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In the United States, lung cancer is the leading cause of cancer deaths and the second most frequently diagnosed cancer for both men and women.[1] The American Cancer Society estimated that in 2016, there would be approximately 224,390 new cases of lung cancer and about 158,080 deaths from the disease.[1] Unlike patients with breast, colon, or prostate cancer, the majority (~75%) of patients with lung cancer will die of the disorder. However, between 2003 and 2012 the incidence of and mortality rate from lung cancer decreased significantly for both men and women.[2] Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. NSCLC is generally divided into three forms: adenocarcinoma, squamous cell carcinoma (SCC), and large cell cancer.
In the above gross photograph, a squamous cell lung carcinoma (yellow arrow) is obstructing the bronchus.
Image courtesy of Wikimedia Commons | John Hayman.
A 65-year-old man with a 20-pack-year smoking history presents to his primary care physician for worsening shortness of breath. Radiography of his chest reveals a mass in the right lung field (yellow arrow). Computed tomography (CT) of his chest demonstrates a mass (see slide 3, left image) and multiple enlarged 1.5-cm mediastinal nodes on the right side. Percutaneous biopsy of the right-side lung mass is positive for adenocarcinoma. The patient has an Eastern Cooperative Oncology Group (ECOG) score of 0.
What is the most appropriate next step for this patient?
Image courtesy of Dr Hani Al Salam | Radiopaedia.org.
Answer: A. Order additional imaging studies (magnetic resonance imaging [MRI] of the brain, positron emission tomography [PET] scanning, or both).
Treatment of NSCLC is based primarily on the disease stage. This patient has not had a complete staging workup; therefore, additional imaging studies, such as PET scanning or brain MRI, are required. If imaging reveals evidence of distant metastasis (stage IV disease), this finding will reduce the need for an invasive mediastinoscopy, which is the gold standard for mediastinal imaging. If no distant metastasis is identified, mediastinoscopy will be the appropriate next step. In this patient, fluorodeoxyglucose (FDG)-PET scanning (right) demonstrates activity in the primary tumor and right mediastinum.
Images courtesy of Dr Hani Al Salam | Radiopaedia.org.
However, MRI of this same patient's brain demonstrates multiple small, ring-enhancing lesions in both hemispheres (shown), confirming stage IV disease. Accordingly, the patient is started on palliative chemotherapy, which improves survival and quality of life (1-year survival rate of 35% for treated patients, compared with 10% for untreated patients). After first-line cisplatin-pemetrexed chemotherapy, disease control is achieved for several months.
Image courtesy of Medscape.
A 53-year-old man presents to his primary care physician with a 1-month history of chronic dry cough and hemoptysis. He has a 40-pack-year smoking history. Radiography of the chest demonstrates a right-lower-lobe opacity (yellow arrow) that raises concerns about possible lung cancer.
Image courtesy of Medscape.
CT scanning of this patient's chest reveals a large 7-cm right-side mass with multiple ipsilateral mediastinal lymph node involvement. Transthoracic CT scan–guided biopsy of the lesion indicates SCC. FDG-PET demonstrates no evidence of distant metastasis. The patient's ECOG score is 0.
Which of the following is the most appropriate treatment for this patient?
Image courtesy of Dr Frank Gaillard | Radiopaedia.org.
Answer: D. Concurrent chemotherapy and radiation therapy over 6 weeks.
The above image demonstrates high-power magnification of moderately differentiated SCC, showing focal areas of keratinization (pink-orange areas) just to the right of center. This patient has bulky stage IIIA SCC, which is generally considered unresectable. Chemotherapy plus radiation therapy is the treatment of choice for patients with bulky or inoperable stage IIIA or IIIB disease. Two randomized trials demonstrated a survival advantage with concurrent delivery of chemotherapy and radiation therapy as compared with a sequential approach in the setting of stage III NSCLC, though there was a slight increase in toxicity with the former.[3,4]
Image courtesy of Medscape.
The patient achieves complete response with concurrent chemoradiation therapy. He elects not to receive maintenance chemotherapy and remains in surveillance.
One year later, the patient complains of new headaches. MRI of the brain reveals multiple brain metastases (left, middle). CT scanning of the abdomen reveals new metastasis in the liver (right). The patient is started on palliative chemotherapy with carboplatin and gemcitabine.
Image courtesy of Medscape.
After completing his second cycle of carboplatin and gemcitabine, the patient presents with a rash and dark urine. Physical examination reveals conjunctival pallor and a bilateral lower-extremity petechial rash. The patient's peripheral blood smear is shown above. Pertinent laboratory findings include the following: hemoglobin, 8.0 g/dL; platelet count, 15 × 109/L; creatinine, 3.1 mg/dL; lactate dehydrogenase, 1200 U/L (normal, <600 U/L); haptoglobin, 15 mg/dL; prothrombin time (PT), 12 s (normal, 10-13 s); and activated partial thromboplastin time (aPTT), 30 s (normal, 27-39 s).
What is the most likely diagnosis?
Image courtesy of Medscape / Yuri Fedoriw, MD.
Answer: B. Thrombotic thrombocytopenic purpura (TTP).
