The predictive role of plasma TGF-beta1 during radiation therapy for radiation-induced lung toxicity deserves further study in patients with non-small cell lung cancer

BACKGROUND: This study aimed to further investigate the role of circulating TGF-beta1 during radiation therapy (RT) in predicting radiation-induced lung toxicity (RILT). METHODS AND MATERIALS: Patients with stages I-III non-small cell lung cancer treated with RT based therapy were included in this study. Platelet poor plasma was obtained pre-RT, at 2 and 4 weeks during-RT, and at the end of RT. TGF-beta1 was measured using an enzyme-linked immunosorbent assay. The primary endpoint for RILT was >or=grade 2 radiation pneumonitis or fibrosis. RESULTS: Twenty-six patients with a minimum follow-up of 12 months were included. Six patients (23.1%) experienced >or=grade 2 RILT. There was no significant difference in absolute TGF-beta1 levels pre-RT, at 2 and 4 weeks during-RT, or at the end of RT between patients with and without RILT. The TGF-beta1 ratios (over the pre-RT levels) for patients with and without RILT at 2, 4 weeks during-, and the end of RT were 2.8+/-2.2 and 1.0+/-0.6 (P=0.123), 2.3+/-1.3 and 0.8+/-0.5 (P=0.001), 1.5+/-0.9 and 0.8+/-0.5 (P=0.098), respectively. Using 2.0 as a cut-off, the TGF-beta1 ratio at 4 weeks during-RT predicted RILT with a sensitivity and specificity of 66.7% and 95.0%, respectively. CONCLUSION: Elevation of plasma TGF-beta1 level 4 weeks during-RT is significantly predictive of RILT. The role of plasma TGF-beta1 in predicting RILT deserves further study.     

Plasma transforming growth factor-beta1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma.

BACKGROUND: Plasma transforming growth factor-beta1 (TGFbeta1) levels are increased in many malignancies at the time of diagnosis, including all forms of lung carcinoma. Therefore, the potential use of TGFbeta1 as a plasma marker to predict the long term outcome of lung carcinoma patients treated with radiotherapy (RT) was evaluated. METHODS: Plasma samples for 59 newly diagnosed lung carcinoma patients were assayed for TGFbeta1 before RT (pre RT), at the end of RT (end RT), and during follow-up after RT. TGFbeta1 was extracted from plasma using an acid-ethanol method. An enzyme-linked immunoadsorbent assay was used to quantify the plasma TGFbeta1 levels. The normal value for this assay is < or =7.5 ng/mL. Disease status at last follow-up was without knowledge of TGFbeta1 levels. Comparisons within groups and between groups were estimated using analysis of variance and the Student t test for unpaired data, respectively. RESULTS: The 59 patients were divided into 2 groups according to their disease status at last follow-up: those with no evidence of disease (NED) (n = 13) and those with disease (WD) (n = 46). The median follow up was 26.8 months and 12.4 months, respectively, for the NED and WD groups. No significant differences were found in the clinical characteristics between the two groups. The plasma TGFbeta1 level before RT was significantly higher in the WD group (mean +/- standard error of the mean [SEM] = 12.5+/-1.7 ng/mL; median = 8.6 ng/mL) compared with the NED group (mean +/- SEM = 6.0+/-1.0 ng/mL; median = 6.0 ng/mL) (P = 0.037). At the time of last follow-up, WD patients had a significantly higher plasma TGFbeta1 level (mean +/- SEM = 11.6+/-1.3 ng/mL; median = 9.6 ng/mL) compared with NED patients (mean +/- SEM = 3.7+/-0.5 ng/mL; median = 3.6 ng/mL) (P = 0.002). CONCLUSIONS: These data demonstrate that plasma TGFbeta1 may be a useful tumor marker in patients with lung carcinoma.     

