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Biomedical subjects

H Goepfert

Publications and source records attributed to H Goepfert.

At least 91 records · Page 5Linked to original sources
PubMed1994

Postoperative radiotherapy for cutaneous melanoma of the head and neck region.

PURPOSE: To assess the efficacy and toxicity of elective-adjunctive radiotherapy given in five 6-Gy fractions to patients with cutaneous melanoma of the head and neck at high risk for local-regional relapse. METHODS AND MATERIALS: From 1983 to August 1992, 174 patients (132 men and 42 women) were enrolled. The ages ranged from 16 to 89 years (median: 54 years). One group (n = 79) received elective irradiation after wide local excision of lesions > or = 1.5 mm thick, or Clark's level IV-V, a second group (n = 32) received adjunctive irradiation after excision of primary lesions plus limited neck dissection, and a third group (n = 63) received irradiation after neck dissection for nodal relapse. Each group had a projected local-regional recurrence rate of approximately 50%. The radiotherapy consisted of five fractions of 6 Gy each, specified at Dmax, delivered twice a week, to a total dose of 30 Gy in 2.5 weeks. Electron beams of appropriate energies were used whenever possible. Junction lines between adjoining fields were moved twice to minimize dose heterogeneity. Patients were seen at regular intervals to assess disease status and therapy-related complications. Patients who relapsed were treated as indicated by the clinical status. RESULTS: With a median follow-up of 35 months, 111 of 174 patients were alive. The disease recurred above the clavicles only in six patients, at distant sites in 58 patients, and both local-regionally and at distant sites in nine patients. The actuarial 5-year local-regional control (LRC) and survival rates for the whole group were 88% and 47%, respectively. The thickness of the primary lesion, presence of more than three positive nodes, and extracapsular extension did not influence the LRC rate after radiotherapy (range: 85-92%). However, lesion thickness strongly affected the 5-year survival rate of group 1 patients (i.e., 100% for < or = 1.5 mm thick, but Clark's level IV, 72% for > 1.5-4 mm, and 30% for > 4 mm). In groups 2 and 3, the 5-year survival rate of patients with > three involved nodes was lower than that of patients with one to three positive nodes (23% vs. 39%). The acute tolerance to adjunctive radiotherapy was excellent. Late radiation complications were observed in only three patients. These were moderate neck fibrosis, mild ipsilateral hearing impairment, and transient exposure of external auditory canal cartilage. CONCLUSION: The safety of this hypofractionated radiotherapy regimen in the management of cutaneous melanoma was established in this study. The overall 5-year actuarial LRC rate of 88% was much higher than that of our historical group and that reported in the literature (50%). The survival rate of patients with lesion of 1.5-4 mm thickness was also higher than that observed in other series. Based on these results a prospective randomized study to further define the role of adjunctive postoperative radiotherapy is planned.

Adolescent↗
PubMed1994

Growth suppression of human head and neck cancer cells by the introduction of a wild-type p53 gene via a recombinant adenovirus.

Mutations of the p53 gene constitute one of the most frequent genetic alterations in squamous cell carcinoma of the head and neck (SCCHN). In this study, we introduced wild-type p53 into two separate SCCHN cell lines via a recombinant adenoviral vector, Ad5CMV-p53. Northern blotting showed that following infection by the wild-type p53 adenovirus (Ad5CMV-p53), cells produced up to 10-fold higher levels of exogenous p53 mRNA than cells treated with vector only (without p53). Western blotting showed that the increased levels of p53 protein produced in the Ad5CMV-p53-infected cells were a reflection of p53 mRNA expression. In vitro growth assays revealed growth arrest following Ad5CMV-p53 infection as well as cell morphological changes consistent with apoptosis. In vivo studies in nude mice with established s.c. squamous carcinoma nodules showed that tumor volumes were significantly reduced in mice that received peritumoral infiltration of Ad5CMV-p53. These data suggest that Ad5CMV-p53 may be further developed as a potential novel therapeutic agent for SCCHN since introduction of wild-type p53 into SCCHN cell lines attenuates their replication and tumor growth.

Adenoviridae↗
PubMed1994

A single center's experience with 308 free flaps for repair of head and neck cancer defects.

Since its inception at our institution in 1988, microvascular reconstructive surgery has become an integral part of the treatment of head and neck cancer patients. This review of 308 free flaps performed over the last 4 years was done to evaluate the complication and flap loss rates and to investigate which factors may contribute to these rates. The overall complication rate was 36.1 percent, the vessel thrombosis rate was 6.8 percent, the flap loss rate was 5.5 percent, and the flap salvage rate was 19.0 percent. Multifactorial analysis of delayed reconstruction, tobacco use, alcohol consumption, previous radiation therapy, previous surgery, and use of vein grafts showed that only previous surgery and the use of vein grafts led to significantly higher rates of flap loss (p < 0.01 for both).

