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Biomedical subjects

R W Byhardt

Publications and source records attributed to R W Byhardt.

At least 91 records · Page 5Linked to original sources

Is immediate chest radiotherapy obligatory for any or all patients with limited-stage non-small cell carcinoma of the lung? Yes.

External irradiation with the greatest technical sophistication available is indicated in all patients with inoperable non-small cell carcinoma of the lung confined to the primary site and to regional lymph nodes including the ipsilateral supraclavicular nodes. Irradiation with moderately high doses results in responses in 40%-65% of all patients. With irradiation to a level of at least 6000 rad in 30 fractions in 6 weeks, greater than 60% of patients never fail in the chest. Some of these patients become long-term, disease-free survivors. Until it is possible clearly to predict those patients who do not respond and thereby to justify an approach other than thoracic irradiation, it is necessary to offer radiation therapy to all of these patients. Since local control is far from satisfactory, one can certainly justify investigating new approaches, including further increases of the total dose, altered fractionation schemes, addition of radiosensitizers, and high linear energy transfer radiations. Since distant metastases frequently appear in spite of thorough pretreatment evaluations, one can also justify investigating the addition of systemic agents, both cytotoxic drugs and biologic response modifiers. Benefit from these systemic approaches may be completely masked, even in patients with disseminated disease, by failure to prevent complications and death due to the intrathoracic tumor.

Adenocarcinoma↗

Changes in the relative risk and sites of central nervous system metastasis with effective combined chemotherapy and radiation therapy for small cell carcinoma of the lung.

Prolongation of survival of patients with small cell carcinoma of the lung with current effective systemic therapy has been accompanied by a marked increase in the frequency of relapse in the central nervous system (CNS). Prophylactic cranial irradiation (PCI) was shown to reduce the frequency of brain metastasis, but there was no increased short-term survival. Therefore, the necessity for PCI early in the course of treatment has been questioned, especially for patients with extensive disease. From January 1974 through March 1982, 205 patients with small cell carcinoma of the lung were treated at the Medical College of Wisconsin Affiliated Hospitals. None had clinical, radioisotopic, or computed tomographic evidence of brain metastasis. Eighty-two patients received radiotherapy and chemotherapy, but no PCI; 123 patients received combination chemotherapy and radiation therapy with PCI. The cumulative probability of brain metastasis without PCI was 36% at 12 months and 47% at 24 months; the probabilities were 6 and 10%, respectively with PCI. The 24-month probability of brain metastasis in patients with limited disease and no PCI was 45%; for those with extensive disease, it was 47%. No patient presented with extracranial central nervous system (ECNS) metastasis and no one without PCI developed it. Twelve patients who received PCI developed ECNS metastasis; the cumulative probabilities rose to 14% at 12 months and 22% at 24 months. The increased frequency of ECNS involvement has led to a phase I trial of PCI followed by six cycles of combination chemotherapy, without maintenance chemotherapy, followed by irradiation of the chest and spinal cord for patients with complete response.

Brain↗

Local control and survival after external irradiation for adenocarcinoma of the prostate.

From 1966 through 1978, 128 patients with biopsy-proven adenocarcinoma of the prostate underwent external irradiation to the entire pelvis followed by additional irradiation with a field that encompassed the entire prostate with generous margins. Local recurrence was diagnosed when palpable regrowth occurred and was confirmed by biopsy. Eighteen patients (14%) had local recurrence. Actuarial (life table) local recurrence rates, however, were 24% for both for Stage B and C patients. Actuarial five year survival was 100% for the 10 Stage A patients, 91% for the 25 Stage B, and 78% for the 93 Stage C patients. Actuarial five year disease-free survival was 59% for Stage B and 69% for Stage C patients. Local recurrence was affected by the total dose to the whole pelvis and the dose at the center of the prostate. Disease-free survival was influenced by differentiation. High dose external irradiation to the prostate and regional lymph nodes offers the greatest probability of long-term disease-free survival for patients with localized disease. Late bowel complications were seen in 14 patients (11%), two of whom required colostomies. Late urinary tract complications were observed in five patients (4%).

Adenocarcinoma↗

The role of thoracic and cranial irradiation for small cell carcinoma of the lung.

