Gabriele Simontacchi

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial

BACKGROUND Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. METHODS This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. FINDINGS A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). INTERPRETATION To our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile.

UTERINE SARCOMA: TWENTY-SEVEN YEARS OF EXPERIENCE

PURPOSE A correlation of treatment for uterine sarcoma with outcome, prognostic importance of pathology, and clinical parameters. PATIENTS AND METHODS One hundred forty-one patients (median age: 56 years, range: 19-85 years) with a histologically verified uterine sarcoma were identified from a database compiled at the Royal Marsden Hospital and the University of Florence between 1974 and 2001. Seventy-two patients had leiomyosarcoma, 42 had mixed müllerian tumors, 22 had endometrial stromal sarcoma, 1 hemangiopericytoma, 1 rhabdomyosarcoma, and 3 patients had unspecified sarcoma. According to FIGO classification, Stage I, II, III, and IV tumors were identified in 71, 13, 31, and 26 patients, respectively. RESULTS At the time of analysis, 73.7% of patients were dead, and 26.3% were alive with a median survival of 2 years from initial diagnosis. Univariate analysis for cause-specific survival demonstrated statistical significance for histology (p = 0.02), grade (p = 0.003), stage (p = 0.007), and age (p = 0.02). Multivariate analysis demonstrated significant prognostic values for stage (p = 0.02) and histology (p = 0.05) only. Postoperative radiotherapy with a total dose higher than 50 Gy seems to be significant (p = 0.001) in reducing local recurrence. CONCLUSIONS Our data favor treatment for Stages I, II, and III of uterine sarcoma with radical surgery plus radical dose irradiation comprising both external beam radiotherapy and brachytherapy.

Accelerated Partial Breast Irradiation With IMRT: New Technical Approach and Interim Analysis of Acute Toxicity in a Phase III Randomized Clinical Trial

PURPOSE To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity. METHODS AND MATERIALS From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations. RESULTS In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm(3) and the mean planning target volume was 123 cm(3). The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results. CONCLUSION In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity.

Stereotactic Radiotherapy for Adrenal Gland Metastases: University of Florence Experience

PURPOSE To evaluate a retrospective single-institution outcome after hypofractionated stereotactic body radiotherapy (SBRT) for adrenal metastases. METHODS AND MATERIALS Between February 2002 and December 2009, we treated 48 patients with SBRT for adrenal metastases. The median age of the patient population was 62.7 years (range, 43-77 years). In the majority of patients, the prescription dose was 36 Gy in 3 fractions (70% isodose, 17.14 Gy per fraction at the isocenter). Eight patients were treated with single-fraction stereotactic radiosurgery and forty patients with multi-fraction stereotactic radiotherapy. RESULTS Overall, the series of patients was followed up for a median of 16.2 months (range, 3-63 months). At the time of analysis, 20 patients were alive and 28 patients were dead. The 1- and 2-year actuarial overall survival rates were 39.7% and 14.5%, respectively. We recorded 48 distant failures and 2 local failures, with a median interval to local failure of 4.9 months. The actuarial 1-year disease control rate was 9%; the actuarial 1- and 2-year local control rate was 90%. CONCLUSION Our retrospective study indicated that SBRT for the treatment of adrenal metastases represents a safe and effective option with a control rate of 90% at 2 years.

Organs at risk in the brain and their dose-constraints in adults and in children: A radiation oncologist’s guide for delineation in everyday practice

PURPOSE Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. METHODS Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. RESULTS A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. CONCLUSIONS This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors.

OUTCOME AFTER CONSERVATIVE SURGERY AND BREAST IRRADIATION IN 5,717 PATIENTS WITH BREAST CANCER: IMPLICATIONS FOR SUPRACLAVICULAR NODAL IRRADIATION

PURPOSE To evaluate the outcome and predictive factors of patients who underwent breast-conserving surgery and adjuvant radiotherapy to the whole breast only, without supraclavicular nodal irradiation. METHODS AND MATERIALS A total of 5,717 patients with pT1-T4 breast cancer were treated at the University of Florence. The median age of the patient population was 55 years (range, 30-80 years). All patients were followed for a median of 6.8 years (range, 1-27 years). Adjuvant chemotherapy was recommended in 1,535 patients (26.9%). Tamoxifen was prescribed in 2,951 patients (51.6%). The patients were split into three groups according to number of positive axillary nodes (PAN): P1, negative axillary lymph nodes; P2, one to three PAN; P3, more than three PAN. RESULTS The P3 patients had a higher incidence of supraclavicular fossa recurrence (SFR) compared with P2 and P1 patients. However, the incidence of SFR in P3 patients was low (only 5.5%), whereas the incidence of distant metastases (DM) was 27.2%. Distant metastasis was the only independent prognostic factor for breast cancer survival. Additionally, in the subgroup of patients who developed local recurrence, DM was the most important death predictor. CONCLUSION Our series suggests that isolated SFR in patients who did not receive supraclavicular radiotherapy is infrequent, as well as in those patients who have more than three PAN, and SFR seems not to influence the outcome, which depends on DM occurrence.

