Survival prediction in high-grade gliomas by MRI perfusion before and during early stage of RT [corrected

PURPOSE: To determine whether cerebral blood volume (CBV) and cerebral blood flow can predict the response of high-grade gliomas to radiotherapy (RT) by taking into account spatial heterogeneity and temporal changes in perfusion. METHODS AND MATERIALS: Twenty-three patients with high-grade gliomas underwent conformal RT, with magnetic resonance imaging perfusion before and at Weeks 1-2 and 3-4 during RT. Tumor perfusion was classified as high, medium, or low. The prognostic values of pre-RT perfusion and the changes during RT for early prediction of tumor response to RT were evaluated. RESULTS: The fractional high-CBV tumor volume before RT and the fluid-attenuated inversion recovery imaging tumor volume were identified as predictors for survival (p = 0.01). Changes in tumor CBV during the early treatment course also predicted for survival. Better survival was predicted by a decrease in the fractional low-CBV tumor volume at Week 1 of RT vs. before RT, a decrease in the fractional high-CBV tumor volume at Week 3 vs. Week 1 of RT, and a smaller pre-RT fluid-attenuated inversion recovery imaging tumor volume (p = 0.01). CONCLUSION: Early temporal changes during RT in heterogeneous regions of high and low perfusion in gliomas might predict for different physiologic responses to RT. This might also open the opportunity to identify tumor subvolumes that are radioresistant and might benefit from intensified RT.     

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.     

2-[(18)F]Fluoro-2-deoxyglucose and glucose uptake in malignant gliomas before and after radiotherapy: correlation with outcome.

PURPOSE: To examine whether quantitative 1-[(11)C]glucose- or 2-[(18)F]fluoro-2-deoxyglucose (FDG)-positron emission tomography performed before and/or after radiotherapy (RT) of malignant gliomas correlates with treatment outcome. Changes in metabolism between the start and finish of RT, and immediate post-RT studies have received little attention. EXPERIMENTAL DESIGN: Adults with malignant gliomas were imaged within 2 weeks before and/or 2 weeks after RT. Four patients were imaged only before RT, 12 only after RT, and 14 both before and after RT. Each 1-[(11)C]glucose and FDG study included arterial plasma sampling. Kinetic parameters, glucose metabolic rate (MRGlc), and FDG metabolic rate (MRFDG) were estimated by an optimization program based on a three compartment, four rate constant model. Changes in MRGlc or MRFDG from pre-RT to post-RT were calculated for the 14 patients studied at both times. Overall survival was examined, and survival was computed relative to historical controls in matched prognostic classes. RESULTS: Low pre-RT MRGlc (P < 0.02) or MRFDG (P < 0.03), or an increase from pre- to post-RT in MRGlc (P < 0.004) or MRFDG (P < 0.006) are correlating with longer survival (4 patients still alive). Strikingly, the post-RT studies (n = 26) showed no correlation between MRGlc or MRFDG and survival (P = 0.73 and P = 0.46 respectively). CONCLUSIONS: Low MRGlc or MRFDG before RT probably indicates less aggressive disease. An increase in MRGlc or MRFDG from pre- to post-RT in the tumors of patients with longer survival could be because of one or more of the following or other reasons: (a) apoptosis of tumor cells in response to RT requires energy; (b) decreased tumor cell density by the RT leaving normal cells with higher metabolism; or (c) inflammatory cells infiltrate and take up glucose or FDG where tumor cells are dying. Quantitative 1-[(11)C]glucose or FDG uptake in the early weeks post-RT correlates poorly with survival.     

Clinically significant prostate cancer local recurrence after radiation therapy occurs at the site of primary tumor: magnetic resonance imaging and step-section pathology evidence

PURPOSE: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. METHODS AND MATERIALS: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm(3) and/or resulting in extraprostatic disease on pathology were considered clinically significant. RESULTS: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm(3)) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci (相似文献   

Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.     

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.     

Dose escalation using twice-daily radiotherapy for nasopharyngeal carcinoma: does heavier dosing result in a happier ending?

