The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases.

PURPOSE: To determine the prevalence and clinical associations of anticardiolipin antibodies (aCL) in a blinded, controlled study of patients with a variety of connective tissue diseases (CTD) using a standardized aCL testing system. PATIENTS AND METHODS: Anticardiolipin antibodies (IgG, IgM, and IgA) were measured by direct enzyme-linked immunosorbent assay (ELISA) in the baseline serum samples of patients enrolled in a Cooperative Study of Systematic Rheumatic Diseases (CSSRD), National Institutes of Health (NIH) supported, 5-year inception-cohort, prospective study of early rheumatic diseases: rheumatoid arthritis (RA, n = 70), systemic lupus erythematosus (SLE, n = 70), scleroderma (PSS, n = 45), myositis (PM/DM, n = 36), and early undifferentiated connective tissue disease (EUCTD, n = 165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjögren's syndrome (SJ, n = 44) was also defined. Serum from 200 blood donors (BB) served as controls. Additional patients with known antiphospholipid syndrome (APS, n = 33) and ANCA-related renal vasculitis (ANCA, n = 52) were also studied. Laboratory personnel were blinded to sample diagnostic group. RESULTS: The prevalence of either IgG or IgM aCL among each diagnostic group was RA 15.7%, SLE 15.76%, PSS 6.7%, PM/DM 8.3%, EUCTD 9.1%, SJ 6.8%, ANCA 3.8%, and BB controls 4.0%. Prevalence of aCL was significantly different for both the RA and SLE groups versus BB controls (P < 0.01) but not among other diagnostic groups. Only 2 study patients had positive tests for IgA aCL (1 with PM/DM and 1 with EUCTD) versus 15% of APS with positive IgA aCL. Study patients positive for IgG or IgM aCL were significantly more likely to have hemolytic anemia or a positive serologic test for syphilis and less likely to have Raynaud's phenomenon. However, no associations were found between aCL positivity and thrombocytopenia, seizures, renal insufficiency, presence of a positive antinuclear antibody or rheumatoid factor, subcutaneous nodules or digital ulcers. CONCLUSIONS: Based on results from this large CSSRD inception cohort, anticardiolipin antibodies are present in approximately 16% of patients with RA or SLE but are less common in patients with PSS, PM/DM, EUCTD, SJ, and ANCA vasculitis, where their prevalence approaches that in the normal population. Few consistent clinical association can be found among patients with CTD who are aCL positive. The complete diagnostic and prognostic importance and specificity of these antibodies remains to be fully determined.

The Quebec Task Force classification for Spinal Disorders and the severity, treatment, and outcomes of sciatica and lumbar spinal stenosis.

STUDY DESIGN: A prospective cohort study of patients in Maine with sciatica and lumbar spinal stenosis treated surgically and nonsurgically. SUMMARY OF BACKGROUND DATA: In 1987, the Quebec Task Force on Spinal Disorders proposed a diagnostic classification to help make clinical decisions, evaluate quality of care, assess prognosis, and conduct research. OBJECTIVES: To assess the Quebec Task Force classification's ability to stratify patients according to severity and treatment at baseline, and to assess changes over time in health-related quality of life, including symptoms, functional status, and disability. METHODS: Five hundred sixteen patients participating in the Maine Lumbar Spine Study who completed baseline and 1-year follow-up evaluations were classified successfully according to the Quebec Task Force classification. Patient characteristics and treatments were compared across Quebec Task Force classification categories. Changes in health-related quality of life over 1 year were assessed according to Quebec Task Force classification category and type of treatment. RESULTS: Among patients with sciatica (n = 370), higher Quebec Task Force classification categories (from 2, pain radiating to the proximal extremity, to 6, sciatica with evidence of nerve root compression) were associated with increased severity of symptoms at baseline. There was no association between Quebec Task Force classification and baseline functional status. Quebec Task Force classification was associated strongly with the likelihood of receiving surgical treatment (P < or = 0.005). Among patients with sciatica treated nonsurgically, improvement at 1 year in back-specific and generic physical function increased with higher Quebec Task Force classification category (P < or = 0.05). Only a nonsignificant trend was observed for surgically treated patients. Patients with lumbar spinal stenosis (Quebec Task Force classification 7, n = 131) had baseline features and outcomes distinct from patients with sciatica. CONCLUSIONS: For patients with sciatica, the Quebec Task Force classification was highly associated with the severity of symptoms and the probability of subsequent surgical treatment. Nonsurgically treated patients in Quebec Task Force classification categories reflecting nerve root compression had greater improvement than those with pain symptoms alone. Among surgical patients, the Quebec Task Force classification was not associated with outcome. These results provide validation for the classification and its wider adoption. Nonetheless, improved diagnostic classifications are needed to predict outcomes better in patients with sciatica who undergo surgery.

