Alessia Caldara

Systemic therapies for recurrent and/or metastatic salivary gland cancers

Salivary gland carcinomas are rare cancers, comprising 1–5% of head and neck cancers. They represent a morphologically and clinically diverse group of tumors. The most commonly histopathologic types are mucoepidermoid cancer, adenoid cystic cancer and adenocarcinomas. Malignant salivary gland tumors generally present as painless, slow-growing tumors that are indistinguishable from benign tumors. Surgery is the principal treatment and is curative in early stage. Radiation therapy should be considered in most patients after surgical resection. Chemotherapy is reserved for palliative treatment of metastatic disease but results are disappointing. Recent studies have investigated the role of targeted therapies in a palliative setting. Multicentre cooperative group clinical trials are required to assess novel therapies to maximize patient resources in this uncommon tumor.

Weekly paclitaxel after first-line failure in patients with advanced non-small-cell lung cancer: everyday clinical practice in a single centre.

To assess the activity of weekly paclitaxel (wPCT) in pretreated patients with advanced non-small-cell lung cancer (aNSCLC). In 2005, we included wPCT 80 mg/m2 for 6 consecutive weeks, followed by a 2-week interval in our department’s everyday clinical practice guidelines for the second-line (or subsequent) treatment of patients with nonsquamous histologies who have previously received pemetrexed-based treatments and patients with squamous histology. In the absence of clinical evidence of disease progression, patients repeat the pretreatment staging procedures after 16 weeks (two cycles) and, in the absence of disease progression or severe toxicity, continue treatment for a maximum of four courses. Between May 2005 and December 2013, we treated 60 patients (47 in second-line and 13 in third/fourth line), who received a median of two courses (range: 1–4). The most frequent toxicity was grade 1–2 neutropaenia (five patients); only four patients experienced grade 3–4 toxicity. When used as a second-line treatment, wPCT led to a disease control rate of 36.2%, with a median progression-free survival of 3.7 months and a median overall survival of 9.0 months; when used in the third/fourth line, the disease control rate was 41.7%, the median progression-free survival was 5.0 months and the median overall survival was 10.3 months. Our data confirm that wPCT is active and well tolerated in an unselected patient population with aNSCLC and can be considered a valuable alternative to docetaxel in a second-line treatment.

Assessment of clinical outcomes and prognostic factors in patients (pts) with non-small cell lung carcinoma (NSCLC) and brain metastases (BM): Results from a single institution.

e20594Background: BM development, which is frequently observed in pts with NSCLC, is usually associated with a poor outcome. Systemic treatments and whole brain radiotherapy (WBRT) are widely used ...

Abstract P5-21-06: Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC)

BACKGROUND: IBC is a heterogeneous disease with several subtypes molecularly identified by gene expression profile. Since subtypes defined by immuhistochemistry (IHC) panel are similar although not identical to molecular subtypes, IHC may represent an easier alternative to identify them. PURPUSE: To assess the clinical outcomes of pts who received NC for IBC and the differences by IHC-related subtypes. METHODS: We retrospectively reviewed the clinical records of the pts treated with NC for stage II-III IBC from 2000 to 2013. For each pt we recorded baseline tumor size, type of NC [which consisted of anthracyclines (A) + taxanes (T) in HER2- and T + trastuzumab (H) ± A in HER2+ pts), type of surgery, pathological response (pCR defined as the absence of invasive cells in the breast and the lymph nodes regardless of DCIS). IHC subtypes were defined according to ER and PgR expression, Ki-67 level, and HER2 status: Luminal A (LA): ER and PR+, neg HER2 and Ki67 Luminal B (LB): ER and/or PR+, neg HER2 and Ki67≥14% (=30%) Luminal HER2 (LHER2): ER and/or PR+, positive HER2 and any Ki67 (=27%) HER2 positive (HER2+): neg ER and PR, positive HER2 and any Ki67 (=12%) Triple negative (TN): neg ER and PR, neg HER2 and any Ki67 (13%) Unknown subtype in 33 cases (15%) The loco-regional and distant RFS and OS were evaluated according to pCR. pCR and survival outcomes were also assessed on the basis of both pre- and post- NC Ki67 levels. RESULTS: In the consecutive series of 213 pts who received NC median age was 50 yrs (r. 25-75). The NC consisted of an A+T based regimen in HER2 negative (145 pts) and of a T+ H with A (31 pts) or without A (34 pts) in HER2+ disease. Only 14 did not receive surgery: 10 for distant metastases development and 4 because still on NC. Quadrantectomy was performed in 120 pts (60%). Among all pts, pCR was achieved in 44 pts(22%) with further 4 pts showing a RT ≤1 mm. All but 19 HER2+ pts (84) received H obtaining pCR in 38% of cases regardless chemotherapy type (A-based 35% vs Not A- 38%) The median follow-up was 45 months (range 1-166 ms). The 4y-RFS and OS were better in which achieved pCR than those did no (RFS 92 vs to 74%; p=0.0014 and OS 95 vs 78%; p=0.0074). Median Ki67 in pretreated core biopsy was 40 compared to 27% in post-NC RT. Patients with high (>30%) post-NC Ki67 levels showed significantly higher risk for disease relapse (4 y-RFS 60%; p=0.0019) and death (4y OS 71%; p=0.018) compared with patients with 15-30 Ki67 levels (4y-RFS 83 and OS 82%). CONCLUSIONS: According to literature data, pts achieving pCR after NC showed better RFS and OS compared to no pCR pts. The pCR rate was significantly higher in aggressive subtypes (HER2 and TN). In HER2 disease, pCR was achieved by using chemo + H, irrespective of A-addition. Interestingly high pre-NC KI67 levels seem to predict the possibility obtaing pCR, while post-NC Ki67 levels seem to be of prognostic value in pts who do not receive pCR. Citation Format: Antonella Ferro, Alessia Caldara, Mariachiara Dipasquale, Chiara Trentin, Renza Triolo, Mattia Barbareschi, Daniela Bernardi, Marco Pellegrini, Daniela Cazzolli, Gabriella Berlanda, Fabio Gasperetti, Francesca Maines, Paolina Tuttobene, Orazio Caffo, Enzo Galligioni. Clinical outcomes according to pathological complete response (pCR) and proliferation index of residual tumor (RT) after neoadjuvant chemotherapy (NC) in invasive breast cancer (IBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-21-06.

