Impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer / Impacto da radioterapia torácica na função respiratória e capacidade de exercício em pacientes com câncer de mama

ABSTRACT Objective: To evaluate the impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer. Methods: Breast cancer patients in whom thoracic radiotherapy was indicated after surgical treatment and chemotherapy were submitted to HRCT, respiratory evaluation, and exercise capacity evaluation before radiotherapy and at three months after treatment completion. Respiratory muscle strength testing, measurement of chest wall mobility, and complete pulmonary function testing were performed for respiratory evaluation; cardiopulmonary exercise testing was performed to evaluate exercise capacity. The total radiotherapy dose was 50.4 Gy (1.8 Gy/fraction) to the breast or chest wall, including supraclavicular lymph nodes (SCLN) or not. Dose-volume histograms were calculated for each patient with special attention to the ipsilateral lung volume receiving 25 Gy (V25), in absolute and relative values, and mean lung dose. Results: The study comprised 37 patients. After radiotherapy, significant decreases were observed in respiratory muscle strength, chest wall mobility, exercise capacity, and pulmonary function test results (p < 0.05). DLCO was unchanged. HRCT showed changes related to radiotherapy in 87% of the patients, which was more evident in the patients submitted to SCLN irradiation. V25% significantly correlated with radiation pneumonitis. Conclusions: In our sample of patients with breast cancer, thoracic radiotherapy seemed to have caused significant losses in respiratory and exercise capacity, probably due to chest wall restriction; SCLN irradiation represented an additional risk factor for the development of radiation pneumonitis.

RESUMO Objetivo: Avaliar o impacto da radioterapia torácica na função respiratória e capacidade de exercício em pacientes com câncer de mama. Métodos: Pacientes com câncer de mama com indicação de radioterapia torácica após tratamento cirúrgico e quimioterápico foram submetidas a TCAR, avaliação respiratória e avaliação da capacidade de exercício antes da radioterapia torácica e três meses após o término do tratamento. Foram realizados teste de força muscular respiratória, medição da mobilidade torácica e prova de função pulmonar completa para a avaliação respiratória; realizou-se teste de exercício cardiopulmonar para avaliar a capacidade de exercício. A dose total de radioterapia foi de 50,4 Gy (1,8 Gy/fração) na mama ou na parede torácica, incluindo ou não a fossa supraclavicular (FSC). Histogramas dose-volume foram calculados para cada paciente com especial atenção para o volume pulmonar ipsilateral que recebeu 25 Gy (V25), em números absolutos e relativos, e a dose pulmonar média. Resultados: O estudo incluiu 37 pacientes. Após a radioterapia, observou-se diminuição significativa da força muscular respiratória, mobilidade torácica, capacidade de exercício e resultados da prova de função pulmonar (p < 0,05). A DLCO permaneceu inalterada. A TCAR mostrou alterações relacionadas à radioterapia em 87% das pacientes, o que foi mais evidente nas pacientes submetidas à irradiação da FSC. O V25% correlacionou-se significativamente com a pneumonite por radiação. Conclusões: Em nossa amostra de pacientes com câncer de mama, a radioterapia torácica parece ter causado perdas significativas na capacidade respiratória e de exercício, provavelmente por causa da restrição torácica; a irradiação da FSC representou um fator de risco adicional para o desenvolvimento de pneumonite por radiação.

Impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer.

OBJECTIVE: To evaluate the impact of thoracic radiotherapy on respiratory function and exercise capacity in patients with breast cancer. METHODS: Breast cancer patients in whom thoracic radiotherapy was indicated after surgical treatment and chemotherapy were submitted to HRCT, respiratory evaluation, and exercise capacity evaluation before radiotherapy and at three months after treatment completion. Respiratory muscle strength testing, measurement of chest wall mobility, and complete pulmonary function testing were performed for respiratory evaluation; cardiopulmonary exercise testing was performed to evaluate exercise capacity. The total radiotherapy dose was 50.4 Gy (1.8 Gy/fraction) to the breast or chest wall, including supraclavicular lymph nodes (SCLN) or not. Dose-volume histograms were calculated for each patient with special attention to the ipsilateral lung volume receiving 25 Gy (V25), in absolute and relative values, and mean lung dose. RESULTS: The study comprised 37 patients. After radiotherapy, significant decreases were observed in respiratory muscle strength, chest wall mobility, exercise capacity, and pulmonary function test results (p < 0.05). DLCO was unchanged. HRCT showed changes related to radiotherapy in 87% of the patients, which was more evident in the patients submitted to SCLN irradiation. V25% significantly correlated with radiation pneumonitis. CONCLUSIONS: In our sample of patients with breast cancer, thoracic radiotherapy seemed to have caused significant losses in respiratory and exercise capacity, probably due to chest wall restriction; SCLN irradiation represented an additional risk factor for the development of radiation pneumonitis.

