lung CA tx Flashcards
PACIFIC trial
durva x1y ⇒ ￪PFS,OS
(after definitive chemoRT)
in locally adv, unresectable III
PD-L1: ???
IMpower 010
atezo x1y ⇒ ￪DFS (overall), OS (only in PD-L1≥50%)
(after adjuvant platinum-based doublet chemo)
in IB(7e:≥4cm)-IIIA
PD-L1: ≥1% (+)
CheckMate 816
neoadjuvant chemoIO:
platinum-based doublet + nivo
⇒ ￪EFS & cPR=24%
KEYNOTE-671
periop chemoIO:
neoadjuvant chemoIO:
platinum-based doublet + pembro
+
adjuvant IO:
pembro x10mo
⇒ ￪EFS & cPR=18%
Lung ART
mediastinal PORT (postop RT) for resected NSCLC with pN2:
non-sig 3% higher 3y DFS;
10% ￬ recurrence offset by 10% ￪ death (mostly cardiopulm)
RT (3D conformal > IMRT) to:
- resected +LNs
- downstaged +LNs (if neoadj)
- bronchial stump
- ipsilateral hilar LN region
- “probable extension to mediastinal pleura adjacent to completely resected tumor bed”
- levels 4,7 routinely
with margin of 1cm for nodes
NCCN guideline adjuvant systemic tx indication(s) & regimens for resected NSCLC
all for xx-IIIA+T3N2-IIIB
**PD-L1⊕(≥1%)** high-risk IIA/IIB+
chemo ￫ atezo x1y
**PD-L1⊖(<1%)** high-risk IIA/IIB+
chemo ± atezo x1y
**PD-L1 any** II+ completing KEYNOTE-671 periop tx
atezo x1y
**EGFR** IB+
chemo ￫ osi x3y
**ALK** II+
alectinib x2y
ADAURA
osi x3y ⇒ ￪DFS(II-IIIA),DFS(all),OS
(after adjuvant platinum-based doublet chemo)
in resected IB(4cm)-IIIA NSCLC (adjuvant)
EGFR⊕
KEYNOTE-024
pembro x2y ⇒ ￪PFS,OS,RR
in IV NSCLC
PD-L1≥50%
NCCN guideline 1st-line tx for NSCLC cIV EGFR/ALK⊖ & PD-L1≥50%
pembro x2y
(KEYNOTE-024)
mgmt of Pancoast/superior sulcus NSCLC with N2 dz
NO BENEFIT from resxn:
definitive chemoRT + durva (PACIFIC)
NCCN guideline mgmt options for locally advanced N2 (IIIA:T1-2N2 & IIIB:T3N2 = T1-3N2) NSCLC
non-Pancoast
- neoadjuvant ￫ resxn
- definitive chemoRT + durva (PACIFIC)
TSRA: IIIA:T1-2N2 neoadjuvant ￫ re-stage ￫ if cleared N2 dz, resxn (if not, NO BENEFIT from resxn per 2000 Bueno study) – also says NOT to resect any IIIB (T3-4N2) and that T3N2 specifically for chest wall invasion do NOT have any benefit from surgery
NCCN guideline recommendation re: re-staging mediastinum after neoadjuvant tx for locally advanced N2 (IIIA:T1-2N2 & IIIB:T3N2 = T1-3N2) NSCLC
non-Pancoast
NOT mandatory
- “Repeat mediastinoscopy, while possible, is technically difficult and has a lower accuracy compared to primary mediastinoscopy. One possible strategy is to perform EBUS (± EUS) in the initial pretreatment evaluation and reserve mediastinoscopy for nodal restaging after neoadjuvant therapy.”
- “Restaging after induction therapy is difficult to interpret, but CT ± FDG-PET/CT should be performed to exclude disease progression or interval development of metastatic disease.”
- “Patients with negative mediastinum after neoadjuvant therapy have a better prognosis.”
TSRA: IIIA:T1-2N2 neoadjuvant → re-stage → if cleared N2 dz, resxn (if not, NO BENEFIT from resxn per 2000 Bueno study) – also says NOT to resect any IIIB (T3-4N2) and that T3N2 specifically for chest wall invasion do NOT have any benefit from surgery
NCCN guideline recommendations re: mgmt of N2 dz NSCLC
non-Pancoast
“A questionnaire was submitted to the NCCN Member Institutions in 2021 regarding their approach to patients with N2 disease. Their responses indicate the patterns of practice when approaching this difficult clinical problem.
