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1.
Int J Radiat Oncol Biol Phys ; 85(4): 1074-81, 2013 Mar 15.
Article in English | MEDLINE | ID: mdl-23154077

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/surgery , Lung/radiation effects , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Algorithms , Carbon Monoxide/metabolism , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/physiopathology , Dose-Response Relationship, Radiation , Female , Forced Expiratory Volume/physiology , Forced Expiratory Volume/radiation effects , Humans , Linear Models , Lung/physiology , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Pulmonary Diffusing Capacity/physiology , Pulmonary Diffusing Capacity/radiation effects , Radiography , Radiotherapy Planning, Computer-Assisted/methods , Retrospective Studies , Tumor Burden/physiology
2.
Int J Radiat Oncol Biol Phys ; 84(5): e565-70, 2012 Dec 01.
Article in English | MEDLINE | ID: mdl-22929860

ABSTRACT

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.


Subject(s)
Breast Neoplasms/radiotherapy , Lung/radiation effects , Adult , Aged , Breast Neoplasms/surgery , Dose Fractionation, Radiation , Female , Forced Expiratory Volume/physiology , Forced Expiratory Volume/radiation effects , Humans , Lung/physiopathology , Lymphatic Irradiation , Mastectomy , Middle Aged , Prospective Studies , Pulmonary Diffusing Capacity/physiology , Pulmonary Diffusing Capacity/radiation effects , Recovery of Function , Reproducibility of Results , Respiratory Function Tests , Vital Capacity/physiology , Vital Capacity/radiation effects
3.
Int J Radiat Oncol Biol Phys ; 83(5): 1573-9, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22768989

ABSTRACT

PURPOSE: Scoring of radiation pneumonitis (RP), a dose-limiting toxicity after thoracic radiochemotherapy, is subjective and thus inconsistent among studies. Here we investigated whether the extent of change in diffusing capacity of the lung for carbon monoxide (DLCO) after radiation therapy (RT) for non-small-cell lung cancer (NSCLC) could be used as an objective means of quantifying RP. PATIENTS AND METHODS: We analyzed potential correlations between DLCO and RP in 140 patients who received definitive RT (≥ 60 Gy) with or without chemotherapy for primary NSCLC. All underwent DLCO analysis before and after RT. Post-RT DLCO values within 1 week of the RP diagnosis (Grade 0, 1, 2, or 3) were selected and compared with that individual's preradiation values. Percent reductions in DLCO and RP grade were compared by point biserial correlation in the entire patient group and in subgroups stratified according to various clinical factors. RESULTS: Patients experiencing Grade 0, 1, 2, or 3 RP had median percentage changes in DLCO after RT of 10.7%, 13%, 22.1%, or 35.2%. Percent reduction in DLCO correlated with RP Grade ≤ 1 vs. ≥ 2 (p = 0.0004). This association held for the following subgroups: age ≥ 65 years, advanced stage, smokers, use of chemotherapy, volume of normal lung receiving at least 20 Gy ≥ 30%, and baseline DLCO or forced expiratory volume in 1 second ≥ 60%. CONCLUSIONS: By correlating percent change in DLCO from pretreatment values at the time of diagnosis of RP with RP grade, we were able to identify categories of RP based on the change in DLCO. These criteria provide a basis for an objective scoring system for RP based on change in DLCO.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Pulmonary Diffusing Capacity/radiation effects , Radiation Pneumonitis/diagnosis , Adult , Aged , Aged, 80 and over , Carbon Monoxide/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/physiopathology , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/physiopathology , Male , Middle Aged , Proportional Hazards Models , Pulmonary Diffusing Capacity/physiology , Radiation Pneumonitis/physiopathology
4.
Int J Radiat Oncol Biol Phys ; 83(4): e537-43, 2012 Jul 15.
Article in English | MEDLINE | ID: mdl-22420964

