Lung Cancer ASTRO refresher 2022

Small Cell Lung Cancer

Staging

AJCC
Limited stage vs. Extensive stage

Non Small Cell Lung Cancer

Limited stage

Treatment

  • Concurrent platinum/etoposide based CHT x4 w/ chest RT 45 Gy / 30 fractions (CREST Trial)
    • 1.5Gy daily BID
    • Target
      • if Free breathing (fb), use motion management
      • contour w/ mediastinal and lung windows
      • GTV: fb, GTV: min, GTV max = iGTV or ITV
      • CTV: +5mm (variable)
      • PTV: institudion specific (4mm radial, 7mm sup/inf)
  • +/- PCI pending restaging
    • HA-PCI 25Gy/10fx
  • Enrollment on the ADRIATIC study:
    • Randomized study of consolidative immunotherapy in LS-SCLC

Tx considerations

  • Concurrent > Seq
  • Shorter time from start to end of RT assd. Improved outcomes
  • Targets
    • Involved nodal irradiation: initially involved nodal regions are included
    • post CHT volume can be targeted
      • if not starting concurent on D1
    • Elective nodal irradiation (ENI)
      • evolving—not really done for SCLC
      • current studies use nodal staging as long a

Does the timing of CHT and completion of RT drive outcomes?

  • Meta-analysis of 4 randomized studies in LS-SCLC
  • De Reysscher D, JCO 2006
  • metric of SER (start to end of RT)
    • Low SER had improved 5 yr survival
    • ea wk extending SER beyond the shortest SER studied decreased absoluet 5y OS by 1.83%
  • confounders drive timing of tx
  • but, decreased SER improves outcomes in LS-SCLC

Why involved nodal versus elective for RT?

  • Selective Nodal Irradiaiton on basis of FDG PET Scans in LS-SCLC: prospective study.
  • Van Loon et al, IJROBP 2010
  • n=60
  • RT 45 Gy/30fx BID w/ concurrent plat/etop CHT
  • targets: only 1º tumor and mediastinal LN involved on pretreatment PET

Results:

  • A difference in involved nodal stations between CT alone and PET/CT was found in 30% of patients.
    • Isolated regional failure rate: 3% (2 patients): v. low
  • Grade 3 esophagitis: 12% low

Conclusion

  • If PET/CT is used for target delineation, involved nodal RT planning can be used with low risk of elective nodal failure

Why BID in LS-SCLC?

  • CONVERT trial:

    • BID vs QD CRT in LS-SCLC, open label phase 3 randomized superiority trial
    • Faivre-Finn, Lancet 2017
  • n = 547
  • Cis/etop 66/33 vs Cis/etop 45/30
  • Median OS
    • BID: 30 mo 🏆
    • QD: 25 mo
  • 2y OS: 56% vs 51%
  • ☣ No diff in G3/G4 esophagitis (19%)
  • was designed to show superiority of QD RT, not equivalence.
  • BID should continue to be considered SoC

Plan Evaluation

  • get a sense of what you are treating and attention to DVH
  • safety
  • coverage
  • isodose lines: hot and cold spots
  • recheck prescriptions
  • dose limits are generally the same as QD vs BID
  • exception is spinal canal
    • < 31
    • <41

Coverage

  • 100% of Rx dose to GTV
  • 99% to CTV
  • 95% to PTV

if tx begins >1wk after CTV

  • carefully look at daily image guidance
    • adapt plan if necessary
  • treatment toxicity ☣
  • watch CBC, if neutropenic they will have esophagitis concurently
    • often hospitalized in the week after finishing CRT

Response

After x4 cycles CRT


  • CT CAP
    • Brain MRI

Next?

