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Lung Cancer > NSCLC > Flashcards

NSCLC Flashcards

1
Q

PACIFIC: What phase?

A

Phase III

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2
Q

PACIFIC: How many pt’s w/ NSCLC have stage III disease?

A

1/3

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3
Q

PACIFIC: Median PFS in pt’s w/ locally advanced NSCLC after chemoRT only?

A

~8 mos

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4
Q

PACIFIC: What is Durvalumab and what is it’s MoA?

A

Monoclonal Ab

Prevents PD-L1 binding to PD-1 and CD80, allowing NK cells and T cells to kill tumor cells

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5
Q

PACIFIC: Dose of Durvalumab used?

A

10 mg/kg

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6
Q

PACIFIC: Durvalumab schedule?

A

Every 2 weeks for up to 12 mos

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7
Q

PACIFIC: What were some secondary endpoints reported?

A

PFS at 12 and 18 mos
Duration of response
Time to death or mets

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8
Q

PACIFIC: Pt characteristics?

A

Avg age ~64
Male: ~70%
Non-smoker ~9%
Induction chemo ~ 30%

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9
Q

PACIFIC: Reported PFS?

A

Placebo: 5.6 mos
Durvalumab: 17.2

~11 mo PFS benefit

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10
Q

PACIFIC: PFS at 12 and 18 mos?

A

Placebo: ~35% (12 mos) and ~27% (18 mos)
Durvalumab: ~55% (12 mos) and ~44% (18 mos)

Durable effect w/ Durvalumab

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11
Q

PACIFIC: What was surprising about the results as they pertain to subgroups?

A

Benefit shown in both smokers and non smokers
Benefit independent of PD-L1 expression
Lower rate of brain mets w/ Durvalumab (6% vs. 12%)

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12
Q

PACIFIC: Most common AE’s w/ Durvalumab

A
  • Diarrhea
  • Radiation pneumonitis
  • Rash
  • Pruritis

Side effects easily manageable

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13
Q

PACIFIC: OS @ 12 and 24-months

A

Placebo: 75% (12 mo); ~55% (24 mo)
Durvalumab: ~80% (12 mos); ~66% (24 mos)

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14
Q

PACIFIC: Frequency of new lesions?

A

Placebo: ~33%
Durvalumab: 22%

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15
Q

PACIFIC: Incidence of brain mets

A

Placebo: ~12%
Durvalumab: ~6%

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16
Q

PACIFIC: Time to death or distant mets?

A

Placebo: 15 mos
Durvalumab: ~24 mos

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17
Q

RTOG 0617: Which phase?

A

Phase III

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18
Q

RTOG 0617: Randomization?

A
  • 2x2
    1. 60 vs 72 Gy
    2. w/ vs w/o cetuximab

0617 → 60 vs. 72

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19
Q

RTOG 0617: RT Regimen?

A 
2 Gy fx's
5 days/week
99% of PTV >93% dose
Motion Management required
NO Elective nodal irradiation
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20
Q

RTOG 0617: Chemotherapy Regimen?

A

Carbo/taxol

During RT:
Paclitaxel: 45 mg/m2 per week
Carboplatin: AUC 2 per week

After RT: Consolidative chemo 2 weeks post-RT for 2C
Paclitaxel: 200 mg/m2
Carboplatin: AUC 6

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21
Q

RTOG 0617: Immunotherapy regimen?

A

Cetuximab given during RT and consolidation

Loading dose (1 week prior to chemoRT): 400 mg/m2
Weekly: 250 mg/m2
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22
Q

RTOG 0617: Primary Outcome?

A

OS

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23
Q

RTOG 0617: Secondary end-points?

A

PFS
Toxicity
QoL
Biological marker status vs. clinical outcome

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24
Q

RTOG 0617: How many pts?

A

~500

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25
Q

RTOG 0617: What’re the main findings?

A

74 Gy vs. 60 Gy might worsen OS: ~20 mos vs. 29 mos

Cetuximab: 25 mos w/ and 24 mos w/o

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26
Q

RTOG 0617: What’re the findings w/ respect to cetuximab and EGFR expression?

A

EGFR H score < 200: OS 20 w/ vs. 30 mos w/o

EGFR H score > 200: OS 42 w/ vs. 21 mos w/o

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27
Q

RTOG 0617: What’re some possible reasons for decreased OS in the high-dose group?

A

More common tx-related deaths
Concurrent chemo more difficult to complete
RT planning more likely to be non-compliant
Higher heart V5 and V30 predict patient death

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28
Q

RTOG 0617: Pt characteristics?