Adolescent↗
PubMed1993

Polymerase chain reaction-based restriction fragment length polymorphism analysis of the short arm of chromosome 3 in primary head and neck squamous carcinoma.

BACKGROUND: Deletion or loss of heterozygosity (LOH) at the polymorphic loci on the short arm of chromosome 3 has been reported in a large number of renal cell, small cell lung, non-small cell lung, and cervical carcinomas, suggesting the presence of one or more putative tumor suppressor genes at chromosome 3p. Similar studies in primary head and neck carcinoma are lacking. METHODS: To investigate the possibility of chromosome 3p deletions, the authors applied a polymerase chain reaction (PCR)-based, restriction fragment length polymorphism analysis, in conjunction with conventional Southern blot techniques, to DNA samples of matched normal mucosa and head and neck squamous cell carcinomas from 18 patients. The authors also assessed the merit of the PCR-based assay as a rapid screening tool, particularly in assaying limited tissue samples. RESULTS: Constitutional heterozygosity at the polymorphic loci varied in the 18 normal samples that the authors studied: 12 at the D3F15S2 locus (on telomeric 3p21), 7 at the D3S32 locus (on centromeric 3p21), and 9 at the THRB locus (on 3p24). In 18 matched carcinoma specimens, LOH (deletion) was observed at D3S32 in 0 of 7, at D3F15S2 in 9 of 12 (75%), and at THRB in 3 of 9 cases (33%). CONCLUSIONS: The results of the PCR-based assay and Southern blotting were completely concordant in all specimens the authors studied. This study indicates that deletion at 3p is a frequent abnormality in primary head and neck carcinoma and that the most common deletion region is telomeric to D3S32. The authors also observed an apparent correlation among poor histologic differentiation, DNA aneuploidy, and 3p deletions. Most poorly and moderately differentiated and aneuploid carcinomas manifested the 3p deletion. Therefore, the authors suggest an association between deletion at 3p and aggressive biologic behavior.

Aged↗
PubMed1993

Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial.

PURPOSE: This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors. METHODS AND MATERIALS: Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving > 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk. RESULTS: The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of < or = 54 Gy had a significantly higher primary failure rate than those receiving > or = 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at > or = 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, > or = 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status > or = 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received > or = 63 Gy. CONCLUSION: With daily fractions of 1.7 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio.

Adult↗
PubMed1993

Regulation of urokinase-type plasminogen activator expression in squamous-cell carcinoma of the oral cavity.

We undertook a study to determine the role and regulation of expression of urokinase-type plasminogen activator in squamous-cell carcinoma of the oral cavity. The contribution of urokinase to the invasive process was clearly demonstrated in experiments in which in vitro invasion by a cultured squamous-cell carcinoma cell line was substantially reduced by a monoclonal antibody directed at the catalytic site of urokinase. The conditioned medium from 2 invasive cell lines contained high levels of urokinase. Examination of resected tumors for urokinase revealed (a) localization of the antigen to the tumor cells and (b) higher levels of the plasminogen activator in tumor tissue than in adjacent non-malignant tissue. These results suggested that elevated expression of urokinase is a common feature of this malignancy. The mRNA half-lives of cell lines expressing high and low levels of urokinase were similar, indicating that elevated levels of mRNA for the plasminogen activator were not a consequence of a more stable transcript. No evidence of u-PA gene amplification was obtained by Southern blotting of DNA derived from the cell lines expressing high urokinase levels. Transfection of squamous-cell carcinoma cells, which express high levels of urokinase, with a construct bearing the chloramphenicol acetyl transferase gene driven by the full-length (2345 bp) urokinase promoter indicated activation of the urokinase promoter in trans. In conclusion, our results suggest that transcriptional activation of the urokinase gene, in squamous-cell carcinomas of the oral cavity, leads to elevated levels of urokinase mRNA/protein which, in turn, can promote the invasive phenotype.

Blotting, Western↗
PubMed1993

Discordant p53 gene mutations in primary head and neck cancers and corresponding second primary cancers of the upper aerodigestive tract.

