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Biomedical subjects

J C Hutchinson

Publications and source records attributed to J C Hutchinson.

At least 19 recordsLinked to original sources
PubMed1999

Prognostic significance of p27 expression in carcinoma of the oral cavity and oropharynx.

OBJECTIVE: To study the role of p27, a cyclin-dependent kinase inhibitor, as a prognostic indicator in squamous cell carcinoma of the oral cavity and oropharynx. STUDY DESIGN: Retrospective review of 35 patients with squamous cell carcinoma of the oral cavity and oropharynx who presented to Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, between 1986 and 1995. METHODS: Inclusion criteria were the availability of clinical information, archival pretreatment biopsy material, and a minimum follow-up of 24 months. p27 staining was scored for frequency and intensity of tumor cell expression following immunoperoxidase staining using standard techniques. Samples of squamous epithelium from the uvula of 15 nonsmoking patients without past or present squamous cell carcinoma were used as normal controls. RESULTS: The association of p27 staining and other factors with response to treatment was evaluated by Fisher's Exact Test and with overall and disease-free survival by the Kaplan-Meier method with multivariate Cox regression. Low levels of p27 expression correlated significantly with unfavorable treatment response (P<.0001), shorter overall survival (P = .0001), and shorter disease-free survival (P = .003). Tumor site (alveolus) was also associated with shorter disease-free (though not overall) survival, but the association with p27 was independent of stage and site in multivariate analysis.

Adult↗
PubMed1998

Regulators of proliferation and apoptosis in carcinoma of the larynx.

Expression of interrelated gene products regulating cell proliferation and apoptosis may be disordered in squamous cell carcinoma (SCC) of the larynx compared with normal squamous mucosa. Certain of these abnormalities, alone or in combination, may be of prognostic significance in low-stage carcinomas of the larynx. A retrospective study of archival material was made. Expression of the Bcl-2 family of apoptosis-related genes (bcl-2, bcl-X, mcl-1, and bax) and the proliferation- and apoptosis-related genes p53 and cyclin D-1 were determined in 40 low-T-stage laryngeal carcinomas and in uvular epithelium from patients without SCC. Among the antiapoptotic members of the Bcl-2 family, Bcl-X and Mcl-1 showed more intense and widespread staining than Bcl-2 itself in both normal squamous mucosa and SCC. The well-ordered expression patterns of Bcl-2-related proteins found in normal epithelium were lost in SCC, and patterns of expression varied widely among individual tumors. Also, mean expression levels for Bax and cyclin D-1 were significantly lower than in normal epithelium (P = .036 and P = .009, respectively), whereas expression of p53 was higher in tumors (P = .034). Expression of Bcl-X and Mcl-1 was greater in poorly differentiated than in well-differentiated tumors (P = .014 and P = .031, respectively). No associations were seen between marker expression patterns and clinical outcome in this group of patients. Bcl-x and Mcl-1 appear to be the most abundantly expressed antiapoptotic proteins of the Bcl-2 family in both normal squamous mucosa and SCC of the larynx. Multiple genes regulating proliferation and apoptosis are expressed abnormally in laryngeal SCC compared with normal epithelium. In particular, loss or measurable decrease in expression of the proapoptotic protein Bax in tumors may contribute to the deranged growth control of SCC. Further study is needed to evaluate the prognostic significance of particular patterns of disordered expression of proteins regulating proliferation and apoptosis in SCC of different head and neck sites.

Adult↗
PubMed1997

Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer: 8-year analysis of results.

BACKGROUND: The purpose of this study was to analyze long-term follow-up of a single institution's experience with a regimen of concomitant cisplatin/fluorouracil (5-FU) infusion and radiation given every other week. This analysis was stimulated by results of a randomized trial showing superiority for this regimen over induction cisplatin/5-FU chemotherapy followed by radiotherapy, especially in regional disease control. METHODS: All patients with stage III/IV disease who were referred by surgeons for nonoperative therapy and had a follow-up of at least 2 years were included. Concomitant chemoradiotherapy was administered days 1-5 of a 2-week treatment cycle, for a total of 7 cycles, with cisplatin 60 mg/m2 day 1, 5-FU 800 mg/m2 given over 24 hours days 1-5, and radiation 2 Gy days 1-5. RESULTS: Seventy-eight patients with stage III (n = 16) or IV (n = 62) were treated and followed for a median of 8 years. Six patients died during treatment, of aspiration pneumonia, sudden death, gastrointestinal bleeding, and stroke. When assessed 6 weeks after the end of treatment, 45 patients (63%) had no clinical evidence of disease, whereas 27 (37%) still had some persistent abnormality. However, 17 of these "partial responders" have not recurred. In all, 24 patients (31%) have recurred or progressed, 13 at the primary site, 5 after 3 years. None of 16 stage III and 24 (39%) of 62 stage IV patients ever progressed. Tongue and glottic larynx did best, with only 1 of 22 patients ever failing (none locally). Supraglottic and oral cavity cancers other than tongue had the worst failure rates. Nineteen patients (24%) died of other causes (DOC), tumor-free. Patients who DOC correlated strongly with T stage (p < .002) but not with N stage or with AJC stage. The 5-year progression-free survival was 60% (confidence interval [CI] = 49% to 72%), and overall survival was 43% (CI = 33% to 56%). CONCLUSIONS: Disease control for this advanced head and neck cancer population was excellent. This regimen was especially effective in advanced tongue and glottic cancers and all stage III disease sites. Advanced supraglottic and hypopharynx cancers are problematic. These, and especially T4 lesions, are associated with high DOC rates, possibly in part related to swallowing malfunction. Nevertheless, the long-term survival without surgical intervention was high with this regimen.