ABSTRACT

PURPOSE: To investigate the extent of change in pulmonary function over time after definitive radiotherapy for non-small-cell lung cancer (NSCLC) with modern techniques and to identify predictors of changes in pulmonary function according to patient, tumor, and treatment characteristics. PATIENTS AND METHODS: We analyzed 250 patients who had received ≥ 60 Gy radio(chemo)therapy for primary NSCLC in 1998-2010 and had undergone pulmonary function tests before and within 1 year after treatment. Ninety-three patients were treated with three-dimensional conformal radiotherapy, 97 with intensity-modulated radiotherapy, and 60 with proton beam therapy. Postradiation pulmonary function test values were evaluated among individual patients compared with the same patient's preradiation value at the following time intervals: 0-4 (T1), 5-8 (T2), and 9-12 (T3) months. RESULTS: Lung diffusing capacity for carbon monoxide (DLCO) was reduced in the majority of patients along the three time periods after radiation, whereas the forced expiratory volume in 1 s per unit of vital capacity (FEV1/VC) showed an increase and decrease after radiation in a similar percentage of patients. There were baseline differences (stage, radiotherapy dose, concurrent chemotherapy) among the radiation technology groups. On multivariate analysis, the following features were associated with larger posttreatment declines in DLCO: pretreatment DLCO, gross tumor volume, lung and heart dosimetric data, and total radiation dose. Only pretreatment DLCO was associated with larger posttreatment declines in FEV1/VC. CONCLUSIONS: Lung diffusing capacity for carbon monoxide is reduced in the majority of patients after radiotherapy with modern techniques. Multiple factors, including gross tumor volume, preradiation lung function, and dosimetric parameters, are associated with the DLCO decline. Prospective studies are needed to better understand whether new radiation technology, such as proton beam therapy or intensity-modulated radiotherapy, may decrease the pulmonary impairment through greater lung sparing.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Lung/radiation effects , Proton Therapy , Pulmonary Diffusing Capacity/radiation effects , Radiotherapy, Conformal/methods , Adult , Aged , Aged, 80 and over , Algorithms , Analysis of Variance , Carbon Monoxide/metabolism , Carcinoma, Non-Small-Cell Lung/physiopathology , Female , Forced Expiratory Volume/physiology , Humans , Lung/physiopathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Pulmonary Diffusing Capacity/physiology , Radiotherapy, Intensity-Modulated , Respiratory Function Tests , Retrospective Studies , Vital Capacity/physiology
5.
Int J Radiat Oncol Biol Phys ; 82(2): e257-64, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-21621341

ABSTRACT

PURPOSE: To propose multivariate predictive models for changes in pulmonary function tests (ΔPFTs) with respect to preradiotherapy (pre-RT) values in patients undergoing RT for breast cancer and lymphoma. METHODS AND MATERIALS: A prospective study was designed to measure ΔPFTs of patients undergoing RT. Sixty-six patients were included. Spirometry, lung capacity (measured by helium dilution), and diffusing capacity of carbon monoxide tests were used to measure lung function. Two lung definitions were considered: paired lung vs. irradiated lung (IL). Correlation analysis of dosimetric parameters (mean lung dose and the percentage of lung volume receiving more than a threshold dose) and ΔPFTs was carried out to find the best dosimetric predictor. Chemotherapy, age, smoking, and the selected dose-volume parameter were considered as single and interaction terms in a multivariate analysis. Stability of results was checked by bootstrapping. RESULTS: Both lung definitions proved to be similar. Modeling was carried out for IL. Acute and late damage showed the highest correlations with volumes irradiated above ~20 Gy (maximum R(2) = 0.28) and ~40 Gy (maximum R(2) = 0.21), respectively. RT alone induced a minor and transitory restrictive defect (p = 0.013). Doxorubicin-cyclophosphamide-paclitaxel (Taxol), when administered pre-RT, induced a late, large restrictive effect, independent of RT (p = 0.031). Bootstrap values confirmed the results. CONCLUSIONS: None of the dose-volume parameters was a perfect predictor of outcome. Thus, different predictor models for ΔPFTs were derived for the IL, which incorporated other nondosimetric parameters mainly through interaction terms. Late ΔPFTs seem to behave more serially than early ones. Large restrictive defects were demonstrated in patients pretreated with doxorubicin-cyclophosphamide-paclitaxel.


Subject(s)
Breast Neoplasms/radiotherapy , Lung/radiation effects , Lymphoma/radiotherapy , Models, Biological , Radiation Injuries/physiopathology , Adolescent , Adult , Age Factors , Aged , Algorithms , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Bleomycin/administration & dosage , Bleomycin/pharmacology , Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Cyclophosphamide/pharmacology , Dacarbazine/administration & dosage , Dacarbazine/pharmacology , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Female , Humans , Lung/drug effects , Lung/physiopathology , Lymphoma/drug therapy , Male , Middle Aged , Multivariate Analysis , Organs at Risk/physiopathology , Organs at Risk/radiation effects , Prednisone/administration & dosage , Prednisone/pharmacology , Prospective Studies , Pulmonary Diffusing Capacity/drug effects , Pulmonary Diffusing Capacity/physiology , Pulmonary Diffusing Capacity/radiation effects , Radiotherapy Dosage , Respiratory Function Tests , Smoking/adverse effects , Smoking/physiopathology , Spirometry , Vinblastine/administration & dosage , Vinblastine/pharmacology , Vincristine/administration & dosage , Vincristine/pharmacology , Young Adult
6.
Int J Radiat Oncol Biol Phys ; 82(2): 701-7, 2012 Feb 01.
Article in English | MEDLINE | ID: mdl-21398052

ABSTRACT

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.