A

Median Age: 64
More men than women
Non-smokers: 4-7%

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29
Q

Does heterogeneity on or off deliver more doses at the center of the PTV? What about the periphery?

A
  • More Dose:
    – Center: Heterogeneity off
    – Periphery: Heterogeneity on
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30
Q

What was the size cut-off for tumors included in the SBRT trial RTOG 0236 for NSCLC?

A

≤ 5 cm

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31
Q

What was the fx used in RTOG 0236?

A
  • 18 Gy x 3 fx

##

Hook: 6*3 = 18!

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32
Q

What were the GTC → CTV, and CTV → PTV expansions used in RTOG 0236 and 0813?

A
  • GTV → CTV = 0 cm
  • CTV → PTV
    – no 4D-CT: 1 cm CC, 0.5 cm rad
    – 4D-CT: 0.5 cm geometric
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33
Q

What were the main findings of RTOG 0236?

A
  • 3-yr LCR: 91%
  • 3-yr regional control rage: 87%
  • 3-yr disseminated failure: 22%
  • 3-yr OS: 56%
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34
Q

What fx was used in RTOG 0813?

A

Dose-escalation trial for central tumors
- 10 Gy x 5 fx
- 10.5 Gy x 5 fx
- 11 Gy x 5 fx
- 11.5 Gy x 5 fx
- 12 Gy x 5 fx

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35
Q

Is there evidence for SBRT being safe for lung tumors > 5 cm?

A

Yes, but it is currently limited to single institutional experiences

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36
Q

What kind of resection techniques were tested in LCSG 821 (Ginsberg et al., 1995) surgical trial and what were the main findings?

A
  • Sublobar resection (2 cm margin around the tumor) vs. lobectomy
    – LR: 82% vs. 94% (SS)
  • These findings established lobectomy as the minimum acceptable standard
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37
Q

What were the findings of the pooled analysis of ROSEL and STARS trials re. surgery vs. SABR for early-stage NSCLC?

A
  • SABRT vs. surgery:
    – 3-yr OS: 95% vs. 79% (SS)
    – 3-yr EFS: 86% vs. 80% (SS)
    – No differences in LRR, or DM
  • Limited FU, so more data is needed before making conclusions about the superiority of OS w/ SABR. Additionally, some series have shown the opposite.
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38
Q

What is the threshold for LN- NSCLC primary tumor size for adj. CHT to be recommended?

A

> 4 cm

39
Q

How much OS benefit is attributed to the addition of CHT per the LACE MA?

A
  • 5% at 5 yrs
40
Q

What is the recommended prophylaxis for pts w/ a contrast allergy undergoing CT sim w/ IV contrast?

A
  • Steroid + Anti-histamine
  • Oral prednisone: 50 mg at 13, 7, and 1 hour prior to contrast administration (pediatrics: 0.5-0.7 mg/kg)
  • Diphenhydramine: 50 mg 1 hour prior to contrast administration (pediatrics: 1.25 mg/kg)
41
Q

How is epinephrine administered in someone experiencing an allergic rx to IV contrast?

A
  • Epinephrine administration (IM preferred)
    – Adults (>25 kg): 0.3 mg IM (1mg/ml)
    – Children (10-25 kg): 0.15 mg IM (1mg/ml)
    – Infants (<10 kg): 0.1 mg IM (1mg/ml)
  • Epinephrine administration (IV if refractory to 2 IM doses)
    – Adults (>25 kg): 0.1 mcg/kg/min and increased every two to three minutes by 0.05 mcg/kg/minute until blood pressure and symptoms improve
    – Infants and children (<25 kg): 0.1 to 1 mcg/kg/minute and titrated to blood pressure
42
Q

What are the steps in the initial management of an IV contrast allergy?

A
  • Calling code team
  • Provide supplemental oxygen
  • Obtain IV access
  • Epinephrine administration
43
Q

What SBRT fx regimen did RTOG 0915 compare and what were its mail findings?

A
  • 34 Gy in 1 fx vs. 48 Gy in 4 fx
  • 5-yr LF: 10.6% vs. 6.8%
  • Gr 3+ tox: 2.6% vs. 11.1%
44
Q

Is PORT SOC for occult N2 disease found at the time of resection?

A
  • Questionable (PORT improves LRR but not DFS or OS, per LungART trial)
  • Can be considered in select cases
    – +margins
    – Gross residual disease

LungART → Lung Adjuvant RT

45
Q

What kind of RT dosing can be considered for PORT for N2 NSCLC s/p resection?

