12/24/2004 Calcutta, India SANJAY MANDAL The Telegraph S.K. Ladla was having difficulty in swallowing and his voice had become hoarse. The doctors diagnosed the 65-year-old to be suffering from laryngo pharynx cancer — the most common variety of cancer among males in the city. In the past, such patients had no option but to go in for radiotherapy, as surgery was not possible. But not any more. Doctors at Advanced Research and Medicare Institute removed Ladla’s larynx and pharynx, and reconstructed his foodpipe with a free flap from the forearm. Indirect laryngoscopic examinations had earlier revealed a large growth involving the larynx, pharynx, respiratory pipe and the foodpipe. The cancer was detected after direct laryngoscopic biopsy, and a CT scan found that it was locally advanced, affecting both pipes. “Since the cancer was locally advanced, we had to remove both the pipes. Through micro-vascular reconstruction, pharynx was repaired and the patient is doing well,” said oncologist Subhankar Deb, who along with a team of other doctors, performed the 10-hour surgery. The carotid artery and internal jugular vein of the neck was rejoined with the vein and artery of the flap, thus maintaining nutrition and blood supply to it. “Had there not been such a reconstruction, the flap would not have survived,” Deb said. Tracheotomy was done to enable the patient to breathe. “We had planned to reconstruct the pharynx with a flap from the intestine. Since a wall of the pharynx could be retained, the flap was taken from the [...]

12/24/2004 Ivanhoe Newswire The Triangle and Fayetteville A promising new option for people with throat cancer is combining surgery and laser treatment to save patients' voices. The benefactors are people like Dolly Sigel, who used to be a speech therapist. Ironically, she was recently faced with the possibility of losing her voice. "I was devastated," Sigel said, recalling the diagnosis of a cancerous tumor on her right vocal chord. "I couldn't believe that this was happening to me." One treatment option was seven weeks of radiation, but Dolly was afraid it might affect her voice. Luckily, she came across a doctor who sought a superior remedy. "Dr. Strome was doing a new procedure that would eliminate radiation, and there was a very good chance that voice quality would be retained," Sigel said. In the new procedure, Otolaryngologist Marshall Strome, of the Cleveland Clinic in Ohio, uses a laser to remove the tumor and then uses cryosurgery to freeze any remaining tissue. "What the freezing does, at least to our knowledge at this point in time, is enables that scar tissue to be less dense, more pliable and gives us a better voice quality," he said. Strome explained that key to removing a tumor is to leave as much normal tissue as possible. He says cryosurgery does just that. After Sigel's treatment, her voice returned almost immediately. "I'm very optimistic," she said. "I just think it's terrific. Without a doubt, with no question, this has been a blessing." And it is [...]

12/24/2004 staff Genomics & Genetics Weekly, Dec. 17, 2004 Gene expression patterns associated with invasive oral squamous cell tumors have been identified. "There are limited studies attempting to correlate the expression changes in oral squamous cell carcinoma with clinically relevant variables," scientists in the United States noted. In their study, G.A. Toruner and coauthors at the University of Medicine and Dentistry of New Jersey "determined the gene expression profile of 16 tumor and 4 normal tissues from 16 patients by means of Affymetrix Hu133A GeneChips." "The hybridized RNA was isolated from cells obtained with laser capture microdissection, then was amplified and labeled using T7 polymerase-based in vitro transcription," the investigators explained. "The expression of 53 genes was found to differ significantly (33 upregulated, 20 downregulated) in normal versus tumor tissues under two independent statistical methods." "The expression changes in four selected genes (LGALS1, MMP1, LAGY and KRT4) were confirmed with reverse transcriptase polymerase chain reaction," according to the report. "Two-dimensional hierarchical clustering of the 53 genes resulted in the samples clustering according to the extent of tumor infiltration: normal epithelial tissue, tumors less than or equal to4 cm in dimension, and tumors more than 4 cm in dimension (p=0.0014)." "The same pattern of clustering was also observed for the 20 downregulated genes. We did not observe any associations with lymph node metastasis (p=0.097)," the researchers concluded.