PURPOSE: Recently, imaging-based tumor volume before, during, and after radiation therapy (RT) has been shown to predict tumor response in cervical cancer. However, the effectiveness of different methods and timing of imaging-based tumor size assessment have not been investigated. The purpose of this study was to compare the predictive value for treatment outcome derived from simple diameter-based ellipsoid tumor volume measurement using orthogonal diameters (with ellipsoid computation) with that derived from more complex contour tracing/region-of-interest (ROI) analysis 3D tumor volumetry. METHODS AND MATERIALS: Serial magnetic resonance imaging (MRI) examinations were prospectively performed in 60 patients with advanced cervical cancer (Stages IB2-IVB/recurrent) at the start of RT, during early RT (20-25 Gy), mid-RT (45-50 Gy), and at follow-up (1-2 months after RT completion). ROI-based volumetry was derived by tracing the entire tumor region in each MR slice on the computer work station. For the diameter-based surrogate "ellipsoid volume," the three orthogonal diameters (d1, d2, d3) were measured on film hard copies to calculate volume as an ellipsoid (d1 x d2 x d3 x pi/6). Serial tumor volumes and regression rates determined by each method were correlated with local control, disease-free and overall survival, and the results were compared between the two measuring methods. Median post-therapy follow-up was 4.9 years (range, 2.0-8.2 years). RESULTS: The best method and time point of tumor size measurement for the prediction of outcome was the tumor regression rate in the mid-therapy MRI examination (at 45-50 Gy) using 3D ROI volumetry. For the pre-RT measurement both the diameter-based method and ROI volumetry provided similar predictive accuracy, particularly for patients with small (<40 cm3) and large (> or =100 cm3) pre-RT tumor size. However, the pre-RT tumor size measured by either method had much less predictive value for the intermediate-size (40-99 cm3) tumors, which accounted for the majority of patients (55%). Tumor regression rate (fast vs. slow) obtained during mid-RT (45-50 Gy), which could only be appreciated by 3D ROI volumetry, had the best outcome prediction rate for local control (84% vs. 22%, p < 0.0001) and disease-free survival (63% vs. 20%, p = 0.0005). Within the difficult to classify intermediate pre-RT size group, slow ROI-based regression rate predicted all treatment failures (local control rate: 0% vs. 91%, p < 0.0001; disease-free survival: 0% vs. 73%, p < 0.0001). Mid-RT regression rate based on simple diameter measurement did not predict outcome. The early-RT and post-RT measurements were least useful with either measuring method. CONCLUSION: Our preliminary data suggest that for the prediction of treatment outcome in cervical cancer, initial tumor volume can be estimated by simple diameter-based measurement obtained from film hard copies. When initial tumor volume is in the intermediate size range, ROI volumetry and an additional MRI during RT are needed to quantitatively analyze tumor regression rate for the prediction of treatment outcome.     

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).     

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.     

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   

DNA ploidy analysis of effectiveness of radiation therapy for cervical carcinoma

Cellular DNA content from 30 patients with cervical carcinoma was determined using flow cytometry before and after radiation therapy (RT). The authors attempted to correlate changes in DNA content, tumor response to RT, and post-RT pathologic findings. Before RT, tumors from eight of 30 patients (26.7%) were diploid or near-diploid; tumors from 22 patients (73.3%) were aneuploid. After RT, diploid or near-diploid tumors were found in 23 patients (76.7%), and aneuploid tumors were observed in seven patients (23.3%). Aneuploidy disappeared in 15 of the patient tumors, and complete tumor response (CR) was observed in 13 of these 15 patients (86.7%). Pathologic examinations were negative in 12 of 15 cases and suspicious in one of 15 cases. Of the seven patients whose tumor aneuploidy did not change after RT, CR was observed in only two (28.7%). Pathologic examinations were positive in five of seven cases and suspicious in one of seven cases. The CR for the 22 patients with pre-RT aneuploid tumors was 15 of 22 (68.2%); the CR for the eight patients with pre-RT diploid tumors was two of eight (25%, P less than 0.01). From these data the authors conclude there is a direct correlation between DNA content and radiosensitivity in cervical carcinoma. Aneuploid tumors from these patients were more radiosensitive than diploid tumors, and they patients had a better clinical tumor response and improved pathologic findings.     

Metastatic lymph-node clearance from head and neck epidermoid carcinomas following radiotherapy

Although tumor clearance is a common criterion in assessing the impact of radiotherapy (RT), it is not always reliable. Patterns of tumor clearance were determined using 91 metastatic lymph nodes (LNs) from 51 patients with head and neck tumors treated by definitive RT (61-80 Gy) or preoperative RT (43-65 Gy). Clearance rate (CR) was estimated as a daily volume decrement expressed as a ratio to the pre-RT LN volume. CR was greater for the so-called radioresponsive nasopharyngeal subgroups and more poorly differentiated than those of oral cavity and well-differentiated, respectively. Histologically, LNs that were removed following RT consisted mainly of fibrous tissues, necrotic tissues, and few cancer cells. There was no difference in CR between the cancer-cell-positive group (n=21) and the cancer-cell-negative group (n=31). Although the CR may reflect inherent radiosensitivity of tumor cells, tumor persistence predicts the amount of oncologically inactive materials rather than that of remaining cancer cells.     

