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S. Burri

Moderator of

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    MINI 33 - Radiotherapy and Complications (ID 164)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 14
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      MINI33.01 - Prospective Phase II Trial of SBRT for Centrally-Located Lung Cancer (ID 162)

      18:30 - 20:00  |  Author(s): J.D. Bradley, F. Gao, P.J. Parikh, M. Roach, S. Rehman, R. Kashani, J. Ganachaud, T. Dewees, C.G. Robinson

      • Abstract
      • Presentation
      • Slides

      Background:
      We report safety and efficacy results for an institutional prospective phase II trial for medically-inoperable patients with centrally-located early-stage non-small cell lung cancers receiving dose escalated SBRT. The Phase II objectives were to determine the overall survival and patterns of local failure.

      Methods:
      Eligible patients with biopsy-proven NSCLC within 2cm of the proximal bronchial tree (RTOG definition) were enrolled on an IRB-approved institutional clinical trial between 2006-2015. All patients were medically inoperable. The Phase I portion consisted of 4 radiation dose levels using 5 fraction regimens. Dose levels were 9, 10, 11, and 12 Gy/fraction. Phase I was previously reported (ASTRO 2011). Based on an early analysis of efficacy, the Phase II radiation dose was 11 Gy x 5 fractions.

      Results:
      64 patients were enrolled to the trial; 23 to Phase I and 41 to Phase II. The median follow up for phase II patients alive is 6.2 months (range 1.3-46.3 months). 41 patients are eligible for toxicity analysis and 37 with at least 1 post-treatment visits are eligible for efficacy. Regarding treatment-related toxicity, 1 patient experienced acute Grade 3 hypoxia (2.4%; 95% CI 0.1-12.8%), 3 patients developed late Grade 3, 2 had late grade 4, and 1 had late grade 5 events. The grade 4 events were lung atelectasis resulting in hospitalization and dyspnea, respectively. The grade 5 event was fatal hemoptysis in a patient with tumor involving the pulmonary artery. The one-year local lobar recurrence rate using 11 Gy x 5 fractions is 4.6% (95% CI 0.7-13.6%). The one-year OS is 81.2% (60.0-91.8%).The predominant causes of death were distant metastasis (N=6), intercurrent illness without recurrence (N=6), and secondary lung cancer (N=2). One patient is alive with gastric cancer. Two patients developed nodal recurrence and two developed local failures.

      Conclusion:
      SBRT for central tumors using 11 Gy x 5 fractions was tolerable, but can contribute to severe toxicity as shown by others where tumor involves the pulmonary vasculature. The lobar tumor control was excellent using 11 Gy x 5 fractions. The results of RTOG 0813, which was methodologically based on this trial, may help to clarify the preferred dose for central lesions.

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      MINI33.02 - Dose-Escalated Radiotherapy for NSCLC: Heart Doses versus Survival in IDEAL-CRT (ID 454)

      18:30 - 20:00  |  Author(s): S. Vivekanandan, N. Counsell, E. Parsons, Y. Ngai, L. Hughes, M. Hawkins, D.B. Landau, J.D. Fenwick

      • Abstract
      • Slides

      Background:
      Radiotherapy dose-escalation trials have achieved inconsistent levels of overall survival (OS) for non-small cell lung cancer (NSCLC). For stage III NSCLC, RTOG-0617 reported poorer OS for 74Gy than for 60Gy delivered in 2Gy fractions with concurrent chemotherapy (median OS 20·3 vs 28·7 months). The phase I/II IDEAL-CRT CRUK funded trial (Sponsor: University College London (C13530/A10424)) of isotoxic dose-escalation delivered mean and maximum doses of 67.5 and 73Gy in 30 fractions over 40 days, equivalent to 69 and 75.6Gy in 2Gy fractions (EQD2), and reported 1- and 2-year OS rates 87.8% (95% CI:80.7-94.9) and 67.1% (95% CI:56.3-78.0) respectively. Here we investigate associations between OS and dose-distributions delivered to heart, left ventricle (LV), lung minus gross tumour volume (lung-GTV) and oesophagus.

