Patterns of failure after adjuvant "sandwich" chemo-radio-chemotherapy in locally advanced (stage III-IVA) endometrial cancer.

PURPOSE: To investigate oncological outcomes and patterns of recurrence of patients undergoing adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer. METHODS: This is a multi-institutional retrospective study evaluating chart of consecutive patients undergoing chemo-radio-chemotherapy for FIGO stage III-IVA endometrial caner. RESULTS: The study population included 45 patients who had adjuvant sandwich regimen. Median age of the study population was 66 years. The majority of patients were diagnosed with endometrioid histology and with stage III disease. After a median follow-up of 35 months, 15 patients developed recurrent disease. Three-year disease-free and overall survivals was 45% and 81%, respectively. Three-years site-specific disease-free survival was 85%, 92% and 48% for local, loco-regional, and distant recurrence, respectively. All patients included in the study had nodal dissection. Nodal assessment included: sentinel node mapping, sentinel node mapping plus backup lymphadenectomy and lymphadenectomy in 15, 6 and 24 patients, respectively. The latter group included four patients detected by suspected enlarged nodes, intraoperatively. Even after the exclusion of patients with enlarged nodes, the type of nodal assessment did not impact on survival outcomes (p > 0.2). Positive peritoneal cytology was the only factor associated with an increased risk of developing (any site) recurrence and distant-specific recurrence, independently. No factor predicted for overall survival. CONCLUSION: Adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer guarantee promising local and loco-regional controls, but distant failure rate is high, thus suggesting the need for applying other systemic treatment strategies for these patients.

A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups.

BACKGROUND: Recent studies have reported improvement of outcomes (progression-free survival, overall survival, and prolongation of androgen deprivation treatment-free survival) with stereotactic body radiotherapy (SBRT) in non-small cell lung cancer and prostate cancer. The aim of this retrospective, multicenter study (MITO RT-01) was to define activity and safety of SBRT in a very large, real-world data set of patients with metastatic, persistent, and recurrent ovarian cancer (MPR-OC). MATERIALS AND METHODS: The endpoints of the study were the rate of complete response (CR) to SBRT and the 24-month actuarial local control (LC) rate on "per-lesion" basis. The secondary endpoints were acute and late toxicities and the 24-month actuarial late toxicity-free survival. Objective response rate (ORR) included CR and partial response (PR). Clinical benefit (CB) included ORR and stable disease (SD). Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) and Common Terminology Criteria for Adverse Events (CTCAE) scales, according to center policy. Logistic and Cox regression were used for the uni- and multivariate analysis of factors predicting clinical CR and actuarial outcomes. RESULTS: CR, PR, and SD were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions, giving a rate of CB of 96.4%. Patient aged ≤60 years, planning target volume (PTV) ≤18 cm3 , lymph node disease, and biologically effective dose α/ß10 > 70 Gy were associated with higher chance of CR in the multivariate analysis. With a median follow-up of 22 months (range, 3-120), the 24-month actuarial LC rate was 81.9%. Achievement of CR and total dose >25 Gy were associated with better LC rate in the multivariate analysis. Mild toxicity was experienced in 54 (20.7%) patients; of 63 side effects, 48 were grade 1, and 15 were grade 2. The 24-month late toxicity-free survival rate was 95.1%. CONCLUSIONS: This study confirms the activity and safety of SBRT in patients with MPR-OC and identifies clinical and treatment parameters able to predict CR and LC rate. IMPLICATIONS FOR PRACTICE: This study aimed to define activity and safety of stereotactic body radiotherapy (SBRT) in a very large, real life data set of patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC). Patient age <60 years, PTV <18 cm3 , lymph node disease, and biologically effective dose α/ß10 >70 Gy were associated with higher chance of complete response (CR). Achievement of CR and total dose >25 Gy were associated with better local control (LC) rate. Mild toxicity was experienced in 20.7% of patients. In conclusion, this study confirms the activity and safety of SBRT in MPR-OC patients and identifies clinical and treatment parameters able to predict CR and LC rate.

Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up.

