Citations

PURPOSE: Subcutaneous (SC) octreotide acetate effectively relieves the diarrhea and flushing associated with carcinoid syndrome but requires long-term multiple injections daily. A microencapsulated long-acting formulation (LAR) of octreotide acetate has been developed for once-monthly intramuscular dosing. PATIENTS AND METHODS: A randomized trial compared double-blinded octreotide LAR at 10, 20, and 30 mg every 4 weeks with open-label SC octreotide every 8 hours for the treatment of carcinoid syndrome. Seventy-nine patients controlled with treatment of SC octreotide 0.3 to 0.9 mg/d whose symptoms returned during a washout period and who returned for at least the week 20 evaluation constituted the efficacy-assessable population. RESULTS: Complete or partial treatment success was comparable in each of the four arms of the study (SC, 58.3%; 10 mg, 66.7%; 20 mg, 71.4%; 30 mg, 61.9%; P ≥ .72 for all pairwise comparisons). Control of stool frequency was similar in all treatment groups. Flushing episodes were best controlled in the 20-mg LAR and SC groups; the 10-mg LAR treatment was least effective in the control of flushing. Treatment was well tolerated by patients in all four groups. CONCLUSION: Once octreotide steady-state concentrations are achieved, octreotide LAR controls the symptoms of carcinoid syndrome at least as well as SC octreotide. A starting dose of 20 mg of octreotide LAR is recommended. Supplemental SC octreotide is needed for approximately 2 weeks after initiation of octreotide LAR treatment. Occasional rescue SC injections may be required for possibly 2 to 3 months until steady-state octreotide levels from the LAR formulation are achieved.

259 Background: Belinostat is a novel histone deactylase inhibitor which demonstrates preclinical activity in HCC. We report the results of a phase I/II study on belinostat in patients (pts) with unresectable HCC. Methods: Major eligibility criteria included histologically confirmed HCC not amenable to curative treatment; PS ≤ 2; adequate organ function; prior systemic therapy was allowed. In the phase I portion, belinostat was given i.v. on D1-5 every 3 weeks with dose levels of 600, 900, 1200 and 1400 mg/m2/day. In the phase II portion, belinostat was tested at the MTD. Primary endpoint was PFS and secondary endpoints were RR according to RECIST and OS. CT assessment was done every 8 weeks. Results: Phase I portion: a total of 18 pts were accrued; no DLTs were observed at 1400mg/m2/day for 5 days, and this dose was selected for phase II development. Phase II portion: 42 pts were accrued; Median age = 57.5 years; 41 had Child’s A function, and 24 pt had ECOG 0. Sixteen (38%) had previous systemic therapy, and 21 (50%) had previous transarterial therapy. Median follow-up was 20.0 months. The PR and SD rate was 2.4% (1/42) and 45.2% (19/42). Median PFS was 2.64 months (95%C.I. 1.55-3.17) and OS was 6.60 months (95%C.I. 4.53-11.60). Grade 3 or higher toxicities (>5% rate) were abdominal pain (9.5%), (9.5%) hyperbilirubinemia (9.5%), raised ALT (9.5%); anemia (7.1%) and vomiting (7.1%). Conclusions: Belinostat demonstrates disease stabilization in a predominantly pretreated population of pts with unresectable HCC with an acceptable safety profile. Further randomized studies are warranted.Supported in part by N01-CM-62205.

LBA504 Background: Limited efficacy and serious toxicities have limited uptake of tamoxifen or raloxifene as preventatives of breast cancer. Aromatase inhibitors (AIs) prevent contralateral breast cancers more than tamoxifen in adjuvant trials and have fewer serious side effects. This is the first report of an AI used in primary prevention. Methods: NCIC CTG MAP.3 is a randomized trial designed to detect a 65% reduction in annual incidence of invasive breast cancer (IBC) on exemestane (E) versus placebo (P). Eligible postmenopausal women had ≥ one of the following risk factors: Gail score >1.66%, prior ADH, ALH, LCIS or DCIS with mastectomy, age over 60. Health-related and menopause-specific quality of life (QOL) were assessed by SF-36 and MENQOL questionnaires. Results: From 2004-2010, 4,560 women were randomized: age 62.5 yrs (37-90); Gail Score 2.3 % (0.6-21); BMI 28.0 kg/m2 (15.9-65.4). Risk factors included: age >60 yrs (49%); Gail score >1.66 (40%); and prior ADH, ALH, LCIS or DCIS with mastectomy (11%). At median follow-up of 35 months there were 11 IBCs on E and 32 on P (annual incidence 0.19% vs 0.55%; HR= 0.35, 95% CI 0.18-0.70, p = 0.002); ductal (10E/27P), lobular (1E/5P). Most tumors were ER positive (7E/27P); Her2/neu negative (10E/26P); TNM stage T1 (8E/28P), N0 (7E/22P), M0 (11E/30P). E was superior in all subgroups: by Gail score, age, BMI, prior LCIS and DCIS. The annual incidence rate of IBC or DCIS was 0.35% E and 0.77% P (HR=0.47;95% CI 0.27-0.79; p = 0.004) based on 64 IBCs or DCISs (20E/44P). Clinical bone fractures, osteoporosis, hypercholesterolemia or cardiovascular events were equal in both arms. No clinically meaningful differences in QOL were detected. Conclusions: Exemestane significantly reduced invasive and pre-invasive breast cancers in postmenopausal women at increased risk for breast cancer with no serious toxicities. Exemestane should be considered a new option for primary prevention of breast cancer. Supported by the Canadian Cancer Society; Pfizer Inc. PEG supported in part by Avon Foundation.

