Small cell lung cancer Flashcards
SCLC vs NSCLC in terms of doubling time, mets
SCLC = rapid doubling time, higher growth fraction, early widespread hematogenous metastases.
SCLC chemo and radiosensitivity
highly sensitive to initial chemo and radiation
typical clinical course
High initial response rates, but then most patients relapse within a few months of completing initial therapy and die (tumor rapidly develops resistance)
Driver mutations and SCLC?
No driver mutations amenable to currently available targeted drug therapies.
Impact on mortality from lung cancer screening.
None. All mortality reduction from screening is for NSCLC.
Common sites of mets
Brain, *liver, bone, *adrenal glands.
Most frequent cause of paraneoplastic syndromes
SCLC!
paraneoplastic syndromes associated with SCLC
1) *SIADH
2) ectopic adrenocorticotropic hormone (ACTH) production, Cushing syndrome
3) Lamber-Eaton syndrome
4) Subacute cerebellar degeneration
5) encephalomyelitis
6) Myoclonus-opsoclonus)
staging workup
MRI brain
PET/CT to confirm limited stage (especially if lymphadenopathy suspected)
IF PET/CT not done –> CT chest/abdomen/pelvis
basic staging classification
Limited stage and extensive stage
Median survival of limited stage
About 16 months
Median survival of extensive stage
About 10 months
Limited stage definition
Tumor confined to ipsilateral hemithorax and regional nodes able
- tumor must be be encompassed in a single tolerable radiotherapy port (for chemoradiotherapy)
Extensive stage definition
Tumor beyond ipsilateral hemithorax or metastatic disease.
Typical presentation
- Typically disseminated at presentation
- Rapid onset of symptoms (cough, SOB, wheezing, PNA)
- Often with signs of metastatic disease (abdominal pain, bone pain, vomiting, headache)
Main chemotherapeutic agents
- Cisplatin/carboplatin
- etoposide
- topotecan/irinotecan
- atezolizumab
Goal of therapy for limited and extensive stage
Limited stage = cure
Extensive stage = palliative
Standard of care for limited-stage SCLC (including cycles + adjuvant treatment)
- Concurrent chemoradiation ASAP w/ 4 to 6 cycles of cisplatin plus etoposide with concurrent radiation
- followed by PCI for 4 to 6 weeks after completion of therapy
What is PCI?
prophylactic cranial irradiation
Treatment in general of extensive-stage SCLC
Palliative chemoimmunotherapy, followed by PCI
what is WBRT?
whole-brain radiation therapy
Complications of concurrent chemoradiation
Increased risk of esophagitis, dysphagia, odynophagia, oropharyngeal/esophageal candidiasis, pneumonitis
role for maintenance chemo in SCLC?
None (no survival benefit)
Definition of refractory
tumor progresses during the initial therapy or did not respond to initial therapy
Definition of sensitive relapse
Tumor progression occurs 90 days or more after last day of initial treatment
Definition of resistant relapse
Tumor progression occurs within 90 days or more of last day of initial treatment
Treatment of relapse if no clinical trial available
IF >6 months, repeat original regimen
If between 3 and 6 months, topotecan
Preferred management of refractory or relapsed disease
Clinical trial
Role for surgery?
- In rare cases, SCLC is diagnosed at an early stage and surgery is recommended followed by adjuvant chemo
Follow up imaging timeframe
CT chest q3 months during first 2 years
most common lung cancer types/breakdown statistically
Non-small cell lung cancer (NSCLC) accounts for the majority (approximately 85 percent) of lung cancers with the remainder as mostly small cell lung cancer (SCLC).
Evidence/utility for PET/CT for SCLC diagnosis
*Routinely used but has never shown a survival benefit.
- LIMITED STAGE: More accurate in detecting occult disease, so should really be used if concern for occult disease (patients with limited stage, potentially resectable disease, ie finding occult met would change management).
- More accurate in determining mediastinal disease.