  • PCI

PCI

No single study shows OS benefit


  • Metaanalysis: PCI for pts with LS-SCLC

    Auperin, NEJM 1999

  • 7 trials
  • n = 987
  • 3y OS: PCI had 5.4% absolute improvement (20% vs 15%)
    • incidence of brain mets decreased (59% vs 33%)

Limitations of the study era

  • complete remission was defined as results of CXR

Frontiers in LS-SCLC

  • Dose escalation
  • consolidative IO
  • HCP avoidance PCI

Consolidative IO

Phase III randomized, double blind, placebo controlled, Durvalumab vs Durvalumab & Tremelimumab for consolidation in LS-SCLC:

ADRIATIC

  • Placebo vs. PDL1i vs. PDL1i & CTLA4i

High Dose vs Std Dose BID RT with LS-SCLC Phase 2

Henning B, Lancet 2021

  • n = 176
  • 60 Gy/ 40 🏆
    • 2y OS: 74%
    • PFS: HR = 0.75 (p=.13)
  • 40 Gy / 30
    • 2y OS: 48%

Toxicity ☣

  • about equal
  • both groups 85% got PCI

HCP Avoidance (HA) PCI

NRG CC001: for brain mets

  • HA-PCI vs PCI
  • lower rates of neurocog failure
  • no diff in
    • OS
    • CNS relapse
    • toxicity
  • Dr Cho says this is Dutch? Spanish study says there is effect.

Other HA PCI studies

RTOG CCOO3

  • enrolling

NKI/Dutch Cancer Agency

  • negative study

Spain/PREMER

  • positive study
  • limited replication of the endpoint

RTOG 0538

LS-SCLC definitive CRT

  • OS
  • n=927
  • median F/up 4 y:
  • statistically insignificant difference btw QD vs BID

ES-SCLC

Treatment

  • Concurrent plat/etop x4-6 C & concurrentIO (IMPOWER133)
  • after, assess response and
    • Chest RT
      • CREST: 30Gy/10fx 3DCRT
  • MRI brain surveillance
    • mostly defer PCI
  • maintenance IO

Immunotherapy in ES-SCLC

IMpower 133: randomized Phase 3

NEJM

  • AteZOlizumab & plat/etoposide (doublet) + maintenance AteZOlizumab
  • plat/etoposide (doublet)
  • Median OS
  • IO arm: 12 mo 🏆
  • doublet: 10mo

also improved PFS

in the trial they kept giving IO for at least a year and beyond

Chest RT ⚠

  • consolidative chest RT with definitive doses should be used with caution
  • However, in patients with good PS, excellent response CHT, a higher dose of thoracic RT
    • (i.e. 45 Gy in 15 fractions)
    • (from ASTRO clinical practice guidelines for SCLC)

Jeremic B, JCO 1999

RT in combined modality for ES-SCLC: randomized study

  • n=210
  • If CR/PR in distant sites
  • x3 more CRT 60Gy/40 🏆
    • OS: 17 mo vs. 11 mo
  • 3yS: 22% vs. 9%
    • 5yS: 9% vs 4%
  • x3 CHT along

Definitive CRT improves outcomes in ES-SCLC

Caveats

  • This hasnt been replicated

Gore, JTO 2017

RTOG 0937: Randomized phase 2 comparing PCI to PCI w/ Consolidative RT for ES-SCLC

  • consolidation: 3Gy x 45
    • distant sites: 4Gy x 10
  • n = 97
  • PCI vs PCI with Consolidative RT to chest and other met sites
  • ended early, futile study, negative study
  • 1yS
    • PCI: 60%
    • PCI w/ Chest: 51%

PCI

CREST: Thoracic RT for ES-SCLC, randomized phase 3

Slotman, Lancet 2015

  • PCI
  • PCI w/ RT, 30Gy/10fx
    • nondefinitive dose
      • 1yS; no diff : ~30%
      • 2yS: 13% vs 3%
      • 6m PFS: 24% vs 7%

Progression sites??
w/ CREST PCI the recurrence is about 40% of non-PCI brain mets

Target volumes

  • residual gross 1º disease
  • all initially involved LN stations
    • GTV to CTV: 1.5 cm

Caveats: 🤔

  • Patients with brain metastases and malignant effusions were not included.
  • The 2 year OS and 6-month PFS outcomes were unplanned secondary analysis
  • Pts w/ CR did not benefit from CREST consolidation

