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G. Pratt
Moderator of
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O14 - Radiotherapy - Toxicity and Clinical Trials (ID 105)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Radiation Oncology + Radiotherapy
- Presentations: 8
- Moderators:G. Pratt, S.K. Vinod
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Ballroom A, Level 1
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O14.01 - Memory preservation with conformal avoidance of the hippocampus during whole-brain radiotherapy for patients with brain metastases: Preliminary results of RTOG 0933 (ID 2262)
10:30 - 10:40 | Author(s): V. Gondi, M.P. Mehta, S. Pugh, W.A. Tome, B. Corn, C. Caine, A. Kanner, H. Rowley, V. Kundapur, J.N. Greenspoon, A.A. Konski, G.S. Bauman, W. Shi, V. Kavadi, L. Kachnic
- Abstract
- Presentation
Background
Preclinical and clinical evidence suggests that hippocampal dose during whole-brain radiotherapy (WBRT) plays a role in cognitive decline. This may be preventable by conformally avoiding the hippocampus during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with cognitive function assessments and pre-specified comparison to a historical control of WBRT without hippocampal avoidance.Methods
Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function assessments were performed at baseline, 2, 4, and 6 months. The primary endpoint was change in the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-DR) at 4 months. The historical control consisted of brain metastases patients treated with WBRT on the PCI-P-120-9801 phase III trial, which demonstrated a 30% mean relative loss in HVLT-DR from baseline to 4 months. To detect a minimum relative 50% improvement in this end-point, leading to an absolute 15% or less mean relative loss in HVLT-DR following HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with a one-sided alpha=0.05.Results
113 patients were accrued from April 2011-November 2012; 56 out of 100 eligible patients had non-small cell lung cancer (NSCLC). One grade 3 toxicity of cerebral edema and no grade 4 or higher toxicities were reported. Median survival was 6.9 months (95% confidence interval (95% CI) 4.8-15.2 months). 41 patients were analyzable at 4 months. Mean relative change in HVLT-DR from baseline to 4 months was +3.3% (95%CI: -8.0% to +14.6%), which was significant in comparison to the historical control (p<0.0001) and substantially exceeded the hypothesized -15% value. 28 patients were analyzable at 6 months with a mean relative change in HVLT-DR from baseline to 6 months of +4.6% (95%CI: -8.6% to +17.8%), a finding in dramatic contrast to expected continued deterioration in HVLT-DR scores from other WBRT trials. In terms of patients with NSCLC, 21 patients were analyzable at 4 months, with a mean relative change in HVLT-DR from baseline to 4 months of +10.0% (95%CI: -9.5% to +27.1%). At 6 months, 14 patients with NSCLC were analyzable, with a mean relative change in HVLT-DR from baseline to 6 months of 0.0% (95%CI: -18.5% to +18.5%).Conclusion
Conformal avoidance of the hippocampus during WBRT is associated with memory preservation at 4 and 6 months follow-up in NSCLC patients, who comprised the majority of accrued and analyzable patients on this trial. These promising phase II results warrant further validation in a phase III trial, currently under development in the RTOG.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.
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O14.02 - Vertebral fractures in NSCLC patients treated with IMRT and concurrent chemotherapy (ID 1880)
10:40 - 10:50 | Author(s): W. Uyterlinde, C. Chen, J.J. Sonke, J. De Bois, J. Belderbos, M. Van Den Heuvel
- Abstract
- Presentation
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.
