Simona Borghesi

Second-line chemotherapy with fotemustine in temozolomide-pretreated patients with relapsing glioblastoma: a single institution experience.

To evaluate efficacy and safety of fotemustine chemotherapy in temozolomide (TMZ) pretreated adults with recurrent glioblastoma multiforme (GBM). Primary endpoint was progression-free survival at 6 months. Twenty-seven patients (median age: 56 years; median Karnofsky performance status at progression: 80) with relapsed glioblastoma multiforme underwent fotemustine as second-line chemotherapy after failure of homogeneous postoperative treatment consisting of conformal radiotherapy (60 Gy in 30 fractions) with concomitant TMZ (75 mg/m2 per day), followed by six courses of TMZ (150–200 mg/m2 for 5 days every 28 days). Patients were assigned to Radiation Therapy Oncology Group recursive partitioning analysis classes for gliomas. After MRI-proven tumor relapse or progression, all patients underwent chemotherapy with fotemustine, given intravenously 100 mg/m2 every week for 3 consecutive weeks (induction phase) and then every 3 weeks (maintenance phase). Adequate liver, renal, and bone marrow functions were required. Toxicity grading was based on the National Cancer Institutes Common Toxicity Criteria (version 2.0). Response to treatment was assessed on MacDonald criteria. According to an intention-to-treat-analysis, data on all enrolled patients were included in statistical analysis. Eight partial responses (29.6%) and five cases of stable disease (18.5%) were observed. Median time to progression was 5.7 months. Progression-free survival at 6 months was 48.15%. Median survival from the beginning of fotemustine chemotherapy was 9.1 months. Median survival from diagnosis of glioblastoma was 21.2 months. Toxicity was manageable and mainly hematological (grade 3 thrombocytopenia: three cases; grade 4 leukopenia: one case). Fotemustine has shown therapeutic efficacy as single-drug second-line chemotherapy in treatment of TMZ pretreated patients.

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.

Concurrent Cyclophosphamide, Methotrexate, and 5-Fluorouracil Chemotherapy and Radiotherapy for Early Breast Carcinoma

PURPOSE The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. PATIENTS AND METHODS We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and 5-fluorouracil 600 mg/m(2)) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. RESULTS A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). CONCLUSIONS Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.

Could Machine Learning Improve the Prediction of Pelvic Nodal Status of Prostate Cancer Patients? Preliminary Results of a Pilot Study

ABSTRACT We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48–86%, 35–91%, and 17–79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

Adjuvant Trastuzumab in Breast Cancer: Experience from the University of Florence

Abstract The objective of this study was to evaluate the efficacy and tolerability profile of sequential trastuzumab in the adjuvant treatment of non-metastatic breast cancer. We analyzed 94 patients with non-metastatic breast cancer who under went postoperative treatment between November2003 and December 2008 at the University of florence. All patients received one year of sequential trastuzumab after adjuvant chemotherapy. Cardiac monitoring in our study consisted of assessment of left ventricular ejection fraction (LVEF) by echocardiography at baseline, after the completion of chemotherapy, then every 3 months during trastuzumab treatment and every 6 months thereafter. 91.6% of patients were alive without evidence of distant or local relapse, while 8.4% developed disease recurrence. The cumulative incidence of cardiotoxicity was 14.5%. In our experience trastuzumab given postoperatively with adjuvant chemotherapy was well tolerated and produced optimal clinical results in terms of disease-free survival.

Doxorubicin and Cyclophosphamide versus Cyclophosphamide, Methotrexate, and 5-Fluorouracil as Adjuvant Chemotherapy in Breast Cancer

Abstract This study evaluated whether doxorubicin and cyclophosphamide are superior to cyclophosphamide, methotrexate and 5-fluorouracil as adjuvant chemotherapy in breast cancer patients. Between July 1976 and December 2004, 1045 breast cancer patients received adjuvant chemotherapy at the Radiotherapy Unit of the University of florence. 927 were administered i.v. CMF (cyclophosphamide 600 mg/m2, methotrexate 40mg/m2 and 5-fluorouracil 600 mg/m2 on days 1 and 8, repeated every 28 days for a total of six cycles) and 118 i.v. DC (doxorubicin 60 mg/m2and cyclophosphamide 600 mg/m2 on day 1 repeated every 21 days for a total of four cycles). All patients under-went adjuvant radiotherapy as well. The survival analysis, stratified according to treatment, did not show any significant difference in metastasis occurrence between the two groups (log rank test p=0.42). According to multivariate analysis four parameter semerged as independent prognostic factors for distant metastases in patients treated with the CMF regimen: pT (p=0.0005), number of positive axillary lymph nodes(p=<0.0001), tamoxifen use (p=0.0109) and local relapses (p=<0.0001). Only number of positive axillary lymph nodes and local relapses were significant predictors of metastases occurrence according to multivariate analysis in the DC group, 17 and p=0.028, respectively. No significant difference between the two regimens was ob-served with regards to number of involved nodes. DC and CMF produced similar out-come in breast cancer patients.

Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of Italian version in head and neck cancer patients

AimTo translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL.MethodsThe XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing.ResultsThe questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5.ConclusionA valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT.

Advantage of deep inspiration breath hold in left-sided breast cancer patients treated with 3D conformal radiotherapy.

Purpose To compare 3D-conformal radiotherapy (3D-CRT) treatment plans based on free-breathing (FB) and deep inspiration breath hold (DIBH) and investigated whether DIBH technique enables a decrease of cardiac left anterior descending coronary artery (LADCA) and lungs dose with respect to the FB. Methods Twenty-three left-sided breast cancer patients referred for breast radiotherapy were included. The planning target volume (PTV) encompassed the breast and organs at risk including heart, LADCA, lungs, and contralateral breast, which were contoured in FB and DIBH CT scans. Dose to PTV was 50 Gy in 25 fractions. Two treatment plans were generated for each patient: FB-3D-CRT and DIBH-3D-CRT. Dosimetry parameters were obtained from dose volume histograms. Data were compared using the paired-sample Wilcoxon signed rank test. Results For heart, LADCA, and left lung, a significant dose reduction was found using DIBH technique. By using DIBH, an average reduction of 25% was observed in LADCA for the volume receiving 20 Gy and of 48% considering the mean heart dose. Conclusions The DIBH technique results in a significant decrease of dose to the heart, LADCA, and left lung compared to FB.

PO-0695: Lobectomy vs Stereotactic Ablative Radiotherapy in NSCLC:a multicentric series in four centers

S325 ________________________________________________________________________________ Patients were treated consecutively in the University Hospitals of Leuven between 2005 and 2014 and their data were retrospectively retrieved. PORT MPM patients were treated with RT doses up to 64 Gy in 2-Gy fractions. PORT NSCLC were treated with RT doses up to 60 Gy in 2-Gy fractions. Non-surgical patients were treated with RT doses up to 66 Gy in 2.75 Gy sequentially with chemotherapy or up to 70 Gy in 2 Gy fractions concurrently with chemotherapy. Dyspnea scores (CTCAE 4.03) before and after RT were retrieved and delta dyspnea was calculated as the difference between the dyspnea after RT (worse at any time point) and before RT. For every patient, 2 CT scans were retrieved: 1) CT0: a free breathing planning CT scan; 2) CT3M: deep inspiration breath-hold diagnostic follow up CT scan 3-6 months after the end of RT. CT0 and CT3M were non-rigidly co-registered in MIM. Differences in Hounsfield Unit (delta HU=HU3M-HU0) were represented as the slope of the dosedependent delta HU between 0 and 20 Gy (expressed in delta HU/Gy). Primary endpoint was delta dyspnea >= 2. Univariate and multivariate logistic regression analysis were performed in order to identify significant predictors of delta dyspnea >= 2. A p-value of < 0.05 was considered statistically significant.

Adjuvant whole pelvic radiotherapy in 43 patients with uterine serous cancer: outcome and patterns of failure

AIMS AND BACKGROUND Uterine serous cancer is associated with a poor outcome and poses a therapeutic challenge. We retrospectively evaluated the experience of the Radiotherapy Department of the University of Florence. METHODS Forty-three patients with stage I-III uterine serous cancer underwent surgery with (18 patients, group 1) or without complete surgical staging (25 patients, group 2) followed by adjuvant whole pelvic radiotherapy alone or combined with vaginal brachytherapy (in 35 and 8 cases, respectively). The median dose delivered with whole pelvic radiotherapy was 50 Gy (range, 45-56) and for brachytherapy was 20 Gy (range, 20-30). RESULTS Actuarial overall survival and disease-free survival rates at 5 years were 62.5% and 61%, respectively. Local failure was observed in 17 patients (39.5%) and distant metastasis in 10 (23.2%). Nine patients had both local failure and distant metastasis, which had developed concurrently in 7 cases. Isolated abdominal failure occurred in 4 cases (9.3%). Local relapse was noted in 22.2% of patients in group 1 compared to 52% in group 2. A trend towards a better 5-year overall survival (67.2% vs 58%), disease-free survival (63% vs 59%) and local control (70% vs 59%) was observed in group 1 than group 2, although the difference between the two groups failed to reach statistical significance. CONCLUSIONS Given the patterns of failure of patients with uterine serous cancer, adjuvant whole pelvic radiotherapy may be a reasonable approach, although novel integrated strategies are needed because the results achieved remain disappointing. Adjuvant whole pelvic radiotherapy might improve overall survival, disease-free survival and local control in complete surgically staged patients, but further investigations are required.