First Prospective Multicenter Italian Study on the Impact of the 21-Gene Recurrence Score in Adjuvant Clinical Decisions for Patients with ER Positive/HER2 Negative Breast Cancer.

BACKGROUND: The Breast DX Italy prospective study evaluated the impact of the 21-gene recurrence score (RS) result on adjuvant treatment decisions for patients with early breast cancer. MATERIALS AND METHODS: Nine centers (two Hub and seven Spoke centers of the Veneto Oncology Network) participated. Consecutive patients with estrogen receptor positive, human epidermal growth receptor negative, T1-T3, N0-N1 early breast cancer were prospectively registered; only those meeting protocol-defined clinicopathological "intermediate risk" criteria were eligible for the RS test. Pre-RS and post-RS physicians' treatment recommendations and treatment actually received were collected. RESULTS: A total of n = 124 N0 and n = 126 N1 patients underwent the RS assay. The majority had Grade 2 tumors (71%); median age was 55 years, median tumor size was 16 mm, and median Ki67 expression was 20%. Patients enrolled at Hub centers presented higher-risk features. The distribution of RS results was <18 (60.8%), 18-30 (32.4%), and >30 (6.8%). The indication before RS was hormonal therapy (HT) alone in 52% of cases. An indication before RS of chemotherapy (CT)+HT was more frequent for patients with N1 versus N0 tumors (57% vs. 39%, p = .0035) and for patients enrolled at Hub versus Spoke centers (54% vs. 36%, p = .007).The overall rate of change in treatment decision was 16% (n = 40), mostly from CT+HT to HT (n = 30). According to nodal status, rate of change in treatment decision was 12% for the N0 cohort and 20% for the N1 cohort. The proportion of patients recommended to CT+HT was significantly reduced from before to after RS (48% to 40%, p < .0016), especially in the N1 cohort (57% to 45%, p = .0027) and at Hub centers (54% to 44%, p = .001). CONCLUSION: Despite frequent indication of HT before RS, the use of the RS assay further contributed to sparing CT, especially for patients with N1 tumors and at Hub centers. IMPLICATIONS FOR PRACTICE: This study shows that, although a high proportion of patients were recommended to receive endocrine treatment alone before knowing the recurrence score (RS) assay, the RS test further contributed in sparing chemotherapy for some of these patients, especially in case of the N1 stage or for patients enrolled at referral centers. These data highlight the need for further work in collaboration with health authorities and companies in order to define strategies for the implementation of the use of RS testing in clinical practice in the Italian setting.

A multidisciplinary expert opinion on CINV and RINV, unmet needs and practical real-life approaches.

Introduction: A range of combination chemotherapy regimens are currently used in clinical practice. However, international antiemetic guidelines often only categorize the emetogenic potential of single agents rather than the emetogenicity of combination chemotherapy regimens. To manage the nausea and vomiting induced by antineoplastic combinations, guidelines suggest antiemetics that are appropriate for the component drug with the highest emetogenic potential. Furthermore, antiemetic guidelines generally do not consider the influence of other factors, including individual patient characteristics, on the emetic effects of cancer treatments. Similarly, the emetogenic potential of radiotherapy is stratified only according to the site of radiation, while other factors contributing to emetic risk are overlooked.Areas covered: An Expert Panel was convened to examine unresolved issues and summarize the current clinical research on managing nausea and vomiting associated with combination chemotherapy and radiotherapy.Expert opinion: The panel identified the incidence of nausea and vomiting induced by multi-drug combination therapies currently used to treat cancer at different anatomic sites and by radiotherapy in the presence of other risk factors. Based on these data and the clinical experience of panel members, several suggestions are made for a practical approach to prevent or manage nausea and vomiting due to chemotherapy regimens and radiation therapy.

Hemorrhagic peritoneal carcinomatosis treated with a weekly schedule of carboplatin and paclitaxel. A case report.

Ovarian carcinomas are chemosensitive tumors. Chemotherapy plays a pivotal role also in advanced disease, and the response to chemotherapy appears to be predictive of prolonged survival. Only performance status seems to limit therapy administration and affect patient survival. Here we report on a 66-year-old patient with a clinical status heavily compromised by peritoneal carcinomatosis associated with bloody effusion, which required increasingly frequent paracentesis and transfusions. The clinical conditions worsened under carboplatin monochemotherapy. A further attempt with carboplatin and paclitaxel in a weekly schedule resulted in a clinical response in terms of reduced need for paracentesis and blood support and improved performance status. This case confirms that treatment is the only chance to improve clinical status even in patients with very advanced ovarian cancer and an extensive tumor load. In our opinion, the modified schedule adopted in the case presented here may be worthwhile for future phase II studies in a selected patient population.