Slotman, NEJM 2007

PCI vs None

  • ES-SCLC
  • PCI 🏆
    • less symptomatic brain mets: HR 0.27
    • cum risk of brain mets at 1y: 14% vs 40%
    • 1yOS: 27% vs 13%

Caveats 🤔

  • CNS staging not required prior to study entry
  • CNS imaging done only for symptomatic disease, not for routine surveillance.
    • occult brain mets possible in randomization

Takahasi, Lancet Onc 2017

PCI vs obs in ES-SCLC, randomized, open label, phase 3

  • n = 224
  • Brain imaging prior to enrollment
  • imaging throughout observation course

Negative study

  • PCI
    • MOS: 12 mo
    • however trends to benefit PCI
    • 6m incidence: 15% vs. 46%
    • 12m incidence: 33% vs 59%
    • 18m incidence: 40% vs 64%
  • Obs
    • MOS: 14 mo

Caveats 🤔

  • study was terminated early because of futility on interim analysis
  • Brain RT given to 83% of patients who developed brain mets in the observation group.
    • maybe there's no need for PCI if theres close f/up
  • If PCI is deferred in ES-SCLC, brain MRI every 3 months is critical!

Oligomets

Caution ⚠

  • The studies that showed benefit:
    • Had limited numbers
    • Had significant toxicity
    • Were largely not done in the immunotherapy era.
  • Who should get consolidative RT?
    • Good performance status
    • Shared decision making
    • Enroll on NRG-LU002 : Maintenance Systemic vs SBRT

Digression:
Principles of local therapy

  • old paradigm
    • local therapies early
    • systemic therapies late

  • more often now consider


    • systemic therapy in early disease
    • local therapy in late disease

  • in General, consider local therapies in Lung cancer for


    • Palliative
    • CNS disease
    • Oligomets
    • Isolated progressive disease Screenshot 2023-02-05 at 3.19.40 PM

Local Consolidative Therapy

Local Consolitative therapy(LCT) vs Maintenance or Obs in Oligomet NSCLC, Phase 2, randomized

Gomez JCO 2019

  • crit: ≤ 3 mets, no prog s/p 3m systemic tx
  • Maintenance/obs (MT/O)
  • LCT 🏆
    • PFS: 4.4m vs. 14m
    • OS: 41m vs 17m

Caveats 🤔

  • Closed at interim analysis of PFS benefit in LCT arms
  • LCT given to all active disease sites
  • Role of LCT in the era of IO is being defined
    • this was not examined
  • LCT was non-uniform and optimal dose, fractionation and technique needs to be defined.

Oligomets vs Isolated Progression

  • Oligo
    • limited # of mets sites
    • treated w/ definitive therapy
    • then consolidative therapy to primary
  • Isolated Progressive
    • Mets treated with systemics
    • favorable response
    • some area with isolated progression
      • ablative therapy to this area
      • can continue to use effective systemic therapies

Consolidation in Oligomets

SABR-COMET: SABR vs SoC palliative in Oligomets, Randomized phase 2, open label

  • Inc.crit: Life exp ≥6m, ECOG 0-1, 1-5 mets

Randomized to

  • SoC
  • SoC then SABR
    • OS: 28m vs 41m
    • PFS: 6m vs 12m

Caveats 🤔

  • Only 18% of patients had primary lung cancer (n = 20)
  • ~50% of all mets from any histo were to the lung
  • 3 treatment related deaths

Oligomets EGFR mutated NSCLC: Role of Consolidative RT

SINDAS

  • EGFR mut.
    • Oligo-mets (≤5 mets, ≤ 2 lesions in any organ)
    • No brain metastases
    • Randomization
      • 1st Generation TKI alone
      • 1st Generation TKI+RT to all metastases and primary tumor/involved regional lymphatics. (25-40 Gy in 5 fractions)
    • Outcomes:
      • Progression Free Survival
      • Overall Survival
      • Toxicity

