Genetic alterations in head and neck squamous cell carcinomas.
The genetic alterations observed in head and neck cancer are mainly due to oncogene activation (gain of function mutations) and tumor suppressor gene inactivation (loss of function mutations), leading to deregulation of cell proliferation and death. These genetic alterations include gene amplification and overexpression of oncogenes such as myc, erbB-2, EGFR and cyclinD1 and mutations, deletions and hypermethylation leading to p16 and TP53 tumor suppressor gene inactivation. In addition, loss of heterozygosity in several chromosomal regions is frequently observed, suggesting that other tumor suppressor genes not yet identified could be involved in the tumorigenic process of head and neck cancers. The exact temporal sequence of the genetic alterations during head and neck squamous cell carcinoma (HNSCC) development and progression has not yet been defined and their diagnostic or prognostic significance is controversial. Advances in the understanding of the molecular basis of head and neck cancer should help in the identification of new markers that could be used for the diagnosis, prognosis and treatment of the disease. (+info)
First year after head and neck cancer: quality of life.
PURPOSE: Treatment regimens for head and neck cancer patients profoundly affect several quality-of-life domains. Rehabilitative needs have been identified through cross-sectional analyses; however, few studies have prospectively assessed quality of life, included assessment of psychosocial variables, and identified predictors of long-term follow-up. PARTICIPANTS AND METHODS: The present study addresses these limitations through a prospective assessment of 105 patients with a newly diagnosed first primary squamous cell carcinoma of the oral cavity, pharynx, or larynx. Participants were enrolled onto a larger randomized controlled trial comparing a provider-delivered smoking cessation intervention with a usual-care-advice control condition. Participants completed a battery of self-report measures after diagnosis and before treatment and additional quality-of-life instruments at 1 and 12 months after initial smoking cessation advice. RESULTS: Participants displayed improvements at 12 months in functional status (P = .006) and in the areas of eating, diet, and speech; however, the latter three represent areas of continued dysfunction, and the changes were not statistically significant. Despite these improvements, patients reported a decline in certain quality-of-life domains, including marital (P = .002) and sexual functioning (P = .017), as well as an increase in alcohol use (P < .001). Predictors of quality of life at 12 months included treatment type, the Vigor subscale of the Profile of Mood States instrument, and quality-of-life scores obtained 1 month after initial smoking cessation advice. CONCLUSION: Results reinforce the need for rehabilitation management through the integration of psychologic and behavioral interventions in medical follow-up. (+info)
Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin.
PURPOSE: To review the pharmacodynamics, pharmacokinetics, toxicities, and relative clinical activities of cisplatin and carboplatin. Through a search of the MEDLINE database, we identified phase III clinical trials and pharmacologic studies comparing cisplatin and carboplatin published in the English language medical literature from January 1966 to December 1997. RESULTS: Prospective randomized trials comparing cisplatin to carboplatin were identified for ovarian (n = 12), germ cell (n = 4), non-small-cell lung (n = 1), small-cell lung (n = 3), and head and neck (n = 4) cancers. Carboplatin and cisplatin were equally effective in suboptimally debulked ovarian cancer and extensive-stage small-cell lung cancer. One study each showed a trend toward better survival in favor of cisplatin for patients with optimally debulked ovarian and limited-stage small-cell lung cancers. These results were, however, based on subset analyses. In germ cell tumors, carboplatin was inferior because of lower relapse-free survival rates. Cisplatin produced superior response rates and survival in head and neck cancers. There are no published randomized phase III studies of bladder, cervical, endometrial, and esophageal cancers. CONCLUSION: Carboplatin does not possess equivalent activity to cisplatin in all platinum-sensitive tumors. Carboplatin can replace cisplatin in chemotherapy regimens for suboptimally debulked ovarian cancer. Two ongoing studies will address the same question in optimally debulked disease. Carboplatin can also be substituted for cisplatin in the treatment of non-small-cell and extensive-stage small-cell lung cancers. Its role in limited-stage small-cell lung cancer needs to be investigated further. Carboplatin is inferior to cisplatin in germ cell, head and neck, and esophageal cancers. Randomized studies are needed to determine whether carboplatin has equivalent efficacy to cisplatin in bladder, cervical, and endometrial cancers. (+info)
Thallium-201 single-photon emission CT versus CT for the detection of recurrent squamous cell carcinoma of the head and neck.
