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Cheryl Houston-Harris



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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.05 - Characteristics & Survival of Resected Stage IV Non-Small Cell Lung Cancer (NSCLC) in the Mid-South Quality of Surgical Resection Cohort (ID 13381)

      14:00 - 14:05  |  Author(s): Cheryl Houston-Harris

      • Abstract
      • Presentation
      • Slides

      Background

      Surgical resection is potentially curative in subsets of oligometastatic NSCLC. We evaluated the characteristics and survival of resected stage IV NSCLC in a population-based cohort.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients were included who had curative-intent resections from 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions in the mid-Southern USA from 2009-2018. Statistical analyses were performed using univariate and multiple Cox regression models.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 3092 resections, 96 (3.1%) were stage IV: 38 M1a, 54 M1b, and 4 M1c. Of the M1a patients, 1 had a pleural effusion, 37 had a contralateral lung nodule. The most common sites of extrathoracic metastasis were bone (13 (13.5%)), and brain (25 (26%)). Other extrathoracic sites were distant lymph nodes, liver, adrenals, thyroid, pancreas, colon, soft tissue, and esophagus.

      Stage IV patients had a younger median age (63 vs 67 (p<0.0001)), less Medicare coverage but more Medicaid or Commercial insurance (p=0.0248), fewer comorbid conditions (p=0.0096), higher cT (p<0.0001), and higher-grade tumors (p=0.0002).

      58% (22) of M1a patients did not receive treatment to the site of metastatic disease, compared to 72% (39) and 75% (3) of M1b and M1c, respectively (p=0.0086).

      For patients with bone metastases, median/5 year survival was 1.28 years/0%, compared to 5.16 years/51% for all other metastatic sites and 6.39 years/56% for non-stage IV NSCLC (p=0.0058) (Figure 1). In fully adjusted models, survival for Stage IV patients without bone metastasis did not differ significantly from Stage I-III patients (HR: 1.3, p=0.15). However, Stage IV patients with bone metastasis had significantly worse survival (HR:3.2, p=0.0006).

      image001.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Bone metastasis connotes a very poor prognosis in patients with oligometastatic NSCLC, but survival of patients with other sites of metastasis was remarkably good in this highly selected group of patients from a population-based multi-institutional cohort.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.16-46 - A Population-Based Validation Study of the Proposed ‘R-Factor’ Classification in a Lung Cancer-Endemic Region of the US. (ID 13985)

      16:45 - 18:00  |  Author(s): Cheryl Houston-Harris

      • Abstract
      • Slides

      Background

      The IASLC has proposed a definition of completeness of surgical resection beyond margin status. We sought to validate the proposed classification in a US cohort, and evaluated the impact of a lymph node (LN) specimen collection kit on resection status.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The population-based Mid-South Quality of Surgical Resection cohort includes >95% of lung cancer resections in 4 contiguous US Dartmouth Hospital Referral Regions from 2009-2018. Resections were classified as Complete (R0), Uncertain (R[un]), or Incomplete (R1-R2) based on the proposed classifications. We evaluated overall survival (OS) using the Kaplan-Meier method and proportional hazards models. Adjusted models included age, sex, histology, extent of resection, pTNM categories, and co-morbidities. A subset of resections used a LN specimen collection kit.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 3,099 resections, 18% were R0, 76% R(un), and 6% R1-R2. 5-year OS was 69%/54%/35% for R0/R(un)/R1-R2 (p<0.0001, Figure 1A). Compared to R0, the increased hazard of death for R(un)/R1-R2 was 1.6/3.0 overall, 1.5/2.3 in node negative patients, 1.7/3.1 in node positive patients, and 1.5/1.9 in fully adjusted models (all p<0.0001).

      Of 2,351 R(un) resections, the highest mediastinal LN positive increased the hazard of death 1.6 times (vs. negative, p=0.0008). However, 626 (27%) had no mediastinal LN examined (MLE). R(un) resections with 0 MLE had 1.2 times the hazard of death compared to R(un) with >1 MLE (p=0.0212, Figure 1B).

