Silvia Bertocci

Pegylated Liposomal Doxorubicin (Caelyx®) and Oral Vinorelbine in First-Line Metastatic Breast Cancer Patients Previously Treated with Anthracyclines

Abstract Doxorubicin is highly effective and widely used in breast cancer; however, its use is limited by cardiotoxicity related to its cumulative dose. In previous studies, pegylated liposomal doxorubicin (PLD) has shown an acceptable toxicity profile with minimal cardiotoxicity. Between June 2006 and October 2009, 27 metastatic breast cancer patients were treated with first-line PLD and vinorelbine at the University of Florence, Radiotherapy Unit. PLD (30 mg/m2) was administered on day 1, and oral vinorelbine (60 mg/m2) was administered on days 1 and 8 of a 4-week cycle. All patients were previously treated with anthracycline-based adjuvant chemotherapy. Median age was 52 years (range 38–69) and median time to metastasis was 78.5 months. There were no treatment interruptions or discontinuation for cardiac toxicity and no treatment-related deaths. Grade 3 hematological toxicity was observed in 18.6% of patients, and 3.7% had grade 3 non-hematological adverse events. With a median follow-up of 13.2 months (range 3–33), median response duration was 6.1 months, and median PFS was 5.3 months. The overall clinical benefit rate was 55.5%. Our experience adds to evidence supporting the activity and cardiac safety of PLD and vinorelbine in metastatic breast cancer patients previously treated with anthracycline-based adjuvant chemotherapy.

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.

Use of Doxorubicin Plus Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy for Breast Cancer

Abstract We evaluated the feasibility and incidence of hematological toxicity in a series of 39 breast cancer patients treated at our institute with doxorubicin plus cyclophos-phamide (AC) followed by docetaxel, using prophylactic G-CSF (Pegfilgrastim). We prescribed G-CSF as secondary prophylaxis during the AC regimen and as primary prophylaxis during treatment with docetaxel. for the AC treatment, we recorded 6 cases of grade III (15.3%) and one case of grade IV (2.5%) neutropenia; we found one case of Grade IV anemia. for the docetaxel regimen, we registered one case of Grade IV (2.5%) neutropenia and three cases of Grade III leukopoenia without neutropenia. No patients experienced cardiac symptoms or baseline LVEF rate decrease. All patients concluded the programmed chemotherapy. Our experience shows the safety of docetaxel in combination with anthracyclines and the efficacy of prophylaxis with G-CSF in breast cancer adjuvant chemotherapy.

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.

Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival

Aims and Background Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. Methods and Study Design A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. Results With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radiochemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). Conclusions Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

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.

Abstract P1-01-25: Predictive factors of micrometastases in the sentinel node of patients affected by invasive early breast cancer

Aim: nodal metastatic involvement is the most important prognostic indicator in breast cancer. Sentinel node biopsy led to an increase in the detection of micrometastases. The aim of our analysis was to identify predictive factors of micrometastases and macrometastases of sentinel node. Materials and Methods: between January 2000 and December 2006, 675 patients were treated with breast surgery and sentinel node evaluation at University of Florence (Florence, Italy). Estrogen receptor status, progesterone receptor status, and Ki-67 labeling index determined with the MIB1 monoclonal antibody were assessed. HER2 immunohistochemistry (IHC) expression was scored as follows: 0, no staining or faint membrane staining; 1+, faint membrane staining in >10% of tumor cells, incomplete membrane staining; 2+, weak to moderate membrane staining in >10% of tumor cells; and 3+, intense circumferential membrane staining in >10% of tumor cells. HER2 scores of 0 and 1+ were considered negative. HER2 IHC 3+ and fluorescent in situ hybridization (FISH) – amplified tumors were considered positive. All IHC 2+ tumors and indeterminate tumors were tested for gene amplification by FISH. The sentinel node was examined by hematoxylin and eosin. The patients were divided into three groups based on AJCC TNM staging: sentinel node negative (n = 601); micrometastases if tumor deposit more than 0.2 mm but Results: at the logistic regression with polytomous analyses (outcome micrometastases or macrometastases), age (p = 0.048), menopausal state (p = 0.013), breast quadrant (p = 0.005), lymph vascular invasion (p = 0.0001), post-surgical T stage (p = 0.0001), histotypes (p = 0.023), HER2 status (p = 0.02), Ki-67 proliferative index (p = 0.001) and nuclear grade (p = 0.024) were significantly correlated with sentinel node macrometastases. Sentinel node biopsy technique (cytological aspiration versus histological biopsy) was not associated with micrometastases (p = 0.89) or macrometastases (p = 0.48) occurrence. The only feature significantly associated with micrometastases in sentinel node was the lymph vascular invasion (p = 0.0001). Conclusion: the presence of micrometastases remained fairly constant over time if compared to macrometastases. In our experience the only feature significantly associated with micrometastases in sentinel node is the lymph vascular invasion. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-25.