Lung cancer Flashcards
General Mx of pts with advanced lung cancer
1) Communication & family conference
- clarify pt & family’s expectation
- make clear decision re direction of care
- consider stopping life-sustaining therapy if it’s futile/ not in pt’s best interest/ refused by pt
2) Other non-chemotherapy Rx
- consider Next Generation Sequencing (NGS) to look for rarer mutation (e..g. KRAS, NTRK, RET), which may enable pt to have directed therapy (which may be given in poor ECOG status)
3) Mx of Sx
A) SOB
- Ix causes & Rx accordingly:
Anaemia –> transfusion
Effusion: pleural/ pericardial
PE –> tapping
Obstruction - SVCO/ tumour compression –> Dexa 8mg TDS wean down weekly until lowest dose pt can cope with/ stenting
Lymphangitis carcinomatosis –> dexa as per dosing for SVCO
Infection - pneumonia –> Abx
Also use opioid for SOB
B) pain
- bone pain: XRT
- hyperCa: hydration, calcitonin, bisphosphonate, denosumab
- optimise opioid use with oral/ subcut opioids e.g. use Targin (oxycodone & naloxone)
- use laxatives
C) cough
- Abx
- Mucolytics & neb saline
- bronchodilator
- in haemoptysis: tranexamic acid
- cough suppressant (e.g. codein)
- sedation
4) Psychosocial
- Ax depression –> psychiatric referral
- delirium - Ix & Rx e.g. constipation, hypoglycemia, electroly imbalance, sepsis, drugs). Consider benzo, antipsychotic
ECOG performance status
0: fully active
1: able to do light work
2: able to self-care, up & about >50% of time
3: limited self-care, up & about <50% of time
4: cannot do any self-care, bed/ chair bound
5: dead
Lung cancer staging
Based on 8th edition of TNM staging
- tallies with 5y survival rate:
IA1: 90%
IA2: 85%
IA3: 80%
IB: 70%
IIA: 65%
IIB: 55%
IIIA: 40%
IIIB: 25%
IIIC: 12%
IVA: 10%
IVB: 0%
Lung cancer screening - previous studies & outcome
(reference: Journal of Thoracic Oncology, Lung Cancer Screening in Asia: An Expert Consensus Report 2023)
1) Previous studies & outcome:
- The National Lung Screening Trial (NLST), US: Annual LDCT reduces mortality vs CXR
- NELSON study, Netherlands, Belgium: lower mortality in LDCT vs no LDCT
- The Taiwan Lung Cancer Screening in Never Smoker Trial (TALENT): LDCT for never smokers (12k subjects from 2015-2019 with risk factors of FHx of lung Ca within 3rd-deg relatives, passive smoker, TB, COPD, cooking index ≥110 & not using ventilator during cooking):
96.5% NSCLC diagnosed at stage 0 or I
- LUSI trial, Germany: reduced mortality after LDCT esp among women
Risk factors for lung cancer
Smoking
Age
FHX of lung cancer
Hx of other cancers
Second-hand/passive smokers
indoor cooking & heating fumes
outdoor air pollution
Environmental or occupational lung carcinogens (e.g. asbestos, silica, radon)
pulmonary diseases (e.g. TB, COPD, ILD)
Lung cancer screening - Benefits & Disadvantages
(reference: Journal of Thoracic Oncology, Lung Cancer Screening in Asia: An Expert Consensus Report 2023)
1) Benefit:
- incidence & mortality of lung ca is highest in Asia vs Europe/USA
- detect early is amenable to curative treatment, thus reducing mortality
- cost effective
2) Potential disadvantages:
- risk of radiation (but lower with LDCT)
- stress to pt
Lung cancer screening - Challenges in Asia
(reference: Journal of Thoracic Oncology, Lung Cancer Screening in Asia: An Expert Consensus Report 2023)
Challenges in Asia:
- economic limitation
- lack effort for early detection
- lack gov prog
- Cases among non-smoker Asian women higher compared to Europe/US
- lack of public awareness & smokers reluctance to screening, reluctance of pts with nodules to have invasive procedure of Bx
- Nodule related to infection in high prevalence countries with TB
Lung cancer screening - Established screening programs in other countries
(reference: Journal of Thoracic Oncology, Lung Cancer Screening in Asia: An Expert Consensus Report 2023)
1) The US Preventive Services Task Force (USPSTF): annual screening with LDCT, age 50-80y with ≥20pack-years in current & former smokers who quit smoking within the past 15y
2) Indonesia:
Lung cancer screening and smoking cessation are recommended with TB screening program in high-risk individuals (smoking, occupational & FHx) - LDCT once every 2y for high-risk pts negative for TB but persistent cough >2w.
