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W.J. Curran

Moderator of

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    ED 01 - Update in Radiation Oncology (ID 1)

    • Event: WCLC 2015
    • Type: Education Session
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 4
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      ED01.01 - Current Status of Proton and Heavy Particle Therapy (ID 1770)

      14:15 - 15:45  |  Author(s): H. Choy

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology. Proton therapy is a type of radiation treatment that uses protons rather than x-rays to treat cancer. Protons, however, can target the tumor with lower radiation doses to surrounding normal tissues. Proton therapy is particularly useful for treating cancer in children because it lessens the chance of harming healthy, developing tissue. In addition, proton therapy may be used to treat Lung cancer. Compared with standard radiation treatment, proton therapy has several benefits. It reduces the risk of radiation damage to healthy tissues; may allow a higher radiation dose to be directed at some types of tumors, which may keep the tumor from growing or spreading; and may result in fewer and less severe side effects (such as low blood counts, fatigue, and nausea) during and after treatment. However, there are some drawbacks such as higher cost and lack of convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. Carbon ion therapy is another type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. There are several centers in Asia and Europe using carbon beam to treat lung cancer patients. In this session, we will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy for lung cancer. We will also attempt to highlight some of the challenges that surround clinical trials in particle therapy.

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      ED01.02 - Optimal Dose and Fractionation (ID 1771)

      14:15 - 15:45  |  Author(s): J. Urbanic

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      ED01.03 - Post-Operative Radiotherapy for Stage III Disease (ID 1772)

