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S.S. Yom

Moderator of

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    MINI 18 - Radiation Topics in Localized NSCLC (ID 139)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 15
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      MINI18.01 - Stereotactic Body Radiation v. Observation for Early-Stage NSCLC in Elderly Patients (ID 137)

      16:45 - 18:15  |  Author(s): R.H. Nanda, T.W. Gillespie, J.L. Mikell, Y. Liu, J. Libscomb, S.S. Ramalingam, F. Fernandez, W.J. Curran, K.A. Higgins

      • Abstract
      • Presentation
      • Slides

      Background:
      Stereotactic body radiotherapy (SBRT) has demonstrated high rates of local control with low morbidity and has now emerged as the new standard of care for medically inoperable, early-stage non-small cell lung cancer (NSCLC). However, the impact of lung SBRT on survival in the elderly population is less clear given competing co-morbid conditions. An analysis of the National Cancer Data Base (NCDB) was undertaken to determine whether definitive SBRT in patients 70 and older improves survival relative to observation alone.

      Methods:
      The NCDB, a retrospective national database capturing up to 80% of all patients treated for cancer, was queried for patients ages 70 or higher with early stage (T1-T3N0M0) NSCLC from years 2003-2006. Overall survival was compared between patients treated with stereotactic body radiotherapy alone and patients receiving no treatment. Extended Cox proportional hazards model was applied to estimate the treatment effect of SBRT.

      Results:
      A total of 3,147 patients met the selection criteria for this analysis. SBRT was delivered to 258 patients (8.2%) and 2889 patients (91.8%) received no treatment. There was no significant difference in the distribution of Charlson/Deyo comorbidity index scores between the two groups (p=0.076). Multivariable analysis revealed improved overall survival with SBRT compared with observation for the entire cohort (HR 0.64, p<0.001), as well as for each age group as follows: 70-74, HR=0.72; 75-79, HR=0.66; 80-84, HR=0.59; 85 and above, HR=0.56.

      Conclusion:
      SBRT is associated with improved survival in elderly patients with early stage NSCLC with concurrent comorbid conditions compared to observation alone . The data support the use of SBRT for treatment of elderly patients with early stage NSCLC that have limiting co-morbid conditions.

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      MINI18.02 - Stereotactic Body Radiotherapy Is Safe and Effective in Octo- and Nonagenarians for the Treatment of Early Stage Lung Cancer (ID 3072)

      16:45 - 18:15  |  Author(s): M. Giuliani, A. Hope, M. Johnson, M. Guckenberger, F. Mantel, H. Peulen, J. Sonke, J. Belderbos, M. Werner-Wasik, H. Ye, I. Grills

      • Abstract
      • Slides

      Background:
      To determine the safety and efficacy of lung SBRT in older patients and to compare their outcomes to those of younger patients.

      Methods:
      Patients with primary lung cancer treated with SBRT were identified from a multi-institutional (5) database of 1192 cases. Details of patient factors, treatment specifics, toxicity and clinical outcomes were extracted from the database. All events were calculated from the end of radiotherapy. Estimates of local (LR), regional (RR), and distant metastases (DM) were calculated using the competing risk method. Cause specific (CSS) and overall survival (OS) were calculated using the Kaplain-Meier method. Outcomes were compared for those <70, 70-79, >=80. Toxicity was graded per CTCAE V3.0. The 90 day mortality was reported for those <70, 70-79, >=80. Univariable analysis was performed to determine associations with CSS in patients aged >70.

      Results:
      The median follow-up was 1.7years (1-10y) and median age 75 (41-94). There were 364 patients age <70 (28%), 546 age 70-79 (42%) and 387 age ³80 (48%). 621(48%) were female, 1125(87%) were peripheral and 852(66%) were biopsied. There was no difference in baseline SUV (p=0.6), histology (p=0.4), radiation dose (p=0.1), gender (p=0.3) or biopsy rate (p=0.2) among the three age groups. Patients aged >=80 had significantly more T2 tumors 21% vs 23% vs 32 % (p<0.01). There was no difference in 5 year LR (10% vs 11.5% vs 10%, p=0.7), RR (22% vs 10% vs 9%, p=0.1), DM (17% vs 16% vs 21%, p=0.07) or CSS (80% vs 80% vs 75%, p=0.6). Those age ³80 had significantly lower 5 year OS (75% vs 44% vs 23%, p<0.01). The grade 3+ pneumonitis rate was 1.3% vs 1.6% vs 1.5% (p=0.9) in patients ages <70,70-79, >=80 respectively. The 90 day mortality rates for patients aged <70,70-79, >=80 were 1.4%, 2.7%, and 2.6% respectively. In patients aged >70 CSS was associated with tumor size (p<0.01; HR1.4) and baseline SUV max (p=0.03; HR1.04).

