Biomedical subjects

W C Constable

Publications and source records attributed to W C Constable.

At least 19 recordsLinked to original sources

PubMed1994

Esthesioneuroblastoma. Long-term outcome and patterns of failure--the University of Virginia experience.

BACKGROUND: Esthesioneuroblastoma is a rare tumor arising from olfactory epithelium. This retrospective review analyzed the patterns of failure and long term outcome of patients with esthesioneuroblastoma evaluated at a single institution. METHODS: Forty patients with esthesioneuroblastoma were evaluated at the University of Virginia, with a median follow-up of 130 months. In most cases, treatment consisted of combined-modality therapy, including radiotherapy and surgery for Stages A and B disease and the addition of chemotherapy for Stage C disease. Fifteen patients received chemotherapy that included cyclophosphamide plus vincristine. Thirty-eight patients received radiotherapy, with a median dose of 50 Gy. Initial surgery for 23 patients included craniofacial resection, whereas the remainder had less extensive surgery (3 had no initial surgery). Five patients were salvaged with high dose chemotherapy and autologous bone marrow transplantation (CTX/BMT). RESULTS: Actuarial survivals at 5, 10, and 15 years are 78%, 71%, and 65% respectively. Fifty-five percent of patients failed therapy, and 68% of the failures were locoregional. Thirty-nine percent of recurrences occurred later than 5 years from diagnosis. Three of the five patients were successfully salvaged with CTX/BMT compared with four of seventeen patients who underwent conventional salvage therapy. CONCLUSIONS: Esthesioneuroblastoma is associated with long term survival and late recurrences. Multimodality therapy should be used initially. Durable remissions of failures can be achieved with CTX/BMT:

Adolescent↗

PubMed1992

Glomus jugulare tumors. Long-term control by radiation therapy.

The records of 49 patients with glomus jugulare tumor seen at the University of Virginia from 1932 to 1985 were retrospectively reviewed with the objective of assessing long-term results of treatment. Follow-up ranged from 5 to 31 years, with a minimum of 10 years in 36 patients (73%). According to McCabe's classification, 17 patients (35%) were Group I, 11 patients (22%) were Group II, and 21 patients (43%) were Group III. Analysis by therapeutic technique revealed that 20 patients received surgery alone (41%), 15 patients received radiation therapy alone (31%), and 14 patients received combined therapy (28%). Only 7 patients (14%) have had clinical or radiologic evidence of disease progression. Three of these patients were treated by surgery alone and three by a combination of surgery and radiation, but the dose was less than 4000 cGy. Only one patient treated by radiation therapy alone or with surgery and radiation to a dose in excess of 4000 cGy demonstrated disease progression. Salvage radiation therapy was given to three of the seven patients when progressive disease was detected. Radiation therapy is an effective treatment for glomus jugulare tumor with minimal late progression of disease in adequately treated patients and no significant long-term complications.

Adolescent↗

PubMed1991

The role of definitive radiation therapy in squamous cell carcinoma of the oral tongue.

Between 1968 and 1985, 114 patients with squamous cell carcinoma of the tongue were evaluated in the Department of Radiation Oncology at the University of Virginia (Charlottesville, VA); of these, 86 received treatment with curative intent. The majority were treated with radiation therapy alone, whereas the remainder were treated with radiation therapy with preoperative or postoperative surgery. There were 17 T1 primary malignancies, 40 T2, 27 T3, and 2 T4. Clinically positive adenopathy was present in 48% of the patients overall and ranged from 35% in the T1 group to 100% in the T4 group. Twenty-six percent of patients either presented with or later had second malignancies. At 36 months, the patient status was evaluated as dead of disease (37%), dead of intercurrent disease (23%), alive with disease (1%), and alive without evidence of disease (38%). Seventy-five patients received external beam therapy and 32 patients received an implant as either all or part of their treatment. Average doses were in the range of 6000 Gy. Adjusted local control rate at 3 years was not statistically different for different treatment techniques used on either T1 or T2 primary malignancies. The rates were 89% versus 88% for T1 lesions treated with definitive radiation therapy versus postoperative radiation therapy. For T2 primary malignancies, the rates were 67%, 71%, and 83% for the definitive, preoperative, and postoperative radiation therapy groups, respectively. For T3 lesions, there was close to statistical significance with the corresponding rates being 47%, 50%, and 100%, respectively. When the effect of implants was examined for T1 and T2 lesions, no difference in local control rate at 3 years was noticed with or without an implant. Survival was improved for the group presenting with positive neck disease when compared with the N0 group. The external beam severe complication rate was less than 5%, and the implant complication rate was 6%.