A
  • PORT for N2 disease:
    – R1 resection: 50-54 Gy
    – +ECE: 54-60 Gy
    – R2 resection: 60-66 Gy
46
Q

What kind of imaging FU is recommended after lung SBRT?

A
  • CT Chest w/wo contrast q 6-12 mos x 2 yrs
  • A PET scan is not currently recommended as persistent inflammation after SBRT may make the results harder to interpret
47
Q

What is the risk of isolated nodal failure when using PET/CT to plan RT to involved nodal stations as opposed to elective nodal RT?

A
  • ~ 5%
  • Due to the low risk of isolated nodal failure w/ just involved nodal RT, elective nodal RT is not recommended.
48
Q

What were the findings of the TROG 09.02 CHISEL trial for peripherally located NSCLC randomized to SBRT (54/3 or 48/4) vs. CFRT (66/33 vs. 50/20)?

A
  • SBRT (54/3 or 48/4) vs. CFRT (66/33 vs. 50/20)
    – LC: 89% vs. 65% (SS)
    – Median OS: 5 yrs vs. 3 yrs (SS)
    – 2-year OS: 77% vs. 59%
49
Q

What is defined as a centrally-located tumor?

A

Tumor within 2 cm of the proximal bronchial tree

50
Q

Is there any difference in outcomes b/w QD vs. QOD scheduled for lung SBRT?

A

No, per Samson et. al, PRO 2018

51
Q

How many w/ presumed early-stage NSCLC are upstaged at the time of surgery?

A
  • 25%-33%
  • This makes direct comparisons w/ RT/SBRT difficult, as those pts are only clinically staged
52
Q

What are the main tox differences b/w 3D CRT vs. SBRT?

A

3D CRT is a/w more cardiopulmonary tox

53
Q

When may segmentectomy instead of lobectomy be performed for early-stage NSCLC?

A

Per NCCN
- ≤ 2 cm → segmentectomy
- > 2 cm → lobectomy

54
Q

What is the rate of Gr ≥ 3 tox for centrally-located tumors w/ lung SBRT?

A
  • 28% (RTOG 0236)
  • 56% (Timmerman, JCO, 2006)
55
Q

What is the 5-yr OS for pts w/ severe COPD?

A
  • ~ 70%
  • Therefore, curative tx should still be pursued for this patient pop
56
Q

How does RFA compare to SBRT w/regard to LC?

A
  • RFA has superior LC
57
Q

When can RFA be considered for early-stage NSCLC? What is the most sig. risk?

A
  • Size ≤ 3cm
  • Sig. risk of pneumothorax requiring CT placement
58
Q

Is there any FEV1 cut-off for SBRT?

A

No, unlike surgery

59
Q

What is the approach to the management of solitary pulmonary nodules?

A
  • < 6 mm
    – No high-risk factors: No fu needed
    – High-risk factors: Repeat CT at 12 mos
  • 6-8 mm
    – At least one follow-up CT scan at 6-12 mos.
    – If stable, pts with high-risk factors should repeat the CT scan at 18-24 mos.
  • High-risk factors regardless of size
    – Repeat CT in 6-12 mos.

##

High risk factors:
- Personal hx of smoking
- Hx of lung cancer in a first-degree relative
- Exposure to asbestos, radon or uranium

60
Q

What is the annual risk of a 2nd lung primary in a pt w/ NSCLC?

A

1-2%

61
Q

What is the annual risk of a 2nd lung primary in a pt w/ SCLC?

A

6%

62
Q

What are the NCCN guidelines for SABR dose regimens for lung cancers?

A
  • 25-34 Gy (1 fx)
    – Peripheral, small (< 2cm) tumors, especially > 1 cm from the chest wall
  • 45-60 Gy (3 fx)
    – Peripheral tumors > 1 cm from the chest wall
  • 48-50 Gy (4 fx)
    – Central or peripheral tumors < 4-5 cm, especially < 1cm from the chest wall
  • 50-55 Gy (5 fx)
    – Central or peripheral tumors, especially < 1cm from chest wall
  • 60-70 Gy (8-10 fx)
    – Central tumors
63
Q

Which isodose line is the dose rx to for Linac-based SBRT/SABR?

A

80%

64
Q

What is the standard neoadjuvant radiation dose and concurrent CHT for NSCLC undergoing neoadj. CRT prior to resection?

A
  • RT Dose: 45 Gy / 25 fx
  • CHT: Carbo/taxol
65
Q

Per RTOG 0617, which dosimetric parameter is a/w ≥ Gr 3 pneumonitis for locally advanced lung cancer?

