Elisa Zanardi

Patterns of Care and Clinical Outcomes of First-Line Trastuzumab-Based Therapy in HER2-Positive Metastatic Breast Cancer Patients Relapsing After (Neo)Adjuvant Trastuzumab: An Italian Multicenter Retrospective Cohort Study

BACKGROUNDnWe evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab.nnnMATERIALS AND METHODSnA total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models.nnnRESULTSnIn the 202 trastuzumab-naïve patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p = .131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p = .370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p = .045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p = .404). Patients with a trastuzumab-free interval (TFI) <6 months, visceral involvement, and hormone receptor-negative disease showed a worse OS compared with patients with a TFI of ≥6 months (29.5 vs. 48.3 months; p = .331), nonvisceral involvement (48.0 vs. 60.3 months; p = .270), and hormone receptor-positive disease (39.8 vs. 58.6 months; p = .003), respectively.nnnCONCLUSIONnDespite the inferior median PFS, trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients.

Adjuvant Carboplatin Treatment in 115 Patients With Stage I Seminoma: Retrospective Multicenter Survey

BACKGROUNDnThe administration of carboplatin AUC 7 has become a standard adjuvant option for patients undergoing orchiectomy for stage I seminoma, in alternative to radiotherapy on retroperitoneal lymphnodes or surveillance. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial of Oliver et al, but dose ranges were not reported. Fear of toxicity may induce arbitrary dose reductions, which may potentially compromise patients outcome.nnnPATIENTS AND METHODSnWe reviewed adjuvant carboplatin administration in 115 stage I seminoma patients followed in 11 Italian medical oncology centers since 2005. Clinical and pathological data, modality of carboplatin dose calculation, dose reductions, toxicities, and relapses were recorded.nnnRESULTSnMedian age was 35 years (range, 18-65 years), adverse prognostic factors were either T ≥ 4 cm (17.4%) or rete testis invasion (28.7%), both of them (35.7%), none or unspecified (18.3%). GFR was estimated mainly by Cockroft-Gault formula (55.7%) or Jeliffe formula (26.1%), with a median of 105 mL/min (range, 75-209 mL/min). The median dose of carboplatin was 900 mg (range, 690-1535 mg). A dose reduction > 10% was applied to 14 patients. Toxicities were mild fatigue, moderate nausea/vomiting, 5.2% of grade 3 to 4 thrombocytopenia. After a median follow-up of 22.1 months, 5.2% of patients have relapsed in the retroperitoneal lymph nodes. None of the patients that relapsed were treated with reduced dose. All but one achieved complete remission with salvage chemotherapy.nnnCONCLUSIONSnAdjuvant AUC 7 carboplatin reduce relapses of stage I seminoma patients to 5.2%, with manageable toxicities. Dose reductions should be proscribed.

Relevance of HBV/HBcAb screening in lymphoma patients treated in the Rituximab era

The addition of Rituximab (anti-CD20 monoclonal antibody) to chemotherapy has dramatically increased survival of non-Hodgkin’s lymphoma (NHL) patients [1]. However, in view of the intrinsic immunosuppressive effect of this drug [2], new questions are emerging in clinical practice. Among these, the assessment and proper interpretation of HBV serological status in patients undergoing Rituximabbased chemotherapy are of special concern. This topic was the object of a recently interesting review published on your journal [3]. However, in the last few months, two other studies [4, 5] were published, which investigated the incidence of HBV in NHL patients treated with Rituximabbased regimens. In the past, only HBsAg patients were considered at risk for hepatitis reactivation when receiving conventional chemotherapy [3]. In 1991, Lok et al. [6] reported that reactivation rate in HBsAg NHL patients was only 2.7%, compared with 48% in HBsAg patients. Recently, Fukushima et al. [4] conducted a retrospective and prospective study involving NHL patients treated with chemotherapy ± Rituximab. Two out 32 (6%) of Rituximab-treated patients experienced HBV reactivation. The prevalence of HBsAg/HBcAb patients was 35% in this cohort and similar values (44%) were reported in a recent prospective study by Yeo et al. [7]. In this study the incidence of HBV reactivation was higher (25%, 5/21) and one of the patients died of hepatic failure. Besides, Pei et al. [5] reported an incidence of HBV reactivation of 4% in 95 HBsAg patients. However, due to the retrospective design An answer to this letter to the editor is available at doi: 10.1007/s12185-010-0523-y.

