Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.

Orbital amyloidosis and radiotherapy: A case report and review of literature.

An 80 year-old woman was referred for a one-eyed palpebral edema. She had ptosis and oblique diplopia resistant to corticotherapy. An orbit magnetic resonance imaging showed a mass infiltrating the optic nerve, with an enhancement of the whole orbital musculature. Biopsies of the lacrimal gland were positive for immunoglobulin light chain amyloidosis. Debulking surgery is the main treatment modality for symptomatic patients with localized orbital amyloidosis. Diffuse orbital involvement may make excision difficult. We managed to treat her through radiation therapy to allow a surgical procedure, delivering 20Gy in 10 fractions. The main aim of radiation therapy was to eradicate the B cells that produced the amyloid light chain deposition. After radiation therapy, the orbital inflammatory caused by the lymphoid infiltration diminished and corticotherapy could be stopped. The surgery could be performed with excellent clinical results. At 2-year follow-up, neither tumor regrowth nor late complications were detected.

Small cell carcinoma of the esophagus: a multicentre Rare Cancer Network study.

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The aims of this retrospective study were to analyze the epidemiology, clinical characteristics, and treatment outcomes of these patients. Between 1994 and 2004, 24 patients with SCCE from several centers were reviewed for data on demographics, presenting symptoms, diagnosis, disease stage, type of treatment, and outcome. SCCE occurs in the sixth decade: median age (interquartile range [IQR]): 65 (59-69) years with a male predominance (63%). The most common complaining symptoms were rapidly progressive dysphagia (79%), weight loss (54%), and retrosternal/epigastric pain (46%). The tumor arises primarily in the middle (52%) or in the lower (35%) third of the esophagus. History of tobacco and alcohol exposure was present in 90% and 70% of case, respectively. Extensive disease was present in 13 cases (54%) at initial diagnosis. The overall median survival (IQR) was 11 (8-20) months for all 24 patients, and the 2-year overall survival was 25.1%. Four patients were alive more than 2 years after treatment. Chemotherapy increased the survival compared with symptomatic management in extensive disease (median survival [IQR]: 9.5 [6-14] vs. 6 [4-7] months, P= 0.05). In limited disease, concurrent chemo-radiotherapy was more effective than non-concurrent treatment (median survival [IQR]: 36 [14-93] vs. 11 [9-15] months, P= 0.04). Two patients were treated by surgery and chemoradiation therapy with a survival of 35 and 66 months. Chemotherapy is the cornerstone of treatment of SCCE in all stage. For limited disease SCCE, concurrent chemo-radiotherapy is the primary choice compared with sequential approach. The role of surgery was not assessable in our study.

Does adjuvant radiation therapy increase loco-regional control after optimal resection of soft-tissue sarcoma of the extremities?

Adjuvant radiotherapy (RT) is routinely recommended for most soft-tissue sarcomas (STS) of the extremities. However, its impact on local control is not clearly established after wide complete excision. We performed a retrospective analysis of patients who underwent wide resection in our institution (first or second resection in cases of incomplete surgery) and either did or did not receive adjuvant RT. All histological specimens of patients operated upon between 1975 and 1996 were carefully analysed and only patients with free tumour margins (ftm) were retained for the analysis. The histopathological classification was as follows: minimal resection (mR) (ftm<10 mm) and optimal resection (oR) (ftm >/=10 mm). There were 133 patients with a median age of 44 years (range 16-88 years). The median tumour size was 6 cm (range 1-20 cm) with 28, 44 and 28% of stage I, II and III lesions, respectively. 93 patients (70%) were reoperated upon and residual tumour was found in 55% of the patients (51/93). 69 patients (17 oR and 52 mR) received adjuvant RT and 64 patients did not (54 oR and 10 mR). Other patient characteristics (age, tumour size, stage, deep-seated lesion, histoprognostic grade, adjuvant chemotherapy) were similar in both the RT and no-RT groups. Median follow-up was 10 years (3-25 years). The 5- and 10-year local relapse-free survival rates were 78 and 71%, respectively. 33 patients relapsed locally: 11 in the RT group and 22 patients in the control group (P=0.01). In the univariate analysis, adjuvant RT was correlated with relapse-free survival, while tumour grade and tumour margin status were correlated with overall survival. The multivariate analysis demonstrated a favourable impact of RT and negative influence of malignant fibrous histiocytoma (MFH) on local relapse-free survival; the tumour grade was correlated with overall survival. RT had a positive influence on local control exclusively in patients with mR resection (P=0.005) and in patients with residual tumour cells after re-excision (P=0.001). RT had no influence on 5- and 10-year overall survival. The 5- and 10-year overall survival for the entire population were 77 and 67%, respectively. Optimal resection seems to be the best predictive parameter for a favourable outcome in localised STS. Adjuvant RT is indicated after mR resection and for residual tumour after definitive surgery, but its role after oR resection (primary resection or no residual tumour after re-excision) should be evaluated in a prospective randomised trial.