A

Lung V20

66
Q

For a pt receiving CRT per RTOG 0617 trial, what CHT is used and what is the regimen?

A
  • Paclitaxel (45 mg/m2/wk)
  • Carboplatin (AUC=2/wk) on days 1, 8, 15, 22, 29, and 36
67
Q

What were the main findings of the RTOG 0214 trial, which randomly assigned patients to PCI (30 Gy in 15 fx) or observation post definitive CRT?

A
  • PCI vs. Obs:
    – 5-yr brain met rates: 16.7% vs. 28.3%, SS
    – At the cost of a decline in memory (immediate and delayed recall) at 1 yr
    – 5-yr DFS: 19% vs. 16.1%, SS
    – 5-yr OS: 24.7% vs. 26%, NS

##

RT Dose (30/15) → ~5yr brain met rates (30 vs. 15)

68
Q

What are the symptoms of Pancoast syndrome?

A
  • Brachial plexopathy
  • Pain in the shoulder and ulnar distribution in the arm
  • Horner’s syndrome
    – Horner’s syndrome is caused by disruption of the ascending cervical sympathetic chain
    – Sx include miosis, ptosis, anhidrosis, and enophthalmos
69
Q

What is the SOC for a Pancoast tumor?

A
  • NACRT
    – CHT x 2C: cisplatin 50mg/m2 and etoposide 50mg/m2
    – RT (45 Gy in 25 fx)
  • Surgical resection
  • Adj CHT x 2C

##

Pancoast → cisplatin + etopoide
Rusch et al. INT 0160/SWOG 9416 JCO 2007

70
Q

What are the 5-yr outcomes survival outcomes for pts w/ pancoast tumors s/p SOC tx (NACRT → Resection → Adj. CHT)?

A

5-yr OS
- All: 44%
- Complete resection: 54%

##

Rusch et al. INT 0160/SWOG 9416 JCO 2007

71
Q

What was the randomization and results of CheckMate 816 for NSCLC?

A
  • Stage IB-IIIA NSCLC randomized to:
    1. Neoadjuvant nivolumab w/ platinum-doublet chemotherapy
    2. Platinum-based chemotherapy alone (every 3 weeks for three cycles)
  • Results: Niv + CHT vs. CHT alone
    – EFS: 31.6 mos vs. 20.8 months (SS)
    – pCR: 24.0% vs. 2.2% (SS)
    – Most benefit in:
    — Stage IIIA
    — PDL1 > 1%
    — non-SqCC
72
Q

What’s the mnemonic for immune checkpoint inhibitors and their targets?

A
  • NP, ADd IT
    – PD-1: Nivolumab, Pembrolizumab
    – PD-L1: Atezolizumab, durvalumab
    – CTLA-4: Ipilimumab, Tremelimumab
73
Q

What was the pt population, randomization, and results of RTOG 7301 for locally advanced NSCLC?

A
  • Stage III NSCLC randomized to
    – 40 Gy split course (20 Gy/5 fx, 2-week break, then another 20 Gy/5 fx)
    – 40 Gy, 50 Gy, or 60 Gy given 5 fx/week.
  • Results:
    – 2-yr OS: 10-18% with split course giving worst rates.
    – Response was better in 50 and 60 Gy arms.
  • Conclusion: 60 Gy is the standard dose.
74
Q

What were the main findings of RTOG 0617, a trial for stage III NSCLC randomized to 60 Gy vs. 74 Gy w/ concurrent CHT ± cetuximab?

A
  • 60 Gy had better control, numerically
  • 74 Gy was more harmful and offered no benefit
  • Cetuximab added no benefit
75
Q

Which dosimetric factor is most predictive of developing esophagitis for pts undergoing concurrent CRT for NSCLC?

A

The volume of esophagus receiving 60 Gy

76
Q

What are the usual esophageal constraints for pts undergoing CRT for NSCLC?

A
  • V60 < 17%
    – > 60 Gy has been reliably linked to esophagitis
  • Mean esophageal dose < 34 Gy (17 x 2)
77
Q

Can N2 nodal staging for lung cancer be based on PET/CT alone?

A
  • No, it requires path confirmation via mediastinoscopy, mediastinotomy, EBUS, EUS, or CT-guided bx
  • ~ 25% false negative rates
78
Q

What is the % risk reduction in DFS for pts w/ EGFR-mutant NSCLC s/p resection w/ osimertinib x 3 yrs (ADAURA Trial)?

A
  • Osimertinib vs. placebo
    – 24-mo DFS: 88% vs. 32% (SS)
    – 88% ↓ in recurrence or death
79
Q

What was the pt population, randomization, and findings of the INT 0139 trial for NSCLC?