SUV criteria for determining what defines a malignant nodule
There are no standardized criteria defining what constitutes a positive PET result and no ideal cut-off point for the standardized uptake value (SUV).
how to determine if lymph node is malignant based on SUV criteria
lymph nodes with FDG uptake greater than that observed in the mediastinal blood pool are highly suspicious for metastatic disease
Where SCLC typically arises
Central airways, infiltrating the submucosa, and gradually narrowing the bronchial lumen through extrinsic or endobronchial spread.
Most common radiographic presentation of SCLC
large hilar mass with bulky mediastinal adenopathy.
Etoposide SE’s
- myelosuppression
- hypersensitivity reaction
- pulmonary toxicity/ILD
- nausea/vomiting
- see others on package insert
Preferred regimen for extensive stage SCLC
- Cis or carboplatin + etoposide
atezolizumab
Histology of small cell lung cancer
neuroendocrine
Typical clinical course of small cell
Responds rapidly to both chemotherapy and radiotherapy (RT), it commonly relapses within months despite treatment.
Staging classification
limited-stage (LS) versus extensive-stage (ES) disease
Preferred regimen for extensive stage
Carboplatin-etoposide and atezolizumab, followed by maintenance atezolizumab
why carboplatin etoposide is preferrable if extensive stage
Less nephrotoxicity, neurotoxic, and less emetogenic, with comparable outcomes to cisplatin
general term for irinotecan class of drugs
camptothecin analogues
duration of induction chemotherapy for SCLC
The optimal duration of induction chemotherapy for patients with SCLC is not well defined; conventional approach is to give 4-6 cycles.
Initial management of SCLC patient with brain mets
If asymptomatic – Upfront systemic therapy followed by WBRT.
IF symptomatic brain metastases – Upfront WBRT, followed by induction systemic therapy (no point in surgery going to come back)
Why WBRT is used for SCLC and not SRS
WBRT is typically preferred for those with SCLC and any degree of intracranial disease, due to the propensity for SCLC to recur intracranially.
Response assessment following induction chemo
Ct chest/abdomen/pelvis with contrast + brain MRI
Treatment of SCLC relapse within 6 months
Topotecan OR
Lurbinectedin OR
Clinical trial
What is intensification therapy?
Consolidation therapy, just another term
Targeted agents approved for SCLC
None with proven benefit to date
EP regimen is
Etoposide/cisplatin
Standard of care chemo regimen for extensive stage + duration
- EP (etoposide + cisplatin or carbon-latin doublet) + immunotherapy with a CPI
- 4-6 cycles
Why EP is standard of care in the US
Many regimens have been shown to be equally effective but EP is less toxic
Role for maintenance chemotherapy
None, hasn’t been shown to be effective in SCLC (resistance)
Common change in regimen when patients become extensive stage
Change from cisplatin to carboplatin (better tolerated, equal efficacy)
FDA-approved IO drugs for SCLC
- atezolizumab
- durvalumab
Evidence for PCI in extensive stage
- controversial (conflicting data, including a study with shorter OS + a lot of people develop brain mets even with PCI)
New FDA approved drug for relapsed SCLC
Lurbinectedin (“lure”)
Treatment of relapsed SCLC depends on…
How long after from 1L therapy patient relapses
Lurbinectidin MOA in general
Pro-apoptotic + alters the tumor microenvironment
Preferred chemo regimen for limited stage
Cisplatin + etoposide
initial branch point in management of extensive stage aside from brain mets
presence of localized symptomatic sites, which warrant RT before systemic therapy
Preferred management of sensitive relapse
Repeat original regimen
limited stage management in poor PS
Systemic therapy and RT often done sequentially rather than concurrently
management of relapse in SCLC
- if greater than 6 months out, rechallenge original regimen
- if within 6 months, lurbinectidin
fractionation schedule in limited stage SCLC
BID fractions
first line for limited stage SCLC, followed by PCI
- concurrent chemoRT with cisplatin-etoposide, followed by PCI
Radiation fractonation for limited stage small cell
Twice daily
adjuvant management of resected early stage SCLC
4 cycles of cisplatin, etoposide