Neoadjuvant strategies for pancreatic cancer.

Pancreatic cancer (PC) is the fourth cause of cancer death in Western countries, the only chance for long term survival is an R0 surgical resection that is feasible in about 10%-20% of all cases. Five years cumulative survival is less than 5% and rises to 25% for radically resected patients. About 40% has locally advanced in PC either borderline resectable (BRPC) or unresectable locally advanced (LAPC). Since LAPC and BRPC have been recognized as a particular form of PC neoadjuvant therapy (NT) has increasingly became a valid treatment option. The aim of NT is to reach local control of disease but, also, it is recognized to convert about 40% of LAPC patients to R0 resectability, thus providing a significant improvement of prognosis for responding patients. Once R0 resection is achieved, survival is comparable to that of early stage PCs treated by upfront surgery. Thus it is crucial to look for a proper patient selection. Neoadjuvant strategies are multiples and include neoadjuvant chemotherapy (nCT), and the association of nCT with radiotherapy (nCRT) given as either a combination of a radio sensitizing drug as gemcitabine or capecitabine or and concomitant irradiation or as upfront nCT followed by nRT associated to a radio sensitizing drug. This latter seem to be most promising as it may select patients who do not go on disease progression during initial treatment and seem to have a better prognosis. The clinical relevance of nCRT may be enhanced by the application of higher active protocols as FOLFIRINOX.

18F-FDG-PET/CT in patients with breast cancer and rising Ca 15-3 with negative conventional imaging: a multicentre study.

OBJECTIVES: Breast cancer is the second cause of death in women in Europe and North America. The mortality of this disease can be reduced with effective therapy and regular follow up to detect early recurrence. Tumor markers are sensitive in detecting recurrent or residual disease but imaging is required to customize the therapeutic option. Rising tumor markers and negative conventional imaging (US, X-mammography, CT and MR) poses a management problem. Our aim is to assess the role of 18F-FDG-PET/CT in the management of post-therapy patients with rising markers but negative conventional imaging. MATERIALS AND METHODS: In the period from January 2008 to September 2009, 89 female patients with breast cancer who developed post-therapy rising markers (serum Ca 15-3 levels=64.8±16.3 U/mL) but negative clinical examination and conventional imaging were investigated with 18F-FDG-PET/CT. RESULTS: Tumor deposits were detected in 40/89 patients in chest wall, internal mammary nodes, lungs, liver and skeleton. The mean SUVmax value calculated in these lesions was 6.6±1.7 (range 3.1-12.8). In 23/40 patients solitary small lesion were amenable to radical therapy. In 7 out of these 23 patients a complete disease remission lasting more than 1 year was observed. CONCLUSIONS: 18F-FDG-PET/CT may have a potential role in asymptomatic patients with rising markers and negative conventional imaging. Our findings agree with other studies in promoting regular investigations such as tumor markers and 18F-FDG-PET/CT rather than awaiting the developments of physical symptoms as suggested by current guidelines since the timely detection of early recurrence may have a major impact on therapy and survival.

GAVeCeLT* consensus statement on the correct use of totally implantable venous access devices for diagnostic radiology procedures.

The use of totally implantable venous access devices in radiology may be associated with complications such as occlusion of the system (because of the high density of some contrast), infection (if the port is not handled in aseptic conditions, using proper barrier protections), and mechanical complications due to the high-pressure administration of contrast by automatic injectors (so-called power injector), including extravasation of contrast media into the soft tissues, subintimal venous or myocardial injection, or serious damage to the device itself (breakage of the external connections, dislocation of the non-coring needle, or breakage of the catheter). The last problem - i.e., the damage of the device from a power injection - is not an unjustified fear, but a reality. A warning by the US Food and Drug Administration of July 2004 reports around 250 complications of this kind, referring to both port and central venous catheters and peripherally inserted central catheter systems, which occurred over a period of several years; in all cases, the damage occurred during the injection of contrast material by means of power injectors for computed tomography or magnetic resonance imaging procedures. Though the risk associated with the use of ports in radiodiagnostics is thus clear, it has been suggested that administration of the contrast material via the port may have some advantage in terms of image quality, increased comfort for the patient, and maybe more accurate reproducibility of the patient's own follow-up exams. This contention needs to be supported by evidence. Also, since many cancer patients who need frequent computed tomography studies already have totally implantable systems, it would seem reasonable to try to define how and when such systems may safely be used. The purpose of this consensus statement is to define recommendations based on the best available evidence, for the safe use of implantable ports in radiodiagnostics.

