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Biomedical subjects

R W Byhardt

Publications and source records attributed to R W Byhardt.

At least 73 records · Page 4Linked to original sources
PubMed1987

Cisplatin and fluorouracil as neoadjuvant therapy in head and neck cancer. A preliminary report.

A randomized, prospective trial utilizing cisplatin and fluorouracil as neoadjuvant chemotherapy in the treatment of advanced squamous cell carcinomas of the upper aerodigestive tract was initiated in January 1983. Sixty patients were stratified by site (oral cavity, 19; larynx, 14; hypopharynx, 14; oropharynx, 11; nasopharynx, one; and paranasal sinuses, one) and by stage (III, 19; IV, 41), and then randomized to receive either standard treatment (defined as preoperative irradiation followed by radical excision or irradiation alone) or adjuvant chemotherapy followed by standard treatment. An additional three patients were entered into the study, but withdrew. Chemotherapy consisted of three cycles for those patients in whom an objective tumor response was observed; nonresponders received standard treatment. Response to chemotherapy was complete in five and partial (greater than 50%) in 18 patients, for an overall response rate of 85%. The follow-up for surviving patients was a minimum of 24 months and a maximum of 44 months. Survival was compared for patients in both treatment groups according to the method of Lee and Desu. Despite excellent tumor response, actuarial survival was 70% in the standard treatment group as opposed to 56% in the experimental group. It was therefore evident that the high response rates reported in previous pilot studies do not necessarily result in improved survival in these cancers.

Carcinoma, Squamous Cell↗
PubMed1987

The effects of delay in standard treatment due to induction chemotherapy in two randomized prospective studies.

It is often suggested that tumors will respond to induction chemotherapy and result in improved survival for patients with squamous cell carcinoma of the head and neck. Two regimens of induction chemotherapy were studied in separate randomized, prospective trials over the last 6 years. Eighty-three patients with advanced disease were entered into the first study (43/chemotherapy; 40/control), and 60 into the second (27/chemotherapy; 33/control). Patient randomization was stratified by stage (III/IV) and site (oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, paranasal sinuses). The first study utilized bleomycin, Cytoxan, methotrexate and 5-fluorouracil in two cycles (one cycle if no tumor response), followed by standard treatment which consisted of combined irradiation and surgery or, in some instances, primary irradiation alone. The second study utilized cisplatin and 5-fluorouracil in three cycles prior to standard treatment. An objective tumor response to chemotherapy was observed in 68% in the first study and 85% in the second. The patient survival in both studies (at 24 months in the first; at 19 in the second) was better in the control than that in the experimental groups (43% to 31%; 69% to 46%). In the second study, the average length of delay of standard treatment was longer than in the first study (95 days vs. 66 days; P less than .02). Results combining the P-values of both studies indicate that the relative risk of having persistent disease was 2.9 times greater for patients who received chemotherapy. While toxicity to chemotherapy was not a factor in survival, the number of patients who withdrew from the studies and those who did not comply with treatment were greater in the chemotherapy groups. Except for new drug regimens of exceptional promise, it is recommended that future studies be designed so that chemotherapy is given concurrent with, or following the completion of standard treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Prognostic influence of TNM staging and LDH levels in small cell carcinoma of the lung (SCCL).

To better define the prognostic factors influencing the response to therapy and survival in small cell carcinoma of the lung (SCCL), an expanded "TNM" type staging system was developed and investigated in a series of 73 protocol treated patients. Because serum LDH levels at disease presentation have been correlated to disease extent, response to therapy, and treatment outcome in a number of malignancies, including SCCL, these interrelationships were also analyzed in the protocol patients. The TNM system was found to be a more descriptive and specific "shorthand" for denoting sites of involvement and for indicating the body burden of tumor than the traditional limited-extensive disease (LD-ED) system. A clear statistical advantage could not be shown over the LD-ED system for predicting chemotherapy response or survival, although there were trends suggesting the TNM system could divide patients into three prognostic subgroups. Serum LDH proved to be a useful index of disease extent and therapy outcome. LDH levels at presentation were proportionately higher with more extensive tumor, measured by either the LD-ED or TNM staging. High LDH predicted poorer responses to chemotherapy and lower survival within similar stage subgroups compared to patients with normal LDH levels. The negative effect of elevated LDH was independent of hepatic involvement and did not predict subsequent hepatic failure in any consistent way. The SCCL TNM staging system proposed needs further refinement and should be tested with larger patient numbers. LDH, along with other tumor markers recently identified, need to be integrated into the staging system to form an overall prognostic index.

Aged↗
PubMed1986

A randomized study of adjuvant chemotherapy for cancer of the upper aerodigestive tract.