A
  • Pts: Stage III (T1-3, N2) randomized to
    1. Definitive CRT to 61 Gy vs.
    2. Neoadjuvant CRT to 45 Gy.
      – CHT: Cisplatin and etoposide x4C for both
      – in arm 2, pts w.o evidence of progression went on to receive surgery
  • Results: trimodality vs. bimodality
    – 5-yr OS: 27% vs. 20% (NS)
    – Subgroup analysis: Pts ho only required lobectomy vs. bimodality tx
    – 5-yr OS: 36% vs. 18%
    – Pts who required pneumonectomy had high rates of peri-operative mortality

##

Memory Hook: 0139: 3-modality tx

80
Q

What are the current USPTF guidelines for lung cancer screening:

A
  • Age 50-80
    – ≥ 20 yr smoking hx
    – Active smokers or quit within the last 15 yrs
81
Q

What was the pt population, randomization, and results of RTOG 9410 for NSCLC?

A
  • 3 arms:
    1. CHT → RT
    2. CRT
    3. CRT w/ different CHT and RT dosing
  • Results: 1 vs. 2 vs. 3
    – 5-yr OS: 10% vs. 16% vs. 13% (SS)
82
Q

What is the most important prognostic indicated for a lung cancer pt undergoing def. tx?

A
  • KPS: Most important
  • Age > 60-70
  • Advanced pretreatment stage
  • Weight loss (>5% past 6 months)
  • Pleural effusion
83
Q

What’s the order for the main superior branches of the aortic arch?

A

“Beyonce Cant Sing”
- Brachiocephalic Trunk
- Common Carotid
- L Subclavian

84
Q

Which CHT regimen is better for CRT for NSCLC, EP (etoposide, cisplatin) or PC (paclitaxel, carboplatin)?

A
  • They are both equivalent
  • EP may have a numerically higher OS, but not SS (Liang et al. Ann Oncol 2018)
  • EP may have a higher rate of ≥ Gr 3 esophagitis
  • PC may have a higher rate of ≥ Gr 3 radiation pneumonitis
85
Q

For pts undergoing def CRT for lung cancer, what is the contralateral lung constraint?

A
  • Lung V20 < 30%
    – Yields a <20% risk of sx pneumonitis

##

QUANTEC

86
Q

What is the incidence of ≥ Gr 2 pneumonitis broken down by the doses delivered to the lungs?

A
87
Q

Which paraneoplastic syndromes are a/w NSCLC (SqCC)?

A

Hypercalcemia from PTH-related peptide (PTHrP)

88
Q

What benefit does adding pembrolizumab to standard CHT for pts w/ metastatic non-SqCC NSCLC w/o sensitizing mutations carry?

A

The addition of pembrolizumab to standard CHT in patients with metastatic non-squamous NSCLC without sensitizing mutations decreases the risk of progression or death by approximately half

89
Q

What are the standard CHT for thoracic malignancies?

A
  • NSCLC
    – Carboplatin and paclitaxel
    – Cisplatin and etoposide
  • SCLC
    – Cisplatin and etoposide
  • Mesothelioma
    – Cisplatin and pemetrexed
    – + Bevacizumab, if unresectable
  • Thymoma
    – Cisplatin, doxorubicin, and cyclophosphamide
  • Thymic carcinoma
    – Cyclophosphamide, adriamycin, cisplatin, prednisone (CAPP)
90
Q

What RT regimens are available for inoperable, incurable, symptomatic lung cancer pts? Is any of them better than the other?

A
  • Regimens:
    – 17 Gy in 2 fx weekly
    – 42 Gy in 15 fx
    – 50 Gyt in 25 fx
  • Outcomes
    – Equivalent health-related QOL, symptom relief, and OS

Sundstrom et al. Norwegian Lung Cancer Study Group JCO 2004

91
Q

Is there any role for induction CHT for locally advanced NSCLC planned for def. CRT?

A
  • Level 1 evidence does not support induction chemotherapy for locally advanced
    NSCLC
  • Induction CHT may be useful to downsize large volume diseases if dose constraints cannot be achieved
92
Q

Historically, what CTV margins are recommended for SqCC and ACA to cover 95% of microscopic disease for lung cancer?

A
  • SqCC: 6 mm
  • ACA: 8 mm
93
Q

What features are predictive of occult N2 disease?

A
  • Centrally located tumors
  • RUL tumors
  • PET-positive uptake in N1 nodes

Lung Cancer (4 decks)

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