Additional value of FDG-PET/CT in management of "solitary" liver metastases: preliminary results of a prospective multicenter study.

BACKGROUND AND AIM: The most common malignancy affecting the liver is metastasis from a wide variety of tumors, particularly those of gastrointestinal origin. Successful surgical removal of a solitary liver metastasis may significantly extend survival and optimal preoperative assessment in this regard is a mandatory prerequisite for proper patient selection. The addition of positron emission tomography/computed tomography (PET/CT) to other more conventional imaging procedures (e.g., ultrasound (US), CT, and magnetic resonance) has the potential to greatly improve the selection process by the combination of high-resolution anatomy afforded by CT directly combined with the functional scintigraphic map of intra- and extrahepatic lesions depicted by 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET. In this study, we assess the additional value of PET/CT in the management strategy of patients with solitary liver metastasis from colorectal and other cancers identified by conventional imaging methods. METHODS: We evaluated 43 consecutive patients (17 males, 26 females, mean age 53 +/- 6 years) with known solitary liver metastasis. This sample consisted of 18 patients with colorectal cancer, 15 with nonsmall cell lung cancer, six with breast carcinoma, and four ovarian cancers. In addition to contrast-enhanced CT and US, all patients were studied with FDG-PET/CT before surgery. PET/CT was performed within 3 weeks of the initial diagnosis and the scans were read by two experienced radiologists/nuclear medicine specialists blinded to the clinical data. A final diagnosis was obtained at surgery in 31 patients, by fine needle biopsy in five, and long-term clinical, biochemical, and follow-up imaging in seven patients. RESULTS: In 12 out of 43 patients (28%), PET/CT resulted in restaging disease and a change in therapy. Twenty-two of 31 patients with confirmed solitary liver lesions (71%) were disease-free, eight of 31 (26%) developed a new recurrence, and one of 31 (3%) died from disease progression over a 17 +/- 6-month follow-up interval. Nine of 12 patients (75%) with multiple metastases demonstrated by FDG-PET/CT were alive with disease and three of 12 (25%) deceased due to disease progression (p < 0.01) over a 17 +/- 6-month follow-up interval. CONCLUSION: The addition of FDG-PET/CT to the routine assessment of patients with liver metastasis has a significant impact on disease staging and selection of suitable candidates for solitary liver metastasis resection and outcome.

M30 neoepitope expression in epithelial cancer: quantification of apoptosis in circulating tumor cells by CellSearch analysis.

PURPOSE: This study aimed to detect the M30 neoepitope on circulating tumor cells (CTC) as a tool for quantifying apoptotic CTC throughout disease course and treatment. EXPERIMENTAL DESIGN: An automated sample preparation and analysis platform for computing CTC (CellSearch) was integrated with a monoclonal antibody (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 (CK18) in early apoptosis. The assay was validated using cell lines and blood samples from healthy volunteers and patients with epithelial cancer. RESULTS: M30-positive CTC could be detected in >70% of CTC-positive carcinoma patients, which were free for both chemotherapy and radiologic treatments. The fraction of M30-positive CTC varied from 50% to 80%, depending on the histotype. To investigate the potential application of the M30 CTC assay for the evaluation of response in early phase trials, CTC and M30-positive CTC were enumerated in a small case series of breast cancer patients during treatment. Results indicate that changes in the balance of M30-negative/positive CTC may be used as a dynamic parameter indicating an active disease, as documented by consistent radiologic findings. CONCLUSIONS: M30 expression on CTC is detectable by immunofluorescence. The M30-integrated test has potential for monitoring dynamic changes in the quote of apoptotic CTC (in addition to CTC count) to evaluate response in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research, in which there is a pressing need for informative circulating biomarkers.