      14:15 - 15:45  |  Author(s): F. Mornex

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Despite advances in treatment, lung cancer remains the leading cause of cancer mortality in most countries. About one third of patients with non-small cell lung cancer (NSCLC) presents with locally advanced non-metastatic disease (stages IIIA and B). Although 5-year overall survival (OS) ranges from 60 to 73% for completely resected pathologic stage I disease, OS decreases to less than 25% for pathological stage III disease. Patients with potentially resectable stage IIIA-N2 can be treated with induction chemotherapy followed by radical surgery. Prospective studies report 5-year OS rates from 20% to 30%, with about 30% of the patients reporting local recurrence (LR). When surgery is performed first, for patients presenting with node-positive disease at the time of resection, meta-analysis data demonstrate that adjuvant platinum-based chemotherapy has been shown to decrease distant metastases and locoregional recurrence (LRR), resulting in an approximately 5% OS advantage, and is now considered standard of care for patients with resected node-positive NSCLC. However, these patients have a 20% to 40% risk of LRR, and LRR correlates independently with worse OS. Thus, postoperative radiotherapy (PORT) holds great appeal as a means to reduce LRR and improve OS. Several phase III trials investigated the role of PORT after surgical resection in NSCLC. In 1998, the PORT Meta-analysis Trialists Group undertook an individual participant data (IPD) meta-analysis (of both published and unpublished trial data) of PORT versus surgery alone in NSCLC [1]. The original meta-analysis, based on 9 randomised controlled trials and 2128 patients, concluded that PORT was detrimental with a 7% absolute reduction in 2-year OS and a 4% reduction in recurrence-free survival. Subgroup analyses suggested that PORT was increasingly detrimental with decreasing stage (p = 0.0003) and lower nodal status (p = 0.016). The updated results for OS, and for local, distant and overall recurrence-free survival are unchanged, continuing to show a detrimental effect of PORT(2) : For the whole patient group, PORT decreased the OS at two years by 6% (52% vs. 58%). This deleterious effect was detected in patients with pN0–1 disease. No effect was detected in patients with pN2 disease. The PORT meta-analysis raised a lot of criticism for the following reasons: significant heterogeneity between trials, inclusion of trials with old radiotherapy techniques (notably, most of these trials, conducted principally in the 1960s to 1970s, included outmoded RT techniques and doses). The deleterious effect of PORT has been attributed to an excess of intercurrent deaths, with a high incidence of cardiac and respiratory complications due to poor radiotherapy techniques. In support of this hypothesis, several more recent trials with contemporary radiation techniques did not report an increase of death from intercurrent disease. Kepka et al. did not detect a difference in QoL scores, cardiopulmonary morbidity or non-cancer related deaths between patients receiving PORT and those treated with surgery alone (3). Two Surveillance, Epidemiology, and End Results (SEER) analyses and a secondary analysis of data from the Adjuvant Navelbine International Trialist Association (ANITA) trial suggest that PORT may be safely delivered in a modern cohort of patients with a potential OS benefit for stage IIIA (N2) disease (4, 5). In addition, being now established that the use of adjuvant chemotherapy in stage III disease prolongs OS, it is then hypothesised that with the reduction of distant metastases with chemotherapy, the survival benefit by improved local control after three-dimensional conformal (3D-CRT) PORT will occur. Then, recently, the National Cancer Data Base (NCDB), joint program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, has been queried to study the impact of modern PORT in the setting of standard-of-care adjuvant chemotherapy for pathologic stage IIIA (N2) NSCLC (6). Data of 1850 patients who received PORT between 1998 and 2010 were obtained. Use of PORT, compared with no PORT, was associated with a significant increase in median OS (45.2 v 40.7 months, respectively), 3-year OS (59.3% v 55.2% , respectively), and 5-year OS (39.3% v 34.8%, respectively; P=.014. This analysis of the NCDB for patients with pathologic N2 disease, receiving adjuvant chemotherapy, shows that PORT seems to confer an additional improvement in OS. In conclusion, modern radiotherapy techniques should be evaluated in stage III patients, as already stated in the initial individual-patient-data meta-analysis. This new evaluation is justified for several reasons: (a) the N2 population has changed because of a better selection with pre-treatment PET-CT scan and brain imaging; (b) adjuvant chemotherapy has become a standard of care in these patients; (c) technical advances of radiotherapy may enhance the ability of PORT to improve local relapse-free survival and possibly overall survival. Thus, based on the previous studies, the underlying hypotheses remain to be proven, with sufficiently powered new randomised trials. A prospective randomized phase III trial, LungART (Lung Adjuvant Radiotherapy Trial), designed with the primary aim of investigating the benefits of conformal radiotherapy in completely resected pN2 NSCLC, together with adjuvant chemotherapy, is currently ongoing in Europe, and should help answering definitely this question, investigators are strongly encouraged to enroll patients on this randomized trial. 1 : PORT Meta-analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet 1998; 352:257-63. 2 : PORT Meta-analysis Trialists Group: Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2:CD002142, 2005 3 : Kepka L, Bujko K, Orlowski TM, et al. Cardiopulmonary morbidity and quality of life in non-small cell lung cancer patients treated with or without postoperative radiotherapy. Radiother Oncol 2011;98:238–43. 4 : Lally BE, Zelterman D, Colasanto JM, et al. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 2006; 24:2998-3006. 5 : Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer. Adjuvant Navelbine International Trialist Association ANITA: a randomised controlled trial. Lancet Oncol 2006;7: 719-27. 6 : Robinson CG, Patel AP, Bradley JD et al. Postoperative radiotherapy for pathologic N2 Non small Cell lung cancer treated with adjuvant chemotherapy : A review of the National Cancer Data Base. J Clin Oncol 2015 ; 33 :870-77

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      ED01.04 - Evolving Role of Radiation for Oligometastases (ID 1773)

