Jung: Lung Cancer

What risk factors other than first- and second-hand tobacco smoke are associated with an increased risk of developing lung cancer?

1. Age 

2. Smoking 

3. COPD or pulmonary Fibrosis 

4. Occupational Exposure 

5. Residential radon exposure 

6. Air pollution 

7. Prior radiation to chest 

8. Family history of cancer or previous hx of lung cancer 

9. Veterans 

What abnormal mutations or expressions of molecular markers are associated with an increased risk of developing lung cancer?

1. some common mutations

   1. EGFR

   2. KRAS * more common in smokers

   3. ALK

What three sub-types of histologies comprise the majority of non-small cell lung cancer (NSCLC)?

1. Adenocarcinoma

2. Squamous

3. Large Cell 

Why is surgery typically not a treatment option for small cell lung cancer (SCLC), even for limited stage disease?

Dr Jung notes: "Surgery IS an option for localized SCLC, however, it is rare that we have patients diagnosed with localized small-cell lung cancer (< 5% of patients with SCLC will have a disease that can be surgically removed). Tumor location can be a contraindication to surgery; especially if that tumor is located on/near major blood vessels or generally in a place that would be difficult to resect safely. More commonly, if there is a large amount of lymph node involvement or if patient is not a surgical candidate (due to patient comorbidities or tumor location) then treatment will consist of concurrent chemotherapy + radiation without surgery for localized SCLC."

Name 5 signs or symptoms that would suggest the presence of lung cancer.

1. Cough 

2. Dyspnea

3. Hemoptysis/and or hoarseness 

4. Supervena cava syndrome (more common in SCLC)

5. Metastatic: weight loss, bone pain, headaches, confusion and/or spinal cord compression 

SCLC Limited Stage Treatment and side effects

Surgery (only 5% of patients eligible)  Concurrent chemoradiation  1st line: Cisplatin / Etoposide q21 days x 4 cycles  If CKD/HF/hearing loss: use carboplatin instead Prophylactic cranial irradiation(PCI)  May be offered after finishing chemoradiation  Good option for those at risk of brain metastasis Caution in patients > 60+ d/t cognitive decline  Durvalumab consolidation x 24 months (ADRIATIC)  Use after chemoradiation  Improved overall survival + prolonged progression-free survival

Cisplatin: nephrotoxicity (must dose using Calvert equation), ototoxicity, peripheral neuropathy  Highly emetogenic Etoposide: infusion related hypotension & bronchospasm, myelosuppression, low emetogenicity, secondary leukemia  Durvalumab: rash, pruritis, hyperglycemia, hypocalcemia, hyponatremia, lymphocytopenia, fatigue

SCLC Extensive Stage Treatment and side effects

1st line: chemoimmunotherapy is SOC, 4 cycles (21 days): 4 cycles (21 days):  Carboplatin  Etoposide  Atezolizumab  → Followed by atezolizumab maintenance until progression OR 4-6 cycles(21 days):  Carboplatin  Etoposide   Durvalumab  → Followed by durvalumab maintenance until progression  OTHER recommended trx:  If ineligible for immunotherapy(autoimmune disorder, use of immunosuppressive agents), then 1st line:  Carboplatin  Cisplatin  Optional: Irinotecan w/ platins  6 cycles max, re-assess at cycle 4 Whole brain irradiation Give BEFORE chemo in symptomatic brain metastases Give AFTER chemo in asymptomatic patients  Memantine reduces cognitive decline during/after radiation therapy

SCLC Subsequent therapy Treatment and side effects

Second line:  Progression > 6 months following chemo:  Platinum doublet (carbo/etop)  AVOID PDL-1 agent if progression on atezolizumab/durvalumab maintenance  Progression ≤ 6 months:  Lurbinectedin  Topotecan (PO or IV)  Irinotecan  Tarlatamab-dlle  Other 2nd line:  Docetaxel, pacitaxel, gemcitabine, temozolomide, vinorelbine Combo therapy: Cyclophosphamide, doxorubicine, vincristine  3rd line:  Depends on performance status

Of what significance is renal function in a patient who is to receive SCLC treatment including cisplatin and etoposide?

1. Cisplatin is known to have nephrotoxicity

2. If someone has impaired renal function (CKD), they should switch to carboplatin

What is the likely cause of hypotension arising during the treatment of a patient with SCLC with atezolizumab, carboplatin, and etoposide?

Etoposide (infusion related hypotension & bronchospasm)

How will the presence of specific somatic mutations alter the treatment of NSCLC?

1. some common mutations

   1. EGFR

   2. KRAS * more common in smokers

   3. ALK

2. These can drive what agents we used in treatment

   1. If we have EGFR and ALK mutations, they are known to have a lower response rate to immunotherapy, regardless of PDL-1 expression

How would a patient with superior vena cava (SVC) syndrome present?

face/neck swelling, distended neck veins, cough, dyspnea, orthopnea, upper extremity swelling, distended chest vein collaterals, and conjunctival suffusion.

What is the preferred, first-line treatment for limited stage small cell lung cancer?

1. Concurrent chemotherapy + radiation, followed by adjuvant immunotherapy 

2. 1st line: Cisplatin / Etoposide q21 days x 4 cycles 

What is the preferred, first-line treatment for extensive stage small cell lung cancer for patients without a contraindication to immunotherapy?

1. Extensive (metastatic): chemotherapy + immunotherapy, unless Contraindications to immunotherapy 

2. Carboplatin + Etoposide + Atezolizumab(4 cycles) or Dorvalumab(4-6 cycles)

What is the preferred, first-line treatment for extensive stage small cell lung cancer for patients with a contraindication to immunotherapy?

1. carboplatin and etoposide

2. Cisplatin and etoposide

can sub etopo for irino

For what histologic subtypes of NON-small cell lung cancer(adenocarcinoma, squamous, large cell) is pemetrexed considered less effective than for others?

Squamous cell NSCLC

What additional medications are needed for pemetrexed therapy?

Folic Acid
Vitamin B12
Dexamethasone

(from chat)

For what patients is immunotherapy NOT recommended for neoadjuvant treatment of NSCLC (comorbidities)?

1. → note: same as SCLC w/ addition of mutation 

   1. AVOID immunotherapy: 

      1. EGFR(+) or ALK(+) mutation 

      2. Active or previously documented autoimmune disorder 

      3. Current use of immunosuppressive agents (mycophenolate, vedolizumab, prednisone >10mg/day) 

What is the molecular target in SCLC for which atezolizumab (IMpower 133) and durvalumab (CASPIAN) were added to carboplatin and etoposide?  What additional toxicities would you anticipate from the addition of either of these compounds?

Immunomodulators: atezolizumab and durvalumab

Could see increase immune related adverse effects

In extensive-stage small cell lung cancer (SCLC), atezolizumab (IMpower133) and durvalumab (CASPIAN) were added to chemotherapy to target PD-L1 (programmed death-ligand 1), enhancing the immune system’s ability to attack tumor cells.

The addition of these immune checkpoint inhibitors introduces risks of immune-related toxicities, including pneumonitis, colitis, hepatitis, endocrinopathies (e.g., hypothyroidism, adrenal insufficiency), and skin rash or pruritus.