Significance of plasma transforming growth factor-β levels in radiotherapy for non–small-cell lung cancer

PURPOSE: In dose-escalation studies of radiotherapy (RT) for non-small-cell lung cancer (NSCLC), radiation pneumonitis (RP) is the most important dose-limiting complication. Transforming growth factor-beta1 (TGF-beta1) has been reported to be associated with the incidence of RP. It has been proposed that serial measurements of plasma TGF-beta1 can be valuable to estimate the risk of RP and to decide whether additional dose-escalation can be safely applied. The aim of this study was to evaluate prospectively the time course of TGF-beta1 levels in patients irradiated for NSCLC in relation to the development of RP and dose-volume parameters. METHODS AND MATERIALS: Plasma samples were obtained in 68 patients irradiated for medically inoperable or locally advanced NSCLC (dose range, 60.8-94.5 Gy) before and 4, 6, and 18 weeks after the start of RT. Plasma TGF-beta1 levels were determined using a bioassay on the basis of TGF-beta1-induced plasminogen activator inhibitor-1 expression in mink lung cells. All patients underwent chest computed tomography scans before RT that were repeated at 18 weeks after RT. The computed tomography data were used to calculate the mean lung dose (MLD) and to score the radiation-induced radiologic changes. RP was defined on the basis of the presence of either radiographic changes or clinical symptoms. Symptomatic RP was scored according to the Common Toxicity Criteria (Grade 1 or worse) and the Southwestern Oncology Group criteria (Grade 2 or worse). Multivariate analyses were performed to investigate which factors (pre- or posttreatment TGF-beta1 level, MLD) were associated with the incidence of RP. To improve our understanding of the time course of TGF-beta1 levels, we performed a multivariate analysis to investigate which factors (pre-RT TGF-beta1 level, MLD, RP) were independently associated with the posttreatment TGF-beta1 levels. RESULTS: The pre-RT TGF-beta1 levels were increased in patients with NSCLC (median 21 ng/mL, range, 5-103 ng/mL) compared with healthy individuals (range, 4-12 ng/mL). On average, the TGF-beta1 levels normalized toward the end of treatment and remained stable until 18 weeks after RT. In 29 patients, however, TGF-beta1 was increased at the end of RT with respect to the pre-RT value. The multivariate analyses revealed that the MLD was the only variable that correlated significantly with the risk of both radiographic RP (p = 0.05) and symptomatic RP, independent of the scoring system used (p = 0.05 and 0.03 for Southwestern Oncology Group and Common Toxicity Criteria systems, respectively). The TGF-beta1 level at the end of RT was significantly associated with the MLD (p <0.001) and pre-RT TGF-beta1 level (p = 0.001). CONCLUSION: The MLD correlated significantly with the incidence of both radiographic and symptomatic RP. The results of our study did not confirm the reports that increased levels of TGF-beta1 at the end of RT are an independent additional risk factor for developing symptomatic RP. However, the TGF-beta1 level at the end of a RT was significantly associated with the MLD and the pre-RT level.     

Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.

PURPOSE: The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. PATIENT AND METHODS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.     

Long-term results and predictive factors of three-dimensional conformal salvage radiotherapy for biochemical relapse after prostatectomy

PURPOSE: Salvage radiotherapy (RT) is used to treat patients with biochemical failure after radical prostatectomy (RP). Although retrospective series have demonstrated that salvage RT will result in biochemical response in approximately 75% of patients, long-term response is much lower (20-40%). The purpose of this study was to determine prognostic factors related to the prostate-specific antigen (PSA) outcome after salvage RT. METHODS AND MATERIALS: Between 1991 and 2004, 171 patients received salvage RT at the University of Heidelberg. Patient age, margin status, Gleason score, tumor grading, pathologic tumor stage, pre-RP and pre-RT PSA levels, and time from RP to rise of PSA were analyzed. RESULTS: Median follow-up time was 39 months. The 5-year overall and clinical relapse-free survival were 93.8% and 80.8%, respectively. After RT serum PSA decreased in 141 patients (82.5%). The 5-year biochemical relapse-free survival was 35.1%. Univariate analysis showed following statistically significant predictors of PSA recurrence after RT: preoperative PSA level (p = 0.035), pathologic tumor classification (p = 0.001), Gleason score (p < 0.001), tumor grading (p = 0.004), and pre-RT PSA level (p = 0.031). On multivariate analysis, only Gleason score (p = 0.047) and pre-RT PSA level (p = 0.049) were found to be independently predictive of PSA recurrence. CONCLUSIONS: This study represents one of the largest retrospective studies analyzing the outcome of patients treated with salvage RT at a single institution. Our findings suggest that patients with Gleason score <7 and low pre-RT PSA levels are the best candidates for salvage RT, whereas patients with high-grade lesions should be considered for additional treatment (e.g., hormonal therapy).     

