Reversibility of Left Ventricle Longitudinal Strain Alterations Induced by Adjuvant Therapy in Early Breast Cancer Patients.

Left ventricular ejection fraction (LV-EF), despite its high feasibility, is not sensitive enough to detect early and subtle LV systolic dysfunction during oncologic treatments. Therefore, we used systolic global longitudinal strain (GLS) by speckle tracking echocardiography to verify whether early LV systolic dysfunction induced by adjuvant therapy in early breast cancer patients at low risk for cardiotoxicity can be reversed. Thirty patients (aged 53 ± 11 y) with no previous cardiac and oncologic disease who were receiving adjuvant trastuzumab and taxane (group HER2+, n = 15) or taxane only (group HER2-, n = 15), after treatment with anthracyclines, were studied. LV-EF and GLS were measured at baseline, after anthracyclines (end of week 7 or 8), short term after trastuzumab and/or taxane (end of week 18) and after completion of therapy. Significant LV systolic dysfunction was defined as a relative reduction in GLS of >10% with respect to baseline values. Mean and individual LV-EFs did not change significantly during the oncologic treatment and after completion of therapy, although GLS varied significantly. In particular, during the course of therapy, four patients in the trastuzumab-docetaxel HER2+ subgroup and two patients in the taxane HER2- subgroup had a relative decrease (>10%) in GLS. However, after the end of adjuvant treatment, strain modification was fully or partially reversible. Speckle tracking echocardiography is more sensitive than LV-EF in recognizing subtle myocardial impairment during adjuvant chemotherapy. However, in patients at low risk for cardiotoxicity, these alterations may be reversible and not associated with clinically significant cardiotoxicity or late development of decreased LV-EF.

The management of skin toxicity during cetuximab treatment in advanced colorectal cancer: how much does it cost? A retrospecive economic assessment from a single-center experience.

AIMS AND BACKGROUND: Skin rash is a predictable and manageable side effect of anti-EGFR therapy such as cetuximab. The aim of this study is to estimate the costs for the foreseeable management of skin toxicity in patients treated with cetuximab in our institute in order to assess the direct medical economic impact. METHODS AND STUDY DESIGN: We retrospectively analyzed all consecutive patients with advanced colorectal cancer treated with cetuximab at our institute from June 2006 to May 2011. We evaluated the severity and mean duration of skin rash for each grade and we identified the costs for the different therapeutic interventions. Patients were treated according to the general consensus management of skin toxicity associated with cetuximab treatment. RESULTS: We evaluated 31 patients. The median follow-up was 28.95 months (range, 1.84-75.49). At last follow-up 10 patients (32.3%) were alive with metastases, 18 patients (58.1%) had died, 1 patient (3.2%) was alive without evidence of disease, and 2 patients (6.5%) were lost to follow-up. The median progression-free survival was 8.26 months and the median overall survival 32.89 months. Nineteen patients (61.3%) developed skin toxicities: 7 patients (22.6%) grade 1, 9 patients (29.0%) grade 2, 3 patients (9.7%) grade 3; no grade 4 skin toxicity was observed. The median duration of grade 1 toxicity was 79 days (no specific treatments were started), of grade 2 toxicity 95 days (cost range, € 199.50-294.50) and of grade 3 toxicity 64 days (cost range, € 159.42-233.90). CONCLUSIONS: Our experience, through the analysis of nonselected cases, showed that the management of skin toxicities related to cetuximab is not so expensive. We recommend proper care of low-grade toxicities in order to reduce progression to high-grade toxicities and the resulting risk of hospitalization, which really impacts on costs.

[Oncological quality indicators and Colorectal Cancer Program: data from 2009-2010 of University Hospital in Ferrara, Italy]. / Gli standard oncologici nel Percorso Diagnostico Terapeutico Assistenziale del paziente con carcinoma del colon: dati del biennio 2009-2010 presso l'UO di Oncologia Clinica dell'AOU di Ferrara.

The aim of this study is to analyse the oncological quality indicators on our Colorectal Cancer Program, that are reflective of the scope of care, feasible to implement and supported by evidence. We compared two different populations during the same period: patients referring to our Clinical Oncology Unit coming from Regional Colorectal Cancer Screening Program and the other population that was not in any Colorectal Cancer Program. On the basis of our experience, we concluded for high-quality care for both population. Any critical point should be carefully analysed in order to implement quality of care.

