BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed...BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy p lus temozolomide, given concomitantly with and after radiotherapy, in terms of e fficacy and safety. METHODS: Patients with newly diagnosed, histologically confi rmed glioblastoma were randomly assigned to receive radiotherapy alone (fraction ated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 we eks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (7 5 mg per square meter of body-surface area per day, 7 days per week from the fi rst to the last day of radiotherapy), followed by six cycles of adjuvant temozol omide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 8 5 centers underwent randomization. The median age was 56 years, and 84 percent o f patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12. 1 months with radiotherapy alone. The unadjusted hazard ratio for death in the r adiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P < 0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiother apy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologie toxic effects in 7 percent of patients. CONCLUSIONS: T he addition of temozolomide to radiotherapy for newly diagnosed glioblastoma res ulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.展开更多
PURPOSE: Preoperative, high- dose radiotherapy for rectal cancer reduces local recurrence rates and improves overall survival. However, adverse effects in varying degrees include impaired wound healing and local infec...PURPOSE: Preoperative, high- dose radiotherapy for rectal cancer reduces local recurrence rates and improves overall survival. However, adverse effects in varying degrees include impaired wound healing and local infection. This study investigates the influence of preoperative, high- dose radiotherapy on subcutaneous accumulation of collagen in a primary rectal cancer group operated on with or without adjuvant radiotherapy. METHODS: Forty- two eligible patients who underwent total mesorectal excision surgery with or without radiotherapy were included in the study. Polytetrafluoroethylene tubings were implanted in the arm ten days before surgery (three days before the start of radiotherapy). Implants were extracted the day before surgery. New implants were inserted before surgery and were extracted ten days after surgery. The hydroxyproline and proline contents of the implants were measured and the hydroxyproline/proline ratio was calculated as a measure for deposited collagen relative to protein. Blood loss, postoperative complications, and blood levels of hemoglob- in, leukocytes, and albumin were recorded. RESULTS: The two groups were similar in relation to Dukes stage, age, and body mass index. Infectious complications developed in 39 percent of patients after radiotherapy compared with 16 percent in the nonirradiated group. In the irradiated patients with infective complications we found a significant decrease in the hydroxyproline/proline ratio compared with that of irradiated patients without infections (P = 0.037). There was a significant decrease in the leukocyte count preoperatively and postoperatively in the irradiated group compared with surgery alone. CONCLUSIONS: Highdose, short- term radiotherapy does not have a systemic effect on collagen accumulation, but a significant reduction is manifested in infected patients. Radiotherapy also impairs leukocyte production and increases the postoperative infective complication rate.展开更多
Objective. Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)- 99 trial improves the e...Objective. Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)- 99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG- 99. Methods. From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I- II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium- 192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG- 99. The median follow up of our patients and the GOG- 99 were 3.2 years and 5.8 years, respectively. Results. Patient characteristics including age, stage, and grade were similar in our study and the GOG- 99. The local recurrence rate in our study, the pelvic RT arm of the GOG- 99, and the no RT arm of the GOG- 99 were 4% (n =2), 2% (n=3), and 9% (n= 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG- 99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2- year cumulative recurrence rate in our study was 2% , which compares favorably with the GOG- 99 pelvic RT arm (3% ) and observation arm (12% ). Four-year survival rates of the no RT arm of the GOG- 99, the RT arm of the GOG- 99, and our study with HDR VB were 86% , 92% , and 97% , respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs 34% (P value < 0.001), and GI obstruction 0% vs 7% (P value = 0.08). Conclusion. Stage I- II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.展开更多
BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glio...BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing i n the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and ad juvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RE SULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. I rrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P < 0.001 by the log-rank test; hazard ratio, 0.45; 95 perc ent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a m ethylated MGMT promoter, a survival benefit was observed in patients treated wit h temozolomide and radiotherapy; their median survival was 21.7 months (95 perce nt confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radioth erapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in sur vival between the treatment groups. CONCLUSIONS: Patients with glioblastoma cont aining a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.展开更多