A prospective study of the impact of nasopharyngeal cancer and radiotherapy on the psychosocial condition of Chinese patients

BACKGROUND: Radiotherapy (RT) promises optimistic results in the treatment of nasopharyngeal cancer (NPC). The objective of the current study was to map out prospectively the impact of NPC and RT on patients from diagnosis to 1 year posttreatment. METHODS: For this study, 67 Chinese patients (46 men and 21 women) with newly diagnosed stage I or II NPC who received primary RT were recruited. Physical and psychosocial adjustments were measured by using the Rotterdam Symptom Checklist, Beck Anxiety Inventory, Beck Depression Inventory, Perceived Stress Scale, and the 36-item Short-Form Health Survey (SF-36). Semistructured clinical interviews were conducted at bimonthly intervals from pre-RT to 1 year post-RT. RESULTS: Physical and psychosocial adjustments were poorest from pre-RT to the end of RT. Rapid improvements in all areas were noted in the first 2 months post-RT and reached a plateau at around the 6th month. At 1 year, except for physical symptoms and perceived stress, patient measures recovered to their pre-RT levels. At 1 year, patients had more physical complaints (P < .001) but less perceived stress (P = .002). The percentage of patients who expressed fear of dying dropped from 28% pre-RT to 2% at 1 year. However, patients who expressed "fear of the worst happening" increased from 51% pre-RT to 57% at 1 year. CONCLUSIONS: Different periods in treatment of NPC imposed different psychosocial demands on patients. The current results indicated that the period from diagnosis to 2-month post-RT was a high-risk period both physically and emotionally. After treatment, most patients showed resilience despite persistent side effects of RT and successfully resumed their pretreatment level of functioning by the end of the year. Despite resuming a normal or near-normal living, patients still noted a subdued fear of recurrence.     

Comparison of adjuvant versus salvage radiotherapy policies for postprostatectomy radiotherapy

PURPOSE: We compared the long-term results of postprostatectomy radiotherapy (RT) from two institutions, one adapting a prospective policy of adjuvant RT and the other salvage RT. METHODS AND MATERIALS: Between 1989 and 1997, 69 patients were referred for adjuvant RT to the institution using adjuvant RT and 88 patients with evidence of recurrence were treated in the institution using salvage RT. The salvage group underwent RT after longer postoperative intervals (median, 40.3 vs. 2.9 months; p <0.0001) and had higher prostate-specific antigen (PSA) values before starting RT (4.5 vs. 0.86 ng/mL; p = 0.003). Both groups were routinely treated to a minimal total dose of 60 Gy. The treatment groups were analyzed for overall survival, disease-specific survival, distant metastasis-free survival, and biochemical recurrence-free survival (BRFS) using Cox proportional hazards modeling. RESULTS: Of the 69 patients referred for adjuvant RT, 22 (32%) had nonzero PSA values before RT. Multivariable modeling of BRFS found only the PSA value before RT to be statistically significant (p <0.0001). RT after prostatectomy was equally effective in either setting when the pre-RT PSA level was <1 ng/mL. When the PSA value before RT was >or=1 ng/mL, the 5-year BRFS for each group was inferior. CONCLUSION: Although the adjuvant treatment policy was associated with significantly improved BRFS, this was attributable to low pre-RT PSA values. When the treatment groups were stratified for pre-RT PSA level, the differences in BRFS were not statistically significant. Patients with a rising PSA level after prostatectomy, regardless of their initial risk, should receive prompt referral for RT.     

