BMT unit recommends less frequent measurement of vital signs during blood transfusion.
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Biomedical subjects
Publications and source records attributed to M Roach.
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For more than 20 years, black women with breast cancer have been reported to have a lower survival rate than white women with breast cancer. Despite correcting for stage and socioeconomic status, some studies continue to report race-related excess mortality. A reliability scoring system was developed, based primarily on the precision of the staging system used, and the likelihood that the quality of treatment was comparable. Studies that compared the survival of blacks and whites treated for breast cancer from 1968 to 1988 were included in this study. Studies that demonstrated relatively large differences in the 5-year survival between blacks and whites were associated with low reliability scores. Studies that reported little or no difference in 5-year survival rates were associated with relatively high reliability scores. This model and the literature on which it is based suggest that the reported survival differences associated with race can be explained by differences in stage at presentation and by differences in the quality of care received. Efforts directed at early detection and improvements in the quality of care delivered are likely to reduce the excess breast cancer mortality experienced by black women.
PURPOSE: To evaluate the use of pretreatment prostate specific antigen, Gleason score, and clinical stage as predictors of the risk of seminal vesicle involvement in patients with clinically localized prostatic cancer, and to determine the impact of excluding the seminal vesicles on the dose received by surrounding normal tissues. METHODS AND MATERIALS: An empirically derived equation combining the preoperative prostate specific antigen and Gleason score was applied to 188 patients treated with radical prostatectomy, for whom pathologic evaluation of the seminal vesicles was available. High and low risk groups for seminal vesicle involvement were defined using this equation. The observed risks of seminal vesicle involvement was compared to the predicted risk using the preoperative prostate specific antigen, Gleason score or clinical stage alone or using the empirical equation. Dose-volume histograms for five patients treated using six-field conformal radiotherapy were compared including and excluding the seminal vesicles. RESULTS: Using the empirically derived equation, a low risk group of 109 patients was identified with a calculated risk of seminal vesicle involvement of < or = 13% and an observed incidence of 7.3%. Among the high risk group of 79 patients, which included all patients with a calculated risk > 13%, 37% had seminal vesicle involvement (p < 0.001 low vs. high risk). Twenty percent of the rectal volume received on average above 86% of the total dose for the five plans which included the seminal vesicles compared to 68% for the five plans excluding the seminal vesicles. The doses to 40% of the rectal volume were 64% and 37% if the seminal vesicles were included and excluded, respectively. The dose to the bladder and femoral heads was also decreased but to a lesser extent. CONCLUSION: The empirical formula predicts risk of seminal vesicle involvement with a higher degree of significance for a larger number of patients than either Gleason score, clinical stage, or prostate specific antigen alone. Based on an analysis of our first 100 patients treated with definitive conformal therapy alone, approximately 47% of those patients could have been treated excluding the seminal vesicles. Excluding the seminal vesicles may allow us to go to a higher total dose with less rectal toxicity.
BACKGROUND: Classic human immunodeficiency virus (HIV) negative primary central nervous system lymphoma (PCNSL) is a relatively uncommon occurrence, whereas the incidence of HIV positive PCNSL has increased dramatically during the past 5 years. Between 2% and 6% of all patients with acquired immune deficiency syndrome (AIDS) will have PCNSL develop clinically, and as many as 11% will have PCNSL found at autopsy. In the United States, some of the earliest and most extensive experience with HIV positive PCNSL has occurred in San Francisco. This article reports on PCNSL in patients with and without HIV. METHODS: Using our diagnosis-based computer retrieval system, we identified all patients treated with radiotherapy for PCNSL between January 1982 and January 1992 and reviewed their medical records. Population characteristics, risk factors and length of survival (LOS), were analyzed. Statistical methodology included the Cox proportional hazards model and Kaplan-Meier survival curves. RESULTS: Fifty-six patients were identified with PCNSL, of which 41 were HIV positive and 15 were HIV negative. There was a fourfold increase in the total number of PCNSL cases during the time period 1987-1991 as compared with the preceding 5 years; these cases primarily were in the HIV positive group. The average Karnofsky performance score (KPS) in the HIV positive group was 50, whereas in the HIV negative group, the KPS was 35. However, the median LOS in the HIV positive group was 3 months, whereas in the HIV negative group it was 20 months. Within each group, there was a statistically significant correlation between KPS and LOS. CONCLUSIONS: Patients with HIV and PCNSL have a much shorter median LOS than do patients with PCNSL but without HIV; however, the outcome for both groups is dismal. Randomized clinical trials are needed to determine which patients with HIV might benefit from more aggressive therapy and to determine the optimal choice and dosages of chemoradiation therapy for patients with PCNSL without HIV.
