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R W Byhardt

Publications and source records attributed to R W Byhardt.

At least 55 records · Page 3Linked to original sources

Is long-term survival possible with external beam irradiation for stage D1 adenocarcinoma of the prostate?

From 1972 to 1986, 354 patients with local and locoregional adenocarcinoma of the prostate were treated with curative intent at the Medical College of Wisconsin. Fifty-six of these patients were found to have Stage D1 disease (evidence of pelvic lymph node involvement). Using external beam irradiation alone, these patients were treated aggressively to the pelvis followed by a boost to the prostate. The median dose to the prostate was 6800 cGy, and to the pelvis, it was 5040 cGy. The median period of observation after treatment was 9 years. Actuarial survival was 76% at 5 years, and disease-free survival was 61% at 5 years. Twenty-three patients had biopsy-proved pelvic lymph node involvement; the other 33 were considered to have Stage D1 disease based on abnormal computed tomographic scans, lymphangiograms, or both. Actuarial survival and disease-free survival were calculated for both groups separately, and there was no statistical difference in the results. Major complications occurred in 3.6% (two patients) of this group with Stage D1 disease. These results support the continued use of aggressive external beam irradiation in patients with locoregional adenocarcinoma of the prostate.

Actuarial Analysis↗

High-dose local irradiation plus prophylactic hepatic irradiation and chemotherapy for inoperable adenocarcinoma of the pancreas. A preliminary report of a multi-institutional trial (Radiation Therapy Oncology Group Protocol 8801).

Adenocarcinoma of the pancreas is an extremely malignant neoplasm with a particular propensity to spread to the liver. In an effort to combine chemotherapy with high-dose local irradiation plus a modest dose of irradiation to suspected (subclinical) hepatic metastasis, patients with unresectable pancreatic carcinomas with no known distant metastasis were treated on a prospective multi-institutional Radiation Therapy Oncology Group (RTOG) Phase I/II trial. High total dose continuous radiation therapy to the pancreas (6120 cGy in 34 fractions over 7 weeks) and simultaneous prophylactic hepatic irradiation (PHI, 2340 cGy in 13 fractions for the last 2.5 weeks) were combined with administration of 5-fluorouracil 1000 mg/m2/day (maximum, 1500 mg) by intravenous continuous infusion for 5 days starting on day 1 and repeated on day 30 for 5 days, followed by a dose of 600 mg/m2 as a weekly bolus injection starting during week 9 for 6 months. In 18 months, 81 patients were enrolled in the study; 79 were evaluable with a minimum potential follow-up of 8.2 months. The patients ranged in age from 32 to 75 years (median, 64 years). Karnofsky performance status was 80 to 100 in 74% of patients. The tumor was confined to the head of the pancreas in 72% of patients. The planned radiation therapy for the pancreas was completed in 87% of patients, 80% received the planned PHI, and 85% completed the first two cycles of chemotherapy. Seventy-five percent of patients completed both treatments according to the protocol. Most patients who did not complete both treatments had tumor progression or refused additional therapy. During all cycles of chemotherapy and radiation therapy, 2 patients died of complications (Grade 5, 1 hepatic and 1 infection), 9 had life-threatening reactions (Grade 4, 7 hematologic, 1 neurologic, and 1 mucositis), and 31 patients had severe effects (Grade 3) according to the RTOG toxicity scale. Overall hepatic metastasis was documented in 32% (13% as the first site of failure), persistent or progressive pancreatic tumor was evident in 73%, and abdominal and extra-abdominal spread were reported in 27% and 8% of patients, respectively. Eighty percent (63 patients) died (median survival, 8.4 months). Although this study suggests that PHI may reduce the frequency of hepatic metastasis, failure to control the primary tumor and intraabdominal spread remain overwhelming.

Adenocarcinoma↗

Phase II trial of combination chemotherapy and irradiation in non-small-cell lung cancer, Radiation Therapy Oncology Group 88-04.