- All NCCN Member Institutions treat select N2 patients with multimodality therapy that includes surgery.
- The majority of NCCN Member Institutions prefer EBUS for initial mediastinal staging, reserving mediastinoscopy for possible restaging.
- The majority of NCCN Member Institutions do not pathologically restage mediastinal lymph nodes after induction therapy and prior to surgery.
- All NCCN Member Institutions consider surgery for single-station non-bulky N2 disease.
- Approximately half of the institutions consider surgery for single-station bulky disease, 39% for multi-station non-bulky disease, and 21% for multi-station bulky disease.
- Two-thirds of NCCN Member Institutions prefer induction chemotherapy; one-third prefer chemoradiation.
- The majority require at least stable disease after induction, but do not require radiologic or pathologic response prior to surgery.
- Roughly a half would consider pneumonectomy after induction chemotherapy, but less than a quarter would consider pneumonectomy after chemoradiation.
- Approximately three-fourths would give adjuvant RT for positive residual N2 disease, but only approximately one-fourth would give RT for N2 pathologic complete response.
NCCN guideline mgmt options for locally advanced N2 (IIIB:T4N2) NSCLC
non-Pancoast
- definitive chemoRT + durva (PACIFIC)
TSRA: IIIA:T1-2N2 neoadjuvant → re-stage → if cleared N2 dz, resxn (if not, NO BENEFIT from resxn per 2000 Bueno study) – also says NOT to resect any IIIB (T3-4N2) and that T3N2 specifically for chest wall invasion do NOT have any benefit from surgery
Pancoast/superior sulcus tumor (NSCLC) Intergroup (IG) 0160/SWOG 9416 trial
III: T3-4 N0-1 superior sulcus NSCLC
induction chemoRT (with platinum-based doublet):
cisplatin + etoposide x2cycles + 45Gy over 5w ￫ resxn ￫ cis/etopo x2cycles
NCCN guideline mgmt of Pancoast/superior sulcus T3-4 N0-1 NSCLC
induction chemoRT (with platinum-based doublet):
cisplatin + etoposide x2cycles + 45Gy over 5w ￫ resxn ￫ cis/etopo x2cycles ± adjuvant systemic tx
(per IG 0160/SWOG 9416 trial on III: T3-4 N0-1 superior sulcus NSCLC)
Pancoast/superior sulcus tumor (NSCLC) trial
IG 0160/SWOG 9416 trial
(III: T3-4 N0-1 superior sulcus NSCLC = induction chemoRT x2 cycles → resxn ￫ chemo x2cycles)
NCCN guideline 1st-line chemo regimen for adenoCA NSCLC
platinum-based doublet:
cis/pem (cisplatin + pemetrexed)
NCCN guideline 1st-line chemo regimen for SCC NSCLC
platinum-based doublet:
cis/gem (cisplatin + gemcitabine)
cisplatin + docetaxel
adjuvant chemo benefit for NSCLC
5% OS
NCCN guideline 1st-line adjuvant systemic tx for resected NSCLC
platinum-based doublet chemo (cis/pem adeno & cis/gem squam) ± IO/TT
except ALK⊕ (direct to alectinib)
NCCN guideline adjuvant chemo indication(s) for resected NSCLC
- > 4cm (T2bN0) + high-risk features
- > 5cm (T3+N0)
- N+ (any)
high-risk = poorly-diff, +LVI, +VPI, pNx, [inadequate] wedge resxn
NCCN guideline pathologic high-risk features for consideration of adjuvant chemo for resected NSCLC
- poorly-diff
- +LVI
- +VPI
- pNx
- [inadequate] wedge resxn
NCCN guideline adjuvant IO/TT indication(s) & regimens for resected NSCLC
all for xx-IIIA+T3N2-IIIB
- ALK II+: alectinib (only 1 without chemo)
- EGFR IB+: chemo ￫ osimertinib
- PD-L1⊕(≥1%) high-risk IIA/IIB+: chemo ￫ atezo x1y
- PD-L1⊖(<1%) high-risk IIA/IIB+: chemo ± atezo x1y
- PD-L1 any II+ completing KEYNOTE-671 periop tx: atezo x1y
common biomarker in smoker NSCLC
KRAS
Is NSCLC in a smoker more or less likely to respond to IO than in a non-smoker, with the same molecular profile?