Since 1974, 120 previously untreated patients with small cell carcinoma of the lung seen in Therapeutic Radiology at The Medical College of Wisconsin have been entered into one of 4 successive studies. Study I used thoracic irradiation (TI) alone (4500-6000 rad in 3-6 weeks) with chemotherapy at progression. Study II randomized patients with limited disease to TI (3000 rad in 2 weeks) plus either cyclophosphamide, doxorubicin, vincristine (CAV) or total body irradiation (TBI); patients with extensive disease received TI + CAV. Study III employed prophylactic cranial irradiation (PCI) plus CAV and withheld TI unless there was incomplete response or recurrence. Of 93 evaluable patients from the first three studies, 55 had limited and 38 extensive disease. Study I (37 patients) showed a 62% complete response (CR) rate; 43% failed in the chest, 14% had brain metastases, and the median survival was only 22 weeks in spite of a preponderance of limited disease patients. Study II (27 patients) showed a CR of 59%; 30% had brain metastases and the median survival was 48 weeks. Study II patients (29) had a 69% rate; 72% failed in the chest, 4% with PCI developed brain metastases, and the median survival was 50 weeks. In March, 1979, Study IV was initiated; patients receive PCI (2500 rad in 2 weeks) plus high dose CAV, methotrexate and leucovorin. After 6 cycles, consolidation TI (3750 rad in 3 weeks) is given to patients with complete response. Preliminary results with 27 patients treated on this study show a 67% CR rate, a 41% chest failure rate (but only 11% for the patients who received thoracic irradiation) and no intracranial failures, but a 13% extracranial CNS failure rate. PCI, TI and spinal irradiation may be necessary to maximize the probability of long term disease free survival.

Antineoplastic Combined Chemotherapy Protocols↗

The role of consolidation irradiation in combined modality therapy of small cell carcinoma of the lung.

Forty-four patients with small cell carcinoma of the lung (SCCL) were treated with a program of combined chemotherapy and radiation therapy. Prophylactic cranial irradiation was given concurrent with the first of six planned cycles of chemotherapy consisting of Cyclophosphamide, Adriamycin, Vincristine and high dose Methotrexate (CAV-M). All patients judged as complete responders (CR) received consolidative thoracic irradiation (CTI) to the locoregional primary lung involvement. The CR rate to chemotherapy alone was 84% for patients with limited disease (LD) and 44% for extensive disease. In comparison to a prior trial, which used similar chemotherapy, but with irradiation withheld until primary site relapse, the actuarial primary site relapse rate at 2 years was reduced by CTI from 92% to 18% (P less than .01). The median primary site remission duration has not yet been reached in the CTI group and was 34 weeks without CTI (P less than .01). CTI increased the 2 year actuarial survival from 6% to 66% (P less than .01) in the chemotherapy CR patients. Median survival has not yet been reached in the CTI group, but was 48 weeks without CTI (P less than .01). Leptomeningeal spinal cord relapse in patients with no prior central nervous system (CNS) involvement occurred in 16% of patients relapsing.

Aged↗

Integration of chemotherapy and radiation therapy for small cell carcinoma of the lung.

Two chemotherapy trials using cyclophosphamide, doxorubicin hydrochloride and high-dose vincristine sulfate with or without methotrexate have induced a 93% incidence of complete remission in limited disease presentation of small cell bronchogenic carcinoma of the lung and 39% incidence in extensive disease. The first trial without consolidation radiotherapy had a local failure rate of 65%, which dropped to 17% with consolidation radiotherapy to the primary and mediastinum. Prophylactic whole brain radiotherapy prevented local recurrence in 98% of evaluable patients. One carcinomatous meningitis and 5 intraspinal recurrences were noted among the 38 patients in the CAV-M trial. We conclude that high-dose vincristine sulfate is associated with an improved incidence of complete remission; that prophylactic whole brain radiotherapy has been highly successful; that prevention of intraspinal recurrence will necessitate the use of craniospinal axis radiation therapy and consolidation radiation therapy improves local control of primary and mediastinum.

Antineoplastic Agents↗

Advanced carcinoma of the nasopharynx. A clinical study of 274 patients.