Soluble TGFbeta type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats

PURPOSE: To assess whether administration of recombinant human adenoviral vector, which carries soluble TGFbeta1 Type II receptor (TbetaRII) gene, might reduce the availability of active TGFbeta1 and thereby protect the lung from radiation-induced injury. METHODS AND MATERIALS: Female Fisher 344 rats were given a single 30 Gy dose of right hemithoracic irradiation 24 h after the injections of control (AdGFP) or treatment (AdexTbetaRII-Fc) vectors. Different end points were assessed to look for lung tissue damage. RESULTS: There was a significant increase in the plasma level of soluble TbetaRII 24 h and 48 h after injection of treatment vector. In the radiation (RT) + AdexTbetaRII-Fc group, there was a significant reduction in respiratory rate at 4 weeks after treatment as compared to the RT-alone group. Histologic results revealed a significant reduction in lung damage and decrease in the number and activity of macrophages in the RT + AdexTbetaRII-Fc group as compared to the RT-alone group. The tissue level of active TGFbeta1 was significantly reduced in rats receiving RT + AdexTbetaRII-Fc treatment. There was also an upregulation of transmembrane TbetaRII in lung tissue in the RT-alone group as compared to the RT + gene therapy rats. CONCLUSIONS: This study shows the ability of AdexTbetaRII-Fc gene therapy to induce an increase in circulating levels of soluble receptors, to reduce the tissue level of active TGFbeta1, and consequently to ameliorate acute radiation-induced lung injury.     

Influence of radiation treatment on serum transferrin and tumor necrosis factor-alpha.

This study deals with the effect of radiation treatment (RT) on serum transferrin and tumor necrosis factor-alpha (TNF-alpha) in patients with malignant tumors. In 21 patients who received 36-60 Gy in 20 to 30 sessions of RT, serum transferrin and TNF-alpha were determined pre-RT, after 10 to 15 sessions (middle of RT) and after 20 to 30 sessions (end of RT). The values of serum transferrin pre-RT were significantly higher than those in the middle and at the end of RT (p < 0.001). The values of TNF-alpha were increased by RT and were significantly higher at the end of RT as compared to the pre-RT values (p < 0.05). The values of serum transferrin and TNF-alpha show a tendency to negative correlation, either as a whole or separately pre- and under-RT. However, no correlation was statistically significant.     

Correlation between tumor volume response to radiotherapy and expression of biological markers in patients with cervical squamous cell carcinoma

Objective

To determine the factors associated with tumor volume response to radiotherapy (RT) in cervical cancer patients, and the relationship between the tumor volume response and alteration of the expression of biological markers during RT.

Methods

Twenty consecutive patients with cervical squamous cell carcinoma who received definitive RT were enrolled. Tumor volumes were calculated by MRI examinations performed at the start of RT (pre-RT), at the fourth week of RT (mid-RT), and 1 month after RT completion (post-RT). Two serial punch biopsies were performed at pre- and mid-RT, and immunohistochemical staining was performed for cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR).

Results

For the pre-RT evaluation, fourteen (70%) and eleven (55%) patients showed positive immunoreactivity for COX-2 and EGFR, respectively. Among the seven patients whose median percentage residual tumor at mid-RT (V2R) was greater than 0.5, seven (100%, p=0.0515) and five (71.4%, p=0.3742) patients showed positive immunoreactivity for COX-2 and EGFR, respectively. The logistic regression analysis showed that positive immunoreactivity for both COX-2 and EGFR at pre-RT were associated with V2R (p=0.0782). For the mid-RT evaluation, eight cases showed an interval increase in the distribution of immunoreactivity for COX-2, and six out of the eight patients had a V2R greater than 0.5 (p=0.2222).

Conclusion

The poor mid-RT tumor response was associated with the coexpression of COX-2 and EGFR.     

Urinary incontinence in prostate cancer patients treated with external beam radiotherapy.

