Stereotactic radiosurgery for brain metastases from primary head and neck carcinomas: a retrospective analysis

Journal of Neuro-Oncology - Patients with head and neck malignancies commonly develop metastatic disease, yet rarely do these carcinomas metastasize to the brain. Stereotactic radiosurgery (SRS) is...     

Multidisciplinary Symposium on Head and Neck Cancer. 2 December 2005, Philadelphia, PA, USA

The Multidisciplinary Symposium on Head and Neck Cancer focused on the emerging data that underlie optimal treatment for head and neck cancers, with a particular focus on squamous cell carcinoma of the head and neck. In-depth discussions showcased the published Phase II and Phase III data on the treatment of locally advanced disease with both induction chemotherapy and concurrent chemoradiotherapy. Molecular targets of interest and relevance in this tumour type were identified, as were the agents which target these putative proteins or pathways of carcinogenesis. Preliminary results from trials incorporating molecularly-targeted agents have shown a promising role for these compounds in the management of both locally advanced and recurrent/metastatic squamous cell carcinoma of the head and neck. The Symposium brought a clear message. The management of squamous cell carcinoma of the head and neck has evolved considerably, and with the advent of newer chemotherapeutic agents and molecularly targeted therapies, this field will continue to expand over time.     

Paclitaxel, carboplatin, and concomitant radiotherapy for resected patients with high risk head and neck cancer

Many resected patients with locally advanced head and neck cancer are found on pathological assessment to have high-risk features for recurrence. We thus performed a feasibility trial of post-operative radiotherapy with paclitaxel and carboplatin in high-risk carcinoma of the head and neck. All patients were planned for 6 cycles of weekly paclitaxel (40 mg/m2) and carboplatin (AUC=1) and concomitant radiotherapy, 60 Gy in 6 weeks. The most common side effect was grade 3 and 4 mucositis in 5/6 patients and g-tube placement in 4/6 patients. Five out of 6 patients remain alive without evidence of disease at a mean time of 19 months since completion of therapy. Our pilot study treated 6 postoperative patients. Since 4 of 6 enrolled patients were unable to complete the treatment as prescribed, we conclude that this regimen is not feasible. With an 83% grade 3 or 4 mucositis rate and 67% of patients enrolled requiring feeding tube placement, this regimen is not tolerable.     

Malignant lymphoma of mucosa-associated lymphoid tissue of the lacrimal gland: case report and review of literature

Mucosa-associated lymphoid tissue (MALT) lymphomas are increasingly recognized as a distinct clinical-pathologic entity among the non-Hodgkin's lymphomas. It usually presents as a localized disease process in extranodal tissues or organs such as stomach, salivary gland, thyroid gland, and not infrequently in orbital adnexa. Radiotherapy has an important role in the management, although long-term clinical results specifically addressing localized MALT lymphomas are lacking. We report a case of localized MALT lymphoma of the lacrimal gland, with successful treatment by radiation therapy (total dose 25 Gy) with 3 years of clinical follow-up. A review of the published literature was undertaken to assess the role of radiotherapy in the treatment of this disease involving orbital tissues, specifically, the lacrimal gland. Based on previous reports of patients with orbital lymphomas (low grade) and pseudolymphomas, of which many will now be recognized as MALT lymphomas, radiotherapy has an excellent local control rate and would be the treatment of choice. However, long-term results of pathologically confirmed cases of MALT lymphomas need further study because occasional relapses at distant sites can occur.     

A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens

A new mouse Y chromosome gene, Smcy, has been isolated fromthe region encoding Spy, a spermato-genesis gene and Hya andSdma, the genes that, respectively, control the expression ofthe male specific minor histocompatibility antigen H-Y, as measuredby specific T-cell assays and the serologically detected maleantigen SDMA. Smcy is well conserved on the Y in mouse, manand even marsupials. It is expressed in all adult male tissuestested and can also be detected during mouse development fromas early as two cells. In addition, its human Y homologue, SMCY,is expressed in multiple tissues and maps to the same Yq deletioninterval as the human H-Y antigen controlling locus, HY.     

Absence of DAZ gene mutations in cases of non-obstructed azoospermia

Sequenced-tagged site (STS) analysis of the Y chromosome long arm (Yq) of azoospermic males has identified a minimum common deleted region of several hundred kilobases in approximately 13% of cases. A candidate azoospermia gene, DAZ (deleted in azoospermia), has been isolated from this region. DAZ has also been shown to be absent in severely oligozoospermic males albeit at a much lower frequency. These data, although highly suggestive, do not constitute formal proof that DAZ actually plays a role in azoospermia, as no small intragenic deletions, rearrangements or point mutations in the gene have been found. In this study we report the screening of DNA from 168 azoospermic/oligospermic males for the presence of the DAZ gene. Deletions involving DAZ were detected in five out of 43 (11.6%) azoospermic males whereas none were found in the remaining 125 oligospermic patients. We present the genomic structure of the 5' end of the DAZ gene together with its sequence analysis in 30 non-obstructed azoospermic males. No mutations in DAZ were found in any of the patients sequenced. These data provide no formal proof that DAZ is AZF. Thus the possibility is still valid that another gene(s) mapping to the deletion interval may be responsible for, or contribute to, the observed phenotypes. Alternatively, if DAZ is AZF, they suggest that the most frequent cause of gene inactivation is via large deletions possibly mobilized by Y chromosome repetitive sequences.      

Targeted therapy and promising novel agents for the treatment of advanced soft tissue sarcomas

Introduction: Soft tissue sarcomas (STS) are a rare and difficult to treat malignancy. Efforts to utilize targeted therapy have been ongoing for the last decade and have resulted in the approval of pazopanib for treatment of advanced disease. Although several other agents have been investigated, the inability to predict responses remains a limiting factor to the incorporation of these agents into treatment.

Areas covered: The authors summarize recent clinical findings from studies focused on targeted agents in STS. The authors also discuss the potential approaches and ongoing clinical trials with novel agents.

Expert opinion: A major challenge in the treatment of advanced STS remains a lack of predictive biomarkers to guide therapy and the heterogeneity of response among different histologies of sarcoma. Incorporation of predictive biomarker analysis into clinical trials is warranted. Additionally, mechanisms of treatment resistance and parallel pathways of tumor growth pose challenges in how we treat these tumors. An active area of research in STS is the use of novel combinations of agents, such as chemotherapy combined with multi-targeted agents. The potential of immune check point inhibitors is being explored in advanced STS and is hoped to further expand our treatment armamentarium.