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O14.03 - Using generalized equivalent uniform dose (gEUD) to model volume effects for brachial plexopathy after high-dose stereotactic body radiation therapy (SBRT) (ID 2835)
10:50 - 11:00 | Author(s): S.U. Din, E.L. Williams, Y. Yamada, E. Yorke, A. Foster, E. Poppens, A.J. Wu, A. Jackson, A. Rimner
- Abstract
- Presentation
Background
Brachial plexopathy is a rare but important toxicity of radiation therapy because of its significant impact on quality of life. For standard fractionated raiation therapy, good models of brachial plexus (BP) tolerance exist. However, the tolerance of the BP to SBRT is not well understood. We combined data from SBRT for apical lung and metastatic lesions near the BP spanning a wide range of doses and hypofractionation schemes. We determined the clinical incidence of brachial plexopathy and modeled the correlation with generalized equivalent uniform dose (gEUD) for both physical and biologically effective doses (BED) using a range of fractionation-sensitivity parameters (α/β) and volume effect parameters (a).Methods
Between 2004 and 2012, 180 lesions (76 lung lesions and 104 metastatic lesions) located above the aortic arch and below the level of C3 were treated with SBRT. Patients with prior radiation therapy to this region were excluded. Metastases were treated to 14-30 Gy in 1-5 fractions and lung tumors to 22-60 Gy in 1-5 fractions. The BP was contoured per RTOG atlas definitions. For 54 centrally located spine metastases, both left and right BP were contoured and analyzed separately for a total of 234 BPs in 180 patients. Brachial plexopathy of ≥grade 1 (CTCAE v4.0) was the primary endpoint. Maximum dose to the BP (Dmax), minimum dose to the hottest 5% of the BP (D05), and their respective BEDs were calculated using α/β= 3 Gy. The gEUD was also calculated with the volume effect parameter (a) ranging from log~10~a= -1.0 to +1.0 in log~10~a steps of 0.1. A logistic regression model (LR) was fit to the data as a function of a. Clinical dose recommendations were derived with logrank tests using median splits.Results
With median follow-up of 15.1 months, brachial plexopathy due to SBRT occurred in 9/234 BPs. Severity of brachial plexopathy was grade 1 in two, grade 2 in five and grade 3 in two patients. Median time to onset of brachial plexopathy was 6.2 months and the 1-/2-year actuarial rates were 3.3%/5.6%. For all patients the median BED for BP Dmax was 117.5 Gy and for D05 was 89.3 Gy. Median BED Dmax for patients with and without brachial plexopathy was 234 Gy and 115.2 Gy respectively (p=0.002). Brachial plexopathy was significantly associated with BP BED Dmax (p=0.002), and D05 (p=0.015), but not with physical dose. Using LR, the strongest correlation of gEUD with brachial plexopathy occurred for log~10~a= 1.0 using BED (p=0.002), which is representative of the BED Dmax. LR models of BED Dmax versus brachial plexopathy for various α/β values showed that any α/β<25 was a significantly better predictor than physical dose.Conclusion
Brachial plexopathy is significantly associated with BED Dmax ≥117.5 Gy (equivalent to a physical dose of 17 Gy x1, 9.3 Gy x3 or 7 Gy x5 fractions) and D05 ≥89.3 Gy. BED Dmax was the most important predictor of this rare but serious toxicity.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.
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O14.04 - DISCUSSANT (ID 3931)
11:00 - 11:15 | Author(s): F. Mornex
- Abstract
- Presentation
Abstract not provided
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O14.05 - Effect of Postoperative 3D-Conformal Radiotherapy (3DCRT) for Patients with pIIIA-N2 non-small-cell lung cancer (NSCLC) after Complete Resection and Adjuvant Chemotherapy: Interim Analysis of a Prospective Phase III Study (ID 2299)
11:15 - 11:25 | Author(s): Z. Hui, J. Liang, J. Lv, X. Wang, Z. Zhou, Q. Feng, Z. Xiao, D. Chen, H. Zhang, W. Yin, L. Wang
- Abstract
- Presentation
Background
For patients with completely resected pⅢA-N2 NSCLC, the role of postoperative radiotherapy (PORT) is not well defined. 3D-conformal radiotherapy (3DCRT) can deliver high dose to the target volume while decreasing the toxicity of normal tissues, which may improve the treatment outcomes. This interim analysis of our phase III randomized clinical trial (NCT00880971) is to evaluate the effect of postoperative 3DCRT on the overall survival (OS) and failure pattern in pⅢA-N2 NSCLC patients after complete resection and adjuvant chemotherapy.Methods
Between Jan. 2009 and May 2012, 128 consecutive patients with pⅢA-N2 NSCLC, after complete resection and four courses of platinum based chemotherapy, were randomized into PORT group or control group. Only patients who had finished the first follow-up 3 months after treatment were included in this interim analysis. PORT, using 3D conformal techniques, was 60 Gy by 30 fractions to the subcarinal nodes, ipsilateral mediastinum and ipsilateral hilum. The effect of PORT on survival was evaluated with Kaplan-Meier method and log-rank test. The treatment failure pattern was also analyzed. Pearson chi-Square test was used to compare the constituent ratios in different groups.Results
Totally 96 patients were analyzed, including 49 in the PORT group and 47 in the control group. The clinical features were comparable between the two groups. For all the patients, the 3-y OS, disease free survival (DFS), loco-regional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) were 68.4%, 54.6%, 68.6% and 63.0%, respectively. The survival rates of patients in the PORT and control groups are listed in the table. PORT markedly increased the 3-y OS, DFS, LRFS and DMFS by 21.6%, 18.7%, 16.4% and 20.4%, respectively. But the difference was not statistically significant due to the limited samples. There were 33 patients (34.3%) with treatment failure, including 7 (7.3%) with loco-regional recurrence only, 13 (13.5%) with distant metastasis only, and 13 (13.5%) with the both. PORT markedly decreased the loco-regional recurrence from 27.7% to 14.3% (P=0.107), but not the distant metastasis (from 29.8% to 24.5%, P=0.559). Eight deaths were observed up to the last follow-up, which were all caused by cancer progression. No death caused by radiation toxicities was observed.
