Thoracic Cancer
Michael Cheng, MD
Julia Kathleen Rotow, MD
A 55-year-old man presents with an FDG-avid 5.4-cm left upper lobe lung mass with associated FDG-avid and enlarged left hilar lymphadenopathy. No distant disease by imaging and a brain MRI shows no CNS metastases. A bronchoscopic biopsy of a left hilar lymph node reveals a squamous cell carcinoma, and a subcarinal lymph node is negative for malignancy.
What is the clinical stage for this patient and what do you advise as definitive management?
View Answer
Stage IIIA (T3N1 disease) NSCLC.
Absent medical or technical contraindications, stage IIIA NSCLC with N1 lymph node involvement should be managed with surgical resection for curative intent.
Management of patients with stage IIIA NSCLC with N2 lymph node involvement is more variable and includes induction therapy followed by resection or chemoradiation.
If surgical pathology confirms a T3N1 lesion, then adjuvant chemotherapy with four cycles of a platinum doublet should be offered.
Patients with lymph node-positive NSCLC should be offered adjuvant chemotherapy.
Suggested Readings:
Mohamed A, Waqar SN. Lung cancer. In: Govindan R, ed. The Washington Manual of Oncology. 3rd ed. Wolters Kluwer; 2015.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 62-year-old woman presents following right upper lobe lobectomy and mediastinal lymph node dissection for a 5.2-cm adenocarcinoma which is TTF1+ and Napsin A+ by IHC. Her preoperative PET/CT did not identify any enlarged or FDG-avid lymph nodes; however, on surgical pathology, one right hilar lymph node is found to contain adenocarcinoma, out of ten hilar and mediastinal lymph nodes evaluated. Margins are negative. The tumor is well-differentiated, without visceral pleural invasion or lymphovascular invasion.
How do you advise the patient regarding postoperative therapy?
View Answer
Patients with lymph node-positive resected NSCLC should be offered adjuvant chemotherapy.
Other criteria for use of adjuvant chemotherapy include primary tumor size >4 cm, and consideration for adjuvant chemotherapy in some patients with tumors >3 cm and high-risk pathologic features (poorly differentiated, visceral pleural invasion, lymphovascular invasion).
For lung adenocarcinoma, standard adjuvant chemotherapy is cisplatin/pemetrexed × 4 cycles. Pemetrexed regimens should be used only for nonsquamous NSCLC. The LACE meta-analysis offers overall survival data for inclusion of adjuvant chemotherapy.
Suggested Readings:
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Früh M, Rolland E, Pignon J, et al. Pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small-cell lung cancer. J Clin Oncol. 2008;26(21):3573-3581.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 79-year-old man with CAD, CHF, CKD, hearing aids, and COPD presents for medical oncology evaluation with a 7.1-cm RLL lung mass without invasion of adjacent structures with right hilar lymphadenopathy. A bronchoscopic biopsy of a station 10R lymph node reveals a squamous cell carcinoma. Clinically ECOG PS2. They are seen by thoracic surgery and found to be medically inoperable due to comorbidities.
What is the most appropriate management in this patient for their respective stage of NSCLC?
View Answer
Surgically “fit” patients with stage IIIA should undergo definitive surgical resection. Surgically ineligible patients with stage IIIA (N1+) should proceed with concurrent chemoradiation, followed by 1-year consolidation durvalumab.
For patients with IIIA (N1+) disease who are unable to undergo surgical resection due to medical comorbidities, treatment is with definitive chemoradiation.
For patients with squamous NSCLC receiving chemoradiation, concurrent cisplatin/etoposide is preferred. For patients with contraindications to cisplatin/etoposide (eg, baseline hearing loss, limited performance status), weekly low-dose carboplatin/paclitaxel is an appropriate regimen. Pemetrexed-based regimens are not appropriate for squamous NSCLC.
Patients without progression following definitive chemoradiation should be offered 1 year of consolidation therapy with the immune checkpoint inhibitor durvalumab, which demonstrated improved overall survival compared to placebo (PACIFIC study).
Suggested Readings:
Antonia SJ, Villegas D, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 65-year-old man presents with chest pain and is found to have a 9-cm RML mass with extensive direct invasion into the mediastinum with cardiac and great vessel involvement. No definitive hilar or mediastinal lymphadenopathy is seen. A percutaneous biopsy of the RML mass returns as a lung adenocarcinoma. A brain MRI is negative.
What is the optimal definitive treatment strategy for this patient with T4 NSCLC?
View Answer
NSCLC patients with T4 disease are surgically unresectable due to invasion of adjacent structures (chest wall, mediastinum) and, thus, should be treated with definitive chemoradiation.
Select patients with T4 N0/N1 disease may be candidates for neoadjuvant chemotherapy or chemoradiation therapy followed by reevaluation of surgical resectability.
For lung adenocarcinoma, a pemetrexed-based chemotherapy regimen (cisplatin + pemetrexed) or the use of cisplatin/etoposide are appropriate choices for concurrent chemoradiation. For patients who cannot receive cisplatin or pemetrexed, weekly carboplatin/paclitaxel is an appropriate alternative.