Adult↗
PubMed1994

Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer.

PURPOSE: To compare two published schedules of cisplatin plus fluorouracil (5-FU) infusion and radiation as either sequential or concomitant treatment for toxicity and efficacy in patients with unresectable head and neck cancer. PATIENTS AND METHODS: This was a randomized trial between cisplatin 100 mg/m2 over 15 minutes on day 1 plus 5-FU 1.0 g/m2 by continuous infusion on days 1 to 5, repeated every 3 weeks for three cycles, followed by 70 Gy of radiation in 7 to 8 weeks, versus cisplatin 60 mg/m2 over 15 minutes on day 1 plus 5-FU 800 mg/m2 by continuous infusion on days 1 to 5 plus radiation 2 Gy on days 1 to 5, repeated every other week for seven cycles. Unresectable head and neck squamous cancer patients not previously treated with radiation or chemotherapy and with a performance status of 0 to 2 were stratified by tumor (T) and node (N) groupings and performance status and randomized. RESULTS: Two hundred fifteen patients were entered and 214 analyzed, 107 on each arm. After all treatment, overall response rates were different (P = .003), with similar complete response rates, but more partial responses and fewer patients with no change or progression with concomitant treatment. Cox regression analysis for progression-free survival identified concomitant treatment (P = .003), Radiation Therapy Oncology Group (RTOG) stage III grouping (P < .0001), performance status (P = .0002), concomitant treatment (P = .003), and treating institution (P = .006) as significant. The sequential and concomitant treatments showed similar distant failure patterns (10% and 7%, respectively), but divergent regional failure rates (55% and 39%). Severe and worse toxic events were similar between the treatment programs, but radiation-induced mucositis combined with cisplatin-induced water-losing nephropathy, in the concomitant arm only, demanded more supportive care. Survival duration was similar between the treatment arms, but significantly more patients in the sequential arm died of their cancer (P = .011). CONCLUSION: Concomitant treatment offered improved disease control, predominantly of regional disease, but benefit was dependent on the experience of the treating institution. Translation of this benefit into improved survival is not yet evident, with an excess of deaths from other causes in the concomitant arm.

Adult↗
PubMed1992

Nucleolar organizer regions in squamous cell carcinoma of the head and neck.

Nucleolar organizer regions are collections of nucleolar proteins associated with ribosomal genes that can be visualized in histologic sections using a silver colloid stain, thus the term silver-staining nucleolar organizer region (AgNOR). In some tissues, the number of AgNORs per nucleus correlates with cellular proliferation and, independently, with malignant change. AgNORs were studied in 66 paraffin-embedded head and neck squamous cell carcinomas and in 12 samples of normal tonsillar squamous epithelium. Carcinomas had a significantly higher mean AgNOR count than the benign epithelium (P less than .0001). Among carcinomas, mean AgNOR count increased with stage of the disease (P less than .001), but there was no significant correlation with histologic grade or DNA ploidy as determined by flow cytometry. These data suggest that AgNOR count should be evaluated as a possible aid in differentiating benign from malignant squamous epithelial proliferations in the head and neck, and also possibly as a prognostic marker in these carcinomas.

Aneuploidy↗
PubMed1991

Concomitant chemotherapy and split-course radiation for cure and preservation of speech and swallowing in head and neck cancer.