Physician response to patient insurance status in ambulatory care clinical decision-making. Implications for quality of care.

OBJECTIVES: Individuals without health insurance in general receive fewer health services and are more likely than insured patients to experience poor outcomes. The main goal of this research was to study whether physicians' clinical recommendations vary for insured and uninsured patients, implying that physicians' choices of care may mediate insurance-related differences in health care use. METHODS: The authors designed clinical scenarios that describe routine decisions encountered by primary care physicians in ambulatory settings. Scenarios were designed to include discretionary, nondiscretionary, preventive, and diagnostic/therapeutic services. Insurance status of patients was indicated as either insured or uninsured for the service under consideration. Scenarios were presented to a nationally representative sample of primary care physicians (n = 1182) as part of the American Medical Association 1992 Socio-economic Monitoring System Survey. Physicians were assigned randomly to receive eight scenarios in which patients were either insured or uninsured. For each scenario, physicians were asked to indicate the percentage of patients for whom they would recommend a given service. RESULTS: After controlling for variables associated with nonresponse, we found that physicians who were presented scenarios with insured patients recommended service for 72% of patients, and physicians who were presented scenarios with uninsured patients recommended the same services for 67% of patients (P < 0.001). Physicians recommended both discretionary services (50% versus 42%; P < 0.001) and nondiscretionary services more often for insured than uninsured patients (93% versus 91%; P < 0.05). CONCLUSIONS: In self-reports, physicians are more likely to recommend services for insured than for uninsured patients, and more so when services are discretionary. This provides evidence that physicians' recommendations may be important mediators of insurance-related variation in the use of health-care services. Higher rates of use among the insured may not always reflect higher quality of care, particularly when the service is discretionary in nature.

Age-race interaction in prostatic adenocarcinoma treated with external beam irradiation.

The most important predictors of long-term survival in patients with adenocarcinoma of the prostate are histological grade and stage of disease. However, the role of other epidemiological factors, particularly age and race, remains controversial. There is a school of thought that black patients and younger patients have a biologically more aggressive disease. We analyzed the survival of 914 patients (867 whites and 47 blacks) with localized adenocarcinoma of the prostate treated with external beam irradiation from the Connecticut SEER Tumor Registry data base. Patients were treated from 1973-1987, and those with Stages A1, A2 and D2 were excluded. Patients < or = 60 years of age had a 5-year survival rate of 72% compared to 61% for those > 60 years of age (p = 0.06). When stratified by race, white patients had a 63% 5-year survival rate versus 47% in black patients (p = 0.02). When analyzed by race and age, and age-race interaction was noted. Although younger whites fared better than older whites, 77% versus 61% survival at 5 years (p = 0.02), younger blacks fared worse than older blacks, 31% versus 52% survival at 5 years (p = 0.21). Blacks, on average, presented at an earlier age than whites, 65 years versus 69 years (p = 0.001). Both races had similar stage and similar grade of disease. In older patients, both races presented with similar stage and grade of disease and had similar survival. However, in the younger age group, black patients presented with similar grade, but higher stage disease than whites. This may explain the worse survival in young blacks compared to young whites, 31% versus 77% at 5 years (p = 0.007). Multivariate analysis revealed that, even controlling for stage and grade, blacks still fared worse than whites. Increased age was associated with decreased survival in whites but increased survival in blacks.