Patients without progression following definitive chemoradiation should be offered 1 year of consolidation therapy with the immune checkpoint inhibitor durvalumab, which demonstrated improved overall surgical compared to placebo (PACIFIC study).
Suggested Readings:
Antonia SJ, Villegas D, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 50-year-old man presents with a 4.1-cm LLL lung mass with associated FDG-avid left hilar lymphadenopathy by PET/CT. A brain MRI shows no evidence of CNS metastases. The patient undergoes bronchoscopy, with squamous cell carcinoma present in a sampled left hilar lymph node. A station 7 lymph node is also sampled and is negative for malignancy with clinical staging revealing cT2bN1 (involved hilar lymph nodes). They then undergo a left lower lobe lobectomy with mediastinal lymph node dissection. Final surgical pathology reveals a 4.2-cm squamous cell carcinoma in the LLL. Three left hilar lymph nodes are found to be involved, as well as several subcarinal and left lower paratracheal lymph nodes. Margins are negative.
What postoperative therapy should be recommended for this patient with NSCLC?
View Answer
Patients with locally advanced NSCLC with positive mediastinal lymph node involvement on surgical staging (N2 disease) should receive adjuvant chemotherapy followed by postoperative radiation therapy.
Standard therapy for NSCLC without mediastinal lymph node involvement is surgical resection followed by adjuvant chemotherapy. The presence of ipsilateral mediastinal lymph node involvement upstages patients to N2 disease (upstaging to pT2bN2 in the scenario described).
Indications for evaluation for postoperative radiation therapy:
Positive N2 lymph nodes on surgical pathology
Positive surgical margins
Suggested Readings:
Mohamed A, Waqar SN. Lung cancer. In: Govindan R, ed. The Washington Manual of Oncology. 3rd ed. Wolters Kluwer; 2015.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 58-year-old male presents with a 4.6-cm right lower lobe mass with bulky right hilar, right lower paratracheal, and subcarinal lymphadenopathy which is FDG-avid by PET/CT. There are no CNS metastases by brain MRI. Bronchoscopic biopsy of a subcarinal lymph node is positive for lung adenocarcinoma.
What is this patient’s clinical stage and what do you recommend as definitive therapy?
View Answer
NSCLC patients with multiple involved ipsilateral mediastinal lymph nodes by imaging and confirmed on biopsy are appropriated T2bN2 stage IIIA disease. Patients with stage IIIA NSCLC should be treated with definitive chemoradiation followed by consolidation durvalumab.
The management of stage III N2 lymph node-positive disease is variable. Selected patients with single-site, nonbulky N2 lymph node involvement may be candidates for subsequent surgical resection after induction therapy (chemotherapy or chemoradiation); however, upfront definitive chemoradiation is also a standard of care option for these patients. Patients with large/invasive primary lesions (T4), multistation N2 disease, or bulky N2 disease are treated with definitive chemoradiation.
Definitive chemoradiation should be followed by 1 year of consolidation immunotherapy with the checkpoint inhibitor durvalumab in those without progression on chemoradiation (PACIFIC).
Suggested Readings:
Antonia SJ, Villegas D, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A patient is diagnosed with stage III NSCLC. Match the clinical scenario with preferred treatment strategy.
1. Stage IIIA (N1+) NSCLC
2. Stage IIIA (multiple/bulky N2 LN) NSCLC
3. Stage IIIA (single station 1 cm N2 LN) NSCLC
4. Stage IIIB (with N3 LN) NSCLC
A. Chemoradiation versus neoadjuvant therapy/surgical resection
B. Chemoradiation
C. Surgical resection
View Answer
1. Stage IIIA (N1+) NSCLC: Surgical resection
2. Stage IIIA (multiple/bulky N2 LN) NSCLC: Chemoradiation
3. Stage IIIA (single station 1 cm N2 LN) NSCLC: Chemoradiation versus neoadjuvant therapy/surgical resection
4. Stage IIIB (with N3 LN) NSCLC: Chemoradiation
Patients with multiple/bulky N2(ipsilateral mediastinal) involved lymph nodes, or N3 (supraclavicular or contralateral mediastinal) involved lymph nodes should be managed with definitive chemoradiation. Selected patients with single station, nonbulky ipsilateral mediastinal lymph nodes can be considered for neoadjuvant therapy followed by evaluation for resection.
Suggested Readings:
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Select the clinical scenario(s) which warrant use of consolidation durvalumab:
A. Stage IIIA (N1+) NSCLC surgically resected
B. Stage IIIA (N2+) NSCLC treated with neoadjuvant chemoradiation followed by surgical resection
C. Stage IIIA (N2+) NSCLC treated with chemoradiation
D. Medically inoperable stage II (N1+) NSCLC treated with chemoradiation
View Answer
(C) Stage IIIA (N2+) NSCLC treated with chemoradiation warrants the use of consolidative durvalumab.
The PACIFIC study demonstrated improved overall survival with 1-year consolidation immunotherapy with durvalumab for patients with stage III NSCLC treated without disease progression following definitive chemoradiation.