      Conclusion:
      SBRT is a safe treatment modality in elderly patients (aged >80). Despite larger tumor volumes, the tumor control outcome were identical to the younger patients treated with SBRT. All patients, regardless of age, should be considered for treatment of early stage lung cancer (T1-T2) with SBRT.

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      MINI18.03 - Immune Activation in Early Stage Non-Small Cell Lung Cancer (NSCLC) following Stereotactic Ablative Radiotherapy (SABR) and Surgery (ID 2123)

      16:45 - 18:15  |  Author(s): J.G. Aerts, P. De Goeje, M. Schram, K. Bezemer, M. Kaijen-Lambers, J. Hegmans, J. De Langen, A. Maat, J. Nuyttens, R. Hendriks, E. Smit, S. Senan

      • Abstract
      • Presentation
      • Slides

      Background:
      An anatomical surgical resection is considered to be the standard of care in fit patients, but non-randomized comparative effectives studies suggest that survival outcomes may be similar following SABR. An antitumor immune microenvironment was found to be a prognostic factor in surgically resected early stage NSCLC. SABR has been reported to activate the immunesystem in malignant diseases via a number of mechanisms. We investigated the impact of both surgery and SABR in early stage NSCLC on the immunesystem, studied in peripheral blood over time.

      Methods:
      This is a non-randomised trial. Treatment by either surgery or SABR treatment for early stage (cT1-T2aN0M0) were determined by an institutional multi-disciplinary tumorboard, and in accordance with the patient’s preference . SABR was typically delivered in 3-8 fractions in 1-2 weeks, based on risk-adapted radiotherapy schemes that delivered a biologically effective dose of >100 Gy. Surgery generally involved a VATS lobectomy. Blood was collected prior to treatment, and at weeks 1, 2, 3 and 6 after start of treatment. The peripheral blood mononuclear cell (PBMC) fraction was isolated and was stimulated for 4 hours with phorbol 12-myristate 13-acetate (PMA) and ionomycin, to activate the T cells. Subsequently, the T-cells cells were harvested and analyzed by flow cytometry on the expression of CD4 and/or CD8, granzyme B and interferon (IFN) γ. As PD-1 expression is induced in T-cells after antigen exposure the expression of PD-1 was determined. Changes of population proportions between the different time points were analyzed with the related-samples Wilcoxon signed rank test.

      Results:
      23 early stage non-small cell lung cancer (NSCLC) patients were included in the study. Of these, 13 patients underwent surgical resection at a mean age (±standard deviation) of 62,9± 8,4 years, and 10 patients who underwent SABR at a median age of 70,0 ±10,4 years. SABR patients had more comorbidities, and a poorer WHO performance score, but clinical tumor stage was comparable. A significant increase in the proportion of IFNγ[+]Granzyme B[+] CD8 T cells (p<.05) was observed at week 2 in the SABR treated group, whereas no difference was found after surgical resection. The PD1[+] fraction of CD4[+] T cells was significantly increased at week 2 in the SABR treated group (p<.05), whereas no differences were seen at two weeks after surgical resection. Proportions of PD1[+ ]CD4 T cells remained elevated in the SABR group at week 3 and 6. A similar trend was observed in the CD8[+] T cell population, although this did not reach statistical significance (p<.1).

      Conclusion:
      SABR but not surgery, enhances T-cell activation and PD-1 upregulation. The results of our study warrant further investigation as to whether SABR induces an anti-tumor response in patients with early stage NSCLC . The upregulation of PD-1 inherently accompanied with this activation of the immune system potentially warrants combination treatment with PD-(L)1 blockade.

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      MINI18.04 - Tumor Volume Variations and Related Dosimetric Impact During Stereotactic Body Radiation Therapy for Lung Cancer (ID 958)

      16:45 - 18:15  |  Author(s): L. Moretti, Y. Jourani, F. Charlier, T. De Brouwer, P. Van Houtte

      • Abstract
      • Slides

      Background:
      This study aimed to evaluate the importance of interfraction variations in gross tumor volume (GTV) during stereotactic body radiotherapy (SBRT) for early lung cancer patients and assess its impact on dosimetric GTV coverage