Adult↗

PubMed1991

The influence of extent of neck treatment upon control of cervical lymphadenopathy in cancers of the oral tongue.

This is a retrospective analysis of the management of the neck in 84 patients with squamous cell carcinoma of the oral tongue treated with curative intent between 1968 and 1985. Patients with a clinically negative neck were treated to the neck only if the patient was thought to have a reasonable probability of occult neck metastases. This policy resulted in a 3-year adjusted neck control rate for N0 patients treated with limited (no, bilateral-partial, or ipsilateral) neck therapy of 38% compared with 95% for patients treated with bilateral, whole neck irradiation (p less than .001). None of the relapses in the patients with limited irradiation were in the treatment portal. Attempted salvage with a neck dissection resulted in cure in only 30%. The 3-year adjusted neck control rate for the N1 and N2 patients treated with total neck irradiation and surgery was 75% and 63%, respectively. The location of recurrence in these patients was in the field of irradiation, but contralateral to the side of the neck dissection.

Carcinoma, Squamous Cell↗

PubMed1991

Phase I/II trial of superselective arterial 5-FU infusion with concomitant external beam radiation for patients with either anaplastic astrocytoma or glioblastoma multiforme.

From August 1987 through September 1989, 25 patients with either anaplastic astrocytoma (8 patients) or glioblastoma multiforme (17 patients) were entered into a Phase I trial of combined intra-arterial 5-fluorouracil (5-FU) and external beam radiation therapy. The intra-arterial 5-FU was given in a superselective, supraopthalmic fashion, in escalating doses from 200 mg to 600 mg on a weekly basis during the radiotherapy. Each patient received from 1-4 courses of 5-FU. Radiotherapy consisted of 5,000 rads in 25 fractions given to partial brain fields including the mass and surrounding edema plus a 3-cm margin as defined by computed tomography scan. There were a total of 4 significant acute complications out of a total of 70 infusions. These included 3 ischemic events of which 2 were transient. In addition, 1 patient experienced a cerebral bleed. No patients developed ocular complications. Electroencephalograms (EEGs) were performed immediately before and during 21 intra-arterial infusions. Two patients developed significant EEG changes during intra-arterial infusion, and both of these patients experienced untoward reactions. The remaining patients showed no EEG changes during their infusions. The median survival for patients with glioblastoma multiforme was 15 months. We believe the toxicity of superselective intra-arterial 5-FU infusion combined with external beam radiotherapy is acceptable. This type of treatment deserves further study.

Adult↗

PubMed1990

A phase I-II trial of multimodality management of bulky gynecologic malignancy. Combined chemoradiosensitization and radiotherapy.

Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5-fluorouracil (5-FU) 1g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External-beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow-up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3-month partial response, 43%; 3-month complete response, 45%; 8-month partial response, 15%; 8-month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.

Adult↗

PubMed1990

Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy.

A retrospective analysis was performed on all patients diagnosed with biopsy-proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda, MD), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow-up of 4.0 years and a mean follow-up of 10.8 years, the 5-year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the nonseminomatous tumors do not appear to be as radioresponsive.

Adolescent↗

PubMed1990

Curative radiotherapy in non-small cell carcinoma of the lung.

Recent reports suggest radiotherapy administered to the 5000-6000 cGy level can result in significant long-term survival in non-small cell carcinoma of the lung. This is particularly true for many cases that are technically operable but for medical or other reasons thoracotomy cannot be performed. Such patients drawn from Southern Appalachia where the principal industry is coal mining are the subject of this report. In this region coal miners pneumoconiosis (black lung) is common as well as other chronic respiratory disorders resulting in poor tolerance for surgery. Three hundred and eleven cases of non-small cell carcinoma were irradiated during the 4 years of 1980 through 1983. This group consisted of 77 patients with clinical Stage T1, T2, T3 all N0, M0 tumors, the majority of which were technically operable but upon whom no thoracotomy was performed because of medical reasons or patient refusal. All are available for 5-year study. Each of these patients was uniformly irradiated to 6000 cGy target dose in 30 fractions over 6 weeks using standard techniques. Absolute or crude survival in these 77 patients is as follows: 1 year, 57%; 2 year, 36%; 3 year, 21%; 4 year, 17%; and 5 year, 17%. Comparison with reported surgical series treated for cure show little difference in survival up to 2 years. Thereafter, the survival curves diverge with radiotherapy patients dying at a somewhat higher rate although by 4 years both survival curves slope similarly. A possible explanation for this difference is the advantage thoracotomy offers in early case selection allowing exclusion of advance cases from surgical reports whereas radiotherapy must include patients with occult local metastasis not identifiable on clinical grounds. This experience, among other reports include evidence that radiotherapy can result in long-term survival or cure with minimal morbidity in lung cancer patients in whom surgery carries excessive risk.