To assess the short term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5×4 Gy fract ions among patients having age related macular degenera...To assess the short term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5×4 Gy fract ions among patients having age related macular degeneration (AMD). A multicente r prospective randomized controlled pilot study. Eighty eight patients were enr olled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N=41]) or no radiotherapy (sham radiother ap y [N=22]or observation [N=25]). Eligibility criteria included visual acuity of a t least 20/320 and subfoveal CNV not amenable to treatment. Randomization was st ratified by lesion type (new or recurrent CNV) and blood ( < 50%or ≥50%of the lesion [N=13]). The primary outcome measure was loss of ≥3 lines of visual a cu ity. Secondary outcome measures were angiographic response and side effects. At baseline, patient and ocular characteristics were similar between treatment grou ps. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost ≥3 lines of visual acuity (P=. 04; stratified χ2 test). At 12 months, 13 radia ted eyes (42%) and 9 observed eyes (49%) lost ≥3 visual acuity lines (P=.60). The radiated group demonstrated smaller lesions and less fibrosis than the nonr adiated group (P=.05 and. 004, respectively) at 12 months. Radiation induced co mplications were not observed except for one radiated eye with numerous cotton w ool spots and possible radiation retinopathy. External beam radiation at 5×4 Gy may have a modest and short lived (six month) benefit in preserving visual acui ty.展开更多
Objectives. Invasive cervical cancer that is discovered only after si mple hyst erectomy remains a problem. Little is known about the best management of this gr oup since there are no relevant outcome studies. This st...Objectives. Invasive cervical cancer that is discovered only after si mple hyst erectomy remains a problem. Little is known about the best management of this gr oup since there are no relevant outcome studies. This study aimed to quantify th e benefits of guideline-based treatment by comparing outcome data in patients t reated by inappropriate simple hysterectomy and adjuvant radiotherapy with data in patients treated with primary radical surgery, radiotherapy, or radiochemothe rapy. Methods. Records of 288 patients who had undergone radical hysterectomy wi th pelvic lymphadenectomy or simple hysterectomy were extracted and divided into three groups -radical hysterectomy alone (n = 89), radical hysterectomy and ad juvant radiotherapy (n = 119), and simple hysterectomy with adjuvant radiotherap y (n = 80). Disease-free and overall survival were calculated using Kaplan-Mei er analyses. Results. There was a trend towards better overall survival in the r adical hysterectomy group. Disease-free survival was significantly better in pa tients treated by radical hysterectomy, followed by simple hysterectomy plus rad iotherapy, and then radical hysterectomy plus radiotherapy (PlogrankDFS < 0.002) . When the two radical surgery groups were combined and compared with the subopt imally treated group, no significant differences were seen for overall survival. Conclusion. Postoperative radiotherapy is a good treatment for patients with ce rvical cancer who have undergone suboptimal simple hysterectomy. Appropriate sel ection criteria for further surgery remain to be defined.展开更多
文摘BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy p lus temozolomide, given concomitantly with and after radiotherapy, in terms of e fficacy and safety. METHODS: Patients with newly diagnosed, histologically confi rmed glioblastoma were randomly assigned to receive radiotherapy alone (fraction ated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 we eks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (7 5 mg per square meter of body-surface area per day, 7 days per week from the fi rst to the last day of radiotherapy), followed by six cycles of adjuvant temozol omide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 8 5 centers underwent randomization. The median age was 56 years, and 84 percent o f patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12. 1 months with radiotherapy alone. The unadjusted hazard ratio for death in the r adiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P < 0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiother apy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologie toxic effects in 7 percent of patients. CONCLUSIONS: T he addition of temozolomide to radiotherapy for newly diagnosed glioblastoma res ulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
文摘PURPOSE: Preoperative, high- dose radiotherapy for rectal cancer reduces local recurrence rates and improves overall survival. However, adverse effects in varying degrees include impaired wound healing and local infection. This study investigates the influence of preoperative, high- dose radiotherapy on subcutaneous accumulation of collagen in a primary rectal cancer group operated on with or without adjuvant radiotherapy. METHODS: Forty- two eligible patients who underwent total mesorectal excision surgery with or without radiotherapy were included in the study. Polytetrafluoroethylene tubings were implanted in the arm ten days before surgery (three days before the start of radiotherapy). Implants were extracted the day before surgery. New implants were inserted before surgery and were extracted ten days after surgery. The hydroxyproline and proline contents of the implants were measured and the hydroxyproline/proline ratio was calculated as a measure for deposited collagen relative to protein. Blood loss, postoperative complications, and blood levels of hemoglob- in, leukocytes, and albumin were recorded. RESULTS: The two groups were similar in relation to Dukes stage, age, and body mass index. Infectious complications developed in 39 percent of patients after radiotherapy compared with 16 percent in the nonirradiated group. In the irradiated patients with infective complications we found a significant decrease in the hydroxyproline/proline ratio compared with that of irradiated patients without infections (P = 0.037). There was a significant decrease in the leukocyte count preoperatively and postoperatively in the irradiated group compared with surgery alone. CONCLUSIONS: Highdose, short- term radiotherapy does not have a systemic effect on collagen accumulation, but a significant reduction is manifested in infected patients. Radiotherapy also impairs leukocyte production and increases the postoperative infective complication rate.