A peripheral smear of the patient's blood reveals schistocytes (arrows) and thrombocytopenia. The presence of microangiopathic hemolytic anemia, renal impairment, and thrombocytopenia is suggestive of TTP. Gemcitabine is known to cause secondary TTP, which is thought to arise from pathophysiologic mechanisms different from those of idiopathic TTP (caused by decreased levels of the enzyme ADAMTS13).
Gemcitabine is discontinued, and the patient is switched to carboplatin and vinorelbine for management of metastatic SCC.
Image courtesy of Medscape / Yuri Fedoriw, MD.
A 53-year-old woman undergoes a preoperative evaluation for laparoscopic cholecystectomy, and a right-lung mass is incidentally found on chest radiography during the evaluation (arrows). Percutaneous needle biopsy reveals differentiated adenocarcinoma. CT scanning of the chest and PET scanning demonstrate ipsilateral hilar lymph node involvement with no evidence of distant metastasis. Mediastinoscopy reveals no mediastinal lymph node involvement.
Image courtesy of Medscape.
The patient undergoes a complete surgical resection (shown), and the cancer is staged pathologically as stage IIB (T2bN1M0).
Which of the following is most appropriate for this patient?
Image courtesy of Medscape / Winston W Tan, MD, FACP.
Answer: C. Adjuvant platinum-based doublet chemotherapy.
Histologic evaluation demonstrates differentiated adenocarcinoma with rounded nests of pale-staining tumor cells and gland lumina within some of the clusters. The standard of care for patients with stage II and minimal stage IIIA NSCLC is surgical resection followed by adjuvant platinum-based doublet chemotherapy. In a trial comparing surgery alone with surgery followed by four cycles of cisplatin-vinorelbine chemotherapy, a significant survival benefit (51% vs 43%) at 5 years was documented for patients with stage II NSCLC who received adjuvant chemotherapy.[5]
Image courtesy of Medscape.
CT scanning of the patient's chest and abdomen demonstrates a 5-cm left-lower-lobe mass and heterogeneously enhancing and partially necrotic bilateral adrenal metastases. FDG-PET scanning confirms stage IV disease with increased uptake in the left lower lobe, pleura, and bilateral adrenal nodes. CT scan–guided biopsy of the left lung mass is performed. Molecular evaluation of the tissue reveals no specific mutation that would help guide therapy. The patient's ECOG score is 1.
In addition to platinum-based doublet chemotherapy, which, if any, of the following agents should be included in this patient's treatment regimen?
Image courtesy of Medscape.
Answer: D. Bevacizumab.
Results from the ECOG 4599 phase III trial demonstrated that in non-SCC NSCLC patients, median survival was significantly longer for those who received chemotherapy plus bevacizumab 15 mg/kg every 3 weeks than for those who received chemotherapy alone (12.3 months vs 10.3 months).[6] Patients with SCC are not eligible for bevacizumab, because of the risk of pulmonary hemorrhage (arrow), as seen in the image (from a different patient). The patient under discussion has metastatic adenocarcinoma; thus, bevacizumab should be added to platinum-based doublet chemotherapy.
Image courtesy of Dr Frank Gaillard | Radiopaedia.org.
A 53-year-old woman is diagnosed with metastatic SCC of the lung. Initial CT scanning of the chest reveals a large hilar tumor on the right side, with loculated pleural effusion. There is also nodular thickening of the pleura, suggesting pleural metastasis. Chemotherapy with carboplatin and paclitaxel is started. The patient tolerates the chemotherapy well and achieves a partial response, with subsequent disease stabilization after the completion of four cycles of chemotherapy. Her ECOG score is 1. She is currently still able to work at her job as a secretary.
Which of the following is the most appropriate treatment for this patient?
Image courtesy of Medscape.
Answer: D. Stop therapy for now, and start chemotherapy at the time of disease progression.
The role of maintenance chemotherapy in patients with metastatic NSCLC is unclear. Randomized studies did not show a survival advantage with prolonged chemotherapy (>6 cycles) as compared with standard-length therapy (4-6 cycles).[7] Accordingly, giving another four cycles of chemotherapy or providing continuous maintenance therapy with paclitaxel would not be recommended. Currently, only switch-maintenance therapy with pemetrexed and erlotinib has been approved by the US Food and Drug Administration (FDA). Because this patient has SCC, pemetrexed would not be an option.
The patient opts for switch-maintenance therapy with erlotinib. Two weeks after starting erlotinib, she reports a rash (shown).
Image courtesy of Medscape.
Erlotinib is an epidermal growth factor receptor (EGFR) inhibitor. About 75% of patients on EGFR inhibitors develop a characteristic acneiform rash, which typically resembles acne or folliculitis and is usually most prominent on the head, neck, and upper chest or back, as illustrated in the above image (from a different patient). Treatment of EGFR inhibitor–associated acneiform eruptions depends on the severity of the rash. For mild or localized eruptions, topical 1% clindamycin is usually recommended. Oral antibiotics used for acne (eg, doxycycline and tetracycline) have also been employed, because they have anti-inflammatory effects and can prevent secondary infection.
Image courtesy of Medscape.
Three months later, the 53-year-old female patient presents with a headache and is found to have a solitary ring enhancing lesion on brain MRI (shown). Because she continues to have controlled disease with an isolated cerebral metastasis in a resectable area, she is treated with surgical resection followed by whole-brain radiation therapy.
Image courtesy of Dr Frank Gaillard | Radiopaedia.org.
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