Locally Advanced

Many Treatment options

  • Induction CRT ☢ followed by resection 🔪(Albain)
  • Def. CRT ☢ followed by consolidative IO 💊(PACIFIC)
  • Induction CHT 💊 followed by resection 🔪 (Pless) ?(PORT)
  • Induction chemoIO 💊 followed by resection 🔪(CheckMate 816)

NCCN is a compendium for IO and CHT. NAC is key.
All the NAC trials needed to be resectable at baseline.
IO path CR rates 18-24%
5-20% dont mate it to sx. of them 50% have progression while on CHT/IO NAC
Path CR: EFS 80-90%

Albain

Trimodality is not as good, surgery deaths (5) remove benefit

  • Induction CRT ☢ followed by resection 🔪(Albain)

Stage III NSCLC

  • phase 3, randomized controlled
  • n= 202

Randomized

  • Arm 1: Cis/Etop (2 cycles)/RT (45 Gy) → rescan (no progression) → resection 🔪 → 2 cycles chemo
    • MOS: no diff. (~23m)
    • PFS: 13m vs 11m
  • Arm 2: Cis/Etop/RT (61 Gy) → 2 cycles chemo

Unplanned exploratory analysis 🤔

  • Improved OS for lobectomy
    (vs. chemoRT alone)
    • not for patients who underwent pneumonectomy (vs chemoRT)

Negative study: no evidence for resection 🔪 with stage III disease

  • however selecting for lobectomy, may be appropriate

PACIFIC: non surg (unresectable)

  • Def. CRT ☢ followed by consolidative IO 💊(PACIFIC)
  • randomized, Double blind, placebo controlled
  • inc.crit: unresectable, st. III NSCLC 👎🏾w/o progression after ≥2 cycles plat. CRT
    • WHO PS 0-1
    • PDL1 status doesnt matter
  • n=713

Until progression

  • Durvalumab(PD-L1i) ≤1 year
    • 5y PFS: 17m vs 6m
    • 5y OS: 48m vs 29m
  • Placebo ≤1 year

Tox
Grade 3 pneumonitis: 15%

NCCN guidelines endorse IO after chemoRT in stage III unresectable disease

no EGFR/ALK: we dont know what to do for these mutations.

  • LAURA study ASCO loc adv following chemoRT, unlimited Osimertinib
  • ALK several studies show no benefit.
    low PDL1, no benefit
    • TPS only includes tumor cells
  • CPS both immune and tumor cells

benefit for starting Durva w/in 2 weeks

PORT

  • Induction CHT 💊 followed by resection 🔪 (Pless) ?(PORT)
  • Operative st. IIIa/N2 NSCLC 👍
  • n = 232

Randomized to

  • chemo x 3 cycles →RT alone (44 Gy/22 fr) →resection
  • chemo x 3 cycles → resection

Negative study

  • event free or OS
    • CHT alone is reasonable
  • disappointing nodal downstaging (to N1 or N0)
    • CRT (65%); CHT (53%)

Caveats 🤔

  • sequential CHT and RT; not done today
  • Dose is wrong (44Gy/22)

CheckMate 816 neo adj IO only 3C

  • Induction chemoIO (NIVOlumab) (PD-1i) 💊 followed by resection 🔪(CheckMate 816) 2021
  • randomized, open label, Phase III
  • n = 358
  • inc.crit: newly dx resectable st. IB to IIIA NSCLC 👍
    • stratified by IB, IIA, IIB, IIIA
      • no EGFR or ALK mut
    • ECOG PS 0-1

... Nivo killed it

  • pCR
    • IB: 40% vs 0%
    • IIA: 25% vs 3%
    • IIB: 24% vs 9%
    • IIIA: 23% vs 1%

prelim improvement in OS.