      Use of the LN kit intervention resulted in R0 in 40% of cases, compared to 6% without the kit (p<0.0001). Kit cases had improved OS across the entire cohort (p=0.0002), but when restricted to R0 patients, OS did not differ based on kit use (p=0.96).

      figure 1 5-3-18 final.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      The proposed ‘R-factor’ classifications are prognostic. R(un) rates were high, but significantly lower in cases where a LN collection kit was used. Further delineation of R(un) cases based on MLE should be considered.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 949)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.17-11 - Pattern and Survival Impact of Neoadjuvant Treatment of Non-Small Cell Lung Cancer (NSCLC) in a Prospective Lung Resection Cohort (ID 14169)

      16:45 - 18:00  |  Author(s): Cheryl Houston-Harris

      • Abstract
      • Slides

      Background

      Neoadjuvant therapy may benefit locally-advanced NSCLC patients. We evaluated patterns of neoadjuvant therapy and the impact on stage-shift and survival.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All curative-intent NSCLC resections were collected from 12 hospitals in 4 contiguous Dartmouth Hospital Referral Regions in mid-Southern USA from 2009-2018. Comparisons made using Chi-square tests and non-parametric t-tests, survival impact assessed using Cox-proportional hazard models.

      4c3880bb027f159e801041b1021e88e8 Result

      182 of 3,297 resections (5.5%) had neoadjuvant therapy: 118 (64.8%) chemoradiation, 47 (25.8%) chemotherapy, and 17 (9.3%) radiation. Neoadjuvantly treated patients were younger, more likely to be commercially insured, have immediate preoperative brain MRI, and invasive mediastinal staging than those with primary resection (p<0.001 for all, Table 1). They also had more advanced stage, but 27% were clinical stage IA/IB.

      Despite evidence of more difficult surgery, perioperative complications, hospital length of stay and postoperative mortality rates were similar to the primary resection cohort. Despite delay to surgery, they had significantly greater down-staging (p<0.001). However, down-staging had no impact on survival, regardless of type of neoadjuvant therapy (Table 2).

      Table 1. Demographic and clinical characteristics between patients who received neoadjuvant therapy and those who did not.

      Demographic Variables

      Neoadjuvant Therapy

      Primary Resection Only

      N

      N=182

      N=3115

      Race (p: 0.0324)

      Caucasian

      125 (69)

      2425 (78)

      Black or AA

      56 (31)

      651 (21)

      Asian

      0 (0)

      16 (1)

      AI/AN

      0 (0)

      2 (0)

      Other/NR

      1 (1)

      19 (1)

      Age (p: <0.001)

      63 (56, 69)

      68 (61, 74)

      Sex (p: 0.4323)

      Male

      104 (57)

      1686 (54)

      Female

      78 (43)

      1427 (46)

      Insurance (p: <0.001)

      Medicare

      45 (25)

      1417 (45)

      Medicaid

      42 (23)

      438 (14)

      Commercial

      91 (50)

      1148 (37)

      Self/ None

      4 (2)

      112 (4)

      Non-Invasive Staging

      CT Scan ϯ

      135 (74)

      2879 (92)

      PET/CT ϯ

      106 (58[RO2] )

      2553 (82)

      Brain Scan (p: <0.001)

      98 (54)

      877 (28)

      Invasive staging tests (p: <0.001)

      No

      144 (79)

      2778 (89)

      Yes

      38 (21)

      337 (11)

      Histology (p: <0.001)

      Adenocarcinoma

      65 (40)

      1547 (54)

      Squamous

      57 (35)

      985 (34)

      Other including but limited to Adenosqamous, large cell, carcinomas, and other

      40 (22)

      339 (11)

      Grade (p: <0.001)

      Well/Moderately

      50 (30)

      1684 (54)

      Poorly/Undifferentiated

      60 (33)

      1040 (34)

      Not Reported

      66 (36)

      390 (13)

      Tumor Size (p: 0.50312)

      <= 3 cm

      123 (68)

      1984 (64)

      >3-5 cm

      36 (20)

      733 (24)

      >5-7 cm

      17 (9)

      255 (8)

      >7 cm

      6 (3)

      143 (5)

      8th Clinical T (p: <0.001)

      Tx

      0 (0)

      2 (0)

      T0

      14 (8)

      184 (6)

      Tis

      1 (1)

      0 (0)

      T1a(mi)

      0 (0)

      1 (0)

      T1b

      25 (14)

      865 (28)

      T1c

      24 (13)

      621 (20)

      T2a

      27 (15)

      521 (17)

      T2b

      18 (10)