A total of 274 patients with a diagnosis of nasopharyngeal carcinoma was treated in eight Veterans Administration Hospitals over a period of 22 years. Of the 274 patients, 256 (93%) had squamous-cell carcinoma, while 18 (7%) had other tumors. Most of the squamous-cell carcinoma patients (82%) had Stage IV disease; cervical lymph node metastases were found in 193 (75%), and distant metastases were present in 22 (9%). The actuarial 5-, 10-, and 15-year survival rates for the 256 squamous-cell carcinoma patients were 15%, 10%, and 7%, while they were 49%, 42%, and 35% for the 18 patients with other tumors (p = 0.006). There was a progressive decrease in 5-year survival with the increase in the stage of tumor. The survival of the 63 patients without metastases was better than the survival of the 193 patients with cervical metastases (24% vs. 12% at 5 years, p = 0.03). The presence of T4 disease or Initial Performance Status of less than 80 on the Karnofsky Scale indicated a poor prognosis (p = 0.0001). Treatment failure occurred in 83% of the patients by 2 years after therapy and was due to the lack of tumor control at the primary site. Advanced (N3) cervical lymph node metastases indicated that systemic tumor dissemination of the nasopharynx is an uncommon malignancy.

Adult↗

Local control of intrathoracic disease with chemotherapy and role of prophylactic cranial irradiation in small-cell carcinoma of the lung.

Between 1978 and 1979, 39 consecutive patients at the Medical College of Wisconsin were seen with small-cell carcinoma of the lung; of these, 31 were treated with chemotherapy and prophylactic CNS irradiation (2500 rad/10 fractions) and were evaluable after 22 month median follow-up. The intrathoracic primary was not irradiated unless there was no response to chemotherapy or subsequent recurrence. Of the 31 patients, 12 had limited disease (LD) and 19 had extensive disease (ED). Twenty, including all the patients with LD, had a complete response, eight had a partial response, and three were nonresponders. Of 24 patients with complete response at the primary site, 20 subsequently displayed local failure of the intrathoracic primary tumor, most developing disseminated extrathoracic disease simultaneously with or shortly after primary failure. The median survival time (MST) of the evaluable group was ten months with an actuarial one-year survival of 39%. Patients with LD had a median remission duration of 13 months and a MST of 16 months. Three patients are still alive with no evidence of disease at 14, 20, and 27 months. Of 26 patients receiving prophylactic cranial irradiation, all are free of CNS relapse. Chemotherapy alone appears insufficient to permanently control the bulky intrathoracic tumor, leading to the use of "consolidation" irradiation of moderate dose (3750 rad/15 fractions) to follow chemotherapy. Prophylactic CNS irradiation should be used routinely.

Antineoplastic Agents↗

Dose-time relationships and the local control of small cell carcinoma of the lung.

Since 1971, 66 patients with small cell carcinoma of the lung--32 with limited and 34 with disseminated disease--have received irradiation to the primary tumor. There were 20 local failures, 90% of which were apparent within 30 weeks of the start of irradiation. Patients were treated with local irradiation only (32), irradiation plus combination chemotherapy (25), or local plus total body irradiation (9). With local irradiation alone, tumor control increased with increasing biologic dose. When chemotherapy or total body irradiation was added, doses of irradiation that were otherwise insufficient for local control proved to be effective.

Adult↗

A combined modality approach to the treatment of Hodgkin's disease. Preliminary results of a prospectively randomized clinical trial.

Eighty-seven previously untreated patients with pathologic Stage IA, II (A or B), or IIIA Hodgkin's disease were randomized over a 48-month period to receive either megavoltage extended field radiotherapy alone or megavoltage radiotherapy limited to involved lymph node sites (including at least an upper mantle field) followed by combination chemotherapy with nitrogen mustard, vincristine, prednisone, and procarbazine (MOPP). Four patients (4.6%) failed to achieve remission with initial radiotherapy. Seventy-two evaluable patients have currently completed therapy. Ten of 41 patients achieving remission with radiation alone have relapsed, compared to only 1 of 31 receiving radiation plus chemotherapy. Seven patients have died, 3 of whom failed to achieve remission with initial radiotherapy. The other 4 had Stage IIIA disease treated with radiation alone. Severe myelosuppression occurred infrequently during chemotherapy, and neither serious infections nor second neoplasms have observed. Although these preliminary results are encouraging, longer followup is required to determine the ultimate effects of combined modality therapy on survival and long-term complications.