A prospective, randomized trial of induction chemotherapy in advanced squamous cell carcinomas of the upper aerodigestive tract (UAD) was conducted between July 1979 and September 1982. Eighty-three patients with locally advanced Stage III-IV tumors received standard treatment (STD RX; defined as preoperative irradiation and radical excision or irradiation alone), or induction chemotherapy (CTX) followed by STD RX. Chemotherapy consisted of two cycles of bleomycin (30 units/day by continuous infusions Days 1-4), cyclophosphamide (200 mg/m2 IV Days 1-5), methotrexate (30 mg/m2 Days 1 + 5), and 5-fluorouracil (400 mg/m2 IV Days 1-5). Response to CTX was complete in 2 and partial (greater than 50% reduction) in 27; the overall response rate was 68%. Tumor clearance was documented in 30/40 STD RX patients at completion of irradiation and/or surgery and in 24/43 CTX patients (17/29 responders, 7/14 non-responders). Freedom from local-regional disease was noted at 2 years in 53% STD RX and 35% CTX patients (p less than .06). CTX patients had a higher proportion of local-regional persistence and recurrence. The difference was apparent only in the subset of patients treated with primary irradiation; local-regional control following irradiation and surgery was equal in STD RX and CTX groups. Survival at 2 years was 43% STD RX and 31% CTX. Disease-free survival in those with clearance was 64% STD RX and 59% CTX. Induction chemotherapy did not improve tumor clearance or survival in this series. Caution regarding local-regional control with CTX and primary irradiation is noted.

Bleomycin↗
PubMed1986

Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung?

Radiation therapy is widely considered the primary treatment for inoperable "non-small" cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung.

Adenocarcinoma↗
PubMed1986

Extended-field radiation therapy for prostatic carcinoma with para-aortic lymph node metastasis.

The finding of involvement of para-aortic lymph nodes in patients with adenocarcinoma of the prostate has been considered so ominous that further therapy has often only been palliative. What is the proportion of patients with carcinoma of the prostate with regional metastasis limited to the infra-diaphragmatic lymph nodes who might be cured or at least offered long-term progression-free survival by aggressive treatment? From June 1970 through March 1983, 114 patients were treated with curative intent for adenocarcinoma of the prostate, clinical Stage III, at the Medical College of Wisconsin Affiliated Hospitals. Twenty-three of these patients had evidence of metastasis to the para-aortic lymph nodes. These patients were treated aggressively with external radiation therapy to the entire pelvis and para-aortic region. The median dose to the prostate was 70 Gy, the pelvis 54 Gy, and the para-aortic region 50 Gy. The median period of observation after treatment was 53.5 months. The actuarial survival was 90% at 5 years and progression-free survival was 73% at 5 years. The rate of major complications was 4.3%. Although the number of patients is small, the data suggest that extended field radiation therapy can result in prolonged progression-free survival and perhaps cure many patients with juxtaregional dissemination of adenocarcinoma of the prostate.

Adenocarcinoma↗
PubMed1985

Combined methotrexate and high-dose vincristine chemotherapy with radiation therapy for small cell bronchogenic carcinoma.

The addition of methotrexate to a previously described regimen of cyclophosphamide, Adriamycin (doxorubicin), and high-dose vincristine (VAC) was tested in 50 evaluable patients with small cell bronchogenic carcinoma. Prophylactic whole brain radiation therapy was given during the first chemotherapy course and consolidation radiation therapy was given to the mediastinum and primary site after achieving partial or complete remission. The addition of methotrexate did not improve the incidence of complete remission as compared to a previous regimen without it. The addition of radiation therapy improved the local control rate. The high-dose vincristine in this and a previous CAV study improved the incidence of complete remission in both limited and extensive disease presentation as compared with the authors' previous experience and induced an acceptable and reversible neurotoxicity. Moderate dose consolidation radiotherapy to the lung primary and mediastinum was effective in improving local control. The distinction between limited and extensive disease was found to be vague, as 22% of the patients could be shifted from one group to the other depending on definition. The evaluation of the various staging procedures indicates that bone scan gave a small number of truly abnormal tests. Isotopic brain and liver-spleen scan could be duplicated by computerized axial tomography (CAT). CAT scan of abdomen disclosed unexpected extension to the retroperitoneal nodes and adrenals. It is concluded that radionuclide studies of brain, liver-spleen, and bone can be eliminated and can be replaced by CAT scan of brain, chest, and abdomen. Site of recurrence indicate that most intrathoracic recurrences took place outside the radiation therapy field and in the pleural space. An incidental finding was the high incidence of intramedullary spinal cord recurrence.

Adult↗
PubMed1985

Computed tomography in the staging of small cell lung cancer: implications for combined modality therapy.