      201 (6)

      T3

      39 (22)

      321 (10)

      T4

      25 (14)

      228 (7)

      T1a

      5 (3)

      156 (5)

      Insufficient Records

      3 (2)

      11 (0)

      8th Clinical N (p: <0.001)

      Nx

      0 (0)

      1 (0)

      N0

      130 (71)

      2709 (87)

      N1

      13 (7)

      196 (6)

      N2

      35 (19)

      176 (6)

      N3

      1 (1)

      20 (1)

      Insufficient

      3 (2)

      9 (0)

      8th Clinical M (p: <0.001)

      M0

      131 (73)

      2525 (87)

      M1a

      9 (5)

      116 (4)

      M1b

      30 (17)

      208 (7)

      M1c

      9 (5)

      61 (2)

      8th Clinical Stage (p: <0.001)

      Occult Carcinoma

      0 (0)

      2 (0)

      Stage 0

      13 (7)

      167 (5)

      Stage IA1

      2 (1)

      141 (5)

      Stage IA2

      15 (8)

      807 (26)

      Stage IA3

      12 (7)

      537 (17)

      Stage IB

      21 (12)

      424 (14)

      Stage IIA

      10 (5)

      160 (5)

      Stage IIB

      29 (16)

      373 (12)

      Stage IIIA

      41 (23)

      364 (12)

      Stage IIIB

      15 (8)

      63 (2)

      Stage IVA

      0 (0)

      3 (0)

      Stage Unknown

      21 (12)

      59 (2)

      Extent of resection (p: <0.001)

      Pneumonectomy

      24 (13)

      174 (6)

      Bilobectomy

      13 (7)

      145 (5)

      Lobectomy (+/-wedge)

      131 (72)

      2338 (75)

      Segmentectomy(+/-wedge)

      4 (2)

      146 (5)

      Wedge

      10 (5)

      307 (10)

      Surgical Technique (p: 0.1280)

      Open

      124 (68)

      1926 (62)

      RATS

      39 (21)

      701 (23)

      VATS

      19 (10)

      484 (16)

      Margin Status (p: <0.001)

      Positive

      15 (8)

      142 (5)

      Negative

      152 (84)

      2880 (93)

      Not Reported

      15 (8)

      88 (3)

      Peri- and Post-Operative Characteristics

      Surgery duration (in minutes, med, IQR) (p: 0.0172)

      156 (109, 221)

      135 (97, 186)

      Estimated blood loss (CCs, med, IQR) (p: <0.001)

      250 (100, 500)

      150 (100, 300)

      Duration of chest tube (in days, med, IQR) (p: 0.1364)

      4 (2, 6.5)

      4 (3, 7)

      ICU duration (in days, med, IQR) (p: 0.0282)

      2 (1, 3)

      1 (1, 3)

      Hospital duration (in days, med, IQR) (p: 0.7868)

      6 (4, 9)

      6 (4, 9)

      Rate of blood transfusions (p: <0.001)

      38 (21)

      215 (7)

      Rate of cardiac arrhythmias (p: 0.8513)

      27 (15)

      478 (15)

      Rate of any post-op complications (p: 0.1323)

      102 (56)

      1567 (50)

      Rate of ICU re-admittance prior to discharge (p: 0.0560)

      14 (8)

      143 (5)

      Rate of hospital re-admittance within 30 days (p: 0.1285)

      29 (17)

      378 (13)

      Clinical to pathologic T-Category Migration (<0.001)

      Down stage

      76 (42)

      742 (24)

      No change

      40 (22)

      1019 (33)

      Up stage

      66 (36)

      1354 (43)

      Unknown

      0 (0)

      0 (0)

      Clinical to pathologic N Category Change (p: <0.001)

      Down stage

      48 (26)

      566 (18)

      No change

      112 (62)

      2122 (68)

      Up stage

      22 (12)

      422 (14)

      Unknown

      0 (0)

      1 (0)

      Clinical to pathologic aggregate stage Migration (p: <0.001)

      Down stage

      89 (49)

      879 (28)

      No change

      49 (27)

      953 (31)

      Up stage

      41 (23)

      1268 (41)

      Unknown

      3 (2)

      11 (0)

      Postoperative Mortality Rates

      30 Day (p: 0.5109)

      11 (6)

      154 (5)

      60 Day (p: 0.4222)

      16 (9)

      224 (7)

      90 Day (p: 0.2216)

      22 (12)

      291 (9)

      120 Day (p: 0.1850)

      26 (14)

      345 (11)

      ϯ CT and PET/CT scan are after neo-adjuvant therapy for neoadjuvant patients.