To assess the ability of simultaneous cisplatin, 5-Fluorouracil, and radiation to substitute for surgery and radiation in advanced head and neck cancer, we have retrospectively selected from our phase II study a subgroup of 29 patients having primary disease requiring either more than a hemiglossectomy or a laryngectomy for control. Patients included 22 with stage IV and 7 with stage III disease, 12 tongue, 10 hypopharynx, and 7 larynx primaries. The treatment consisted of concurrent cisplatin, 5-Fluorouracil, and split-course radiation every other week for a total of 7 cycles within 13 weeks. With a median follow-up of 5 years, 86% of patients had preservation of speech and/or swallowing function. Median survival was 45 months, with 14 (48%) patients currently alive and disease free, 11 (38%) dead from their cancer, and 4 (14%) dead of other causes. The overall failure rate was 38%. Advanced-stage presence of N3 nodal disease and fewer than 7 cycles of chemotherapy received were significantly associated with increasing failure rates. This program of concomitant cisplatin, 5-Fluorouracil, and radiation produced control rates quite competitive with surgery and radiation and is appropriate for definitive testing in a randomized trial.

Adult↗
PubMed1989

Combined simultaneous cisplatin/fluorouracil chemotherapy and split course radiation in head and neck cancer.

Fifty-three patients with stage III (eight patients, 15%), stage IV (36 patients, 68%), or recurrent disease (nine patients, 17%) entered a study of simultaneous cisplatin, 60 mg/m2 day 1, fluorouracil (5-FU) infusion, 800 mg/m2 days 1 to 5, and radiation, 2 Gy days 1 to 5, every other week for a total of seven cycles (70 Gy in 13 weeks). Patient acceptance was high, with only two patients (4%) refusing to complete therapy. The median actual dose delivered was 88% of the planned dose for cisplatin, 78% for 5-FU, and 70 Gy for radiation. Weight loss of 10% or more and severe mucositis were the most common side effects (53% and 48% incidence, respectively). All patients were followed at least 1 year (median, 51 months). While the complete response rate (55%) seemed no better than that reported in other series, freedom of progression of regional disease (73%), and the survival of all patients (median, 37 months) were substantially improved. Only 33% of partial responders have failed regionally, while 15% of complete responders have failed regionally (P greater than .10), which indicates that clinical assessment of response was unreliable. Stage, the presence of N3 disease, and delivery of less than the median actual dose received of 5-FU (but not cisplatin) were significantly associated with failure. This regimen is feasible and tolerable in this difficult patient population. It generally requires no special forced feeding techniques. Survival results from this limited institution study appear better than those using sequential multimodality therapies. With such favorable regional control, this approach may offer an alternative in the future to radical surgery and radiation in resectable disease. More definitive evaluation seems warranted.

Actuarial Analysis↗
PubMed1988

Concomitant therapy with infusion of cisplatin and 5-fluorouracil plus radiation in head and neck cancer.

We have combined cisplatin, 5-fluorouracil infusion, and radiation in an every-other-week schedule in a phase I-II study of 44 patients with head and neck cancer to assess toxicity and response. Ten patients were treated palliatively with 2 to 6 cycles of therapy, and 34 were treated curatively with a planned 7 cycles. Of 34 patients treated curatively, all were initially controlled. Three died during treatment (1 myocardial infarction, 1 bowel perforation, and 1 renal failure after amino-glycoside antibiotics). Four patients have had regional recurrences, 7 failed at distant sites (follow-up 2 to 5 yr). Thirty-three percent of 20 patients with complete clinical disappearance of all evidence of their cancer have had a recurrence, as have 38% of 14 (P greater than .1) with some residual abnormalities (partial responders) following treatment. All failures were in the 25 patients with T4 and/or N3 disease. None of the 9 patients with lesser stage IV or stage III disease who were followed for 24 months or more had recurrences. Eighteen patients (53%) survive with a projected 3-year survival of 63% (95% confidence interval 47% to 77%). Nine (27%) have died of disease, 1 (3%) died of a second primary in the head and neck, 3 (9%) of intercurrent disease at 15 to 45 months, and 3 (9%) during treatment. Of the 10 patients treated palliatively, 1 died during treatment with hepatic failure, 6 had complete responses, and 2 had partial responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Treatment of advanced head and neck cancer with concomitant radiation and chemotherapy.

Forty-four patients with predominantly inoperable or recurrent head and neck cancers were treated with combined chemotherapy (CT) and radiation therapy (RT) in a Phase I/II study. CT and RT were combined in a concomitant fashion to take advantage of radiosensitizing properties of the chemotherapeutic agents. Each treatment cycle consisted of cisplatin 60 mg/M2 on day 1, 5-FU infusion at a dose of 800 mg/M2 per day continuously for 5 days and RT at 200 cGy per day, days 1 through 5. The treatment cycle was repeated every 2 weeks for 7 cycles in patients treated curatively and for 2 to 6 cycles in patients treated palliatively due to prior radiation therapy or the presence of metastatic disease. Regional control was achieved in 98% of the patients. Regional control has persisted in 87% of the patients treated curatively with a minimum follow-up of 24 months. Distant failure occurred in 23% of this group. Actuarial survival of 2 years for the curative group is 66%. Concomitant combination of radiation with radiation potentiating chemotherapeutic agents shows promise of increase in local control.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Surgical complications in patients with head and neck cancer receiving chemotherapy.

