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From OncoLog, March 2013, Vol. 58, No. 3

Advances in Pulmonary Medicine Facilitate Cancer Diagnosis, Treatment

By Sarah Bronson

Photo: Tumor obstructing the right bronchus
Photo: Right bronchus after tumor removal
Bronchoscopic images show a tumor obstructing the right main bronchus (top) and the same bronchus after tumor debulking (bottom).

The lungs present unique challenges in cancer diagnosis and treatment—navigating a maze of bronchi to find and sample tissue that will lead to an accurate diagnosis of lung cancer, for example, or deciding whether to proceed with treatment for cancer in the presence of concomitant lung disease.

For these reasons, pulmonologists play an important role in the care of cancer patients. “We help diagnose lung cancer, diagnose and alleviate lung complications associated with cancer and cancer treatment, and optimize respiratory status so patients can undergo treatment safely,” said Rodolfo Morice, M.D., a professor in the Department of Pulmonary Medicine and chief of the Section of Interventional Pulmonology at The University of Texas MD Anderson Cancer Center.

Suspected lung cancer necessitates accurate diagnostic procedures and proper consideration of the lungs’ susceptibility to complications. And if cancer is present, lung function should, ideally, be optimized and conditions such as pleural effusions and pneumonia cured before cancer treatment begins. Sensitive, minimally invasive bronchoscopies and up-to-date management of lung disease can help ensure that cancer treatments are as effective as possible.

Increasing the diagnostic yield of bronchoscopy


Imaging modalities such as radiography often provide the first indication of lung cancer, but only by directly examining the tissue that had suspicious radiographic findings can a cancer diagnosis be made or ruled out. Techniques for sampling lung lesions and mediastinal lymph nodes vary in accuracy, reach, and invasiveness. The choice between an invasive diagnostic procedure such as mediastinoscopy and a less invasive procedure such as bronchoscopy depends on the location of the target, the size and hence the visibility of the target, and the patient’s ability to tolerate the potential complications from these procedures.

Previously, opting for a less invasive biopsy often meant sacrificing accuracy. But with the use of endobronchial ultrasonography (EBUS), “navigation” bronchoscopy, and autofluorescence bronchoscopy, sites of suspected lung cancer can be more accurately targeted without subjecting patients to open surgical biopsy or transthoracic needle biopsy and to increased risks such as pneumothorax, which occurs in up to 30% of patients who undergo transthoracic needle biopsies.

EBUS

Conventional white-light bronchoscopy illuminates only the inside of the airway and can sample lymph nodes based on their locations relative to endobronchial landmarks; the procedure has a diagnostic yield of only 30%–50%. Adding an ultrasonography probe to the end of a bronchoscope reveals the lymph nodes near the trachea and main bronchi as far as 5 cm beyond the bronchial walls, increasing the diagnostic yield to about 95%. Using the airway as a passage, EBUS can sample the high mediastinal, paratracheal, subcarinal, and hilar lymph nodes, reaching farther into the peribronchial tissues than mediastinoscopy, which cannot access the hilar lymph nodes.

Adding ultrasonography to bronchoscopy, already a relatively safe procedure, introduces little risk; EBUS is associated with the same infrequent complications and contraindications as conventional bronchoscopy.

Navigation bronchoscopy

Navigation bronchoscopy tracks and maps the bronchoscope’s position in real time within a three-dimensional rendering of the airways based on recently acquired computed tomography data. The end of a sampling catheter is equipped with an electromagnetic position sensor that disturbs a magnetic field encompassing the patient’s lungs and thus can be pinpointed within that field or, alternatively, with a sensor that emits electrical signals indicating its position. The sensor is placed at key points selected during the planning phase. Each of these points within the actual airways is then mapped to the corresponding point in the digital rendering, and the real-time view and the digital rendering are merged. Thus, physicians can navigate the bronchi using not only the immediate white-light view of the airways but also a detailed map that is integrated with the computed tomography images.

Photo: Bronchoscopic image using white light imaging shows a squamous cell carcinoma.
Photo: Bronchoscopic image using autofluorescence imaging shows a squamous cell carcinoma.
Photo: Bronchoscopic image using narrow-band imaging shows a squamous cell carcinoma.
Bronchoscopic images using white light (top), autofluorescence (center), and narrow-band imaging (bottom) show a squamous cell carcinoma (arrows) in the lower trachea.

Navigation bronchoscopy can go much farther into the lung than EBUS, entering not only the trachea and mainstem bronchi but also branches as peripheral as fifth-generation bronchi 2 mm wide. Navigation bronchoscopy facilitates the bronchoscopist’s ability to sample peripheral pulmonary lesions and complements the role of EBUS for sampling mediastinal and hilar lymph nodes, allowing for a complete diagnostic workup and nodal staging of lung cancer with a single intervention.

Autofluorescence bronchoscopy

Autofluorescence bronchoscopy uses blue light together with white light to detect changes in the airway that portend cancer, and this technique can direct biopsies of premalignant tissue and carcinoma in situ before the disease becomes evident on noninvasive imaging or with white light bronchoscopy alone.

