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Andrea Bezjak



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    MA 09 - The Current Status of Radiation Oncology (ID 666)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      MA 09.02 - Ultra-Central Tumours Treated with Stereotactic Body Radiotherapy: A Single Institutional Experience (ID 8758)

      11:05 - 11:10  |  Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Background:
      Stereotactic body radiotherapy of “ultra-central” (UC) lung tumours, PTV directly abuts/overlaps the proximal bronchial tree (PBT), trachea, esophagus, pulmonary vein/artery, are considered to be at higher risk of toxicity. The purpose of this study is to review the outcomes and toxicities of Ultra-central lung tumours, compared to central tumours.

      Method:
      A retrospective review based on a prospective database of patients treated with lung SBRT from January 2006- December 2015 was conducted. Patients with central tumours defined using RTOG 0813 criteria and ultracentral tumours were included. 115 patients (53%) received 60Gy/8 and 61 (28%) received 48Gy/4. At our institution, the recommended Dmax for esophagus is 45Gy and 40Gy for 8 and 4 fractions, respectively. The Dmax and D10cc constraints for trachea, proximal bronchial tree, heart, and major vessels (including pulmonary artery and vein) are 48Gy and 40Gy for 4 fractions and 64 and 60Gy for 8 fractions. Toxicity was graded using CTCAE v3.0. Log-rank test was used to compare overall and cause-specific survival. Local, regional, and distant recurrence were compared using Gray’s test.

      Result:
      215 tumours were analyzed (189 C and 26 UC). The median age for C and UC were 75 years and 72.5 years. Median tumour size and PTV volume were 2.2 cm (range 0.9-5.7) and 41.7 cm3 (range 9.7-246.3) (C group) and 2.5 cm (0.8-5.5) and 58.2 cm3 (16.8-238.3) (UC group). The percentage of squamous cell carcinoma was higher in the UC group (15%, n=29 in C; 38%, n=10 in UC). The median follow-up was 20.3 months (24.5 mo for patients still alive). Median overall survival (OS) and cause-specific survival (CSS) was 34 mo and 53.8 mo for C and 20.1 mo and 28.2 mo for UC, respectively. Differences in OS and CSS between the two groups did not meet statistical significance (p=0.24 and p=0.14, respectively). Local, regional, and distant failure rates were 3%, 8% and 18% in the central tumour group and 0%, 9% and 25% in the ultra-central tumour group at 2 years. There was no statistically significant difference found in the rates of recurrence between the two groups. The rates of any grade 2 or higher toxicity (hemoptysis, esophageal toxicity, cough, dyspnea, pneumonitis) was 9% (n=17) in the C and 7.7% (n=2) in UC group (p=0.89). There were no known grade 4 or 5 toxicities.

      Conclusion:
      In our experience, SBRT to ultra-central tumours resulted in effective local control and no excessive risk of toxicity compared to central tumours.

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    MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      MA 16.03 - Health Utility Scores in Patients with Thymic Malignancies Treated with Multimodality Therapy (ID 9651)

      15:55 - 16:00  |  Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Background:
      The management of patients with locally advanced thymic malignancies remains controversial. Various combinations of surgical resection, chemotherapy and radiation are currently used. Given the generally favorable prognosis, treatment related toxicities and quality of life (QOL) could inform therapeutic options. For economic analyses, QOL can be measured as health utilities. This study describes health utility scores (HUS) in patients with locally advanced thymic malignancies, while determining the impact of multimodality regimens on HUS.

      Method:
      In a cross-sectional study (2014-2017), patients with Masaoka stage II-IVa thymic malignancies seen at a comprehensive cancer centre completed various self-reported questionnaires at routine medical visits. HUS as measured by the EuroQol-5-Dimensions (EQ-5D) with visual analogue scale (VAS) and self-reported Eastern Cooperative Oncology Group (ECOG) performance status were compared in patients treated with trimodality versus uni- or bimodality regimens. Patient-reported Edmonton Symptom Assessment Scale (ESAS) scores were also collected to explore symptom burden. Regression analysis was used to compare groups; multivariable analysis investigating potential confounders was also conducted.