Patients with primary head and neck malignancies have a 3-7% yearly incidence of second primary cancers. It is thought that these second primary cancers arise independently following exposure to a common carcinogen by a process that has been called field cancerization. Since mutations in the p53 tumor suppressor gene represent a genetic alteration occurring during the evolution of premalignant lesions to malignancies of the upper aerodigestive tract, we analyzed mutations in the p53 gene of patients with cancer of the head and neck who developed second primary tumors of the upper aerodigestive tract epithelium to test the field cancerization hypothesis. DNA was extracted from primary head and neck cancers and second primary cancers of 31 patients. DNA from exons 5-8 of the p53 gene was analyzed by the single strand conformation polymorphism technique to identify the locations of the mutations in different regions of the gene. DNA from 6 patients was also sequenced by the chain termination method to confirm the presence of mutations and determine the base substitutions. Twenty-one of the 31 patients had 1 or more p53 mutations. In all 21 cases the genetic lesions were discordant such that the presence or location of the mutations in the initial primary cancer differed from those of the second and third primary cancers. In each of the five patients with mutations in both primary tumors, the mutations occurred in different regions of the p53 gene. Of the other 16 patients, 8 had a p53 mutation in the first primary but not the subsequent primary cancer and the other 8 had no mutation in the initial primary but did have a mutation in subsequent primary cancers. Sequencing confirmed the single strand conformation polymorphism analysis and showed that 73% of the mutations were transitions. The discordant p53 mutations in second primary cancers arising in patients with primary epithelial cancer of the upper aerodigestive tract suggest that these cancers arise as independent events. These observations provide the first demonstration of a molecular basis for field cancerization effects in cancers of the upper aerodigestive tract.

Adult↗
PubMed1993

Pulmonary metastases in children and young adults with differentiated thyroid cancer.

BACKGROUND: The prognostic significance and optimal care of children with differentiated thyroid cancer and pulmonary metastases are not well established. METHODS: Of 209 patients younger than 25 years of age who were treated at University of Texas M. D. Anderson Cancer Center between 1960 and 1990 and for whom there was sufficient information, 19 (9%) had pulmonary metastases at presentation. RESULTS: All of these patients had regional lymphadenopathy at the time of diagnosis. All but two had intense, diffuse radioiodine uptake in the lungs; there were two false-negative scans immediately after surgical procedure caused by competing thyroid residual. The chest radiograph (CXR) was normal in 8 of 17 (42%) patients with abnormal radioiodine scans. After therapy with radioiodine (100-499 mCi), CXR appeared normal in 7 of 9 patients with initial abnormal radiographs (within 6-75 months). Radioiodine uptake by the lungs normalized in 3 of 8 patients with initially normal radiographs, and in 3 of 9 patients with initially abnormal radiographs. There have been no deaths in these 19 patients. CONCLUSION: Pulmonary metastases are not uncommon in children and young adults with differentiated thyroid cancer, especially those who have regional lymphadenopathy. The lung metastases almost always concentrate radioiodine diffusely and may be associated with a normal CXR in almost half of the patients. Pulmonary metastases may be overlooked unless near total thyroidectomy is followed by total body radioiodine scan (TBS) in all children and young adults who have regional lymphadenopathy of the neck.

Adenocarcinoma↗
PubMed1993

Comparison of low-dose isotretinoin with beta carotene to prevent oral carcinogenesis.

BACKGROUND: High-dose isotretinoin therapy has been determined to be an effective treatment for leukoplakia. However, a high rate of relapses and toxic reactions led us to conduct a trial of a much lower dose of isotretinoin in the hope of maintaining a response and limiting toxicity. METHODS: In the first phase of the study, 70 patients with leukoplakia underwent induction therapy with a high dose of isotretinoin (1.5 mg per kilogram of body weight per day) for three months; in the second phase, patients with responses or stable lesions were randomly assigned to maintenance therapy with either beta carotene (30 mg per day) or a low dose of isotretinoin (0.5 mg per kilogram per day) for nine months. RESULTS: In the first phase, the rate of response to high-dose induction therapy in the 66 patients who could be evaluated was 55 percent (36 patients). The lesions of seven patients progressed, and therefore they did not participate in the second phase of the trial. Of the 59 patients included in the second phase, 33 were assigned to beta carotene therapy and 26 to low-dose isotretinoin therapy; these two groups did not differ significantly in prognostic factors. Of the 53 patients who could be evaluated, 22 in the low-dose isotretinoin group and 13 in the beta carotene group responded to maintenance therapy or continued to have stable lesions (92 percent vs. 45 percent, P < 0.001). In situ carcinoma developed in one patient in each group, and invasive squamous-cell carcinoma in five patients in the beta carotene group. Toxicity was generally mild, though greater in the group given low-dose isotretinoin therapy. CONCLUSIONS: When preceded by high-dose induction therapy, low-dose isotretinoin therapy was significantly more active against leukoplakia than beta carotene and was easily tolerated.

