Correspondence

Multidisciplinary Management of Lung Cancer

N Engl J Med 2004; 350:2008-2010May 6, 2004

Article

To the Editor:

In their review of lung-cancer management (Jan. 22 issue),1 Spira and Ettinger fail to mention the value of endoscopic ultrasonography with fine-needle aspiration in the staging of non–small-cell lung cancer. This method can identify lymph nodes as small as 4 mm in the subcarinal, paraesophageal, and paratracheal regions, but not the pretracheal space or intrapulmonary regions. Transesophageal fine-needle aspiration guided by endoscopic ultrasonography provides tissue for cytologic diagnosis, and the procedure can be performed on an outpatient basis with sedation similar to that used for other endoscopic procedures. This technique has been shown to be both accurate (>90 percent) and safe for nodal staging in patients with previously documented lung cancer,2-4 and it has detected malignant adenopathy in patients with normal results on computed tomography (CT) and positron-emission tomography (PET) of the mediastinum.3,5 Endoscopic ultrasonography is now available at most tertiary care facilities, as well as an increasing number of community hospitals. Because of the range of nodal stations amenable to examination by endoscopic ultrasonography with fine-needle aspiration, this technique should be regarded as complementary to noninvasive imaging and mediastinoscopy.

Brian C. Jacobson, M.D., M.P.H.
Boston University Medical Center, Boston, MA 02118
brian.jacobson@bmc.org

5 References

1
Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med 2004;350:379-392
Full Text | Web of Science | Medline

2
Gress FG, Savides TJ, Sandler A, et al. Endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study. Ann Intern Med 1997;127:604-612
Web of Science | Medline

3
Wallace MB, Silvestri GA, Sahai AV, et al. Endoscopic ultrasound-guided fine-needle aspiration for staging patients with carcinoma of the lung. Ann Thorac Surg 2001;72:1861-1867
CrossRef | Web of Science | Medline

4
Fritscher-Ravens A, Soehendra N, Schirrow L, et al. Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer. Chest 2000;117:339-345
CrossRef | Web of Science | Medline

5
Fritscher-Ravens A, Bohuslavizki KH, Brandt L, et al. Mediastinal lymph node involvement in potentially resectable lung cancer: comparison of CT, positron emission tomography, and endoscopic ultrasonography with and without fine-needle aspiration. Chest 2003;123:442-451
CrossRef | Web of Science | Medline

To the Editor:

As Drs. Spira and Ettinger imply, it is essential to obtain biopsy confirmation of mediastinal metastasis before excluding a patient with non–small-cell lung cancer from receiving potentially curative surgery. However, the different invasive staging procedures have different advantages and disadvantages. Although it is less invasive, bronchoscopy with transbronchial needle aspiration is less sensitive than mediastinoscopy, especially when the mediastinal nodes are not enlarged.1 Furthermore, although both transbronchial needle aspiration and mediastinoscopy can reliably confirm the presence of nodal metastasis when performed properly, negative results with these procedures do not completely rule out the presence of metastasis, because neither affords access to all potentially involved nodal stations.2

Unfortunately, many studies of tests for lung-cancer staging are limited because they do not apply an acceptable “reference standard” in excluding the presence of mediastinal metastasis.3 An appropriate reference standard for ruling out nodal involvement is systematic sampling at all accessible mediastinal stations during thoracotomy. When this standard is not applied, studies will seriously overestimate the true negative rate and underestimate the false negative rate for the test being evaluated.

Michael K. Gould, M.D.
Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304
gould@stanford.edu

Gerard A. Silvestri, M.D.
Medical University of South Carolina, Charleston, SC 29425

Frank Detterbeck, M.D.
University of North Carolina, Chapel Hill, NC 27599

3 References

1
Toloza EM, Harpole L, Detterbeck F, McCrory DC. Invasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003;123:Suppl:157S-166S
CrossRef | Web of Science | Medline

2
Detterbeck FC, DeCamp MM Jr, Kohman LJ, Silvestri GA. Lung cancer: invasive staging: the guidelines. Chest 2003;123:Suppl:167S-175S
CrossRef | Web of Science | Medline

3
Gould MK, Kuschner WG, Rydzak CE, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 2003;139:879-892
Web of Science | Medline

To the Editor:

A notable omission in the otherwise excellent review by Spira and Ettinger is that of any mention of palliative care. This is a type of treatment that most patients (including many who undergo ultimately curative resection) will require at some stage. In fact, national guidelines in the United Kingdom recommend that palliative care be an integral part of management from the outset.1 In our quest for new and more effective therapies, we should not lose sight of the reality that we are unlikely to develop a “magic bullet” for lung cancer in the foreseeable future. Palliative care rarely makes high-impact headlines; it has more to do with good old-fashioned interpersonal relationships, symptom relief, and care to the end. In our management of lung cancer we should always keep in mind not just the disease but also the person who has it.