No nationwide screening program via universal health coverage, but if Sx appear, pt can be referred to secondary hosp for LDCT (covered by national insurance)
3) Japan:
Screening among smokers by plain CXR& sputum cytology as population-based screening. LDCT as opportunistic screening method
4) Spore:
LDCT screening as individual-level decision & conducted as opportunistic screening method.
Lung cancer screening - Suggested screening programs
Suggested screening:
- LDCT yearly for high risk pts (age 50-75y) and ≥20pack/years smoking
- Stop screening age >80y or unwilling curative Rx
- Non-smokers age 50-75 with FHx of lung Ca among 1st deg relatives
Smoking cessation program and reduction in environmental exposure ti carcinogens
From ESMO:
Screening:
- LDCT: reduces mortality in high risk subjects (≥30pack years or ≤15y since cessation, age 55-74y)
- LDCT to be offered to current or former heavy smokers age 55-74y
- CXR, sputum cyto, biomarkers are not recommended
Pulmonary carcinoid tumour
- Epi
- Sx
- Ix
- Mx
= neuroendocrine tumour
Types: (depends on mitotic frequency & necrosis)
1) low grade typical carcinoids (TC) - usu non-smokers
2) intermediate grade atypical carcinoids (AC) - usu smokers
Epi:
- 1-2% of all lung tumours
- F>M
- Age: 40-50s
- prognosis 5-y survival: TC (87-100%), AC (40-60%)
Sx:
- in endobronchial lesion (70%): haemoptysis, cough, recurrent infection, wheeze)
- in peripheral lesion: ASx
- paraneoplastic syndrome:
a) Cushing’s syndrome (2-6%): releases ectopic ACTH) –> truncal obesity, moon facies, HTN, hirsutisgm, hyperpigmentation
b) Carcinoid syndrome (1-5%): releases serotonin –> flushing, diarrhoea, palpitations, wheeze
c) Acromegaly: releases GHRH
Ix:
1) CECT Thorax:
- well-defined rounded lesion with contrast enhancement (due to vascularity)
2) PET CT:
- not suitable for TC due to being hypometabolic
3) PET with Gallium-68-labelled somatostatin analogues - much more sensitive
4) Bronchoscopy: for central lesion
5) image-guided Bx: peripheral lesion
6) Serum cortisol, 24h urine cortisol
7) Serum ACTH
8) Serum GHRH, growth hormone, insulin-like growth factor 1
Mx:
1) Surgical resection for cure
2) Metastatectomy - in limited site, with aim for cure
3) Chemo in inoperable disease: temozolomide (platinum-based does not work)
4) mTOR inhibitor evarolimus - new
5) Somatostatin analogue (e.g. octreotide): for Sx of hypersecreting tumours, response 60%. Also to be given before surgery to prevent carcinoid crisis
Hamartomas
- Epi
- Sx
- Ix
- Mx
= benign mesenchymal tumours, composed of cartilage, fat, smooth muscle, connective tissue & bone
Epi:
- 3% of lung tumours (most common benign lung tumours)
- M>F
- Age: 60s
Sx:
- Usu ASx
- Sx when in endobronchial space
Ix:
- CT: peripheral solitary well-circumscribed rounded nodule with hypodense areas (fat) with flakes of calcification (popcorn-like)
- Bx
Mx:
- conservative
- surgery when aggressive & symptomatic
Pneumocytomas
- Epi
- Sx
- Ix
- Mx
= rare benign tumour
From type II pneumocytes, containing macroscopic haemorrhagic component
Epi:
- F>M
- Age: 50s
Sx: ASx
Ix:
1) CECT Thorax: solitary well-circumscribed rounded homogenous nodule, with marked contrast uptake (if contain haemorrhagic component)
2) PET CT: hypermetabolic
3) Bx
Mx:
1) Resection as has potential for malignant transformation in 4%
What is the work-up for lung cancer
1) General:
Hx, exam, Ax comorbids, Ax performance status
2) Imaging:
CT Thorax & abdomen, PET-CT, MRI brain
3) Laboratory:
FBC, RP, LFT
4) Cardiopulm function:
Spiro, DLCO +/- CPET
ECG
5) Tissue Bx:
Via bronchoscopy/ EBUS/EUS/ CT-guided
6) Genomic profiling: EGFR, ALK, PD-L1
Staging in non-mets NSCLC
1) Do CT or PET-CT - decide whether there is mediastinal LN involvement
2) In LN negative - decide the position of the tumour and size:
- If N0 and peripheral tumour (outer third) and ≤3cm –> surgery
- If N1 or central tumour or tumour >3cmm–> tissue Bx (EBUS/EUS/VAM) –> mediastinal LN negative –> surgery
3) In LN positive - tissue Bx (EBUS/EUS) –>
if negative, confirm Bx by doing video-assisted mediastinoscopy –> if negative again, for surgery
if positive on Bx (EBUS/EUS/VAM), for multimodality Rx
4) Others:
A) CNS imaging:
- Contrast-enhanced MRI brain is more sensitive than CECT brain (which is used if MRI not available)
- Maybe useful in curative therapy (for hilar/mediastinal LN).