  • updates will include event free survival improved.
    • not yet published

FDA approved(can use the regimens and insurance wll cover)

Evaluating locally advanced disease. How to do it rationally

LA-NSCLC

Medical inoperability

  • Will pt medically tolerate it?
    • NAC wont change medical operability of pt
      • mostly wont change extent of resection either
      • unclear if induction ChemoIO converts bulky disease into resectable (prob not)
      • caution using Checkmate 816 for unresectable disease to turn an inoperable into operable (not good practice)

        Technical inoperability

  • Can oncologic resection be achieved?
    • Nature of N2 disease
  • single vs multistation
  • bulky vs not
    • R0 resection possible
    • Extent
  • Lobectomy vs. Pneumonectomy
    • Pulmonary reserve allows this to occur
  • PFT
  • quant V/Q

    Patient preference

Dose

Studies (ROTG 0617) fail to show benefit in unresectable NSCLC >60Gy

Neoadjuvant CRT

  • Studies have gone higher than Albain #
    • 60Gy instead of 45 Gy

RTOG 0617

  • 60Gy vs 74 Gy
    • mOS: 29m vs 20m

IMRT vs 3D

  • IMRT
    • larger PTV
    • more stage IIIB disease in cohort
    • No OS, PFS, LC, met control difference
    • fewer gr. 3 pneumonitis (3.5% vs 8%)
  • lower heart ❤ dose; lower V40

RTOG 0229

  • 61.2Gy preop
    • 14% gr. 3 pulm complications
      • 3% gr. 5 tox
      • 2yOS = 54%

higher dose both reasonable and safe to consider

Technique

IMRT vs 3D

  • RTOG 0617

Technique

Protons vs. Photons

Liao, JCO 2018

  • n=149
    • Protons= 57
  • nonsurgical locally adv. NSCLC
  • proton plans had better heart sparing
  • no diff in lung or eso dose

IMRT had better 12 mo gr. ≥3 pneumonitis (6.5% vs 10.5%)

  • loc failure at 12m no diff

Caveats 🤔

  • enrollment required acceptable plans for both IMRT and PSPT
    • Passive Scatter protons is now antiquated
  • PSPT had diff rates of pneumonitis depending if enrolled early (31%) vs late (13.1%)
    • there may be a learning curve

ongoing phase II study of IMRT vs next gen Protons

Unresectable Stage III disease

Most with unresectable St. III lung cancer will get CCRT (concurrent CRT) regimen followed by IO

  • SOC: CCRT → Durva

Where are we going? Unresectable Stage III

  • NAC+IO → CCRT + Pembro
  • PARPi
  • other novel therapies

Keynote 799

  • Jabbour JAMA onc 2021
    • NAC chemoIO → CCRT + Pembro
    • outstanding obj response rate
    • 6m: 90%
  • 12m: 75-80%
    • 2 diff chemo regimens
    • Toxicity ☣
    • Gr 5 4%

Resectable disease

Checkmate 816 and Albain

  • if induction given with CRT, higher mediastinal clearance, but no data shows it improves outcomes over chemo alone
  • if induction given with CHT, PORT should be cautiously administered.
    • pN2 disease can improve mediastinal relapse, but PORT hasnt shown OS benefit.

pN2 after resection

PORT metaanalysis

  • suggested PORT was harmful
  • retrospective data and subgroup analysis shows improvement in PORT with N2
    • ANITA subgroup
      • Doullard IJROBP 2008
    • NCDM, JCO 2015
      • Robinson JCO 2015

Lung-ART

  • Le Pechoux Lancet 2022

RCT PORT after resection for N2 st. III NSCLC

  • n= 501
  • R0 resection and x4 cycles platinum CHT
  • pre- and or post op CHT
  • 3y DFS not changed in PORT vs no PORT
    • 3yOS: no diff
  • Mediastinal relapse PORT benefit (25% from 46%)

in N2 mediastinal resected disease, PORT had 8% CV ❤ deaths vs. 0%

✏ No 3DCRT for pN2 dz, heart dz.

PORT-C

  • N2 NSCLC with R0 resection & x4 cycles platinum CHT
  • 3y DFS no diff
  • mDFS no diff
  • Per protocol analysis
    • 3yDFS PORT (43%) vs no PORT (31%)

Some use PORT-C to justify PORT

IMRT didnt improve outcomes vs. Lung-ART, but had better LC and cardiac profile

Early Stage

Resection?