      Methods:
      For 80 of 82 IDEAL-CRT patients, heart, LV, lung-GTV and oesophagus differential dose volume histograms (DVHs) were extracted from planning data using CERR. Since prescribed doses-per-fraction varied, physical DVHs were converted to EQD2s using the linear-quadratic equation with an α/β of 3Gy for heart, LV and lung-GTV, and 1.7Gy for oesophagus. Patient-to-patient DVH variability was efficiently represented using a small number of Varimax-rotated principal components (PCs) which explained 95% of the total variance: four for oesophagus, five each for heart and LV, and fourteen for lung-GTV. OS was modelled from the start of treatment using Cox regression.

      Results:
      On univariate analysis there is evidence that larger planning target volumes (PTVs) and greater Heart-PC3 and LV-PC4 coefficients are associated with worse OS (see table). Heart-PC3 represented heart volumes receiving doses of 65-75Gy, and LV-PC4 represented LV volumes receiving 1-5Gy. No lung-GTV or oesophageal dosimetric parameters were significantly associated with OS (p-values>0.1). Although OS improved with increasing prescribed dose, this trend did not reach statistical significance. The estimates of these effects did not change markedly after adjusting for other covariates in the multivariate analysis, and the relationship between greater Heart-PC3 and worse OS remained highly significant.

      Results (n=80)
      Mean values
      Parameters Mean Minimum Maximum
      EQD2 lung-GTV dose 12.1Gy 6.2Gy 18.5Gy
      PTV 448.6cm[3] 138.7cm[3] 1262.2cm[3]
      Heart volume receiving >5Gy (V5) 33.9% 0% 99.9%
      Heart volume receiving >30Gy (V30) 11.3% 0% 47%
      Univariate Cox model for OS
      Covariate Hazard Ratio 95% Confidence Interval p-value
      EQD2 prescribed dose 0.951 0.883-1.024 0.185
      PTV 1.002 1.000–1.003 0.026
      Heart-PC3 1.257 1.070-1.478 0.005
      LV-PC4 1.257 0.998–1.584 0.052
      Multivariate Cox model for OS
      Covariate Hazard Ratio 95% Confidence Interval p-value
      EQD2 prescribed dose 0.977 0.900-1.060 0.570
      PTV 1.001 0.999-1.003 0.179
      Heart-PC3 1.228 1.039-1.452 0.016
      LV-PC4 1.203 0.943-1.536 0.137


      Conclusion:
      We found strong evidence of an association between lower OS in IDEAL-CRT patients and heart volumes receiving 65-75Gy. There was some evidence of a negative association between OS and LV volumes receiving 1-5Gy. RTOG0617 has reported a negative relationship between OS and heart volumes receiving greater than 5Gy. Thus OS gains potentially achievable through tumour dose-escalation may be offset by associated heart dose increases. Further studies are required to improve understanding of radiation effects on heart substructures, aiming to identify avoidance structures for possible cardiac-sparing dose-escalated NSCLC treatments.

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      MINI33.03 - Heart Dose Is Associated with Shorter Overall Survival for Patients Treated with Chemo-Radiation for Locally Advanced NSCLC (ID 2755)

      18:30 - 20:00  |  Author(s): E. Van Der Bijl, M.M.G. Rossi, H. Peulen, J. Belderbos, J. Sonke

      • Abstract
      • Slides

      Background:
      Traditionally, sparing the heart in chemo-radiotherapy of locally advanced lung cancer has a low priority compared to the lungs and esophagus. Recently, however, the randomized phase III trial RTOG 0617 showed that the volume of the heart receiving a dose of at least 5Gy (V5) was associated with a lower overall survival (OS). The aim of the current study is to validate this in an independent database.

      Methods:
      Patients treated with IMRT (24x2.75Gy with daily low-dose cisplatin) at our hospital between 2006 and 2014 were retrospectively selected. For the heart both mean dose and Vx denoting the volume receiving x Gy or more (x in range 5-50Gy with 5Gy increments) were calculated. Associations of these parameters with OS were evaluated using univariate and multivariate proportional hazards analysis. In multivariate analysis we separately paired the total GTV (primary tumor plus involved lymph nodes) to Vx and mean dose.

