Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Head and neck cancer remains a common cause of mortality and morbidity in the United States and throughout the world. In spite of advances in the management of patients with advanced disease, overall survival in this group remains poor. Furthermore, although cancer mortality is lower in patients with early-stage disease, treatment results in significant morbidity, and these patients also face the risk of developing a second primary tumor. Chemoprevention is an innovative approach to decrease overall cancer morbidity and mortality using substances that are capable of preventing cancer progression. Head and neck cancer is an excellent model for chemoprevention, as its biology is consistent with the two concepts important for the development of chemoprevention strategies: field cancerization and multistep carcinogenesis. Several classes of compounds have been evaluated in chemoprevention trials. The most frequently studied agents, the retinoids, were found frequently to induce remissions in patients with oral leukoplakia. Furthermore, retinoids prevented progression to malignancy in one randomized maintenance study. Other agents, including beta-carotene and vitamin E, have been found also to have activity in the management of oral leukoplakia. However, the clinical role of chemopreventive agents in reducing cancer mortality remains to be defined. Two studies, one in head and neck cancer and one in lung cancer, have shown the ability of retinoids to prevent the development of second primary tumors. Current large randomized trials are defining the effectiveness of these agents in reducing the mortality of aerodigestive tract tumors in individuals at high risk.
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PMID:Biology and chemoprevention of head and neck cancer. 805 3

The development of an original conformal technique for neck cancer is in progress in our Institute. This technique uses a computer-controlled moving bar (CCMB): a portion of a blocking bar rotates during the rotation of the gantry in a 2 pi arc field in order to shield the spinal cord over the whole irradiated volume. This technique should solve in a relatively simple way some problems for different clinical situations when cervical node irradiation is required together with the primary tumor. The technique has been tested in an acrylic cylindrical phantom and in the humanoid RANDO phantom for two different irradiation conditions (neck completely bent and partially aligned).
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PMID:Development of a computer-controlled moving bar (CCMB) conformal technique for neck irradiation. 835 28

Elective supraomohyoid neck dissection is considered part of standard treatment of oral and oropharyngeal cancer in most institutions, but its role in the treatment of clinically positive neck cancer remains a subject of controversy. The main object of this study is to report the results of 212 consecutive patients who underwent supraomohyoid neck dissections from 1954 to 1990. Most patients had squamous cell carcinoma of the oral cavity. Eighty-six patients (40.6%) had histologically positive lymph nodes in the surgical specimen (sensitivity, 0.55; specificity, 0.53). At the study closing date there were 58.8% actuarial 10-year overall survival rates. Forty-five patients (21.2%) had 50 tumor recurrences (32 local, 13 regional, five distant), and in 40 patients (18.8%) a second primary tumor was diagnosed. A multivariate regression technique based on Cox's proportional hazards model was used, and age (65 years or younger vs older than 65 years) represented the variable with the highest predictive strength with respect to overall survival (relative risk, 2.3). Tumor site, sex, and histologically proved metastasis were also associated with overall survival rates. The same variables were also related to the risk of recurrence. In conclusion, the death rate is mainly related to the control of the primary site tumor and the occurrence of a second primary tumor rather than to neck recurrences. It confirms that supraomohyoid neck dissection is an adequate elective procedure and possibly sufficient in the treatment of a selected group of patients with lip cancer with positive nodes at level 1.
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PMID:Supraomohyoid neck dissection in the treatment of head and neck tumors. Survival results in 212 cases. 835 96