MORE
ever smokers tend to respond better to IO than never smokers
r/t higher PD-L1?
Which biomarkers safely tolerate and/or respond well to IO?
KRAS (smokers)
poss BRAF
approved + effective in PD-L1 neg?
none???
- neoadj nivo (with chemo): ⊕approved / ⊖effective
- adjuvant pembro (after chemo): ⊕approved / ⊖effective
minimum predicted postoperative FEV1 to tolerate resxn
40%
minimum predicted postoperative DLCO to tolerate resxn
40%
minimum preop FEV1 to tolerate pneumonectomy
2L
minimum preop FEV1 to tolerate lobectomy
1L
minimum preop FEV1 to tolerate segmentectomy
0.6L
minimum VO2max to tolerate a surgery
15 mL/min/kg
TSRA Red Book ≥15
Chest 2009 <12 v >20
“Compared to patients with a peak Vo(2) of > 20 mL/kg/min, those with a peak Vo(2) of < 12 mL/kg/min had 5-fold, 8-fold, 5-fold, and 13-fold higher rates, respectively, of total cardiopulmonary complications pulmonary complications, cardiac complications, and mortality.”
Eur Respir J 2011 >17 v <10
Respirology 2007 <15 v >15
JTO 2007 (CALGB 9238) <16
NSCLC involving:
T1 nerve root
= resectable?
YES
⇒ medial UE parasthesia
NSCLC involving:
C8 nerve root
= resectable?
NO
⇒ Klumpke paralysis (claw-like contracture of intrinsic hand & forearm muscles)
surgical approach to Pancoast with NO brachial plexus/subclavian vessel involvement
extended posterolateral thoracotomy (Shaw-Paulson):
- to C7/base of neck
- through 4th rib space (≥1 rib space below tumor)
- transects: trapezius, latissimus, rhomboids, serratus
- anterior then posterior division of ribs 1-4
https://drive.google.com/file/d/1xQlHz1pY73eywgGB2z_DrCpEr1A6Yu9n/view
surgical approach to Pancoast WITH brachial plexus/subclavian vessel involvement
anterior transcervical-thoracic thoracotomy (Dartevelle):
L-shaped incision following ant border SCM and inf border clavicle to deltopectoral groove
- either resect anterior clavicle or bisect manubrium to preserve SCJ
- through chest wall resxn/resected ribs 1-3 (no true thoracotomy within an ICS)
https://drive.google.com/file/d/1xKKlg4uI9cAJn_9EYEOA9qPs8YlkLnUI/view
extended posterior thoracotomy (Shaw-Paulson) technique
extended posterolateral thoracotomy (Shaw-Paulson):
- ant ax line around scap to C7/base of neck
- through 4th rib space (≥1 rib space below tumor)
- transects: trapezius, latissimus, rhomboids, serratus
- divide ribs 2,3,4 anteriorly to do lobectomy & MLND
- divide 1st rib with Gigli saw to expose brachial plexus
- resect entire posterior ribs (disarticulate costotransverse jxn OR resect with TP if involved) + ligate neurovasc bundles
- [frozens; clips]
- mesh sewn to sup: scalenes/clavicular fascia / ant: intercostal fascia/muscle around cut rib ends / post: paraspinous muscles/fascia / inf: pericostal
https://drive.google.com/file/d/1xQlHz1pY73eywgGB2z_DrCpEr1A6Yu9n/view
anterior transcervical-thoracic thoracotomy (Dartevelle) technique
anterior transcervical-thoracic thoracotomy (Dartevelle):
L-shaped incision following ant border SCM and inf border clavicle to deltopectoral groove
- either resect anterior clavicle or bisect manubrium to preserve SCJ
- transect: SCM (both heads), omohyoid, ant scalene, middle scalene
- dissect: vein (incl ant jug, EJ, IJ ± ligation for exposure) ± thoracic duct ligation on L, arteries (± thyrocervical trunk/branches, IMA, costocervical trunk ligation for exposure), brachial plexus
- chest wall resxn of 1,2,±3 ribs
- lobectomy & MLND
https://drive.google.com/file/d/1xKKlg4uI9cAJn_9EYEOA9qPs8YlkLnUI/view
- “The right phrenic nerve passes inferiorly down the neck to the lateral border of anterior scalene, medially across the border of the muscle, and parallel to the internal jugular vein that lays inferomedially. At the anterior, inferomedial margin of the anterior scalene muscle, the nerve is superficial to the second part of the right subclavian artery. The phrenic nerve passes medially to cross the pleural cupola deep to the subclavian vein. More medially, it crosses the internal thoracic artery at approximately the level of the first costochondral junction. The phrenic nerve should be carefully mobilized, avoiding traction injury or thermal injury from electrocautery, and retracted away from the ongoing dissection (typically medially). Anesthetic techniques that avoid muscle relaxation will facilitate the intraoperative testing of nerve function.”