文摘Objective. Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)- 99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG- 99. Methods. From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I- II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium- 192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG- 99. The median follow up of our patients and the GOG- 99 were 3.2 years and 5.8 years, respectively. Results. Patient characteristics including age, stage, and grade were similar in our study and the GOG- 99. The local recurrence rate in our study, the pelvic RT arm of the GOG- 99, and the no RT arm of the GOG- 99 were 4% (n =2), 2% (n=3), and 9% (n= 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG- 99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2- year cumulative recurrence rate in our study was 2% , which compares favorably with the GOG- 99 pelvic RT arm (3% ) and observation arm (12% ). Four-year survival rates of the no RT arm of the GOG- 99, the RT arm of the GOG- 99, and our study with HDR VB were 86% , 92% , and 97% , respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs 34% (P value < 0.001), and GI obstruction 0% vs 7% (P value = 0.08). Conclusion. Stage I- II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.
文摘BACKGROUND: Epigenetic silencing of the MGMT (O6-methylguanine-DNA methyltra nsferase) DNA-repair gene by promoter methylation compromises DNA repair and ha s been associated with longer survival in patients with glioblastoma who receive alkylating agents. METHODS: We tested the relationship between MGMT silencing i n the tumor and the survival of patients who were enrolled in a randomized trial comparing radiotherapy alone with radiotherapy combined with concomitant and ad juvant treatment with temozolomide. The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis. RE SULTS: The MGMT promoter was methylated in 45 percent of 206 assessable cases. I rrespective of treatment, MGMT promoter methylation was an independent favorable prognostic factor (P < 0.001 by the log-rank test; hazard ratio, 0.45; 95 perc ent confidence interval, 0.32 to 0.61). Among patients whose tumor contained a m ethylated MGMT promoter, a survival benefit was observed in patients treated wit h temozolomide and radiotherapy; their median survival was 21.7 months (95 perce nt confidence interval, 17.4 to 30.4), as compared with 15.3 months (95 percent confidence interval, 13.0 to 20.9) among those who were assigned to only radioth erapy (P=0.007 by the log-rank test). In the absence of methylation of the MGMT promoter, there was a smaller and statistically insignificant difference in sur vival between the treatment groups. CONCLUSIONS: Patients with glioblastoma cont aining a methylated MGMT promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not have such a benefit.
文摘To assess the short term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5×4 Gy fract ions among patients having age related macular degeneration (AMD). A multicente r prospective randomized controlled pilot study. Eighty eight patients were enr olled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N=41]) or no radiotherapy (sham radiother ap y [N=22]or observation [N=25]). Eligibility criteria included visual acuity of a t least 20/320 and subfoveal CNV not amenable to treatment. Randomization was st ratified by lesion type (new or recurrent CNV) and blood ( < 50%or ≥50%of the lesion [N=13]). The primary outcome measure was loss of ≥3 lines of visual a cu ity. Secondary outcome measures were angiographic response and side effects. At baseline, patient and ocular characteristics were similar between treatment grou ps. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost ≥3 lines of visual acuity (P=. 04; stratified χ2 test). At 12 months, 13 radia ted eyes (42%) and 9 observed eyes (49%) lost ≥3 visual acuity lines (P=.60). The radiated group demonstrated smaller lesions and less fibrosis than the nonr adiated group (P=.05 and. 004, respectively) at 12 months. Radiation induced co mplications were not observed except for one radiated eye with numerous cotton w ool spots and possible radiation retinopathy. External beam radiation at 5×4 Gy may have a modest and short lived (six month) benefit in preserving visual acui ty.
文摘Objectives. Invasive cervical cancer that is discovered only after si mple hyst erectomy remains a problem. Little is known about the best management of this gr oup since there are no relevant outcome studies. This study aimed to quantify th e benefits of guideline-based treatment by comparing outcome data in patients t reated by inappropriate simple hysterectomy and adjuvant radiotherapy with data in patients treated with primary radical surgery, radiotherapy, or radiochemothe rapy. Methods. Records of 288 patients who had undergone radical hysterectomy wi th pelvic lymphadenectomy or simple hysterectomy were extracted and divided into three groups -radical hysterectomy alone (n = 89), radical hysterectomy and ad juvant radiotherapy (n = 119), and simple hysterectomy with adjuvant radiotherap y (n = 80). Disease-free and overall survival were calculated using Kaplan-Mei er analyses. Results. There was a trend towards better overall survival in the r adical hysterectomy group. Disease-free survival was significantly better in pa tients treated by radical hysterectomy, followed by simple hysterectomy plus rad iotherapy, and then radical hysterectomy plus radiotherapy (PlogrankDFS < 0.002) . When the two radical surgery groups were combined and compared with the subopt imally treated group, no significant differences were seen for overall survival. Conclusion. Postoperative radiotherapy is a good treatment for patients with ce rvical cancer who have undergone suboptimal simple hysterectomy. Appropriate sel ection criteria for further surgery remain to be defined.