*Between PORT and control groups.All Patients (n=96) PORT Group (n=49) Control Group (n=47) P Value* OS 68.4% 80.8% 59.2% 0.432 DFS 54.6% 64.2% 45.5% 0.256 LRFS 68.6% 76.4% 60.0% 0.105 DMFS 63.0% 67.1% 46.7% 0.542 Conclusion
For pⅢA-N2 NSCLC patients after complete resection and adjuvant chemotherapy, postoperative 3DCRT can markedly improve the survival and loco-regional control. Further accumulation of patients in our prospective randomized study is warranted.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.
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O14.06 - Investigation of a Patient Reported Outcome (PRO) tool to assess radiotherapy-related toxicity in patients with lung cancer (ID 1614)
11:25 - 11:35 | Author(s): M. Christodoulou, P. McCloskey, N. Stones, N. Bayman, P. Burt, A. Chittalia, M. Harris, L.W. Lee, L. Pemberton, H. Sheikh, R. Swindell, C. Faivre-Finn
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Background
Discrepancies between clinician and patient reported symptoms validate the investigation of a PRO tool in clinical trials and routine practice. There is a paucity of data regarding the feasibility and relevance of PRO tools to assess radiotherapy toxicity in patients with lung cancer.Methods
From January to June 2013, lung cancer patients undergoing thoracic radiotherapy or chemo-radiotherapy completed a PRO toxicity tool (adapted Radiogenomics Biorepository and Databank lung questionnaire) consisting of 9 patient-adapted Common Terminology Criteria for Adverse Events (CTCAE) items and World Health Organisation (WHO) performance status (PS) at baseline, at the end of radiotherapy and at 4-10 weeks follow-up (FU). At the same time points, patients completed the European Organisation for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire along with its lung cancer specific module (EORTC QLQ-C30/LC13) and the Hospital Anxiety and Depression Scale (HADS). Clinicians completed the same CTCAE items for each time point. Agreement between patients’ and clinicians’ toxicity reports was assessed using weighted kappa coefficients. The patients’ QoL and HADS scores were correlated with the patients’ and clinicians’ reported toxicity using Spearman rank correlation coefficients.Results
Of the 116 patients consented, 70 (85 paired responses) completed all 3 questionnaires for at least one time point excluding baseline. Median age was 71.5 years (39-89 years), 54.3% of the patients were male and 85.7% had a diagnosis of non-small cell lung cancer. Agreement between patients’ and clinicians’ reported toxicity ranged from poor to substantial (Figure 1). Perfect agreement was ≥50% for all assessed items with the exception of PS for both the end of radiotherapy and FU. The majority of discrepancies (≥74%) differed by 1 grade of toxicity. At the end of radiotherapy patients reported greater severity than clinicians for all items but not for PS; however this was less pronounced at FU. QoL scores were generally more strongly correlated with the patients’ compared to clinicians’ matching toxicity grades at the exception of dyspnoea. The correlation of HADS scores with patients’ CTCAE anxiety and depression grades ranged from moderate-to-low to moderate. There was no correlation with clinicians’ grading for depression and no-to-moderate correlation for anxiety. The adapted Radiogenomics Biorepository and Databank lung questionnaire demonstrated a high Cronbach’s α value (0.848) indicating good reliability. Figure 1Conclusion
The use of a PRO tool in radiotherapy for lung cancer is feasible, reliable and acceptable to patients and complements the clinicians’ assessment. Further research is required to evaluate its validity.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.