Suggested Readings:
Antonia SJ, Villegas D, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 68-year-old woman presents with a 4.5-cm RML lung mass, with bilateral FDG-avid hilar lymphadenopathy, subcarinal adenopathy, and bilateral upper paratracheal lymphadenopathy. She undergoes bronchoscopic mediastinal lymph node staging, which includes a right hilar, subcarinal, and left hilar lymph nodes positive for lung adenocarcinoma. Brain MRI is negative.
What is the appropriate management for the respective stage of this patient with NSCLC?
View Answer
NSCLC patients with contralateral mediastinal lymph node involvement are considered to have N3 disease. For patients with IIIB/C N3-positive disease, treatment is with definitive chemoradiation, followed by consolidation durvalumab.
For adenocarcinoma concurrent chemotherapy with cisplatin/etoposide or cisplatin/pemetrexed is appropriate. For patients who are not candidates for these regimens due to comorbidities, weekly carboplatin/paclitaxel is an alternative option.
Suggested Readings:
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 72-year-old woman presents with an FDG-avid 4.2-cm left lower lobe lung mass, with associated FDG-avid subcarinal, left hilar, and right hilar lymphadenopathy. A brain MRI is negative. They have undergone a percutaneous biopsy of the left lower lobe lung mass which demonstrated a squamous cell carcinoma.
Do they require additional evaluation prior to proceeding with definitive chemoradiation?
View Answer
Patients with suspected N2 or N3 lymph node involvement by imaging studies which may preclude surgical resection should undergo pathologic lymph node staging with bronchoscopy or mediastinoscopy to confirm suspected involvement prior to proceeding with definitive therapy.
Suggested Readings:
Brzezniak C, Cheringal J, Thomas A. Non-small cell lung cancer. In: Abraham J, ed. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2019:26-42.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
Match the clinical scenario with appropriate chemotherapy regimen for use during definitive chemoradiation for stage III NSCLC.
1. Squamous cell in a 50 year old female, ECOG 1, without comorbidities
2. Adenocarcinoma in a 65 year old male, ECOG 1, without comorbidities
3. Squamous cell in a 80 year old male, ECOG 2, with hearing aids
A. Carboplatin/paclitaxel (weekly)
B. Cisplatin/etoposide
C. Cisplatin/pemetrexed or cisplatin/etoposide
View Answer
Match the clinical scenario with appropriate chemotherapy regimen for use during definitive chemoradiation for stage III NSCLC.
Stage III squamous cell in a 50 year old female, ECOG 1, without comorbidities: Cisplatin/etoposide
Stage III adenocarcinoma in a 65 year old male, ECOG 1, without comorbidities: Cisplatin/pemetrexed or cisplatin/etoposide
Stage III squamous cell in a 80 year old male, ECOG 2, with hearing aids: Carboplatin/paclitaxel (weekly)
Patients with squamous cell NSCLC have inferior survival when treated with pemetrexed. Ototoxicity is a major dose-limiting side effect of cisplatin.
Suggested Readings: Albain KS, Crowley JJ, Turrisi AT, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002;20(16):3454-3460; Belani CP, Choy H, Bonomi P, et al. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005;23(25):5883-5891; Senan S, Brade A, Wang LH, et al. PROCLAIM: randomized phase III trial of pemetrexed-cisplatin or etoposide-cisplatin plus thoracic radiation therapy followed by consolidation chemotherapy in locally advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2016;34(9):953-962; Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018; and DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 62-year-old male with history of COPD presents to his primary care physician with complaint of weight loss, right hand weakness, shoulder pain, and difficulty opening his right eye.
What is the most likely diagnosis?
View Answer
Superior sulcus tumor (also known as a Pancoast tumor).
Common symptoms of a superior sulcus tumor include shoulder pain, paresthesias in the arm, hand weakness/atrophy, and Horner syndrome as a result of direct invasion of local structures including the paravertebral sympathetic nerve chains, lower cervical, and upper thoracic nerve roots.
For resectable or potentially resectable lesions (T3 invasive or T4, N0-1), standard therapy is with neoadjuvant chemoradiation therapy followed by surgery + adjuvant chemotherapy.
Suggested Readings:
Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Thorac Cardiovasc Surg. 2001;121(3):472-483.
Abraham J, Gulley JL. The Bethesda Handbook of Clinical Oncology. 5th ed. Wolters Kluwer; 2018.
DeVita VT, Rosenberg SA, Lawrence SL. DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology. 11th ed. Wolters Kluwer; 2018.
A 68-year-old woman presents with a 3.3-cm RUL mass with a second solid lung nodule in the RML, with an enlarged, FDG-avid right hilar lymph node. Biopsy of the hilar lymph node demonstrates a lung adenocarcinoma.
What is the stage of disease for this patient with NSCLC?
View Answer
Stage cT4N1 (IIIA)
T4 disease due to the presence of a lung nodule in an ipsilateral lobe, stage cT4N1 (IIIA).
Satellite nodule in same lobe as the primary = T3
Nodule in a differing lobe ipsilateral to the primary = T4
Nodule in the contralateral lung: If solitary nodule management as second primary is often appropriateRelated posts:
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