Computed tomography of the thorax and abdomen, from the thoracic inlet to the renal hila, was performed as part of initial staging in 51 patients with small cell carcinoma of the lung (SCCL). The computed tomographic (CT) scans were repeated after completion of chemotherapy, as part of routine restaging and assessment of response to therapy. To identify the ways in which CT scanning uniquely benefited evaluation of initial disease extent in comparison to other diagnostic studies exclusive of CT scan, all diagnostic and clinical data were reviewed. CT scan identified more advanced intrathoracic disease than chest radiography in 82% of patients. Mediastinal node involvement not appreciated by chest radiography was seen in 61% of patients. Adrenal and retroperitoneal node involvement, not suspected by other studies, was identified by CT scan in 31% and 12% of patients, respectively. Thirty percent of the patients staged as limited disease (LD) were advanced to extensive disease (ED) by CT scan findings. While confirmation, by biopsy, of positive CT findings was not consistently accomplished, restaging CT scans provided indirect confirmation by displaying improvement or worsening that correlated with disease regression or progression. Thoraco-abdominal CT scanning more accurately identifies the extent of small cell carcinoma than other imaging procedures. This has important implications for reporting results by extent of disease. In addition, CT more accurately identifies the magnitude of intrathoracic primary and nodal tumors, which may influence the choice and conduct of local treatment--surgery and/or radiation therapy--in combination with systemic chemotherapy.

Carcinoma, Small Cell↗
PubMed1985

Characteristics of long-term survivors after treatment for inoperable carcinoma of the lung.

Between January, 1971 and August, 1978, 410 patients with histologically or cytologically confirmed inoperable or unresectable carcinoma of the lung of all cell types were treated with curative intent. Forty-five patients lived a minimum of 3 years and 32 patients lived 5 or more years. The 3-year survival rate increased from 7.6% (15/197) between January, 1971 and June, 1975 to 14.1% (30/213) for the interval from July, 1975 to August, 1978 (p less than 0.01). Factors associated with long-term survival were performance status (p less than 0.01), early stage (p less than 0.001), high total dose of radiation (p less than 0.02), large cell carcinoma (p less than 0.01), inoperable for medical reasons (p less than 0.001), and thoracotomy to determine unresectability (p less than 0.04). The difference in survival rates between the two time periods was not related to different patient factors. Survival rates were most improved in the second time period for patients with Stage II or Stage III carcinoma of the lung. Eight patients died from cancer between 36 and 54 months of initial treatment. Five patients died of intercurrent disease without evidence of cancer of the lung after 3 years. An increasing proportion of long-term survivors of inoperable carcinoma of the lung can be expected to result from a better understanding of these diseases, more technically sophisticated external irradiation, and the use of combination chemotherapy for small cell carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Multiagent chemotherapy, prophylactic neuraxis irradiation, and consolidative irradiation for small cell carcinoma of the lung.

Between 6/81 and 6/83, 73 patients with small cell carcinoma of the lung were treated according to a prospective protocol in which cyclophosphamide, doxorubicin, and vincristine (CAV) were given concurrently with prophylactic craniocervical irradiation to the level of C5. Both limited and extensive disease patients with normal computed tomography of the brain received 25 Gy in 10 fractions in 2 weeks. Complete responders to CAV received consolidative thoracic irradiation (CTI) to the local-regional primary (37.5 Gy in 15 fractions in 3 weeks), the first 25 Gy in 10 fractions serving as prophylaxis of the C6 to T12 spinal cord. The neuraxis from L1 to S2 then received 25 Gy in 10 fractions in 2 weeks. Consolidative irradiation of localizable metastatic sites was given in extensive disease patients. Partial and nonresponders to CAV received 50-60 Gy in 5-6 weeks to local-regional disease. With a median followup of 29 months, survival was significantly better (p less than .01) in patients receiving CTI to the chest after complete response to CAV (both limited disease and extensive disease) than without CTI. Of 41 patients completing the protocol and without central nervous system (CNS) involvement at presentation, four (9%) failed initially in the CNS (two brain, two spinal axis); CNS failure was the cause of death in all four patients with no other sites of metastases at death in two of these. Failure to complete protocol treatment was due to disease progression during chemotherapy in 25/73 (34%) and chemotherapy related complications (three sepsis, one gastrointestinal bleed) in four of 73 (5.5%) patients. CTI and prophylactic neuraxis irradiation did not increase morbidity or result in mortality in the sequence utilized; prophylactic neuraxis irradiation appears to reduce the CNS relapse rate, and CTI benefits survival.

Actuarial Analysis↗
PubMed1985

What is the lowest effective biologic dose for prophylactic cranial irradiation?