BACKGROUND AND PURPOSE: Thallium-201 single-photon emission computed tomography (SPECT) can be used to detect primary squamous cell carcinoma (SCCA) of the head and neck. Nevertheless, there have very few studies performed to evaluate the ability of thallium-201 to depict recurrent SCCA. The purpose of this study was to compare the ability of thallium-201 SPECT with CT to enable detection of recurrent SCCA of the upper aerodigestive tract. METHODS: Thirty-three patients with a history of previously treated SCCA of the extracranial head and neck underwent thallium-201 SPECT imaging and contrast-enhanced CT. A neuroradiologist and nuclear medicine physician with knowledge of the primary site evaluated all thallium-201 studies for abnormal radiotracer uptake at the primary site. These results were correlated with histologic findings and clinical follow-up in all patients. All patients were followed up for a minimum of 2 years after completion of treatment. The McNemar test was used to determine statistical significance. RESULTS: The diagnostic accuracy of thallium-201 SPECT was as follows: sensitivity, 88%; specificity, 94%; positive predictive value, 93%; and negative predictive value, 89%. The diagnostic accuracy of CT was as follows: sensitivity, 100%; specificity, 24%; positive predictive value, 55%; and negative predictive value, 100%. The diagnostic accuracy of thallium was superior to CT (P = .01). CONCLUSION: Thallium-201 SPECT is superior to CT for differentiating recurrent tumor from post-treatment changes and may complement CT in the evaluation of previously treated SCCA of the extracranial head and neck. (+info)
Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines.
Because regional spread to lymph nodes without systemic spread is a relatively common event in squamous cell cancer of the head and neck (SCCHN), it is possible that lymphoid-related receptors or cytokines might directly impact the growth of these tumors. In the present study, we have shown by flow cytometry and Western blotting that the central lymphoid regulatory molecule, CD40, is expressed on the surface of all seven SCCHN tumor cell lines studied. Tumor cell lines also expressed epidermal growth factor (EGF) receptor, MHC class I, and CD95 (Fas) but did not uniformly express other important lymphoid regulatory molecules such as CD80, CD86, or interleukin (IL) 2 receptor components. CD40 ligation by trimeric CD40 ligand (CD40L) resulted in a 20-45% inhibition of tumor cell growth in three of seven cell lines tested. The cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-11, and IL-15 neither inhibited nor stimulated growth in any of the cell lines tested. EGF had pleiotropic effects on cell growth; it inhibited growth in two cell lines, stimulated growth in one cell line, and had no effect in four cell lines. When coligation by EGF and CD40L was studied, additive or supra-additive growth inhibition was seen in four cell lines. Three cell lines were unaffected by EGF, CD40, or coligation with both reagents. Examination of tumor tissues from 12 previously untreated patients representing a broad spectrum of patients presenting with SCCHN demonstrated CD40 expression in all 12 tumor specimens. This study supports the notion that CD40 is a regulatory molecule for the growth of SCCHN. The important role of CD40-CD40L interactions in the regulation of immune cells in the lymph node and the unique high-level expression of CD40L by these immune cells lend support to the hypothesis that this ligand/receptor pair is an important mediator of cell growth in SCCHN. (+info)
A comparison of bleomycin-induced damage in lymphocytes and primary oral fibroblasts and keratinocytes in 30 subjects.
The number of chromatid breaks in peripheral blood lymphocytes (PBL) after exposure to bleomycin in the S/G2 phase of the cell cycle (in the literature referred to as 'mutagen sensitivity') is associated with an increased risk of environmentally related cancers, including oral cancer. The aim of this study was to elucidate whether mutagen sensitivity measured in lymphocytes actually reflects chromosomal instability of normal cells in the areas in which tumors develop. Therefore, bleomycin-induced chromosomal damage in and growth inhibition of cultured oral fibroblasts and oral keratinocytes from 30 persons were compared with the standard mutagen sensitivity score in PBL. A correlation was found for the percentage of aberrant metaphases between PBL and oral fibroblasts but not for the number of breaks per cell. These data do not allow a conclusion to be drawn on the use of fibroblasts to study cancer risk. Within the fibroblasts it was found that a high number of breaks per cell was associated with less growth inhibition, indicative of damage-resistant growth. Oral keratinocytes were extremely sensitive to bleomycin, as indicated by a strong cell cycle block which resulted in a mitotic index too low to determine chromosomal breaks. Moreover, in the cell proliferation assay keratinocytes were found to be 100 times more sensitive as compared with fibroblasts. There was no correlation between bleomycin sensitivity of keratinocytes compared with fibroblasts from a single patient as measured by growth inhibition. This may be due to the strong influence of alcohol consumption by the subjects, which was found to increase the sensitivity of keratinocytes but not of PBL and fibroblasts. In conclusion, oral fibroblasts but not keratinocytes can be used to measure sensitivity for chromatid breaks. The apparent influence of environmental factors on keratinocytes makes them a useful source to study exposure characteristics but limits their application for the determination of genetic factors. (+info)
Correlative 201Tl SPECT, MRI and ex vivo 201Tl uptake in detecting and characterizing cervical lymphadenopathy in head and neck squamous cell carcinoma.