Subject(s)
Breast Neoplasms/radiotherapy , Lung/radiation effects , Respiratory Function Tests , Adult , Aged , Analysis of Variance , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Carbon Monoxide/metabolism , Cyclophosphamide/administration & dosage , Female , Fluorouracil/administration & dosage , Forced Expiratory Volume/radiation effects , Humans , Lung/physiopathology , Methotrexate/administration & dosage , Middle Aged , Pulmonary Diffusing Capacity/radiation effects , Radiation Pneumonitis/physiopathology , Recovery of Function , Respiratory Function Tests/methods , Tamoxifen/adverse effects , Time Factors , Total Lung Capacity/drug effects , Total Lung Capacity/radiation effects , Vital Capacity/radiation effects
7.
Int J Radiat Oncol Biol Phys ; 82(4): e631-8, 2012 Mar 15.
Article in English | MEDLINE | ID: mdl-22197235

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/radiotherapy , Dyspnea/diagnostic imaging , Dyspnea/physiopathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/physiopathology , Dyspnea/diagnosis , Female , Forced Expiratory Volume/physiology , Forced Expiratory Volume/radiation effects , Humans , Lung/diagnostic imaging , Lung/radiation effects , Lung Neoplasms/pathology , Lung Neoplasms/physiopathology , Male , Middle Aged , Organ Sparing Treatments/methods , Prospective Studies , Pulmonary Diffusing Capacity/physiology , Pulmonary Diffusing Capacity/radiation effects , Radiotherapy Dosage , Respiration/radiation effects , Tomography, Emission-Computed, Single-Photon/methods , Vital Capacity/physiology , Vital Capacity/radiation effects
8.
Med Oncol ; 27(3): 697-701, 2010 Sep.
Article in English | MEDLINE | ID: mdl-19636975

ABSTRACT

The aim of this article was to investigate the effect of ambroxol on radiation lung injury and the expression of transforming growth factor beta(1) (TGF-beta(1)), as well as tumor necrosis factor alpha (TNF-alpha) in plasma. Totally, 120 patients with locally advanced lung cancer in radiotherapy were randomized into treatment and control groups. Patients in the treatment group took ambroxol orally at a dosage of 90 mg, three times per day for 3 months from the beginning of radiotherapy. The expression of TGF-beta(1) and TNF-alpha in plasma was analyzed. The clinical symptoms and lung diffusing capacity were monitored using high resolving power computed tomography. The level of TGF-beta(1) in the control group was increased (11.8 +/- 5.5 ng/ml), whereas in ambroxol-treated patients, the increase was not significant (5.6 +/- 2.6 ng/ml, P < 0.001). Radiotherapy-induced elevation of TNF-alpha levels, seen in control patients, was also abolished after treatment with ambroxol (5.1 +/- 1.0 vs. 2.4 +/- 0.8 ng/ml, P < 0.001). In the treatment group, carbon monoxide diffusion capacity was not significantly decreased at 6, 12, and 18 months post-radiotherapy, compared with the control group (P < 0.05). Ambroxol decreased the expression of TGF-beta(1) and TNF-alpha, and minimized the diminishment of lung diffusion capacity after radiotherapy.


Subject(s)
Ambroxol/therapeutic use , Free Radical Scavengers/therapeutic use , Lung Neoplasms/radiotherapy , Pulmonary Fibrosis/prevention & control , Radiation Pneumonitis/prevention & control , Transforming Growth Factor beta1/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Ambroxol/adverse effects , Ambroxol/pharmacology , Carbon Monoxide/metabolism , Female , Free Radical Scavengers/adverse effects , Free Radical Scavengers/pharmacology , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Male , Middle Aged , Pulmonary Diffusing Capacity/drug effects , Pulmonary Diffusing Capacity/radiation effects , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/metabolism , Radiation Pneumonitis/drug therapy , Radiation Pneumonitis/metabolism , Radiotherapy, Conformal , Single-Blind Method , Transforming Growth Factor beta1/blood , Tumor Necrosis Factor-alpha/analysis
9.
Ann Thorac Surg ; 88(3): 930-5; discussion 935-6, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19699923

