NCI monographs : a publication of the National Cancer Institute最新文献

The highly variable and often prolonged clinical course of prostate cancer poses difficult problems. Some patients appear to be at such low risk that overtreatment should be avoided. Many patients must be studied for many years before 2 treatments can be compared. If the patients could be sorted into groups with predictably different survival rates, such studies could be completed in less time and/or with fewer patients. Accumulated experience indicates that the survival rates for patients with a diagnosis of prostate cancer are determined largely by three factors: the clinical stage, histologic grade of the tumor, and the patient's age. Treatment is a fourth variable factor that requires further study. In this paper, the relationships are interactions among grade, stage, and age are analyzed and discussed, and ways are suggested in which they can be combined to enhance stratification and discrimination in clinical trials of treatment. The information can also be applied broadly to the management of individual patients, but it is painfully obvious that we need a much larger body of accumulated treatment data that must include more uniform clinical staging, uniform histologic grading, and detailed patient-age reporting. These data would help adjust for the nonuniform mixture of patients in different studies. The problem of variable patient selection processes before admission to a study affects the results of many reported studies and remains a difficult problem.

Over the past 5 years, 129 patients have been treated with a combination of high-dose cisplatin (CDDP) and radiation for locally advanced epithelial malignancies. The CDDP was administered at a dose of 100 mg/m2 by iv infusion over one-half hour, no more than 1 hour before irradiation, every 3 weeks during a full course of external beam irradiation. An attempt was made to take advantage of the interaction of high-dose CDDP and radiation. Tumor systems studied included head and neck, ovary, lung, cervix, and prostate. Median survival times are as follows: squamous cell carcinoma of the head and neck (trial 1), 36 months; ovarian carcinoma, 19; and squamous cell carcinoma of the lung, 14. Median survival has not yet been reached in trials of squamous cell carcinoma of the head and neck (trial 2), cervical carcinoma, or adenocarcinoma of the prostate.

Controversy exists over the effect of definitive radiotherapy on the ability to administer full doses of adjuvant chemotherapy in primary breast cancer. Ninety-six consecutive women with clinical stage I and II breast cancer were treated with radiotherapy plus chemotherapy. Three combinations of drugs were used: cyclophosphamide and 5-fluorouracil (CF); cyclophosphamide, methotrexate, and 5-fluorouracil (CMF); or cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP). Chemotherapy consisted of two cycles of CF (cyclophosphamide at a dosage of 100 mg/m2 orally on days 1-14+5-fluorouracil at 600 mg/m2 iv on days 1 and 8) during concurrent radiotherapy, followed by six cycles of CMFP (same CF dosages+methotrexate at 40 mg/m2 iv on days 1 and 8+prednisone at 40 mg/m2 orally on days 1-14). The study included 63 premenopausal and 33 postmenopausal patients; 72 had 1-3 positive nodes, had greater than or equal to 4 positive nodes, and 9 had negative nodes and negative estrogen receptors. The mean CF doses delivered during concurrent radiotherapy were 95% of the optimal doses, and the mean CMF doses administered during the six cycles after radiotherapy were 89%. The CMF was delivered at level I (greater than or equal to 85% of optimal doses) to 73% of the patients. With a median follow-up of 36 months, 16 relapses have been observed. Two of these patients had treatment failure only in the breast or axilla and are disease free after mastectomy. Of the 72 patients with 1-3 positive nodes, 10 relapsed in distant sites, while 4 of 15 patients with greater than or equal to 4 positive nodes have had distant failure.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of vincristine (VCR) on hematopoietic stem cell and progenitor compartments and its ability to induce transient periods of radioresistance was investigated so that we could ascertain the drug-radiation intertreatment interval affording optimal radioprotection and determine if its ability to induce increased levels of superoxide dismutase (SOD) is a potential mechanism for this radioprotection. Measurement of marrow stem cell and progenitor compartments demonstrated that these subsets displayed differential sensitivity to VCR and that this sensitivity appeared to be proportional to how "primitive" the subset was. Treatment with VCR prior to irradiation was observed to enhance significantly both 8- and 12-day spleen colony-forming unit recovery with maximal radioprotection occurring for a drug-radiation interval of 12-48 hours. Monitoring of copper-zinc SOD levels demonstrated an increase in activity following VCR that was localized in a fraction of the bone marrow enriched for stem cells and progenitors. The temporal pattern of this increase, however, did not correlate with the drug-radiation schedules affording optimal radioprotection, which indicates that other factors appear to be operative in this radioprotection as well.

The central nervous system is a radiation-dose-limiting structure, and cellularity of the rat subependymal plate (a location of neuroglial stem cells) has been used as a model of radiation damage. In the present work, an attempt has been made to improve its radiation tolerance using 4-OH sodium butyrate (gamma OH). Adult rats received 10-Gy 250-kV (peak) x-rays or 3.5-Gy 15-MeV deuterons plus Be neutrons. Cell counts were obtained by histological examination of the subependymal plate. Photon and neutron irradiation alone resulted in a mean cell depletion of 62% and 58%, respectively, compared with sham-irradiated controls, which was not statistically significant; the relative biologic effectiveness was 2.9. In the absence of radiation, gamma OH did not significantly alter the cellularity of the subependymal plate, compared with that in controls treated with chloral hydrate. At doses greater than or equal to 1 g/kg, gamma OH was associated with a statistically significant reduction of subependymal plate cell depletion in animals treated with photon or neutron radiation, and the magnitude of the effect was similar. Arterial blood gas analysis failed to show a significant difference in arterial oxygen tension between control and test animals.

