Symptomatic Radiation Pneumonitis in Elderly Patients Receiving Thoracic Irradiation

Abstract Objectives We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC). Materials and methods Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30–40 mg/m2 two times daily) on Days 1–14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate. Results Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6–71.4%), and the median PFS was 16.8 months (95% CI 7.8–not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3–4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed. Conclusion Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

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Early variations in lymphocytes and T lymphocyte subsets are associated with radiation pneumonitis in lung cancer patients and experimental mice received thoracic irradiation

Cancer Medicine ◽

10.1002/cam4.2987 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3437-3444 ◽

Cited By ~ 1

Author(s):

Pu Zhou ◽

Lu Chen ◽

Dong Yan ◽

Changlin Huang ◽

Guangpeng Chen ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

T Lymphocyte ◽

Lymphocyte Subsets ◽

Radiation Pneumonitis ◽

T Lymphocyte Subsets ◽

Lung Cancer Patients ◽

Thoracic Irradiation

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Unilateral radiation pneumonitis in sheep: physiological changes and bronchoalveolar lavage

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.3.1273 ◽

1989 ◽

Vol 66 (3) ◽

pp. 1273-1279 ◽

Cited By ~ 6

Author(s):

B. F. Tillman ◽

J. E. Loyd ◽

A. W. Malcolm ◽

B. A. Holm ◽

K. L. Brigham

Keyword(s):

Pulmonary Hypertension ◽

Bronchoalveolar Lavage ◽

Alveolar Macrophages ◽

Radiation Pneumonitis ◽

Lower Surface ◽

Clinical Feature ◽

Thoracic Irradiation ◽

Radiation Port ◽

Lung Irradiation ◽

Immediate Response

Radiation pneumonitis is a life-threatening result of therapeutic thoracic irradiation, yet its mechanisms are poorly understood. We studied the effects of unilateral lung irradiation (3,000 rad) in sheep from the immediate response to the later development of radiation pneumonitis. We defined radiation pneumonitis by its diagnostic clinical feature, radiographic infiltration of the irradiated zone with a straight margin corresponding to the radiation port. The immediate response in the few hours after irradiation was characterized by cough, labored respiration, hypoxemia (arterial PO2 decreased 19 Torr), mild pulmonary hypertension (pulmonary arterial pressure increased 20%), and lymphopenia. Hemodynamics and gas exchange returned to normal by day 2 but became abnormal again before or during radiation pneumonitis at 32 +/- 2 days. Respiratory distress, hypoxemia, and pulmonary hypertension recurred during radiation pneumonitis. Bronchoalveolar lavage during radiation pneumonitis contained increased neutrophils (19 +/- 4%, control = 7%), increased protein (0.27 +/- 0.1 g/dl, control = 0.12 +/- 0.03), and severely impaired ability to lower surface tension. Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase). Normal control alveolar macrophages increased superoxide production after stimulation greater than 400%. We conclude that unilateral lung irradiation in sheep causes a mild immediate response followed by radiation pneumonitis at 1 mo. Unilateral radiation pneumonitis in this model is associated with ipsilateral neutrophilic alveolitis, increased bronchoalveolar lavage protein, and impaired surfactant function, as well as bilateral functional abnormalities of alveolar macrophages.

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Early variations of circulating IL-6 and IL-10 during thoracic irradiation are predictive for incidence of radiation pneumonitis in patients with non small cell lung cancer: Results from a prospective study

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.7079 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 7079-7079

Author(s):

M. Perol ◽

D. Perol ◽

D. Arpin ◽

J. Y. Blay ◽

L. Falchero ◽

...

Keyword(s):

Lung Cancer ◽

Prospective Study ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Radiation Pneumonitis ◽

Small Cell ◽

Small Cell Lung ◽

Thoracic Irradiation ◽

A Prospective Study

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The role of anti-epithelial cell antibodies in the pathogenesis of bilateral radiation pneumonitis caused by unilateral thoracic irradiation

Respiratory Medicine ◽

10.1053/rmed.2000.0858 ◽

2000 ◽

Vol 94 (9) ◽

pp. 875-880 ◽

Cited By ~ 5

Author(s):

J. FUJITA ◽

S. BANDOH ◽

Y. OHTSUKI ◽

N. DOBASHI ◽

M. HIROI ◽

...

Keyword(s):

Epithelial Cell ◽

Radiation Pneumonitis ◽

Thoracic Irradiation

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Lung stereotactic body radiation therapy for elderly patients aged ≥ 80 years with pathologically proven early-stage non-small cell lung cancer: a retrospective cohort study

Radiation Oncology ◽

10.1186/s13014-021-01769-7 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Kenta Watanabe ◽

Kuniaki Katsui ◽

Soichiro Sugiyama ◽

Kotaro Yoshio ◽

Masahiro Kuroda ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Elderly Patients ◽

Stereotactic Body Radiation Therapy ◽

Radiation Pneumonitis ◽

Early Stage ◽

Small Cell ◽

Small Cell Lung ◽

Survival Curves ◽

Early Stage Nsclc

Abstract Background Stereotactic body radiation therapy (SBRT) is an established therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). Many elderly patients are medically inoperable owing to comorbidities. Therefore, SBRT may be a useful therapy for elderly patients. However, the application of SBRT for patients aged ≥ 80 years has not been completely elucidated. Therefore, this study aimed to assess the clinical utility of SBRT for elderly patients aged ≥ 80 years with pathologically proven early-stage NSCLC. Methods We retrospectively evaluated the data of patients aged ≥ 80 years with pathologically proven primary NSCLC who underwent SBRT at our institution between January 2009 and March 2020. Treatment outcomes and toxicities were analyzed. We used the Kaplan–Meier method to estimate survival curves and the log-rank test to compare the survival curves. We performed univariate and multivariate Cox regression analyses. p-values < 0.05 were regarded significant. Results Sixty-four patients (65 lesions) were included, and the median follow-up period was 38.7 (range 3.5–95.7) months. The median age was 82.9 (range 80.0–94.8) years. Sixteen patients were medically operable, and 48 patients were medically inoperable. The prescribed dose of SBRT was either 48 Gy in four fractions or 60 Gy in 10 fractions. The median survival time was 60.0 months (95% confidence interval, 43.5–71.1). The 1-, 3-, and 5-year local control, cancer-specific survival, progression-free survival, and overall survival rates were 98.4%, 98.4%, 81.0%, and 88.9%; 90.1%, 93.7%, 58.9%, and 68.3%; and 87.4%, 83.5%, 38.2%, and 47.5%, respectively. Multivariate analysis revealed that inoperability and solid nodules were the predictors of poor overall survival after SBRT in elderly patients. Two patients (3.1%) had grade 3 radiation pneumonitis, and one patient (1.6%) had grade 5 radiation pneumonitis. Conclusions SBRT was feasible in patients aged ≥ 80 years with NSCLC. It achieved good local control with minimal toxicity. SBRT may be beneficial in elderly patients with early-stage NSCLC.

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