Wound healing after preoperative radiation for sarcoma of soft tissues.

Morbidity from wound healing was retrospectively analyzed in a series of 202 consecutive patients with tumors of the soft tissue of the extremities, torso and head and neck region who were treated with preoperative irradiation and conservative operation at the Massachusetts General Hospital between January 1971 and June 1989. A radiation boost dose was given to 143 patients (71 percent) postoperatively. The overall wound complication rate was 37 percent. One patient died because of necrotizing fasciitis. In 33 instances (16.5 percent), secondary operation was necessary, including six patients (3 percent) who required amputation. The wounds in the remaining 40 patients (20 percent) were treated without operation. Multivariate analyses of the data showed the factors that were significantly associated with wound morbidity: tumor in the lower extremity (p < 0.001), increasing age (p = 0.004) and postoperative boost with interstitial implant (p = 0.016). Accelerated fractionation (BID, two fractions per day) reached borderline statistical significance (p = 0.074). Two other factors showed association with wound morbidity by univariate analysis, but not in multivariate model: high pathologic grade (p = 0.02) and estimated volume of resected specimen > or = 200 milliliters (p = 0.065). Patient gender, intercurrent disease (diabetes or hypertension), obesity, maximal tumor size, primary versus recurrent tumor, duration of bed rest postoperatively, dose of postoperative boost radiation, the use of postoperative boost, the use of adjuvant chemotherapy and year of treatment did not show significant importance for wound morbidity. When the severe wound complications (defined as requiring secondary operation and including the patient who died because of necrotizing fasciitis) were considered, among all analyzed variables, only localization of tumor in the lower extremity as a single factor was significant (p < 0.001). Techniques for managing the wound are considered which are judged likely to contribute to a decrease of the incidence of wound healing delays.

Patterns of failure after pancreaticoduodenectomy for ampullary carcinoma.

The clinical courses of 41 patients with ampullary carcinoma were retrospectively reviewed to determine patterns of failure after resection. The five year actuarial local control and overall survival rates of 29 patients undergoing only pancreaticoduodenectomy were 69 and 55 percent, respectively. For 12 patients with "low risk" pathologic features (tumors limited to the ampulla or duodenum, well or moderately well-differentiated histologic factors, uninvolved lymph nodes or resection margins), the five year actuarial local control and survival rate was 100 and 80 percent, respectively. Adjuvant treatment may be unnecessary for this favorable subset of patients. On the other hand, the five year actuarial local control and survival after pancreaticoduodenectomy of 17 patients with "high risk" pathologic features (tumors invasive of the pancreas, poorly differentiated histologic findings, involved lymph nodes or resection margins) was only 50 and 38 percent, respectively (p < 0.05). In 12 patients at "high risk" who also received postoperative radiation therapy after pancreaticoduodenectomy, there was a trend toward better local control (83 percent), but there was no improvement in survival. Distant metastases (liver, peritoneum and pleura) were the dominant factor in determining outcome in this group. Therefore, we propose a trial of preoperative irradiation in hopes of enhancing these outcomes by reducing the risk of dissemination of cancer cells during surgical resection, especially among the 70 percent of patients with high risk pathologic features.

Hodgkin disease, nodular sclerosis type. Implications of histologic subclassification.