ABSTRACT

BACKGROUND: Neoadjuvant chemotherapy or chemoradiotherapy increases the risk of pulmonary resection. Changes in specific pulmonary function tests may be predictive. METHODS: A retrospective review of a prospective database of patients with non-small cell lung cancer who underwent neoadjuvant therapy, had pulmonary function tests performed both before and after therapy, and then underwent elective pulmonary resection was performed. Final values and change in the pulmonary function tests before and after treatment were entered as independent variables into a multivariate model in which the dependent variable was major or respiratory morbidity. RESULTS: There were 132 patients. The mean duration between pretherapy and posttherapy pulmonary function tests was 4.1 months. The mean change in the percent forced expiratory volume in 1 second, in the percent diffusion capacity of the lung for carbon monoxide, and in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume was +1.0, -6.4%, and -6.6%, respectively. Fifty-five patients (42%) experienced a postoperative complication, and 39 of those patients experienced a major or respiratory complication. There were 7 (5.3%) operative mortalities (5 were respiratory related). On multivariate analysis the change in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume was the only factor associated with major or respiratory morbidity (p = 0.028). When the posttherapy percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume fell by 8% or more, there was an increased likelihood of major morbidity (p = 0.01). CONCLUSIONS: A decrease in the percent diffusion capacity of the lung for carbon monoxide corrected for the alveolar volume after neoadjuvant chemotherapy or chemoradiotherapy may predict increased risk for pulmonary resection, especially if the decrease is 8% or greater. These results should be considered in the preoperative risk assessment of patients who are to undergo pulmonary resection after induction therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Lung Volume Measurements , Neoadjuvant Therapy/adverse effects , Pneumonectomy , Postoperative Complications/etiology , Pulmonary Diffusing Capacity , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Child , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Infant , Lung/drug effects , Lung/pathology , Lung/radiation effects , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Prognosis , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/pathology , Pulmonary Alveoli/radiation effects , Pulmonary Diffusing Capacity/drug effects , Pulmonary Diffusing Capacity/radiation effects , Radiation Injuries/complications , Radiation Injuries/pathology , Radiotherapy Dosage , Risk Assessment
10.
Ann Thorac Surg ; 88(3): 945-50; discussion 950-1, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19699925

ABSTRACT

BACKGROUND: Concurrent neoadjuvant chemoradiotherapy can potentially impact on the results of sleeve lobectomy. The purpose of this study was to examine this effect in terms of morbidity, mortality, and long-term survival in patients with non-small cell lung cancer. METHODS: Clinical records of patients with non-small cell lung cancer undergoing sleeve lobectomy between 1983 and 2008 were reviewed for age, sex, type of sleeve resection, clinicopathologic TNM stage, complications, and 90-day mortality. Chemotherapy and radiation therapy regimens were recorded for the patients undergoing neoadjuvant treatment. Kaplan-Meier survival curves were compared. RESULTS: There were 64 patients identified as having undergone sleeve resection for non-small cell lung cancer. Of the 64 total patients, 43 did not receive concurrent neoadjuvant chemoradiotherapy [NCR] versus 21 patients who did [CRS]. All of the CRS patients underwent platinum-based chemotherapy and radiation (range, 2,000 to 6,100 cGy). Thirteen patients (62%) were downstaged, with 4 complete responders. The 90-day mortality was 2.7% (2 patients) in the NCR group and 0% in the CRS group. The incidence of major complications in the NCR group was 46.5% (20 of 43) with 4.7% (2 of 43) anastomosis-related complications (stenosis, 1; bronchovascular fistula, 1). The incidence of major complications in the CRS group was 42.9% (9 of 21) with no anastomosis-related problems. Five-year survival in the NCR group was 48% compared with 41% in the CRS group (p = 0.63). There were 9% (4 of 43) of patients with local recurrence in the NCR group versus 10% (2 of 21) of patients in the CRS group (p = 0.65). CONCLUSIONS: Anastomosis-related complications were not increased among the patients receiving neoadjuvant therapy compared with those who did not. In addition, local recurrence was also similar between the two groups. Furthermore, the survival of the two groups was not statistically different. Sleeve lobectomy after chemoradiotherapy for advanced non-small cell lung cancer can be performed with acceptable morbidity and mortality.