      Results:
      375 pts were available for analysis. Median follow up was 16 months and median OS was 26 months. Using univariate proportional hazard modeling mean dose and all Vx for x<40Gy were significantly associated (p<0.05) with OS. For V5, which was most significant in the analyzed set, the hazard ratio (HR) was 1.008. When pts are split at the median V5 = 37.0%, the median OS was 29 ± 2.5 months versus 19 ± 2.4 months for pts below and above the median respectively (p=0.03, Log Rank). Similarly, the figure illustrates significant separation in Kaplan-Meier plots of OS with the pts divided in V5 quartiles. In the multivariate analysis the correlation between GTV (median volume 109 cc) and mean dose or Vx was less than 0.15, indicating that a higher heart dose is not the effect of larger tumor volumes and hence a worse survival due to more advanced decease. Both GTV (p<0.001, HR=1.001) and V5 (p=.003, HR=1.007) were significant in multivariate analysis as was the case with GTV (p<0.001, HR=1.001) and mean dose (p=0.033, HR=1.018).

      Conclusion:
      For pts treated with chemoradiation the dose received by the heart is strongly associated with overall survival. Our results are in accordance with the results of RTOG 0617 [1] for the V5 with similar HR despite the different fractionation scheme and chemo regimen. This indicates that cardial toxicity might be more important in lung cancer patients treated with chemoradiation than previously anticipated. Consequently, better sparing of the heart potentially improves outcome. [1] Bradley et.al. J Clin Oncol 31, 15 pp. 7501

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      MINI33.04 - Acute Radiation Pneumonitis in Lung Cancer Treated with Volumetric Modulated Arc Therapy (ID 2634)

      18:30 - 20:00  |  Author(s): K. Wu, B. Xia, R. Zhao, X. Xu, B. Wang, L. Xu, J. Wang, X. Li, Z. Wu, K. Zhang, X. Liang, Q. Deng, S. Ma

      • Abstract

      Background:
      Thoracic radiotherapy plays an important role in the treatment of lung cancer. However, the safety of thoracic radiotherapy delivery is restricted to the risk of radiation pneumonitis(RP), which is the major dose limiting toxicity for patients undergoing thoracic radiotherapy. Few studies to date have assessed risk factors associated with the development of RP in lung cancer patients treated with volumetric modulated arc therapy (VMAT). This study aimed to report the RP incidence and clinical and dosimetric risk factors associated with RP in lung cancer patients treated with VMAT at a single institution.

      Methods:
      In this retrospective study, lung cancer patients treated with VMAT from 2013 through 2015 were reviewed. RP was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version.4.0. Clinical factors and dosimetric parameters were evaluated using logistic multivariate regression for estimating the correlation with RP. The results were considered statistically significant when the p-value was<0.05.

      Results:
      Thoracic radiotherapy with VMAT was administered in 77 lung cancer patients. Of these patients, 58 were men and 19 were women, with a median age of 60 years (range 22-84 years); 25 patients received concurrent chemoradiotherapy, and the median radiation dose was 60Gy (range 45-64Gy). VMAT plans were performed with single arc in 9 patients, double in 55 patients, triple in 4 patients, and the mean (±SD) delivery time was 189.1s±42.0s. VMAT allowed us to respect most planning objectives on target volumes and organs at risk, for PTV V~95% ~= 96.8 ± 6.1%; for lung V~5~ = 41.3 ± 8.7%, V~10~ = 29.9 ± 7.1%, V~20~ = 20.9 ± 5.7%, mean dose=1150.9±277.6Gy. With regard to acute RP after thoracic radiotherapy, 10.4% were grade 1 (G1), 16.9% G2, 9.1% G3, 2.6% G5. The overall incidence rate of symptomatic RP (grade ≥ 2 by CTCAE) was 28.6% in the entire cohort. Based on the clinical data and dosimetric parameters analysis, factors predictive of symptomatic RP were lung volume receiving ≥10Gy (V~10~) [OR: 1.39, 95% CI 1.07–1.80, p=0.014], PS score[OR:5.44, 95% CI 1.29–23.08, p=0.021], concurrent chemotherapy[OR:3.85, 95% CI 1.07–13.86, p=0.039]and CRP changing level[OR:1.06, 95% CI 1.01–1.12, p=0.014].

      Conclusion:
      VMAT, a novel technique, provides a viable option for the thoracic radiotherapy of lung cancer with acceptable toxicities. However, for patients with higher V~10~, poorer PS score, greater increasing level of CRP and undergoing concurrent chemotherapy, VAMT technique should be administrated with cautions. Several molecular biomarkers have been reported that correlated with the development of RP, which will be tested in our further analysis.