Phase II Trial of SBRT for Stage I NSCLC: Survival, Local Control, and Lung Function at 36 Months.

OBJECTIVES: The long-term impact of stereotactic body radiotherapy (SBRT) on respiratory function in patients with inoperable non-small cell lung cancer (NSCLC) has not been well studied. The aim of this phase II trial was to assess local control, survival, and lung function at 36 months after treatment. METHODS: From July 2008 to February 2012, 42 patients in whom inoperable NSCLC with peripheral lesions was diagnosed were consecutively enrolled. Lung function testing included measurement of forced expiratory vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide. All lung function parameters were registered at baseline and evaluated prospectively after SBRT every 6 months for 2 years and annually thereafter. RESULTS: Of the 42 initial patients, four were excluded. At 36 months after SBRT, 22 patients were still evaluable (12 deaths and four patients lost to follow-up). At 36 months, the rate of local control was 94%. At 1, 2, and 3 years, respectively, overall survival rates were 92%, 75%, and 66%. Median overall survival was 57 months. Grade (G) 3 acute toxicity was observed in four patients (10%). Chronic G1 toxicity was observed in all 38 cases (100%), with the most common type being pneumonitis (26 patients [68%]). The mean lung function parameters at baseline and at 36 months after treatment were as follows: forced expiratory vital capacity 83% versus 79%; forced expiratory volume in 1 second 62% versus 57%; and diffusing capacity for carbon monoxide 54% versus 54%. These changes were not significant. CONCLUSIONS: In this trial, local control and survival rates after SBRT were very good. Treatment with SBRT had no significant impact on lung function at 36 months. These findings provide further support for the use of SBRT as a radical treatment for NSCLC. Lung toxicity is minimal, even in patients with poor pulmonary function before treatment.

Effects of Definitive Chemoradiotherapy on Respiratory Function Tests and Quality of Life Scores During Treatment of Lung Cancer.

BACKGROUND: Chemoradiotherapy is an important treatment modality for lung cancers. The aim of this study was to investigate alterations in, as well as the interrelationship between, lung function and quality of life of patients receiving chemoradiotherapy due to locally advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) limited to the thorax. MATERIALS AND METHODS: The study included patients receiving definitive chemoradiotherapy for lung carcinoma. The respiratory function of the patients was assessed by measuring forced expiratory volume in 1 s per unit (FEV1) and forced expiratory volume in 1s per unit of vital capacity (FEV1/VC) before, in the middle of and after treatment. During the study, EORTC QLQ C30 and LC13 questionnaires developed by the Committee of the European Organization for Research and Treatment of Cancer (EORTC) were employed to evaluate the quality of life on the same day as respiratory function tests (RFT). FINDINGS: The study included 23 patients in total: 19 (82.6%) diagnosed with NSCLC and 4 (17.4%) with SCLC. The average percentage FEV1 was 55.6±21.8% in the pre-treatment period, 56.2±19.2% in the middle of treatment and 60.4±22% at the end of treatment. The improvement in functional scores, symptom scores and general health scores during treatment was not statistically significant (P=0.568, P=0.734, P=0.680, P=0.757 respectively). CONCLUSIONS: Although this study showed an improvement in respiratory function and quality of life of patients during treatment with thoracic chemoradiotherapy, no statistically significant results were obtained. While evaluating the effectiveness of treatments for lung carcinoma, the effects of treatment on respiratory function and quality of life should be considered.

Long-term functional and radiological pulmonary changes after radiation therapy for breast cancer.