Subject(s)
Anastomosis, Surgical/methods , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Neoadjuvant Therapy/adverse effects , Pneumonectomy/methods , Postoperative Complications/etiology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bronchoscopy , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Disease-Free Survival , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Postoperative Complications/mortality , Pulmonary Diffusing Capacity/drug effects , Pulmonary Diffusing Capacity/radiation effects , Radiotherapy Dosage , Retrospective Studies
11.
Respir Med ; 100(1): 101-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-15946833

ABSTRACT

AIM OF THE STUDY: The diffusion capacity of the lung for carbon monoxide (DL(CO)) is an important tool in the diagnosis and follow-up of patients with pulmonary diseases. In case of a decreased DL(CO) the K(CO), defined as DL(CO)/V(A) (V(A) is alveolar volume), can differentiate between normal alveolocapillary membrane (normal K(CO)) and abnormal alveolocapillary membrane (low K(CO)). The latter category consists of decreased surface of the membrane, increased thickness or decreased perfusion of ventilated alveoli. The V(A)/TLC (TLC is total lung capacity determined by whole body plethysmography) can partially differentiate between these categories. The aim of this study was to investigate the diagnostic value of the specific diffusion disturbances, which can be constructed by combining the DL(CO), K(CO) and V(A)/TLC. METHODS: In 460 patients the diagnosis made by clinicians were fitted into five diagnostic categories: asthma, chronic obstructive pulmonary disease (COPD), treatment effects of haematologic malignancies, heart failure and diffuse parenchymal lung diseases (DPLD). These categories were linked to the pattern of diffusion disturbance. RESULTS: Almost all patients with asthma have a normal DL(CO), most patients in the other groups do not have the expected pattern of diffusion disturbance, especially in the group with DPLD a bad match is observed. CONCLUSION: In this study the pattern of diffusion disturbance is of limited use in establishing a diagnosis. The use of the K(CO) next to the DL(CO) has no additional diagnostic value. Regional ventilation-perfusion inequality probably forms an important underlying mechanism of decreased DL(CO).


Subject(s)
Blood-Air Barrier/pathology , Carbon Monoxide/metabolism , Lung Diseases/diagnosis , Pulmonary Diffusing Capacity/radiation effects , Total Lung Capacity/radiation effects , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Diffusion , Female , Forced Expiratory Volume , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/radiotherapy , Humans , Male , Middle Aged , Predictive Value of Tests , Vital Capacity
12.
Int J Radiat Oncol Biol Phys ; 62(3): 639-44, 2005 Jul 01.
Article in English | MEDLINE | ID: mdl-15936539

ABSTRACT

PURPOSE: To evaluate the changes in pulmonary function after high-dose radiotherapy (RT) for non-small-cell lung cancer in patients with a long-term disease-free survival. METHODS AND MATERIALS: Pulmonary function was measured in 34 patients with inoperable non-small-cell lung cancer before RT and at 3 and 18 months of follow-up. Thirteen of these patients had a pulmonary function test (PFT) 36 months after RT. The pulmonary function parameters (forced expiratory volume in 1 s [FEV(1)], diffusion capacity [T(lcoc)], forced vital capacity, and alveolar volume) were expressed as a percentage of normal values. Changes were expressed as relative to the pre-RT value. We evaluated the impact of chronic obstructive pulmonary disease, radiation pneumonitis, mean lung dose, and PFT results before RT on the changes in pulmonary function. RESULTS: At 3, 18, and 36 months, a significant decrease was observed for the T(lcoc) (9.5%, 14.6%, and 22.0%, respectively) and the alveolar volume (5.8%, 6.6%, and 15.8%, respectively). The decrease in FEV(1) was significant at 18 and 36 months (8.8% and 13.4%, respectively). No recovery of any of the parameters was observed. Chronic obstructive pulmonary disease was an important risk factor for larger PFT decreases. FEV(1) and T(lcoc) decreases were dependent on the mean lung dose. CONCLUSION: A significant decrease in pulmonary function was observed 3 months after RT. No recovery in pulmonary function was seen at 18 and 36 months after RT. The decrease in pulmonary function was dependent on the mean lung dose, and patients with chronic obstructive pulmonary disease had larger reductions in the PFTs.