Carcinoma, Non-Small-Cell Lung↗

PubMed1990

Early glottic carcinoma: patterns and predictors of relapse after definitive radiotherapy.

Although definitive radiotherapy in the management of early glottic carcinomas continues to offer excellent control, a small proportion of patients will have relapse. Between January 1972 and December 1984, 148 patients with squamous cell carcinoma of the glottis (stage I in 95 patients and stage II in 53 patients) had definitive radiotherapy at the University of Virginia Medical Center. We retrospectively analyzed patient data in an attempt to identify patients at risk for relapse and the patterns of failure. The three-year determinate survival for the entire population was 94.5% (stage I--100%, stage II--86%). Twenty of the 148 patients (14%) had relapse after radiotherapy. Failure in the primary site alone was observed in 17 patients (11%), two patients (1%) had relapse in the lymphatics of the neck without evidence of primary recurrence, and one patient (0.7%) had both neck and distant disease. Of the 19 patients who had definitive surgery after recurrence, 13 (68%) were successfully salvaged. Multivariate analysis was done to identify independent factors on relapse and survival. Statistically significant factors included persistent hoarseness after radiotherapy (P = .00005), impaired cord mobility (P = .00002), subglottic extension (P = .02), anterior commissure extension (P = .001), and multifocal involvement in stage I disease (P = .0008). We conclude that a majority of the small patient population with recurrent glottic carcinoma after radiotherapy may be salvaged with surgery, and we have identified patients at increased risk for recurrence.

Adult↗

PubMed1989

Partial laryngectomy and radiotherapy for supraglottic cancer: a conservative approach.

This is a retrospective study of 33 patients with supraglottic cancer treated with partial laryngectomy and moderate-dose radiotherapy at the University of Virginia from 1967 through 1986. All patients had a 2-year minimum follow-up. Ten patients received preoperative radiotherapy, and 23, postoperative radiotherapy. The 2-year adjusted survival rate was impressive at 97%. Local control at 2 years was 96%, including one patient who was salvaged with total laryngectomy. Control of the neck was 90% at 2 years. Ninety percent of the patients alive at 2 years had a functional voice. One patient required a completion laryngectomy for chronic aspiration. Conservation surgery with radiotherapy provides excellent survival as well as locoregional control rates with preservation of function in selected patients with supraglottic cancer. This approach may be especially helpful in the management of bulky T2 lesions as well as T4 lesions with minimal vallecula or base of tongue involvement.

Adult↗

PubMed1989

Definitive radiotherapy in the management of stage I and II carcinomas of the glottis.

Definitive radiotherapy for early glottic carcinoma continues to offer excellent control and the advantage of voice preservation. In the 13 years from January 1972 through December 1984, there were 187 patients diagnosed with squamous cell carcinoma of the glottis at the University of Virginia Medical Center. One hundred forty-eight patients were treated with definitive radiotherapy as the initial management. The 3-year disease-free survival for the irradiated population was 93.6% in stage I and 75.5% in stage II. Twenty patients had recurrences following radiotherapy, and 13 of 20 were successfully surgically salvaged for an overall determinate survival of 100% in stage I and 85.7% in stage II at 3 years. These statistics are comparable to those from our previous 16-year review of 147 patients from 1956 through 1971. Factors of prognostic significance were persistent hoarseness after radiotherapy, impaired cord mobility, subglottic extension, and multiple sites of involvement in stage I. We conclude that definitive radiotherapy offers excellent survival and that a majority of the small number of treatment failures can be managed with surgical salvage.

Adult↗

PubMed1989

The influence of the surgical wound on local tumor recurrence.

Failure of a primary surgical treatment for cancer is often caused by recurrence of the tumor at the surgical site. The KHT mouse tumor system recapitulates this experience and provides a useful model to test strategies for reducing the incidence of local recurrence after surgical excision. There was an 82% local recurrence of the KHT tumor after surgery. A cell dilution assay indicated that it would require only 39 tumor cells injected into the wound site to result in the same (82%) incidence of tumors. This figure is in contrast to 340 cells required when the cells were injected into an unwounded flank. With the B16 melanoma in C57B1 mice and the Meth A sarcoma in BALB/c mice, the number of cells necessary to induce a tumor (TD/50) was also significantly reduced when the cells were injected into a surgical wound rather than into nonwounded tissue. The difference in cell number was interpreted as the result of the presence of growth factors derived from the traumatized tissue and the inflammatory cells at the wound site. Neither a 5 nor a 15 Gy dose of x-radiation delivered to the wound site immediately after surgical excision of the KHT tumor resulted in a significant reduction in the incidence of local recurrences. When the same doses of x-radiation were given immediately after injecting 36 KHT cells into a wound, no tumors developed. This difference was believed to have resulted from the hypoxic condition in the wound site and the presence of residual clonogenic tumor cells in a nonproliferating (radioresistant) state.