      Methods:
      Forty-seven consecutive patients undergoing SBRT were treated with 48 Gy in 4 fractions (group 1: n=35) or 60 Gy in 8 fractions (group 2: n=12). For each patient, Cone-Beam Computed Tomography (CBCT) imaging obtained at each fraction and initial planning 4DC (CT) were analyzed. GTVs were delineated on all CBCTs, and individual treatment planning was recalculated on each CBCT. Statistical analyses were performed to compare differences between independent samples: the Mann-Whitney U test was used for non-normal continuous variables analyses between groups and the χ2 test for proportions within each SBRT group. Wilcoxon signed rank test was also used to assess changes in volume, dosimetric parameters, and tumor localization. All significance tests were two-tailed and p<0.05 was considered significant

      Results:
      A total of 236 CBCTs were processed and analyzed. Median total treatment times were 8 days for group 1 and 19.5 days for group 2. There was a significant tumor volume change between the initial CT and the 1st CBCT (p=0.003) in group 1. This was not found in group 2 (p=0.67). GTV was significantly larger at the 2nd CBCT (p=0.003 for group 1 and p=0.049 for group 2) compared to the 1st CBCT. Volume changes were not significantly different at the 3rd fraction compared to 1st CBCT. In group 1, GTV volume significantly decreases at the 4th fraction compared to the 2nd (p=0.047). In group 2, the significant decrease in volume occurs at the 6th fraction (p=0.026). There was no association between the overall treatment time and tumor volume variations. Taken individually (n=47) 83% of tumors have at least one occurrence of a greater than 15% volume change during SBRT compared to the 1[st] CBCT. Variations of more than 20%, 30% and even 40% were observed in ~60%, 40%, and 17% of treatments, respectively. No factor that would predict a significant volume change during SBRT for the patients analyzed could be identified. In group 1, tumor coverage factor (>95%) for any given fraction deviated no more than 5% from optimised coverage obtained in the initial treatment plan. Although sample size is smaller, there was a trend towards lower tumor coverage factors in group 2 compared to group 1. Conformity index for all tumors still ranged from 3.41 to 13.35 in group 1, and 0.95 to 10.48 in group2, without any association with tumor volume variations or treatment time

      Conclusion:
      There was considerable variation in tumor volumes and more frequent than initially expected for patients undergoing lung SBRT. However, these volume changes did not significantly impact dosimetric parameters. Whether these results affect treatment and/or patient outcome remains to be investigated in prospective clinical trials

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      MINI18.05 - Discussant for MINI18.01, MINI18.02, MINI18.03, MINI18.04 (ID 3407)

      16:45 - 18:15  |  Author(s): H. Choy

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MINI18.06 - Validation of High Risk Features on CT for Detection of Local Recurrence After SBRT for Stage I NSCLC (ID 2138)

      16:45 - 18:15  |  Author(s): H. Peulen, F. Mantel, M. Rossi, B. Stam, I. Grills, M. Giuliani, M. Werner-Wasik, A. Hope, J. Belderbos, M. Guckenberger, J. Sonke

      • Abstract
      • Presentation
      • Slides

      Background:
      Fibrotic changes after SBRT for stage I NSCLC are difficult to distinguish from local recurrences (LR), hampering proper selection for salvage therapy. Huang et al. (1) defined CT high risk features (HRF) for detection of LR. This study attempts to validate these HRFs in an independent patient cohort.

      Methods:
      From a multicenter combined database of patients treated with SBRT for stage I NSCLC between 2006 and 2012, 53 LR were detected of which 14 were biopsy proven. The biopsy proven LR (N=14) were matched 1:2 to patients without LR (n=28) based on: 1) dose 2) PTV 3) follow up time 4) central/peripheral location 5) lung lobe. Of the resulting 42 patients 18 were male and 24 female with a median age of 73 years (range 56-89years). Median tumor size, PTV and dose were 2.3 cm (range 1.0-4.9cm), 49cc (range 9-166cc), 48 Gy (range 48-60Gy) in 4 fractions (range 3-8) respectively. Most tumors were peripheral (76%) and located in the upper lobes (55%). Median follow up (FU) was 36 months (range 14-78months) and median time to LR was 18 months (range 12-45months). For all patients, planning CT scans and at least two follow up scans were available. Two blinded observers scored eight HRFs for each scan. Sensitivity and specificity in predicting LR were assessed and compared using Fisher’s exact test. Analysis for best fit was done using AUC.