This report describes a laboratory model that permits study of the radiochemotherapy interactions in the CNS. Rats are stereotaxically implanted with a cerebroventricular cannula attached to an osmotic minipump, which slowly infuses a chemotherapeutic agent into CSF for up to 14 days. The cervical cord is irradiated, and forelimb paralysis develops 4-6 months later at an effective dose for paresis in 50% of the animals; the doses with radiotherapy alone are 2,125 cGy for a single fraction and 2,950 cGy for split fractions. Investigations with the model indicate that mature CNS tissue is not sensitized to either single-fraction or split-dose irradiation with either simultaneous or post-radiation exposure to high concentrations of methotrexate.

Recognition of the clinical importance of prostate cancer undoubtedly was delayed by the failure of clinicians or pathologists to distinguish consistently between benign and malignant prostatic growths until well into the 19th century. White used castration for prostatic enlargements in 1895, but Huggins and Hodges first placed endocrine therapy on a rational basis in 1941. Although a number of surgeons had attempted excision of prostate cancer, Young is credited with planning and performing the first radical perineal prostatectomy in 1904. Orthovoltage irradiation and various techniques of interstitial and intracavitary radium therapy were used in the treatment of prostate cancer early in the 20th century, but it was the development of megavoltage irradiation that reopened the door to the exploration of irradiation for localized prostate cancer following World War II. Endocrine manipulation, surgery, and irradiation remain the keystones of treatment. The management of prostate cancer is controversial for several reasons: 1) The disease occurs in an age range in which competing causes of mortality are high. 2) The natural evolution of the disease is varied, often long, and not consistently predictable. 3) Long-term survival has been reported for each of the principal modes of therapy, but randomized controlled studies have been limited. Uniformity in histologic grading, clinical staging, and evaluation of response to treatment would improve the quality of the data. Predictions of host life expectancy, tumor growth rate, metastatic potential, and tumor responsiveness to irradiation and endocrine therapy would enhance the rationale of treatment.

Data are presented from the Patterns of Care Study and other sources that define the role of external-beam irradiation in the management of localized prostate cancer as practiced in the United States as a whole. Patients must be treated with complex treatment techniques and high-energy linear accelerators and careful adjustment of radiation dose. Transurethral resection of the prostate should be avoided in the intermediate and poorly differentiated subgroup of stage C patients. The excellent 5- and 10-year survival for patients treated by radiation therapy is demonstrated for all stages of prostate cancer and for T1 or early stage B patients. It is noted that the national averages for survival have improved between 1973 and 1978. Stages A2 and B patients with negative lymph node dissections show freedom from recurrence that is equal to patient reports for radical surgery. Complications resulting from radiation therapy were modest, and potency was maintained in 73% of the patients. Adjuvant irradiation is necessary for pathologic stage C patients after recovery from surgery. Radiation therapy is equally effective though less costly than surgery for early prostate cancer. A particular need of future research is the study of the patterns of care in the United States regarding the surgical management of prostate cancer so that health professionals can determine if this care is generally available throughout the United States and if good outcome and acceptable morbidity result after it is given.

Adenocarcinomas of the gastrointestinal tract have generally been considered to be radioresistant. In 1974-1975, following an early lead from the Mayo Clinic (Rochester, MN), the Gastrointestinal Tumor Study Group initiated a series of clinical trials of radiation therapy and chemotherapy as surgical adjuvant programs for patients with pancreatic and rectal cancer and for the treatment of locally unresectable gastric and pancreatic adenocarcinomas. The first protocols for pancreatic cancer included a controlled trial of radiation therapy and chemotherapy following pancreatoduodenectomy or total pancreatectomy and also a randomized trial of high-dose radiation therapy, with or without chemotherapy, compared to a lower dose of radiation therapy combined with chemotherapy for patients with locally unresectable tumors. In the treatment of locally incurable gastric cancer, radiation therapy plus chemotherapy was compared to chemotherapy alone, while the rectal trial was a randomized comparison of radiation therapy; chemotherapy; the combination of radiation therapy and chemotherapy; and no further treatment following surgical extirpation. In all cases, the agent used during the course of radiation was 5-fluorouracil. Subsequent trials in pancreatic cancer compared radiation combined with either 5-fluorouracil or doxorubicin and included a pilot study of hyperfractionated radiation therapy combined with 5-fluorouracil. Confirmatory trials were undertaken and are still under analysis in gastric cancer and in rectal cancer. A follow-up trial in pancreatic cancer was developed to establish the importance of the radiation therapy component of combined modality therapy in the treatment of patients with locally unresectable disease. A final study examined the potential for radiation therapy of the liver and systemic chemotherapy in the prevention of metastatic adenocarcinoma of the colon.(ABSTRACT TRUNCATED AT 250 WORDS)