Carla De Luca Cardillo

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.

Post-operative radiotherapy in N2 non-small cell lung cancer: A retrospective analysis of 175 patients

BACKGROUND AND PURPOSE Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated. MATERIAL AND METHODS We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT). RESULTS At a median follow-up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p=0.015; HR: 0.45; 95%CI: 0.24-0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p=0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild. CONCLUSION Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity.

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.

ACCELERATED INTENSITY-MODULATED EXTERNAL RADIOTHERAPY AS A NEW TECHNICAL APPROACH TO TREAT THE INDEX QUADRANT AFTER CONSERVING SURGERY IN EARLY BREAST CANCER: A PRELIMINARY STUDY

Purpose We present a novel technical approach to treat the index quadrant after conserving surgery in patients with early breast cancer and study its clinical feasibility. Methods and material Patients selected for the study, after breast conserving surgery with histologically verified breast carcinoma, signed a full informed consent to intensity-modulated external radiotherapy of the partial breast. Treatment was performed with the 6 MV beam from one of the Elekta Precise LINAC units installed in our Department. The prescribed dose was 30 Gy in 5 fractions in 10 days. Results Acute toxicity was minimal. No skin changes were noted during treatment or during the first 6 months after radiotherapy treatment. Conclusions Accelerated partial breast irradiation using intensity-modulated external radiotherapy is technically feasible. We think the approach will give good results in terms of local control, toxicity and quality of life, at the same time sparing resources for the patient and health care system.

Non-pegylated liposomal doxorubicin in combination with cyclophosphamide or docetaxel as first-line therapy in metastatic breast cancer: a retrospective analysis

Aims and background Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer. Methods Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria. Results The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1–2 leucopenia, alopecia, nausea and vomiting; no grade 3–4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity. Conclusions Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.

Impact of age on cytotoxic-induced ovarian failure in breast cancer treated with adjuvant chemotherapy and triptorelin

AIM This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy. PATIENTS & METHODS Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy. RESULTS Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries. CONCLUSION We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation.

Limited-stage small-cell lung cancer treated with early chemo-radiotherapy: the impact of effective chemotherapy

AIMS AND BACKGROUND Small cell lung cancer is characterized by an aggressive clinical course and a high sensitivity to both chemotherapy and radiotherapy. We present the Florence University experience in concurrent early radio-chemotherapy in patients affected by limited-stage small cell lung cancer, with particular emphasis on treatment safety, disease outcome and prognostic factors. METHODS AND STUDY DESIGN Fifty-seven patients were treated between June 2000 and February 2005. All patients underwent platinum-based chemotherapy, administered intravenously following two different regimens, for at least three cycles. Eighteen patients (31.6%) received epirubicin and ifosfamide in 3-week cycles alternating with etoposide and cisplatin, administered on day 1 to 3; 39 patients (68.4%) received etoposide and cisplatin. A total of 6 cycles were planned. Radiotherapy was administered concurrently to the first cycle of etoposide and cisplatin. RESULTS Clinical stage (P = 0.036) and number of chemotherapy courses (P = 0.009) emerged as the only significant death predictors at univariate analysis. Number of chemotherapy courses persisted as a significant death predictor also at multivariate regression analysis, with a reduced death risk for 5-6 chemotherapy cycles in comparison to 3-4 cycles (hazard ratio, 0.44). At a mean follow up of 38.5 months (standard deviation, 3.24 years; range, 6-164 months), considering the best overall tumor response achieved at any time during the whole treatment period, we obtained 32 complete responses (56.1%), 23 partial responses (40.3%) and 2 stable diseases. CONCLUSIONS Our analysis showed that concurrent early radio-chemotherapy in limited-stage small cell lung cancer treatment represents a safe and effective approach in patients. We confirmed the relevant impact on overall survival of effective chemotherapy delivery.

Vinorelbine-based chemo-radiotherapy in non-small cell lung cancer.

AIMS AND BACKGROUND Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control. METHODS AND STUDY DESIGN We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence. RESULTS A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients. CONCLUSIONS Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Safety of eribulin mesylate and concomitant radiotherapy for metastatic breast cancer: a single-center experience.

AIM This study evaluates, for the first time, the safety of eribulin in metastatic breast cancer patients concomitantly treated with palliative radiotherapy (RT). Patients & materials: A total of 17 patients were pretreated for metastatic breast cancer. Patients received eribulin mesylate and bone RT. RESULTS The most frequent grade 3 hematologic adverse events were neutropenia (56%) and anemia (20%). Mean pain score decreased from 2 (baseline) to 0.7 (end of observation). Analgesic score remained stable (1.8 vs 1.6). Bone pain scores dropped within a few weeks and remained below baseline values throughout the analysis. The overall response rate was 29%, and the clinical benefit rate was 59%. CONCLUSION Eribulin is characterized by a manageable safety profile also when combined with palliative RT.

Predictive factors for additional non-sentinel lymph node involvement in breast cancer patients with one positive sentinel node

Aim The aim of this study was to identify a subgroup of breast cancer patients in whom it is possible to avoid axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is positive. Methods A series of 292 patients treated with breast-conserving surgery or mastectomy underwent ALND after positive SLN detection. To correlate SLN metastasis with the chances of finding additional metastasis in non-SLNs we evaluated the main clinicopathological characteristics. No patients received adjuvant radiotherapy to the axillary region. Results Fifty-six patients (35.4%) with positive SLNs for macrometastases (n = 158) had additional metastases upon completion ALND compared with 7 patients (5.2%) with micrometastases in the SLN (n = 132). Cases with a higher number of positive axillary lymph nodes tended to have higher pT stage (p = 0.004). In multivariate analysis, pT was confirmed as an independent predictor of non-SLN metastases (OR = 2.40; 95% CI = 1.16-4.99). No patients with micrometastases in SLN and cancer <10 mm had additional positive non-SLNs. Conclusions Our results, in agreement with the major published studies, suggest that ALND can be avoided in selected patients without the need for additional treatment to the axillary region.