Anthony Papagiannis, M.D.
St. Luke's Hospital, 55236 Thessaloniki, Greece
antpap@the.forthnet.gr

1 References

1
NHS Executive. Guidance on commissioning cancer services. Improving outcomes in lung cancer: the research evidence. Leeds, England: Department of Health, 1998.

To the Editor:

Spira and Ettinger did not discuss the non–platinum-based combinations in the treatment of advanced non–small-cell lung cancer. Just recently, the results of three phase 3 trials comparing non–platinum-based combination chemotherapy with platinum-based chemotherapy in the treatment of patients with advanced non–small-cell lung cancer have been reported.1-3 One such combination, gemcitabine plus vinorelbine, seems to be an alternative to the platinum-based chemotherapy regimens in the treatment of such patients, given concern about the toxicity of cisplatin, though cisplatin-based chemotherapy conferred a slight, nonsignificant survival advantage.1

Abdullah Buyukcelik, M.D.
Bulent Yalcin, M.D.
Gungor Utkan, M.D.
Ankara University School of Medicine, Ankara 06100, Turkey

3 References

1
Gridelli C, Gallo C, Shepherd FA, et al. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2003;21:3025-3034
CrossRef | Web of Science | Medline

2
Alberola V, Camps C, Provencio M, et al. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J Clin Oncol 2003;21:3207-3213
CrossRef | Web of Science | Medline

3
Smit EF, van Meerbeeck JP, Lianes P, et al. Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group -- EORTC 08975. J Clin Oncol 2003;21:3909-3917
CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Papagiannis emphasizes an essential part of treating patients with lung cancer. Given that most patients will not be cured and that treatments, at their best, offer only moderate survival benefits, palliative care is first and foremost essential to the good care of any patient with cancer. U.S. guidelines also emphasize palliative care.1

Dr. Gould and colleagues make important points about the negative predictive value of a mediastinal biopsy; we concur that clinical trials involving surgery should require sampling of all nodal stations during thoracotomy. Even with the excellent results of PET scans,2 which are likely to improve even further with the advent of combined PET–CT, a tissue evaluation remains important, particularly in the context of a clinical trial. For patients receiving neoadjuvant chemotherapy, nodal evaluation before and after treatment can provide an in vivo assessment of the effectiveness of chemotherapy. Furthermore, such an evaluation has been shown to affect the prognosis3; therefore, it is also important for patients not enrolled in trials. Current treatment paradigms are likely to change on the basis of the results of the recent International Adjuvant Lung Cancer Trial, in that chemotherapy will be delivered to more patients as part of their treatment plans, thus making mediastinal assessment before and after surgery even more important.4

Future studies should evaluate the concept of changing regimens on the basis of the responses to neoadjuvant chemotherapy as determined at the time of surgery. We did not mention all the possible two-agent combinations one can use as therapy for non–small-cell lung cancer, and we agree with the assertion of Dr. Buyukcelik et al. that non–platinum-containing two-agent combinations are indeed a viable alternative to platinum-containing regimens. Most trials have focused on regimens containing cisplatin or carboplatin, mainly for historical reasons. Given the multitude of potential combinations available, even though platinum-containing therapy remains the standard for most physicians, alternative regimens are available and should be considered as circumstances dictate.

Dr. Jacobson comments on the use of endoscopic ultrasonography in the mediastinal staging of lung cancer. We agree that such an approach should be considered an alternative to mediastinoscopy in appropriate patients, in a manner complementary to the use of bronchoscopy and PET. As Dr. Jacobson notes, endoscopic ultrasonography for mediastinal staging of lung cancer is becoming increasingly available.

Alexander Spira, M.D., Ph.D.
Fairfax Northern Virginia Hematology/Oncology Group, Fairfax, VA 22031

David S. Ettinger, M.D.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000
ettinda@jhmi.edu

4 References

1
National Comprehensive Cancer Network. Practice guidelines in oncology table of contents. (Accessed April 16, 2004, at http://www.nccn.org/physician_gls/f_guidelines.html.)

2
Pieterman RM, van Putten JWG, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 2000;343:254-261
Full Text | Web of Science | Medline

3
Betticher DC, Hsu Schmitz SF, Totsch M, et al. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial. J Clin Oncol 2003;21:1752-1759
CrossRef | Web of Science | Medline

4
The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351-360
Full Text | Web of Science | Medline

Citing Articles (1)