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O14.07 - IDEAL CRT: Isotoxic Dose Escalation and Acceleration in Lung Cancer ChemoRadiotherapy - a phase I/II trial of concurrent chemoradiation with dose-escalated radiotherapy in patients with stage II or stage III Non-Small Cell Lung Cancer. (ID 1368)
11:35 - 11:45 | Author(s): D.B. Landau, I. Khan, Y. Ngai, L.L. Hughes, E. Miles, D. Wilkinson, E. Parsons, P. Mayles, H. Mayles, A.T. Bates, N. Mohammed, J. Hicks, S. Harden, M. Illsley, A. Garcia, Z. Malik, S. Hughes, J. Spicer, A. Baker, P. Wells, V. Laurence, J. Fenwick
- Abstract
- Presentation
Background
The IDEAL-CRT trial uses an individual patient approach to radiotherapy (RT) dose escalation, escalating the dose within a fixed overall treatment time, 6 weeks, by increasing dose per fraction. Isotoxic RT is based on the calculated risk of RT-pneumonitis (RTPN), RT dose being escalated so that all patients are exposed to the same RTPN risk. We investigated the feasibility and safety of individualised, isotoxic dose escalation for once daily RT delivered in 30 once-daily fractions with concurrent chemotherapy.Methods
Eligibility; NSCLC stage II/III, PS 0/1, FEV~1~ (≥40% predicted or ≥1L), DCLO (≥40% predicted). A radiobiological model was used to individualize RT dose-prescription – selecting a dose which, in 30# once daily for 6 weeks, is associated with a 10% risk of grade 3+ RTPN, but limiting prescribed doses to between 63Gy - 73Gy (2Gy dose equivalent α:β=10, 63.5Gy-86Gy). Dose constraints were fixed for spinal cord, heart, brachial plexus. In Arm 1, initially the maximum dose to 1cc oesophageal did not exceed 63Gy. Arm 2 comprised patients in whom oesophageal dose rather than lung dose limited the prescription dose: the oesophageal dose was raised from 65Gy to 68Gy, 71Gy and 73Gy in consecutive cohorts, the prescribed dose lying between 63Gy and 73Gy and being the highest consistent with the oesophageal limit. Dose escalation was determined using a 6+6 design. Dose limiting toxicity (DLT) was defined as Grade 3+ oesophagitis. MTD was determined if grade 3+ oesophagitis >42% (>5/12). Two cycles of Cisplatin-Vinorelbine chemotherapy given concurrently during RT. All contouring and dosimetry on planning CT scans was centrally reviewed. IMRT was introduced in November 2012. Primary endpoints: oesophagitis and RTPN. Serial pulmonary function tests and ECGs performed. Efficacy endpoints: overall survival (OS), progression free survival (PFS), and tumour response.Results
Between October 2010 and February 2013, 84 patients recruited (9 UK centres), 49 patients Arm 1, 35 patients Arm 2 (13 at 65Gy, 12 at 68Gy, 10 at 71Gy; none at 73Gy as the 73Gy upper prescription dose limit was only rarely associated with an oesophageal dose higher than 71Gy). Median follow up was 11 months (range 2,24); median age 66 years (range 43-84); 74% male; 39%/60% WHO 0/1; 30% adenocarcinoma, 54% squamous. Mean GTV 121cc (range 14-602cc). Mean prescribed dose for patients completing RT (n=80) 67.6Gy (range 63-73Gy) in Arm 1 and 70.1 Gy (63-73) in Arm 2. Mean 1cc-oesophageal-dose in Arm 1 55.5Gy (range 14.2-68.0Gy). In Arm 1 grade 3+ oesophagitis was 6% (3/49). In Arm 2, Grade 3+ oesophagitis was 17% (2/12) at 68Gy; no Grade 3+ oesophagitis in 65Gy (0/12) and 71Gy (0/10) cohorts. Grade 3+ RTPN 2% (1/49) in Arm 1 and 6% (2/35) in Arm 2. 1 year OS and PFS rates were 92% and 74% respectively.Conclusion
Isotoxic RT dose escalation was safe and feasible. The MTD for oesophagus was not reached. Acceleration of the IDEAL-CRT schedule to five weeks is under investigation in a second study, currently recruiting.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.
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O14.08 - DISCUSSANT (ID 3932)
11:45 - 12:00 | Author(s): S.K. Vinod
- Abstract
- Presentation
Abstract not provided
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