12/24/2004 Avraham Eisbruch, MD Medscape (medscape.com) The superiority of radiation concurrent with chemotherapy in local/regional tumor control and disease-free survival, compared with radiation alone, has been established in several randomized studies and meta-analyses.[1] The combination of chemotherapy and radiotherapy is characterized by increased toxicity, notably acute mucositis and late dysphagia, which limit the intensity of therapy and further improvement of the therapeutic results. A new and exciting radiosensitizing strategy which has emerged in recent years for head and neck cancer is the blockage of the epidermal growth factor receptor (EGFR), which is overexpressed in the majority of head and neck carcinoma cells. Such blockage can be done by antibodies to EGFR (C225, or cetuximab), or by inhibitors of tyrosine kinase, the enzyme that is activated when EGFR is expressed. Encouraging results of phase 1/2 studies suggesting radiosensitization of head and neck cancer by cetuximab were presented several years ago. Radiotherapy in Tandem With Cetuximab In a special session devoted to the topic of innovations in head and neck cancer management at the 46th Annual Meeting of the American Society of Therapeutic Radiology and Oncology (ASTRO), J.A. Bonner, MD, University of Alabama, Birmingham, and colleagues[2] presented initial results of a phase 3 study of radiotherapy with and without cetuximab for locally advanced head and neck cancer. This group of investigators randomized 424 patients with stage III or IV cancer, the majority having larynx, oropharynx, and hypopharynx cancer. The 2 treatment arms were well balanced and several radiation regimens were used, including [...]

12/22/2004 Jennifer Barrett Ozols Newsweek Health (msnbc.com) New screening tools could help dentists save lives through the early detection of oral cancer. Should insurance companies be paying for the tests? A couple weeks before he was scheduled to have his teeth cleaned, Gerald Zember felt a slight pain in the back of his mouth. The retired lawyer figured he had burnt his tongue sipping hot soup or developed an ulcer from one too many spicy meals. And at first glance, Zember’s Ft. Lauderdale, Fla., dentist, William Balanoff, didn't notice anything unusual during a routine examination—until he pulled out a new oral-cancer screening tool called ViziLite. After Zember rinsed with a raspberry-flavored acetic solution, Balanoff inserted a ViziLite light stick into his patient’s mouth. Suddenly, a tiny white lesion became visible on the side of Zember's tongue. "It was tiny, but I couldn't explain it away," says Balanoff, since Zember had no history of canker sores that could have left such a mark. Zember, 78, did have a history of smoking, though, which put him at higher risk for oral cancer. So Balanoff referred him to an oral surgeon to have the lesion checked out. A biopsy revealed the cells were cancerous. "It was so tiny, I might not have noticed it until a year or a year and a half later [once it had grown]," says Balanoff. "By then, it would have been a stage-three cancer, and his chances wouldn't have been that good." About 30,000 Americans will be diagnosed [...]

12/21/2004 Fu-Min Fang et al. Japanese Journal of Clinical Oncology 2004 34(11):641-646 Background: Health-related quality of life (HRQL) data are becoming an important supplement to information pertaining to treatment outcome for cancer patients. The purpose of this study was to evaluate the HRQL outcome for oral cancer survivors after surgery plus postoperative radiotherapy (RT) and to investigate the variables associated with their HRQL. Methods: Sixty-six oral cancer patients with cancer-free survival after surgery plus postoperative RT of >2 years were enrolled. The Short Form-36 (SF-36) questionnaire in the Taiwan Chinese version was self-reported by all participants at the clinics. The linear regression model was used to analyze the socio-demographic and medical-related variables correlated with the physical component summary (PCS) and mental component summary (MCS) in SF-36. Results: The mean scores of the eight functional domains in the SF-36 were markedly lower for oral cancer survivors compared with the Taiwanese and US norms. Those with older age, lower annual family income, more advanced cancer stage and flap reconstruction had significantly worse PCS, and those with lower annual family income, unemployment and more advanced cancer stage reported significantly worse MCS. This model accounts for 63% of variance in PCS, and 51% in MCS. Conclusions: These results provided patient-reported evidence that oral cancer survivors lived with a worse HRQL compared with the general Taiwanese population. Socio-economic factors and cancer stage were important factors correlated with their HRQL. Authors: Fu-Min Fang(1), Wen-Ling Tsai(2), Chih-Yen Chien(3), Herng-Chia Chiu(4) and Chong-Jong Wang(1) Authors' Affiliation: (1) Department [...]

12/21/2004 Djillali Annane et al. Journal of Clinical Oncology, Vol 22, No 24 (December 15), 2004: pp. 4893-4900 Purpose: To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis. Patients and Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety. Results: At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms. Conclusion: Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation. Authors: Djillali Annane, Joël Depondt, Philippe Aubert, Maryvonne Villart, Pierre Géhanno, Philippe Gajdos, Sylvie Chevret [...]