BACKGROUND AND PURPOSE: To describe the incidence of urinary incontinence among prostate cancer patients treated with external beam radiotherapy (RT) and to investigate associated risk factors. PATIENTS AND METHODS: One thousand and hundred ninety-two patients with >or=24 months follow-up were the subjects of this series. All patients received between 50 and 72 Gy in 20-37 fractions (median 66 Gy/33#). Post-RT urinary incontinence was scored by direct patient interviewing according to the modified RTOG/SOMA scale: Grade 1--occasional use of incontinence pads, Grade 2--intermittent use of incontinence pads, Grade 3--persistent use of incontinence pads, and Grade 4--permanent catheter. Risk-factors investigated were: age, diabetes, TURP prior to RT, elapsed time from TURP to RT, clinical stage, RT dose and presence of Grade >or=2 acute GU and GI toxicity. Non-parametric, actuarial univariated (Kaplan-Meier) and multivariated tests (MVA, Cox regression) were performed. RESULTS: Median follow-up for the group is 52 months (24-109). Thirty-four patients (2.9%) had incontinence prior to RT, which was more common in TURP patients (7.8% vs 1.6% P<0.001). These are excluded from further analysis. Fifty-seven patients (4.9%) developed Grade 1 incontinence, 7 (0.6%) Grade 2, and 7 (0.6%) Grade 3. There was no Grade 4 incontinence. Actuarial rates for Grade >or=1 and >or=2 incontinence at 5 years are 7 and 1.7%, respectively. Risk factors on MVA associated with the development of Grade 1 or worse incontinence are pre-RT TURP (5-year rates 10% vs 6%, P=0.026), presence of Grade >or=2 acute GU toxicity (5-year rates 11% vs 5%, P=0.002). Age, diabetes, clinical stage, elapsed time from TURP to RT, RT dose or fraction size, acute GI toxicity were not significant. Patients who underwent post-RT TURP or dilatation for obstructive symptoms (4.3%), were more likely to develop Grade 2-3 incontinence (5-year rate 8 vs 1.5%, P=0.0015). CONCLUSIONS: Grade 2 or greater urinary incontinence is rare among patients who have been treated with external beam radiotherapy. Associated risk factors are pre-RT TURP and the presence of increased acute GU toxicity. Post-radiaton TURP increases the risk of incontinence five-fold.     

MRI as a central component of clinical trials analysis in brainstem glioma: a report from the Pediatric Brain Tumor Consortium (PBTC)

We report MRI findings from 2 pediatric clinical trials of diffuse intrinsic brainstem glioma (BSG) incorporating concurrent radiation therapy (RT) with molecularly targeted agents (gefitinib and tipifarnib). We determined associations of MRI variables with progression-free survival and overall survival and investigated effects of treatment on these variables. MRI (including diffusion and perfusion) was done before treatment, every 8 weeks (first year), every 12 weeks (thereafter), and at the end of treatment or disease progression. Reduced tumor volume (P < .0001) and tumor diffusion values (P <.0001) were apparent on the first post-RT/drug studies. Decreases in tumor volume correlated with pre-RT volume (P < .0001) and pre-RT diffusion values (P < .0001); larger decreases were noted for tumors with higher volumes and diffusion values. Patients with larger pre-RT tumors had longer progression-free survival (P < .0001). Patients with ≥ 25% decrease in tumor volume and diffusion values after RT had longer progression-free survival (P = .028) and overall survival (P = .0009). Enhancement at baseline and over time was significantly associated with shorter survival. Tumor diffusion values with baseline enhancement were significantly lower than those without (P = .0002). RT of BSG is associated with decreased tumor volume and intralesional diffusion values; patients with ≥ 25% decrease in values post-RT had relatively longer survival intervals, apparently providing an early imaging-based surrogate for relative outcomes. Patients with larger tumors and greater decreases in tumor volume and diffusion values had longer survival intervals. Tumor enhancement was associated with shorter survival, lower tumor diffusion values (increased cellularity), and a smaller drop in diffusion values after RT (P = .006). These associations justify continued investigation in other large clinical trials of brainstem glioma patients.     

Influence of tumor grade on time to progression after irradiation for localized ependymoma in children