Encouraging results of several clinical trials utilizing combination chemotherapy and irradiation in unresectable non-small-cell lung cancer have been reported. A recent report from a cooperative group study suggested that preirradiation vinblastine and cisplatin improved survival over irradiation alone. In an attempt to enhance the possible effectiveness of combination chemotherapy and irradiation, the Radiation Therapy Oncology Group embarked on a Phase II trial utilizing preirradiation vinblastine (5 mg/m2 weekly x 5) and cisplatin (100 mg/m2) on days 1 and 29 prior to irradiation and on days 50, 71, and 92 during irradiation. The irradiation began on day 50 and consisted of 6300 cGy in 7 weeks. Between May 20, 1988 and May 1, 1989, 30 patients were entered on study. Seventy-two percent of patients had Karnofsky status greater than 90, and 76% had weight loss less than 5%. Forty-eight percent of the patients were younger than 60 years of age. Forty-five percent of the patients had Stage IIIA disease. Eighty-three percent of the patients received at least four courses of vinblastine, and 59% received at least four courses of cisplatin. Seventy-eight percent of the patients received at least 95% of the prescribed irradiation. The major toxicity was hematologic, and there were two fatal complications in the study group. The preliminary survival figures are encouraging. This combination of chemotherapy and irradiation appears to be tolerable and may merit further investigation.

Aged↗

Intraoperative radiation therapy of extrahepatic biliary carcinoma: a report of RTOG-8506.

Twenty-three patients with unresected, resected but residual, or locally recurrent biliary duct cancer were entered on a Radiation Therapy Oncology Group (RTOG) Phase I-II study. Of 16 patients who were properly entered and eligible for study, eight patients (50%) completed protocol treatment including intraoperative radiation therapy (IORT). Minor acute complications from therapy were common. There was no early grade 3 or 4 toxicity. Major long-term toxicity (grade 4) was noted in one patient who suffered a perforated viscous related to salvage radiation therapy for a scar recurrence and died of infection 1 month after retreatment. With a median follow up of 10.5 months, two of the eight patients who received IORT are alive. Of the six patients who died, one had persistent disease, one had the tumor recur in the surgical wound and subsequently died of complications related to retreatment with high dose radiation, and one died of intercurrent disease. In addition, two patients died with liver metastasis, and one died with intraabdominal disease outside of the IORT volume. Bulk of disease may be an important determinant of outcome.

Adenocarcinoma↗

Comparison of the Radiation Therapy Oncology Group and American Joint Committee on Cancer staging systems among patients with non-small cell lung cancer receiving hyperfractionated radiation therapy. A report of the Radiation Therapy Oncology Group protocol 83-11.

Since 1973, the Radiation Therapy Oncology Group (RTOG) has staged and stratified patients in non-small cell lung cancer (NSCLC) protocols according to the RTOG staging system. In 1985, the American Joint Committee on Cancer (AJCC) revised its lung cancer staging system, with the principle differences from the RTOG system being the staging of involvement of the chest wall and of contralateral mediastinal and hilar lymph nodes. To determine if the AJCC system discriminated outcome differently than the RTOG system in a nonoperative series, all 850 evaluable patients treated with hyperfractionated radiation therapy (RT) on the RTOG protocol 83-11 were restaged by the AJCC system. There was 67% agreement in patient distribution between the following comparable stages in each system: RTOG Stage II/AJCC Stage II; RTOG Stage III/AJCC Stage IIIA; and RTOG Stage IV/AJCC Stage IIIB. Both systems successfully predicted for survival (P less than 0.001), although the RTOG staging was more discriminating (relative risk ratios, 1.59 versus 1.38). Among the 507 favorable patients (those with less than or equal to 5% weight loss and Karnofsky performance status [KPS] of 70 to 100), the RTOG staging was also more predictive (P = 0.004 versus P = 0.01). When RTOG Stage III (462 patients) was divided into those without contralateral mediastinal or hilar adenopathy (AJCC Stage II/IIIA) and those with (AJCC Stage IIIB), a significant survival (P = 0.0001) was noted with 2-year survival rates of 26% versus 4%, respectively. When AJCC Stage IIIA (348 patients) was divided into the patients without chest wall invasion (RTOG Stage II/III) and those with (RTOG Stage IV), a difference in 2-year survival of 22% versus 10% was observed (P = 0.002). Although both staging systems independently predict for survival, a fusion of both staging systems is the most discriminating of outcome. Future nonoperative studies in locally advanced NSCLC should stratify for contralateral nodal involvement (per AJCC staging) and chest wall invasion (per RTOG staging).