Adult↗
PubMed1993

Predicting occult lymph node metastasis in parotid cancer.

To determine the factors predictive of occult cervical metastases, we retrospectively reviewed the charts of 99 previously untreated patients with a primary parotid malignancy who underwent elective neck dissection between 1960 and 1985. Univariate and multivariate analyses were performed to determine the predictive value of 11 factors. The univariate study found facial nerve paralysis, extraparotid extension, and perilymphatic invasion statistically significant. In the multivariate analysis of preoperative factors, facial nerve paralysis was most predictive of occult disease. If the variable pool was expanded to include a fine-needle biopsy, tumor grade became the most important preoperative variable. When the analysis was further expanded to include a parotidectomy, the most influential factors were patient age, perilymphatic invasion, and extraparotid tumor extension. This report identifies the variables predictive of occult neck disease in parotid cancer.

Adolescent↗
PubMed1993

Squamous cell carcinoma of the maxillary sinus.

Eighty-five patients with squamous cell cancer of the maxillary sinus received all of their treatment at The University of Texas M.D. Anderson Cancer Center between the years 1971 and 1986. Their records were evaluated according to stage, disease at presentation, symptoms and signs at presentation, treatment, and outcome. There were no differences in locoregional control or survival between groups treated with surgery alone vs surgery plus radiotherapy. Careful analysis of the data indicates that there was almost certainly some selection bias for the patients undergoing combination therapy, as most of this group had historically adverse prognostic factors identified. Those patients who underwent radiotherapy alone or chemotherapy presented with either metastatic or locally advanced disease and were treated with palliative intent; therefore, comparison between this group and standard therapy groups was impossible in this retrospective review. Although it is tempting to speculate that combination therapy improved locoregional control and survival in patients with more advanced disease, none of the data presented in this review reach statistical significance. Furthermore, there is no difference in survival in this population compared with a study at this institution 20 years ago. Squamous cell cancer of the maxillary sinus continues to be a challenging neoplasm. Radiotherapy may improve locoregional control and survival in a group of patients with more advanced disease and may have its greatest utility in earlier-stage disease. A multi-institutional prospective trial is needed to find ways to improve outcome in this patient population.

Adolescent↗
PubMed1993

Influence of prior radiotherapy on the development of postoperative complications and success of free tissue transfers in head and neck cancer reconstruction.

The purpose of this study was to determine whether prior radiotherapy had any effect on the development of postoperative complications in patients undergoing microvascular tissue transfers for reconstruction of head and neck cancer. A prospective database was used to review 354 consecutive patients who had a total of 368 free tissue transfers limited to the head and neck during the 4-year period from July 1988 to June 1992. Postoperative complications in 167 patients who received preoperative radiotherapy (XRT) were compared with those of 187 patients who did not undergo radiotherapy preoperatively (NR). No statistical differences in complications or flap loss between the two groups were noted using the chi 2 test or Fisher's exact test (p > 0.2). Total flap loss occurred in 5.3% of the XRT group (9 of 169) and 5.0% of the NR patient group (10 of 199), and partial flap loss occurred in 4.1% of the irradiated patients and 2.5% of the nonirradiated patients. Major wound complications requiring additional surgery occurred in 16% of the XRT group and 11% of the NR group. Minor wound complications that did not require further surgery occurred in 21% of the irradiated patients and 18% of the nonirradiated patients. No significant difference in the timing or dose of preoperative radiation, previous neck dissection, or anastomotic type could be documented in failed versus successful flaps (two-tailed t-test, p > 0.80, and chi 2, p > 0.2). Our results show that, in a large group of cancer patients undergoing free tissue transfers to the head and neck, prior radiotherapy or surgery did not predispose them to a higher rate of acute flap loss or wound complications than their nonirradiated cohorts.

Adolescent↗
PubMed1993

Rhabdomyosarcoma of the adult head and neck: a clinicopathological and DNA ploidy study.

We investigated the DNA ploidy patterns in thirteen primary and four recurrent rhabdomyosarcomas of the head and neck from thirteen adult patients and correlated the findings with other clinicopathological factors and clinical outcome. Twelve (92.7 per cent) of the primary neoplasms manifested an aneuploid DNA pattern, five had more than one stemline, and one neoplasm displayed a diploid DNA pattern. All recurrent lesions were DNA aneuploid with DNA indices (DIs) corresponding to their primary neoplasms. No correlation between the ploidy pattern and histological subtypes, tumour location, clinical stage and patient's clinical course was found. In this study, only two patients were long-term survivors. Both patients had stage I neoplasms that were located in non-parameningeal sites which manifested an alveolar histological pattern. Our data indicate that adult rhabdomyosarcomas of head and neck are preponderantly DNA aneuploid and are highly aggressive malignant neoplasms. Our results also suggest that tumours which are low stage and in a non-parameningeal location may pursue a less aggressive course.