      14:15 - 15:45  |  Author(s): B. Movsas

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Evolving Role of Radiation for Oligometastases The key objectives of this presentation are to review the fundamental biology underlying metastatic disease, understand the definition and clinical evidence for oligo- (or limited) metastatic disease, analyze key clinical trials showing the potential role of stereotactic body radiation therapy (SBRT) for oligometastases and address challenges regarding this “high-tech” strategy. In the early 1900s, Halsted suggested that breast cancer spread via the local regional lymphatic vessels in a stepwise manner. Thus, once there are metastases, local therapy had no clear role. Later in the 20[th] century, an opposing theory (the “Fisher” theory) suggested that cancer is a systemic disease that, if it will ever metastasize, will already have done so early in the disease course. Local therapies are therefore less important than systemic therapies. A counterpoint to these approaches was proposed by Hellman and Weichselbaum, postulating that cancer is a spectrum from localized to wide-spread disease at the time of diagnosis, with many intermediate states (Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995 Jan;13(1):8-10). “Oligometastases” are essentially early metastases which are limited in number and location and based on a state of limited metastatic capacity. The hypothesis based on this approach is that there may be a subset of patients with oligometastatic disease for whom aggressive local treatment (such as surgery or SBRT) could change their outcome. Clinical evidence for oligometastasis includes the surgical experience for lung or liver metastases showing long-term survivals of approximately 20%. Studies are now emerging suggesting similar results utilizing SBRT. In an individual patient data meta-analysis of outcomes after surgery or SBRT, Ashworth et al. reported a 5-year survival rate of approximately 30% in patients with oligometastatic non-small cell lung cancer (Ashworth AB, et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer. 2014 Sep;15(5):346-55). They developed a risk classification schema showing a better prognosis for metachronous vs. synchronous oligometastases (of which node-negative was favorable to node-positive). Other studies have shown that, among patients treated with SBRT for 1-5 oligometastases, those with ≤3 metastases had better outcomes compared to those with 4-5 metastases. The size of the metastases also appears to be important, as well as the biological equivalent dose (BED) of the SBRT. Studies have begun to explore the role of SBRT for oligometastases involving the lung, liver, adrenal, and other sites. It is likely that host-related factors (for example, immune mediated anti-cancer activity) and tumor related factors (such as genomics and proteomics) also affect the spectrum of disease aggressiveness. Challenges to this new “high-tech” approach will also be addressed, including issues related to patient selection, the level of evidence, and the cost effectiveness of this approach. Other approaches for improving the outcome for patients with metastatic disease will also be discussed, including the role of early palliative interventions. In summary, emerging (albeit non-randomized) data suggests that SBRT appears to be a promising strategy in selected patients with oligometastases. The patients most likely to benefit from SBRT have metachronous (vs. synchronous) metastases, N0 (vs. N+) disease, 1-3 metastases (vs. more), small metastases, and the ability to receive a higher radiation dose (BED >100Gy). Randomized trials are needed to establish whether SBRT improves progression free and/or over survival in this setting.

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Author 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: 1
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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): W.J. Curran

      • 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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    ORAL 05 - Surgery (ID 97)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      ORAL05.05 - Trimodality Therapy in the Treatment of Stage IIIA Non-Small Cell Lung Cancer (NSCLC): A National Cancer Database Analysis (ID 2962)

      10:45 - 12:15  |  Author(s): W.J. Curran

      • Abstract
      • Slides

      Background:
      Significant controversy remains regarding the care of patients (pts) with clinical stage IIIA NSCLC. While multi-modality therapy is an acceptable strategy in selected pts, the optimal approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database (NCDB), an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society.

      Methods:
      The NCDB was queried from 2003-2011 for NSCLC pts diagnosed with stage IIIA-N2 disease and treated with chemotherapy and radiation (CRT). Data was extracted on patient demographics, tumor pathology, treatments and outcomes. Three cohorts of pts were studied - CRT only/no surgery (NS), CRT + lobectomy (L) and CRT + pneumonectomy(P). The univariate and multivariable analyses (MV) were conducted using Cox proportional hazards model and log rank tests. All analyses were performed using SAS Version 9.3.

      Results:
      A total of 29,584 pts were included in this analysis: NS-91.7%, L-7%, and P-1.5%. Pt characteristics: median age 66 years (yrs); males 56%; whites 86%; academic centers 27%; metro locations 78%; government insured 63%; Charlson/Deyo comorbidity score 0 in 66%. Pts < 60 yrs were more likely to receive TT- L (47%), P (60%) vs. NS (29%); p<0.001. Pts in academic centers were more likely to get TT than NS (42% vs. 25%). On MV analysis, L and P had significantly better survival vs. NS: HR 0.43 (0.38-0.48) and HR 0.57 (0.46-0.71) respectively; p <0.001. The median survival of L, P and NS were 44.5 m vs. 25.6 m vs. 15.7 m (p<0.001) and 5- year survival rates (SR) were 44% vs. 33% vs. 14% respectively. 30-day mortality was higher in P vs. L [7% vs. 2.6%; OR 0.26(0.16-0.45); p<0.001]. Pts with <2 lymph nodes (LN) had better survival than pts with >2 LNs in L (50% vs. 37%; 60m vs. 38.8m) but worse in NS (13.8% vs.16.4%; 15.3m vs.18.5m). On MV analysis of LNs, L had better survival than NS: HR 0.4 (0.35-0.46) in <2 LN pts and HR 0.56 (0.46-0.69) in ≥2 LN pts; p<0.001. In pts with <2 LN, L had better survival than P (60m vs. 25.5m; p<0.0001). L and P had better SR than NS in all ages: 48% vs.37% vs. 19% in ≤60 yrs; 42% vs. 30% vs.14% in 61-70 yrs, 36% vs.19% vs. 10% in >70 yrs.