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      MINI33.05 - Discussant for MINI33.01, MINI33.02, MINI33.03, MINI33.04 (ID 3553)

      18:30 - 20:00  |  Author(s): D. Raben

      • Abstract
      • Presentation

      Abstract not provided

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      MINI33.06 - Prospective Monitoring of Lung Function Test with CO and NO Diffusion during Thoracic Radiotherapy: Preliminary Results of the CONORT Study (ID 2402)

      18:30 - 20:00  |  Author(s): C. Fontaine-Delaruelle, I. Selmaji, Y. Hamou, N. Girard, V. Zarza, C. Prevost, G. Letanche, C. Viart-Ferber, P. Souquet, S. Couraud, F. Mornex

      • Abstract
      • Presentation
      • Slides

      Background:
      Thoracic radiotherapy is a usual treatment for lung cancer; either at early-stages (stereotactic mode) or at locally advanced stages (conventional radiotherapy mode). Thoracic irradiation appears to have little impact on lung volume such as forced expiratory volume in one second (FEV1) or forced vital capacity (FCV). By contrast, carbon monoxide diffusing capacity (TLCO) may be altered under thoracic radiotherapy. Pulmonary diffusion may be also evaluated by the NO (azote monoxide) diffusion capacity (TLNO). Moreover, double assessment of NO and CO diffusing capacities open the way to understand if alteration of lung diffusion is due to alveolar membrane and/or a pulmonary capillary alteration. CONORT aims at measuring pulmonary function tests (PFTs), in particular the CO and NO diffusing capacity, during thoracic radiotherapy.

      Methods:
      Prospective multicenter study. CONORT study was approved by the Lyon Sud-Est IV ethics committee and the database was declared to the national information registry authority as required by French laws. Overall 112 patients must be included to estimate a difference of 15% in diffusing capacity test, with a 90% power and a 5% alpha risk. All consecutive patients treated by thoracic radiotherapy in Lyon Sud Hospital were included regardless of histology and radiotherapy technique. PFTs including double diffusion are performed by the same operator and using the same technic, before-, during-, at the end-, six weeks after- and six months after- thoracic irradiation. All included patients gave their consent. Results at PFTs were expressed in % of theoretical value (%th), and were compared using Student t test.

      Results:
      Between 1[st] February 2014 and 14 April 2015, 88 patients were included and 62 have been analyzed. Patients were male in 73%, mean age was 67.4 years. Radiotherapy technique was intensity-modulated radiation therapy (IMRT) in 61%, stereotactic radiotherapy (SBRT) in 32%, and 3D conformal radiotherapy in 7%. Mean pretreatment FEV1 was 2.06L (78.9% of the standard), mean FCV was 3.17L (94.9%), mean TLCO was 16.5 (64.7%) and mean TLNO was 72.7 (60.3%). FEV1 and FCV were stable during and after radiotherapy. However, mean TLCO decreased by 4.4% (P=0.01) between first and fourth PFT, mean DLNO decreased by 4% (P=0.001) between first and second PFT, mean VC (capillary lung volume) decreased by 6.24% between first and fourth PFT (P=0.011), and DM (membrane diffusing capacity) decreased by 3.6% between first and second PFT (P=0.001).

      Conclusion:
      CONORT is the first study evaluating the potential impact of thoracic radiotherapy on double measurement of lung diffusing capacity. These preliminary results showed that thoracic radiotherapy has little impact on lung volumes. However, lung diffusion decreases, initially by membrane alteration and then by capillary alteration. Results at 6 months showed that this alteration is fully recovered. Updated data will be presented at meeting.

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      MINI33.07 - A Restrospective Study of Shrinking Field Radiation Therapy in Chemoradiothrapy for Stage III Non-Small Cell Lung Cancer (ID 3195)

      18:30 - 20:00  |  Author(s): H. Shuiyun, G. Lin, X. Sun, Y. Xu, W. Mao

      • Abstract
      • Presentation
      • Slides

      Background:
      The study aimed at investigating the feasibility of shrinking field after complete or partial response during Chemoradiothrapy without surgery for stage III non-small cell lung cancer (NSCLC).