BACKGROUND: We assessed late functional and radiological pulmonary changes in breast cancer patients after a median of 11 years following radiotherapy (RT). MATERIAL AND METHODS: Seventy women who received adjuvant loco-regional RT for breast cancer during November 1994-May 1998 accepted to participate in this follow-up study. Pulmonary function tests (PFTs) (n = 56) were compared to pre-RT examinations and diagnostic computer tomography (CT) of the lungs (n = 70) were performed and compared to four months post-RT examinations. RESULT: The median-matched vital capacity (VC), forced expiratory volume in one second (FEV1), and total lung capacity (TLC) were reduced 15%, 9%, and 7%, respectively, at the long-term follow-up (p < 0.001). We could not, however, detect a correlation between ipsilateral V20 and VC-changes. Diffusion capacity (DLCO) appeared to improve compared with the pre-RT baseline level probably due to transient chemotherapy-induced toxicity. The median-matched percentage of the predicted DLCO 11 years after RT was, however, only 86%, indicating a chronic therapy-induced reduction also of this metric. According to the Arriagada classification, ipsilateral V20 and long-term CT-changes showed a significant correlation (rs: 0. 57; p < 0.001) in a small subset of the women. CONCLUSION: A chronic clinically significant reduction of PFTs compared to pre-RT values and CT-changes four months after RT were still detectable after a median follow-up of 11 years. There was a statistical correlation between V20 and abnormalities on CT but no statistical correlation between V20 and VC-changes.

Acute effects of light emitting diodes therapy (LEDT) in muscle function during isometric exercise in patients with chronic obstructive pulmonary disease: preliminary results of a randomized controlled trial.

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to early muscle fatigue. Light-emitting diodes therapy (LEDT) has been used to minimize muscle fatigue in athletes and healthy subjects. The aim of this study is to investigate the acute effects of LEDT on muscle fatigue and perception of effort in patients with COPD during isometric endurance test of the quadriceps femoris (QF). Ten patients (VEF1 50 ± 13% of predicted) underwent a single LEDT and sham application, 48 h apart, in a randomized crossover design. The LEDT and sham were applied in three localized areas of the QF (rectus femoris, vastus lateralis, and vastus medialis). Before and after exposure to LEDT and sham, the patients performed an isometric endurance test (60 % of the maximum voluntary isometric contraction), until the limit of tolerance concomitant to surface electromyography recording (median frequency as mean outcome). The slope obtained from linear regression analysis of the median frequency (MF) over endurance time was also used as an endurance index. Endurance time increased significantly after exposure to LEDT (from 26 ± 2 to 53 ± 5 s) as compared to sham (from 23 ± 3 to 30 ± 4 s) (F = 64, P = 0.0001). A greater decline in MF was observed during isometric endurance test after sham, compared to LEDT (F = 14.6, P = 0.004). The slope of the MF over time was lower post-LEDT compared to post-sham (-0.7 ± 0.3 vs. -1.5 ± 0.8; P = 0.004). The dyspnea score corrected for endurance time was lower post-LEDT (P = 0.008) but similar for fatigue both post-LEDT and post-sham. A single application of LEDT minimizes muscle fatigue and increases isometric endurance time.

Lack of a dose-effect relationship for pulmonary function changes after stereotactic body radiation therapy for early-stage non-small cell lung cancer.

PURPOSE: To evaluate the influence of tumor size, prescription dose, and dose to the lungs on posttreatment pulmonary function test (PFT) changes after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: The analysis is based on 191 patients treated at 5 international institutions: inclusion criteria were availability of pre- and post-SBRT PFTs and dose-volume histograms of the lung and planning target volume (PTV); patients treated with more than 1 SBRT course were excluded. Correlation between early (1-6 months, median 3 months) and late (7-24 months, median 12 months) PFT changes and tumor size, planning target volume (PTV) dose, and lung doses was assessed using linear regression analysis, receiver operating characteristics analysis, and Lyman's normal tissue complication probability model. The PTV doses were converted to biologically effective doses and lung doses to 2 Gy equivalent doses before correlation analyses. RESULTS: Up to 6 months after SBRT, forced expiratory volume in 1 second and carbon monoxide diffusion capacity changed by -1.4% (95% confidence interval [CI], -3.4% to 0) and -7.6% (95% CI, -10.2% to -3.4%) compared with pretreatment values, respectively. A modest decrease in PFTs was observed 7-24 months after SBRT, with changes of -8.1% (95% CI, -13.3% to -5.3%) and -12.4% (95% CI, -15.5% to -6.9%), respectively. Using linear regression analysis, receiver operating characteristic analysis, and normal tissue complication probability modeling, all evaluated parameters of tumor size, PTV dose, mean lung dose, and absolute and relative volumes of the lung exposed to minimum doses of 5-70 Gy were not correlated with early and late PFT changes. Subgroup analysis based on pre-SBRT PFTs (greater or equal and less than median) did not identify any dose-effect relationship. CONCLUSIONS: This study failed to demonstrate a significant dose-effect relationship for changes of pulmonary function after SBRT for early-stage non-small cell lung cancer.

