No Relationship Between Head And Neck Cancer Tumor Site And Location Of Swallowing Dysfunction

Over the past twenty years there has been a significant shift from surgery towards chemoradiation therapy as primary treatment for certain head and neck cancers. While primary chemoradiation allows many patients to avoid surgery and its concurring postoperative complications, it may be associated with significant post-treatment dysphagia, or difficulty in swallowing,

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which can be debilitating and potentially lethal. During treatment, radiation is typically given over a wide field which encompasses both

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the primary tumor and its associated lymphatic drainage. As a consequence, structures vital to swallowing are subjected to high doses of radiation which may result in complications such as silent aspiration and feeding tube dependence. The addition of chemotherapy to radiation provides a synergistic effect which has been shown to further improve locoregional control. While chemotherapeutic agents act as radiosensitizers and thereby increasing tumor control rates, they also result in increased acute toxicity as well as late complications secondary to collateral injury to surrounding healthy tissue. A team of scientists from Philadelphia, PA have conducted a study to identify which stages of swallow function are differentially affected by chemoradiation treatment for head and neck cancer, to describe the incidence of long term complications including clinical pneumonia and prolonged feeding tube dependence, and to correlate the clinical variables to the modified barium swallow findings. The authors of the study, “Post Chemoradiation

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Dysphagia” are Benjamin S. Bleier MD, Marc S. Levine MD, Rosemarie Mick PhD, Stephen E. Rubesin MD, Stephen Z. Sack MD, PhD, Kibwei McKinney BA, and Natasha Mirza, MD. They are presenting their findings at the 110th Annual Meeting & OTO EXPO of the American Academy of Otolaryngology-Head and Neck Surgery Foundation, being held September 17-20, 2006, at the Metro Toronto Convention Centre, Toronto, Canada.

Methodology:

A retrospective review of 30 patients treated at an academic, tertiary care referral medical center between 1996 and 2005 was conducted. All patients completed a modified barium swallow study after presenting with dysphagia following primary radiation therapy with or without concomitant chemotherapy for Stage I-IV squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, and larynx. Patients were excluded from the study if they had any prior history of radiotherapy, primary tumor resection except neck dissection, or any other head and neck lesions. None of the patients had documented dysphagia prior to radiotherapy.

Results:

Pharyngoesophagrams were analyzed for 21 separate criteria by one of three attending gastrointestinal radiologists and experienced speech-language pathologists. The most common abnormalities included laryngeal penetration, impaired epiglottic tilt, and abnormal pharyngeal contraction. The least common abnormalities included impaired cricopharyngeal opening, and soft palatal atrophy. A Fisher’s exact test was used to correlate several clinical variables to modified barium swallow findings. No significant relationship was found between pharyngoesophagram abnormalities and a history of neck dissection, tumor stage, or patient age. Duration from radiotherapy to modified barium swallow also had no significant impact on swallow findings.

Conclusions:

The research team found no significant relationship between primary tumor site and location of swallow dysfunction. The researchers did note that while patients with oral and oropharyngeal lesions demonstrated abnormalities throughout the swallowing cascade, all patients with laryngeal lesions had normal function in the oral phase of swallow. The study also demonstrated abnormal epiglottic inversion and laryngeal penetration to be the most common problems in post radiation patients who had treatment for oropharyngeal and pharyngeal malignancies. The next most frequent problem identified in the study was abnormal pharyngeal contraction. Functional disturbances in this area manifest as abnormalities in clearance of swallowed boluses from the pharynx. Weakness or incoordination in this pharyngeal contraction sequence results in portions of the bolus remaining in the pharynx at the end of the swallow. Both the oropharyngeal and laryngeal group suffered from this pharyngeal muscle hypomobility. While the relatively normal oral swallowing apparatus in patients with laryngeal lesions may relate to the use of parotid and oral cavity sparing radiotherapy techniques, further studies with larger patient populations are needed to truly understand the significance of these findings. The study also suggests that close follow up of these patients with a modified barium swallow early in the post treatment period may help identify sites of swallowing impairment. This may in turn help reduce subsequent morbidity form pneumonias and long term feeding tube dependence. American Academy of Otolaryngology Head and Neck Surgery (AAOHNS) One Prince St. Alexandria, VA 22314 United States American Academy of Otolaryngology Head and Neck Surgery