OBJECTIVE: To assess the long-term safety of no axillary clearance in elderly patients with breast cancer and nonpalpable axillary nodes. BACKGROUND: Lymph node evaluation in elderly patients with early breast cancer and clinically negative axillary nodes is controversial. Our randomized trial with 5-year follow-up showed no breast cancer mortality advantage for axillary clearance compared with observation in older patients with T1N0 disease. METHODS: We further investigated axillary treatment in a retrospective analysis of 671 consecutive patients, aged ≥ 70 years, with operable breast cancer and a clinically clear axilla, treated between 1987 and 1992; 172 received and 499 did not receive axillary dissection; 20 mg/day tamoxifen was prescribed for at least 2 years. We used multivariable analysis to take account of the lack of randomization. RESULTS: After median follow-up of 15 years (interquartile range 14-17 years) there was no significant difference in breast cancer mortality between the axillary and no axillary clearance groups. Crude cumulative 15-year incidence of axillary disease in the no axillary dissection group was low: 5.8% overall and 3.7% for pT1 patients. CONCLUSIONS: Elderly patients with early breast cancer and clinically negative nodes did not benefit in terms of breast cancer mortality from immediate axillary dissection in this nonrandomized study. Sentinel node biopsy could also be foregone due to the very low cumulative incidence of axillary disease in this age group. Axillary dissection should be restricted to the small number of patients who later develop overt axillary disease.

Neoadjuvant chemoradiation followed by radical hysterectomy in FIGO Stage IIIB cervical cancer: feasibility, complications, and clinical outcome.

OBJECTIVE: To demonstrate the efficacy and feasibility of preoperative chemoradiation followed by radical surgery in a consecutive series of patients with stage IIIB cervical cancer. METHODS: Between October 1997 and July 2007, 39 patients with International Federation of Gynecology and Obstetrics stage IIIB cervical cancer were consecutively staged and treated at the Catholic University of Rome and Campobasso and at the National Cancer Institute of Milan. Radical surgery was performed 5 to 6 weeks after the end of the cisplatinum-based neoadjuvant chemoradiation. RESULTS: Clinical responses were observed in 35 patients (92.1%): 6 (15.8%) complete and 29 (76.3.8%) partial. Radical surgery was performed in 35 patients (89.7%). According to Chassagne classification, we observed 7 (20.0%) grade 3, 17 (48.6%) grade 2, and 28 (80%) grade 1 surgical complications. At pathological examination, 12 patients (34.3%) showed complete response, 7 patients (20.0%) had only a microscopic disease, 8 patients (22.8%) had a partial response, and the last 8 patients (22.8%) had no change in disease. We registered 11 (31.4%) operative and 4 (11.4%) early postoperative complications. Median follow-up was 33 months (range, 3-80 months). The percentages of 3-year disease-free survival and overall survival were 67.6% and 70.0%, respectively. Patients with complete response and microscopic disease showed better prognosis than patients with partial response and no change (3-year disease-free survival, 100% vs 31%; and 3-year overall survival, 100% vs 39%). CONCLUSIONS: Chemoradiation followed by radical hysterectomy could be administered in patients with stage IIIB cervical cancer with an acceptable rate of complications and with a survival outcome similar to that of chemoradiotherapy, allowing the assessment of pathological response with its implication on clinical outcomes.

Breast cancer in the elderly: the role of adjuvant radiation therapy.

PURPOSE: To evaluate available data on breast conserving surgery (BCS) with or without radiation therapy (RT), and alternative options (e.g. Tamoxifen alone) (Tam), focusing specifically on the older patients. METHODS AND MATERIALS: The MEDLINE was searched for the terms elderly, BCS, adjuvant/postoperative RT, Tamoxifen, and randomized trials from 1992 to 2002. RESULTS: Authors reviewed papers of general interest on the elderly and breast cancer (BC), meta-analysis, randomized trials on BCS+/-RT and Tam+/-surgery without RT, retrospective non-randomized trials, and reported on prognostic factors for local recurrence in BCS alone, including biomarkers, attempts made to define a low-risk group, and methods of modification of the current, protracted standard adjuvant RT course. CONCLUSIONS: Postoperative RT after BCS has a firm rationale; in current clinical practice, if the BCS+RT is medically appropriate and the patient shares the choice, after a full information of the available options and their implications, it is clinically sound to propose this approach. However, there is controversy whether a subgroup of elderly patients could be safely spared: in this setting a randomized trial is clearly warranted.