12/21/2004 Houston, TX K. Kian Ang Journal of Clinical Oncology, Vol 22, No 23 (December 1), 2004: pp. 4657-4659 Improving the outcome for patients with locally advanced head and neck carcinomas (HNC) by rational modification of radiation fractionation regimens or combinations of radiation with chemotherapy has been the subject of intensive clinical investigations for more than three decades. The two prototypes of biologically sound-altered radiation fractionation regimens are hyperfractionation and accelerated fractionation.(1) Hyperfractionation was based on preferential sparing of late-responding tissues when the radiation dose per fraction is reduced. Accelerated fractionation regimens emerged through the recognition that tumor clonogen proliferation occurring during radiotherapy has a detrimental effect on outcome.(2,3) Results of large randomized trials addressing the optimization of radiation fractionation collectively show that a number of biologically sound altered fractionation schedules improve the locoregional (LR) control rate on the order of 10% to 15%, but have only a modest impact on overall survival.(1,4) Although several altered fractionation regimens consistently induce more severe acute mucositis than standard 7-week radiotherapy, the general consensus is that late toxicities are not appreciably increased. Scores of clinical trials testing combined-modality therapy have also been published. Meta-analyses of studies completed before 1995 reveal that cytotoxic agents given before or after surgery or radiation do not significantly improve the therapeutic outcome over LR treatment alone. In contrast, chemotherapy given concurrently with radiation improves 2- and 5-year overall survival rates by 8%.(5) Although a variety of cytotoxic agents have been studied, cisplatin is the most extensively investigated, and [...]

12/21/2004 press release Yahoo! Finance (biz.yahoo.com) 90.6% complete responses seen with no evidence of skin toxicity YM BioSciences Inc. today announced preliminary results from a randomized Phase II pivotal trial assessing the efficacy and safety of its EGF receptor monoclonal antibody, TheraCIM h-R3 (nimotuzumab), combined with radiation compared to radiation alone in locally advanced, Stage 3-4, nasopharyngeal carcinoma, a subset of head-and-neck cancer. The study was conducted by YM's licensor, CIMAB S.A. and Biotech Pharmaceuticals Limited, CIMAB's joint-venture partner in China. Of the 130 patients in the intent-to-treat analysis, those in the combination arm were reported to have a 90.6% Complete Response compared to 51.5% in the radiation-alone group. "Complete Response" is defined as the elimination of tumour at the primary site, locoregional lymph nodes and distant metastases. TheraCIM h-R3 was administered intravenously at a dose of 100 mg/person once a week for eight weeks beginning on the first day of radiotherapy. There was no evidence of the acneiform rash commonly associated with administration of therapeutic agents designed to block the EGF receptor system, corroborating the results of a previous study for TheraCIM h-R3 in head-and-neck cancer (Journal of Clinical Oncology, Volume 22, No. 9, May 1, 2004). "No other product targeting the EGF receptor has demonstrated a difference in response rates of this magnitude," said David Allan, Chairman of YM BioSciences. "This result adds further justification to YM's approach of combining TheraCIM h-R3 with radiation or as a monotherapy in a variety of cancers including head-and-neck, metastatic pancreatic and [...]

12/21/2004 Ranjiv Sivanandan et al. Arch Otolaryngol Head Neck Surg. 2004;130:1369-1373. Objective The optimal surgical procedure for the neck in patients with squamous head and neck cancers is controversial. Selective neck dissections have replaced modified radical neck dissections as the procedure of choice for the clinically negative (N0) neck and are now being considered for patients with early-stage neck disease. We report the long-term local recurrence rates in 100 consecutive patients undergoing a radical or modified radical neck dissection for clinically positive (N+) and N0 neck disease and review comprehensively the literature reporting and comparing regional control rates for both neck dissection types. Patients The clinical records of 100 consecutive patients who underwent a comprehensive neck dissection (levels I-V) for squamous head and neck cancers with a minimum of a 2-year follow-up were retrospectively reviewed for primary site of disease, clinical and pathologic neck status, histopathologic grade, neck dissection type, and the site and time of recurrence. Results Complete data were available for 97 patients on whom 99 neck dissections were performed. Three patients died from unknown causes. Seventy-six patients with N+ disease underwent a therapeutic neck dissection, while 24 patients with clinically N0 disease underwent an elective dissection. The overall neck recurrence rate in patients with controlled primary disease was 7%. The neck or regional failure rate for patients completing the recommended adjuvant radiotherapy was 4%. Six (25%) of 24 patients with clinically N0 disease had occult metastases. The recurrence rate for this group was 4%. Conclusion Further study [...]