Subject(s)
Carcinoma, Non-Small-Cell Lung/physiopathology , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/physiopathology , Lung Neoplasms/radiotherapy , Aged , Aged, 80 and over , Disease-Free Survival , Female , Forced Expiratory Volume/radiation effects , Humans , Male , Middle Aged , Pulmonary Diffusing Capacity/radiation effects , Pulmonary Disease, Chronic Obstructive/physiopathology , Radiation Pneumonitis/physiopathology , Vital Capacity/radiation effects
13.
Cancer ; 88(9): 2135-41, 2000 May 01.
Article in English | MEDLINE | ID: mdl-10813726

ABSTRACT

BACKGROUND: The aim of this study was to determine whether preradiation (pre-RT) single photon emission computed tomography (SPECT) lung perfusion scans can be used to predict RT-induced changes in pulmonary function tests (PFTs). METHODS: Ninety-four patients irradiated for thoracic tumors had pre-RT SPECT lung perfusion scans. The presence of SPECT hypoperfusion distal to a central mediastinal tumor was qualitatively assessed visually without knowledge of PFT changes. Patients were grouped based on whether the diffusion capacity (DLCO) ever increased post-RT. Comparisons of patient groups were performed using 1-tailed Fisher exact tests. Patient follow-up was 6-56 months (mean, 30 months). To assess SPECT hypoperfusion objectively, the average dose to the computed tomography (CT)-defined lung was compared with the weighted-average dose (based on relative perfusion) to the SPECT-defined lung. The ratio between the CT- and SPECT-defined mean lung dose provided a quantitative assessment of hypoperfusion. The mean ratio for patients with central tumor and adjacent hypoperfusion was compared with that of the others (Wilcoxon rank-sum one-sided test). RESULTS: In patients with central tumors, 41% (9 of 22) with adjacent hypoperfusion had improvements in DLCO following radiation, versus 18% (3 of 17) of those without hypoperfusion (P = 0.11). In patients with lung carcinoma, the corresponding ratios were 40% (8 of 20) and 10% (1 of 10), respectively (P = 0.10). The mean ratio of CT dose to SPECT dose was 1.35 for patients with central tumors and adjacent hypoperfusion versus 1.16 for others (P = 0.017). CONCLUSIONS: The presence of SPECT hypoperfusion adjacent to a central mediastinal mass may identify patients likely to have improved PFTs following RT. Thus, SPECT imaging may be useful in models for predicting radiation-induced changes in PFTs.


Subject(s)
Lung/diagnostic imaging , Respiratory Function Tests , Thoracic Neoplasms/radiotherapy , Tomography, Emission-Computed, Single-Photon , Adult , Aged , Aged, 80 and over , Carcinoma/physiopathology , Carcinoma/radiotherapy , Female , Follow-Up Studies , Forecasting , Humans , Lung/physiopathology , Lung/radiation effects , Lung Neoplasms/physiopathology , Lung Neoplasms/radiotherapy , Lung Volume Measurements , Male , Mediastinal Neoplasms/physiopathology , Mediastinal Neoplasms/radiotherapy , Middle Aged , Prospective Studies , Pulmonary Diffusing Capacity/radiation effects , Radiation Dosage , Radiopharmaceuticals , Spirometry , Statistics as Topic , Technetium Tc 99m Aggregated Albumin , Thoracic Neoplasms/physiopathology , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed
14.
Radiother Oncol ; 36(1): 15-23, 1995 Jul.
Article in English | MEDLINE | ID: mdl-8525021

ABSTRACT

PURPOSE: To predict the pulmonary function 3-4 months after irradiation for malignant lymphoma from the three-dimensional (3-D) dose distribution. METHODS: Dose-effect relations for the relative reduction of local perfusion (Q) and local ventilation (V), were calculated in 25 patients, using correlated SPECT (Single Photon Emission Computed Tomography) and CT data. By combining the 3-D dose distribution of an individual patient with the dose-effect relations averaged over all patients, the average reduction of local Q and V (i.e., the overall response parameters) in the whole lung was estimated for each patient. Correlation coefficients were calculated between these overall response parameters and the change in standard lung function tests. In addition, the relation between the overall response parameters and the incidence of radiation pneumonitis was determined. RESULTS: The overall response parameter for perfusion was correlated with the change in standard lung function tests, with correlation coefficients varying between 0.53 (p = 0.007) and 0.71 (p < 0.001) for the change of Vital Capacity and Forced Expiratory Volume at 1 s, respectively. For the overall response parameter for ventilation similar correlations were observed. Four out of the 25 patients developed radiation pneumonitis; in these four patients the overall response parameter for perfusion was on average somewhat higher (13.2 +/- 1.4% (1 standard error of the mean)) than in patients without radiation pneumonitis (10.5 +/- 1.0%), but this difference was not significant. A higher incidence of radiation pneumonitis was observed for larger values of the overall response parameter for perfusion; in patient groups with an overall response parameter for perfusion of 0-5%, 5-10%, 10-15%, and 15-20%, the incidence of radiation pneumonitis was 0 (0/1), 10 (1/10), 13 (1/8) and 33% (2/6), respectively. CONCLUSION: By combining the 3-D dose distribution with the average dose-effect relations for local perfusion or ventilation, an overall response parameter can be calculated prior to irradiation, which is predictive for the radiation-induced change in the overall pulmonary function, and possibly for the incidence of radiation pneumonitis, in this group of patients.


