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K. Wang



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    OA24 - Radiotherapy of Lung Cancer: Recent Developments (ID 411)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Radiotherapy
    • Presentations: 1
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      OA24.03 - Cardiac Toxicity after Radiation for Stage III NSCLC: Pooled Analysis of Dose-Escalation Trials Delivering 70-90 Gy (ID 4322)

      14:20 - 15:50  |  Author(s): K. Wang

      • Abstract
      • Presentation
      • Slides

      Background:
      Radiation (RT) associated cardiac injury in patients with lung cancer is of unclear significance. RTOG 0617 demonstrated reduced overall survival (OS) with dose-escalated RT for Stage III NSCLC, with higher heart doses predicting for worse OS. We assessed the impact of heart doses on toxicity and survival for patients enrolled on several prospective RT dose-escalation trials.

      Methods:
      From 1996-2009, 133 patients with Stage III NSCLC (ECOG PS 0-1) were treated on six prospective trials using induction/concurrent chemotherapy and dose-escalated conformal RT to 70-90 Gy. Broad clinical outcomes (e.g. OS) were prospectively assessed. RT plans were reviewed, cardiac structures were defined, and dose/volume metrics were computed. Patient records were retrospectively reviewed for post-RT symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, and pericarditis). Baseline cardiac risk was calculated using the World Health Organization / International Society of Hypertension (WHO/ISH) score. A competing risks model accounting for the risk of death was used for statistical analysis.

      Results:
      112 patients were included in the final analysis. Median f/u was 19 mo. (75 mo. for the 39 patients without documented progression). Median OS and PFS were 22 and 12 mo. Median prescribed RT dose was 74 Gy. 15 patients (13%) had symptomatic cardiac events (6 pericardial effusion, 5 myocardial infarction, 2 unstable angina, 2 pericarditis) at median 26 mo. post-RT (range, 7-68). On univariate analysis, Heart mean dose (p=0.001), Heart V5Gy (p<0.001), and Heart V30Gy (p=0.002) were associated with symptomatic cardiac events, whereas baseline WHO/ISH score (p=0.204) and coronary artery disease (p=0.109) were not. Heart doses were higher in patients with vs without events (mean 22Gy vs 11Gy, V5Gy 60% vs 35%, V30Gy 35% vs 14%). On multivariate pair analysis accounting for baseline risk, heart doses remained significant predictors of cardiac events (e.g. Heart mean dose, p=0.001, HR 1.05 / 1Gy). 2-year competing risk-adjusted rate of symptomatic cardiac events was 11.1% vs 1.5% for Heart mean dose ≥15Gy vs <15Gy (p=0.003, HR 6.7). 34 patients (30%) had asymptomatic pericardial effusions. There was no association between heart doses and OS.

      Conclusion:
      Clinically significant symptomatic cardiac events following high-dose thoracic RT for Stage III NSCLC occurred in 13% of patients at a median 2 years post-RT, with the rate appearing to be heart dose dependent. RT-associated cardiac toxicity in the definitive treatment of Stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized. Supported in part by NIH grant CA69579.

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    P1.03 - Poster Session with Presenters Present (ID 455)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Radiology/Staging/Screening
    • Presentations: 1
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      P1.03-070 - The Impact of Advances in Systemic Staging on the Rate of Metachronous and Synchronous Metastases in Patients Lung Cancer (ID 4335)

      14:30 - 15:45  |  Author(s): K. Wang

      • Abstract
      • Slides

      Background:
      To quantify the impact of advances in systemic staging (i.e. from CT-based to PET-based over the last ≈ 20 years) on the rate of distant metastases detected at their time of initial diagnosis (synchronous) and sometime after initial diagnosis (metachronous) in patients with lung cancer.

      Methods:
      The Surveillance, Epidemiology, and End Results (SEER) data base, representing 10 % of the US population was used to analyze lung cancers from 1988-2008. (a) The fraction of patients with overt synchronous metastases at diagnosis was noted. (b) Among patients without overt metastasis at diagnosis, their 5-year mortality rate was taken as an estimate of their rate of metachronous metastasis (as most deaths were due to distant metastases). (c) The overall rate of metastases (synchronous + metachronous) amongst all patients was computed. (d) The fraction of all metastases detectable at initial diagnosis (synchronous / [synchronous + metachronous]) was computed. Rates were computed for patient cohorts diagnosed in different time intervals from 1988-2008, to reflect the use of different systemic staging methods over the 20-year interval.

      Results:
      (a) The rate of synchronous metastatic disease slowly increased from ≈ 53% in the earlier years to ≈ 55% in 2008. (b) Among patients without overt metastasis at diagnosis, the rate of metachronous metastatic disease slowly decreased from ≈ 73% in the earlier years to ≈ 62% in 2008. (c) If one assumes that most of the metachronous metastatic lesions were present (but covert) at the time of the initial diagnosis of the primary disease, then one can estimate that ≈ 83-87% of patients have micro/macro metastatic disease at presentation (this rate is basically unchanged over time, but small changes over time may reflect the impact of systemic chemotherapy). (d) Among all patients with metastatic disease, ≈ 60.4% of metastatic lesions were detectable clinically or with CT at the time of diagnosis in the pre-PET era, vs. ≈ 66.6% of these lesions being detectable clinically or with CT and/or PET in the PET era.

      Conclusion:
      The addition of PET appears to have a small but measurable impact on the rates of synchronous and metachronous metastasis, resulting in stage migration from metachronous to synchronous (i.e. from covert to overt) metastases at the time of diagnosis. The addition of PET to the pre-treatment evaluation increases the ability to detect metastatic disease by ≈ 6% (from 60.4 to 66.6%).