      Methods:
      This retrospective study was carried on 97 consecutive patients with stage III non-small cell lung cancer (NSCLC), who were good responders to cheomoradiation without surgery between September 2009 and November 2014. Computed tomography scans were performed after 40-50 Gy to evaluate the curative effect. Fifty three-dimensional-conformal treatment or intensity-modulated radiation therapy were redelineated to shrink the radiation volume once or twice during conventionally fractionated radiotherapy, leading to a boost of 6-20Gy delieverd to the shrunk PTV. The gross tumor volume (GTV) and planned target volume (PTV) were messured. The acute symptomatic irradiation-induced pneumonia(ASIP) as well as first progression patterns and overall survival were investigated through follow-up.

      Results:
      Among 97 patients who obtained complete or partial response with median total dose of 60.0 Gy (range, 46.0-70.0 Gy), 50 patients received shrinking field radiation therapy with a median 184.24 cm[3 ](range, 28.1- 449.7cm[3]) reduction of PTV between the first and last plan. The primary GTV and PTV in shrinking field group was greater than that in non-shrinking field group, as well as the 59Gy-greater radiation dose rate(GTV, 116.8 cm[3] vs 102.9 cm[3 ]; PTV, 493.0 cm[3 ]vs 458.0 cm[3]; 59Gy-greater dose rate, 70 % vs 61.7 %). The incidence of ASIP was 20.6%(20/97) for all the population, shrinking field group of 18%(9/50) and non-shrinking field group of 23.4%(11/47). Fifteen patients progressed locoregionlly, 12 distantly and 3 in both patterns in shrinking field group, while 22 locoregionlly, 16 distantly and 3 in both patterns in non-shrinking field group. Four regional-progression located out of PTV in both groups. The locoregion-progression rate and out-PTV rate were not significant difference(60% vs 61%, P=0.934; 63.3% vs 56.1%, p=0.54). As compared with non-shrinking field group, shrinking field had a similar overall survival(median OS, 29 mouths vs 30 mouths, P=0.546), an improved median progression free survival (median PFS, 19 mouths vs 14 mouths, P=0.945) and a lower incidence of acute irradiation-induced pneumonia, but they were all not statistically significant.

      Conclusion:
      Shrinking field and dose escalation for good responders during chemoradiotherapy seem safe with acceptable toxicity and outPTV relapse, especially for the lung cancer with a bulky mass. More prospective trials are needed to validate these results.

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      MINI33.08 - Feasibility & Efficacy of Hypofractionated Radiotherapy in LA-NSCLC: A Phase II Study (ID 452)

      18:30 - 20:00  |  Author(s): S. Pathy, S. Roy, R. Kumar, B.K. Mohanti, V. Raina, A. Jaiswal

      • Abstract
      • Presentation
      • Slides

      Background:
      Accelerated repopulation of tumour cells causes inferior local control in locally advanced NSCLC (non-small cell lung cancer). Hypofractionated radiation schedule with a shorter overall treatment time may address this issue. The current study was aimed at evaluating the feasibility and efficacy of using hypofractionated radiotherapy with concurrent chemotherapy after neoadjuvant chemotherapy in locally advanced NSCLC.

      Methods:
      Thirty patients of locally advanced NSCLC were enrolled in this randomized controlled study and were allocated to one of the two treatment arms between October 2011 and July 2013. Arm A (n=15) received neoadjuvant chemotherapy (NACT) (paclitaxel 200mg/m2 and carboplatin AUC 5) followed by external radiotherapy (EBRT) (60Gy/30fractions/6weeks). Arm B (n=15) received the same NACT followed by EBRT (48Gy/20fractions/4weeks) with concomitant chemotherapy (cisplatin 30mg/m2 weekly). Quality of life analysis was done using EORTC (European organization for Research and Treatment in Cancer) QLQ C30 and LC13. Toxicity scoring was done using CTCAE (Common Terminology Criteria for Adverse Events) version 3.0. The treatment response between two arms was computed using Fisher’s exact test. The difference in QOL parameters were compared by Wilcoxon signed rank test and Mann-Whitney U test for paired and unpaired samples. Survival time was estimated by Kaplan–Meier survival analysis. Survival pattern was compared using the log-rank test. Factors which had p value <0.25 in univariate analysis were subjected to multivariate analysis using Cox regression analysis. Statistical analysis was carried out using Stata software version 12.0.