- Should be done in:
a) For stage IIIA with curative intent, brain met screening should be done
b) Mets disease
c) Pt with neuro deficits
- Also to scan the spine in leptomeningeal disease (e.g. pt presents with bowel/urinary Sx/ bilat LL weakness)
B) HPE required in single PET-positive distant lesion
C) PET-CT is required TRO bone mets (most sens)
Treatment that causes acute pneumonitis
Resource:
Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline
doi:10.1200/JCO.2017.77.6385
1) Immune check inhibitor therapy (Anti PD-1/ PDL-1): usu 2-4/12 up to 20/12 after Rx (incidence 3%)
- Mx: depends on grading.
In grade 3-4 -
a) permanent discontinuation & steroid iv MTP 1-2mg/kg/d tapering over 4-6w.
b) Add on infliximab/ IVIG/ MMF/ cyclophosphamide if no improvement after 48h
c) Offer BAL
d) Give empirical Abx
2) XRT - 1-3/12 post XRT
Treatment that do not cause pulmonary SE: Carboplatin & permetrexed
Treatment of early stage NSCLC inc locally advanced stage
Treatment:
Stage I-IIIA
1) Surgery
- Offer to Stage I & II
- If not a surgical candidate (or not willing to take surgical risk) –> curative RT (e.g. Stereotactic Ablative Body Radiotherapy, SABR)
- Lobectomy for tumours ≥2cm. It has lower recurrence compared to wedge resection or segmentectomy
- LN dissection should be done
2) Systemic therapy
3) Adjuvant chemotherapy
- Offer to Stage IIB and IIIA
- To be considered in Stage IIA
- Chemo of choice: two-drug combination with cisplatin (cisplatin + vinorelbine/ gemcitabine/ docetaxel/ pemetrexate)
- Carboplatin is alternative to cisplatin (cisplatin has better survival benefit but higher toxicity: N,V, alopecia, AKI, neuropathy)
4) Adjuvant targeted therapy
- Osimertinib: indicated after complete tumour resection with stage IB-IIIA with EGFR exon 19 deletion or exon 21 L858R substitution mutation
ADAURA study: 80% reduction in disease recurrence following complete resection
5) Primary RT & postop RT
- For non-surgical Rx in stage I: in pt with comorbidities/ refuse surgery
- Option: SABR (stereotactic ablative body radiotherapy), but not suitable for central tumours (within 2cm of mediastinal structures) –> radical RT/ radiofrequency ablation
- Post-op RT (PORT) for R1 (microscopic residual tumour at resection margin/chest wall)
- No role for prophylactic cranial RT in stage III
Locally advanced NSCLC
- Divided into resectable and unresectable
- Resectable =
1) single station N2 (other LN already cleared from Bx) –> postop chemo to be advised
2) T4 N0, and R0 is considered feasible
3) After induction therapy, nodal down-staging achieved and pneumonectomy avoided
- Unresectable – R0 not possible after induction therapy (as per MDT discussion) –>
Rx:
1) concurrent CRT has higher 5y survival compared to induction chemo followed by RT.
2) Immune checkpoint inhibitor durvalumab (given 1-42d after concurrent CRT) has survival benefit –> recommended in those who has not progressed from concurrent CRT (FDA approval is for all pt, European Med Agency EMA approval is for PD-L1 ≥1%
6) Follow-up:
- Surveillance every 6m for 3y, then depends on pt – do Hx, examination, CECT TAP (for PET-CT)
- Look out for Rx-related complications, relapse, occurrence of second primary tumour
Rx of advanced NSCLC:
- general consideration
- specific molecular oncogenic drivers +ve:
** (EGFR)
- molecular oncogenic drivers -ve
- PD-L1 +ve
- SCC
Rx of advanced NSCLC:
general consideration:
a) Rx is based on ECOG, age, comorbids, molecular pathology, pt’s preference
b) Systemic chemo to be offered for ECOG 0-2
c) Smoking cessation
d) Rx for targeted therapy first if available before immunotherapy
Treatment of EGFR-mutated NCSLC
- Continuous use of EGFR TKI in combination with chemo is not recommended, but
- combination of carboplatin + pemetrexed to gefitinib improved OS & PFS
- Almost all pt will develop resistance from acquired EGFR exon 20 T790M mutation (most common) –> to be checked for all pt on Gen1/2 EGFR TKI.
Rx: Osimertinib - Other less common acquired resistance to EGFR TKI: MET, HER2, PIK3CA, KRAS, small cell transformation.