Until now, there have not been any parameters to monitor opioid therapy in cancer patients with pain. In this study, 325 consecutive advanced cancer patients were scheduled for a prospective longitudinal survey. After exclusions, 67 patients were surveyed. All included patients were advanced cancer patients with pain that required opioid therapy for more than 6 weeks before death. Opioid escalation, symptoms associated with opioid therapy, pain mechanism, and pain intensity were recorded. Indices were calculated to categorize the response to opioids. The opioid escalation index (OEI) was used to index the mean increase of the starting opioid dosage, expressed as a percentage or in mg. The length of the period of stable dose (MLD) and the effective analgesic score (EAS), that is, the analgesic consumption/pain relief ratio calculated at fixed intervals, were also used. Patients with a mean visual analogue scale score (VAS) of less than 4 and regular OEI and EAS were considered responsive; patients with a mean VAS less than 4 but with an OEI more than 5 or increases of more than 100% of EAS when compared to that calculated the week before were considered mildly responsive; and patients with a mean VAS more than 4 were considered unresponsive. Advanced age, female gender, and previous chemotherapy were all factors reducing OEI. Head and neck cancer was associated with a higher OEI. Regarding the influence of the opioid-related symptoms, an increased OEI was associated with the presence of confusion. Moreover the presence of confusion was associated with neuropathic pain. Neuropathic pain taken alone, however, did not influence this score. Gender-specific cancer, such as breast cancer, influenced the gender differences reported for MLD (significantly longer than that reported for males and other primary tumor). Good responsiveness was observed in 28 patients, partial responsiveness in 33 patients, unresponsiveness in six patients. Psychological factors were associated with poor pain relief, probably reducing the patient's compliance. The tools used in this study may be useful in monitoring the effects of opioid therapy in cancer pain patients. Simple numbers are easy to compare and make it possible to profile opioid responsiveness and differences among patients.
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PMID:Monitoring of opioid therapy in advanced cancer pain patients. 913 31

Carcinoma cell lines are frequently refractory to transforming growth factor-beta (TGF beta)-mediated cell cycle arrest. Whether and how TGF beta signaling is disrupted in the majority of human tumors, however, remains unclear. To investigate whether TGF beta signaling might be disrupted by inactivation of the key signaling molecule, the TGF beta type I (T beta R-I) receptor, and whether or not T beta R-I inactivation is associated with late stage disease, we conducted a comprehensive structural analysis of the T beta R-I gene in fine-needle aspirates of 23 head-&-neck cancer metastases. We encountered 4 different mutations of T beta R-I, 3 of which have not been previously identified. In 1 case, we found a somatic intragenic 4-bp deletion predicting for a truncation of the receptor protein. This is the first example of a true loss-of-function mutation of T beta R-I in a human epithelial neoplasm. In 2 other cases, we identified missense mutations located between the juxtamembrane- and serine-threonine kinase domains. One of these resulted in an alanine-to-threonine substitution (A230T), which disrupts receptor signaling activity by causing rapid protein degradation within the endoplasmatic reticulum. This represents a novel mechanism of inactivation of a TGF beta signaling intermediate. Finally, we identified a serine-to-tyrosine substitution at codon 387 (S387Y) in a metastasis but not in the corresponding primary tumor. We had previously shown this S387Y mutant to be predominantly associated with breast cancer metastases and to have a diminished ability to mediate TGF beta-dependent signaling. In aggregate, these findings provide further support for the hypothesis that inactivation of the TGF beta signaling pathway occurs in a significant subset of human cancers.
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PMID:Novel inactivating mutations of transforming growth factor-beta type I receptor gene in head-and-neck cancer metastases. 1147 74