Impact of 3D conformal radiotherapy on lung function of patients with lung cancer: a prospective study.

BACKGROUND: The development of three-dimensional conformal radiotherapy (3D-RT) has enabled the restriction of the dose to normal lung, limiting radiation-induced lung injury. OBJECTIVES: This study was designed to describe the time course of lung function until 7.5 months after 3D-RT in patients with lung cancer, and assess the relationship between lung function changes and dose-volume histogram (DVH) analysis or computed tomography scan changes. Radiation doses were optimized according to recent guidelines. METHODS: Sixty-five lung cancer patients treated with 3D-RT agreed to participate in this prospective, hospital-based study. Lung volumes, forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) were measured before radiotherapy (RT), 10 weeks, 4 and 7.5 months after the beginning of 3D-RT. RESULTS: Eleven lung cancer patients (17%) developed grade 2-3 respiratory symptoms after RT. At 7.5 months, vital capacity (VC) was 96 ± 2%, total lung capacity (TLC) 95 ± 2%, FEV1 93 ± 2% and DLCO 90 ± 2% of the initial value. Only 15% of patients showed pulmonary function reduction > 20%. Patients with FEV1 or DLCO < 60% before RT did not show significant changes after RT. There were weak correlations between reduction of VC, TLC, FEV1 or DLCO and radiation dosimetric parameters and between reduction of VC or FEV1 and radiation-induced pneumonitis images. CONCLUSIONS: In lung cancer, the reduction of lung function within 7.5 months after 3D-RT was small and correlated, albeit weakly, with DVH parameters. Patients with initially impaired lung function showed tiny changes in spirometry and DLCO values.

HDR brachytherapy: an option for preventing nonmalignant obstruction in patients after lung transplantation.

PURPOSE: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. PATIENTS AND METHODS: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. RESULTS: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. CONCLUSIONS: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm.

Long-term changes in pulmonary function after incidental lung irradiation for breast cancer: a prospective study with 7-year follow-up.

PURPOSE: To evaluate late pulmonary function changes after incidental pulmonary irradiation for breast cancer. METHODS AND MATERIALS: Forty-three consecutive female patients diagnosed with breast carcinoma and treated with postoperative radiation therapy (RT) at the same dose (50 Gy) and fractionation (2 Gy/fraction, 5 days/week) were enrolled. Pulmonary function tests (PFT) and ventilation/perfusion scans were performed before RT and 6, 12, 24, and 84 months afterward. RESULTS: Forty-one patients, mean age 55 years, were eligible for the analysis. No differences were found in the baseline PFT values for age, smoking status and previous chemotherapy; women undergoing mastectomy showed baseline spirometric PFT values lower than did women treated with conservative surgery. The mean pulmonary dose was 10.9 Gy, being higher in women who also received lymph node RT (15.8 vs 8.6, P<.01). Only 1 patient experienced symptomatic pneumonitis. All PFT values showed a reduction at 6 months. From then on, the forced vital capacity and forced expiratory volume in 1 second began their recovery until reaching, and even exceeding, their baseline values at 7 years. Diffusing capacity of the lungs for carbon monoxide and ventilation/perfusion scans continued to reduce for 24 months and then partially recovered their baseline values (-3.5%, -3.8%, and -5.5%, respectively). Only the percentage difference at 7 years in the ventilation scan correlated with the dosimetric parameters studied. Other variables, such as age, smoking status, previous chemotherapy, and concomitant tamoxifen showed no significant relation with changes in PFT (ΔPFT) values at 7 years. CONCLUSIONS: The study of reproducible subclinical parameters, such as PFT values, shows how their figures decrease in the first 2 years but practically recover their baseline values in the long term. The extent of the reduction in PFT values was small, and there was no clear association with several dosimetric and clinical parameters.

Effect of CT fluoroscopy-guided transpulmonary radiofrequency ablation of liver tumours on the lung.