Rx: chemo platinum doublet + atezolizumab + bevacizumab
Management of Stage IV NSCLC with specific oncogen mutation drivers
Rx of advanced NSCLC:
- general consideration
- specific molecular oncogenic drivers +ve:
** (ALK)**
- molecular oncogenic drivers -ve
- PD-L1 +ve
- SCC
Treatment of ALK-rearranged NCSLC
- 1st line: alectinib/ crizotinib/ ceritinib/ brigatinib.
Lorlatinib showed better outcome compared to crizotinib
- In progressive disease:
a) oligopregression: surgery/ XRT
b) systemic disease: re-Bx recommended but not mandatory.
- can give Lorlatinib after ≥1 ALK TKI
- then to consider chemo + VEGF inhibitor (bevacizumab) + PD-L1 inhibitor (atezolizumab)
Rx of advanced NSCLC:
- general consideration
- specific molecular oncogenic drivers +ve:
ROS1
BRAF
Other oncogenic drivers
- molecular oncogenic drivers -ve
- PD-L1 +ve
- SCC
Treatment of ROS1-rearranged NCSLC
- 1st line or 2nd line: crizotinib
-Pt who received crizotinib as 1st line, 2nd line: platinum based chemo
Treatment of BRAF V600-mutated NCSLC
- 1st line: Debrafenib-trametinib, or
platenum based chemo
*Dabrafenib is a BRAF inhibitor
* Trametinib is a MEK inhibitor
Treatment of other oncogenic driver mutation NCSLC
- RET: Selpercatinib who have received immunotherapy +/- chemo
- MET: Crizotinib/ Capmatinib/ Tepotinib for METex14 variant
- NTRK: Larotrectinib/ Entrectinib
Rx of advanced NSCLC:
- general consideration
- specific molecular oncogenic
- molecular oncogenic drivers -ve
- PD-L1 +ve
- SCC
Rx of advanced NSCLC:
molecular oncogenic drivers -ve
a) EGFR - & ALK -, PD-L1 ≥50%: Pembrolizumab or Atezolizumab
b) EGFR - & ALK -, regardless PD-L1 (in non-squamous):
i) Pembrolizumab + Pemetrexate + Platinum based chemo
ii) Other options (in EGFR exon 19 deletion or L858R mutation): Atezolizumab, bevacizumab, carboplatin + paclitaxel
c) EGFR - & ALK -, regardless PD-L1 (in squamous):
Pembrolizumab + Paclitaxel + Carboplatin
d) EGFR - & ALK -, regardless PD-L1 in high tumour burden, for both non-squamous and squamous NSCLC:
Nivolumab + Ipilimumab
*Ipilimumab: CTLA-4 Ab
d) No actionable oncogenic driver + contraindication to immunotherapy:
i) In PS 0-2: Chemo with platinum doublets (preferred: Carboplatin + nab-P (albumin bound paclitaxel)
ii) In SCC: Platinum-based + gemcitabine/ vinorelbine/ taxane
ii) In Non-SCC: Platinum based + gemcitabine/ vinorelbine/ taxane for 4 cycles, the pemetrexed or gemcitabine (or Erlotinib in EGFR mutation) maintenance
iv) In PS 3-4: best supportive care (BSC) or immunotherapy
Small Cell Lung Cancer (SCLC)
- b/ground
- Ix
B/ground:
- So far no molecular studies for SCLC
- May lead to autoimmune mediated paraneoplastic neurological Sx
Ix:
a) Bloods:
FBC, RP, Ca, LFT, LDH, BSL
b) Imaging:
i) CECT Thorax & Abdomen.
ii) MRI brain is for limited disease & stage IV eligible for but choose not to do prophylactic cranial irradiation (PCI)
iii) PET CT for limited disease
iv) Bone scintigraphy when PET-CT not done in limited disease
c) Biopsy:
- inc BMAT in limited disease TRO bone marrow infiltrate
d) PFT, CPET in surgical candidates
Small Cell Lung Cancer (SCLC)
- staging
- Rx
- F/up
Staging:
- 2 stages: Limited and Extensive
Limited-stage
= tumour confined to one hemithorax & regional lymph nodes
- Rx:
1) Limited-stage: Surgical resection
- R0: adjuvant cisplatin-etoposide
- R1-2: concurrent CRT, then consider PCI
Extensive-stage:
- Rx:
i) concurrent CRT (for PS 0-1) or sequential CRT (for PS≥2), then consider PCI
- Preferred chemo: cisplatin (or carboplatin) + etoposide
- Other chemo options: Cisplatin + irinotecan (or topotecan)/ gemcitabine – carboplatin
ii) Systemic Rx: Anti-PD-L1 inhibitors Atezolizumab and Durvalumab + 4 cycles of platinum + etoposide (in PS 0-1 with no contraindication to immunotherapy)
iii) RT: PCI
Follow-up:
- Limited-stage: 3-6m for 2y, then lengthen the duration