Adolescent↗

The role of splenic irradiation in chronic lymphocytic leukemia.

Fourteen patients with chronic lymphocytic leukemia (CCL) who received a total of 23 courses of splenic irradiation (SI)for various combinations of painful splenomegaly, progressive leukocytosis, lymphocytosis, thrombocytopenia, and anemia are reviewed. Splenic midplane doses ranged from 200-1750 rads (3-14 days), while the most typicalregimen was 300-450 rads in two to three fractions of 150 rads given over 3-8 days. Response to SI was rated according to a scoring system which evaluated the splenic and hematologic response, as well as the response of disease-related symptons. According to this scoring system, most patients demonstrated a significant relief of painful splenomegaly, along with improvement of hemogram and bone marrow parameters. While those patients judged as failures to prior chemotherapy or total body irradiation showed improvement following SI, those who had received minimal therapy prior to SI showed a superior response. SI, in those showing a satisfactory response, was repeated successfully in several patients (up to six times in one instance). The onset and duration of response to SI, dose-reponse data, survival, clinical and hemotologic responses, and the possible mechanism of action of SI are discussed with reference to the available literature.

Anemia↗

Radiation-related pericardial effusions in patients with Hodgkin's disease.

Pericardial effusions following radiotherapy for Hodgkins Disease have previously been described as infrequent and related to the total dose of radiation received. Analysis of all chest x-rays on 81 patients who received upper-mantle radiotherapy for Hodgkins Disease at the Baltimore Cancer Research Center between 1968 and 1972 disclosed an incidence of pericardial effusions of 30.9% (25 of 81), with 13.6% (11 of 81) requiring limitation of activity (5) or pericardiectomy (6). Clinical presentation of radiation-related percardial effusions was subtle, with signs and symptoms a late finding if they occurred. Radiotherapy data was reviewed and no difference in total dose (rads) or time-dose relationships (rets) was found between the groups who did or did not develop effusions. Analysis of multiple pre-treatment clinical and pathological characteristics disclosed four parameters that were felt to be related to the development of pericardial effusions; elevated ESR, normal absolute lymphocyte count, initial presence of extensive mediastinal adenopathy and the addition of adjuvant chemotherapy. The presence of increasing combinations of these pretreatment 'risk factors' led to an increasing likelihood of developing a radiation-related pericardial effusion such that six of seven patients with all four 'risk factors' developed a pericardial effusion. Nine of 13 clinically significant effusions were associated with the addition of adjuvant chemotherapy. Possible pathogenetic mechanisms that include factors other than radiation dosage and the clinical management of radiation-related pericardial effusions are discussed.

Adult↗

Recurrence patterns by treatment modality of carcinomas of the floor of the mouth and oral tongue.

Recurrence patterns were examined by stage of disease and treatment modality in 139 patients with 141 squamous cell carcinomas of the floor of the mouth and oral tongue, reflecting an 11-year experience at two hospitals. Treatment categories included surgery, irradiation, and combined treatment. Patients who were without evidence of disease at two years, or at the time of death, were considered cured. Cures were achieved in 87 per cent of patients with Stage I disease, 83 per cent with Stage II, 40 per cent with Stage III, and 34 per cent with Stage IV. Similar results were achieved by irradiation alone and by surgery alone in controlling early lesions. Combined treatment offered the best chance of cure for patients with advanced disease. Failure was most often associated with persistence at the primary site. No patient with advanced disease was salvaged after local treatment failure. One of 51 patients who received prophylactic treatment of the neck in the absence of clinical evidence of metastases had a regional treatment failure, while seven of 26 such patients who did not receive prophylactic treatment developed regional metastases. The ten-year adjusted survival rate, as calculated by the actuarial method, was 53 +/- 4.7 per cent. Forty-two multiple primary lesions were found in the 139 patients.

Carcinoma, Squamous Cell↗