OBJECTIVE: We retrospectively evaluated the effect of transpulmonary radiofrequency ablation (RFA) of liver tumours on the lung. METHODS: 16 patients (10 males and 6 females; mean age, 65.2 years) with 16 liver tumours (mean diameter 1.5 cm) underwent transpulmonary RFA under CT fluoroscopic guidance. The tumours were either hepatocellular carcinoma (n=14) or liver metastasis (n=12). All 16 liver tumours were undetectable with ultrasonography. The pulmonary function values at 3 months after transpulmonary RFA were compared with baseline (i.e. values before RFA). RESULTS: In 8 of 16 sessions, minor pulmonary complications occurred, including small pneumothorax (n=8) and small pleural effusion (n=1). In two sessions, major pulmonary complications occurred, including pneumothorax requiring a chest tube (n=2). These chest tubes were removed at 4 and 6 days, and these patients were discharged 7 and 10 days after RFA, respectively, without any sequelae. The pulmonary function values we evaluated were forced expiratory volume in 1 s (FEV1.0) and vital capacity (VC). The mean values of FEV1.0 before and 3 months after RFA were 2.55 l and 2.59 l, respectively; the mean values of VC before and 3 months after RFA were 3.20 l and 3.27 l, respectively. These pulmonary values did not show any significant worsening (p=0.393 and 0.255 for FEV1.0 and VC, respectively). CONCLUSION: There was no significant lung injury causing a fatal or intractable complication after transpulmonary RFA of liver tumours.

Changes in pulmonary function up to 10 years after locoregional breast irradiation.

PURPOSE: To evaluate the long-term impact of locoregional breast radiotherapy (RT) on pulmonary function tests (PFTs). METHODS AND MATERIALS: This study included 75 women who underwent postoperative locoregional breast RT. PFTs were performed before RT and 3, 6, and 12 months and 8 to 10 years after RT. By use of univariate and multivariate analyses, the impact of treatment- and patient-related factors on late changes in PFTs was evaluated. RESULTS: During the first year after RT, all PFTs significantly worsened at 3 to 6 months after RT (p < 0.05). At 12 months, forced vital capacity (FVC), vital capacity (VC), and forced expiratory volume in 1 second (FEV(1)) recovered almost to baseline values, whereas total lung capacity (TLC) and diffusion capacity of carbon monoxide (DL(CO)) recovered only slightly and were still found to be decreased compared with baseline (p < 0.05). At 8 to 10 years after RT, mean reductions in FEV(1) of 4% (p = 0.03) and in VC, DL(CO), and TLC of 5%, 9%, and 11% (all p < 0.0001), respectively, were observed compared with pre-RT values. On multivariate analysis, tamoxifen use negatively affected TLC at 8 to 10 years after RT (p = 0.033), whereas right-sided irradiation was associated with a late reduction in FEV(1) (p = 0.027). For FEV(1) and DL(CO), an early decrease was predictive for a late decrease (p = 0.003 and p = 0.0009, respectively). CONCLUSIONS: The time course of PFT changes after locoregional RT for breast cancer follows a biphasic pattern. An early reduction in PFTs at 3 to 6 months with a partial recovery at 12 months after RT is followed by a late, more important PFT reduction up to 8 to 10 years after RT. Tamoxifen use may have an impact on this late decline in PFTs.

Changes in global function and regional ventilation and perfusion on SPECT during the course of radiotherapy in patients with non-small-cell lung cancer.

