- Typically disseminated at presentation - Rapid onset of symptoms (cough, SOB, wheezing, PNA) - Often with signs of metastatic disease (abdominal pain, bone pain, vomiting, headache)

Small cell lung cancer Flashcards by Ned Jones

SCLC vs NSCLC in terms of doubling time, mets

SCLC = rapid doubling time, higher growth fraction, early widespread hematogenous metastases.

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SCLC chemo and radiosensitivity

highly sensitive to initial chemo and radiation

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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)

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Driver mutations and SCLC?

No driver mutations amenable to currently available targeted drug therapies.

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Impact on mortality from lung cancer screening.

None. All mortality reduction from screening is for NSCLC.

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Common sites of mets

Brain, *liver, bone, *adrenal glands.

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Most frequent cause of paraneoplastic syndromes

SCLC!

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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)

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staging workup

MRI brain
PET/CT to confirm limited stage (especially if lymphadenopathy suspected)
IF PET/CT not done –> CT chest/abdomen/pelvis

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basic staging classification

Limited stage and extensive stage

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Median survival of limited stage

About 16 months

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Median survival of extensive stage

About 10 months

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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)

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Extensive stage definition

Tumor beyond ipsilateral hemithorax or metastatic disease.

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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)

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Main chemotherapeutic agents

Cisplatin/carboplatin
etoposide
topotecan/irinotecan
atezolizumab

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Goal of therapy for limited and extensive stage

Limited stage = cure
Extensive stage = palliative

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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

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What is PCI?

prophylactic cranial irradiation

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Treatment in general of extensive-stage SCLC

Palliative chemoimmunotherapy, followed by PCI

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what is WBRT?

whole-brain radiation therapy

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Complications of concurrent chemoradiation

Increased risk of esophagitis, dysphagia, odynophagia, oropharyngeal/esophageal candidiasis, pneumonitis

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role for maintenance chemo in SCLC?

None (no survival benefit)

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Definition of refractory

tumor progresses during the initial therapy or did not respond to initial therapy

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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