PURPOSE: To investigate the influence of histologic grade on progression-free survival (PFS) after irradiation (RT) for pediatric patients with localized ependymoma. METHODS AND MATERIALS: Fifty patients with localized ependymoma (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT between December 1982 and June 1999. Anaplastic features were identified in 14 of 50 patients. The extent of resection was characterized as gross-total in 36 patients, near-total in 5, and subtotal in 9. The median dose to the primary site was 54 Gy. Of the 50 patients, 23 received pre-RT chemotherapy. RESULTS: Thirty-nine patients were alive at a median follow-up of 46 months (range 21-214) from diagnosis. Thirty-four patients remained progression free at a median follow-up of 35 months (range 13-183) after the initiation of RT. Progression occurred in 16 patients (12 local and 4 local and distant), with a median time to failure of 21.2 months (range 4.6-65.0). The tumor grade significantly influenced the PFS after RT (p < 0.0005). The estimated 3-year PFS rate was 28% +/- 14% for patients with anaplastic ependymoma compared with 84% +/- 8% for patients with differentiated ependymoma. These results remained significant when corrected for age at diagnosis (<3 years), pre-RT chemotherapy, and extent of resection. Patients who received pre-RT chemotherapy had an inferior 3-year PFS estimate after RT (49 +/- 12%) compared with those who did not (84% +/- 10%; p = 0.056). Anaplastic ependymoma was found more frequently in the supratentorial brain (p = 0.002). Six of 12 patients with supratentorial tumor developed recurrence; recurrence was restricted to patients with anaplastic ependymoma. CONCLUSION: Tumor grade influences outcome for patients with ependymoma independent of other factors and should be considered in the design and analysis of prospective trials involving pediatric patients treated with RT. Chemotherapy before RT influences the PFS and overall survival after RT. The effect is more pronounced when progression occurs during chemotherapy.     

Prospective validation of serum CYFRA 21-1, beta-2-microglobulin, and ferritin levels as prognostic markers in patients with nonmetastatic nasopharyngeal carcinoma undergoing radiotherapy

BACKGROUND: Patients with undifferentiated nasopharyngeal carcinoma (NPC) have elevated serum levels of CYFRA 21-1 (CYFRA), ferritin, and beta-2-microglobulin (beta2M) compared with healthy control individuals. The prognostic value of these markers has never been validated prospectively. METHODS: Paired serum samples from 160 patients with newly diagnosed, nonmetastatic, undifferentiated NPC were collected before radiotherapy (RT) and at 4-6 weeks after the completion of RT. Pre-RT and post-RT levels of serum CYFRA, ferritin, and beta2M were analyzed and correlated with overall survival (OS), progression-free survival (PFS), time to locoregional recurrence, (TLR) and time to distant recurrence (TDR). The results of pre-RT and post-RT plasma Epstein-Barr virus (EBV) DNA levels available from a previous study were included in a Cox regression model together with age, tumor (T) classification, and lymph node (N) classification. RESULTS: Sixty percent of patients had International Union Against Cancer Stage III-IV disease. At a median follow-up of 116 weeks (range, 37-239 weeks), 38 patients had disease progression. On multivariate analysis, pre-RT CYFRA and post-RT EBV DNA levels were independent predictors of poor OS, post-RT EBV DNA level and N classification predicted poor PFS and TDR; and only T classification predicted TLR. Patients who had pre-RT CYFRA levels > or = 1.5 U/mL were more likely to die (hazard ratio, 1.18; 95% confidence interval, 1.10-1.26) compared with patients who had pre-RT CYFRA levels < 1.5 U/mL. There were no associations between age, post-RT CYFRA levels and pre-RT or post-RT serum ferritin and beta2M levels, and the survival and recurrence rates on multivariate analysis. CONCLUSIONS: Serum CYFRA levels taken before RT predicted reduced survival in patients with nonmetastatic, undifferentiated NPC who underwent RT.     

ROC curves and evaluation of radiation-induced pulmonary toxicity in breast cancer

PURPOSE: To study clinical, radiologic, and physiologic pulmonary toxicity in 128 women after adjuvant radiotherapy (RT) for breast cancer in relation to dosimetric factors. METHODS AND MATERIAL: The patients underwent pulmonary function testing before and 5 months post-RT. Similarly, computer tomography of the chest was repeated 4 months post-RT and changes were scored with a semiquantitative system. Clinical symptoms were registered and scored according to Common Toxicity Criteria. All patients underwent three-dimensional dose planning, and the ipsilateral lung volume receiving > or = 13 Gy (V13), V20, and V30 were calculated. Multiple logistic or regression analyses were used for multivariate modeling. The relation between the dosimetric factors and side effects was also analyzed with receiver operating characteristic (ROC) curves. RESULTS: V20 was, according to multivariate modeling, the most important variable for the occurrence of the three studied side effects (p < 0.01). Age was also related to symptomatic and radiologic pneumonitis. Reduced pre-RT functional level was more common in patients developing symptomatic toxicity. The ROC areas for symptomatic pneumonitis in relation to V13, V20, and V30 were 0.69, 0.69, and 0.67, and for radiologic pneumonitis 0.85, 0.85, and 0.81. CONCLUSIONS: Our results support the use of three-dimensional planning aimed at minimizing the percent of incidentally irradiated lung volume to reduce pulmonary toxicity. Age was also correlated with post-RT side effects. According to ROC analysis, V20 could well predict the risk for radiologic pneumonitis for the studied semiquantitative model.     

