An Open-Label, Multinational, Multicenter, Phase IIIb Study with Subcutaneous Administration of Trastuzumab in Patients with HER2-Positive Early Breast Cancer to Evaluate Patient Satisfaction.

OBJECTIVE: This study was designed to investigate treatment satisfaction in patients and Health Care Professionals (HCP) and to evaluate the safety and tolerability of subcutaneous (SC) trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (eBC). MATERIALS AND METHODS: Two-hundred and twenty-three patients with eBC were screened, of whom 173 patients met the eligibility criteria and received at least one dose of SC trastuzumab. The primary efficacy endpoint was to assess patient satisfaction via a questionnaire. RESULTS: The majority of patients (n = 166, 97.6%) reported satisfaction with the SC route. Patients and HCPs stated that SC trastuzumab was easy to use (93.5% and 62.5%, respectively) compared to the intravenous (IV) route and all HCPs (n = 16) expressed satisfaction with the SC route. Progression, disease recurrence or death was reported in 24 patients (13.8%) by two years of follow up. Four-year disease-free survival (DFS) and overall survival (OS) rates were 84.2% (±3.1) and 90.5% (±4.7), respectively. A total of 1299 adverse events (AEs) were recorded over 4-years follow-up, nearly 97% of which were judged non-serious. The most common AEs were arthralgia (n = 54, 4.2%), flu-like symptoms (n = 41, 3.2%) and nausea (n = 39, 3.0%). Fifty-four cardiac events, including left ventricular dysfunction, left ventricular failure and cardiotoxicity, were reported. Ejection fraction (EF) decrease [median decrease 3.5% (0.12-19.0)] was reported in 5.4% of cases. SC trastuzumab treatment was interrupted due to decreased EF in two cases. CONCLUSION: SC trastuzumab was widely acceptable to both patients and HCPs. The safety and tolerability of SC trastuzumab was consistent with the known safety profile of SC and IV administration.

A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study.

BACKGROUND: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated. METHODS: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year. RESULTS: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively. CONCLUSIONS: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study.

OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

Gastrointestinal complications after open heart surgery: incidence and determinants of risk factors.

Acute mesenteric ischemia is a rare but serious complication of open heart surgery. Between January 2009 and January 2012, 1360 adult patients underwent open heart surgery with cardiopulmonary bypass at our institution; 29 patients presented gastrointestinal complications. Eight patients developed acute mesenteric ischemia and all of them died. Significant predictors of the complication were New York Heart Association functional class III/IV, history of extensive atherosclerosis and chronic renal failure, acute renal failure following surgery, low cardiac output, use of 2 or more vasoconstrictor drugs, prolonged mechanical ventilation, and multiorgan failure. Atherosclerosis is a multisystemic disease that affects several organs. Radiologic evaluation of mesenteric arterial system should be performed in high-risk patient populations. Perioperative percutaneous and open vascular procedures will reduce the risk of acute mesenteric ischemia that may develop after cardiac surgery and consequent morbidity and mortality rates.

A case of abdominal aortic pseudoaneurysm associated with right heart mass.

We present a patient with right-sided endocarditis associated with abdominal aortic pseudo-aneurysm presenting only with high fever and pulsating abdominal mass. A higher clinical awareness of aortic pseudoaneurysms associated with intracardiac lesions disease, leading to early computed tomography evaluation and prompt surgical intervention appears to offer the best chance of survival. In this aspect, single-stage surgical treatment of both endocarditis and the aortic pathology is necessary.

Mid-term outcome with surgery for type B aortic dissections: a single center experience.

BACKGROUND: The approach to acute and chronic type B aortic dissection has changed significantly over the past years. In this aspect, we have reviewed our single-center experience in surgery for type B dissections and compared the current data presented by other centers. METHODS: Twenty-nine patients operated at our center for type B aortic dissection (14 acute, 15 chronic) were reviewed over the years between 1996 and 2004. All patient data in addition to immediate and late outcome following surgery were noted. RESULTS: The mean age in acute and chronic groups was 53 +/- 16 versus 62 +/- 12 years, respectively (p = 0.1). Hospital mortality was 4 patients. The mean period in the intensive care unit was 4.2 +/- 3.1 days. Follow-up time was 36 +/- 11 months. Median interval between the initial symptoms and surgery was 3.8 days for acute cases. No patients underwent reoperation in acute patients; whereas 3 underwent reoperation in the chronic group. False lumen patency rates in acute and chronic dissections were 16.7% versus 46% after 24 months (p< 0.05). Distal anastomoses included both true and false lumens in 83% of the chronic cases with false lumen patency. The mean reoperation-free survival was 79.35 months with standard error of 5.57 months (95% CI, 68.42 to 90.27) in all patients. CONCLUSIONS: Open surgery in acute type B dissections yielded excellent immediate and long-term durability in our series with no false lumen patency or aortic expansion. However, incorporation of both false and true lumina into distal anastomosis in patients with chronic dissection resulted in false lumen patency with aortic expansion.

Aortic arch branches are occluded: which artery nourishes the brain?

Takayasu arteritis is an inflammatory vascular disease that primarily affects the aorta and its major branches. In this report, we present a 47-year-old woman whose aortic arch branches were totally occluded and the cerebral circulation is dependent on a dilated right vertebral artery.