      Result:
      From 2014 to 2017, 72 patients were included in the study; 43 (59.7%) were male with a median age of 58 years, 65 (90.3%) had thymoma while 7 (9.7%) had thymic carcinomas and median time since diagnosis was 50.5 months (range: 3-266). Compared to patients treated with uni/bimodality regimens (n=48), those treated with trimodality (n=24) had higher stage of disease at diagnosis and were more likely to have received multiple lines of chemotherapy. Median HUS and VAS did not differ between groups (trimodality vs uni/bimodality: HUS=0.77 vs 0.80, p=0.26; and VAS=80 vs 75, p=0.79, respectively). The distribution of patient-reported ECOG at assessment was also similar (p=1.00). ESAS scores for pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, wellbeing and shortness of breath were neither statistically nor clinically different by number of modalities of therapy. Subset analyses of individuals who were 1+ year since diagnosis affirmed these findings.

      Conclusion:
      Patients with stage II-IVa thymic malignancies report favorable HUS, VAS and self-reported ECOG with minimal symptom burden. Trimodality therapy appears similarly tolerable when compared to uni- and bimodality regimens in this population.

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    P1.14 - Radiotherapy (ID 700)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Radiotherapy
    • Presentations: 1
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      P1.14-016 - Assessing the Feasibility of FLT-PET for Evaluation of Non-Small Cell Lung Cancer (NSCLC) Treated with Stereotactic Body Radiotherapy (SBRT) (ID 8455)

      09:30 - 09:30  |  Author(s): Andrea Bezjak

      • Abstract

      Background:
      Distinguishing fibrosis from tumor recurrence following lung SBRT remains a clinical challenge since CT has poor sensitivity and specificity for detecting recurrence. 18F-Fluoro-L-thymidine-PET (FLT-PET) uptake correlates with cell proliferation. The purpose of this study is to investigate the feasibility of FLT-PET as an imaging biomarker for lung SBRT response assessment.

      Method:
      In this prospective study, three groups were included: 1) newly-diagnosed biopsy-proven NSCLC pre-SBRT, 2) established post-SBRT mass-like fibrosis on serial follow-up CT scans by co-investigators’ consensus, and 3) biopsy-proven locally-recurrent NSCLC after SBRT. Non-gated, helical gated (3D-CT/4D-PET) and phase-matched (4D-CT/4D-PET) FLT-PET images were obtained. Group-1 underwent fluorodeoxyglucose (FDG)-PET scan according to clinical guidelines. FLT uptake was measured by SUV95 and SUV50 (95% and 50% of maximum pixel value plus average background value, respectively), SUV2Dpeak and SUV3Dpeak (1cm diameter circular or spherical around region of interest, respectively), SUVmean and SUVmax. Descriptive statistics were gathered. Kolmogorov–Smirnov test was used to determine normality. Statistical significance was reported using student’s t-test.

      Result:
      27 patients were included, with 19 primary tumors (group-1), 12 established fibrosis (group-2) and 1 recurrence (group-3). In group-1, 16 tumors were T1. Group-1, mean FDG-PET SUVmax, SUV95, SUV50, SUV2Dpeak, SUV3Dpeak and SUVmean were 7.40, 5.88, 2.39, 5.59, 6.02 and 2.78, respectively. Mean FLT-PET values for group-1 were 3.43, 2.84, 1.71, 2.9, 2.82 and 1.78, respectively. Group-2 SBRT dose was either 48Gy in 4 fractions (83%) or 60Gy in 8 fractions. Median time from radiation to FLT-PET scan in group-2 was 19.5 months (5.8-83.8mos). The patient in group-3 had SUV50, SUV95, SUV2Dpeak, SUV3Dpeak, SUVmean and SUVmax of 2.27, 3.85, 6.37, 6.05, 2.39 and 7.64, respectively. Mean FLT-PET SUVmax for groups 1 and 2 was significantly different (p=0.03) at 3.42(1.14-7.04) and 2.34(1.23-4.35) respectively. Similarly, mean (range) of SUV50, SUV95 and SUVmean for group-1 was 1.8(0.74-3.43), 2.97(1.03-5.83), 1.87(0.73-3.44), and for group-2 was 1.22(0.81-2.26), 1.85(1.13-3.8) and 1.25(0.83-2.39), respectively (p<0.01, <0.01 and <0.01). There was no statistically-significant difference between SUV2Dpeak and SUV3Dpeak between groups 1 and 2, with a mean of 2.97(0.99-6.30) and 2.91(0.90-6.11) for group-1 and 2.10(1.11-3.91) and 2.03(1.00-3.86) for group-2 (p=0.06 and 0.06), respectively. There was no statistically significant difference between the 3D and 4D image acquisition in group-1. There were no FLT-PET-related toxicities.