Carcinoma, Non-Small-Cell Lung↗

N2 (clinical) non-small cell carcinoma of the lung: prospective trials of radiation therapy with total doses 60 Gy by the Radiation Therapy Oncology Group.

Clinical Stage III (N2) non-small cell carcinoma of the lung encompasses a large group of patients, frequently treated with radiation therapy alone, who are now considered to have borderline-resectable tumors. Pilot studies are proceeding which use combinations of resection, radiation therapy, and chemotherapy. To place trials of combination therapy in perspective with contemporary results of radiation therapy alone, recently completed trials of the RTOG were analyzed specifically for clinical Stages T1-3N2. A prospective randomized trial of hyperfractionated radiation therapy (HFX), conducted from 1983 through 1987, compared total doses of 60.0, 64.8, and 69.6 Gy using 1.2 Gy bid with greater than or equal to 4 hr interval. After acute and late effects were considered tolerable, 74.4 Gy and 79.2 Gy arms supplanted the two lowest dose arms. Survival was compared among the five total dose arms, and with 60 Gy in 30 fractions in 6 weeks (standard fractionation-STD) from earlier RTOG studies. Of 516 HFX patients analyzed, 296 (57.3%) with Performance Status (PS) 70-100 and less than 5% weight loss (favorable) had a significantly (p = .001) better survival than those with PS 50-69 or weight loss greater than 5%. Patients with RTOG Stage III (361, 70.0%) experienced better survival (p = .027) than RTOG Stage IV M0. The 69.6 Gy total dose arm was significantly (p = .031) better in favorable RTOG Stage III patients than all other total dose arms: the 1-year survival rate was 58% and the 3-year rate was 20%. The 69.6 Gy HFX results were significantly (p = .002) better than results with STD fractionation in comparable patients from earlier RTOG trials (1-year survival = 30%, 3-year survival = 7%). A prospective, randomized Phase III comparison of STD with 60 Gy versus HFX with 69.6 Gy is underway. These results provide benchmarks for studies of surgical resection combined with chemotherapy and/or radiation therapy until results of prospective comparisons with concurrent controls are available.

Adenocarcinoma↗

Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aerodigestive tracts: preliminary report of radiation therapy oncology group protocol 83-13.

A prospective, randomized Phase Ilate/II trial of hyperfractionated radiation therapy was conducted: 1.2 Gy minimum tumor dose was administered twice daily with a minimum interval of 4 hr, 5 days per week. Patients with Stage III and IV carcinomas of the oral cavity, oropharynx, nasopharynx, hypopharynx, and supraglottic larynx were stratified by site, presence or absence of nodal metastases, and performance status. They were assigned to four total doses between 67.2 Gy and 81.6 Gy to all known tumors. The highest dose arm was opened after preliminary assessment indicated acceptable late morbidity rates with the three lower doses. Of 479 patients entered, 260 patients were randomized to the three lower total doses and 237 were analyzed for this preliminary report: 63 were assigned to receive 67.2 Gy, 58 to 72.0 Gy, and 116 to 76.8 Gy. Estimates of grade 4 necrosis at 2 years were 10.0%, 5.1%, and 13.9%, respectively, for patients who received total doses of 67.2 Gy, 72.0 Gy, and 76.8 Gy. There was a suggestion of a trend toward increased local control at 24 months (Kaplan-Meier estimates of 25% for 67.2 Gy, 37% for 72.0 Gy, and 42% for 76.8 Gy) (p = .08). No difference was observed in survival. Assessment of the results using Cox regression models to correct for slight inequalities of pretreatment prognostic variables supported a total dose-tumor control relationship (p = .054). Results for the lowest dose arm were comparable to previous RTOG studies of common fractionation with similar total doses. The higher local control rates with 72.0 and 76.8 Gy using hyperfractionated radiation therapy suggest an improvement in outcome with radiation therapy for advanced carcinomas of the upper aerodigestive tracts. These preliminary findings have led to a Phase III comparison of hyperfractionated radiation therapy with 1.2 Gy b.i.d. with standard fractionation.