Clinical review--breast adenoid cystic carcinoma.

OBJECTIVES: To review the published literature on the diagnosis and management of adenoid cystic carcinoma (ACC) of the breast. MATERIALS AND METHODS: Papers were identified by searching PubMed using the terms « adenoid cystic carcinoma ¼ and « breast ¼. Additional papers were identified by reviewing references of relevant articles. RESULTS: ACC of the breast is a rare tumour comprising less than 0.1% of breast malignancies. Its cellular origin in the breast remains unclear. The histological characteristics of ACC in the breast are similar to those of ACC of the salivary glands. However the prognosis of ACC of the breast is better than that of other localizations with prolonged survival. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients. CONCLUSIONS: ACC of the breast has a favourable prognosis. An accurate diagnosis and appropriate treatment are therefore important.

[What's new in the treatment of seminomas?]. / Quoi de neuf dans le traitement des séminomes ?

Pure testicular seminoma is a rare disease with an excellent prognosis. Its management is controversial. In stage I disease, several treatment options are considered. Those are radiation therapy alone, chemotherapy alone or active surveillance, which is becoming increasingly popular. For more advanced stages, treatment is based on chemotherapy with or without radiation therapy. In this article, we review thoroughly the existing literature and recent recommendations the various treatment options, their advantages and disadvantages in different stages of the disease.

Tyrosine kinase inhibitor AG1024 exerts antileukaemic effects on STI571-resistant Bcr-Abl expressing cells and decreases AKT phosphorylation.

Chronic myelogenous leukaemia (CML) is a clonal malignancy of the pluripotent haematopoietic stem cell, characterised by an uncontrolled proliferation and expansion of myeloid progenitors expressing a fusion oncogene, BCR-ABL, the molecular counterpart of the Ph1 chromosome. The tyrosine kinase (TK) activity of BCR-ABL is known to activate several major signalling pathways in malignant cells, including Ras, JAK/STAT and PI3K/Akt with evidence of proteasome-mediated degradation of other targets such as the DNA repair protein DNA-PKcs and cyclin-dependent kinases inhibitor p27. Targeting these abnormalities by blocking TK of BCR-ABL with STI571 provided a promising approach for the therapy of CML. The recent development of resistance to STI571 illustrates, however, that the use of other TK inhibitors could be of major interest for therapeutic purposes. To this end, the TK inhibitor Tyrphostin AG1024 was used to evaluate effect on regulation of BCR-ABL expression, inhibition of cell proliferation and tumour formation in vivo in human and murine BCR-ABL expressing cell lines. Tyrphostin AG1024 was shown to downregulate expression of BCR-ABL and P-Akt, and to upregulate DNA-PKcs expression. In addition, Tyrphostin AG1024 was able to inhibit cell proliferation, and delay tumour growth in vivo. Thus, AG1024 is able to interfere with three major targets of BCR-ABL in leukaemic cells. Interestingly, Tyrphostin AG1024 was also effective against cells resistant to STI571 by distinct mechanisms including Bcr-Abl mutation. Therefore, these data suggest that Tyrphostin AG1024 could represent the basis of a novel therapy for STI571 refractory CML.