PURPOSE: This study aimed to (1) examine changes in dyspnea, global pulmonary function test (PFT) results, and functional activity on ventilation (V)/perfusion (Q) single-photon emission computerized tomography (SPECT) scans during the course of radiation (RT), and (2) factors associated with the changes in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Fifty-six stage I to III NSCLC patients treated with definitive RT with or without chemotherapy were enrolled prospectively. Dyspnea was graded according to Common Terminology Criteria for Adverse Events version 3.0 prior to and weekly during RT. V/Q SPECT-computed tomography (CT) and PFTs were performed prior to and during RT at approximately 45 Gy. Functions of V and Q activities were assessed using a semiquantitative scoring of SPECT images. RESULTS: Breathing improved significantly at the third week (mean dyspnea grade, 0.8 vs. 0.6; paired t-test p = 0.011) and worsened during the later course of RT (p > 0.05). Global PFT results did not change significantly, while regional lung function on V/Q SPECT improved significantly after ∼45 Gy. The V defect score (DS) was 4.9 pre-RT versus 4.3 during RT (p = 0.01); Q DS was 4.3 pre-RT versus 4.0 during RT (p < 0.01). Improvements in V and Q functions were seen primarily in the ipsilateral lung (V DS, 1.9 pre-RT versus 1.4 during RT, p < 0.01; Q DS, 1.7 pre-RT versus 1.5 during RT, p < 0.01). Baseline primary tumor volume was significantly correlated with pre-RT V/Q DS (p < 0.01). Patients with central lung tumors had greater interval changes in V and Q than those with more peripheral tumors (p <0.05 for both V and Q DS). CONCLUSIONS: Regional ventilation and perfusion improved during RT at 45 Gy. This suggests that adaptive planning based on V/Q SPECT during RT may allow sparing of functionally recoverable lung tissue.

Meta-analysis of the efficacy and safety of bronchial thermoplasty in patients with moderate-to-severe persistent asthma.

This meta-analysis assessed the efficacy and safety of a novel intervention for asthma, bronchial thermoplasty (BT), in patients with moderate-to-severe persistent asthma. An electronic literature search identified three randomized controlled trials (RCT) of BT that recruited 421 patients in total. Outcomes of interest were the Asthma Quality of Life Questionnaire (AQLQ) score, morning peak expiratory flow (PEF), tolerability and safety. Compared with standard medications and sham BT treatment, BT significantly improved AQLQ scores and PEF from baseline to the end of the trials. There were more respiratory adverse events and hospitalizations for adverse respiratory events with BT than with medications or sham treatment during the treatment period, but most events resolved, on average, within a week. This effect of BT treatment was not seen during the posttreatment period. Additional long-term RCT are required to confirm whether BT provides benefit to patients with moderate-to-severe persistent asthma.

Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy.

BACKGROUND: To evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS: We analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP. RESULTS: Median follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p < 0.05). In multivariate analysis, NTCP value (p = 0.001) and V10 (p = 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP 50% were 5.7% and 29.2%, respectively (p < 0.01). CONCLUSIONS: NTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

CT-guided interstitial brachytherapy of primary and secondary lung malignancies: results of a prospective phase II trial.

BACKGROUND AND PURPOSE: CT-guided interstitial brachytherapy of primary lung malignancies and pulmonary metastases represents a novel interventional technique, combining conventional high-dose-rate (HDR) iridium-192 ((192)Ir) brachytherapy with modern CT guidance for applicator positioning and computer-aided 3-D radiation treatment planning. The purpose of this study was to assess safety and efficacy of this technique. PATIENTS AND METHODS: 30 patients with 83 primary or secondary lung malignancies were recruited in a prospective nonrandomized trial (Table 1). After catheter positioning under CT fluoroscopy, a spiral CT was acquired for treatment planning (Figure 1). All but two patients received a defined single dose (coverage > 99%) of at least 20 Gy from a (192)Ir source in HDR technique. RESULTS: Adverse effects were nausea (n = 3, 6%), minor (n = 6, 12%) and one major pneumothorax (2%). Post intervention, no changes of vital capacity and forced expiratory volume could be detected. The median follow-up period was 9 months (1-21 months) with a local tumor control of 91% at 12 months (Figure 2). CONCLUSION: CT-guided interstitial brachytherapy proved to be safe and effective for the treatment of primary and secondary lung malignancies.

Effect of obesity on breathlessness and airway responsiveness to methacholine in non-asthmatic subjects.