The value of SPECT with 201Tl chloride, in combination with MRI (particularly short inversion-time inversion recovery [STIR] sequences that suppress fat signals) to detect and characterize cervical lymphadenopathies (nodes > or = 1 cm), and ex vivo lymph node 201Tl uptake were studied in patients with squamous cell carcinoma of the head and neck. METHODS: Preoperative SPECT and MRI, displayed in similar planes, were compared with the histologic findings in 15 neck dissection specimens from 12 patients with squamous cell carcinoma of the head and neck (9 with unilateral and 3 with bilateral neck dissection). Results were evaluated topographically with regard to the lymph node compartments (levels) of the neck. In addition, in 8 of these patients, the 201Tl activity of dissected lymph nodes of 10 neck sides was measured immediately after surgery in a gamma counter and expressed as percentage of the injected dose per gram tissue (%ID/g). RESULTS: Sixty-two lymph node levels were evaluated histologically. The high sensitivity of MRI (92% versus 71% for 201Tl SPECT), which correctly detected lymph node involvement in 22 of 24 levels, and the high specificity of 201Tl SPECT (92% versus 71% for MRI), which correctly characterized as negative 35 of 38 lymph node levels without metastasis on histology, led to a combined 201Tl SPECT/MRI accuracy of 92%. 201Tl SPECT was particularly effective in excluding involvement in 9 tumor-free neck levels with pathologically enlarged lymph nodes on MRI but failed to confirm involvement in 5 other tumor-positive levels. Mean 201Tl uptake in 53 lymph nodes with confirmed histologic involvement was significantly higher than uptake in 145 tumor-free lymph nodes (0.0043+/-0.0022 %ID/g versus 0.0023+/-0.0014 %ID/g, P = 0.0001), muscle and fat tissue but clearly lower than salivary gland uptake. CONCLUSION: Although 201Tl SPECT is not sensitive enough to be used as an independent imaging modality for staging of the neck, its correlative application with MRI appears to be an accurate method for the assessment of regional spread in head and neck squamous cell carcinoma. The ability of 201Tl SPECT to characterize neck lymphadenopathies detected by MRI appears to be based on the difference in 201Tl concentration found in lymph nodes with and without tumor involvement. (+info)
Analysis of 57 nonagenarian cancer patients treated by radical radiotherapy: a survey of eight institutions.
BACKGROUND: As the human society grows more aged, it is considered important to elucidate factors essential in applying radical radiotherapy (RT) to the elderly, with ages as high as 90 years and greater. METHODS: A retrospective survey was conducted for patients 90 years of age or older who received radiotherapy with radical intent in eight leading institutions in Japan from 1990 through 1995. RESULTS: Fifty-seven nonagenarian patients were studied. Their ages ranged up to 98 (median 91) and there was a strong female preponderance (M/F: 16/41). The distribution by site was as follows: head and neck, 16; skin and adnexae, 11; uterine cervix, 7; esophagus, 6. The prevailing histopathological diagnosis was squamous cell carcinoma (34), followed by adenocarcinomas (8). The highest age at RT was 98 years [female, skin cancer, died of senility 2.5 years after treatment, with no evidence of disease (NED)] and the longest survivor is 102 years old (female, glottic cancer T2, age at RT 93, alive NED for 8 years, uses wheel-chair). The rate of completion of treatment was 75% (43/57), if the treatment field was limited to the gross primary tumor volume only and if the cumulative dose was above 80% of the tolerable adult dose. Familial escort was necessary for most of the patients in completing the day-to-day RT. CONCLUSION: Radiotherapy is feasible with radical intent even in the elderly, if the treatment field is limited to the gross primary tumor volume only, if the cumulative dose is above 80% of the tolerable adult dose and if familial support is adequate. (+info)