      Results:
      Results of sensitivity and specificity are shown in Table 1. The best performing HRF was cranio-caudal growth: sensitivity 86%, specificity 82%. The odds of LR increased on average by 2.6 (95%CI1.5-4.3) for each additional HRF detected, while the AUC was 0.86. The presence of ≥ 3 HRFs resulted in the best cut-off with sensitivity 79% and specificity 86%. Loss of linear margin and bulging margin were scored identical and therefore only the latter was included in the model. The two best combinations of HRFs were: 1) bulging margin & cranio-caudal growth, with a sensitivity of 93% and specificity of 82% or 2) bulging margin & enlarging opacity after 12 months, with a sensitivity of 86% and specificity of 89%. Table 1

      CT high risk factor for local recurrence Sensitivity (%) Specificity (%) p-value
      Any HRF 93 64 .001
      enlarging opacity (≥5mm and ≥20%) 86 68 .003
      sequential enlarging opacity 57 89 .002
      enlarging opacity after 12 months 71 89 <.001
      bulging margin 64 100 <.001
      loss of linear margin 64 100 <.001
      loss of air bronchograms 7 100 0.33
      cranio-caudal growth (≥5mm and ≥20%) 86 82 <.001
      new pleural effusion 14 93 0.59


      Conclusion:
      In this matched group of biopsy proven LR and controls, cranio-caudal growth was the best individual predictor of LR after SBRT. Combining HRF bulging margin with either cranio-caudal growth or enlarging opacity after 12 months resulted in higher sensitivities and specificities than number of HRFs. 1)Huang et al. Radiotherapy&Oncology 2013

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      MINI18.07 - Early Results of a Quality Assurance Program in a Randomized Trial of Stereotactic Body Radiotherapy for Stage I Medically Inoperable Lung Cancer (ID 2887)

      16:45 - 18:15  |  Author(s): A. Swaminath, M. Wierzbicki, J. Wright, T. Tsakiridis, K. Cline, C. Bucci, O. Ostapiak, S. Parpia, J. Julian, T. Whelan

      • Abstract
      • Presentation
      • Slides

      Background:
      A large Canadian multicentre randomized trial (LUSTRE) has recently opened to determine if stereotactic body radiotherapy (SBRT) to 48 Gy in 4 fractions (peripheral) or 60 Gy in 8 fractions (central) improves outcomes compared to conventionally hypofractionated radiotherapy (CRT) to 60 Gy in 15 fractions in early stage non-small cell lung cancer. Given the rapid diffusion of lung SBRT technology across Canada, a unique radiotherapy quality assurance (RTQA) program was devised to minimize variations in practice. This study describes the RTQA experience to date.

      Methods:
      Centres participating in LUSTRE are required to satisfy three RTQA requirements prior to being accredited: (a) Respond to a survey describing treatment equipment, planning system details and image guidance parameters in order to confirm that their centre is compliant with protocol guidelines; (b) Assess SBRT delivery accuracy using a thoracic phantom produced by IROC (Imaging and Radiation Oncology Core); and (c) Successfully complete four treatment plans from the developed trial planning guide using SBRT and CRT for one centrally and one peripherally located cancer.

      Results:
      Currently 13 centres are undergoing RTQA: (a) Surveys have been completed in 8 centres, 2 require revision, and 3 are incomplete. (b) Phantom testing has been completed in 9 centres, 2 are incomplete, 1 has results pending, and 1 is being resubmitted. Although 6/13 centres were identified as having active SBRT programs (>3 patients/month), only 2/6 had completed the IROC phantom prior to study accreditation (most having in-house end-to-end tests). (c) 8/13 centres have successfully submitted their test cases. All 8 submitting centres passed on SBRT/CRT distributions and conformality indices. However, 5/8 centres required resubmission for contouring revisions. In one case, the GTV/ITV was incorrectly contoured. In another case, it was contoured on the incorrect dataset. In the remainder, normal organs (lungs, bronchi, esophagus) had contouring errors, particularly the bronchial tree; contours excluded the major bronchi, and in 2 cases, normal lung parenchyma was included. Some centres did not follow standardized nomenclature for targets and normal organs, as they were likely new to this naming convention. Some issues were related to misinterpretation of the planning guide, prompting the trial group to work with centres to ensure a seamless future workflow.

      Conclusion:
      Preliminary results show that most well-established lung SBRT centres rely on their own in-house standards, while others are using LUSTRE RTQA to implement new SBRT programs. Our experience shows that when centres participate in an independent review, alterations are recommended that can improve their own existing QA processes, and contribute to standardized practice nationwide. Such an RTQA process can be a model worth considering in future radiotherapy randomized trials, and also when instituting new radiotherapy technologies into existing clinical programs.