To produce autofluorescence, a bronchoscope’s light is filtered to a wavelength of about 400–450 nm; this blue light causes normal chemical compounds in the airways to reflect largely green light and premalignant tissue to reflect largely red light. Unlike other fluorescence methods that require a photosensitizing compound, autofluorescence requires only light. Autofluorescence bronchoscopy may be most useful in patients at high risk of airway cancer and lung cancer patients who received radiation therapy for positive margins after resection.

Although adding blue light to conventional bronchoscopy increases the sensitivity of the bronchoscopy, particularly for detecting high-grade lesions, this technique may also increase the rate of false-positive findings. Because autofluorescence may reveal a large number of areas that look abnormal but may not all be malignant, another modality called narrowband imaging often is used in conjunction with autofluorescence bronchoscopy to select the locations that are most likely to contain malignant tissue. Specific wavelengths of blue and green light that are absorbed by hemoglobin reveal hidden blood vessels; a disorganized, tortuous vasculature suggests malignancy. Lesions with suspicious vasculature in addition to abnormal fluorescence can then be biopsied.

Managing lung conditions concomitant with cancer

Conditions affecting the lungs—such as toxicity due to previous treatments, chronic obstructive pulmonary disease, pleural effusions, and pneumonia—can limit cancer treatment and decrease quality of life. Often, these comorbidities must be dealt with and respiratory function improved so that patients can begin or continue cancer treatment. George Eapen, M.D., an associate professor in the Department of Pulmonary Medicine, said, “We help patients feel better so that going into treatment, they have the best shot possible at a successful outcome.”

Pleural effusions, particularly those that recur after thoracentesis, can be a persistent hindrance to cancer treatment readiness. A useful method for managing recurring pleural effusions is the indwelling catheter, which is tunneled under the skin and inserted into the effusion site. The catheter keeps the space between the pleura dry and allows the formation of adhesions to seal the space, eventually preventing fluid from reaccumulating. Previously, patients with such effusions were hospitalized and treated with sclerosing agents or repeated thoracentesis; now these patients can drain the fluid at home and achieve effective symptom resolution. Allowing patients to drain their own effusions also gives them and their families a greater sense of involvement in their care. “The catheter allows patients to reestablish control over their bodies. That sense of empowerment is very important in maintaining their psychological well-being,” Dr. Eapen said.

Another lung comorbidity that commonly occurs with cancer and may hinder treatment is pneumonia, one of the top causes of death in patients with lung cancer or leukemia. Suspected pneumonia presents several diagnostic and treatment challenges: distinguishing inflammation due to a condition such as chemotherapy toxicity from a disease caused by a pathogen; deducing whether a pathogen is a virus, bacterium, or fungus; identifying within these pathogenic categories the particular strain of pneumonia, which will often be a strain that does not typically affect people without cancer; and selecting an effective treatment without subjecting the patient to side effects that may disrupt his or her cancer treatment.

An experimental technique being studied for identifying the organisms responsible for pneumonia is to perform whole-genome microarray analysis on lung cells from the affected patient (often acquired using bronchoalveolar lavage). Preclinical studies show that pathogens elicit specific host gene expression responses that can clarify the cause of pneumonia when other tests are not sufficient. There is hope that this or similar methods could prove clinically useful in the future for diagnosis of pneumonia.

Image: Endobronchial ultrasonography of a subaortic lymph node
Endobronchial ultrasonography shows a subaortic lymph node (dotted line).

In addition to treating specific comorbidities, pulmonologists help prepare patients for cancer treatment by improving the patients’ cardiopulmonary function. Some patients can improve their performance status through carefully titrated rehabilitation, i.e., an exercise program tailored to their particular needs. These programs aim to increase patients’ cardiopulmonary functional capacity and thus their ability to tolerate treatment and their quality of life regardless of whether further treatment is planned.

Sometimes all it takes to determine that a patient with less-than-ideal lung function is ready for a tough treatment is better information. Assessments prior to surgeries such as lung resection or lobectomy have become more comprehensive in recent years, examining not just individual parts of the body but what an entire person can tolerate. Lung, heart, and muscle function can be assessed individually, but broader assessments such as exercise tests show what those systems can achieve in coordination, enabling more accurate predictions of postoperative function. And it turns out that these more accurate predictions often result in more patients receiving treatment. “Of the patients who would traditionally be deemed ineligible for surgery or other treatment on the basis of lung function alone, as many as one third are actually eligible according to the more complete assessment,” said Dr. Morice.

Patients who lack the cardiopulmonary functional capacity to endure curative treatment for their cancer still can be made more comfortable, and patients who cough up blood or struggle to breathe can be given immediate relief. Interventional procedures performed through a bronchoscope can clear the airway of tumors, cauterize bleeding, and place stents to keep airways open. Dr. Eapen said that one of the most valuable services he provides is simply helping patients with obstructed airways or compressed lungs breathe well again. “We can’t always cure, but we can ease patients’ concerns about suffocating and relieve their suffering,” he said.

Pulmonary medicine has been continually gaining and refining tools to guide biopsies of lung disease, manage conditions affecting the lungs, and improve patients’ quality of life. Dr. Morice expressed the hope that pulmonologists and oncologists throughout the medical community can maintain a dialogue and share expertise and perspectives.

For more information, contact Dr. George Eapen at 713-563-4256 or Dr. Rodolfo Morice at 713-563-4257.

Other articles in OncoLog, March 2013 issue:

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