Oncology Self-Assessment: Lung Cancer and Central Nervous System Tumors

Dec 07, 2022

ASCO seeks to advance the education of all oncology professionals and ultimately facilitate and support enhanced patient care. The ASCO Oncology Self-Assessment Series on ASCO Connection consists of free case-based multiple-choice practice questions, educational links, and answer rationales from ASCO-SEP.  
 
Learn more about ASCO’s Educational products, such as the 2022 ASCO-SEP Digital Subscription, which includes the digital book, access to education courses and virtual meeting-related content, plus over 1,000 practice questions in the Question Bank. Oncology trainees and Training Program Directors can visit Education Essentials for Oncology Fellows (EEOF) to learn more and register for the 2022-23 cycle. 
 
Correct answers are listed at the bottom of the page. 

Question 1: Lung Cancer

A 65-year-old man with a 30 pack-year smoking history presents to the thoracic oncology clinic to discuss therapy for his recurrent small cell lung cancer (SCLC). He was diagnosed a year ago with extensive-stage SCLC and was treated with four cycles of carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. He had a good response and tolerated therapy very well. A month ago, he started feeling more dyspneic. A CT of the chest, abdomen, and pelvis showed concerning findings for recurrence in the same lung and three liver metastases. Pathology findings on a liver biopsy were consistent with SCLC. He has an Eastern Cooperative Oncology Group performance score of 0 and good organ function.
 
Which of the following should you recommend now?
  1. Cisplatin and etoposide
  2. Atezolizumab
  3. Topotecan
  4. Carboplatin, etoposide, and atezolizumab

Question 2: Central Nervous System Tumors

After presenting with acute confusion and right hemiparesis, a 62-year-old man underwent biopsy of the left frontal lobe. Biopsy of the lesion was consistent with primary central nervous system (CNS) lymphoma. After extensive workup, there was no evidence of systemic lymphoma, cerebrospinal fluid spread, or eye involvement. He was started on a high-dose methotrexate-based regimen. After six treatment cycles, he achieved a complete radiographic response and total resolution of symptoms.
 
Which of the following is the most appropriate next step?
  1. Maintenance methotrexate
  2. Intrathecal cytarabine
  3. Thiotepa-based high-dose chemotherapy, followed by stem cell rescue
  4. Maintenance ibrutinib

Question 1 Rationale and References

Correct answer: A. Cisplatin and etoposide
 
Rationale: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage SCLC resulted in significantly longer overall survival and progression-free survival than chemotherapy alone in patients who were not exposed to immunotherapy (IMpower133). This patient is considered platinum-sensitive because his cancer progressed more than six months from finishing his initial platinum-based therapy; therefore, cisplatin and etoposide is a reasonable regimen to offer. Re-induction with atezolizumab, combined with carboplatin and etoposide, was not studied in patients with extensive-stage SCLC exposed to immunotherapy. This patient has progressed on atezolizumab, and a new treatment should be recommended. Topotecan is approved in the second-line setting in patients who have extensive-stage SCLC that progressed on platinum-based therapy within six months from completion.
 
References
  • Horn L, Mansfield AS, Szczęsna A, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379(23):2220-9. DOI: https://doi.org/10.1056/NEJMoa1809064 
  • Liu SV, Reck M, Mansfield AS, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-30. DOI: https://doi.org/10.1200/JCO.20.01055

Question 2 Rationale and References

Correct answer: C. Thiotepa-based high-dose chemotherapy, followed by stem cell rescue
 
Rationale: Consolidation strategies for patients with primary CNS lymphoma include low-dose whole brain radiation therapy, thiotepa-based high-dose chemotherapy, followed by stem cell rescue (autologous stem cell transplantation), or a chemotherapy combination of etoposide and cytarabine. There is no clear survival difference between these three approaches. Patients with complete, or even ongoing partial response to a high-dose methotrexate-based regimen, would benefit from consolidation with thiotepa-based chemotherapy and stem cell rescue. A methotrexate dose higher than 3.5 g/m2 is needed for activity in the CNS. Additionally, there is no evidence of benefit from maintenance methotrexate in patients with primary CNS lymphoma. Intrathecal chemotherapy has not shown to be beneficial in managing primary CNS lymphoma. The role of intrathecal methotrexate in preventing secondary CNS lymphoma in patients with high CNS international prognostic index (IPI) is also unclear, given the limited benefit reported in retrospective studies. Although ibrutinib has been studied in patients with methotrexate-refractory or recurrent primary CNS lymphoma, its role in consolidation and maintenance is still being investigated.
 
References
  • Soussain C, Suzan F, Hoang-Xuan K, et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol. 2001;19(3):742-9. DOI: https://doi.org/10.1200/JCO.2001.19.3.742 
  • Rubenstein JL, Gupta NK, Mannis GN, Lamarre AK, Treseler P. How I treat CNS lymphomas. Blood. 2013;122(14):2318-30. DOI: https://doi.org/10.1182/blood-2013-06-453084 
  • Tortorice KL, Heim-Duthoy KL, Awni WM, Rao KV, Kasiske BL. The effects of calcium channel blockers on cyclosporine and its metabolites in renal transplant recipients. Ther Drug Monit. 1990;12(4):321-328. PMID: 2396304
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