NSCLC Flashcards
PACIFIC: What phase?
Phase III
PACIFIC: How many pt’s w/ NSCLC have stage III disease?
1/3
PACIFIC: Median PFS in pt’s w/ locally advanced NSCLC after chemoRT only?
~8 mos
PACIFIC: What is Durvalumab and what is it’s MoA?
Monoclonal Ab
Prevents PD-L1 binding to PD-1 and CD80, allowing NK cells and T cells to kill tumor cells
PACIFIC: Dose of Durvalumab used?
10 mg/kg
PACIFIC: Durvalumab schedule?
Every 2 weeks for up to 12 mos
PACIFIC: What were some secondary endpoints reported?
PFS at 12 and 18 mos
Duration of response
Time to death or mets
PACIFIC: Pt characteristics?
Avg age ~64
Male: ~70%
Non-smoker ~9%
Induction chemo ~ 30%
PACIFIC: Reported PFS?
Placebo: 5.6 mos
Durvalumab: 17.2
~11 mo PFS benefit
PACIFIC: PFS at 12 and 18 mos?
Placebo: ~35% (12 mos) and ~27% (18 mos)
Durvalumab: ~55% (12 mos) and ~44% (18 mos)
Durable effect w/ Durvalumab
PACIFIC: What was surprising about the results as they pertain to subgroups?
Benefit shown in both smokers and non smokers
Benefit independent of PD-L1 expression
Lower rate of brain mets w/ Durvalumab (6% vs. 12%)
PACIFIC: Most common AE’s w/ Durvalumab
- Diarrhea
- Radiation pneumonitis
- Rash
- Pruritis
Side effects easily manageable
PACIFIC: OS @ 12 and 24-months
Placebo: 75% (12 mo); ~55% (24 mo)
Durvalumab: ~80% (12 mos); ~66% (24 mos)
PACIFIC: Frequency of new lesions?
Placebo: ~33%
Durvalumab: 22%
PACIFIC: Incidence of brain mets
Placebo: ~12%
Durvalumab: ~6%
PACIFIC: Time to death or distant mets?
Placebo: 15 mos
Durvalumab: ~24 mos
RTOG 0617: Which phase?
Phase III
RTOG 0617: Randomization?
- 2x2
- 60 vs 72 Gy
- w/ vs w/o cetuximab
0617 → 60 vs. 72
RTOG 0617: RT Regimen?
2 Gy fx's 5 days/week 99% of PTV >93% dose Motion Management required NO Elective nodal irradiation
RTOG 0617: Chemotherapy Regimen?
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
RTOG 0617: Immunotherapy regimen?
Cetuximab given during RT and consolidation
Loading dose (1 week prior to chemoRT): 400 mg/m2 Weekly: 250 mg/m2
RTOG 0617: Primary Outcome?
OS
RTOG 0617: Secondary end-points?
PFS
Toxicity
QoL
Biological marker status vs. clinical outcome
RTOG 0617: How many pts?
~500
RTOG 0617: What’re the main findings?
74 Gy vs. 60 Gy might worsen OS: ~20 mos vs. 29 mos
Cetuximab: 25 mos w/ and 24 mos w/o
RTOG 0617: What’re the findings w/ respect to cetuximab and EGFR expression?
EGFR H score < 200: OS 20 w/ vs. 30 mos w/o
EGFR H score > 200: OS 42 w/ vs. 21 mos w/o
RTOG 0617: What’re some possible reasons for decreased OS in the high-dose group?
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
RTOG 0617: Pt characteristics?
Median Age: 64
More men than women
Non-smokers: 4-7%
Does heterogeneity on or off deliver more doses at the center of the PTV? What about the periphery?
- More Dose:
– Center: Heterogeneity off
– Periphery: Heterogeneity on
What was the size cut-off for tumors included in the SBRT trial RTOG 0236 for NSCLC?
≤ 5 cm
What was the fx used in RTOG 0236?
- 18 Gy x 3 fx
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Hook: 6*3 = 18!
What were the GTC → CTV, and CTV → PTV expansions used in RTOG 0236 and 0813?
- GTV → CTV = 0 cm
- CTV → PTV
– no 4D-CT: 1 cm CC, 0.5 cm rad
– 4D-CT: 0.5 cm geometric
What were the main findings of RTOG 0236?
