Effects of proton and combined proton/photon beam radiation on pulmonary function in patients with resectable but medically inoperable non-small cell lung cancer.

STUDY OBJECTIVES We evaluated the effects on pulmonary function of irradiating lung cancer with protons alone or protons combined with photons. DESIGN Prospective phase I/II study. SETTING University medical center. PATIENTS AND INTERVENTIONS Ten patients with stage I-II non-small cell lung cancer (NSCLC) and FEV(1) < or = 1.0 L were irradiated with protons to areas of gross disease only, using 51 cobalt gray equivalents (CGE) in 10 fractions (protocol 1). Fifteen patients with stage I-IIIA NSCLC and FEV(1) > 1.0 L received 45-Gy photon irradiation to the primary lung tumor and the mediastinum, plus a 28.8-CGE proton boost to the gross tumor volume (protocol 2). MEASUREMENTS Pulmonary function was evaluated prior to treatment and 1 month, 3 months, and 6 to 12 months following irradiation. RESULTS In patients receiving protocol 1, no significant changes in pulmonary function occurred. In patients receiving protocol 2, at 6 to 12 months, the diffusion capacity of the lung for carbon monoxide had declined from 61% of predicted to 45% of predicted (p < 0.05), total lung capacity had declined from 114% of predicted to 95% of predicted (p < 0.05), and residual volume had declined from 160% of predicted to 132% of predicted (p < 0.05). Airway resistance increased from 3.8 to 5.2 cm H(2)O/L/s (p < 0.05). No statistically significant changes occurred in vital capacity, FEV(1), or PaO(2). CONCLUSIONS Our observations indicate that it is feasible to apply higher-than-conventional doses of radiation at a higher-than-conventional dose per fraction without excess pulmonary toxicity when conformal radiation techniques with protons are used.

[1]  H. Dickie,et al.  Pulmonary reaction to upper mantle radiation therapy for Hodgkin's disease. , 1979, Chest.

[2]  S. Hellman,et al.  SEQUELAE OF RADICAL RADIOTHERAPY OF CARCINOMA OF THE LUNG. , 1964, Radiology.

[3]  P. Rubin,et al.  Molecular biology mechanisms in the radiation induction of pulmonary injury syndromes: interrelationship between the alveolar macrophage and the septal fibroblast. , 1992, International journal of radiation oncology, biology, physics.

[4]  P. Rubin,et al.  Patterns of tumor recurrence after definitive irradiation for inoperable non-oat cell carcinoma of the lung. , 1980, International journal of radiation oncology, biology, physics.

[5]  P. Gillam,et al.  Effect of Chronic Bronchitis on Changes in Pulmonary Function Caused by Irradiation of the Lungs , 1965, Thorax.

[6]  N. Masuda,et al.  Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  D. Johns,et al.  Single breath carbon monoxide diffusing capacity (transfer factor) , 1988, The American review of respiratory disease.

[8]  N. Choi Prospective prediction of postradiotherapy pulmonary function with regional pulmonary function data: promise and pitfalls. , 1988, International journal of radiation oncology, biology, physics.

[9]  L. Peters Radiation therapy tolerance limits: For one or for all?‐Janeway lecture , 1996, Cancer.

[10]  K. Harwood Non-small cell lung cancer: an overview of diagnosis, staging, and treatment. , 1996, Seminars in oncology nursing.

[11]  L. Brady,et al.  THE EFFECTS OF RADIATION THERAPY ON PULMONARY FUNCTION IN CARCINOMA OF THE LUNG. , 1965, Radiology.

[12]  V. Rusch,et al.  Survival after resection of stage II non-small cell lung cancer. , 1992, The Annals of thoracic surgery.

[13]  C K Wells,et al.  Evaluation of clinical methods for rating dyspnea. , 1988, Chest.

[14]  Colin M. MacLeod,et al.  Evaluation of chemotherapeutic agents , 1949 .