  • both therapeutic and diagnostic
  • SoC if lobectomy

LCSG 821

classic randomized study of surgical considerations

  • lobectomy vs Limited resection
    • T1N0
  • n=122
  • LRR: x3 in limited resection group (17% vs 6%)
  • OS better in lobectomy (70% vs 61%)

On boards: Lobectomy is SoC

However...
JCOG0802
Segmentectomy vs Lobectomy in small peripheral NSCLC

  • clin stage 1A peripheral or nodule ≤ 2cm
  • Lobectomy (n=554) vs Segementectomy (n=552)
  • 5yOS: Segmentectomy (94%) vs Lobectomy (91%)
  • higher recurrence in Segmentectomy (12%) vs Lobectomy (8%)
    • not meaningful survival difference

We may see smaller resection surgeries become more popular or SoC

SABR?

  • SoC if considering sublobar
  • ASTRO Guidelines: rec Bx for all pulm nodules prior to resection
    • if Pt declines Bx, empiric SABR maybe reasonable

50Gy / 5fx

  • breath hold to limit motion
  • no CTV expansion (GTV → PTV)
  • dont limit PTV to meet CW constraints
    • tell pt there may be CW pain
  • remember to contour skin, as overdose is common
  • prescribe using non-homogenous dose optimization
    • Rx btw 60-90%
    • achieves high dose falloff if low homogeneity
      • dose falloff inversely correlated with homogeneity
      • higher mean dose to tumor = better control
      • less dose to surrounding tissue

SABR Dose

  • BED +100 Gy

Onishi JTO 2007

  • n=257
  • st I NSCLC w/ SABR
  • Local Progression assd. w/ higher RT doses
    • and OS

SABR Technique

Single (34Gy/1fx) vs Multi (48Gy/4fx)

  • Videtic, IJROBP 2015
  • 2yOS: 1 fx (61%) vs 4 fx (78%)
  • 2yDFS: 1 fx(56%) vs 4 fx (61%)
  • 1y primary tumor control: 1fx(97%) vs 4fx(92%)

SABR Technique

Central Tumors

  • Bezjak JCO 2019
  • n=120
  • central tumors T1-2
  • Dose escalating 5 fx SBRT
    • started at 10Gy, increasing 0.5 Gy per fraction until 12Gy x 5 fx cohort filled.
    • no dose limiting toxicities ☣ occured to prevent escalation
    • Dose limiting Toxicity (DLT); 7% in 12Gy x 5 fx group
    • ~90% local control at 2Y… pretty good
    • 2yOS: 70%
      • n=2 Gr 5 events
      • toxicity ☣can come late, ie after finishing RT

Defined central tumor: within/contacting 2cm radius around prox bronchial tree or immediately adjacent to mediastinal or pericardial pleura

  • this study did not look at ultra-central tumors

Comparable outcomes to peripheral SABR

Central SABR is an emerging SoC

Suggestions for treating Central Tumors

Fraction patterns

  • 50 Gy / 5 fx
  • 60 Gy / 15 fx (hypofx)
  • 66 Gy / 33 fx (conventional fx can be reasonable)

Meet published normal tissue constraints

Treat central tumors safely

  • Motion management
  • breath holding
  • 3D and 4D CBCT

✏ Duke series: no benefit to PCI in small tumors

click to edit

Staging completed, Nonmetastatic given PCI vs no PCI, However randomization was done prior to staging.

  • Chemo doesnt penetrate the brain. So those who had

3 m MRI scans in Japan, no matter what. So tend not to favor PCI after chemo for ES SCLC.

PCI
Turrisi ECOG
Murray CONVERT
CALGB

Turrisi : who qualifies for PCI
Systemic therapy was scheduled to last 12 weeks. The stage of disease was then determined again according to the results of chest radiography and head and chest CT. Because of the high frequency of brain metastases (50 percent), patients with a complete response were offered prophylactic cranial irradiation, despite reports of neurotoxicity.11 This treatment consisted of 10 doses of 2.5 Gy to the midplane of the brain over a two-week period, for a total of 25 Gy.12

CONVERT: EUROPEAN
No later than 6 weeks after the last cycle of chemotherapy, patients without evidence of progressive disease on chest X-ray or CT scan and with no clinical evidence of brain metastases were given prophylactic cranial irradiation.