PURPOSE: To evaluate the predictive value of an empirically derived equation for identifying patients with clinically localized prostate cancer at low and high risk for harboring occult lymph node metastasis. METHODS AND MATERIALS: A simple equation for estimating the risk of positive lymph nodes was empirically derived from a nomogram published by Partin et al. demonstrating the value of combining the pre-treatment prostate specific antigen and Gleason Score in predicting the risk of lymph node metastasis for patients with clinically localized prostate cancer. The risk of positive nodes (N+) was calculated using the equation; N+ = 2/3(PSA) + (GS-6) x 10, where PSA and GS are the pre-treatment prostate specific antigen and Gleason Score respectively, and the calculated risk is constrained between 0-65% for a PSA < or = 40 ng/ml (as in the nomogram). To test the general applicability of this equation, we reviewed the pathologic features of 282 of our patients who had undergone a radical prostatectomy. RESULTS: Based on 212 patients for whom the pre-operative prostate specific antigen's and Gleason Scores were available, we identified 145 patients with a calculated risk of positive nodes of < 15%, (low risk group) and 67 patients with a calculated risk as > or = 15% (high risk group). The observed incidence of positive nodes was 6% and 40% among the low and high risk groups respectively (p < 0.001). When used alone neither clinical stage, pre-treatment prostate specific antigen nor the pre-treatment Gleason Score was as useful in identifying the largest low and high risk groups. CONCLUSION: Using the equation described we confirmed the general applicability of the nomogram reported by Partin et al. and identified patients at low and high risk for lymph node involvement. Based on these data we have adopted a policy of omitting whole pelvic irradiation in patients identified as low risk.
PURPOSE: To define the "ideal margins" to be used for the delivery of six-field conformal radiotherapy for localized prostate cancer. METHODS AND MATERIALS: For a typical patient, 3-D based 6-field conformal treatment plans were generated using uniform margins ranging from 0.5-2.5 cm (in 0.25 cm increments). In a step-wise fashion the minimum margins required to encompass the gross tumor volume within the 90% isodose shell were identified. Additional margins were then added to account for extracapsular penetration, setup and patients movement error as well as for organ movement. Assumptions about the relative tolerance of surrounding normal tissues were also incorporated into the final decisions regarding margins. RESULTS: For the various areas of interface, between the prostate and surrounding normal tissues "ideal margins" varied from 0.75-2.25 cm. CONCLUSION: The use of nonuniform "ideal margins" appears to insure adequate coverage of the tumor, while minimizing the volume of surrounding dose limiting normal tissues irradiated. This approach should in theory improve the tumor control and complication probabilities compared to using conventional treatment techniques and to using a 6-field conformal technique with uniform margins.
The purpose of this study is to describe a conformal radiotherapy technique for treating only the prostate with bilateral 120 degrees arcs using "averaged beams-eye-views" (A-BEV). For this study a CT scan from a patient with a large prostate but with a low risk for seminal vesicle involvement was chosen for comparing several different treatment techniques. Dose volume histograms (DVHs) of the prostate, femoral heads, bladder, and rectum were compared for plans using "standard" bilateral 120 degree unblocked arcs (8 x 8 and 9 x 9 cm), similar sized arcs with "generic" (small corner) blocks applied, arcs using hand drawn "semi-conformal" blocks added, and arcs using the A-BEV. The A-BEV was generated by averaging the shapes of fixed lateral and oblique BEVs from a six-field plan. These arc techniques were compared to four-field conformal (4-FC) and six-field conformal (6-FC) techniques. The addition of generic corner blocks to a 9 x 9 field resulted in a more favorable dose distribution than using open unblocked 9 x 9 arcs. The technique employing the A-BEV resulted in an improvement in the DVHs compared to other arc techniques and to 4-FC techniques. The dose volume histograms associated with using this technique approached those associated with using a 6-FC technique. Treating only the prostate with blocked arcs generated using an A-BEV results in an improved dose distribution compared to unblocked arcs and 4-FC techniques. This blocked arc technique also results in a DVH that is comparable to using a more complex 6-FC technique. Blocks that are drawn on manually reduce the dose to the surrounding normal tissues but are associated with a greater risk of underdosing the target volume. This problem is diminished when computer generated conformal blocks are used.
