Chest
Volume 120, Issue 6, December 2001, Pages 1803-1810
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Clinical Investigations
CANCER
Effects of Proton and Combined Proton/Photon Beam Radiation on Pulmonary Function in Patients With Resectable but Medically Inoperable Non-small Cell Lung Cancer

https://doi.org/10.1378/chest.120.6.1803Get rights and content

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 FEV1 ≤ 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 FEV1 > 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 H2O/L/s (p < 0.05). No statistically significant changes occurred in vital capacity, FEV1, or Pao2.

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.

Section snippets

Radiation Therapy With Protons

One of the disadvantages of radiation therapy for NSCLC compared to surgical resection is reduced long-term survival, resulting from local failure.5 Radiation Therapy Oncology Group studies15 have indicated that higher doses of radiation, up to 60 Gy, are associated with increased survival. When doses have been increased to between 65 Gy and 70 Gy with conventional radiation, further survival benefits have not been demonstrated, presumably because significant morbidity supervenes after damage

Patient Eligibility Requirements

Between August 1994 and January 1998, 37 patients with resectable but medically inoperable NSCLC were treated at LLUMC, either with proton radiation therapy alone when very poor pulmonary function was present (protocol 1), or with combined photon beam and proton beam therapy (protocol 2). To be included into the pulmonary function substudy, the patients must have agreed to have their PFT performed at the indicated intervals at Loma Linda University. This was believed to be necessary to ensure

Results

One patient withdrew consent to the study after receiving radiation therapy. Of the remaining 24 patients, 10 patients were treated according to protocol 1 and 14 patients were treated according to protocol 2. In protocol 1, nine patients had stage I tumors and one patient had a stage II tumor. In protocol 2, eight patients had stage I tumors, two patients had stage II tumors, and four patients had stage IIIA tumors.

Data at month 1 are available from 21 patients, since 3 patients did not report

Radiation-Induced Lung Damage

Several investigators divide the clinical picture of radiation-induced lung damage into three main phases: (1) an early phase, characterized by a period of subclinical pneumonitis (first month); (2) an intermediate phase, in which acute pneumonitis supervenes (third week to several months); and (3) a late phase, in which fibrosis appears (6 months and later).27 To account for these phases, we selected to perform PFT testing at month 1 (early phase), month 3 (intermediate phase), and months 6 to

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. Due to its demonstrated low pulmonary toxicity, dose escalation and fractionation studies are warranted to define optimal dosing schedules.

Acknowledgment

The authors thank William Preston, EdD, for editorial contributions, Sandy Teichman, BSN, for assistance with manuscript preparation, and Rudolf Fuerres, MA, for assistance in statistical analysis.

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