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      MINI18.08 - A Systematic Review of Comparative Effectiveness Studies of Surgery versus SABR in Early Stage Lung Cancer: How Good Is the Data? (ID 1549)

      16:45 - 18:15  |  Author(s): A.V. Louie, C.D. Goodman, H. Chen, G.B. Rodrigues, D.A. Palma, B. Slotman, S. Senan

      • Abstract
      • Presentation
      • Slides

      Background:
      Three prospective randomized control trials (RCTs) comparing stereotactic ablative radiotherapy (SABR) and surgery in early stage non-small cell lung cancer (ES-NSCLC) failed to complete accrual. Numerous other comparative effectiveness studies have been published, but such studies may be more prone to bias, and conclusions may vary based on study quality. The goal of this study was to perform a systematic review of comparative effectiveness studies that compare both treatment modalities in this patient population, to assess study quality and conclusions.

      Methods:
      In accordance with PRISMA guidelines, a systematic review was conducted on studies reporting on comparative outcomes of surgery versus SABR for ES-NSCLC. Studies published in the English language over a 10-year period (April 2006-March 2015) were identified using PUBMED with an inclusive search strategy, using the National Library of Medicine’s medical subject headings. Eligible study designs included RCTs, population analyses, match pair comparisons, propensity-match score comparisons, retrospective case-control series, decision analyses, and cost-effectiveness analyses. Letters, editorial and systematic reviews were excluded. Abstracts identified were independently reviewed by two investigators to determine eligibility, with discrepancies settled by a third investigator. Using a standardized data abstraction form, study, patient, tumor, and treatment characteristics were abstracted. As patients undergoing surgery and SABR often differ in their baseline characteristics, we determined the proportion of studies reporting statistical adjustment for baseline characteristic imbalances (e.g. matching in patient studies, sensitivity analyses in modeling studies). The Fisher’s exact test was used to determine if there was an association between the use of statistical adjustment and differences in overall survival (OS) findings.

      Results:
      Of the 568 studies identified by our search strategy, 22 were eligible for analysis. Primary study design was retrospective (n=11), population-based (n=7), or model-based (n=4). Most patient studies (n=17) reported on a statistical adjustment for differences in baseline characteristics, with propensity score matching (n=12) being the most common technique employed. All studies, except for 1, reported details of the type of surgery performed. SABR doses employed ranged from 30 Gy in 1 fraction, to 60 Gy in 3 fractions. The weighted average pathologic confirmation of malignancy rate for SABR patients was 72% (range 22-100%). Of the 20 studies reporting on overall survival, 12 found that SABR and surgery were equal, or sensitive to variability in baseline patient, treatment, or tumor factors. The remaining 8 studies reported an overall survival benefit of surgery over SABR, however, 4 of these studies did not employ statistical adjustments for baseline characteristics. In the other 4 studies reporting overall survival superiority of surgery when controlling for various co-variates, at least one other recurrence endpoint (local, regional, or distant) was found to be equal between surgery and SABR. All but 2 studies stated in their conclusion that future clinical trials are warranted to investigate the role of SABR in the potentially operable ES-NSCLC patient.

      Conclusion:
      A systematic review of the comparative effectiveness literature indicates that the results of well-controlled studies comparing surgery and SABR argue for clinical equipoise. Results of a pooled analysis of two international RCTs that closed prematurely are expected shortly.

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      MINI18.09 - Survival of Elderly Patients after SABR for Early Lung Cancers - A Population Based Retrospective Comparison of Survival among Age Cohorts (ID 3113)

      16:45 - 18:15  |  Author(s): D. Schellenberg, M. Dosani, R. Yang, A. Houle, S. Thomas, C. Lund, H. Carolan

      • Abstract
      • Presentation
      • Slides

      Background:
      As Stereotactic Ablative Body Radiotherapy (SABR) is increasingly used to treat early non-small cell lung cancer, a larger proportion of elderly patients are now receiving radical therapy. This review aims to assess whether age significantly influences overall survival (OS) in patients with early stage lung cancer treated by SABR according to a standard provincial protocol, and to determine if a maximum age guideline should be introduced.

      Methods:
      Using a population database all lung-SABR patients were divided into age categories <70 yo (n=45), 70-74 (n=28). 75-79 (n=39),80-84 (n=33) and ≥85 (n=22). Patient and tumor characteristics were collected including: sex, Charlson comorbidity index (CCI), ECOG performance status, tumor diameter, maximum tumor SUV (SUVmax), forced expiratory volume in 1 second (FEV1), and whether a pathologic diagnosis was obtained. For each cohort, OS from date of SABR was calculated. Variability among tumor characteristics between cohorts was evaluated by Chi-squared test and OS was calculated by Kaplan-Meier.