  • europeans are more ralaxed on who is eligible. PR allowed.

Dr cho prefers metabolic (PET response) PR
1/5 will have something in the chest afer treatmtnet.

QUARTZ trial30825-X/fulltext)
Histo
PS
Age difference

Whole brain NSCLC

Concurrent CRT is SoC

Turrisi didnt believe in a dose response curve beyond 45

Murray in 45 BID sequential

stage II-stage III, select IIIb, since we have good NAC+ IO(adds a lot), almost all patients.
(except

AGEAN
also Durva
not yet FDA approved. No improvement in OS.

Centilmab: from China
not FDA improve

Stage II : NAC IO CHT.

Keynote 671

77T perioperative Nivo, almost a year after
PCR 18%

  • NEJM
  • ME- not yet approved.

Periop studies show among those w/ and w/o adjuvant, postop analysis shows some benefit with adjuvant IO.

New study for introducing Durva during CRT- negative trial


wait 1 month then PET, then start Durva if PCR.

Adjuvant IO
PORT IS EXCLUDED FROM THESE TRUALS

IMPOWER 010 : Adj
Atezo

CHT mandatory
no EGFR ALK
Drven by high PDL 1, associated with high OS

PEARL study: Adj Pembro

CHT not-mandatory

  • some EGFR ALK

Not correlated to PDL1

.77 HR for DFS for both studies.

Atezo: STAGE 2 of higher PDL1 Positive: TPS > 1%

  • Atezo not really benefitting TPS 1-49%
    Pembro: stage 1b or higher, no PDL1 status needed. (basically everyone gets this)

PDL1 negative: offer nothing
1-49: offer

50%: strongly advise pembro

CALGB
outer 1/3 of lung

0813: central
0915: peripheral
SUNSET/HILUS: ultracentral

KEYNOTE 091
DFS benefit of adj pembro in stage IB-IIIA

click to edit

Cord Constraint


Dmax 36Gy in the BID arm
for 1 week field covered the cord, then use of obliques

Cord constraints
Dmax 42Gy in the BID arm
Dmax 48Gy in the QD arm


Lung constraints
Lung-PTV
V20 <35%

Superiority studies:
Is 66 better than 45? No? Then we know its not superior, but we dont have an answer for if 66 is better for patients who can’t get BID.

✏60% of untreated patients get brain mets in 3 years
30% of treated (PCI) patients get brain mets in 3 years

THORA
phase II
60/40 had higher OS rate than 45/30 (74% vs 48%)

TRISS
phase III
45/30 SIB 50

PET based treatment

NRG LU005
SoC + Atezolizumab
negative trial
no OS benefit

  • atezo OS trended worse (33 months vs 39m)
    mDM survival 16 vs 13 months
    STRI

ADRIATIC
Duva after CRT in LS SCLC
3 arms,
Adj. Tremelimumab
Adj. Durva


mOS 56 vs 33m
PFS 17 mo vs 9 mo

PCI Dosing
RTOG 0212
if CR to CRT
Rx: 25Gy/10
2Y brain mets 25/10
vs dose escalated

Hippocampal Avoidance Studies
Dutch
Spanish
NRC-CC03 -American: Positive trial

  • Hopkins verbal learning test
  • Neurocognitive function failure (HR 0.77, p= 0.03)

What about just MRI? Farris 2019 retrospective: PRO
endpoint is only 1Y, does that matter?

Ongoing studies

click to edit

CASPIAN

Durva EC
Drva Trem EC

Constraints

V20 <37%
Mean Heart dose? Probably not achievable
V60 <7% predicts for esophagitis

  • full lumen coverage is assd w/ toxicity (try to underdose half)

Surveillance

q3m

Pneumonitis concern?

walking O2 sat drops from baseline O2
Check CT Chest


1mg/kg up to 60mg for 1 wk
Taper slow (eval for about 6wk)
PPI
bactrim