Impact of body mass index on the clinical outcomes of patients with HER2-positive metastatic breast cancer

BACKGROUNDnOverweight and obesity are associated with an increased risk of developing many types of cancer, including breast cancer. Moreover, increased body mass index (BMI) seems to be associated with a worse prognosis in patients with HER2-positive early breast cancer. However, little is known about the impact of BMI on the clinical outcomes of HER2-positive metastatic breast cancer (MBC).nnnMETHODSnThis was a multicenter retrospective cohort study including 329 consecutive patients with HER2-positive MBC treated with first-line trastuzumab-based regimens. BMI at the time of MBC diagnosis was collected. World Health Organization BMI categories were used: underweight <18.5, normal 18.5-24.9xa0Kg/m2, overweight 25-29.9xa0Kg/m2, and obese ≥30xa0Kg/m2. The analyses were conducted using two categories: BMIxa0<xa025.0 (normal/underweight) and BMIxa0≥xa025 (overweight/obese). Progression-free survival (PFS) and overall survival (OS) rates were estimated using Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Coxs proportional hazards model. Disease response to therapy was analyzed using univariate and multivariate logistic regression.nnnRESULTSnOverall, 176 (53.5%) patients were normal/underweight and 153 (46.5%) overweight/obese. Median PFS was 14.8 months in BMIxa0<xa025 group and 15.7 months in BMIxa0≥xa025 group (adjusted-HR 0.88; 95% CI 0.66-1.17; pxa0=xa00.387). Median OS was 58.6 months in BMIxa0<xa025 group and 52.6 in BMIxa0≥xa025 group (adjusted-HR 0.88; 95% CI 0.59-1.31; pxa0=xa00.525). Overall response rate was 71.7% and 65.9% (pxa0=xa00.296) and clinical benefit rate was 82.1% and 83.3% (pxa0=xa00.781) in BMIxa0<xa025 and BMIxa0≥xa025 groups, respectively.nnnCONCLUSIONSnBMI does not seem to be associated with clinical outcomes in HER2-positive MBC patients.

Response to trabectedin in a patient with advanced synovial sarcoma with lung metastases.

Trabectedin is an alkylating agent registered in Europe for the treatment of advanced metastatic soft-tissue sarcomas, whose activity has been documented mainly in liposarcomas or leiomyosarcomas. Here, we report the response achieved in a patient with lung metastases from synovial sarcoma. A man with a large synovial sarcoma of the axilla underwent three cycles of neoadjuvant epirubicin+ifosfamide before complete excision, followed by three additional cycles of chemotherapy and radiotherapy. After 14 months, bilateral lung metastases appeared and were first treated with a prolonged 14-day continuous infusion of high-dose ifosfamide without response, and then with second-line trabectedin. A partial radiological response was achieved; dosage was reduced to 1.1u2009mg/m2 because of mild asthenia, grade 3 neutropenia, grade 3 nausea and vomiting, and reversible transaminase elevation. After 9 months of treatment, the lung nodules progressed, the patient received sorafenib, but further progressed and died 19 months after the first appearance of lung metastases. Trabectedin was the only drug that led to a radiological response in this patient with synovial sarcoma, despite being administered at 75% of the standard dose because of dose-limiting nausea and vomiting, in line with more recent data demonstrating activity in translocated sarcomas. We believe that trabectedin represents an attractive option for the treatment of metastatic synovial sarcoma and further clinical studies are warranted.

Overexpression of Periostin in Tumor Biopsy Samples Is Associated With Prostate Cancer Phenotype and Clinical Outcome

Background: Overexpression of periostin (POSTN) is associated with prostate cancer (PCa) aggressiveness. We investigated the prognostic significance of POSTN expression in tumor biopsy samples of patients with PCa. Methods: We scored POSTN expression by immunohistochemistry analysis on 215 PCa biopsy samples using an anti–POSTN‐specific antibody. A total immunoreactive score (T‐IRS) was calculated by adding the POSTN staining scores of stromal and epithelial tumor cells. Prostate‐specific antigen (PSA) progression/recurrence‐free survival (PFS), radiographic progression/recurrence‐free survival (rPFS), and overall survival (OS) were the study end points. Results: A total of 143 patients received therapy with radical attempt, whereas 72 had locally advanced or metastatic disease and received hormone therapy alone. Median T‐IRS was 9 and 12 (range, 0‐20), respectively (P = .001). Overall, we found a weak positive correlation of T‐IRS with prebiopsy PSA levels (r = 0.166, P = .016) and Gleason score (r = 0.266, P < .000). T‐IRS ≥ 8 independently predicted for shorter PSA‐PFS and OS (hazard ratio [HR] [95% confidence interval (CI)] ≥ 8 versus < 8: 1.50 [1.06‐2.14], P = .024 and 1.92 [1.20‐3.07], P = .007, respectively). In the subgroup analysis, the association between T‐IRS and patient outcome was retained in patients who received therapy with radical attempt (HR [95% CI] ≥ 8 vs. < 8: rPFS: 2.06 [1.18‐3.58], P = .01; OS: 2.36 [1.24‐4.50], P = .009) and in those with low to intermediate Gleason scores (HR [95% CI] ≥ 8 vs. < 8: PSA‐PFS: 1.65 [1.06‐2.59], P = .028; rPFS: 2.09 [1.14‐3.87], P = .018; OS: 2.57 [1.31‐5.04], P = .006). Conclusion: POSTN T‐IRS on PCa biopsy samples independently predicted the risk of recurrence, progression, and death in patients with localized disease and in those with low to intermediate Gleason scores.

