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Biomedical subjects

R Komaki

Publications and source records attributed to R Komaki.

At least 127 records · Page 7Linked to original sources

Bacillus Calmette-Guérin immunotherapy in ovarian cancer.

Forty-six advanced ovarian cancer patients treated with conventional modalities with the addition of bacillus Calmette-Guérin (BCG) immunotherapy showed prolonged survival when compared to controls not given BCG. Although the data suggest enhancement of survival with the addition of BCG to conventional treatment, the fact remains that disease recurrence ultimately claims the lives of most of these patients. Nonetheless, patients are surviving longer in the face of advanced disease.

BCG Vaccine↗

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↗

Prognostic significance of interval from preoperative irradiation to hysterectomy for endometrial carcinoma.

From 1965 through 1980, 193 patients with histologically proven endometrial carcinoma, FIGO-AJC Stage I-III, received preoperative radiation therapy. One hundred forty-two patients had Stage I (G1:41, G2:68, G3:33), 47 Stage II, and 4 Stage III endometrial carcinoma. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO). They were followed from 3 to 18 years (median, 6.2 years) after the completion of the treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 85%. The interval between the completion of radiation therapy and TAH-BSO ranged from 3 days to 123 days (median, 40 days). Five-year and 10-year survivals were 95% among 65 patients who did not have residual cancer in the hysterectomy specimen compared to 75% and 70%, respectively, among 128 patients who had positive hysterectomy specimens (P less than 0.01). The presence or absence of residual carcinoma in the surgical specimen after preoperative irradiation was the only important prognostic variable. The most significant factors associated with residual cancer cells were the interval from the completion of radiation therapy to TAH-BSO (P less than 0.001) and the method of preoperative irradiation in patients with Stage I Grade 3 and Stage II external pelvic irradiation was less frequently associated with residual cancer than intracavitary applications (P = 0.043). With one exception, all patients who failed had residual cancer in the hysterectomy specimen. The depth of myometrial invasion of residual tumor in the hysterectomy specimen after preoperative irradiation was correlated to the frequency of failures (P = less than 0.05). Failures were distributed equally among the pelvis, para-aortic nodes, and distant sites. Complications of treatment were infrequent (7%) and were mild; no fatal complications were seen. The data suggest an optimal interval for hysterectomy is 29 to 42 days after completion of radiation therapy in unfavorable carcinomas of the endometrium. These patients also benefit from external pelvic irradiation with or without intracavitary applications as this therapy provides the highest probability there will be no residual cancer cells in the surgical specimen.

Adenocarcinoma↗

Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report.

This is the final analysis of Protocol #78-10 which explored increasing single-doses of half-body irradiation (HBI) in patients with multiple (symptomatic) osseous metastases. When given as palliation, HBI was found to relieve pain in 73% of the patients. In 20% of the patients the pain relief was complete; over two thirds of all patients achieved better than 50% pain relief. The HBI pain relief was dramatic with nearly 50% of all responding patients doing so within 48 hours and 80% within one week from HBI treatment. Furthermore, the pain relief was long-lasting and continued without need of retreatment for at least 50% of the remaining patient's life. These results compare favorably with those obtained by the Radiation Therapy Oncology Group (RTOG) using several conventional daily fractionated schemes on similar patients in a prior study (RTOG #74-02). HBI achieves pain relief sooner and with less evidence of pain recurrence in the irradiated area than conventionally treated patients. The most effective and safest of the HBI doses tested were 600 rad for the upper HBI and 800 rad for the lower or mid-HBI. Increasing doses beyond these levels did not increase pain relief, duration of relief, or achieved a faster response; however, the increase in dose was associated with a definite increase in toxicity. Single-dose HBI was well tolerated with no fatalities seen among 168 treated patients. A comprehensive premedication program has proven to decrease the acute radiation syndrome to very acceptable levels. There were excellent responses found in practically all tumors treated, but especially breast and prostate among which over 80% of all patients experienced pain relief, 30% in a complete fashion. Single-dose HBI emerges as one of the safest, fastest, and more effective palliative tools for intractable cancer pain in modern radiation oncology.

Bone Neoplasms↗

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↗

Dose distribution in total skin electron beam irradiation using the six-field technique.

Total skin low energy electron beam irradiation is used to treat superficially widespread skin lesions such as cutaneous T-cell lymphoma. Total skin irradiation involves delivering an adequate dose at a depth of 0.25 to 1.0 cm, while sparing underlying tissue. The dose distributions obtained when using a modified Stanford six-field technique depend upon the beam energy, the beam angle, the diameter and shape of the body part, and other variables. The dose distribution uniformity of six pairs of angulated electron beams has been studied as a function of beam energy, the gantry angle, +/- theta, above and below the horizontal and the diameter of a cylindrical polystyrene phantom. Depth doses and dose uniformity for single and multiple fields have been measured as a function of beam energy, phantom diameter and position.