Gastrointestinal stromal tumors and other malignancies: a case series.

PURPOSE: This paper aims to review the clinical and pathological features of gastrointestinal stromal tumors (GISTs) occurring with other malignancies. METHODS: A retrospective analysis has been worked out considering all consecutive patients with GISTs referred to our institution between February 2002 and June 2010. We analyzed the relationship among clinical and biological characteristics of the disease and the occurrence of second cancer. RESULTS: Twenty-four patients with GIST have been recorded: in eight cases (33.3%), a second cancer was diagnosed and was synchronous in six patients. In the subgroup of synchronous malignancy, GISTs (four of stomach and one of ileum) were discovered during surgery for other gastrointestinal cancers, whereas one case (arising in the duodenum) was diagnosed during the staging procedure for another primary cancer. In the subgroup of GISTs associated with a second cancer, median age at diagnosis was higher (69 vs. 65 years), patients were more frequently male (62.5% vs. 43.8%), GISTs were smaller (median size 3 vs. 8 cm), and spindle cell histology was less frequent (25% vs. 69.2%); all cases were CD117-positive. Other characteristics were similar in the two subgroups, with the exception of risk category, with low or very low cases higher (75% vs. 20%), even if not statistically, in the subgroup of cases associated with other cancers. CONCLUSIONS: Because of the limited number of cases, we cannot exclude an incidental relationship, but this association should be considered, especially during disease staging or surgery for other gastrointestinal cancer, when lesions in other intestinal tracts are detected. Larger studies are needed.

Association of CYP1B1 with hypersensitivity induced by taxane therapy in breast cancer patients.

Taxanes represent a group of anticancer drugs with a wide range of activity against breast cancer. Therapy side effects include haematologic toxicity (neutropenia, leucopenia), peripheral neuropathy and hypersensitivity, and demonstrate inter-individual variations. Since it is known that three genes are implicated in taxane turnover, namely ABCB1 in the transport, CYP2C8 in the metabolism and CYP1B1 in the activity, we explored the association among polymorphisms (single nucleotide polymorphisms, SNPs) in these three genes and the occurrence of taxane-induced toxicity. We studied 95 patients affected by breast cancer and under treatment with taxanes as adjuvant, metastatic or neo-adjuvant therapy. We genotyped them for SNPs in the CYP2C8 (alleles *1, *2, *3 and *4), CYP1B1 (alleles *1 and *3) and ABCB1 (1236 C>T; 2677 G>T/A; 3435 C>T) genes by real-time PCR assay. We observed a significant association between the CYP1B1*3 allele and a lower occurrence of hypersensitivity reactions to taxane treatment. We speculate that the highest production of 4-hydroxyestradiol (4-OHE2) metabolite by CYP1B1*3 allele could increase the formation of the 4-OHE2-taxane adduct and possibly inhibit taxane toxicity. We suggest that CYP1B1 might affect taxane hypersensitivity therefore representing, if confirmed in a large cohort of patients, an exploratory hypersensitivity predictive biomarker.

[Clinical postoperative surveillance of breast carcinoma]. / Sorveglianza clinica post-operatoria del carcinoma mammario.

The problem of post-surgical clinical follow-up for breast cancer patients is still open. A lot of comparative studies between intensive and minimal follow-up showed no advantage of the former vs. the latter modality. The above data have been confirmed also from sistematic revisions and from pharmaco-economic studies. The ASCO guidelines confirm the importance of clinical surveillance, together with annual mammography and pelvic examination, while no blood tests or other instrumental examinations are indicated in absence of specific symptoms. The follow-up program needs to be realized under the supervision of a specialist with specific experience in the oncologic evaluation. Concerning the patients with high risk of recurrence, there is no agreement, even if no advantage seems to exist with an intensive follow-up program in terms of quality or quantity of life. The Authors suggest that the standard follow-up program should include a thoracic X-ray picture and an abdominal USG, in order to detect early a small number (< or = 2 sites) of visceral metastases, amenable of a treatment. The above program should be realized from a multidisciplinary team (surgeon, medical oncologist, radiotherapist) gaining in terms of quality and sparing time and resources.