Cytomorphologic features characteristic of tumor stages of thymomas

The cytologic findings of the tumor cells characteristic of the stages of thymomas were investigated to assess the invasiveness of the tumors. Forty-six patients with thymoma who underwent extensive thymectomy without pre-operative corticosteroid therapy were included in this study. The histologic subtypes included 18 round/oval, 20 mixed, and 8 spindle type. The stages of thymoma classified according to Masaoka's clinicopathological classification included 16 stage I, 20 stage II, 6 stage III, 2 stage IVa, and 2 stage IVb, and myasthenia gravis was recognized in 5 patients. Cytologic findings were retrospectively analyzed in the Papanicolaou-stained stamp smears obtained from the cut surfaces of thymoma specimens. Morphometry of the epithelial tumor cells using Cosmozone-1A was performed to evaluate the validity of our cytologic categories. Compared with the cytologic findings of stage I or II thymomas, those of epithelial tumor cells in stage III or IV more frequently showed necrotic background (50.0%-stage III or IV vs 11.1%-stage I or II, p=0.006), large clusters of epithelial tumor cells (70.0% vs 36.1%, p=0.055), marked nuclear enlargement (90.0% vs 52.7%, p=0.033), marked anisokaryosis (100% vs 52.7%, p=0.006), marked nuclear polymorphism (40.0% vs 5.5%, p=0.004), hyperchromasia (50.0% vs 11.4%, p=0.007) and prominent nucleoli (50.0% vs 16.6%, p=0.028) whereas no significant correlation was observed between cytologic findings and tumor volume. Morphometric studies of thymoma tumor cells revealed that the nuclear size (mean values, 78.8 microm(3)-stage III or IV vs 58.2 microm(3)-stage I or II), the coefficient of variation of the nuclear size (0.326 vs 0.282), and the nuclear rotundity (0.849 vs 0.858) differed significantly between the two categories (p<0.05). Our findings demonstrated that there were significant differences between the cytologic findings of epithelial tumor cells of stage I or II thymomas and those of stage III or IV thymomas, and that the cytologic findings of thymoma tumor cells appear to be useful for distinguishing between non-invasive and invasive thymomas.     

MR imaging assessment of irregular shrinkage of tumor morphology and volume in cervical cancer during radiation therapy

Objective: To study the clinical significance of the morphological and volume changes in cervical cancer during an ongoing course of radiation therapy (RT) using MR imaging. Methods: Serial MR imaging examinations were performed in 60 advanced cervical cancer patients.MR imaging was obtained at the start of RT, at 20-25 Gy(2-2.5 weeks of RT), at 45-50 Gy (4-5 weeks of RT), and 1-2 month post-RT. Tumor morphology was classified qualitatively as well-defmed (round/oval with a well-demarcated smooth margin) vs. lobulated vs. irregular and tumor volume was assessed in each serial MR examination independently by ROI volumetry and diameter volumetry. ROI volumetry was traced on the computer workstation with a trackball in each sagittal T2-weighted image and calculated by the summation of all tumor areas in each slice and multiplication by the slice profile. Diameter volumetry was to measure the largest three orthogonal tumor diameters in each orthogonal measurement plane and calculate as an ellipsoid formula (V=d1 x d2 x d3 x π/6).Serial tumor volume was compared between the two measurement methods. Results: The proportion of lobulated and irregular tumors increased early during RT and declined lately post-RT (68% pre-RT, 80% at 2-2.5 weeks of RT, 72% at 4-5 weeks of RT, 33% post-RT). Accordingly,ROI volumetry and diameter volhmetry correlated well pre-RT (r1=0.89) and post-RT (r4=0.80), but poorly during RT (r2 = 0.17 at 2-2.5 weeks of RT, r3 = 0.69 at 4-5 weeks of RT). Conclusions: Cervical cancers regress in a non-uniform fashion during RT and undergo increasingly irregular shrinkage. Measurement with ROI volumetry techniques, which can optimally measure irregular volumes,provides better assessment of radiation response during treatment than diameter volumetry.     

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.     