      Table 2. Survial impact of downstaging among neo-adjuvant patients.

      Prediction Variables

      Hazard Ratio

      95% Confidence Interval

      P-value

      T-category

      Up-staged vs Down-staged

      1.69

      0.955, 2.977

      0.0715

      No change vs Down-staged

      1.64

      0.971, 2.4757

      0.0642

      N Category (among all patients)

      Up-staged vs Down-staged

      0.73

      0.45, 1.20

      0.2191

      No change vs Down-staged

      1.26

      0.62, 2.58

      0.5270

      N Category (among clinical N2 disease patients)

      Up-staged vs Down-staged

      NA

      NA

      NA

      No change vs Down-staged

      1.44

      0.47, 4.43

      0.5261

      NA – not applicable due to small sample size

      8eea62084ca7e541d918e823422bd82e Conclusion

      Neoadjuvant therapy was safe, but had no survival impact in this cohort, despite increased down-staging, possibly because of an inexplicably high proportion of stage I patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.16-32 - Survival Implications and Factors Associated with the Anatomic Level of Incomplete Non-Small-Cell Lung Cancer (NSCLC) Resection (ID 13589)

      16:45 - 18:00  |  Author(s): Cheryl Houston-Harris

      • Abstract
      • Slides

      Background

      Incomplete resection impairs NSCLC survival, but the relative significance of specific anatomic levels of margin involvement is uncertain. We examined the survival implications of the anatomic level of margin positivity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We analyzed curative-intent primary NSCLC resections from 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions in West Tennessee, East Arkansas, and North Mississippi from 2009-2018. Overall survival (OS) was evaluated with Kaplan-Meier estimates and hazard ratios (HR) from Cox models.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 3097 resections, 137 (4.4%) had positive margins. The anatomic sites of margin positivity were: mainstem bronchus 28%; peribronchial margin 24%; chest wall margin 21%; lung tissue margin 12%; great vessels 1%; mediastinum 2%; bronchial carcinoma in-situ 1%; not reported 11%.

      Compared to patients with negative margins, positive margins were more likely in patients who were male (66% v 51%, p=0.0003), had poorly/undifferentiated tumor grade (45% v 34%, p=0.0143), squamous NSCLC (46% v 33%, p=0.0111), or multi-lobar tumors (15% v 5%, p<.0001). Higher pT (p<.0001) and pN (p<.0001), larger tumor size (4.2cm v 3.0cm, p<.0001), a pneumonectomy (16% v 6%, p<.0001), and an open thoracotomy (77% v 60%, p=0.0004) were also associated with margin positive resections.

      5-year OS varied by the anatomic site of the margin: mainstem bronchus 35%; peribronchial margin 44%; chest wall margin 22%; lung tissue margin 23%. On unadjusted regression, positive margins at mainstem bronchial (HR=1.98, p=0.0041), chest wall (HR=2.82, p<.0001), or lung tissue (HR=2.92, p=0.0007) had a negative prognostic impact. Positive margins at chest wall (aHR=1.66, 0.0310) and lung tissue margins (aHR=2.24, p=0.0137) had the most significant prognostic impact after controlling for age, sex, race, histology, primary site, tumor grade, cT, cN, and adjuvant chemo/radiation (Table).

      table.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Incomplete NSCLC resection at the chest wall or the lung tissue margins connotes worse survival than other anatomic sites of margin involvement.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P2.16-38 - Characteristics of Preoperative N Staging in Patients with Optimal Pathologic N Staging of Non Small Cell Lung Cancer(NSCLC) (ID 14345)

      16:45 - 18:00  |  Author(s): Cheryl Houston-Harris

      • Abstract
      • Slides

      Background

      Despite its prognostic value, the thoroughness of clinical and pathologic nodal staging varies significantly. We compared anatomic preoperative nodal sampling details to anatomic surgical lymphadenectomy details in resections meeting National Comprehensive Cancer Network (NCCN) quality criteria.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients had curative-intent NSCLC resections between 2009-2018 in 12 hospitals in 4 contiguous Dartmouth Hospital Referral Regions in the mid-Southern USA. Univariate statistics were calculated to summarize characteristics.