      Conclusion:
      FLT-PET is feasible in SBRT patients pre- and post-treatment, and may assist in distinguishing fibrosis from recurrent tumor. Further validation studies are needed.

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    PC 02 - Is Radiotherapy Necessary for Extensive SCLC? (Thoracic Radiation/PCI) (ID 582)

    • Event: WCLC 2017
    • Type: Pros & Cons
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      PC 02.03 - PCI---YES (ID 7829)

      11:40 - 12:00  |  Presenting Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Radiation therapy (RT) has an important role in both limited stage and extensive stage (M1) small cell lung cancer (SCLC), although more recent randomized trial results have led to increasing discussion and opposing views regarding the indications and type and degree of benefit conferred. This is one such debate, in which I am arguing in favour of recommending Prophylactic Cranial Irradiation (PCI) in extensive stage (ES) SCLC. There is no disagreement about the prevalence of brain metastases (BM) in SCLC. There is strong randomized trial evidence that delivery of modest doses of RT, such as 25 Gy in 10 fractions (fr) over 2 weeks, can reduce the incidence of BM. The simplistic explanation is that RT reduces the tumor cell burden and affects the ability of cancer cells to multiply, thus delaying or preventing the progression of microscopic intracranial metastases, and reducing the likelihood, that patient will develop symptomatic metastases – thus the term “prophylactic” brain RT. A meta-analysis [1 ]of previously conducted randomized clinical trials (RCTs) in patients with limited stage (LS) or ES SCLC with response to chemotherapy demonstrated not only a reduction in symptomatic BM (from 58% to 33% at 3 yrs) but also a survival benefit (15.3% to 20.7%). A large RCT [2] in LS SCLC confirmed that 25Gy/10 fr is the optimal dose fractionation, and described the potential negative neurocognitive and quality of life (QOL) impact of PCI [3]. Other studies [4 ]provided further data to inform patients regarding the potential risks and benefits of PCI. The EORTC group conducted a RCT in ES SCLC [5], randomizing 286 patients who had a response to 4-6 cycles of chemotherapy and had no clinical evidence of BM (but who did not have brain imaging to confirm absence of radiological metastases) to PCI vs observation. Their primary endpoint was time to symptomatic BM. A range of fractionation schedules was allowed; 62% of pts were treated with 20 Gy/5fr, 22% with 30 Gy/10-12 fr and only 4% with 25Gy/10 fr. There was a large reduction in symptomatic BM, 16.8% in the PCI group vs 41.3% in the control group (p < 0.001, hazard ratio (HR) 0.27 (95% confidence intervals (CI) 0.16-0.44). Disease-free survival (DFS) was significantly longer in the PCI group (median 14.7 weeks, vs 12 weeks, p = 0.02, HR 0.76 (95% CI 0.59-0.96), as was the overall survival (OS) (median 6.7 mo vs 5.4 mo, p = 0.003). This study let to the more widespread recommendation of PCI to patients with ES SCLC who have responded to chemotherapy. Practice guidelines on management of ES SCLC include PCI in their recommendations. A more recent Japanese RCT [6] randomized patients with ES SCLC who had a response to chemotherapy and no BM on MRI, to PCI (25 Gy/10 fr) vs observation. Follow up MRIs were mandated every 3 mo initially, then q6 mo. If patients were discovered to have radiological brain progression, whole brain RT was utilized regardless of whether they were symptomatic or not. Primary endpoint was OS. The study was closed after interim analysis, as the PCI group was not going to have a superior OS; 224 patients were enrolled in all. There was a reduction in BM in the PCI group, with the cumulative incidence at 6 mo15% vs 46% in the observation arm; at 12 months there was also a difference (33% and 59% respectively). PFS was identical, and there was no significant difference in OS (11.5 mo median OS in the PCI group vs 13.7, p = 0.094, HR 1.27 (95% CI 0.96-1.68)). The study concluded that PCI doesn’t result in longer OS and is thus “not essential for patients with ES SCLC (..) and a confirmed absence of BM, if patients will be followed by periodic MRIs”. Those are indeed very fair conclusions of their data, although it is interesting that some, perhaps many, especially in the medical oncology community, after hearing the presentation at ASCO 2015, seem to have concluded that PCI may be detrimental