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Monitoring pulmonary complications in long-term childhood cancer survivors: Guidelines for the primary care physician

Cleveland Clinic Journal of Medicine. 2008 July;75(7):531-539
July 1, 2008|Cleveland Clinic Journal of Medicine
Allen Liles, MD;Julie Blatt, MD;David Morris, MD;Richard Wardrop III, MD;Anjali Sharma, MD;Aimee Sznewajs, MS, PNP;Robert Goldsby, MD
Author and Disclosure Information

Allen Liles, MD
Program Director of the Combined Internal Medicine and Pediatrics Program, Department of Medicine-Pediatrics, The University of North Carolina, Chapel Hill; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

Julie Blatt, MD
Division of Pediatric Hematology-Oncology, The University of North Carolina, Chapel Hill; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

David Morris, MD
Department of Radiation Oncology, The University of North Carolina, Chapel Hill; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

Richard Wardrop III, MD
Director of Resident Research in Internal Medicine, Assistant Clinical Professor of Internal Medicine and Pediatrics, The Carilion Clinic Department of Internal Medicine and Pediatrics and the University of Virginia School of Medicine; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

Anjali Sharma, MD
Division of Pediatric Bone Marrow Transplantation, University of California, San Francisco; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

Aimee Sznewajs, MS
Division of Pediatric Hematology-Oncology, University of California, San Francisco; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

Robert Goldsby, MD
Division of Pediatric Hematology-Oncology, University of California, San Francisco; Pulmonary Task Force, Late Effects Steering Committee, Children’s Oncology Group

Address: Allen Liles, MD, University of North Carolina at Chapel Hill, Pediatric Education Office CB #7593, Room 30137, Women’s Hospital UNC, Chapel Hill, NC 27599; e-mail liles@med.unc.edu

Dr. Morris has disclosed that he has received consulting fees from the Radiosurgery Centers Corporation and that he owns stock in Amgen, Anesiva, and Synarc corporations.

ABSTRACTCurative therapy for childhood cancers poses the risk of long-term complications, necessitating regular lifelong follow-up for survivors. The Children’s Oncology Group (COG) has issued guidelines on this topic (www.survivorshipguidelines.org). This review summarizes the findings of the COG Guideline Task Force on Pulmonary Complications with respect to pulmonary toxicity.

KEY POINTS

  • Radiation therapy causes pulmonary fibrosis, interstitial pneumonitis, and restrictive or obstructive lung disease. The risk is dose-dependent and increases with concomitant chemotherapy, younger age at treatment, atopic history, and smoking.
  • Alkylating agents cause pulmonary fibrosis. Bleomycin can cause interstitial pneumonitis, pulmonary fibrosis, or, very rarely, acute respiratory distress syndrome.
  • Cancer survivors should have a yearly history and physical examination, plus pulmonary function testing and radiography at baseline and repeated as clinically indicated.
  • All patients who smoke should be encouraged to quit.

OTHER RISK FACTORS FOR LUNG DAMAGE

Additional factors contributing to chronic pulmonary toxicity include superimposed infection, underlying pneumonopathy (eg, asthma), cigarette use, respirator toxicity, chronic graft-vs-host disease, and the effects of chronic pulmonary involvement by tumor or reaction to tumor. For example, a subset of patients with Langerhans cell histiocytosis can develop histiocytic pulmonary infiltrates or honeycombing with severe chronic restrictive lung disease unrelated to therapy or the presence of active tumor.

Although not well documented, scuba diving also has been said to exacerbate pulmonary fibrosis through increased underwater pressures and high oxygen levels.34

Lung lobectomy during childhood appears to have no significant impact on long-term pulmonary function,35–37 but the effect of lung surgery for children with cancer is not well defined.

GET THE PATIENT’S TREATMENT SUMMARY

Regardless of the setting for follow-up, the first step in any evaluation is to obtain the patient’s medical history and especially a treatment summary. The treatment summary should outline the cancer diagnosis, involved sites of disease, age at diagnosis, specific treatments (surgery, chemotherapy, radiation), and other key interventions and events during and after cancer therapy. Sample forms for physicians and patients are available at www.survivorshipguidelines.org.

Before the long-term survivor of childhood cancer graduates from the care of a pediatric oncologist, this treatment record and possible long-term problems should be reviewed with the family and, in the case of an adolescent, with the patient. Correspondence between the pediatric oncologist and subsequent caregivers should also include a treatment summary. The treatment summary allows the survivor or his health care provider to interface with the COG guidelines to determine recommended follow-up care. The primary care physician and the patient both should have copies of this document.

We are developing an interactive Web-based version of a standardized summary form, designed to interface with an automated version of the COG guidelines in order to generate individualized follow-up recommendations.

ASK ABOUT LUNG SYMPTOMS

We recommend that health care providers investigate symptoms of pulmonary dysfunction, and specifically ask about chronic cough with or without fever, shortness of breath, and dyspnea on exertion during yearly health care visits.

Baseline pulmonary function testing (including DLCO and spirometry) and chest radiography are recommended 2 or more years after completion of therapy to document persistent deficits and determine the need for continued monitoring. Reevaluation of pulmonary function should be considered in patients with established deficits who require general anesthesia and for those treated with bleomycin.

Scuba diving remains controversial for long-term survivors. Consequently, patients with risk factors for lung disease should be encouraged to consult with a pulmonary specialist to determine if diving poses a health threat to their pulmonary status. If clinical pulmonary dysfunction is identified, referral to colleagues in pulmonology for additional evaluation and treatment is essential. Increasing familiarity of primary care providers with surveillance concepts is a key element in survivorship care.

Smoking cessation can enhance the health of all patients and is particularly important among long-term survivors, especially those who received treatments predisposing to pulmonary injury. Strategies for cessation and patient information can be found at www.cdc.gov/tobacco/how2quit.htm.

Clinicians can take advantage of every patient interaction to assess readiness for smoking cessation and assist patients in this goal. Following the principles of patient-centered counseling, physicians can guide patients into considering a change of behavior with advice and encouragement. Whenever possible, physicians should personalize the risks of smoking as well as the short-term and long-term benefits. As smokers prepare to quit, their physicians can assist in developing a plan that includes a quit date.

Many pharmacologic agents are available to assist patients, ie, nicotine inhalers, sprays, gum, and transdermal patches; the antidepressants bupropion (Wellbutrin) and nortriptiline (Pamelor); the alpha-2 adrenergic agonist clonidine (Catapres); and, most recently, the nicotine receptor partial agonist varenicline (Chantix).38

Follow-up to prevent relapse is an important part of this process.

Acknowledgment. This work was supported in part by the Swim Across America Foundation and the Campini Foundation.

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