Merkel cell carcinoma (MCC) is a rare and biologically aggressive neuroendocrine tumour of the skin. Recent analysis of a surveillance, epidemiology and end results program has shown a statistically significant increase of 8% per year in the age-adjusted rates for MCC of the skin over the past 15 years. MCC commonly presents as a painless, rapidly growing, single red or purple cutaneous nodule. Diagnosis is often delayed until histopathological examination due to the relative rarity of the disease. MCC-specific immunohistochemical markers are available for definitive diagnosis, including anticytokeratin-20-positive stain and thyroid transcription factor-1-negative stains. Because there are no phase III trials to guide management, treatment is often tailored to the individual patient by integrating surgery, radiation and chemotherapy.

Successful dialysis access necessitates superficial arteriovenous fistula (AVF) placement to facilitate identification of anatomical landmarks for safe cannulation. Suction-assisted lipectomy (SAL) may be an alternative to traditional surgical AVF revision procedures for placing fistulas more superficially. Three patients with an average body mass index of 45.2 kg/m 2 , with inaccessible AVFs due to obesity, underwent ultrasound-guided SAL of their upper extremities. Successful cannulation was achieved within two weeks. A clinically insignificant hematoma and arm swelling occurred in one patient. SAL provides a safe and effective alternative for salvaging deep AVFs for dialysis access in the upper extremities of obese patients.

The deep inferior epigastric artery perforator flap is an option for women desiring autologous tissue breast reconstruction. If this reconstruction fails, other autologous tissue flaps, including the gluteal artery perforator and latis-simus dorsi flaps, may be used for salvage. The anterolateral thigh (ALT) flap offers adequate tissue volume for breast reconstruction, acceptable fat quality and a long vascular pedicle. Other advantages include obviating the need for intraoperative position changes and harvesting tissue outside of the radiation field. Two cases involving ALT flaps used in the setting of deep inferior epigastric artery perforator failure are presented with favourable results. A review of the anatomy of the ALT flap is included.

Abstract Aims The presence of cancer can complicate treatment choices for patients with atrial fibrillation (AF) increasing both the risk of thrombotic and bleeding events. Methods and results Using data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we aimed to characterize AF patients with cancer, to describe their management and to assess the association between cancer and cardiovascular (CV) outcomes. Among 9749 patients, 23.8% had history of cancer (57% solid malignancy, 1.3% leukaemia, 3.3% lymphoma, 40% other type, and 2.2% metastatic cancer). Patients with history of cancer were older, more likely to have CV disease, CV risk factors, and prior gastrointestinal bleeding. No difference in antiarrhythmic and antithrombotic therapy was observed between those with and without cancer. Patients with history of cancer had a significantly higher risk of death (7.8 vs. 4.9 deaths per 100 patient-years follow-up, P = 0.0003) mainly driven by non-CV death (4.2 vs. 2.4 per 100 patient-years follow-up; P = 0.0004) and higher risk of major bleeding (5.1 vs. 3.5 per 100 patient-years follow-up; P = 0.02) compared with non-cancer patients; no differences were observed in risks of strokes/non-central nervous system embolism (1.96 vs. 1.48, P = 0.74) and CV death (2.89 vs. 2.07, P = 0.35) between the two groups. Conclusion A history of cancer is common among AF patients with up to one in four patients having both. Antithrombotic therapy, rates of cerebrovascular accident, other thrombotic events and cardiac death were similar in AF patients with or without a history of cancer. Patients with cancer, however, were at higher risk of major bleeding and non-CV death.

PurposeTo investigate the ability of slip interface imaging (SII), a recently developed magnetic resonance elastography (MRE)‐based technique, to predict the degree of meningioma–brain adhesion, using findings at surgery as the reference standard.Materials and MethodsWith Institutional Review Board approval and written informed consent, 25 patients with meningiomas >2.5 cm in maximal diameter underwent preoperative SII assessment. Intracranial shear motions were introduced using a soft, pillow‐like head driver and the resulting displacement field was acquired with an MRE pulse sequence on 3T MR scanners. The displacement data were analyzed to determine tumor–brain adhesion by assessing intensities on shear line images and raw as well as normalized octahedral shear strain (OSS) values along the interface. The SII findings of shear line images, OSS, and normalized OSS were independently and blindly correlated with surgical findings of tumor adhesion by using the Cohen's κ coefficient and chi‐squared test.ResultsNeurosurgeons categorized the surgical plane as extrapial (no adhesion) in 15 patients, mixed in four, and subpial (adhesion) in six. Both shear line images and OSS agreed with the surgical findings in 18 (72%) cases (fair agreement, κ = 0.37, 95% confidence interval [CI]: 0.05–0.69), while normalized OSS was concordant with the surgical findings in 23 (92%) cases (good agreement, κ = 0.86, 95% CI: 0.67–1). The correlation between SII predictions (shear line images, OSS, and normalized OSS) and the surgical findings were statistically significant (chi‐squared test, P = 0.02, P = 0.02, and P < 0.0001, respectively).ConclusionSII preoperatively evaluates the degree of meningioma–brain adhesion noninvasively, allowing for improved prediction of surgical risk and tumor resectability.Level of Evidence: 1Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2017;46:1007–1016.