to survival (given the small and statistically non-significantly longer survival in the observation group). Comments have been made that in the era of staging/ restaging MRIs, there may be no benefit to PCI in ES SCLC, and that perhaps the EORTC study showed improved survival because patients may have had clinically undetected gross metastatic disease (ie not just microscopic disease). That is clearly an incorrect interpretation of the Japanese data, and an assumption that has no proof in terms of the EORTC study. Every study that looked at local control ie ability of PCI to eradicate metastatic disease showed a benefit to RT, whether assessed radiologically or clinically. The incidence of BM in the control arms of the EORTC and Japanese trials was similar, suggesting that patients staged with MRIs did not have a different risk of brain disease than patients staged clinically. Even if restaging MRIs are routinely available in many parts of the world, close surveillance with regular MRIs is not routinely done for ES SCLC; it should be noted that Japan has the highest ratio of MRI to population. A very large proportion of patients in the observation arm of the Japanese study (83%) had whole brain RT for BM – no wonder there was no survival difference as it was really a comparison of early vs late RT. Finally, the risk of systemic disease in ES SCLC is high, so that a treatment that clearly has an impact in reducing brain relapse would be expected to have a relatively small OS benefit. Thus, Japanese study provides valuable data that continue to support the role of PCI in ES SCLC, and emphasize the need for a more realistic and holistic view of the expected role and benefit of RT – ie reducing BM, prolonging survival in some, and aiming to provide good neurological functioning and QOL. Rather than trying to argue against PCI as a strategy, we should continue with attempts to reduce its toxicity, such as through hippocampal sparing techniques [7 ]and to identify groups of patients who are more or less likely to benefit in terms of survival [8], [9]. References: Auperin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 341(7):476-84, 1999. Le Péchoux C, Dunant A, Senan S, et al. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomized clinical trial. Lancet. 10(5):467-74, 2009. Le Pechoux C, Laplanche A, Faivre-Finne C, et al. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in intergroup phase III trail (PC I00-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Annals of Oncology 22: 1154-1163, 2011. Wolfson AH, Kyounghwa B, Ritsuko K, et al. Primary Analysis of a phase II randomized trial radiation therapy oncology group (RTOG) 0212: Impact of different total doses and schedules of prophylactic cranial irradiation of chronic neurotoxicity and quality of life for patients with limited-disease small-cell lung cancer. Int. J. Radiation Oncology Biol. Phys Vol 81 (1): 77-84, 2011. Slotman B, Faivre-Finn C, Kramer G, et al. EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 357(7):664-72, 2007. Takahashi T, Takeharu Y, Takashi S, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicenter, randomized, open-label, phase 3 trial. The Lancet Oncology, 18: 663-71, 2017. Gondi V, Paulus R, Bruner DW et al. Decline in tested and self-reported cognitive functioning following prophylactic cranial irradiation for lunc cancer: Pooled secondary analysis of RTOG randomized trials 0212 and 0214. Int J. Radiat Oncol Biol Phys. 86(4): 656-664, 2013. Rule WG, Foster NR, Meyers JP et al. Prophylactic cranial irradiation in elderly patients with small cell lung cancer: Findings from a North Central Cancer Treatment Group pooled analysis. Journal of Geriatric Oncology 6: 119-126, 2014. Farooqi AS, Holliday EB, Allen PK et al. Prophylactic cranial irradiation after definitive chemoradiotherapy for limited-stage small cell lung cancer: Do all patients benefit? Radiotherapy and Oncology 122: 307-312, 2017.

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    PL 04 - Closing Plenary: Where We Are Now, and Where We Will Be in 10 Years (ID 587)

    • Event: WCLC 2017
    • Type: Plenary Session
    • Track:
    • Presentations: 1
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      PL 04.04 - WCLC 2018 - Welcome to Toronto (ID 7844)

      17:30 - 17:35  |  Presenting Author(s): Andrea Bezjak

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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