Board Preparation: Melanoma, Mesothelioma

Dec 22, 2016

Test your knowledge of melanoma and mesothelioma to assist your preparations for Board examinations with questions from a past edition of ASCO-SEP®, ASCO’s self-evaluation program in oncology.

The new fifth edition of ASCO-SEP is available for purchase in the ASCO University® bookstore. Featuring 21 updated chapters and more than 180 new self-assessment questions in the book, as well as a 120-question comprehensive mock exam online, this resource is perfect for Board preparation, and can be used to earn Maintenance of Certification and continuing medical education credit. Visit ASCO University for information about the latest edition of ASCO-SEP and other self-assessment resources.

Correct answers, rationales, and suggested reading are listed at the bottom of the page.

1. You start a patient with stage III melanoma on standard high-dose adjuvant interferon-α. At follow-up 1 week later, she is pleased to report that other than a mild fever after the initial infusion, she is tolerating therapy quite well. You remind her that following side effects may increase during the 12 months of administration:

  1. Myalgia
  2. Fever
  3. Fatigue
  4. Chills

2. A 40-year-old woman presents with a mild cough, fatigue, and some weight loss. She was treated for melanoma on her left lower leg 3 years ago. Imaging studies reveal multiple pulmonary nodules. A CT-guided biopsy confirms the diagnosis of metastatic melanoma. Analysis of the tumor for which of the following would be most useful in determining treatment options?

  1. KIT
  2. BRAF
  3. NRAS
  4. MEK

3. A patient presents to your clinic with unresectable advanced malignant pleural mesothelioma with epithelioid histology. The patient’s performance status (PS) is 1. What is the best systemic treatment for this patient?

  1. Cisplatin/gemcitabine
  2. Cisplatin/pemetrexed
  3. Navelbine
  4. Cisplatin alone

4. A 70-year-old man is admitted for shortness of breath. Physical examination reveals diminished breath sounds on the right lung and abdominal distension with ascites. A chest x-ray demonstrates a large right pleural effusion. A thoracentesis is performed that is non-diagnostic. A chest CT scan shows a thick pleural rind around the right lung, right pleural effusion, and mediastinal adenopathy. Abdominal CT scan shows six lesions within the liver and ascites. Video-assisted thoracoscopic surgery (VATs) obtains pleural biopsies and confirms the diagnosis of malignant pleural mesothelioma (MPM). Ascites fluid cytology also returns positive for MPM. Serum laboratory results are: hemoglobin 11.0 g/dL; platelets 660/mcL; normal blood urea nitrogen, creatinine, electrolytes, and bilirubin; alkaline phosphatase 250 IU/mL, aspartate aminotransferase 29 IU/mL, alanine aminotransferase 35 IU/mL, lactate dehydrogenase 900 IU/L.

Which of the following treatment options would be most appropriate for this patient?

  1. Front-line chemotherapy with platinum/pemetrexed
  2. Surgery
  3.  Radiation
  4. Neoadjuvant chemotherapy followed by surgery

     

Rationales: 

1: C
Although its impact on overall survival is not clear, interferon is routinely applied in the adjuvant setting for patients with stage III melanoma after primary surgery. Flu-like symptoms, fever, chills, and myalgia usually abate as interferon therapy is continued. Fatigue and depression usually develop later and progress with continued therapy. Frequent laboratory assessments are necessary to monitor hepatic function and granulocyte counts. 

Suggested Reading
Kirkwood JM, Manola J, Ibrahim J, et al. Eastern Cooperative Oncology Group. A pooled analysis of Eastern Cooperative Oncology Group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. 2004;10:1670-7.

Hurley KE, Chapman PB. Helping melanoma patients decide whether to choose adjuvant high-dose interferon-alpha2b. Oncologist. 2005;10:739-42.

 

2: B

BRAF V600 is the most common somatic mutation in melanoma, occurring in about 50% of patients. This mutation also tends to occur in younger patients with melanoma; therefore, it is the most likely mutation in this patient. Importantly, BRAF inhibitors (vemurafenib, dabrafenib) are effective therapies for patients with BRAF-mutant melanoma and are now FDA-approved based upon survival benefit demonstrated in randomized phase III clinical trials. KIT is uncommonly mutated in melanoma, occurring in fewer than 3% of melanomas. KIT mutations are most frequent in acral (occurring on palms and soles or subungual melanoma), mucosal, or cutaneous melanomas associated with chronic sun exposure. In this patient, testing for BRAF mutation first is most appropriate. Although NRAS mutations occur in 20% of patients with melanoma, there are no FDA-approved treatments for this patient population at this time. MEK mutations are extremely rare in melanoma. Many institutions are now testing for multiple cancer-related somatic mutations using next-generation sequencing platforms, which allow for testing of multiple genes simultaneously.

Suggested Reading

Ascierto PA, Kirkwood JM, Grob J-J, et al. The role of BRAF V600 mutation in melanoma. J Transl Med. 2012;10:85.

 

3: B
In a randomized, phase III trial, patients with unresectable mesothelioma treated with cisplatin/pemetrexed had a longer overall survival with the combination than with cisplatin alone (12.1 vs. 9.3 months, p = 0.02).

Suggested Reading
Vogelzang N, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636-44.

 

4: A

In the setting of advanced mesothelioma, surgery and radiation therapy are not options. Front-line chemotherapy for palliative purposes remains the standard of care. In the United States, platinum/pemetrexed is established as the standard regimen.

Suggested Reading
Vogelzang N, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21:2636-44.

Ceresoli GL, Zucali PA, Favaretto AG, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006;24:1443-8.

Castagneto B, Botta M, et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol. 2008;19:370-3.

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