P5-14-23: Clinical Outcomes of Different Subtypes Detected by Immunohistochemistry of Early Invasive Breast Cancers in a Monoinstitutional Series.

Background Early invasive breast cancer (EIBC) is an heterogeneous disease. Immunohistochemical (IHC) markers can be used to classify tumors in different biological subtypes with different clinical behavior. Purpose : The aim of our study was to evaluate survival outcomes for patients (pts) with different subtypes of EIBC as classified using four ICH markers (ER, PR, HER2 and Ki67). Methods : We evaluated data from 3403 consecutive cases of EIBC treated from 1995 to 2008 and classified as: luminal A (positive ER and PR, negative HER2 and Ki67 14%), luminal C (positive ER and/or PR, positive HER2, any Ki67), HER2+ (negative ER and PR, positive HER2, any ki67), triple negative (negative ER and PR, negative HER2, any ki67). Log-rank test and Kaplan-Meyer estimator were performed to evaluate the impact of ICH subtypes on overall survival (OS), Event Free Survival (EFS) and their correlation with other known prognostic factors such as N, G, Size, Age. Results : We identified 917 luminal A (26.9%), 1731 luminal B (50.9%), 279 (8.2%) luminal C, 183 HER2 + (5.4%) and 293 triple negative (8.6%). Median age was 61 years. Luminal A was more frequently (p Considering only Luminal subtypes, Luminal B and C were significantly associated with poor EFS vs Luminal A EIBCs in both N0 (p=0.046) and N+ pts (p Conclusions : Luminal A showed better prognosis in term of EFS and OS than other subtypes regardless other prognostic factors as clinical features (age) and tumor extent (T and N). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-23.

Radical treatment with weekly cisplatin (wCDDP) plus concurrent radiotherapy (XRT) in locally advanced cervical cancer (LACC) patients (pts): A mono-institutional experience.

e15556 Background: Platinum-based radical chemoradiation is the standard treatment for LACC (stage Ib2-IV) pts. We describe in this report the activity and tolerability concurrent wCDDP and XRT in ...

Abstract P3-10-14: The Prognostic Significance of mib-1 (according to St Gallen Criteria) in Patients (pts) with Early Invasive Breast Cancer (EIBC) and Its Relationship with other Biologic Parameters in a Monoinstitutional Series

PURPOSE: To examine interactions between mib-1 and clinical-pathological markers and their impact on outcomes. PATIENTS AND METHODS: Mib-1 was identified by immunohistochemical staining in 3402 EIBC pts treated from 1995 to 2008. Mib-1 was defined as low (15%), intermediate (16%-30%) and high (>30%) value. Correlation between mib-1 and age, tumor size (T), nodal status (N), ER, PR, HER-2, grading (G) was performed by X 2 test. Log-rank test and Cox regression model were performed to test mib-1 as prognostic factor for overall survival (OS) and Disease Free Survival (DFS) and its correlation with other known prognostic factors. RESULTS: Median mib-1 was 25%. Mib-1 was low in 1135, intermediate in 1094 and high in 1173 pts. Median age was 62 years. High mib-1 was significantly (P DFS and OS (P 40 years pts (P 25%) resulted a prognostic factor of worse outcome (P CONCLUSIONS: In our experience, Mib-1 confirms to be a significant prognostic biomarker for DFS and OS in EIBC, providing additional information besides other clinico-pathological parameters to help decision-making of treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-14.

