Immunohistochemical discrimination of wild-type EGFR from EGFRvIII in fixed tumour specimens using anti-EGFR mAbs ICR9 and ICR10.

BACKGROUND: The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours determined by the FDA-approved EGFR PharmDx kit (Dako) or other standard anti-EGFR antibodies and the response to the EGFR inhibitors. METHOD: In this study, we investigated the potential of our anti-EGFR monoclonal antibodies (mAbs; ICR9, ICR10, ICR16) for immunohistochemical diagnosis of wild-type EGFR and/or the type-III deletion mutant form of EGFR (EGFRvIII) in formalin-fixed, paraffin-embedded human tumour specimens. RESULTS: We found that the anti-EGFR mAb in the EGFR PharmDx kit stained both wild-type and EGFRvIII-expressing cells in formalin-fixed, paraffin-embedded sections. This pattern of EGFR immunostaining was also found with our anti-EGFR mAb ICR16. In contrast, mAbs ICR10 and ICR9 were specific for the wild-type EGFR. CONCLUSION: We conclude that mAbs ICR9 and ICR10 are ideal tools for investigating the expression patterns of wild-type EGFR protein in tumour specimens using immunohistochemistry, and to determine their prognostic significance, as well as predictive value for response to therapy with EGFR antibodies.

A phase II trial evaluating two schedules of sagopilone (ZK-EPO), a novel epothilone, in patients with platinum-resistant ovarian cancer.

BACKGROUND: Sagopilone, the first fully synthetic epothilone, has shown promising preclinical activity in tumour models. This open-label randomised phase II study investigated two infusion schedules of sagopilone in women with ovarian cancer. PATIENTS AND METHODS: Women with ovarian cancer recurring within 6 months of end of last platinum-containing treatment received sagopilone 16 mg/m(2) as a 3- or 0.5-h i.v. infusion every 21 days for up to 6 weeks. RESULTS: Sixty-three patients received sagopilone as a 3-h (n=38) or 0.5-h (n=25) infusion. There were nine confirmed tumour responses [by modified RECIST (n=8) and by Gynecologic Cancer Intergroup CA-125 criteria (n=1)] in 57 patients assessable for efficacy overall [three (13%) with 0.5-h and six (18%) with 3-h infusions]. The 0.5-h arm was closed when it failed to meet its target efficacy. Main drug-related adverse events were peripheral sensory neuropathy (73%; 16% grade 3), nausea (37%; 2% grade 3), fatigue (35%; 3% grade 3) and arthralgia (30%; 5% grade 3). Overall incidence of peripheral sensory neuropathy was similar in both treatment arms, with no grade 4 neuropathy events. No acute allergic infusion reactions were observed. CONCLUSION: Sagopilone is effective, with balanced tolerability, in patients with recurrent platinum-resistant ovarian cancer.

Variation in size and position of the planning target volume in the transverse plane owing to respiratory movement during radiotherapy to the lung.

Movement of thoracic tumours with respiration poses a real dilemma in terms of the accuracy of delivering radical radiotherapy in patients with carcinoma of the lung. Movements in the craniocaudal direction have previously been described. This technical note describes ten patients planned for radical lung radiotherapy using CT. The study assesses the maximum impact of respiration on the planning target volume in the transverse plane by comparing the planning CT appearances during quiet respiration with those during full inspiration and full expiration. The study demonstrated the potential impact of respiratory movement on the planning target volume and, hence, implications for local tumour control.

Accuracy of set-up of thoracic radiotherapy: prospective analysis of 24 patients treated with radiotherapy for lung cancer.

In thoracic radiotherapy, a number of factors hinder the use of portal films and electronic portal imaging devices for measuring field placement errors (FPEs). The aim of this study was to assess the accuracy of treatment set-up using simulator check films (SCFs) in radiotherapy for lung cancer. Prospective evaluation was performed on 24 patients. During their radiotherapy, patients returned to the simulator weekly for a minimum of four SCFs, for which the parameters from the original simulator planning film were set, positioning being achieved without fluoroscopy. A total of 96 SCFs were taken. FPEs in left-right (L-R) and superior-inferior (S-I) direction, as well as coronal rotational errors, were measured. The mean absolute FPE was 0.35 cm in the L-R axis and 0.43 cm in the S-I axis. Statistically, the FPEs in the S-I direction were greater than those in the L-R direction (p<0.001). A margin of 0.93 cm between the clinical target volume and the planning target volume would cover 95% of FPEs in the L-R direction, whilst a margin of 1.13 cm is needed for this degree of certainty in the S-I direction. Mean coronal rotational error was 1.6 degrees. Systematic errors were greater than random errors. This study demonstrated that the FPEs were within clinical tolerance (< or = 0.7 cm) in 84.9% of the measurements. The planning margins used in our clinical practice compare favourably with the FPEs in this study.

Sister Mary Joseph's Nodule as a First Manifestation of Primary Peritoneal Cancer.

Sister Mary Joseph's nodule metastasis is a rather rare finding. The primary malignancy in women is usually ovarian, endometrial, gastric, or pancreatobiliary tree cancer. We present a case of an 87-year-old patient with Sister Mary Joseph's nodule metastasis caused by a primary peritoneal malignancy. Through a literature search, we also discuss the pathophysiology, diagnostic approach, management, and prognosis of such a condition.