      Results:
      The overall response rate at the time of first follow-up for arm A was 54.55% as compared to 85.71 %( p=0.08) in arm B. At median follow-up duration of 12 months the ORR was numerically superior in arm B though not statistically significant 33% vs 47%).The median PFS in arm A and B were 9.2 and 17.23 months respectively [hazard ratio 2.92 (95% C.I: 1.02-9.11); p=0.05]. No significant difference was discernible in OS between two arms on multivariate analysis. Social functioning showed a trend towards improvement while alopecia showed a trend towards worsening in arm B. The most common grade 3/4 hematological and non-hematological toxicity were neutropenia peripheral neuropathy and dysphagia (arm A: 3; arm B: 1).

      Conclusion:
      Hypofractionated radiotherapy with concomitant chemotherapy after NACT is feasible for locally advanced NSCLC. Such management approach can expedite treatment with an acceptable morbidity, patient compliance and quality of life and thus reduces the waiting time, machine load, socio-economic burden in patients which is significant in a developing nation.

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      MINI33.09 - Impact of Tumor Regression and Need for Re-Plan during Radiation Therapy for Stage IIIB Lung Cancer: Dosimetric Comparison between IMRT and IMPT (ID 3063)

      18:30 - 20:00  |  Author(s): H. Nam, Y.C. Ahn, S.G. Ju, C. Hong, S.Y. Park, D. Oh, J.M. Noh, J.I. Yu, H. Lee, H. Pyo

      • Abstract
      • Presentation
      • Slides

      Background:
      Radiation pneumonitis (RP) is the most worrying complication following high dose radiation therapy (RT) for loco-regionally advanced lung cancer. Intensity modulated radiation therapy (IMRT) and intensity modulated proton therapy (IMPT) are expected to reduce RP compared with conventional RT technique. Adaptive re-plan is usually indicated to accommodate tumor shrinkage and position changes during fractionated RT course. This study is to comparatively evaluate dosimetric differences between RT techniques and interval changes of these parameters assuming that initial IMRT and IMPT plans are continued throughout RT course without adaptive re-plan.

      Methods:
      Ten patients who were given concurrent chemo-radiotherapy by IMRT (66 Gy/33 fractions, weekly Docetaxel/CDDP #6) for having N3(+) stage IIIB lung cancer were selected. Surrogate rival IMPT plan on each patient was generated to compare with initial IMRT plan. Beam numbers used in IMRT and IMPT were 6-7 and 3. Second CT obtained during 3[rd]-4[th] week for adaptive IMRT plan was used to generate second sets of IMRT and IMPT plans, assuming that adaptive plan had not been done. Differences between initial RT techniques and changes in dosimetric parameters including conformity index (CI), homogeneity index (HI) and dose-volume histogram (DVH) of target and normal organs, which could have occurred by 2 RT techniques, were compared.

      Results:
      When comparing initial IMRT and IMPT plans, IMPT showed advantageous features over IMRT with respects to median HI (1.08 vs. 1.02), mean doses (D~mean~) to lung, esophagus, and heart, lung volumes receiving 5 Gy (V~5~), 10 Gy (V~10~), 20 Gy (V~20~), 30 Gy (V~30~), and 40 Gy (V~40~) and maximum dose (D~max~) to spinal cord (all p<0.05), respectively. Mean gross tumor volumes (GTV) on initial and second CT’s were 90.9 (48.1~163.7) cm[3] and 52.2 (23.1~89.7) cm[3] and median GTV reduction was 42.2% (51.3%-84.4%). More dosimetric parameters could have changed significantly by IMPT (CI, HI, V~5~, V~10~, V~20~, V~30~, D~mean~ to lung and heart, and D~max~ to spinal cord) than IMRT (CI, HI, V~20~, D~max~ to spinal cord and heart), respectively. Absolute increase in D~max~ to spinal cord was estimated as 0.53 Gy by IMRT and 4.79 Gy by IMPT (p=0.003).

      Conclusion:
      Impact of GTV regression during RT course and need for adaptive re-plan seem evident. More uncertainties on dosimetric parameters and higher doses to spinal cord are expected by IMPT than by IMRT if re-plan is not applied. Optimal timing and frequency of adaptive plans, however, need to be further evaluated.