- “The cords of the brachial plexus are identified laterally. The cords are named the lateral, posterior, and medial cord according to their relationship to the axillary artery. The cords pass over the first rib close to the cupola of the lung and immediately posterior to the subclavian artery. The medial cord, arising from the C8 and T1 nerve root, is the cord most commonly involved by tumor. The consequence of medial cord involvement includes compromise of the ulnar nerve as well as medial cutaneous nerves to the arm and forearm. The T1 nerve roots are usually divided lateral to the vertebral foramen with care taken to spare the long thoracic nerve and minimize the risk of scapular winging. The long thoracic nerve arises from branches of the C5-C7 nerve roots.”
- “ The lung and chest wall is resected en bloc with a stapler. The hilar dissection, while possible with video-assistance, is challenging.”
margins needed for NSCLC invading chest wall (incl Pancoast)
superior: 1 rib above
inferior: 1 rib below
lateral: 2-4cm
send frozens
indication(s) for chest wall reconstruction
- anterior defect (per TSRA)
- defect >5cm
- risk for scapular entrapment (5th±4th ICS)
indication(s) for adjuvant tx after R0 resxn of Pancoast NSCLC
all: chemo (cis/etopo) x2cycles
(IG 0160/SWOG 9416 was a periop trial)
typical NSCLC T size limit for SBRT
5cm
(￬effectiveness with ￪size)
NCCN guideline adjuvant RT indication(s) for NSCLC upstaged at resxn to N2
NO PORT unless ⊕margin OR
high-risk N2 features:
- extracapsular extension
- multi-station
- inadequate MLND
- refusal or intolerance of adjuvant systemic
generally postop/adjuvant chemo BEFORE RT
“In patients with clinical stage I/II upstaged surgically to N2 with completely resected disease, two randomized studies did not show an overall survival benefit of PORT, although locoregional control was significantly improved. PORT (generally following postoperative chemotherapy) may be considered for selected patients with high-risk N2 disease, such as extracapsular extension, multi-station involvement, inadequate lymph node dissection/sampling, and/or refusal or intolerance of adjuvant systemic therapy.
To minimize potential lung and heart toxicities, highly conformal RT techniques such as IMRT or proton therapy are preferred.”
NCCN guideline adjuvant RT indication(s) for NSCLC
NO PORT unless ⊕margin OR
high-risk N2 features:
- extracapsular extension
- multi-station
- inadequate MLND
- refusal or intolerance of adjuvant systemic
generally postop/adjuvant chemo BEFORE RT
“In patients with clinical stage I/II upstaged surgically to N2 with completely resected disease, two randomized studies did not show an overall survival benefit of PORT, although locoregional control was significantly improved. PORT (generally following postoperative chemotherapy) may be considered for selected patients with high-risk N2 disease, such as extracapsular extension, multi-station involvement, inadequate lymph node dissection/sampling, and/or refusal or intolerance of adjuvant systemic therapy.
To minimize potential lung and heart toxicities, highly conformal RT techniques such as IMRT or proton therapy are preferred.”
NCCN guideline adjuvant RT indication(s)/recommendation for NSCLC cN2 undergoing neoadj systemic tx + resxn
- “Preoperative systemic therapy and postoperative RT is an option for patients with resectable N2 NSCLC (minimal N2 and treatable with lobectomy).
- Preoperative concurrent chemotherapy/RT is an alternative option for patients with resectable N2 NSCLC and is recommended for resectable superior sulcus tumors.
