We assessed the records of 101 patients with locally advanced transitional cell carcinoma (TCC) of the renal pelvis and ureter treated with postoperative radiation therapy to determine outcome and patterns of failure. Locally advanced disease (i.e., T3–4N0 or N+ disease) was identified in 65 patients. Postoperative radiation was used to treat 86 patients, with a median dose of 35 Gy in 20 fractions over 4 weeks to the tumor bed and regional lymph nodes. There were 15 patients with no residual disease who were offered no further therapy. No patient received postoperative chemotherapy. Prognostic factors were examined using univariate and multivariate analysis, and the patterns of failure were identified after postoperative irradiation. Median follow-up was 9.3 years, during which 76 deaths occurred. The 5-year overall survival was 43% and 10-year survival was 23%. A multivariate analysis identified T3 category, lymph node involvement, and age at diagnosis as significant prognostic factors for survival. Tumor grade was a significant prognostic factor on univariate analysis but not on multivariate analysis. Failure analysis showed that only 36% of patients with locally advanced disease remained relapse free. For this group of patients, distant metastases developed in 53%, and locoregional failured occurred in 35% despite postoperative irradiation. Locoregional failure occurred in 95% of patients with nodal involvement who received postoperative radiation, and 77% of those developed distant relapse. This leads us to conclude that patients with resected locally advanced (T3, T4N0, N+) TCC of the upper urinary tracts have a high risk of relapse and death from disease despite postoperative radiotherapy. Because the main feature of the disease is early distant failure, post-operative chemotherapy is required to improve the outcome for this group of patients. 相似文献
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. 相似文献
: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival.
: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days.
: The 3-year acturial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%,and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grafe 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control.
: These findings suggest that accelerated giben in an overall treatment time of <35 days might be beneficial for easy-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with modeate acure and late toxicity. 相似文献
: To evaluate survival and patterns of recurrence in patients with primary central nervous system germinoma treated with radiation therapy.
: Data regarding 48 patients with histologically confirmed, primary central nervous system germinoma were reviewed. All had been operated on at the Mayo Clinic between the years 1935 and 1993. Thirty-two patients (67%) were treated since 1973. The study group included 39 males and 9 females, with a median age at diagnosis of 17 years (range, 6–42 years). Twelwe patients (25%) were treated with craniospinal axis irradiation, 11 (23%) received whole-brain irradiation without spinal axis irradiation, and 24 (50%) underwent partial-brain irradiation. Treatment volumes were unknown in one patient. The median dose to the primary tumor was 44.00 Gy (range, 7.44–59.40 Gy). The median follow-up was 5.5 years (range, 4 months to 37 years).
: Actuarial 5-year and 10-year survival for the entire study group of patients was 80%. There was a trend toward improved survival in patients treated after 1973 (introduction of computed tomography) with 5-year and 10-year survival of 91% vs. 63% in prior years (p = 0.07). For the group of 31 patients treated since 1973 with known treatment volumes, the spinal axis failure rate at 5 years was 49% for patients treated with partial brain fields (11 patients) vs. 0% for those having undergone whole brain (10 patients) or craniospinal axis (10 patients) irradiation (p = 0.007). The rate of brain failure was also significantly higher in patients receiving less than whole-brain irradiation; at 5 years, 45% of the patients treated with partial-brain fields had intracranial recurrence of disease compared to 6% of patients treated with craniospinal axis or whole-brain irradiation (p = 0.01). Among the 32 modern era patients, the rate of brain failure was higher in patients who received doses less than 40 Gy (median dose, 48.55 Gy; range, 30.60-59.40 Gy) to the primary tumor (5-year brain failure rate 52% vs. 11%, p = 0.002).
: The long-term survival of patients with histologically proven CNS germinoma treated with radiation is excellent. Whole-brain or craniospinal axis irradiation appears to result in fewer spine and brain failures than does partial-brain irradiation. Furthermore, the administration of doses greater than 40 Gy to the primary tumor is associated with better local control. 相似文献
PURPOSE: We retrospectively analyzed prognostic factors for surgical resection and intraoperative radiation therapy to identify indicators for this treatment strategy.
METHODS: Thirty-nine consecutive patients with locally recurrent colorectal cancer who underwent surgical resection with intraoperative radiation therapy from January 1, 1987, to June 30, 1999, were analyzed. The mean electron energy was 10.5 MeV and the mean intraoperative radiation dose was 22.6 Gy. Kaplan-Meier survival estimates were obtained for the 37 patients who recovered postoperatively. Prognostic factors were analyzed univariately by log-rank test and multivariately by Coxs proportional hazards model.
RESULTS: Three-year cumulative survival was 44 percent (standard error = 11) for 26 patients free of unresectable distant metastasis who underwent surgical resection and intraoperative radiation therapy for pelvic recurrence of colorectal cancer, but none of the 11 patients with unresectable distant metastasis survived 3 years. Preoperative prognostic factors which were significant on univariate and multivariate analysis were unresectable distant metastasis (P = 0.001) and elevated preoperative serum CA 19–9 (P = 0.02). Patients with synchronous resection of local recurrence and distant metastasis had a significant survival advantage over those without resection of metastases (P = 0.02). Univariate analysis in a subgroup of 26 patients without unresectable distant metastasis revealed pain (P = 0.0003) to be a useful preoperative prognostic indicator, whereas tumor fixation (P = 0.01) and amount of residual tumor after surgical resection (P = 0.01) were significant intraoperative and postoperative factors, respectively. Fluorouracil-based postoperative systemic chemotherapy produced a significant survival benefit (P = 0.04).
CONCLUSIONS: Patients with unresectable distant metastasis are not suitable candidates for surgical resection and intraoperative radiation therapy, whereas those with resectable metastasis are potential candidates. Intraoperative radiation therapy may be less useful for patients with pain, elevated preoperative CA19–9, fixed tumors, or gross residual tumor after surgical resection. Multimodal treatment strategies combining preoperative and/or postoperative external beam radiation therapy and intraoperative radiation therapy with fluorouracil-based systemic chemotherapy are recommended for patients with these indicators. 相似文献
Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that
DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence
of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression
of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that
were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic
for several DNA damage repair pathways was investigated, as well as expression of genes involved in different
phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was
assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential
gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were
more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two
times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after
radiotherapy in the TCGA breast cancer cohort. Genes involved in G1, G1/S, G2, and G2/M phases were lower
expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two
times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not
associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA
damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in
both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these
cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found. 相似文献