Search

Introduction: A range of combination chemotherapy regimens are currently used in clinical practice. However, international antiemetic guidelines often only categorize the emetogenic potential of si...

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 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 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.

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.

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.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.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 (p0.01) over a 17 +/- 6-month follow-up interval.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.

e12038 Background: The Breast-DX Italy prospective study evaluated the impact of the 21-gene RS on adjuvant treatment decisions for early BC patients. Methods: The study was conducted in 9 centers of the Veneto Region (2 hub and 7 spoke). All consecutive patients with ER+/HER2-, T1 to T3, N0 to N1 early BC who met protocol-defined clinicopathological criteria for “intermediate risk” were included. Pre-RS and post-RS physicians’ treatment recommendations and treatment actually received were collected. Results: From November 2014 to August 2016, n=124 N0 and n=126 N1 patients were enrolled (65% at hub and 35% at spoke centers). The majority had PgR+ (86%), G2 (71%) and pT1c (63%) BC. Median age was 55 yrs, median Ki67 was 20% (range 2-70%). The distribution of RS was: 30 (7%). Main factors associated with higher RS were G3 and higher ki67. The addition of chemotherapy (CT) to hormonal therapy (HT) was initially recommended for 48% of the patients (38% of N0 and 57% of N1 patients; 54% and 37% of patients enrolled at hub and spoke centers, respectively). The post-RS recommendation changed from the pre-RS recommendation for 40 patients, mostly from CT+HT to HT (n=30; n=25 with low and n=5 with intermediate RS). Change was more frequent for N1 patients (Table). Of the 72 N1 patients initially recommended to CT+HT, 28% had a post-RS indication to HT alone. The crude number of patients with pre-RS recommendation to CT significantly exceeded the number of patients who finally received it (absolute difference =31; p

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.

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. Clin Cancer Res; 16(21); 5233–43. ©2010 AACR.

e15512 Background: Several prognostic factors in mRCC have been largely described in the literature. This study was aimed to verify whether some of these factors maintain their prognostic role in a cohort of pts treated in the community setting outside clinical trials. Methods: 902 pts with mRCC treated with TT from 2007 to December 2012 in 28 Italian centres were included in the analysis. Various potential prognostic factors were correlated with overall survival (OS). Results: Median age was 60 (range 25-89), 75% of pts were males; median OS (mOS) was 24 mo. Histology was clear cell (CC), CC with sarcomatoid component, papillary, NOS, not available in 82%, 6%, 4%, 4% and 4 %, respectively. mOS in the CC subgroup was 28 vs 12.5 mo of the non CC subset (p2 in 43% of the pts. mOS of this group was 18 mo vs 31 mo of pts with ≤2 metastatic sites (p=0.0001). MSKCC risk was good in 32%, intermediate in 53% and poor in 15% of the pts. According to MSKCC risk score, mOS was 6.4, 24 and 49 mo in poor, intermediate and good subsets, respectively (p

Thirty-eight patients with histologically confirmed non-small-cell lung cancer were treated with bleomycin, vincristin, mitomycin and cisplatin (BOMP) alternated with cyclophosphamide, 4'-epidoxorubicin and procarbazine (CEP). Twenty patients were randomized to start the treatment with BOMP and 18 with CEP. Patients underwent a median of 4 cycles (range, 1-8). The overall response rate was 36% with 2 clinical complete responses. The median duration of response was 6.5 months, the median survival time was 7.5 months, and 37% of patients survived for more than one year. The comparison between the two arms of this study and between this study and a previous investigation on the effectiveness of BOMP suggests that CEP regimen added to BOMP does not significantly improve patient outcome.

The clinical toxicity of acetic acid-treated « Salmonella minnesota » R595 (Re) organisms was evaluated in 24 cancer patients. Bacteria were injected i.v. four times at increasing doses for a total of 6.5 μg. This therapeutic regimen was free of major side effects (one patient had fever higher than 38 °C and 10 patients complained of pruritus). Furthermore, this bacterial preparation which possesses a more exposed lipid A on its surface, exhibited immunomodulating capacities in that it normalized the inverted T helper/T suppressor ratio and enhanced natural killer activity in tumor patients. The mechanisms of the lower toxicity and immunomodulating activities of these bacteria compared to other lipid A preparations are discussed.

Seventy intraperitoneal administrations of doxorubicin were performed in 12 patients with malignant disease in the abdominopelvic space. Peritoneal and hematologic drug levels were measured by fluorimetric assay. A first-order decline in the peritoneal level was determined (T1/2 96 ± 18 min), with a mean drug absorption of 84 % in 4 h (range 40-96 %) and a mean ratio of a peak dialysate/peak serum level of 111 (range 12-390). Gastrointestinal toxicity was common and peritoneal phlogosis occurred twice. The doxorubicin level and the time of peritoneal exposure seem to be critical factors for major local toxicity. At a moderate concentration doxorubicin can be intraperitoneally administered, but its usefullness is probably confined to patients with minimal abdominal disease.

Four patients refractory to doxorubicin (DX) and 9 patients refractory to 4'epidoxorubicin (4'EpiDX) were treated with verapamil (VRP) (120 mg every 6 h for 3 days) plus 4'EpiDX (80 mg/m2 i.v. bolus, together with the 6th VRP administration). Three patients had partial remissions lasting 3, 3.5 and 7 months, respectively. Toxicity grading did not exceed usual levels. The study demonstrates that VRP, when added at conventional doses to 4'EpiDX, can induce objective responses in some patients refractory to anthracyclines.

Via a surgically implanted Tenckhoff catheter, 5-fluorouracil was intraperitoneally administered to patients with malignant disease confined to abdominal space. Treatment was well tolerated without local complications. Peritoneal and plasmatic drug levels were measured, showing that: 1) peritoneal drug levels declined as a first order function; 2) plasmatic levels were very close to those reported for continuous i.v. administration, but peritoneal concentrations were much higher (log 1 to 3); 3) concentration × time product had a peritoneum: plasma ratio ranging from 120 to 1350. The hypothesized role of intraperitoneal 5-fluorouracil administration and the questions still to be answered are summarized.

The variability of the drug dose actually given to cancer patients was analyzed. Three variability factors were quantitatively examined (body surface calculation, personalized dose calculation, and drug residuum in commercially available vials) and their variability was experimentally measured. A systematic reduction (mean, 7%; range, 2%–15%) and a random variability (4%–5%) of the dose given were demonstrated. These results draw attention to the role of some of the procedures of routine clinical activity in determining the amount of drug actually delivered. The analysis suggests that personalization of doses must be very accurate in both measurement and calculation and that the staff giving the drug needs to be carefully informed about the importance of drug residuum. The variability of the delivered dose can lead to the misclassification of patients in investigations on the dose-response relationship. This factor may be added to pitfalls previously reported to affect this type of retrospective analysis.

Cisplatinum may be synergistic if used in combination with other agents. This study was undertaken to investigate whether a mitomycin plus cisplatin in combination could show any promising data in colorectal cancer. The regimen did not show sufficient activity to encourage further trials.