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      MINI33.10 - Discussant for MINI33.06, MINI33.07, MINI33.08, MINI33.09 (ID 3476)

      18:30 - 20:00  |  Author(s): D. De Ruysscher

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MINI33.11 - Locally Advanced NSCLC Elderly Patients Assessed by Multidimensional Geriatric Assessment and Treated with Concurrent Chemoradiation (ID 2867)

      18:30 - 20:00  |  Author(s): E. Nadal, J. Saldaña, J. Linares, R. Palmero, A. Navarro, M.D. Arnaiz, M. Plana, J. González, F. Formiga, I. Brao, N. Codorniu, J. Ruffinelli, S. Padrones, V. Navarro, F. Cardenal, M. Antonio

      • Abstract
      • Slides

      Background:
      Despite the increasing number of elderly patients (p) with unresectable stage III NSCLC p presenting to our clinic, there is no consensus on the therapeutic approach to these p. The comprehensive geriatric assessment (CGA) and the comorbidity measurement are relevant tools to identify p who may benefit from tolerable combinations of concurrent chemoradiation (CRT).

      Methods:
      Elderly p (≥75 years) with stage III NSCLC underwent multidimensional geriatric assessment (MGA) that incorporated validated instruments to assess comorbidity, polypharmacy, functional status, geriatric syndromes (GS), mood, cognition and vulnerability. P were classified according to the MGA results into 3 risk groups: (1) fit p: independent in all ADL and IADL, no comorbidities and absence of GS; (2) vulnerable p: <3 comorbidities and/or <3 IADL but no ADL disability and absence of GS; (3) dependent p: ≥3 disabilities or presence of GS. P classified into group 1 and 2 were considered candidates for antitumoral treatment, whereas patients into group 3 were candidates to best support care. Clinical, GA and follow-up data were prospectively collected. Overall survival (OS) was calculated using Kaplan-Meier method and the median follow-up time was 13.5 months.

      Results:
      From July 2008 to November 2014, 54 elderly p with stage III NSCLC were identified. The median age was 80 years (74-87) and most p (93%) were males. The most common histological subtype was squamous cell carcinoma (54%), followed by adenocarcinoma (28%) and NOS (18%). MGA classified 20 p (37%) as fit, 23 p (43%) as vulnerable and 11 p (20%) as dependent. Median number of comorbidities: 4 (0-11); median number of drugs: 6 (0-12); median Karnofsky: 80% (60-100); median Barthel: 95 (80-100); Lawton-Brody Scale (<4/≥4): 18%/82%; Pfeiffer (<4/≥4): 89%/11%; Yesavage test (0/≥1): 54%/46%; 1 (0-10); median GS: 1 (1-3); VES-13 (<3/≥3): 50%/50%. Risk groups 1 and 2 had significantly better median OS (20 and 17.5 months, respectively) as compared with group 3 (7.7 months, p=0.004). The number of p treated with concurrent CRT was higher among fit patients (14; 70%) as compared with group 2 (8; 35%) and 3 (0; 0%). Some fit and vulnerable p did not receive concurrent CRT due to patient and physician decision, tumor not amenable for radiotherapy or comorbid conditions. P treated with concurrent CRT received conventional 3D thoracic radiotherapy (2 Gy/fraction) in combination with carboplatin AUC 2.5 and vinorelbine 15 mg/m2 on days 1, 8, 21 and 29. Overall response rate was 68%. Median OS was 22 months (95% CI 10.6 – 33.6). There were no differences in OS when comparing risk groups 1 and 2 (p=0.446). Adverse events (G3-4): neutropenia, 2p (9%); anemia, 1p (4.5%); thrombocytopenia 1p (3%); febrile neutropenia, 1p (3%); pneumonia, 1p (3%); tracheo-bronchial infection, 3p (14%); asthenia 2p (9%); anorexia 1p (4.5%); diarrhea, 1p (4.5%); radiation pneumonitis, 3p (14%) and oesophagitis 0p (0%). Three p (14%) died due to radiation pneumonitis and 1 p (3%) due to a respiratory infection.

      Conclusion:
      MGA may help in the selection of elderly p for concurrent CRT and appeared to be a valuable tool to avoid undertreatment of those p.

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      MINI33.12 - Analysis of Acute Radiation-Induced Esophagitis in NSCLC Pts Using Lyman NTCP Model (ID 113)

      18:30 - 20:00  |  Author(s): J. Zhu, B. Li

      • Abstract

      Background:
      To analyze acute esophagitis (AE) in a Chinese population receiving 3D conformal radiotherapy (3DCRT) for non-small cell lung cancer (NSCLC), combined or not with chemotherapy (CT), using the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model.

