Jinan, China 2 The Second Hospital of Shandong University, Cancer Centre, Jinan, China Purpose/Objective: To investigate the systematical variations of setup errors during radiotherapy for NSCLC by analysis the online setup verification data using kilovoltage cone beam computed tomography (kV CBCT) of several fractions in a row. Then, to investigate the feasibility of using several CBCT scans to presume and correct systematic setup error for irradiation of NSCLC.