Animals↗

PubMed1988

Results of the radiotherapeutic management of carcinoma of the cervix with emphasis on the influence of histologic classification.

The histology of 365 of 396 patients (92%) treated with radiation therapy at the University of Virginia from 1968 to 1978 has been reviewed. Staging and treatment policies were consistent throughout this period, and have enabled the influence of histologic classification on treatment results to be evaluated. Large cell nonkeratinizing carcinoma (LCNK) was the most common type, 69%; followed by keratinizing (KSCC), 13%; and adenocarcinoma, 6.6%. Other varieties included adenosquamous, 3.6%; small cell undifferentiated carcinoma, 2.7%; papillary squamous, 1.6%; and glassy cell, 1.4%. Overall survivals by stage were similar to those reported from other centers. When examined by histologic type, the 5-year survival rates ranged from 64% for adenosquamous to 13% for small cell. The most common varieties, LCNK and KSCC, had survival rates of 61% and 40% (P = 0.008). Considering both stage and histologic type, the differences between LCNK and KSCC persisted and were significant for Stage IIB (P = 0.023). Of particular interest are the poor results in small cell carcinoma and adenocarcinoma, except in the earliest stages, and the good results for adenosquamous carcinoma. The patterns of failure by histologic type showed that local failures were higher in cases of KSCC than in LCNK, indicating a probable difference in radiosensitivity. Distant spread was similar for both types. Both small cell carcinoma and adenocarcinoma showed high rates of distant spread and local failure except in the early stages. Considering survival and failure rates, three prognostic groups could be identified. In descending order of curability these were: 1) LCNK and adenosquamous carcinoma; 2) KSCC, papillary squamous carcinoma, and adenocarcinoma; and 3) small cell carcinoma and glassy cell carcinoma.

Brachytherapy↗

PubMed1988

Primary central nervous system germ cell tumors. Effect of histologic confirmation on radiotherapy.

Primary malignant intracranial germ cell tumors are rare lesions responsible for only 0.5% of all central nervous system (CNS) malignancy. With stereotactic localization these lesions can be safely biopsied, and histologic confirmation will affect the ultimate prognosis. This report is a multi-institutional retrospective analysis of 33 patients diagnosed with a primary CNS germ cell tumor. Tumors in 14 patients (42%) were histologically confirmed (13 germinoma and one embryonal cell carcinoma); 19 patients were treated with a presumptive diagnosis. All patients were irradiated with a dose range of 3950 cGy to 6000 cGy to the primary lesions. Eight patients received craniospinal irradiation, and 25 patients were locally treated. The 5-year actuarial survival for the entire population was 64%. The survival rate in patients with histologic confirmation was 79% versus 53% in the unbiopsied population. Radiation doses greater than 5000 cGy, radiotherapy volume, and age were prognostic factors in determining survival.

Age Factors↗

PubMed1988

Whole abdominal radiotherapy following cytoreductive surgery and chemotherapy in ovarian carcinoma.

Persistent or recurrent disease following surgery and chemotherapy in ovarian carcinoma remains a major therapeutic dilemma. Between January 1980 and December 1985, there were 26 patients who had previously undergone cytoreductive surgery and chemotherapy and were treated with external beam radiotherapy. Twenty-one of these patients had been treated with platinum-adriamycin-cytoxan (PAC) regimen and 5 were treated with other combinations. Surgical reevaluation was performed in 21 of the 26 patients and only 4/21 (19%) patients were free of disease. All 26 patients were irradiated with a planned dose of 2500 cGy/100 cGy/day or 2280 cGy/120 cGy/day to the whole abdomen and a final calculated dose to the pelvis of 4500 cGy. Initial evaluation showed a 3-year actuarial survival rate of 51% and a disease-free survival rate of 42%. Follow-up analysis yields survivals of 45 and 35%, respectively. Severe gastrointestinal complications were observed in 3/26 patients and all hematologic complications resolved. Variables of prognostic significance were chemotherapy tolerance, grade, and volume of residual disease. We conclude that a proportion of patients with disease following cytoreductive surgery and chemotherapy may be salvaged with abdominopelvic irradiation.