      Results:
      185 patients were treated from 2009 to 2013. Median age was 76 (range 49-94). The percentage of patients with pathologic diagnoses and the percentage of males was similar among age categories. FEV1 values, ECOG status, SUVmax values and tumor length were not significantly different among the age categories. Older patients had significantly greater CCI scores (see table p=0.001). Median OS for all patients was 36 months and was not reduced in the oldest cohorts (<70: 34 months, 70-74: 24 months: 75-80: 39 months, 80-84:36 months, ≥85: 36 months).

      Age Categories (years old)
      <70 70-74 75-79 80-84 85+
      CCI
      0-1 5 (%) 0 0 0 0
      2-4 59 (%) 39 35 15 10
      5-7 34 (%) 54 57 76 60
      8 or more 2 (%) 7 8 9 30


      Conclusion:
      Based on 5 years of population based data, an age cutoff for lung-SABR is not endorsed. In our treated population, patients ≥85 yo have similar OS as younger patients despite greater CCI scores.

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      MINI18.10 - Discussant for MINI18.06, MINI18.07, MINI18.08, MINI18.09 (ID 3542)

      16:45 - 18:15  |  Author(s): S.S. Yom

      • Abstract
      • Presentation

      Abstract not provided

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      MINI18.11 - Does Motion Management Technique for Lung SBRT Influence Local Control? (ID 177)

      16:45 - 18:15  |  Author(s): G.M.M. Videtic, N. Woody, C. Reddy, K. Stephans

      • Abstract
      • Presentation
      • Slides

      Background:
      Abdominal compression (COMP) for motion management began with our lung stereotactic body radiotherapy (SBRT) practice. From 11/2009, breath hold technique by automatic breath control (ABC) device is selectively employed typically for fit oligometastatic patients (pts). We now compare local failure (LF) results for COMP versus ABC.

      Methods:
      Our IRB-approved SBRT registry was queried for pts. treated for either a primary lung cancer (PRIME) or an oligometastatic (OLIGO) diagnosis with a minimum 6 months follow up. SBRT was delivered by a stereotactic-specific LINAC platform with vacuum-bag based immobilization, and infrared-based X-ray positioning system+/- CBCT for image-guidance. With COMP, tumor excursion was limited to <1cm and the ITV was created one of two way dependent on treatment era: 1. Fused GTV excursion CTs from free breathing, fixed inhale and exhale travel or 2. by 4DCT, with PTV created from the MIP ITV after adding a 5mm margin. With ABC, 3 serial CT image sets confirmed target immobilization, with the PTV generated after 5 mm was added to the static GTV. SBRT was delivered either with dynamic arcs or step-and-shoot intensity–modulated beams. SBRT dose/fractionation schedules evolved over time and reflected treatment era, tumor location, clinician preference, and trial-based experience. LF was defined as progressive and increasing CT scan abnormalities confirmed by progressive and incremental increases in a lesion’s SUVs on serial PET imaging, with or without biopsy.

      Results:
      For the interval 10/2003 to 7/2014, 873 pts with 931 lesions were treated. Overall pt. characteristics were: 455 (52.1%) female; 83.9% Caucasian; median age 73 years (range 37-97); median KPS 80 (range 40-100); median BMI 26.2 (range 12.1-56.3). Overall tumor characteristics were: median tumor size 2.2 cm (range 0.7-10.0); median PET SUVmax 7.5 (range 0.8-59), per RTOG 0813 definitions 234 (25.4%) were central lesions, with no significant tumor differences between COMP and ABC cohorts. 830 (89.2%) lesions were PRIME, 101 (10.8%) were OLIGO. ABC was used significantly more for OLIGO vs. COMP (34.4% vs.8.3%, p<0.0001). Median follow-up and SBRT dose were 16.4 months (0-109.5) and 50 G/5 fractions respectively. Overall crude rate of LF was 9.9%. Use of ABC was not associated with increased LF compared to COMP: hazard ratio (HR)=1.043 [95% CI 0.48-2.29; p=0.92] Three-year actuarial rates of LF for ABC vs. COMP were 13.8% and 16.5%, respectively. After stratifying by OLIGO/PRIME, neither ABC nor COMP was significantly associated with LF. There is a suggestion that centrality may be associated with LF with ABC (HR =2.087, p=0.066)On univariate analysis, BMI, tumor size, PET SUVmax and central location were associated with failure, with size the most significant.

      Conclusion:
      Although form of motion control overall did not predict for LF in lung SBRT, LF for central tumors may be associated with ABC use.

