Monday, May 9, 2011
To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial.Patients and Methods
Between 1990 and 1997, 714 patients with stage IC grade 1 to 2 or IB grade 2 to 3 EC were randomly allocated to pelvic external-beam radiotherapy (EBRT) or no additional treatment (NAT). HRQL was evaluated with the Short Form 36-Item (SF-36) questionnaire; subscales from the European Organisation for Research and Treatment of Cancer (EORTC) PR25 module for bowel and bladder symptoms and the OV28 and CX24 modules for sexual symptoms; and demographic questions. Analysis was by intention-to-treat.Results
Median follow-up was 13.3 years. The 15-year actuarial locoregional recurrence rates were 5.8% for EBRT versus 15.5% for NAT (P < .001), and 15-year overall survival was 52% versus 60% (P = .14). Of the 351 patients confirmed to be alive with correct address, 246 (70%) returned the questionnaire. Patients treated with EBRT reported significant (P < .01) and clinically relevant higher rates of urinary incontinence, diarrhea, and fecal leakage leading to more limitations in daily activities. Increased symptoms were reflected by the frequent use of incontinence materials after EBRT (day and night use, 42.9% v 15.2% for NAT; P < .001). Patients treated with EBRT reported lower scores on the SF-36 scales "physical functioning" (P = .004) and 'role-physical' (P = .003).Conclusion
EBRT for endometrial cancer is associated with long-term urinary and bowel symptoms and lower physical and role-physical functioning, even 15 years after treatment. Despite its efficacy in reducing locoregional recurrence, EBRT should be avoided in patients with low- and intermediate-risk EC."
Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy.Patients and Methods
Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes.Results
One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally.Conclusion
Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally."
To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.Patients and Methods
Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m2 and gemcitabine 125 mg/m2 weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m2 on day 1, plus gemcitabine, 1,000 mg/m2 on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).Results
Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.Conclusion
Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment."
The Cancer Research UK 'Over 50s' trial compared 5 and 2 years of tamoxifen in women with early breast cancer. Results are reported after median follow-up of 10 years.Patients and Methods
Between 1987 and 1997, 3,449 patients age 50 to 81 years with operable breast cancer who had been taking 20 mg of tamoxifen for 2 years were randomly assigned to either stop or continue for an additional 3 years, if they were alive and recurrence free. Data on recurrences, new tumors, deaths, and cardiovascular events were obtained (April 2010).Results
There were 1,103 recurrences, 755 deaths as a result of breast cancer, 621 cardiovascular (CV) events, and 236 deaths as a result of CV events. Fifteen years after starting treatment, for every 100 women who received tamoxifen for 5 years, 5.8 fewer experienced recurrence, compared with those who received tamoxifen for 2 years. The risk of contralateral breast cancer was significantly reduced (hazard ratio, 0.70; 95% CI, 0.48 to 1.00). Among women age 50 to 59 years, there was a 35% reduction in CV events (P = .005) and 59% reduction in death as a result of a CV event (P = .02); in older women, the effect was much smaller and not statistically significant.Conclusion
Taking tamoxifen for the recommended 5 years reduces the risk of recurrence or contralateral breast cancer 15 years after starting treatment. It also lowers the risk of CV disease and death as a result of a CV event, particularly among those age 50 to 59 years. Women should therefore be encouraged to complete the full course. Although aromatase inhibitors improve disease-free survival, tamoxifen remains a cheap and highly effective alternative, particularly in developing countries."