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    P1.06 - Poster Session with Presenters Present (ID 458)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.06-038 - Survival and Prognostic Factors of Oligometastatic Non-Small Cell Lung Carcinoma: A Single Center Experience (ID 5283)

      14:30 - 15:45  |  Author(s): K. Wang

      • Abstract

      Background:
      In patients without targeted mutations platinum-based chemotherapy is still current treatment method with a median survival rates of 8-11 months. Patients with single side oligo-metastatic disease should be consider for curative aggressive therapies for both primary and metastatic sides for better survival (NCCN 2016).

      Methods:
      Totally 19 oligo-metastatic NSCLC patients was evaluated retrospectively by using hospital database. All patients had single metastatic side.

      Results:
      Among 19 eligible patents there was male predominance (n= 16, 84.2%). Eight patients had co-morbidities requiring regular medication. Histopathological, there were 13 (68.4%) adenocarcinoma and 6 (31.6%) non-adenocarcinoma. While brain was the most common site for metastasis 10 (52.6%), it was followed by bone (n=6, 31.6%). Treatments for primary tumour side were surgery (n=6, 31.7%), concurrent CRT (n=5, 26.3%) and sequential CRT (n=1, 5.3%). Median follow-up for whole cases were 59.1 weeks. Median overall survival (OS) and progression free survival (PFS) were 140 (±33.7) and 76 (±24.2) weeks respectively. Progressions were observed mostly in 45.4. week. Univariate cox regression analyses for OS and PFS is indicated in Table 1. Clinical T and N staging had significant relation with OS (p=0.02 and 0.03 respectively). There was no relation between bone or brain metastasis and histopathology, gender, clinical T and N staging. Median survival after first progression (SAFP) was 63 weeks (±SS 29.05). Among study parameters only clinical T staging had significant relation with SAFP (p=0.026). Median SFAP was better in patients with progression of primary tumour however median OS was better in patients with progression of distant metastasis (p>0.05).

      Factor OS PFS
      Hazard Ratio p Hazard Ratio p
      Age (cut-off=65) 1.034 (0.18-5.1) 0.96 0.4 (0.1-2.2) 0.3
      Co-morbidity 2.3 (0.54-9.8) 0.24 3.4 (0.8-14) 0.07
      Brain Metastasis 0.88 (0.21-3.6) 0.86 1.5 (0.42-5.45) 0.52
      Histopathology (adeno vs non-adeno) 0.22 (0.03-1.4) 0.10 0.67 (0.16-2.8) 0.6
      Bone Metastasis 1.78 (0.43-7.31) 0.42 1.7 (0.47-6.6) 0.4
      pN Staging (n0 and N1-2) 0.12 (0-173) 0.21 0.94 (0.22-4.02) 0.94
      cT Staging 2.17 (1-4.7) 0.02 1.11 (0.73-1.81) 0.54
      cN Staging (n0 and N1-2) 2.3 (0.86-6.6) 0.03 1.77 (0.79-3.97) 0.1
      Non-surgical curative treatment 1.88 (0.41-8.52) 0.42 1.9 (0.50-7.38) 0.34
      Surgery 0.31 (0.06-1.65) 0.14 0.21 (0.02-1.78) 0.09


      Conclusion:
      Even oligo-metastatic NSCLC means stage 4 of disease, curative treatment approaches for both primary and metastasis sides can increase patients’ prognosis than other stage 4 cases. Similar to the existed retrospective studies we had OS more than 2 years and PFS more than 1 year.

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    P2.02 - Poster Session with Presenters Present (ID 462)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Locally Advanced NSCLC
    • Presentations: 1
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      P2.02-005 - A Rare Clinical Presentation Of EGFR-Mutant Non-Small Cell Lung Cancer With Oligo-Acrometastasis (ID 5278)

      14:30 - 15:45  |  Author(s): K. Wang

      • Abstract

      Background:
      44% of acrometastasis are originated from primary lung tumors and metastasis to digits is seen in 0.2% of patients with lung cancer. After clinical staging, amputation or radiotherapy are most often therapeutic options for pain palliation. We want to present an oligo-acrometastasis of fourth proximal phalanx of left hand from EGFR-mutant non-small cell lung cancer.

      Methods:
      A 58-year-old man was admitted with pain and swelling in fourth finger of his left hand (Figure 1A). Magnetic resonance imaging (MRI) of left upper extremity showed a destruction by a soft tissue measuring about 30x17 mm on the distal part of fourth proximal phalanx of left hand (Figure 1B-C). Three phase bone scan with technetium-99m methylene diphosphonate (MDP) revealed increased radiotracer uptake in the fourth finger. Diffuse increased uptake is seen at the left wrist secondary to the old fracture and trauma in both blood pool and metabolic phases and hypertrophic osteoartropathy in both tibia (Figure1E-F). Computed thorax tomography (CTT) revealed a 25x21 mm lobulated contour lesion in the posterior segment of right lower lobe (Figure 1H). CT-guided biopsy was performed and pathological examination showed non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS). A 24x27x24 mm mass with SUV-max value 9.85 in the right lower lobe, right tracheobronchial and right hilar lymphadenopathies 13 mm in diameter was detected (SUV-max: 7.51) on PET-CT. Patient was staged as T1bN2M1b with oligoacrometastasis. Figure 1



      Results:
      His finger was amputated from metacarpophalangeal level and surgery margin was negative for tumour. Pathological diagnosis was metastatic NSCLC-NOS harbouring EGFR-21L858R mutation. After curative treatment of acrometastasis, concurrent chemo-radiotherapy was planned for primary lung cancer as a therapeutic approach. He is still under treatment.

      Conclusion:
      Oligometastatic disease by acral involvement in NSCLC is extremely rare. Curative treatment approach should be consider for both primary tumour and metastasis side.