BACKGROUND: Obesity is associated with increased prevalence and incidence of asthma, but the mechanism is unknown. Obesity reduces lung volumes, which can increase airway responsiveness, and increases resistive and elastic work of breathing, which can increase dyspnea. OBJECTIVE: To determine if the intensity of dyspnea due to airway narrowing or if airway responsiveness is increased in obese, non-asthmatic subjects. SUBJECTS: Twenty-three obese (BMI (body mass index) > or =30 kg m(-2)) and 26 non-obese (BMI <30 kg m(-2)) non-asthmatic subjects, aged between 18 and 70 years. METHODS: High-dose methacholine challenge was used to determine the sensitivity and the maximal response to methacholine. Respiratory system resistance (Rrs) and reactance were measured, using the forced oscillation technique, as indicators of resistive and elastic loads during challenge. Perception of dyspnea was measured by the Borg score during challenge. Static lung volumes were measured by body plethysmography. RESULTS: Static lung volumes were reduced in the obese subjects. There were no significant differences in the sensitivity or maximal response to methacholine between obese and non-obese subjects. The magnitude of change in Rrs was similar in both groups, but obese subjects had more negative reactance after challenge (P=0.002) indicating a greater elastic load. The intensity of dyspnea was greater in obese subjects (P=0.03). CONCLUSIONS: Obesity reduces lung volumes, but does not alter the sensitivity or maximal response to methacholine. However, obese subjects have enhanced perception of dyspnea, associated with greater apparent stiffness of the respiratory system, and may therefore be at greater risk of symptoms.

The impact of induction chemotherapy and the associated tumor response on subsequent radiation-related changes in lung function and tumor response.

PURPOSE: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. METHODS AND MATERIALS: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. RESULTS: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. CONCLUSIONS: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction.

Changes in pulmonary function after incidental lung irradiation for breast cancer: A prospective study.

PURPOSE: The aim of this study was to analyze changes in pulmonary function after radiation therapy (RT) for breast cancer. METHODS AND MATERIALS: A total of 39 consecutive eligible women, who underwent postoperative irradiation for breast cancer, were entered in the study. Spirometry consisting of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), carbon monoxide diffusing capacity (DLCO), and gammagraphic (ventilation and perfusion) pulmonary function tests (PFT) were performed before RT and 6, 12, and 36 months afterwards. Dose-volume and perfusion-weighted parameters were obtained from 3D dose planning: Percentage of lung volume receiving more than a threshold dose (Vi) and between 2 dose levels (V(i-j)). The impact of clinical and dosimetric parameters on PFT changes (Delta PFT) after RT was evaluated by Pearson correlation coefficients and stepwise lineal regression analysis. RESULTS: No significant differences on mean PFT basal values (before RT) with respect to age, smoking, or previous chemotherapy (CT) were found. All the PFT decreased at 6 to 12 months. Furthermore FVC, FEV(1), and ventilation recovered almost to their previous values, whereas DLCO and perfusion continued to decrease until 36 months (-3.3% and -6.6%, respectively). Perfusion-weighted and interval-scaled dose-volume parameters (pV(i-j)) showed better correlation with Delta PFT (only Delta perfusion reached statistically significance at 36 months). Multivariate analysis showed a significant relation between pV(10-20) and Delta perfusion at 3 years, with a multiple correlation coefficient of 0.48. There were no significant differences related to age, previous chemotherapy, concurrent tamoxifen and smoking, although a tendency toward more perfusion reduction in older and nonsmoker patients was seen. CONCLUSIONS: Changes in FVC, FEV1 and ventilation were reversible, but not the perfusion and DLCO. We have not found a conclusive mathematical predictive model, provided that the best model only explained 48% of the variability. We suggest the use of dose-perfused volume and interval-scaled parameters (i.e., pV(10-20)) for further studies.

Attempts to predict the long-term decrease in lung function due to radiotherapy of non-small cell lung cancer.

PURPOSE: To obtain a model which can predict long-term decrease in lung function due to radiation damage from dose-volume data for patients with non-small cell lung cancer. PATIENTS AND METHODS: 27 patients were included, all long-term survivors after radical radiation therapy. For each patient a regression analysis was performed on a post-RT succession of measurements of FEV1 in order to estimate the decrease after 2 years and a standard error (SE) on this regression estimate. The modelling was based on dose-volume histograms (DVH) exported from the treatment planning system, and involved fits of threshold models, a mean lung dose model as well as more complex models based on the relative damaged volume (rdV). RESULTS: Decreases after 2 years of up to 28% in FEV1 was measured (median 10%), with significant day-to-day variation in FEV1 for the individual patient. The threshold models predicted the long-term decrease in FEV1 well when the SE was interpreted as the uncertainty of the measured decrease. The best threshold value, marginally, was 30 Gy with an R(2) of 0.46. The mean lung dose model did not perform so well. A complex model based on rdV performed better than any of the other models (R(2)=0.52). CONCLUSION: The long-term decrease in FEV1 could be predicted from a simple dose-volume model when the SE was interpreted as the uncertainty of the measured decrease.