BACKGROUND: The prognostic significance of the cellular composition of the nodules of Hodgkin disease, nodular sclerosis type (HDNS), is controversial. METHODS: Tumors from 79 patients with HDNS, who had a median follow-up time of 9.3 years, were studied. RESULTS: Based on British National Lymphoma Investigation criteria, 58 cases were classified as NSI (low-grade) and 21 as NSII (high-grade). The study included 24 male and 55 female patients, aged 10-57 years (mean, 27 years), who presented with Stage I (13 patients [12A, 1B]), Stage II (45 patients [40A, 5B]), or Stage III (21 patients [16A, 5B]) disease. Fifty-three patients had no relapse, 4 died of other causes, and 49 are in complete clinical remission. Twenty-six patients had progression of disease during therapy or relapsed and 17 were successfully salvaged. Overall length of survival was significantly shorter with NSII (P = 0.0001), extensive necrosis (P = 0.0034), high stage (P = 0.0058), and B symptoms (P = 0.030). Multivariate analysis showed that grade had the strongest effect on overall survival (P = 0.0042; hazard ratio = 10.19). The 5-year survival was 100% for NSI patients and 75% for NSII patients. Only B symptoms were significantly associated with risk of relapse after initial therapy (P = 0.030). For patients who relapsed, only histologic grade predicted subsequent disease-free survival (P = 0.0023; hazard ratio = 26.5). Five-year disease-free survival after first relapse was 94% for NSI patients and 11% for NSII patients. CONCLUSIONS: Patients with NSI disease who relapse have a more successful salvage and longer period of survival than do those with NSII disease. Histologic subclassification of HDNS appears clinically relevant, and consideration of histologic subtype may be important when planning therapy.

Adjuvant postoperative radiation therapy for rectal adenocarcinoma.

From October 1975 to August 1988, 261 patients at high risk for local recurrence after curative resection of rectal carcinoma underwent high-dose postoperative irradiation. Patients received 45 Gy by a 4-field box usually followed by a boost to 50.4 Gy or higher when small bowel could be excluded from the reduced field. Since January 1986, patients also received 5-fluorouracil (5-FU) for 3 consecutive days during the first and last week of radiotherapy. Five-year actuarial local control and disease-free survival decreased with increasing stage of disease; patients with Stage B2 and B3 disease had local control rates of 83% and 87% and disease-free survivals of 55% and 74%, respectively. In patients with Stage C1 through C3 tumors, local control rates ranged from 76% to 23%, and disease-free survivals ranged from 62% to 10%, respectively. For patients with Stage C disease, disease-free survival decreased progressively with increasing lymph node involvement, but local control was independent of the extent of lymph node involvement. For each stage of disease, local control and disease-free survival did not correlate with the dose of pelvic irradiation. Preliminary data from this study suggest a trend toward improved local control for patients with Stage B2, C1, and C2 tumors who receive 5-FU for 3 consecutive days during the first and last weeks of irradiation compared with patients who do not receive 5-FU. Current prospective randomized studies are addressing questions regarding the optimum administration of chemotherapy with pelvic irradiation for patients following resection of rectal carcinoma.

The role of radiotherapy in the treatment of subtotally resected benign meningiomas.

Thirty-six patients with benign meningioma were treated for primary or recurrent disease by subtotal resection and external beam irradiation from 1968-1986 at Massachusetts General Hospital. Comparison is made with 79 patients treated by subtotal surgery alone from 1962-1980. Progression-free survival for 17 patients irradiated after initial incomplete surgery was 88% at 8 years compared with 48% for similar patients treated by surgery alone (p = 0.057). 16 patients incompletely resected at time of first recurrence were irradiated and 78% were progression-free at 8 years while 11% of a similar group treated by surgery alone were progression free (p = 0.001). Long term overall survival was high and similar in both control and study groups. Two patients were irradiated at second recurrence and 1 patient at third recurrence. Twenty-five patients were treated with photons alone and have a median follow-up of 57 months, 6 patients have recurred at doses 45-60 Gy. Eleven patients were treated with combined 10 MV photons and 160 MV protons utilizing 3-D treatment planning. These patients have been followed for a median of 53 months and none have failed to date. Eight of 11 received 54-60.4 Gy and 3/11 greater than 64.48 Gy. Sex, age, pathology grade and score, surgery and timing of radiation therapy were not associated with significant differences in failure patterns within the irradiated study group (p less than 0.1). Complications have been seen in 6 irradiated patients.

Are there patients with stage I rectal carcinoma at risk for failure after abdominoperineal resection?