Patterns of recurrence analysis in newly diagnosed glioblastoma multiforme after three-dimensional conformal radiation therapy with respect to pre-radiation therapy magnetic resonance spectroscopic findings

PURPOSE: To determine whether the combined magnetic resonance imaging (MRI) and magnetic resonance spectroscopy imaging (MRSI) before radiation therapy (RT) is valuable for RT target definition, and to evaluate the feasibility of replacing the current definition of uniform margins by custom-shaped margins based on the information from MRI and MRSI. METHODS AND MATERIALS: A total of 23 glioblastoma multiforme (GBM) patients underwent MRI and MRSI within 4 weeks after surgery but before the initiation of RT and at 2-month follow-up intervals thereafter. The MRSI data were quantified on the basis of a Choline-to-NAA Index (CNI) as a measure of spectroscopic abnormality. A combined anatomic and metabolic region of interest (MRI/S) consisting of T2-weighted hyperintensity, contrast enhancement (CE), resection cavity, and CNI2 (CNI >or= 2) based on the pre-RT imaging was compared to the extent of CNI2 and the RT dose distribution. The spatial relationship of the pre-RT MRI/S and the RT dose volume was compared with the extent of CE at each follow-up. RESULTS: Nine patients showed new or increased CE during follow-up, and 14 patients were either stable or had decreased CE. New or increased areas of CE occurred within CNI2 that was covered by 60 Gy in 6 patients and within the CNI2 that was not entirely covered by 60 Gy in 3 patients. New or increased CE resided within the pre-RT MRI/S lesion in 89% (8/9) of the patients with new or increased CE. CONCLUSION: These data indicate that the definition of RT target volumes according to the combined morphologic and metabolic abnormality may be sufficient for RT targeting.     

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.     

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.     

Preoperative steroid pulse therapy for invasive thymoma: clinical experience and mechanism of action

BACKGROUND: Glucocorticoid was used in thymomas. The purpose of the study was to evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse) therapy in patients with previously untreated advanced thymoma. Causes were also sought for a possible underlying mechanism of the effect of steroid on thymoma. METHODS: Seventeen patients with invasive thymoma who had not received previous chemotherapy or radiation therapy were enrolled in the study. All cases were treated with 2 courses of glucocorticoid therapy before surgery. Tumor response was assessed by computed tomography (CT) scan 1 week after the steroid pulse therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8 phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and epithelial cells. RESULTS: The overall response rate to the steroid pulse therapy was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1 thymomas; there were significant differences between type AB and type B1 thymomas (P = .0234) and type B1 and type B3 thymomas (P = .0068). The reduction in tumor size was accompanied with a marked reduction in the CD4+8+ double-positive immature thymocytes that expressed higher levels of glucocorticoid receptor. Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte components after glucocorticoid therapy. CONCLUSIONS: The efficiency of preoperative steroid pulse therapy in type B1 thymoma was most prominent, which is probably related to the specific effect on GR-rich CD4+8+ double-positive immature lymphocytes, which are abundant in this type of thymoma.     

Tumor regrowth between surgery and initiation of adjuvant therapy in patients with newly diagnosed glioblastoma

To assess incidence and degree of regrowth in glioblastoma between surgery and radiation therapy (RT) and to correlate regrowth with presurgical imaging and survival, we examined images of 32 patients with newly diagnosed glioblastoma who underwent MR spectroscopic imaging (MRSI), perfusion-weighted imaging (PWI), and diffusion-weighted imaging (DWI) prior to surgery, after surgery, and prior to RT/temozolomide. Contrast enhancement (CE) in the pre-RT MR image was compared with postsurgical DWI to differentiate tumor growth from postsurgical infarct. MRSI and PWI parameters were analyzed prior to surgery and pre-RT. Postsurgical MRI indicated that 18 patients had gross total and 14 subtotal resections. Twenty-one patients showed reduced diffusion, and 25 patients showed new or increased CE. In eight patients (25%), the new CE was confined to areas of postsurgical reduced diffusion. In the other 17 patients (53%), new CE was found to be indicative of tumor growth or a combination of tumor growth and surgical injury. Higher perfusion and creatine within nonenhancing tumor in the presurgery MR were associated with subsequent tumor growth. High levels of choline and reduced diffusion in pre-RT CE suggested active metabolism and tumor cell proliferation. Median survival was 14.6 months in patients with interim tumor growth and 24 months in patients with no growth. Increased volume or new onset of CE between surgery and RT was attributed to tumor growth in 53% of patients and was associated with shorter survival. This suggests that reducing the time between surgery and adjuvant therapy may be important. The acquisition of metabolic and physiologic imaging data prior to adjuvant therapy may also be valuable in assessing regions of new CE and nonenhancing tumor.