Historically, four perpendicular treatment fields or bilateral arcs have been used in the treatment of prostate cancer. As new techniques challenge the four-field box technique for their superiority of tumor coverage and adjacent critical structure sparing, oblique beam angles (in addition to right and left laterals) have been introduced as an alternative to anterior (AP) and posterior (PA) beams. Among the most popular of these alternative approaches is a six-field technique. Traditionally 45 degrees angles have been used with this technique. In this study, opposed coplanar oblique beams angled 20, 25, 30, 35, 40, and 45 degrees off the lateral beam position, were compared for their ability to minimize adjacent critical structure doses, while maintaining maximum clinical target volume (CTV) coverage. This analysis compared rectum, bladder, and femoral head dose volume histograms (DVH) for each of these varying oblique gantry angles. As the angle of the posterior oblique beams became more horizontal, it is more difficult to encompass the apex of the prostate in the 95% isodose value. On inferior CT slices near the apex of the prostate, the density of the pelvic bones in the path of the posterior oblique fields causes the beam to be slightly attenuated, thereby underdosing the CTV. The oblique angles most affected by this bone heterogeneity are beams angled from 20 to 30 degrees off the lateral beam position. As the angles approach the vertical direction, rectal and bladder doses increase, while femoral head doses decrease. Oblique gantry angles approaching the horizontal direction result in a decrease in rectal and bladder doses, while femoral head doses increase. Of the oblique angles studied, 35 degrees off the lateral position provides lower rectum and bladder doses than 30, 40, and 45 degrees; lower femoral head doses than 20, 25, and 30 degrees, and the maximum CTV coverage on all CT slices studied.
We have attempted to initiate a much needed constructive dialogue regarding the participation of African-American patients in clinical cancer research trials. It was our intent to provide a greater understanding of the historical context and evolving nature of clinical research trials pertaining to cancer. Some of the same challenges hold true for acquired immunodeficiency syndrome (AIDS)-related clinical research. Physicians interested in becoming a member of SOCRATES should contact Dr Roach at the University of California San Francisco.
PURPOSE: To determine the magnitude of patient positioning errors associated with six field conformal therapy for carcinoma of the prostate, and to assess the impact of alpha-cradle immobilization on these errors. METHODS AND MATERIALS: The records of 22 patients, treated at two of the treatment facilities within our department, using computed tomography-planned conformal six field therapy for carcinoma of the prostate, were reviewed. At one facility (UCD), patients were routinely treated with immobilization, while at the other (UCSF) no rigid immobilization was used. Portal films of patients treated at both facilities were subsequently reviewed, and the deviation of each portal from the simulation film was determined (simulation-to-treatment variability). In addition, for each patient, the average deviation of each portal film from the average portal film (treatment-to-treatment variability) was determined. RESULTS: The mean and median simulation-to-treatment variability was 0.4 cm for those patients treated with immobilization, versus 0.6 cm for those treated without immobilization. The 90th percentile of simulation-to-treatment variability was 0.7 cm for those patients treated with immobilization, versus 1.1 cm for those not immobilized. There was a significant reduction in the number of portals observed with errors of > or = 0.50 cm (132/201 vs. 37/87, 66% vs. 43%; p < 0.001), 0.75 cm (184/201 vs. 59/87, 92% vs. 68%; p < 0.001), and 1.0 cm (196/201 vs. 74/87, 98% vs. 85%; p < 0.001) for patients treated with immobilization. There was also a significant reduction in the number of patients with treatment-to-treatment variability > or = 0.5 cm (1/10 vs. 8/12; p = 0.01) for patients treated with immobilization. CONCLUSION: The use of immobilization devices significantly reduces errors in patient positioning, potentially permitting the use of smaller treatment volumes. Immobilization should be a component of conformal radiation therapy programs for prostate carcinoma.