Loco regional failure pattern after lumpectomy and breast irradiation in 4185 patients with T1 and T2 breast cancer. Implications for nodal irradiation

The aim of this study is to determinate incidence and risk factors for loco regional failure (LRR) (breast, supraclavicular, axillary and internal mammary nodes) and indications for nodal irradiation. From January 1980 to December 2001, 4185 patients with T1–T2 breast cancer were treated with conservative surgery and whole breast radiotherapy without nodal irradiation at the University of Florence. The median age was 55 years (range 19–86). All patients were followed for a median of eight years (range 3 months to 20 years). Multivariate analysis showed as independent prognostic factors for isolated nodal relapse (NR) the presence of more than three positive lymph nodes (PAN) (p = 0.001), angiolymphatic invasion (p = 0.002) and pT2 (p = 0.02). However, only 4.8% of patients with more than three PAN developed NR as the only site of recurrence. Having one to three PAN was not associated with an increased risk of NR. We believe that it is not necessary to prescribe nodal irradiation to patients with negative or one to three PAN. Regarding patients with more than three PAN, the number of isolated NR is also small to routinely justify a node irradiation.

Breast Cancer in the Elderly: Treatment of 1500 Patients

Abstract:  There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This studys goal was to evaluate disease‐specific survival and local‐regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1–87.3 years).The median follow‐up was 8.7 years (range 1–30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan–Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease‐specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease‐free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors. 

BENEFIT OF RADIATION BOOST AFTER WHOLE-BREAST RADIOTHERAPY

PURPOSE To determine whether a boost to the tumor bed after breast-conserving surgery (BCS) and radiotherapy (RT) to the whole breast affects local control and disease-free survival. METHODS AND MATERIALS A total of 1,138 patients with pT1 to pT2 breast cancer underwent adjuvant RT at the University of Florence. We analyzed only patients with a minimum follow-up of 1 year (range, 1-20 years), with negative surgical margins. The median age of the patient population was 52.0 years (+/-7.9 years). The breast cancer relapse incidence probability was estimated by the Kaplan-Meier method, and differences between patient subgroups were compared by the log rank test. Cox regression models were used to evaluate the risk of breast cancer relapse. RESULTS On univariate survival analysis, boost to the tumor bed reduced breast cancer recurrence (p < 0.0001). Age and tamoxifen also significantly reduced breast cancer relapse (p = 0.01 and p = 0.014, respectively). On multivariate analysis, the boost and the medium age (45-60 years) were found to be inversely related to breast cancer relapse (hazard ratio [HR], 0.27; 95% confidence interval [95% CI], 0.14-0.52, and HR 0.61; 95% CI, 0.37-0.99, respectively). The effect of the boost was more evident in younger patients (HR, 0.15 and 95% CI, 0.03-0.66 for patients <45 years of age; and HR, 0.31 and 95% CI, 0.13-0.71 for patients 45-60 years) on multivariate analyses stratified by age, although it was not a significant predictor in women older than 60 years. CONCLUSION Our results suggest that boost to the tumor bed reduces breast cancer relapse and is more effective in younger patients.

Predictors of Quality of Life after Radical Treatment for Prostate Cancer

Introduction: The usual treatment options for clinically localized prostate cancer carry a significant risk of lasting side effects, including urinary, bowel, and sexual dysfunction, that can alter overall the patient’s quality of life. The aim of this research is to evaluate the impact of treatment timing (age at time of treatment, follow-up duration, age at time of follow-up), pretreatment tumor characteristics (clinical stage, Gleason score, PSA), and posttreatment outcomes (hormonal status, biochemical recurrence), on health-related quality of life (HRQOL) among men who had undergone radical treatment for prostate cancer. Materials and Methods: 595 patients with prostate cancer who had undergone either radical prostatectomy or external beam radiation as primary therapy between 1988 and 2000 were selected for this retrospective, cross-sectional study. The enrolled subjects were asked to complete the Italian validated version of University of California-Los Angeles Prostate Cancer Index. Clinical parameters, hormone therapy status and posttreatment outcomes were considered to perform uni- and multivariate analyses. Results: Both uni- and multivariate analyses demonstrated that timing of radical treatment is a critical predictive factor for sexual activity. Pretreatment tumor characteristics had a significant impact on urinary function, urinary bother and sexual function. Hormone treatment exclusively influenced sexual function and sexual bother, while biochemical recurrence can also worsen urinary symptoms and urinary bother. Conclusion: Our findings suggest that treatment timing, pretreatment tumor characteristics and posttreatment outcomes may have an impact on HRQOL in patients who have undergone radical treatment for prostate cancer: all these items should be considered in order to achieve an accurate interpretation of prostate cancer treatment outcomes.