Tumor Fighters

Source – http://www.medicalnewstoday.com

Genetically Engineered Cells Can Transform Immune Cells Into Tumor Fighters In Humans

A team of researchers has genetically engineered normal immune cells to become specialized tumor fighters, demonstrating for the first time that these engineered cells can persist in the body and shrink large tumors in humans. Two of the 17 people with advanced melanoma who received the experimental treatment saw their tumors shrink and were declared clinically free of disease more than a year and half after the therapy began, Steven A. Rosenberg of the National Cancer Institute and his colleagues report in a study published online by the journal Science at the Science Express website on 31 August. Science and Science Express are published by AAAS, the nonprofit science society. So far, the therapy has only been used in this small group of melanoma patients, but Rosenberg says his team has demonstrated ways to engineer similar immune cells in the laboratory that would attack more common tumors such as breast, lung and liver cancers. The technique developed by the Science researchers “represents the first time that gene manipulations have been shown to cause tumor regression in humans,” Rosenberg says. “This work marks an important next step in harnessing the power of our immune systems to fight cancer. The publication of this paper should help highlight the significant work to a broad spectrum of people, including patients, clinicians and those involved in basic research,” said Stephen Simpson, Science’s senior editor, immunology. Rosenberg and colleagues have a long history of looking for ways to boost the body’s natural immune defenses against cancer, focusing specifically on T cells, a special type of immune cell that can recognize and attack “foreign” cells such as those found in tumors. In their earlier experiments, the researchers removed tumor-fighting T cells from melanoma patients and multiplied these cells in the laboratory. After using chemotherapy to clear out a patient’s old T cells, the researchers repopulated the patients’ immune systems with these new fighters. But some people with melanoma don’t have these

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receptor’s genetic makeup determines the antigen types that the T cell can recognize, so that some cells contain genes that make a T cell receptor that homes in on melanoma cells, while other cells contain genes that make a T cell receptor that recognizes breast or lung cancer cells. With this in mind, Rosenberg and colleagues created tumor fighters by removing normal T cells from people with advanced metastatic melanoma, genetically engineering these normal cells to carry the receptor that recognizes melanoma cells and returning these “re-armed” cells to rebuild the patients’ immune systems. “We can take normal lymphocytes from patients and convert them to tumor-reactive cells,” Rosenberg says, adding that the engineered cells could be tailored to fight tumors other than melanoma. “We’ve identified T cell receptors that will now recognize common cancers,” he notes. The newly engineered T cells showed signs of persistence in 15 of the patients in the study, making up at least 10 percent of their circulating T cells for at least two months after treatment. New T cell levels were higher in the two people whose tumors shrunk noticeably with the treatment. Rosenberg and colleagues are now searching for ways to fine-tune the treatment so that greater numbers of the engineered T cells will survive and continue expressing their new receptor genes, since their expression does seem to wane over time, the Science researchers found. Devising new ways to insert the receptor genes in the T cells, usually encoded in a retrovirus, has been one of the most challenging aspects of the treatment, Rosenberg says. “It’s a lot of sophisticated molecular biology

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and most of our work is going into designing retroviruses, putting genes into cells efficiently and getting them expressed.” ### “Cancer Regression In Patients Mediated by Transfer of Genetically Engineered Lymphocytes” by R.A. Morgan et al. Rosenberg’s co-authors are Richard A. Morgan, Mark E. Dudley, John R. Wunderlich, Marybeth S. Hughes, James C. Yang, Richard M. Sherry, Richard E. Royal, Suzanne L. Topalian, Udai S. Kammula, Nicholas P. Restifo, Zhili Zheng, Azam Nahvi, Christiaan R. de Vries, Linda J. Rogers-Freezer and Sharon A. Mavroukakis of the National Cancer Institute. The study was supported by the National Cancer Institute. The American Association for the Advancement of Science (AAAS) is the world’s largest general scientific society, and publisher of the journal, Science (www.sciencemag.org). AAAS was founded in 1848, and serves some 262 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of one million. The non-profit AAAS (www.aaas.org) is open to all and fulfills its mission to “advance science and serve society” through initiatives in science policy; international programs; science education; and more. For the latest research news, log onto EurekAlert!, www.eurekalert.org, the premier science-news Web site, a service of AAAS.