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      MINI18.12 - Assessment of Dose Response via Regional Lung Perfusion following Stereotactic Radiotherapy for Lung Cancer (ID 910)

      16:45 - 18:15  |  Author(s): R. McGurk, S.K. Das, E. Schreiber, T. Zagar, A. Sheikh, W. McCartney, M. Lawrence, P. Rivera, R. Green, L. Marks

      • Abstract
      • Presentation
      • Slides

      Background:
      Radiation therapy (RT)-induced lung injury is one of the major causes of morbidity in patients with thoracic cancer. Extensive work has been done to understand the predictors of lung injury in patients receiving conventionally fractionated RT. However, less work has been done in the setting of hypo-fractionation. Further, conventional methods to consider lung injury typically assess global lung function (e.g. symptoms, pulmonary function tests), are affected by many other (non-radiation) factors, and are thus non-specific. Single photon emission computed tomography (SPECT) perfusion imaging affords an objective quantitative manner to assess the effects of RT on regional lung function. We herein report the preliminary results of a prospective study to assess the magnitude of RT-induced reductions in regional lung perfusion following hypo-fractionated stereotactic RT.

      Methods:
      Four patients undergoing hypo-fractionated stereotactic lung RT (SBRT: 12 Gy x 4 fractions or 10 Gy x 5 fractions) had a pre-treatment SPECT (single-photon emission computed tomography) perfusion scan providing a 3D map of regional lung perfusion. Scans were repeated 3-6 months post-treatment. Pre- and post SPECT scans were registered to the planning CT scan (and hence the 3D dose data). Changes in regional perfusion (counts per cc on the pre-post scans) were computed in regions of the lung exposed to different doses of radiation (in 5 Gy intervals), thus defining a dose-response function. SPECT scans were internally normalized such that total counts in the regions receiving <5 Gy were equal between pre- and post-treatment scans.

      Results:
      3 months post-RT, changes in perfusion are highly variable. At 6 months, there is a consistent dose-dependent reduction in regional perfusion. Average percent decline in regional perfusion was 10% at 15-20 Gy, 20% and 20-25 Gy, and 30% at 25-30 Gy representing a relatively linear dose response with an approximate 2% reduction per Gray for doses in excess of 10 Gy. Subtle increases in perfusion were seen in lung receiving <10 Gy. Figure 1



      Conclusion:
      Hypo-fractionated stereotactic RT appears to cause a dose-dependent reduction in regional lung perfusion. There appears to be a threshold effect with no apparent perfusion loss at doses <10 Gy, in both normalized and unnormalized dose-response curves. Additional data is needed from a larger number of patients to better assess this issue. This sort of data can be used to assist optimizing RT treatment plans that minimize the risk of lung injury.

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      MINI18.13 - Can Stereotactic Ablative Radiotherapy (SABR) Improve Patient Selection for Lung Cancer Surgery and Reduce Perioperative Mortality? (ID 779)

      16:45 - 18:15  |  Author(s): N. Serrano, B. Adams, S. Szentpetery, C.L. Rogers, M. Chang, D. Moghanaki

      • Abstract
      • Presentation
      • Slides

      Background:
      Comparative effectiveness research has demonstrated similar rates of disease control and overall survival (OS) for patients with stage I non-small cell lung carcinoma (NSCLC) who are treated with either surgery or SABR. It was therefore hypothesized that the introduction of SABR might improve patient selection for surgery, lead to the referral of high operable risk patients for SABR, and consequently reduce the lung cancer surgery perioperative mortality rate.

      Methods:
      Cancer registry data identified all patients with stage I NSCLC who underwent surgery or SABR between 1993-2014 at a Veterans Affairs medical center. Mortality rates from the pre-SABR and post-SABR (after 2007) eras were compared. Clinical records in the Computerized Patient Record System were queried to analyze rates of disease control and overall survival (OS).

      Results:
      A total of 284 patients underwent surgery for stage I NSCLC in the pre-SABR (n=171) and post-SABR (n=113) eras. The majority of patients were male (96.6%) and the median follow-up was 4.1 years. Operative procedures included a pneumonectomy (n=10), lobectomy (n=206), or wedge resection (n=68). The 90-day mortality rate was 3.2%, whereas the 6-month mortality rate was 7.0%. Comparing mortality rates in the pre-SABR to post-SABR eras, there were no declines at 90-days (3.5% vs. 2.7%, p=0.47), or 6-months (7.0% vs. 7.1%, p=0.36). Patients referred for SABR have included 27 medically inoperable patients and 0 operable patients. The mortality rate after SABR was 0% at both 90-days and 6 months. Comparing SABR and surgery, the rate of disease progression was similar (p=0.47); found in 18.5% after SABR (1 distant, 4 regional), 23.4% after lobectomy (9 regional, 2 regional and distant, 11 distant), 33.3% after wedge (3 local, 3 distant), and 0% after pneumonectomy. Two-year OS was numerically superior with SABR (69.4% vs. 63.1%), although this was not statistically significant (p=0.52).