      Methods:
      157 Chinese patients (pts) presented with NSCLC received 3DCRT: alone (34 pts) or combined with sequential CT (59 pts) (group 1) or with concomitant CT (64 pts) (group 2). Parameters (TD50, n, and m) of the LKB NTCP model predicting for > grade 2 AE (RTOG grading) were identified using maximum likelihood analysis. Univariate and multivariate analysis using a binary regression logistic model were performed to identify patient, tumor and dosimetric predictors of AE.

      Results:
      Grade 2 or 3 AE occurred in 24% and 52% of pts in group 1 and 2, respectively (p<0.001). For the 93 group 1 pts, the fitted LKB model parameters were: m=0.15, n=0.29 and TD50=46Gy. For the 64 group 2 pts, the parameters were: m=0.42, n=0.09 and TD50=36Gy. In multivariate analysis, the only significant predictors of AE were: NTCP (p<0.001) and V50, as continuous variable (RR=1.03, p =0.03) or being more than a threshold value of 11% (RR=3.6, p =0.009).

      Conclusion:
      A LKB NTCP model has been established to predict AE in a Chinese population, receiving thoracic RT, alone or combined with CT. The parameters of the models appear slightly different than the previous one described in Western countries, with a lower volume effect for Chinese patients.

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      MINI33.13 - Locally Advanced NSCLC: Patient Preferences Regarding Prophylactic Cranial Irradiation - A Discrete Choice Experiment (ID 1516)

      18:30 - 20:00  |  Author(s): M. Lehman, P. Gorayski, R. Mujcic, S. Watson, D. Edeling, J. Jackson, J. Whitty

      • Abstract
      • Presentation
      • Slides

      Background:
      Brain metastases (BM) develop in 22-55% of patients with locally advanced Non-small cell lung cancer (LA-NSCLC) treated with curative intent. Prophylactic cranial irradiation (PCI) reduces the incidence of BM by40- 60% but is not part of standard practice due to a lack of proven survival benefit and concerns regarding toxicity. This study aimed to determine patient preferences with respect to the survival gain or reduction in BM PCI would need to provide and the amount of toxicity considered acceptable for them to accept PCI.

      Methods:
      A Discrete Choice Experiment (DCE) was used. Patients undergoing definitive chemoradiation therapy for LA-NSCLC were asked to make 15 hypothetical choices between two alternative PCI treatments at each of two time points (i.e. pre- and post their own treatment). Each alternative PCI treatment was described by four attributes: amount of life gained, ability to care for oneself, loss of memory and the chance of BM. Participants were also given the option of no PCI treatment. The choice data were analysed using multinomial and mixed logit regression models, to indicate the relative importance of improvements in each attribute for treatment preference.

      Results:
      There were 54 and 46 surveys completed pre- and post-treatment respectively. Participants had a mean age of 63.6 (range 39-82) years, 74% were male. Participants chose to accept PCI versus no PCI in approximately one third of the choices (34.8% pre- and 33.3% post - treatment). Overall, participants preferred a treatment alternative if it was associated with a longer survival, better ability to take care of oneself, lower loss of memory, and lower chance of BM. Before treatment, an increase in survival of more than 6 months was the most important benefit (relative importance weight 61.2), followed by avoiding severe problems with memory (39.4), avoiding severe problems with self-care (30.3), and a 15% reduction in risk of BM (15.0). After treatment, the rank order of importance remained similar but a reduction in the risk of BM became more important, relative to gains in the other attributes. Preliminary analysis suggests if PCI is able to reduce BM risk by 15% and increase survival by >6months, participants have a probability of uptaking PCI of 0.66 pre- and 0.55 post-treatment, even if they are left with severe problems caring for themselves and severe memory loss.

      Conclusion:
      The majority of patients would accept PCI for an increase in survival >6months, with a reduction in BM by 15%, , even if severe memory/self-care problems occurred. Patients would avoid PCI if it caused severe problems with memory/ self-care versus mild-moderate problems with memory/self-care, when survival gain is less than 6 months. Patients care more about avoiding BM following the completion of therapy.

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      MINI33.14 - Discussant for MINI33.11, MINI33.12, MINI33.13 (ID 3477)

      18:30 - 20:00  |  Author(s): K. Rosenzweig

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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