- 3-yr LCR: 91%
- 3-yr regional control rage: 87%
- 3-yr disseminated failure: 22%
- 3-yr OS: 56%
What fx was used in RTOG 0813?
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
Is there evidence for SBRT being safe for lung tumors > 5 cm?
Yes, but it is currently limited to single institutional experiences
What kind of resection techniques were tested in LCSG 821 (Ginsberg et al., 1995) surgical trial and what were the main findings?
- Sublobar resection (2 cm margin around the tumor) vs. lobectomy
– LR: 82% vs. 94% (SS) - These findings established lobectomy as the minimum acceptable standard
What were the findings of the pooled analysis of ROSEL and STARS trials re. surgery vs. SABR for early-stage NSCLC?
- 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.
What is the threshold for LN- NSCLC primary tumor size for adj. CHT to be recommended?
> 4 cm
How much OS benefit is attributed to the addition of CHT per the LACE MA?
- 5% at 5 yrs
What is the recommended prophylaxis for pts w/ a contrast allergy undergoing CT sim w/ IV contrast?
- 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)
How is epinephrine administered in someone experiencing an allergic rx to IV contrast?
- 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
What are the steps in the initial management of an IV contrast allergy?
- Calling code team
- Provide supplemental oxygen
- Obtain IV access
- Epinephrine administration
What SBRT fx regimen did RTOG 0915 compare and what were its mail findings?
- 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%
Is PORT SOC for occult N2 disease found at the time of resection?
- 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
What kind of RT dosing can be considered for PORT for N2 NSCLC s/p resection?
- PORT for N2 disease:
– R1 resection: 50-54 Gy
– +ECE: 54-60 Gy
– R2 resection: 60-66 Gy
What kind of imaging FU is recommended after lung SBRT?
- 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
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?
- ~ 5%
- Due to the low risk of isolated nodal failure w/ just involved nodal RT, elective nodal RT is not recommended.
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)?
- 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%
What is defined as a centrally-located tumor?
Tumor within 2 cm of the proximal bronchial tree
Is there any difference in outcomes b/w QD vs. QOD scheduled for lung SBRT?
No, per Samson et. al, PRO 2018
How many w/ presumed early-stage NSCLC are upstaged at the time of surgery?
- 25%-33%
- This makes direct comparisons w/ RT/SBRT difficult, as those pts are only clinically staged
What are the main tox differences b/w 3D CRT vs. SBRT?
3D CRT is a/w more cardiopulmonary tox
When may segmentectomy instead of lobectomy be performed for early-stage NSCLC?
Per NCCN
- ≤ 2 cm → segmentectomy
- > 2 cm → lobectomy
What is the rate of Gr ≥ 3 tox for centrally-located tumors w/ lung SBRT?
- 28% (RTOG 0236)
- 56% (Timmerman, JCO, 2006)
What is the 5-yr OS for pts w/ severe COPD?
- ~ 70%
- Therefore, curative tx should still be pursued for this patient pop
How does RFA compare to SBRT w/regard to LC?
- RFA has superior LC
When can RFA be considered for early-stage NSCLC? What is the most sig. risk?
- Size ≤ 3cm
- Sig. risk of pneumothorax requiring CT placement
Is there any FEV1 cut-off for SBRT?
No, unlike surgery
What is the approach to the management of solitary pulmonary nodules?
- < 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
What is the annual risk of a 2nd lung primary in a pt w/ NSCLC?
1-2%
What is the annual risk of a 2nd lung primary in a pt w/ SCLC?
6%
What are the NCCN guidelines for SABR dose regimens for lung cancers?
- 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
Which isodose line is the dose rx to for Linac-based SBRT/SABR?
80%
What is the standard neoadjuvant radiation dose and concurrent CHT for NSCLC undergoing neoadj. CRT prior to resection?
- RT Dose: 45 Gy / 25 fx
- CHT: Carbo/taxol
Per RTOG 0617, which dosimetric parameter is a/w ≥ Gr 3 pneumonitis for locally advanced lung cancer?
Lung V20
For a pt receiving CRT per RTOG 0617 trial, what CHT is used and what is the regimen?
- Paclitaxel (45 mg/m2/wk)
- Carboplatin (AUC=2/wk) on days 1, 8, 15, 22, 29, and 36
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?
- 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
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RT Dose (30/15) → ~5yr brain met rates (30 vs. 15)
What are the symptoms of Pancoast syndrome?