- The optimal timing of RT in trimodality therapy (preoperative with chemotherapy or postoperative) is not established and is controversial.”
post-tx follow-up/surveillance imaging interval after definitive SBRT
Goyal: 3mo CT, 6mo PET, 9mo CT ￫ Q1Y CT
NCCN guideline curative-intent mgmt of oligometastatic/oligoprogressive N0 (by invasive mediastinal staging) NSCLC to brain (single site)
with definitive tx of intrathoracic dz feasible
- SRS (OR resxn if needed for sxs or dx ￫ SRS or whole-brain RT) of brain met
- ± systemic tx + restaging
- invasive mediastinal [re-]staging
- surgical resxn or SBRT of thoracic 1°
- systemic tx if not already given
TSRA: only if N0
NCCN guideline curative-intent mgmt of oligometastatic/oligoprogressive N0 (by invasive mediastinal staging) NSCLC to single site (non-brain)
with definitive tx of intrathoracic dz feasible
- ± systemic tx + restaging
- invasive mediastinal [re-]staging
- surgical resxn or SBRT of thoracic 1°
- surgical resxn or SBRT of met
- systemic tx if not already given
TSRA: best if N0-1
NCCN guideline mgmt of oligometastatic/oligoprogressive N+ (by invasive mediastinal staging) NSCLC to single site (non-brain)
with definitive tx of intrathoracic dz feasible
definitive chemoRT
NCCN guideline [implied] pre-requisites/criteria to be considered for curative-intent oligometastatic/oligoprogressive NSCLC paradigm tx
- limited sites & volume of metastatic dz (<3-5)†
- N0
- definitive tx of thoracic 1° feasible/planned
†”Including selected patients with stage M1c and limited number and volume of metastatic lesions amenable to definitive local therapy. Clinical trials have included up to 3 to 5 progressing sites.”
NCCN guideline criteria for consideration of surgery (neoadj systemic + resxn) in N2 NSCLC
- T<4
- healthy
- single-station
- non-bulky (<3cm)
- ≤lobectomy-requiring
Which actionable mutations have TT as 1st-line systemic tx in advanced (unresectable) NSCLC?
EGFR (osimertinib for ex19del / amivantamab-vmjw + chemo for ex20ins)
ALK (alec/briga/lorla-tinib)
ROS1 (entrec/crizo/repotrec-tinib)
BRAF (dabrafenib+trametinib/encorafenib+binimetinib)
NTRK (laro/en-trectinib)
MET (capma/tepo-tinib)
RET (selperca/pralse-tinib)
even if PD-L1⊕ (≥1%)
1st-line systemic tx options in advanced (unresectable) NSCLC PD-L1⊕ high (≥50%)
IO or chemoIO:
- pembro
- carbo/cis-platin + pemetrexed + pembro
- atezo
- cemiplimab-rwlc
1st-line systemic tx options in advanced (unresectable) NSCLC PD-L1⊕ low (≥1-49%)
platinum-based doublet chemoIO:
- carbo/cis-platin + pemetrexed + pembro
- carbo/cis-platin + pemetrexed + cemiplimab-rwlc
1st-line systemic tx options in advanced (unresectable) NSCLC PD-L1⊖ (<1%)
platinum-based doublet chemoIO:
- carbo/cis-platin + pemetrexed + pembro
- carbo/cis-platin + pemetrexed + cemiplimab-rwlc
NCCN guideline postop surveillance after R0 resxn of pI-II NSCLC
CT chest Q6mo x2-3y ￫ LDCT Q1Y
NCCN guideline postop surveillance after R0 resxn of pIII-IV(oligo) NSCLC
CT chest Q3-6mo x3y ￫ CT chest Q6mo x2y ￫ LDCT Q1Y
NCCN guideline post-tx surveillance after SBRT of cI-II NSCLC
CT chest Q3-6mo x3y ￫ CT chest Q6mo x2y ￫ LDCT Q1Y
my postop surveillance after R0 resxn of NSCLC
early-stage/usu:
CT chest Q6mo x2y ￫ Q1Y
adv/concerns:
CT chest @ 3mo,6mo ￫ Q6mo x2y ￫ LDCT Q1Y
NCCN guideline indication(s) & regimens for adjuvant systemic tx for resected limited stage SCLC
ALL: systemic tx
N+: systemic tx ± mediastinal RT (sequential or concurrent)
NCCN guideline mgmt of limited stage SCLC cI-IIA (T1-2N0M0)
- lobectomy + MLND
- N0: systemic tx
N+: systemic tx ± mediastinal RT (sequential or concurrent)
NCCN guideline mgmt of limited stage SCLC cIIB-IIIC OR cI-IIA (T1-2N0M0) not undergoing resxn