      Conclusion:
      The introduction of SABR neither influenced patient selection for surgery, nor reduced the perioperative mortality rate for patients with stage I NSCLC. These data suggest comparative effectiveness research alone may be insufficient to improve outcomes for this disease. Efforts to complete a prospective randomized trial of surgery vs. SABR should not be abandoned.

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      MINI18.14 - Pre-Existing Pulmonary Fibrosis Increases the Risk of Radiation Pneumonitis (ID 557)

      16:45 - 18:15  |  Author(s): S. Campbell, G. Kerr, J. Murchison, G. Ritchie, S. Erridge, T. Evans, F. Little, M. McKean, A. Price

      • Abstract
      • Presentation
      • Slides

      Background:
      Radiation pneumonitis is a potentially life-threatening complication of curative radiotherapy in individuals with lung cancer. Predicting which patients are at higher risk of pneumonitis is constrained by limited understanding of its causes. The aim of this study was to examine patient characteristics and radiological factors associated with increased risk of radiation pneumonitis in individuals with lung cancer receiving curative radiotherapy.

      Methods:
      Individuals with lung cancer treated with curative radiotherapy between January and June 2009 were identified from our departmental database. Data were extracted on patient sex, age and smoking status, lobe affected by cancer, pathology, T and N stage, radiation dose delivered, the use of concurrent chemotherapy, and the grade of fibrosis present on the diagnostic CT scan. The CT scans were reviewed and the fibrosis scored by two pulmonary radiologists. CTCAEv3.0 toxicity scores were used to grade the pneumonitis. Mann-Whitney, chi-squared and Fisher exact tests were used to determine the impact of the various factors on the risk of developing pneumonitis.

      Results:
      84 patients were identified who underwent curative radiotherapy for lung cancer between January and June 2009. The minimum follow-up for the cohort was 5 years. One year and 3 year survival were 61.9% and 29.8% respectively. 8/84 patients (9.5%) developed significant pneumonitis (CTCAEv3 grade 3 - 5). 6/22 (27.3%) patients with fibrosis on their diagnostic CT developed grade 3 - 5 pneumonitis compared with 2/58 (3.4%) of patients with no fibrosis on the diagnostic CT (Fisher exact test, p=0.0042). Low grade pneumonitis had no impact on survival (grade 0, median survival 80 weeks, grade 1 - 2, median survival 78 weeks) whereas median survival was reduced to 16 weeks in those with grade 3 - 5 pneumonitis. One out of 8 patients in this group survived one year. Only the presence of fibrosis on the diagnostic CT scan and continued tobacco use affected the risk of developing pneumonitis with fibrosis increasing the risk of developing pneumonitis (relative risk 7.9, p < 0.04) and continued tobacco use reducing the risk (relative risk 0.3, p < 0.02). There appeared to be a trend between the fibrosis score on the baseline scan and the risk of developing pneumonitis which did not achieve statistical significance

      Conclusion:
      The data from this small study suggest radiation pneumonitis affects approximately 1 in 10 individuals receiving curative radiotherapy for lung cancer. The presence of pulmonary fibrosis on the diagnostic CT scan increased the risk of developing pneumonitis. Consideration should be given to alternative treatment options for these patients.

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      MINI18.15 - Discussant for MINI18.11, MINI18.12, MINI18.13, MINI18.14 (ID 3474)

      16:45 - 18:15  |  Author(s): W.E.E. Eberhardt

      • Abstract
      • Presentation

      Abstract not provided

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Author of

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    MINI 04 - Clinical Care of Lung Cancer (ID 102)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI04.15 - Discussant for MINI04.11, MINI04.12, MINI04.13, MINI04.14 (ID 3310)

      16:45 - 18:15  |  Author(s): S.S. Yom

      • Abstract
      • Presentation

      Abstract not provided

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    MINI 18 - Radiation Topics in Localized NSCLC (ID 139)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      MINI18.10 - Discussant for MINI18.06, MINI18.07, MINI18.08, MINI18.09 (ID 3542)

      16:45 - 18:15  |  Author(s): S.S. Yom

      • Abstract
      • Presentation

      Abstract not provided

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