Prognostic Value of mib-1 in Patients with Early Invasive Breast Cancer and Its Correlation with Other Biologic Parameters in a Monoinstitutional Series.

INTRODUCTION: Mib-1 is a proliferation biomarker and a prognostic factor for breast cancer as reported in several studies.PURPOSE: The aim of the present study was to examine interactions between mib-1 and other clinical-pathological markers and their impact on outcomes in early invasive breast cancer.PATIENTS AND METHODS: Mib-1 was identified by immunohistochemical staining in 2660 EIBC patients treated in our institution from 2000 to 2008. Mib-1 was dichotomized at the value of 20%. Correlation between mib-1 (> or ≤10620%) and age, tumour size (T), nodal status (N), ER, PR, HER-2, grading (G) was performed by χ 2 test. Log-rank test and Cox regression model were performed to test mib-1 as prognostic factor for overall survival (OS) and Disease Free Survival (DFS) and evaluate its correlation with other known prognostic factors.RESULTS: Mib-1 was > 20% in 1276 and ≤106 20% in 1384. Mib-1> 20% was significantly (p=.000) associated with younger age, greater size, positive lymph nodes, poor grading, absent or low ER and/or PR expression level, HER-2 over-expression or amplification with or without co-expression of ER and/or PR, triple negative subtypes. Mib-1 was a significant predictor of worse DFS and OS (p=.000). At a median follow up of 32 months the DFS and OS were 97.4 and 99.2% respectively in Mib-1 ≤20% group and 92.4 and 97.2% respectively in Mib-1 > 20%. There were 195 relapses (7,3%): 139 (5.2%) in Mib-1 > 20% and 56 (2.1%) in Mib-1 ≤ 20%. Breast cancer related deaths were 74 (2.8%) with 58 (2.2%) in mib-1 > 20% group and 16 (0.6%) in mib-1 ≤ 20%.Mib1 >20% was predictive of poorer prognosis in > 40 years patients, small tumors (T1), lower grading (G1 and G2), positive ER and/or PR group with high or intermediate expression, negative HER-2 tumors. However, in Cox multivariate analysis mib-1 didn9t maintain independent prognostic value.CONCLUSIONS: In our experience, Mib-1 confirms to be a significant prognostic biomarker for DFS and OS in early breast cancer. It could provide additional information beside other clinico-pathological parameters to perform the risk stratification of early breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6054.

Invasive breast carcinoma of 1 cm or smaller: risk of nodal involvement and prognosis.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #1075 Background: Screening mammography has increased the frequency of diagnosis of small (≤1 cm) invasive breast cancer (BC), for which the prognosis after locoregional therapy remains controversial. Patients and methods: We have performed a retrospective analysis of 882 patients with ≤1 cm BC and positive or negative-nodes, treated in our Institution from 1990 to 2005. Risks of axillary nodes involvement (ANI), relapse-free (RFS) and overall survival (OS) were analyzed according to: age, tumor size, histologic type and grading, ER and PgR status and MIB-1, HER-2 and p53 immuno histochemical expression. Results: Median age at diagnosis was 57 years (range: 20 - 86 years). Tumor size was: 71 Tmic (a single focus of invasive carcinoma ≤ 2 mm or up to 3 foci ≤1 mm in greatest dimensions, according to Silver and Tavassoli), 225 T1a (>2 -5 mm) and 586 T1b (>5–10 mm). ANI was found in 122 cases (13,8%): only 1 inT1mic (1,4%), 21 in T1a (9,3%) and 100 in T1b (17%). Tumor size, young age, poor differentiation and ductal histology were significantly associated with ANI (p=0.01). Local relapses were: 3 in Tmic pts(2 DCIS and 1 invasive), 13 in T1a, 22 in T1b. Distant metastases were: 1 in Tmic pts, 11 in T1a, 17 in T1b. At a median follow up of 92 months, RFS was 86,4% (Tmic: 86,8%, T1a: 86,2%; T1b: 86,2%). BC-specific mortality was 2% for T1mic, 3,3% for T1a, 3,8% for T1b accounting for an OS of 96,6%. Nodal involvement was the more relevant prognostic factor for survival, followed by young age, poor differentiation, high MIB-1 and p53. Conclusions : In pts with 1 cm or smaller Invasive Breast Carcinoma, the risk of ANI is low, but not negligible, particularly for T1b tumors. Furthermore, the prognosis of these pts is influenced by high histological grade and young age. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1075.

Gemcitabine (G) and cisplatin (C) in a modified 3-week schedule for non-small cell lung cancer (NSCLC): Impact on hematologic toxicity and dose intensity (DI)

19099 Background: The G+C combination is one of the most widely used treatments for NSCLC. Aimed to enhance DI and reduce toxicity, the original 4-week schedule has been generally modified into a 3...