Abdomen↗

PubMed1988

Concomitant 5-fluorouracil, mitomycin-C, and radiotherapy for advanced gynecologic malignancies.

Advanced gynecologic neoplasms continue to pose major therapeutic problems; 22,500 deaths were estimated for 1987. Between December 1983 and October 1985, there were 25 patients evaluated at our institution who on joint evaluation by the radiation oncologist and gynecologic oncologists were found to have extensive disease not amenable to standard therapy. Patients were to be treated by a combined modality approach with Mitomycin-C and 5-Fluorouracil given concomitantly with radiotherapy. Nineteen patients were treated definitively and six patients were treated with palliative intent (24 primary, 1 recurrent). The patients ranged in age from 27 to 90 years with a mean of 57.3 and a median of 57. Primary sites at presentation were: cervix--14 patients, vagina--7 patients, and vulva--4 patients. The initial FIGO stages at time of the initial diagnosis were: Stage I--1 (recurrent), Stage II--4, Stage III--15, and Stage IV--5. Chemotherapy consisted of 5-fluorouracil 1 gm/m2 given continuous infusion for 4 days with Mitomycin-C 10 mg/m2 IV push on day 1. Radiation therapy was started on day 1. Only 2 of 25 patients (8%) required chemotherapy reductions. All 25 patients received mega-voltage irradiation. The external beam dose range was 2000-6500 cGy and 14/25 patients received intracavitary or interstitial therapy. In the definitive patient group, there was no reduction in the therapeutic dose. Only four patients underwent surgical therapy. With a minimum follow-up of 8 months and a median follow-up of 28 months, the survival for the entire population was 56%. Fourteen of the 19 patients (74%) treated definitively are surviving with 12 patients having no evidence of disease. Survival by site in the definitive therapy group was cervix--70%, vulva--100%, and vagina--66%. The overall response rate was 84% at 3 and 9 months (3 months; CR--36%, PR--48%, and 9 months; CR--60%, PR--24%). There were no local recurrences in the 12 patients who achieved a complete response. Three patients died of metastatic disease alone and the overall local control was 60%. Evaluation of therapeutic side effects was performed. Hematologic analysis by the Southeastern Oncology Group criteria showed neutropenia in 14 patients (1--life-threatening, 2--severe, and 11 patients--mild/moderate) and thrombocytopenia was observed in 11 patients (all mild or moderate). All hematologic complications resolved. Acute complications did not appear increased except for the addition of mild oral mucositis (12 patients). Six patients demonstrated late effects with only 2 patients felt to have severe complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1988

Esthesioneuroblastoma: a comparison of two treatment eras.

This paper is a retrospective review of 30 patients with esthesioneuroblastoma, an uncommon malignancy of the upper nasal cavity, treated at a single institution from 1959 through 1986. Over the period of study, there has been a gradual evolution of treatment policy and technique with the introduction of craniofacial resections and complex field megavoltage radiation, as well as for Stage C disease, the addition of chemotherapy to radiotherapy and surgery. The 25 patients with a 2 year minimum follow-up are divided into 2 groups depending upon treatment era to determine the impact of modern aggressive therapy upon treatment results. Two-year survival for Group I (1959-1975) was 70% as compared with 87% for Group II (1976-85). For Stage C disease, there was a definite improvement in survival in the later era (88% versus 50%), although relapses did not appear to be circumvented. Salvage therapy has an important role in prolonging survival in this disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Combined gold seed implantation and external radiotherapy for stage B2 or C prostate cancer.

Patients with clinical stage B2 or C prostatic carcinoma represent a group for which there are several treatment options. We followed the course and outcome of 72 patients with clinical stages B and C prostate cancer who were treated with surgical staging, insertion of gold grains and external radiation at our institutions between 1975 and 1984. Of the patients 44 (61 per cent) had clinical stage B disease and the majority (89 per cent) of these were stage B2 lesions. The remaining 28 patients (39 per cent) had clinical stage C tumors. In our series 27 per cent of the clinical stage B and 68 per cent of the clinical stage C cancer patients had positive lymph nodes. The 5-year survival free of disease was 52 per cent for patients with both stages of disease. The 7-year survival free of disease was 47 per cent for patients with clinical stage B and 14 per cent for those with clinical stage C cancer. Lymph node status did not have a statistically significant effect on total survival but survival free of disease correlated significantly with node status. Local treatment failures were defined as patients who required transurethral prostatic resection or orchiectomy for palliation of obstructive symptoms related to local tumor regrowth. By these criteria we prevented local progression in 78 per cent of the patients at 5 years.

Actuarial Analysis↗