- 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
What is the SOC for a Pancoast tumor?
- 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
What are the 5-yr outcomes survival outcomes for pts w/ pancoast tumors s/p SOC tx (NACRT → Resection → Adj. CHT)?
5-yr OS
- All: 44%
- Complete resection: 54%
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Rusch et al. INT 0160/SWOG 9416 JCO 2007
What was the randomization and results of CheckMate 816 for NSCLC?
- Stage IB-IIIA NSCLC randomized to:
- Neoadjuvant nivolumab w/ platinum-doublet chemotherapy
- 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
What’s the mnemonic for immune checkpoint inhibitors and their targets?
- NP, ADd IT
– PD-1: Nivolumab, Pembrolizumab
– PD-L1: Atezolizumab, durvalumab
– CTLA-4: Ipilimumab, Tremelimumab
What was the pt population, randomization, and results of RTOG 7301 for locally advanced NSCLC?
- 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.
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?
- 60 Gy had better control, numerically
- 74 Gy was more harmful and offered no benefit
- Cetuximab added no benefit
Which dosimetric factor is most predictive of developing esophagitis for pts undergoing concurrent CRT for NSCLC?
The volume of esophagus receiving 60 Gy
What are the usual esophageal constraints for pts undergoing CRT for NSCLC?
- V60 < 17%
– > 60 Gy has been reliably linked to esophagitis - Mean esophageal dose < 34 Gy (17 x 2)
Can N2 nodal staging for lung cancer be based on PET/CT alone?
- No, it requires path confirmation via mediastinoscopy, mediastinotomy, EBUS, EUS, or CT-guided bx
- ~ 25% false negative rates
What is the % risk reduction in DFS for pts w/ EGFR-mutant NSCLC s/p resection w/ osimertinib x 3 yrs (ADAURA Trial)?
- Osimertinib vs. placebo
– 24-mo DFS: 88% vs. 32% (SS)
– 88% ↓ in recurrence or death
What was the pt population, randomization, and findings of the INT 0139 trial for NSCLC?
- Pts: Stage III (T1-3, N2) randomized to
- Definitive CRT to 61 Gy vs.
- 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
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Memory Hook: 0139: 3-modality tx
What are the current USPTF guidelines for lung cancer screening:
- Age 50-80
– ≥ 20 yr smoking hx
– Active smokers or quit within the last 15 yrs
What was the pt population, randomization, and results of RTOG 9410 for NSCLC?
- 3 arms:
- CHT → RT
- CRT
- CRT w/ different CHT and RT dosing
- Results: 1 vs. 2 vs. 3
– 5-yr OS: 10% vs. 16% vs. 13% (SS)
What is the most important prognostic indicated for a lung cancer pt undergoing def. tx?
- KPS: Most important
- Age > 60-70
- Advanced pretreatment stage
- Weight loss (>5% past 6 months)
- Pleural effusion
What’s the order for the main superior branches of the aortic arch?
“Beyonce Cant Sing”
- Brachiocephalic Trunk
- Common Carotid
- L Subclavian
Which CHT regimen is better for CRT for NSCLC, EP (etoposide, cisplatin) or PC (paclitaxel, carboplatin)?
- 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
For pts undergoing def CRT for lung cancer, what is the contralateral lung constraint?
- Lung V20 < 30%
– Yields a <20% risk of sx pneumonitis
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QUANTEC
What is the incidence of ≥ Gr 2 pneumonitis broken down by the doses delivered to the lungs?
Which paraneoplastic syndromes are a/w NSCLC (SqCC)?
Hypercalcemia from PTH-related peptide (PTHrP)
What benefit does adding pembrolizumab to standard CHT for pts w/ metastatic non-SqCC NSCLC w/o sensitizing mutations carry?
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
What are the standard CHT for thoracic malignancies?
- 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)
What RT regimens are available for inoperable, incurable, symptomatic lung cancer pts? Is any of them better than the other?
- 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
Is there any role for induction CHT for locally advanced NSCLC planned for def. CRT?
- 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
Historically, what CTV margins are recommended for SqCC and ACA to cover 95% of microscopic disease for lung cancer?
- SqCC: 6 mm
- ACA: 8 mm
What features are predictive of occult N2 disease?
- Centrally located tumors
- RUL tumors
- PET-positive uptake in N1 nodes