Between January 1974 and September 1984, 327 consecutive patients with small cell carcinoma of the lung (SCCL) free of clinical and brain scan (radionuclide or computed tomography) evidence of brain metastasis were treated at the Medical College of Wisconsin Affiliated Hospitals. All patients received single agent chemotherapy, consisting of cyclophosphamide or methotrexate (1974-1975), or combination chemotherapy with cyclophosphamide, doxorubicin, and vincristine with or without methotrexate and leukovorin (1976-1984). Between January 1974 and December 1974, 82 patients were treated with chemotherapy without prophylactic cranial irradiation (PCI). Between 1978 and 1984, all patients received PCI during the first week after diagnosis, simultaneous with their first cycle of chemotherapy. Chest irradiation was given to the complete responders to the chemotherapy. During the first 31/3 years of the study with PCI (January 1978-May 1981), 51 patients received 30 Gray (Gy) in 10 fractions in 2 weeks and five of them (10%) developed brain metastasis. Thereafter, 25 Gy in 10 fractions was consistently administered for PCI. Six of 194 patients (3%) developed brain metastasis. The cumulative (time corrected) probability of brain metastasis was approximately 10% at 1 year and was similar for patients who received 25 Gy and those who received 30 Gy. Although detailed neuropsychological testing has not been performed, clinically apparent late sequelae that might be attributed to PCI have not been seen. Nonetheless, the dose fractionation regimen of 25 Gy in 10 fractions with combination chemotherapy, cyclophosphamide, doxorubicin (or methotrexate), and vincristine is as effective in eliminating subclinical metastasis to the brain. It can be recommended for future trials until more data become available about late sequelae of treatment of SCCL and the patient characteristics and treatment factors that may contribute.

Actuarial Analysis↗
PubMed1985

Randomized study of adjuvant chemotherapy for head and neck cancer.

The ability of surgery and radiotherapy to control advanced squamous cell carcinoma of the head and neck has reached its maximal potential. We initiated a randomized, prospective, stratified study of adjuvant chemotherapy. Patients with stage II disease of the pyriform sinus and stage II and IV disease of the oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, and paranasal sinuses were eligible. Patients were randomized to receive either standard therapy alone or two courses of 5-fluorouracil (B-CMF) chemotherapy prior to and two courses after the completion of standard therapy. Standard therapy consisted of preoperative irradiation followed by radical surgery. Of 133 patients with advanced disease, 83 were included in the study--43 in the chemotherapy group and 40 in the control group. Rates of residual and recurrent disease, as well as distant metastases, were similar for the two groups. The survival rates of patients without persistent disease at the end of treatment showed no significant difference for the two groups. The study has been discontinued because statistical analysis indicated that the addition of more patients would not materially increase the statistical significance of the study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Development of a rat lung cancer model.

A rat lung cancer model based on intrabronchial instillation of a tumor cell suspension has been developed for use in therapy and toxicity testing. Two tumors were used in this study, a sarcoma and an adenocarcinoma, both of which were of spontaneous origin in the strain of rats used. The inoculated tumor cells implant on the bronchiolar mucosa, forming a detectable single "primary" tumor resembling the spontaneous lung cancers arising in humans. The tumor growth is detectable by use of diagnostic radiographs, weight loss and other "clinical" signs. The tumors appear on chest radiographs 3 to 5 weeks after inoculation, and the implant rate is proportional to the number of tumor cells inoculated. Untreated animals have a median survival (after radiographic detection of the tumor) of 8 days, and die of local complications of tumor growth. When a slow growing transplantable tumor line of lung origin is developed, this model will be used to evaluate radiotherapy and chemotherapy schedules.

Adenocarcinoma↗
PubMed1984

The prognostic significance of histologic subtyping in small cell carcinoma of the lung.

Previously untreated patients with small cell carcinoma of the lung (SCCL), who were treated at the Medical College of Wisconsin with combined chemotherapy and radiation therapy, were retrospectively subtyped according to the 1981 World Health Organization Lung Cancer Classification. Of 54 evaluated patients, 27 (50%) had "oat cell" subtype, 22 (41%) "intermediate cell" variety, and five (9%) were classified as "combined" type. There was no significant difference in response to therapy or median survival between the subtypes. In addition to the absence of prognostic significance among the subtypes, there were many technical factors affecting accuracy of subtyping, including tissue-crushing artifacts, size of biopsy materials, fixation of tissue samples, and variation of subtypes within the same biopsy. We conclude that subtyping of SCCL should not be construed as a prognostic tool or guideline to therapy. However, the recognition that SCCL may manifest in a variety of histologic patterns, some of which may be misinterpreted as a histology other than SCCL, is probably more important for choice of therapy and prognosis than the individual subtypes.

Carcinoma, Small Cell↗