Adult↗

A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy: possible survival benefit with greater than or equal to 69.6 Gy in favorable patients with Radiation Therapy Oncology Group stage III non-small-cell lung carcinoma: report of Radiation Therapy Oncology Group 83-11.

A phase Ilate/II trial of hyperfractionated (HFX) radiation therapy for non-small-cell carcinoma of the lung (NSCCL) was conducted by the Radiation Therapy Oncology Group (RTOG) between 1983 and 1987. Fractions of 1.2 Gy were administered twice daily with greater than or equal to 4 hours between fractions. Patients were randomized to receive minimum total doses of 60.0, 64.8, and 69.6 Gy. After acceptable risks of acute and late effects were found, 74.4 Gy and 79.2 Gy arms were added, and the lowest total dose arms were closed. No significant differences in the risks of acute or late effects in normal tissues were found among the 848 patients analyzed in the five arms; risks of severe or life-threatening pneumonitis were 2.6% for 60.0 to 64.8 Gy, 5.7% for 69.6 to 74.4 Gy, and 8.1% for 79.2 Gy. Among 350 patients who had the same criteria as Cancer and Leukemia Group B (CALGB) protocol 84-33 (American Joint Committee on Cancer Staging [AJCCS], 1984, stage III; Karnofsky performance status [KPS] 70 to 100; less than 6% weight loss), there was a dose response for survival: survival with 69.6 Gy (median, 13.0 months; 2 years, 29%) was significantly (P = .02) better than the lower total doses. There were no differences in survival among the three highest total-dose arms. Comparisons with results in similar patients treated with 60 Gy in 30 fractions of 2.0 Gy 5 days per week for 6 weeks suggest benefit from HFX radiation therapy with 69.6 Gy. Improvement in survival with HFX radiation therapy at 69.6 Gy total dose without increase in normal tissue effects, justifies phase III comparison with standard fractionation alone and combined with systemic chemotherapy in this common presentation of NSCCL.

Adult↗

Treatment-related toxicities with Fluosol-DA 20% infusion during radiation in advanced head and neck malignancies.

Fluosol-DA 20%, a synthetic perfluorocarbon emulsion first developed as a blood substitute, is currently being investigated as a radiation sensitizer. Theoretically, an oxygen-carrying perfluorocarbon emulsion combined with oxygen inhalation might be able to increase tumor response by decreasing the relative proportion of hypoxic tumor cells. Twenty-one patients with advanced head and neck malignancies receiving primary radiation therapy were evaluated for treatment-related toxicity. Mucosal reactions and weight loss during treatment in the group of patients who received the perfluorocarbon emulsion and the group who did not were comparable. Late sequelae appeared comparable. No patient in either group who completed radiation therapy required an interruption of the treatment course. We conclude that Fluosol-DA 20% is a tolerated adjunct to primary radiation therapy. Further study is needed to determine whether the agent will improve local/regional tumor control.

Blood Substitutes↗

Radiation therapy alone or combined with misonidazole in the treatment of locally advanced non-oat cell lung cancer: report of an RTOG prospective randomized trial.

From September 1979 to February 1983, 268 patients with unresectable, locally advanced (RTOG Stage III), non-small cell lung cancer were randomized to receive radiation therapy alone (RT) (50 Gy large field and 10 Gy boost), or combined with misonidazole (400 mg/m2 2-4 hr prior to RT daily for 5-6 weeks to a maximum dose of 12 g/m2 or until tumor progression). One hundred twenty-three patients who received irradiation alone and 116 given RT + misonidazole were evaluable for toxicity, time to tumor progression, and survival as of April 1987. The distribution of patient characteristics was similar in both treatment groups; 59% of the patients had a Karnofsky score of 90 or better, 53% had adenocarcinoma or large cell tumors, and 47% had Stage T3 tumors. Complete tumor regression was reported for 33 (27%) patients treated with radiation therapy alone and 24 (21%) who received misonidazole + RT. Median survival was 8 months with RT alone and 7.4 months with misonidazole + RT. Ninety-five percent of the patients have died. Seventy percent of the patients treated with radiation alone and 77% of those treated with misonidazole + RT died of progressive disease. Three patients treated with radiation alone and two with RT + misonidazole died subsequent to radiotherapy-related pneumonitis or pulmonary fibrosis. There was no significant improvement in response rates, local control, or survival for patients who received daily misonidazole along with irradiation compared with patients treated by irradiation alone.