[15]  J. Slater,et al.  Pulmonary injury from proton and conventional radiotherapy as revealed by CT. , 1999, AJR. American journal of roentgenology.

[16]  S. Breit,et al.  Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. , 1995, International journal of radiation oncology, biology, physics.

[17]  M. Melamed,et al.  Current status of screening for lung cancer. , 1994, Chest surgery clinics of North America.

[18]  M. W. Peterson,et al.  Predicting postoperative pulmonary function in patients undergoing lung resection. , 1995, Chest.

[19]  H. O. Heinemann,et al.  Effects of irradiation of chest on pulmonary function in man. , 1961, Journal of applied physiology.

[20]  Melamed Mr,et al.  Current status of screening for lung cancer. , 1994 .

[21]  J. H. Auchincloss,et al.  Pulmonary function following mantle-field irradiation for Hodgkin's disease. , 1974, Radiology.

[22]  L. Solin,et al.  Prospective prediction of post-radiation therapy lung function using quantitative lung scans and pulmonary function testing. , 1988, International journal of radiation oncology, biology, physics.

[23]  D. Rosenthal,et al.  The pulmonary effect of mantle irradiation in patients with Hodgkin's disease. , 1973, Radiology.

[24]  T. Raffin,et al.  Pulmonary radiation injury. , 1997, Chest.

[25]  E. Hall,et al.  Radiobiology for the radiologist , 1973 .

[26]  J Ikezoe,et al.  CT appearance of acute radiation-induced injury in the lung. , 1988, AJR. American journal of roentgenology.

[27]  N. Choi,et al.  Toxicity of thoracic radiotherapy on pulmonary function in lung cancer. , 1994, Lung cancer.

[28]  N. Gross Pulmonary effects of radiation therapy. , 1977, Annals of internal medicine.

[29]  P. Wingo,et al.  Cancer statistics, 1996 , 1996, CA: a cancer journal for clinicians.

[30]  R. G. Hoffman,et al.  The pathophysiologic and roentgenologic effects of chest irradiation in breast carcinoma. , 1986, International journal of radiation oncology, biology, physics.

[31]  Buist As Standardization of spirometry. , 1987 .

[32]  J M Slater,et al.  The proton treatment center at Loma Linda University Medical Center: rationale for and description of its development. , 1992, International journal of radiation oncology, biology, physics.

[33]  J. Cox,et al.  Non-small cell lung cancer. Role of radiation therapy. , 1986, Chest.

[34]  D. Karnofsky The clinical evaluation of chemotherapeutic agents in cancer , 1949 .

[35]  L. Brady,et al.  Physiologic changes before and after radiation treatment for carcinoma of the lung. , 1968, JAMA.

[36]  A. Scariato,et al.  Treatment of non-small cell lung cancer with external beam radiotherapy and high dose rate brachytherapy. , 1992, International journal of radiation oncology, biology, physics.

[37]  P. Willcox,et al.  The effect of irradiation on lung function and perfusion in patients with lung cancer. , 1995, International journal of radiation oncology, biology, physics.

[38]  D. Miller,et al.  A review of proton beam radiation therapy. , 1995, Medical physics.

[39]  J M Slater,et al.  Proton-beam radiotherapy for early-stage lung cancer. , 1999, Chest.

[40]  D. Teates,et al.  Some consequences of pulmonary irradiation. , 1966, The American journal of roentgenology, radium therapy, and nuclear medicine.

[41]  R. Peschel,et al.  Results of radical radiation therapy in clinical stage I, technically operable non-small cell lung cancer. , 1987, International journal of radiation oncology, biology, physics.

[42]  J. Smith,et al.  Lung cancer in patients with borderline lung functions--zonal lung perfusion scans at presentation and lung function after high dose irradiation. , 1990, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[43]  L. Verhey,et al.  Relative biological effectiveness of modulated proton beams in various murine tissues. , 1984, International journal of radiation oncology, biology, physics.