Predictors for pneumonitis during locoregional radiotherapy in high-risk patients with breast carcinoma treated with high-dose chemotherapy and stem-cell rescue

BACKGROUND: To study the predictive value of serial pulmonary function testing (PFT) for toxicity in patients who have received high-dose chemotherapy (HDCT) and stem-cell rescue for breast carcinoma. These patients are at risk of developing therapy-related pneumonitis (TRP) during or after radiotherapy (RT). METHODS: Sixty-eight patients who received induction chemotherapy (CT) and consolidation HDCT (cyclophosphamide, cisplatin, carmustine) underwent serial PFTs before induction CT, after HDCT, and before locoregional RT. The rate of TRP, i.e., pulmonary complications of Grade 2 or higher (World Health Organization classification), was studied during and 2 months after RT. We analyzed the time-course of changes in the diffusing capacity of carbon monoxide (DLCO) and forced expiratory volume at one second (FEV(1)) and studied the differences between patients who developed TRP and those who did not. RESULTS: The incidence of TRP was 46%. There were marked reductions in DLCO and FEV(1) at the time of RT compared with baseline (Wilcoxon signed rank test: P < 0.001). However, pre-RT PFT values did not predict subsequent development of TRP. Instead, the ratio of pre-RT DLCO to the minimum post- HDCT DLCO, i.e., trend of improvement, predicted the development of TRP in patients (logistic regression analysis: P = 0.048). At a cutoff level of 1, the positive and negative predictive values for this ratio were 61% and 87%, respectively. There was an association between this ratio and a longer interval between HDCT and RT (Spearman rank correlation: P = 0.002). CONCLUSIONS: The results suggest that the directional trend of DLCO after HDCT, i.e., no recovery from nadir values, is a predictor for TRP. TRP patients have a shorter median interval between HDCT and RT than asymptomatic patients. To minimize the occurrence of TRP, one should consider either delaying RT beyond 2 months following carmustine-based HDCT to allow the PFTs to partly recover, or confirm apositive directional trend for improvement of DLCO at the start of RT compared to the post-HDCT nadir value.     

Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy: the importance of pretreatment hemoglobin levels

BACKGROUND: The current study was performed to evaluate prognostic factors for overall survival (OS), distant metastasis (DM), and local failure (LF) in patients with Stage II/III esophageal carcinoma. METHODS: The following potential prognostic factors were retrospectively investigated in 124 patients treated with radiotherapy (RT) alone or with radiochemotherapy: age, gender, performance status, tumor location, tumor length, histology, histologic grade, T classification, N classification, International Union Against Cancer stage, chemotherapy, RT dose, and pre-RT hemoglobin level. RESULTS: Using univariate analysis (Kaplan-Meier method), pre-RT hemoglobin level, RT dose, tumor length, chemotherapy, and performance status were significantly associated with OS. Hemoglobin levels of 12.1-14.0 g/dL were associated with the best OS, followed by >/= 14.1 g/dL and /= 14 g/dL and 相似文献   

非小细胞肺癌放疗后有症状放射性肺损伤临床特点分析

目的 分析非小细胞肺癌(NSCLC)患者放疗后发生有症状放射性肺损伤(SRILI)的临床特点。方法 回顾分析2000—2007年放疗的NSCLC患者治疗期间或随访中发生并在本院治疗的SRILI临床症状、体征、影像及血液学改变等。SRILI经2名放疗科和1名影像科医生根据不良反应常见术语标准3.0版进行诊断和分级。结果 81例SRILI患者纳入分析,其中2级 35例、3级 42例、4级 0例、5级 4例。自放疗开始SRILI症状出现时间中位数8.3周。SRILI症状主要为咳嗽(95%)、气短(69%)、发热(48%),最高体温中位数38.3℃。临床体征相对较少,常见为呼吸音粗糙(50%)。影像表现为放射野内肺实变、通气支气管征、斑片和条索影,少数出现在放射野外。血象改变为中性粒细胞比例稍高(中位数77.4%)。结论 SRILI出现在放疗开始后平均8.3周,临床特点表现为咳嗽、气短、发热、呼吸音粗糙,放射野内或少数野外实变、斑片、条索影,中性粒细胞比例稍高。     