Adolescent↗
PubMed1993

Paratracheal lymph node dissection for carcinoma of the larynx, hypopharynx, and cervical esophagus.

Paratracheal lymph node (PTLN) metastasis has been implicated as an etiologic factor in peristomal recurrence after laryngectomy. To determine the relationship between the primary site, the risk of peristomal recurrence, and the prognostic significance of PTLN metastasis, the medical records of 645 patients who underwent total laryngectomy between 1978 and 1990 for squamous cell carcinoma of the larynx, hypopharynx, and cervical esophagus were reviewed. Criteria for inclusion were the surgeon's description of PTLN dissection and hemi- or total thyroidectomy, as well as gross and microscopic pathologic identification of PTLNs. These requirements were fulfilled in 141 patients, who composed the cohort analyzed. There were 117 males and 24 females, with a median followup of 20 months (range, 1 to 94 months). Fifty-three patients were treated previously; among these, 21 underwent tracheostomy before laryngectomy. The primary site of origin was the larynx in 64.5% of patients, the hypopharynx in 25.5%, and the cervical esophagus in 9.9%. Of the patients with endolaryngeal primary tumors, 33% had subglottic extension. Postoperative stomal irradiation was administered to 61 patients. The mean number of PTLNs removed was 3.9 (range, 1 to 30), and metastasis was present in 29 patients (20.5%). PTLN metastasis by primary tumor site was the cervical esophagus, 10 of 14 (71.4%) (p < 0.001); the larynx, 16 of 91 (17.6%); and the hypopharynx, 3 of 36 (8.3%). Of the 30 patients with subglottic extension, eight (26.7%) had PTLN metastases. Peristomal recurrences developed in six of 141 patients (4%), and metastasis to PTLNs was identified in one third of these patients. No peristomal recurrence developed in any of the patients who received postoperative radiotherapy to the stoma (p = 0.057). Survival was significantly reduced by the presence of PTLN metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Orbital preservation in maxillectomy.

Twenty-eight previously untreated patients with squamous carcinoma of the maxillary sinus underwent maxillectomy with preservation of the orbital contents at the M. D. Anderson Cancer Center between 1971 and 1986. Eighteen patients had part or all of the orbital floor resected; nine patients were treated with radiotherapy, and nine had surgery only. Only 3 of 18 patients in this group (17%) retained significant function in the ipsilateral eye. Furthermore, local recurrence in this group was common (44%), regardless of whether postoperative radiotherapy was used. Ten patients retained the bony orbital floor; if the radiation fields did not include the eye, problems were minimal. Strong consideration should be given to orbital exenteration at the time of surgery, when the orbital floor is resected--especially if postoperative radiation fields will include the eye.

Carcinoma, Squamous Cell↗
PubMed1993

Effectiveness of combined induction chemotherapy and radiotherapy in advanced nasopharyngeal carcinoma.

PURPOSE: This prospective trial was conducted with the goal of achieving an improvement in both overall and progression-free survival in previously untreated patients with stage IV nasopharyngeal carcinoma who received an induction chemotherapy regimen of fluorouracil (5-FU) and cisplatin followed by radiotherapy. PATIENTS AND METHODS: From January 1985 to January 1990, 47 patients with T1-4N2-3M0 squamous cell carcinoma of the nasopharynx were treated at The University of Texas M.D. Anderson Cancer Center with two to three cycles of 5-FU (1,000 mg/m2 continuous infusion per day x 5 days) plus cisplatin (100 mg/m2 continuous infusion on day 1 only) followed by radiotherapy using the conventional time/dose schedule. RESULTS: The response rate to chemotherapy was 93.2% (20.5% complete response [CR]; 72.7% partial response [PR]), and the overall CR rate after radiotherapy was 86%. With a median follow-up period of 53 months, the 2-, 4-, and 6-year survival rates were 80%, 71.6%, and 67.4%; the overall treatment failure rate was 27%. Treatment was well tolerated and without significant acute or chronic toxic effects. CONCLUSION: The results of this prospective study demonstrate that 5-FU plus cisplatin followed by radiotherapy can induce a durable remission in a high proportion of patients with poor-prognosis stage IV nasopharyngeal carcinoma.

Adolescent↗