Background and purpose. Intensity modulated radiation therapy (IMRT) offers an opportunity to generate dose distributions highly conformal to the target volume. Head and neck cancer patients, referred for radiotherapy, may be good candidates to benefit from IMRT. This paper discusses the clinical implementation of IMRT for oropharyngeal and oral cavity tumors, and reports the clinical results of the 14 patients treated with this technique at Ghent University Hospital (GUH). Patients and Methods. Between May 1999 and May 2001, 14 patients were treated with IMRT at GUH for oropharyngeal or oral cavity tumors. Two groups of patients can be distinguished. The first group consists of eight patients re-irradiated with IMRT for a locoregional relapse. The second group of six patients were treated with IMRT for a primary tumor. For the first group, IMRT was used to treat the relapse by generating a concave dose distribution, i.e. to combine a homogeneous target re-irradiation with a dose to the spinal cord as low as possible. For the second group, IMRT was applied in order to achieve a more homogeneous dose distribution inside the PTV and to preserve parotid gland function. Results. The majority of the patients of group 1 (6/8) relapsed in field within four months after the end of the re-irradiation, with a median overall survival of 7 months. For group 2, two patients died shortly after the end of the IMRT treatment, the other four patients are free of tumor relapse with a median follow-up of 5 months (1-13 months). The acute toxicity due to radiation was acceptable for both patient groups. Dysphagia and pain was more present in group 1. Regarding late complications for the group of re-irradiations (group 1), no myelitis, carotid rupture or cranial nerve palsy was observed. One patient of group 1 developed osteoradionecrosis of the mandible and feeding tube dependency was present for another patient. No fatal late complications were observed in this group. For the first two patients of group 2, sparing of the parotid function was not a treatment objective. For the other patients of group 2, the mean dose to the contralateral parotid gland ranged from 17 to 25 Gy, which resulted in a decrease of subjective symptoms of xerostomia compared to patients treated with conventional radiotherapy. Conclusions. The implementation of IMRT for oropharyngeal and oral cavity tumors results in a homogeneous target irradiation and allows to re-irradiate locoregional relapses with acceptable adverse effects. Sparing of the parotid gland by IMRT is feasible, although this may be significantly influenced by the delineation method of the elective lymph node regions.
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PMID:Intensity modulated radiation therapy for oropharyngeal and oral cavity tumors: clinical use and experience. 1216 38

With a monoisocentric 3-field technique for treating head-and-neck cancer, collimator rotation may be needed for the upper lateral fields to avoid cephalad-positioned shoulders or to avoid unnecessary arytenoid irradiation while maintaining more anterior coverage. For patients with unilateral lymphadenopathy, lateral oblique-opposed boost fields can be used to encompass the primary tumor and ipsilateral lymph nodes without junctioning through gross disease. When initial collimated lateral fields are also rotated with a gantry angle to produce oblique boost fields, however, the resulting matchline with a low anterior neck (LAN) boost field is no longer nondivergent. This can be corrected by manual adjustment of collimator and gantry angles for the LAN field using 3D treatment planning software. The goal of this study was to derive mathematical formulas to simplify this process. We used a transformation matrix to define formulas that could predict the appropriate modifications to the LAN boost field. Output from the formulas was (1) visually tested within 3D treatment planning software and (2) verified using a solid water head-and-neck phantom and radiographic film dosimetry to confirm that a nondivergent matchline was obtained in several clinical scenarios. When evaluated with 3D treatment planning software, the formulas accurately predicted the appropriate gantry and collimator angles of the LAN boost field for a variety of possible beam combinations. When evaluated with film dosimetry, the formulas were shown to accurately predict the appropriate gantry and collimator angles of the LAN boost field to within the +/- 2 mm/1 degrees tolerance specifications of the linear accelerator and acceptable for routine clinical use. The presented formulas are simple and geometrically precise. They predict the necessary manipulations of the LAN boost field to maintain a geometrically precise matchline, as verified by 3D treatment planning software, phantom dosimetry, and actual patient setups.
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PMID:New equations for matching a low neck field to oblique upper neck fields with collimator rotation in a 3-field monoisocentric setup for head-and-neck cancers. 1519 53

Treatment for head and neck cancer has evolved significantly during the past 100 years. Beginning with Bilroth's total laryngectomy on New Year's Day in 1873, "radical" surgery remained the only accepted treatment for head and neck cancer when optimal local and regional control was the goal. Bigger was still better when it came to managing the primary tumor and the neck. The "commando" procedure and radical neck dissection were the hallmarks of this first generation of treatments of head-and-neck cancer. With the advent of microvascular reconstructive techniques, larger and more comprehensive resections could be performed. Despite these large resections and their "mutilating" sequelae, overall survival did not improve. Even for intermediate-stage disease in head-and-neck cancer, the 5-year survival rate did not improve >50%. Many concluded that more than the scalpel was needed for optimal local and regional control, especially for intermediate- and advanced-stage disease. Most important, the multidisciplinary teams must identify and correlate biomarkers in the tumor and host that predict for a response to therapy and for optimal functional recovery. As the pendulum swings back, a scientific approach using tissue biomarkers for the response to treatment in the setting of multidisciplinary trials must emerge as the new paradigm. In the postgenomic era, treatment decisions should be made based on functional and oncologic parameters-not just to avoid perceived morbidity.
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PMID:Swing of the surgical pendulum: a return to surgery for treatment of head and neck cancer in the 21st century? 1784 81