Electrons↗

Correlation of treatment volume with milligram-hours for intracavitary applications for carcinoma of the cervix.

Following the recommendations of the European Curietherapy Group, the three-dimensional dose distribution corresponding to various milligram-hour volumes has been analyzed according to its length, width, and height dimensions. Thus, it is possible to state the dimensions of a number of isodose surfaces for a dose prescription given in milligram-hours. Problems associated with the exact placement of the three-dimensional dose distribution in relation to the patient's anatomy are discussed.

Brachytherapy↗

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↗

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↗

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↗

Malignant lymphoma of the uterine cervix.

Three patients with primary malignant lymphoma of the uterine cervix are reported and the literature is reviewed. All of the patients in the current cases presented with irregular menstruation. Two patients were found to have diffuse histiocytic lymphoma, and one patient had diffuse mixed lymphoma. Histologic diagnosis was confirmed by outside expert pathologists in all cases. In spite of locally advanced disease according to FIGO's classification (Stage IVA-2 and Stage IIB-1), they responded well to external irradiation, and had control of tumor within the pelvis. All are alive at 13, 7, and 3 years, respectively, after the completion of irradiation. One patient developed disseminated disease 4.25 years after the completion of external irradiation, but was successfully treated with combination chemotherapy for 2 years, and is alive at 6.75 years after the completion of chemotherapy without disease. Review of the other 21 cases reported in the literature reveals that 14 were free of disease after treatment. The importance of distinguishing malignant lymphoma from undifferentiated carcinoma or sarcoma is emphasized since cervical malignant lymphoma can be successfully treated with irradiation in spite of locally advanced disease.

Adult↗

Influence of preoperative irradiation on failures of endometrial carcinoma with high risk of lymph node metastasis.

From 1965-1980, 80 patients with adenocarcinoma of the endometrium, FIGO-AJC Stage I, Grade 3 and Stage II received preoperative radiation therapy. Thirty-three patients had Stage I, Grade 3 and 47 had Stage II. All patients were treated with preoperative radiation therapy (intracavitary application, external pelvic irradiation or both) followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. They were followed from 3-18 years (median, 6.2 years) after the completion of treatment and none was lost to follow-up. Overall 5-year actuarial disease-free survival was 75%. Preoperative external whole pelvic plus intracavitary irradiation gave the best 5-year survival of 83%; there were no failures after 20 months. In comparison to this group, survival for the intracavitary alone group was 64% at 5 years and 54% at 8 years. The 5-year survival of Stage II was 81% compared to 66% of the Stage I, Grade 3 group. Prognostic variables were analyzed and showed that the residual tumor in the specimen at the time of surgery after the preoperative irradiation was significantly correlated to a worse prognosis: patients who were found to have no residual tumor had a 5-year survival rate of 96% compared to 65% of those who were found to have residual tumor (p less than 0.01). Age, stage, methods of preoperative irradiation, dose of external pelvic irradiation or intracavitary application were not statistically significant prognostic factors. The grade of the tumor was suggestive as a prognostic variable. The most common failure site was the para-aortic lymph nodes independent of treatment methods and stage. Four patients developed complications possibly related to the radiation therapy. Our study suggests that preoperative external and intracavitary irradiation reduces the frequency of residual microscopic carcinoma and improves survival for patients with Stage I, Grade 3 and Stage II carcinoma of the endometrium.

Adenocarcinoma↗

Production of Coenzyme A by a Mutant of Brevibacterium ammoniagenes Resistant to Oxypantetheine.

For improved production of coenzyme A (CoA), a mutant of Brevibacterium ammoniagenes IFO127071 resistant to oxypantetheine, the corresponding oxygen analog of pantetheine, was obtained. In the mutant, activity of pantothenate kinase (EC 2.7.1.33), the first-step enzyme for the biosynthesis of CoA from pantothenic acid, l-cysteine, and ATP, was about threefold higher than that in the parent strain. As the main regulation mechanism of CoA biosynthesis in this bacterium is negative feedback inhibition of pantothenate kinase by CoA, the mutant is very useful as a catalyst for practical production of CoA. When added to culture broth of the mutant, pantothenate, l-cysteine, and AMP gave 9.3 mg of CoA per ml. With pantetheine and AMP, 11.5 mg of CoA per ml accumulated. These values were about threefold higher than those with the parent strain, and more than 70% of the added AMP was converted to CoA.

Journal Article↗