Subject(s)
Lung/physiopathology , Lung/radiation effects , Lymphoma/radiotherapy , Radiation Injuries/etiology , Adolescent , Adult , Aged , Combined Modality Therapy , Dose-Response Relationship, Radiation , Female , Forced Expiratory Volume/radiation effects , Humans , Incidence , Lung/diagnostic imaging , Male , Middle Aged , Pulmonary Alveoli/radiation effects , Pulmonary Diffusing Capacity/radiation effects , Radiation Injuries/diagnostic imaging , Radiation Injuries/physiopathology , Radiation Pneumonitis/diagnostic imaging , Radiation Pneumonitis/etiology , Radiation Pneumonitis/physiopathology , Radiotherapy Dosage , Radiotherapy, High-Energy/adverse effects , Respiratory Function Tests , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Ventilation-Perfusion Ratio/radiation effects , Vital Capacity/radiation effects
15.
Int J Radiat Oncol Biol Phys ; 31(4): 915-9, 1995 Feb 15.
Article in English | MEDLINE | ID: mdl-7860406

ABSTRACT

PURPOSE: To prospectively study the changes in lung function in patients with lung carcinoma treated with relatively high doses of irradiation. METHODS AND MATERIALS: Lung function was assessed prior to and at 6 and 12 months following radiation therapy by a clinical dyspnea score, formal pulmonary function tests (lung volume spirometry and diffusion capacity) as well as an ipsilateral hemithorax lung perfusion scan. Changes in dyspnea score were evaluated by the chi-square and the Fishers exact test. Changes in formal lung function tests were compared with the t-test for dependent data and correlations with the t-test for independent data. Fifty-one patients were entered into the study. There were 42 evaluable patients at 6 months after irradiation and 22 evaluable patients at 12 months after irradiation. RESULTS: A worsening of dyspnea score from 1 to 2, which is clinically acceptable, occurred in 50% or more of patients. However, a dyspnea score of 3, which is a serious complication, developed in only 5% of patients. The diffusion capacity (DLCO) decreased by 14% at 6 months and 12% at 12 months) (p < 0.0001). The forced vital capacity and total lung capacity decreased between 6% and 8% at 6 months and 12 months, which was statistically significant. The forced expiratory volume in 1 s decreased between 2 and 3% at 6 month and 12 months, which was not statistically significant. The ipsilateral hemithorax perfusion decreased by 17 and 20% at 6 and 12 months (p < 0.0001). There was no correlation between the initial hemithorax perfusion, or its decrease at follow up and the decrease in DLCO. CONCLUSION: Lung irradiation results in some loss of lung function in patients with lung cancer with a projected survival of 6 months or more. The pretreatment DLCO assessment should be useful in predicting clinical tolerance to irradiation.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/radiotherapy , Lung/radiation effects , Adult , Aged , Dyspnea/etiology , Female , Forced Expiratory Volume/radiation effects , Humans , Male , Middle Aged , Prospective Studies , Pulmonary Diffusing Capacity/radiation effects , Total Lung Capacity/radiation effects , Vital Capacity/radiation effects
16.
J Rheumatol ; 16(8): 1050-4, 1989 Aug.
Article in English | MEDLINE | ID: mdl-2573727

ABSTRACT

Six patients with systemic sclerosis and internal organ involvement were randomized to receive total lymphoid irradiation (TLI) or to serve as untreated controls. Despite evidence of profound immunosuppression, we were unable to detect any longlasting clinical benefit in the treated patients, with follow-ups ranging from 1-4 years after TLI. Moreover, the results suggest that this therapy may accelerate pulmonary and gastrointestinal deterioration in scleroderma.