The clinical courses of 64 patients undergoing abdominoperineal resection for Stage I lower rectal carcinoma (tumors confined to the muscularis propria without lymph node involvement) were reviewed to identify subsets at risk for failure. Twelve of 12 patients with tumors limited to the submucosa remained disease free without evidence of recurrence. Of the 52 patients with muscularis propria involvement, there have been eight failures with three patients having local failure only, three patients with local failure and distant metastases, and two patients with distant metastases only. The 6-year actuarial disease-free survival, local control, and freedom from distant metastases rates for patients with tumors invasive of the muscularis propria were 80%, 84%, and 88%, respectively. Patients with tumors exhibiting vascular/lymph vessel involvement were at even higher risk for failure. Although adjuvant treatment is infrequently advised for these patients, the use of radiation therapy and chemotherapy should be reconsidered for patients with Stage I lower rectal carcinoma, specifically for patients with tumors invasive of the muscularis propria with vascular/lymph vessel involvement.

A dose response analysis of injury to cranial nerves and/or nuclei following proton beam radiation therapy.

The low tolerance of the central nervous system (CNS) limits the radiation dose which can be delivered in the treatment of many patients with brain and head and neck tumors. Although there are many reports concerning the tolerance of the CNS, few have examined individual substructures of the brain and fewer still have had detailed dose information. This study has both. A three dimensional planning system was used to develop the combined proton beam/photon beam treatments for 27 patients with skull-base tumors. The cranial nerves and their related nuclei were delineated on the planning CT scans and the radiation dose to each was determined from three dimensional dose distributions. In the 594 CNS structures (22 structures/patient in 27 patients), there have been 17 structures (in 5 patients) with clinically manifest radiation injury, after a mean follow-up time of 74 months (range 40-110 months). From statistical analyses, dose is found to be a significant predictor of injury. Using logistic regression analysis, we find that, for each cranial nerve, at 60 Cobalt Gray Equivalent (CGE) the complication rate is 1% (0.5-3% with 95% confidence) and that the 5% complication rate occurs at 70 CGE (64-81 CGE with 95% confidence). The slope of the dose response curve (at 50%) is 3.2 (2.2-5.4 with 95% confidence). No significant relationship between dose and latency period for nerve injury was found.

Radiation therapy in the management of early stage Hodgkin's disease presenting in later life.

This study examined the contention that although elderly patients with Hodgkin's disease have a worse prognosis overall than younger patients, a subgroup of older patients fit enough to be managed like younger patients can fare just as well. A retrospective analysis was made on 29 patients older than 60 years of age with Stage I and II Hodgkin's disease treated by radiation therapy alone. Fourteen of these patients were managed optimally, i.e., were adequately staged (defined by one or more of the following: laparotomy, computed tomography [CT] scan, and/or lymphangiogram), followed by radical radiation therapy (mantle or inverted-Y). The remaining 15 patients, because of their general medical condition, were managed suboptimally with limited staging and/or involved-field irradiation. None of the 14 patients managed optimally relapsed over a median of 4.75 years of follow-up compared with 10 of 15 patients in the suboptimal group. For the optimally managed versus suboptimally managed groups, the actuarial 5-year disease-free survival rates were 61% and 6%, respectively; the actuarial overall survival rates (death from all causes) were 61% and 19%, respectively; and the disease-specific survival rates were 100% and 39%, respectively. Only three of the patients irradiated radically had acute complications severe enough to warrant a break in treatment. In the opinion of the authors, those elderly patients able to tolerate adequate staging and radical radiation therapy can anticipate a high likelihood of cure.

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.

Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma.

From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance.

Intraoperative electron beam radiation therapy for primary locally advanced rectal and rectosigmoid carcinoma.