Bone Metastases from Prostate Cancer: Hormonal Therapy

The majority of patients diagnosed with prostate cancer develop bone metastases. If untreated, patients affected by bone metastases experience skeletal events, like bone fractures or spinal cord compression, which complicate the course of disease and can further shorten their life expectancy; furthermore, these events are usually associated with pain and other troublesome symptoms, which can seriously affect patients’ quality of life and become a cause of temporary or permanent disability. For these reasons, the treatment of bone metastases represents a main issue in the management of advanced prostate cancer.

May Adjuvant Therapy Play A Role for the Management of Renal Cell Carcinoma? A Review of Literature and Ongoing Trials

BACKGROUNDnRenal cell carcinoma (RCC) is responsible for 4% of all neoplasms in adults and 80% of all primary renal tumours. In the European Union, there are almost 84000 new cases and 35000 deaths each year due to RCC. In the last five decades, patients with localised RCC will develop recurrence of disease after nephrectomy in about 50% of cases. Considering the number of novel targeted therapies approved in the last years for the treatment of mRCC, there has been great interest to assess the efficacy of the same agents in the adjuvant setting.nnnOBJECTIVEnto provide a systematic review of literature on the available data to define whether adjuvant treatment plays a role in the management of RCC.nnnMETHODSnA literature search using PubMed was carried out with no date restriction up to November 2016. A computerized search of the abstracts reported at ASCO and ESMO library, and www.clinicaltrial.gov was performed in order to identify relevant unpublished studies and ongoing trials.nnnRESULTSnthe search strategy returned 908 entries: after the exclusion of 886 irrelevant publications, 22 studies were eligible for the systematic review.nnnCONCLUSIONnCurrently, there is no robust evidence for the adjuvant treatment for patients with localized RCC at high risk of recurrence post-nephrectomy and often data are conflicting. It is necessary to identify new prognostic factors that might better predict the risk of relapse after surgery. The enrolment in adjuvant trials should be encouraged for the identification of selected patients who might benefit from adjuvant treatment.

A Case of Plasmacytoid Variant of Bladder Cancer with a Single Penile Metastasis and a Complete Response to Carboplatin-Based Chemotherapy and Review of the Literature

The plasmacytoid variant of urothelial carcinoma is considered a rare variant of urothelial carcinoma, accounting for 3% of all malignant primary tumors. The histologic and morphologic features are characterized by medium-size and dyshesive tumor cells with abundant eosinophilic cytoplasm, small hyperchromatic nuclei, and frequent mitotic figures, resembling plasma cells. We describe the case of a patient who underwent radical cystectomy, bilateral lymphadenectomy, and adjuvant chemotherapy for locally advanced plasmacytoid variant of urothelial carcinoma. After metastatic spread of the disease to the penis, the patient underwent 4 cycles of a carboplatin and paclitaxel regimen, experiencing a 12-month diseasefree interval. Currently, no role for chemotherapy has been defined, given the absence of data from clinical randomized trials supporting their use. Therefore, we aimed to provide a comprehensive review of the published data focusing on the pathologic diagnosis and therapeutic management of this rare neoplasm.

Dose calculation and tolerability of adjuvant AUC 7 carboplatin in 100 patients with stage I seminoma.

374 Background: Administration of carboplatin AUC 7 has become a standard adjuvant option to be discussed with pts following orchiectomy for stage I seminoma, as alternative to radiotherapy on retroperitoneal lymphnodes or observation. The toxicity of AUC 7 carboplatin appeared manageable in the pivotal trial by Oliver et al. (Lancet, 2005), but dose ranges were not reported. Oncologists use different methods to estimate GFR and to calculate this unusually high dosage of carboplatin, and fear of toxicity may induce arbitrary dose reductions and potentially compromise the outcome. Methods: In 9 Italian centers we conducted a retrospective review focusing on adjuvant carboplatin administration to stage I seminoma pts. Modality of dose calculation, dose reductions and toxicities were recorded. Results: Since August 2006, 100 pts have been treated, median age 35 years (range 26 to 58). Adverse prognostic factors were either T >4 cm (14% of pts) or rete testis invasion (32), both (36), none or unspecified (18)...