Adenocarcinoma↗

Assessment of pain during head and neck irradiation.

Radiation therapy for patients with head and neck malignancies frequently results in painful mucositis, which is usually poorly controlled with standard analgesics or topical anesthetics. To better understand the temporal development of radiation-induced pain and the effects of this pain on activities of daily living, 14 patients undergoing radiation therapy for a newly diagnosed head and neck malignancy completed daily pain diaries during the course of irradiation. All patients developed painful mucositis, usually beginning during the second or third week of radiation. Despite the use of analgesics/anesthetics, pain was rated as moderate or severe on 37% of treatment days and was noted to be constant or present throughout most of the day on 58% of treatment days. Eating and sleep disturbances related to pain occurred on 55% and 34% of treatment days, respectively. Eight patients had greater than a 2-kg weight loss. Radiation induces a predictable pattern of pain and comorbidity, which may be amenable to earlier and more aggressive analgesic treatment.

Activities of Daily Living↗

The association of adult respiratory distress syndrome (ARDS) with thoracic irradiation (RT).

The authors report two cases of apparent adult respiratory distress syndrome (ARDS) following limited thoracic irradiation for lung cancer. Respiratory failure followed rapidly after irradiation with diffuse bilateral infiltrates, both in and out of the irradiated volume along with progressive hypoxemia unresponsive to oxygen management. Other potential causes of lung injury such as lymphangitic tumor, cardiac failure, and infections were excluded by both premortem and postmortem examination. Autopsy findings in both irradiated and unirradiated volumes of lung were consistent with hyaline membrane changes. The possible relationship between radiation therapy to limited lung volumes and the development of adult respiratory distress syndrome is discussed.

Carcinoma, Squamous Cell↗

The role of radiation therapy in the treatment of recurrent adult laryngeal papillomatosis.

Laryngeal papillomatosis is an uncommon condition in the adult, but it can be severe enough to require tracheostomy for obstructive changes following multiple recurrences, despite surgical local excisions and medical therapies. Few satisfactory treatments are available for such cases to restore both airway function and speech. Some patients may require laryngectomy for progressive dysfunction. The role of radiation therapy has been controversial, with some reports of malignant transformation following treatment. The authors describe two cases treated with irradiation, resulting in complete clearance of the lesions and return of airway and vocal function. Follow-up is given, and the available literature is reviewed.

Carcinoma, Squamous Cell↗

Brain metastasis in patients with superior sulcus tumors.

During a 20-year period, from 1963 to 1983, 68 patients were treated for carcinoma of the lung presenting in the superior sulcus. Their ages ranged from 41 to 79 years (median, 56 years). Thirty-six patients had squamous cell carcinoma, 13 had adenocarcinoma, 14 had large cell carcinoma, two had small cell carcinoma, and three had clinical diagnosis only. All tumors were considered to be inoperable or unresectable and were treated with external irradiation alone. The 3-year disease-free survival was 25%. Brain metastasis developed in 23 patients (34%); the brain was the first site of metastasis in 16 patients (24%), five of whom eventually developed other sites of metastasis. The cumulative probability of brain metastasis was 53% at 3 years. Brain metastases were seen in ten patients (28%) with squamous cell carcinoma, five patients (38%) with adenocarcinoma, seven patients (50%) with large cell carcinoma, and one patient without a histocytologic diagnosis. The proportion of patients younger than 60 years (19/41, 46%) who developed brain metastasis was significantly greater than that for patients 60 years or older (4/27, 15%) (P less than or equal to 0.01). Nine of 11 patients with metastasis only to the brain died as a consequence of the intracranial disease 1 to 13 months (median, 6 months) after the diagnosis of brain metastases. The other two patients received therapeutic irradiation to the entire brain and survived longer than 5 days after the whole-brain irradiation: one died at 62 months of intercurrent disease, and the other is alive and well 129 months after diagnosis. The high probability of brain metastasis from superior sulcus tumors, regardless of histopathologic type and the frequency with which the brain is the only site of clinical failure, suggest that systematic prophylactic cranial irradiation could reduce the morbidity and perhaps even contribute favorably to the survival of these patients.

Adult↗