- cI-IIA: SBRT ￫ systemic tx OR concurrent chemoRT
- cIIB-IIIC: concurrent chemoRT
NCCN guideline mgmt of extensive stage SCLC
combination systemic tx ± selective RT for sxs
￫ re-staging (CT C/A/P + MRI brain):
- complete or partial response to limit stage: PCI > brain surveillance
- complete or partial response to extensive stage: brain surveillance > PCI ± thoracic RT
- stable dz: surveillance
- progression: 2nd-line/palliative
NCCN guideline 1st-line systemic tx for extensive stage SCLC
platinum-based doublet chemoIO:
carboplatin + etoposide + atezo/durva ￫ atezo/durva maintenance
NCCN guideline 1st-line systemic tx for resected limited stage SCLC
platinum-based doublet:
cisplatin + etoposide
NCCN guideline mgmt of small bx-“proven” SCLC in never-smoker
resect
(presume mis-dx carcinoid)
NCCN guideline indication(s) for PCI (ppx cranial irradiation) in SCLC
- all non-surgical pts with good response to systemic tx
- resected >pI (>T1-2aN0M0)
consider PCI only if good neurocog status
adjunct Rx to reduce neurocognitive impairment 2/2 whole-brain RT (WBRT) for SCLC
memantine
during & after
RT technique to reduce neurocognitive impairment 2/2 whole-brain RT (WBRT) for SCLC
hippocampal-sparing/-avoidance (HA) with IMRTs
NCCN guideline mgmt of cI-IIIA (resectable) bronchopulmonary carcinoid/NET
anatomic resxn + MLND
NCCN guideline indication(s) for adjuvant systemic tx for resected bronchopulmonary carcinoid/NET
NONE
NCCN guideline postop surveillance for resected bronchopulmonary carcinoid/NET
CT chest with contrast + CT A/P with contrast (multi-phase) ± biochem markers @3-12mo ￫ Q1-2Y x≥9y/til 10y ￫ ±cont
heparin dose prior to clamping PA (/PV?) for rx and/or sleeve
2000u
maximum PA involvement (circumference) amenable to 1° rx
<25% circumference
mgmt of >25% PA involvement during lung resxn
tangential pericardial patch rx OR circumferential resxn + re-anastomosis or recon
risk of radiation pneumonitis with SBRT in ILD
30-50%
6% risk of fatal complications (SESATS)
differentiating features of typical v atypical bronchopulmonary carcinoid/NET
- ￪mitotic index (2-10/mm2)
- ⊕necrosis
average survival after dx of malignant pleural effusion
4-7mo (SESATS)
SESATS:
“Approximately 150,000 patients are found to have malignant pleural effusions in the United States each year. Although some patients are initially asymptomatic, most will eventually develop dyspnea. Considering that malignant pleural effusions are associated with an average survival of only 4–7 months, the management strategy should be focused on controlling symptoms while minimizing repeat procedures and treatment-related morbidity.”
rate of repeat thoracentesis requirement after initial thora for malignant pleural effusion
60% within 9d (SESATS)
SESATS:
“The initial management strategy when a suspected malignant pleural effusion is found is large-volume thoracentesis to establish a diagnosis and determine whether or not any symptoms improve after drainage. However, a recent study has shown that approximately 60% of patients will require another drainage procedure within 9 days of initial malignant pleural effusion drainage. Repeat thoracenteses can be a management option if it is patient preference, but this strategy generally means that the patient will necessarily go through a cycle of worsening dyspnea symptoms between drainage procedures. Historically, the preferred treatment for patients with recurrent malignant pleural effusions is chemical pleurodesis with talc, which can be performed through an indwelling tube or at the time of thoracoscopy. However, pleurodesis will only be effective at preventing effusion recurrence if the visceral and parietal pleura are in apposition after effusion drainage.”