      4c3880bb027f159e801041b1021e88e8 Result

      1,346 of 3,297 resections (40.8%), met all 4 NCCN criteria (anatomic resection, negative margins, examination of >0 N1 nodes and ≥3 mediastinal stations). Of these 1,346, 1,114 (83%) received PET/CT scans and 148 (11%) received invasive nodal staging (all had EBUS/EUS/TBNA; 10 [16%] also had mediastinoscopy). Among 148 invasively staged patients, 72% were histologically node-negative, 19% were node-positive; 34 (23%) were down-staged and 20 (13.5%) were up-staged after surgery. Stations 4 (70.3%), 7 (73.6%), and 10 (33.8) were most frequently sampled preoperatively, 4, 7 and 9 intraoperatively (Table 2). Except for station 7, there was little overlap in anatomic station examination between invasive clinical and pathologic nodal staging.

      Table 1. Preoperative characteristics among those patient with NCCN quality resections.

      Variables

      NCCN Met

      N (%)

      N

      1346 (40.8)

      PET/CT scan

      1114 (83)

      Invasive staging

      148 (11)

      EBUS/EUS/TBNA

      148 (100)

      Mediastinoscopy

      10 (16)

      Results of invasive staging (n=148 )

      Conclusive, benign

      106 (72)

      Conclusive, malignant

      28 (19)

      Inconclusive/Results not found

      14 (9)

      Clinical* to pathologic N category change among those receiving invasive staging (n=148)

      Up-stage

      20 (13.5)

      No Change

      94 (63.5)

      Down-stage

      34 (23)

      *Clinical stage includes findings on PET/CT scan

      Table 2. Sampling information during invasive staging and surgical resections.

      Sampled during invasive staging

      N=148 (100%)

      Sampled during surgery

      N=148 (100%)

      Stations Resampled

      N (%)

      Stations not Resampled

      N (%)

      Stations Sampled

      Station 2L

      5 (3.4)

      5 (3.4)

      2 (1.4)

      6 (4.1)

      Station 2R

      14 (9.5)

      57 (38.5)

      9 (6.1)

      53 (35.8)

      Station 3a

      4 (2.7)

      3 (2)

      3 (2)

      1 (0.7)

      Station 3p

      1 (0.7)

      2 (1.4)

      1 (0.7)

      1 (0.7)

      Station 4L

      66 (44.6)

      52 (35.1)

      38 (25.7)

      42 (28.4)

      Station 4R

      91 (61.5)

      90 (60.8)

      66 (44.6)

      49 (33.1)

      Station 5

      7 (4.7)

      59 (39.9)

      7 (4.7)

      52 (35.1)

      Station 6

      2 (1.4)

      43 (29.1)

      2 (1.4)

      41 (27.7)

      Station 7

      113 (76.4)

      140 (94.6)

      109 (73.6)

      35 (23.6)

      Station 8

      3 (2)

      94 (63.5)

      2 (1.4)

      93 (62.8)

      Station 9

      6 (4.1)

      108 (73)

      5 (3.4)

      104 (70.3)

      Station 10R

      39 (26.4)

      57 (38.5)

      20 (13.5)

      41 (27.7)

      Station 10L

      24 (16.2)

      81 (54.7)

      30 (20.3)

      60 (40.5)

      N2-NOS

      1 (0.7)

      24 (16.2)

      0 (0)

      25 (16.9)

      Station 11L

      18 (12.2)

      7 (4.7)

      1 (0.7)

      23 (15.5)

      Station 11R

      21 (14.2)

      14 (9.5)

      5 (3.4)

      25 (16.9)

      Station 12L

      0 (0)

      5 (3.4)

      0 (0)

      5 (3.4)

      Station 12R

      1 (0.7)

      2 (1.4)

      0 (0)

      3 (2)

      Station 13R

      0 (0)

      4 (2.7)

      0 (0)

      4 (2.7)

      N1-NOS

      0 (0)

      103 (69.6)

      0 (0)

      103 (69.6)

      8eea62084ca7e541d918e823422bd82e Conclusion

      In a pathologic well-staged cohort of NSCLC recipients, invasive clinical nodal staging was infrequently and less-than-thoroughly used.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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