PURPOSE: To determine if prolonged treatment time adversely affects survival for patients with inoperable non-small cell carcinoma of the lung. METHODS AND MATERIALS: Patients enrolled on three randomized studies (RTOG 8311, 8321, 8403) between 1983-1989 formed the database. Previous analyses found that the addition of thymosin (8321) or prophylactic cranial irradiation (8403) failed to prolong survival: both studies used thoracic irradiation with standard fractionation to 55-60 Gy in 30 fractions. In 8311, patients were treated by hyperfractionated radiation therapy to randomly assigned total doses of 60.0 Gy, 64.8 Gy, 69.6 Gy, 74.4 Gy or 79.2 Gy, 1.2 Gy twice daily, 5 days per week. Patients analyzed received +/- 4% of the assigned total dose and lived > 90 days (to ensure that all patients would have completed treatment). Completion < 5 days beyond protocol specifications was classified as "per protocol." Elapsed treatment time exceeding specifications by 5-9 days was a minor deviation, 10-13 days was a major deviation-acceptable, and > or = 14 days was a major deviation-unacceptable. Absolute survival was the endpoint to evaluate the effect of delays. The log rank statistic was used to test for survival differences in the univariate setting, the Cox regression model was used in the multivariate setting. RESULTS: Of 293 patients treated with standard fractionation, eight (2.7%) had deviations from the specified treatment time (six minor, two major-acceptable). With hyperfractionation, 90 (15%) patients had deviations (40 minor, 21 major-acceptable, 29 major-unacceptable). As the assigned dose increased, the deviation rate increased (9.7% for 60.0 Gy vs. 20.8% for 79.2 Gy). Survivals for hyperfractionation patients with any deviations in treatment time were significantly shorter than those treated "per protocol" (p = 0.16): estimated 2- and 5-years rates were 24% and 10% versus 13% and 3%, respectively. Multivariate analyses showed the delay effect to be entirely in patients treated with 69.6 Gy or higher; there was also dependence upon the patients' prognosis. In patients with favorable prognosis (KPS 90-100, weight loss < or = 5%, no N3), the difference in survival was pronounced (33% and 15% vs. 14% and 0% at 2- and 5-years, respectively). Such differences were not found in patients with unfavorable prognostic factors. CONCLUSIONS: Interruptions delaying completion of planned radiation therapy were more frequent with higher total doses (> or = 69.6 Gy). Favorable patients (high KPS, little weight loss, < N3 nodal metastasis) had markedly adverse effects on long-term survival associated with delays to completion of the planned total dose.
PURPOSE: To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy. METHODS AND MATERIALS: This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the "treatment arm" receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale. RESULTS: Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl. CONCLUSION: (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.
Urethrograms on 89 consecutive patients with localized prostate cancer were evaluated retrospectively, and the inferior border of the treatment field based on this study was compared with the inferior border that would have been defined by using the lower border of the ischial tuberosities. An analysis of the relationship between the margin used and the dose at the inferior border of the prostate supported our policy of requiring a 2 cm margin for optimal coverage of the prostate. Inclusion of at least 1 cm of proximal penile urethra was essential to ensure this 2 cm margin. Based on this assumption, twenty-five percent of patients would have had an inadequate margin if the lower border of the ischial tuberosities had been used instead of the urethrogram to define the inferior border of the treatment field. Assuming that a margin of more than 3 cm inferiorly is excessive, 11% of patients would have had excessive urethral irradiation if the bottom of the ischial tuberosities had been used to define the inferior border. Combining these two extremes, more than one in three patients would have had an inappropriate inferior margin if the bottom of the ischial tuberosities had been used to define the inferior border of the treatment field. There was no apparent increase in morbidity as a result of the urethrograms or an increase in treatment related toxicity in association with using the treatment fields defined by urethrography. Computed tomography was complimentary in defining the apex of the prostate. These data support the routine use of the urethrograms during simulation for localized prostate cancer. The use of the lower border of the ischial tuberosities to define the inferior border of the treatment field is associated with an unacceptable risk of either underdosing the apical portion of the prostate or overdosing the urethra.