Subject(s)
Lymphatic Irradiation/adverse effects , Scleroderma, Systemic/radiotherapy , Adult , Aged , CD4-Positive T-Lymphocytes/radiation effects , Female , Follow-Up Studies , Gastrointestinal Motility/radiation effects , Humans , Lymph Nodes/radiation effects , Male , Prospective Studies , Pulmonary Diffusing Capacity/radiation effects , Random Allocation , Scleroderma, Systemic/physiopathology , Spleen/radiation effects
17.
Z Erkr Atmungsorgane ; 173(2): 170-3, 1989.
Article in German | MEDLINE | ID: mdl-2588690

ABSTRACT

The value of lung perfusion scintigraphy (Tc99m) and lung diffusing capacity are compared with references to early detection of radiogenic pneumonitis. Perfusion scintigraphy completed by diffusing capacity is excellent suitable for early detection. Risk cases are recognized up to 40 days earlier than by X-ray. Severity of radiogenic pneumonitis can be diminished remarkable by prevention therapy.


Subject(s)
Breast Neoplasms/radiotherapy , Lung/radiation effects , Pulmonary Diffusing Capacity/radiation effects , Radiation Injuries/diagnostic imaging , Testicular Neoplasms/radiotherapy , Ventilation-Perfusion Ratio/radiation effects , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Humans , Male , Radionuclide Imaging
18.
Cancer Treat Rep ; 64(4-5): 701-03, 1980.
Article in English | MEDLINE | ID: mdl-6933006

ABSTRACT

Six patients received whole-lung irradiation at a dose of 2000 rads/4 weeks (nominal standard dose = 700 Rets) after surgery for primary osteogenic sarcoma. Pulmonary function tests performed before and 6-20 months after pulmonary irradiation failed to demonstrate any pulmonary function impairment in any of the patients studied.


Subject(s)
Bone Neoplasms/physiopathology , Lung/physiopathology , Osteosarcoma/physiopathology , Adolescent , Adult , Bone Neoplasms/radiotherapy , Female , Humans , Male , Osteosarcoma/radiotherapy , Pulmonary Diffusing Capacity/radiation effects , Vital Capacity/radiation effects
19.
Chest ; 75(6): 688-92, 1979 Jun.
Article in English | MEDLINE | ID: mdl-436520

ABSTRACT

To study the effects of upper mantle radiation therapy on pulmonary function, forced expiratory volume in one second (FEV1), vital capacity (VC), inspiratory capacity (IC), diffusing capacity for CO (DLCO) and diffusion per unit of alveolar volume (DL/VA were determined in 28 patients with Hodgkin's disease, stages 1--3, before therapy and at regular intervals thereafter. Within the first year of follow-up there were significant declines in DLCO, VC, and IC, whereas there were no significant changes in FEV1 or DL/VA. DLCO showed the greatest decline in the largest number of subjects (22/28). Eleven of the 22 had 20 to 60 percent decline of DLCO from baseline. The maximum mean decline in DLCO was -12.7 +/- 3 percent at the 87th +/- 3 days from initiation of therapy postradiation sustained through the 150th day and improving to pretreatment value (+/- 5 percent) by the 8th to 12th month. The changes in DLCO seemed to be independent of the radiation dose ranges evaluated, clinically apparent intrathoracic lymphoma, postradiation radiographic abnormalities and respiratory symptoms. We concluded that impairment in diffusing capacity and loss of vital capacity will develop in most patients receiving upper mantle radiation therapy, indicating that pulmonary reaction occurs despite lung shielding. The functional losses were prolonged and occasionally severe, but were transient and subclinical in most but not all cases. A case of fatal radiation pneumonitis affecting the lung beyond the field of irradiation is reported.


Subject(s)
Hodgkin Disease/radiotherapy , Lung/radiation effects , Radiation Injuries , Radiotherapy/adverse effects , Respiration Disorders/etiology , Respiration/radiation effects , Thoracic Neoplasms/radiotherapy , Adolescent , Adult , Dose-Response Relationship, Radiation , Female , Follow-Up Studies , Forced Expiratory Volume , Humans , Inspiratory Capacity , Male , Middle Aged , Pulmonary Diffusing Capacity/radiation effects , Radiation Injuries/diagnosis , Radiation Injuries/physiopathology , Radioisotope Teletherapy/adverse effects , Respiration Disorders/diagnosis , Respiration Disorders/physiopathology , Vital Capacity/radiation effects
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