Salvage Radiotherapy After Postprostatectomy Biochemical Failure: Does Pretreatment Radioimmunoscintigraphy Help Select Patients with Locally Confined Disease?

PURPOSE: Radioimmunoscintigraphy (RIS) has the potential to demonstrate early recurrences after prostatectomy and might be useful in selecting patients for salvage radiotherapy (RT). METHODS: A total of 82 patients with adenocarcinoma of the prostate were treated with salvage RT between 1988 and 2005, for an elevated prostate-specific antigen (PSA) level after prostatectomy. Of the 82 patients, 32% had Gleason score 6 or less disease, 54% Gleason score 7 disease, 70% had Stage pT3 disease, 55% had positive margins, and 5% had pathologic lymph node involvement. The median pre-RT PSA level was 0.63 ng/mL. Of the 82 patients, 47 (57%) had a pre-RT RIS (ProstaScint) scan, which was used for both patient selection and target delineation. The RT regimen was a median dose of 66 Gy to the prostate bed. Also, 64% received androgen deprivation therapy. Biochemical failure was defined as a PSA level >0.1 ng/mL and increasing. RESULTS: Patients with a pre-RT RIS scan had a lower preoperative PSA level (p = 0.0240) and shorter follow-up (p = 0.0221) than those without RIS. With a median follow-up of 44 months, the biochemical control rate was 56% at 3 years and 48% at 5 years. Margin status was the only factor associated with biochemical control on univariate (p = 0.0055) and multivariate (p = 0.0044) analysis. Patients who had prostate bed-only uptake on RIS (n = 38) did not have improved outcomes, with biochemical control rates of 51% at 3 years and 40% at 5 years. CONCLUSION: Patients treated with salvage RT had modest responses. Patients who were selected for treatment with RIS did not have better biochemical outcomes. Our results indicated that patients with positive margins were most likely to benefit from salvage RT.     

Observations on the predictive value of perfusion lung scans on post-irradiation pulmonary function among 210 patients with bronchogenic carcinoma.

As a component of treatment planning for thoracic irradiation (RT), 210 bronchogenic carcinoma patients seen at the Fox Chase Cancer Center from 1983 to 1990 underwent quantitative perfusion scans, superimposition of their RT treatment fields onto these scans, and pulmonary function testing. These studies were used to prospectively estimate the influence of the planned thoracic irradiation on pulmonary function, as measured by the forced expiratory volume in one second (FEV1). Among the 156 patients with unresected lesions, the mean pre-RT FEV1 was 1.71 +/- 0.67 liters (+/- standard deviation), and the mean percentage of total lung perfusion within the treatment field was 31.0 +/- 12.1%. Mean values for the 54 patients treated post-operatively were 1.79 liters (pre-RT FEV1) and 28.8% (% perfusion within RT field). Using this technique, the prospectively predicted post-RT FEV1 is the product of the pre-RT FEV1 (1% of total lung perfusion within the treatment field). The mean predicted post-treatment FEV1 for the nonoperative patients was 1.15 +/- 0.43 liters and 1.25 +/- 0.41 liters for the postoperative patients. Forty-three nonoperative and 19 postoperative patients had FEV1 determinations following RT, at a mean post-RT interval of 11 months for nonoperative patients and 23 months for post-operative patients. Among nonoperative patients, 53% had no change in post-RT FEV1, 19% improved, while 22% had readings declining toward the predicted value. Only 5% had readings below predicted. Among postoperative patients, 37% had no change or improvement, 37% declined toward the predicted, 10% declined to predicted, and 11% had values worse than predicted. This technique of superimposing RT fields onto lung perfusion scans predicts for a degree of pulmonary impairment which is observed in only a minority of patients (10%) and which is rarely exceeded (6%).