      Conclusion:
      TT was utilized in less than 10% of pts with stage IIIA-N2 disease, suggesting high degree of pt selection. In this selected group, TT was associated with favorable outcomes relative to CRT alone.

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    ORAL 20 - Chemoradiotherapy (ID 124)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      ORAL20.01 - A Systematic Review of Carboplatin-Paclitaxel versus Cisplatin-Etoposide Concurrent with Thoracic Radiation for Stage III NSCLC Patients (ID 600)

      10:45 - 12:15  |  Author(s): W.J. Curran

      • Abstract
      • Presentation
      • Slides

      Background:
      The two most commonly used chemotherapy regimens deployed concurrently with thoracic radiation (RT) for patients with unresectable IIIA and IIIB non-small cell lung cancer (NSCLC) are carboplatin/paclitaxel (CP) and cisplatin/etoposide (CE). Because there are no prospective comparisons of these two regimens in this setting, we conducted a systematic review of published trials to compare outcomes and toxicities between CE and CP.

      Methods:
      Studies which enrolled stage III patients receiving RT with CP or CE were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library) and meeting abstracts. Trials were excluded if they were phase I, enrolled less than 10 pts, or included surgical resection. A systematic analysis of extracted data was performed using Comprehensive Meta Analysis (Version 2.2) software using random and fixed effect models. Clinical outcomes were compared using point estimates for weighted values of median overall survival (OS), progression free survival (PFS), response rate (RR) and toxicities. Two-tailed T-test with a significance level of 0.05 was used for all comparisons.

      Results:
      3194 patients were included from 32 studies in the CE arm, and 3789 patients from 51 studies in CP. Baseline characteristics of patients on the CE arm versus CP arm were: median age 61 vs. 63 years, male 67.6% vs. 78%, squamous histology 39% vs. 40%, and median radiation dose 62 Gy vs. 63 Gy. There was no significant difference in response rates between CE and CP (65% vs. 56%, p =0.6), respectively. There was no significant difference in median progression free survival (11.5m vs. 9.3m p =0.2), overall survival (19.8m vs. 18.4m, p=0.48), 1-year survival rate (66% vs. 65%, p=0.8), or 3-year survival rate (31% vs. 25%, p=0.4) for CE vs. CP. CE was associated with higher grade 3/4 hematological toxicities than CP, such as neutropenia (53% vs. 23% p<0.0001), thrombocytopenia (14% vs. 6% p=0.001), anemia (16% vs. 8% p=0.06), as well as grade 3/4 nausea/vomiting (20% vs. 9% p=0.018), while rates of grade 3/4 pneumonitis and esophagitis were similar.

      Conclusion:
      CE and CP regimens were associated with comparable efficacy when used with concurrent radiotherapy for stage III unresectable NSCLC pts. The toxicity profile favored the CP regimen.

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    PC 03 - Pro vs Con: Prophylactic Cranial Irradiation (PCI) Post Chemotherapy Response / Pro vs Con: Is There a Role for Radiation in Oligometastatic Disease? (ID 49)

    • Event: WCLC 2015
    • Type: Pro Con
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      PC03.04 - Is There a Role for Radiation in Oligometastatic Disease? - Con (ID 2037)

      14:15 - 15:45  |  Author(s): W.J. Curran

      • Abstract
      • Presentation

      Abstract not provided

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