To improve local control and survival in patients with primary locally advanced rectal and rectosigmoid carcinoma, intraoperative electron beam radiation therapy (IORT) has been used with a combination of moderate- to high-dose preoperative radiation therapy and surgical resection. Sixty-five patients underwent resection with the intention of using IORT if areas at high risk for local recurrence were apparent at surgery. For 20 patients undergoing complete resection with IORT, the 5-year actuarial local control and disease-free survival (DFS) was 88% and 53%, respectively. The results for 22 patients with pathologically documented residual carcinoma were less satisfactory with a 5-year actuarial local control and DFS of 60% and 32%, respectively. In this latter group, local control and DFS correlated with the extent of residual disease: patients with only microscopic disease had a 5-year actuarial local control and DFS of 69% and 47%, respectively, whereas for patients with macroscopic disease, these figures were 50% and 17%, respectively. For 18 patients undergoing complete resection without IORT or additional postoperative radiation therapy, the 5-year actuarial local control and DFS was 67% and 53%, respectively. Because local failure will occur in at least 30% of patients undergoing partial resection with or without IORT as well as patients undergoing complete resection of advanced tumors without IORT, additional postoperative radiation therapy should be considered.

Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma.

A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

Correlates of survival and the Daumas-Duport grading system for astrocytomas.

In order to examine the correlation between prognosis and the histological features of nuclear atypia, mitosis, endothelial proliferation, and necrosis in supratentorial adult astrocytomas, the authors reviewed 251 such cases treated at the Massachusetts General Hospital between 1972 and 1980. One point was given for the presence of each feature. The total number of features was translated into a grade as follows: none of the four features = Grade 1 (one patient), one feature = Grade 2 (36 patients), two features = Grade 3 (33 patients), and three or four features = Grade 4 (181 patients). The period of survival was significantly associated with grade, the presence or absence of each of the four histological features, patient's age, type of operation, radiation therapy, and extent of tumor (log rank, p less than 0.05). The variables associated with grade were age (p less than 0.001) and radiation therapy (p less than 0.02). After adjustment for these variables using a Cox proportional-hazards model, the difference in overall survival time between patients in Grades 2 and 3 was not statistically significant. When comparable groups of patients were examined in terms of age or receipt of radiation therapy, the median survival times differed markedly. Patients 50 years of age or less had a median survival time of 68 months (Grade 2 tumors), 29 months (Grade 3 tumors), and 13 months (Grade 4 tumors). Patients over 50 years of age had a median survival time of 6 months (Grade 2 and 4 tumors) and 9 months (Grade 3 tumors). Those patients who had received radiation therapy had a median survival time of 68 months (Grade 2 tumors), 21 months (Grade 3 tumors), and 11 months (Grade 4 tumors). Those patients who did not receive radiation therapy had a median survival time of 1 month (Grade 2 tumors) and 2 months (Grade 3 and 4 tumors); over half of these patients died within 2 months of surgery. This grading system, originally proposed by Daumas-Duport, et al., is simple, objective, and reproducible, and correlates well with survival times. The authors recommend that astrocytomas be graded on a scale of 1 to 4, with Grade 1 reserved for the rare adult supratentorial astrocytoma with none of the four histological features.

Clinical interest in determinations of cellular radiation sensitivity.

Determinations of cell sensitivity in terms of survival fraction after doses employed in clinical radiation therapy, say 1-3 Gy, are of increasing interest to clinicians as they provide direct experimental data which can be employed without reference to models of cell inactivation. SF2 values are expected ultimately to prove valuable as response predictors. Even so, SF2 values would surely be combined with other predictors also under development to give the best feasible estimate of response of tumor and normal tissue. There are, however, several concerns with the SF2 data currently available. These include: SF2 depends upon the cell system employed (established cell lines vs primary cultures) and the method of assaying survival fraction (colony formation vs population growth); dose-response curves for inactivation of tumors characterized by the reported distribution of SF2 values are, in many instances, not close to those judged to obtain in clinical practice; the broad distribution of SF2 values indicates a rather flatter dose-response curve for tumor control or normal tissue than seems true from clinical experience. There appears to be a potential for clinical gain by determination of sensitivity of normal tissues in order to identify patients who are of increased sensitivity (for example heterozygotes for AT, 5-oxoprolinuria, etc.). Although the absolute SF2 values obtained by current technologies of culturing human cells often appear to be poorly related to values expected from observed radiation response in patients, intensive research on cell viability assays will almost certainly yield more realistic results.