We evaluated postoperative complications in a randomized series of patients with head and neck cancer who received preoperative chemotherapy. Forty-two patients with advanced squamous carcinoma of the head and neck were randomized to receive either high-dose methotrexate with leucovorin calcium rescue (23 patients) or no chemotherapy (19 patients) prior to definitive conventional treatment. The two groups of patients were balanced by sex, disease site, stage, histologic grade, and prior therapy. Sixteen of the 23 patients receiving preoperative chemotherapy had postoperative complications, whereas only eight of 19 patients not receiving chemotherapy had postoperative complications. Surgical complications included wound infections, orocutaneous fistulas, and flap necrosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

A randomized trial of adjuvant chemotherapy in head and neck cancer.

Ninety-five patients with squamous cell carcinoma of the head and neck were entered into a randomized study testing a two-week course of induction chemotherapy with methotrexate and leucovorin given prior to regional therapy. In addition, following regional therapy, patients randomized to chemotherapy were to receive similar methotrexate courses every three months for one year. Poor tolerance to this regimen after radiation and surgery led to a change in the chemotherapy following regional therapy to a combination of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin every three weeks for four cycles after the first 35 patients had been entered. Nine cases were ineligible and four lacked any follow-up data, leaving 82 analyzable cases. Using Cox regression analysis, no differences in the percentage of patients achieving disease control, the relapse-free survival, or the overall survival were identified between any treatment group. As has been described in many pilot studies of induction chemotherapy of head and neck cancer, chemotherapy responders had a more favorable disease-free survival than chemotherapy nonresponders in the total group of patients receiving adjuvant chemotherapy. However, correcting for imbalances in the expected three year disease-free survival of these patients, based on their disease site and stage, erased this difference, indicating tumor response to this regimen of chemotherapy is not an independent factor affecting disease outcome. The division of patients into arbitrary prognostic categories based on the expected outcome for each specific tumor site and stage proved to be a useful method for balancing treatment groups, given the multiple site-stage combinations within the upper aerodigestive tract. The defined prognostic categories were the single most sensitive predictors of relapse-free and overall survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Improved control in advanced head and neck cancer with simultaneous radiation and cisplatin/5-FU chemotherapy.

Chemotherapy with cisplatin plus 5-FU infusion was given simultaneously with radiation therapy; both were administered every other week. Twenty-seven patients with stage IV disease and three with stage III disease were treated; 57% had T4, 33% had N3, and 10% had M1 disease. Of these patients, 17 (57%) achieved complete response and the rest achieved partial response. However, whether or not a clinically complete response occurred had no effect on subsequent risk for disease recurrence. With a median follow-up of 16 months (range, 6-35), only 11 patients (37%) have had disease recurrence and eight (27%) have died. Of those patients who recurred, six failed in distant sites only, one developed a second head and neck primary, and four (36% of all failures) failed regionally. Normally, greater than 50% of patients who are initially controlled (usually less than 60% of stage IV patients) would have failed within the first 12 months and greater than or equal to 75% of these would be expected to fail regionally. Nine patients who had received previous treatment or who had M1 disease accounted for six of the recurrences and four of the deaths. Because of the excellent local control, we have cautiously limited surgery to conserve laryngeal, tongue, and mandibular function in selected cases. Neither immediate nor long-term toxicity from radiation appeared increased. Although no patient with such advanced disease can be considered cured at this time, these results seem to represent a substantial improvement in the quality of life and degree of local control over other approaches. Controlled trials of the sequencing of radiation and chemotherapy in head and neck cancer appear indicated.

Aged↗
PubMed1981

Acinic cell carcinoma of minor salivary gland origin.

A rare case of acinic cell carcinoma of minor salivary gland origin is reported and the literature regarding this type of tumor is reviewed. These tumors arise from either an intercalated duct stem cell or the reserve cell of the salivary gland terminal tubule but not from both simultaneously. Rarely these neoplasms arise from more mature acinar cells. It is clear that these tumors behave ominously. The 25 year determinate survival rate is 50 per cent, with a 20 per cent incidence of metastasis. Surgical excision is the treatment of choice. Radiotherapy, especially neutron therapy, has a place in the treatment of this tumor. The role of chemotherapy is not known at this time.

Aged↗