UNLABELLED: In a major study that showed a treatment advantage for induction chemotherapy followed by radiation therapy (CALGB 8433), there was a significantly (P = 0.02) lower proportion of patients dying within 105 days of registration in the chemotherapy/radiation arm than the radiation therapy arm; without this difference, the overall survival was marginally better (P = 0.059) for the chemotherapy/radiation group. A retrospective analysis of RTOG trials sought explanations for the phenomenon. MATERIALS AND METHODS: Patients who fit the CALGB eligibility criteria and received radiation therapy alone in four prospective trials of the RTOG conducted between 1983 and 1989 were analyzed to determine factors that distinguished patients dying within 105 days from longer survivors. Two were trials of altered fractionation and two used standard fractionation. Of 683 patients identified, 107 (15.7%) died within 105 days after registration. The log linear model was used to evaluate relationships between death within 105 days and known prognostic factors. Karnofsky performance status (KPS), < 90 vs. > or = 90, was the only factor significantly related to death within 105 days (P = 0.0052). A Cox model with the same factors plus fractionation and total dose found KPS and T-stage associated with overall survival (P = 0.0005 and 0.025, respectively). The choice of the hyperfractionation arm (HFX) for Phase III study (69.6 Gy at 1.2 Gy b.i.d.) was based in part on comparison with standard fractionation (STD) from a concurrent RTOG protocol, 8321. Review of early deaths showed that this HFX arm had a lower proportion of patients dying within 105 days (7.9%) than STD in 8321 (21.0%).(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND: Many studies have reported differences in cancer incidence and survival between populations of Blacks and Whites. A 45% higher death rate from lung cancer for Black men and a survival duration for Black patients with lung cancer that is generally shorter than that for White patients have also been reported. PURPOSE: The purpose of this study was to evaluate whether race affects known prognostic factors for non-small-cell lung cancer in Black versus White patients. This analysis attempts to determine which prognostic factors may contribute to the reported differences in disease outcome. METHODS: We used data from 1565 patients with non-small-cell lung cancer treated in four randomized prospective trials conducted by the Radiation Therapy Oncology Group (RTOG). The data were pooled for a retrospective analysis of survival and prognostic factors by race. RESULTS: Univariate analysis showed significant differences between Blacks and Whites with regard to sex, weight loss, histology, and RTOG T stage (P < .05), but the only clinically significant difference (P < or = .01) was weight loss. Despite these findings, overall survival for Blacks and Whites did not differ significantly (P = .67). Median survival for Blacks and Whites with a Karnofsky performance status (KPS) of 90 or more was 12.1 and 11.3 months, respectively (P = .45). Survival for Blacks and Whites with a KPS of less than 90 was 7.8 and 6.8 months, respectively. Cause of death did not differ between the two races. For both races, KPS, age, sex, weight loss, and RTOG T and N stages were significant prognostic factors for survival (P < .01), but race was not a significant prognostic factor. CONCLUSION: Further studies of the differential in cancer survival for Blacks and Whites may be indicated, but greater impact may be achieved by addressing socioeconomic factors, lifestyle and occupational risk factors, health education, and access to adequate health care.
A number of studies have identified race as a prognostic factor for survival from prostate cancer. To evaluate the prognostic significance of race in a controlled setting, we evaluated 1294 patients treated on three prospective randomized trials conducted by the Radiation Therapy Oncology Group between 1976 to 1985. One-hundred and twenty (9%) of the patients were coded as black, while 1077 (83%) of the patients were coded as white. Protocol 7506 included 607 patients with clinical Stage T3-T4Nx or T1b-T2N1-2. Protocol 7706 included 484 patients with clinical Stage T1b or T2 who were node negative. Protocol 8307 included 203 Stage T2b-T4 patients with no lymph node involvement beyond the pelvis. Univariate and multivariate analyses were used to assess the possible independent significance of race and other prognostic factors, including Gleason score, serum acid phosphatase, nodal status, and hormonal status. Protocols 7706 and 8307 revealed that race was not of prognostic significance for disease-free or overall survival by either univariate or multivariate analysis. Univariate analysis of Protocol 7506 revealed that the median survival for blacks was somewhat shorter (5.4 years vs. 7.1 years, p = 0.02). This difference persisted after a multivariate analysis. A higher percentage of blacks treated on 7506 had an abnormally elevated serum acid phosphatase compared to whites (p = 0.006), and the time to distant failure tended to be shorter (p = 0.07). These findings suggest that blacks treated on 7506 may have had more extensive disease at presentation. Based on these prospective randomized trials, it is most likely that the lower survival noted for black Americans with prostate cancer reflects the tendency for blacks to present with more advanced disease. Differences in access to care, the quality of care received, and the impact of co-morbid conditions may explain the lower survival reported for black Americans elsewhere in the literature.