Metastatic spread of tumor cells to vital organs is the major cause of mortality in cancer patients. Bcl-2, a key antiapoptotic protein, is expressed at high levels in a number of human tumors. We have recently shown that Bcl-2 is also overexpressed in tumor-associated blood vessels in head-and-neck cancer patients. Interestingly, enhanced Bcl-2 expression in tumor blood vessels is directly correlated with metastatic status of these cancer patients. In addition, endothelial cells (ECs) expressing Bcl-2 showed increased production of interleukin-8 (IL-8) resulting in significantly enhanced tumor cell proliferation and tumor cell invasion. Therefore, we hypothesized that Bcl-2 expression in tumor-associated ECs may promote tumor metastasis by enhancing tumor cell invasiveness and release in the circulation. To test our hypothesis, we coimplanted tumor cells along with ECs expressing Bcl-2 (EC-Bcl-2) in the flanks of SCID mice. Our results demonstrate that incorporation of EC-Bcl-2 in primary tumors significantly enhanced tumor cell metastasis to lungs and this EC-Bcl-2-mediated tumor metastasis was independent of primary tumor size. In addition, Bcl-2-mediated tumor metastasis directly correlated with increased tumor angiogenesis. Bcl-2 expression in ECs also promoted transendothelial cell permeability, blood vessel leakiness and tumor cell invasion. EC-Bcl-2-mediated tumor cell proliferation and tumor cell invasion were significantly mediated by IL-8. These results suggest that Bcl-2, when expressed at higher levels in tumor-associated ECs, may promote tumor metastasis by enhancing tumor angiogenesis, blood vessel leakiness and tumor cell invasiveness.
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PMID:Endothelial cells expressing Bcl-2 promotes tumor metastasis by enhancing tumor angiogenesis, blood vessel leakiness and tumor invasion. 1849 Aug 95

Head and neck cancer patients are at high risk for developing second primary tumors. This is known as field cancerization of the aero-digestive tract. In a previous study, we showed that patients with multiple primary tumors were more likely to have p53 mutations in histologically normal mucosae than patients presenting with an isolated tumor. Based on this observation, we postulated that p53 mutations in normal tissue samples of patients bearing a single primary tumor could have a clinical value as a biomarker for the risk of developing second primary tumors. Thirty-five patients presenting with a single primary tumor were followed-up for a median of 51 months (range 1 month to 10.9 years) after biopsies of histologically normal squamous cell mucosa had been analyzed for p53 mutations with a yeast functional assay at the time of the primary tumor. During this follow-up, recurrences and non-sterilization of the primary tumor, occurrence of lymph node metastases, and of second primary tumors were evaluated. Sixteen (45.7%) patients were found to have p53 mutations in their normal squamous cell mucosa, and 19 (54.3%) patients showed no mutation. No relationship was found between p53 mutations and the occurrence of evaluated events during follow-up. Notably, the rate of second primary tumors was not associated with p53 mutations in the normal squamous mucosa. The correlation between p53 mutations in histologically normal mucosae and the incidence of second primary tumors is generally low. The benefit of analyzing p53 mutations in samples of normal squamous cell mucosa in every patient with a primary tumor of the head and neck is doubtful.
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PMID:p53 Mutation in histologically normal mucosa of the aero-digestive tract is not a marker of increased risk for second primary carcinoma in head and neck cancer patients. 1903 74


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