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R Chappell

Publications and source records attributed to R Chappell.

At least 37 records · Page 2Linked to original sources
PubMed1998

Estimating survival curves with left-truncated and interval-censored data under monotone hazards.

We show that the nonparametric maximum likelihood estimator (NPMLE) of a survival function may severely underestimate the survival probabilities at very early times for left-truncated and interval-censored data. As an alternative, we propose to compute the (nonparametric) MLE under a nondecreasing hazard assumption, the monotone MLE, by a gradient projection algorithm when the assumption holds. The projection step is accomplished via an isotonic regression algorithm, the pool-adjacent-violators algorithm. This gradient projection algorithm is computationally efficient and converges globally. Monte Carlo simulations show superior performance of the monotone MLE over that of the NPMLE in terms of either bias or variance, even for large samples. The methodology is illustrated with the application to the Wisconsin Epidemiological Study of Diabetic Retinopathy data to estimate the probability of incidence of retinopathy.

Algorithms↗
PubMed1998

Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment.

PURPOSE: To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS: Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS: Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS: Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

Animals↗
PubMed1997

The prediction of late rectal complications in patients treated with high dose-rate brachytherapy for carcinoma of the cervix.

PURPOSE: The aim of this work is to investigate an unusually high rate of late rectal complications in a group of 43 patients treated with concomitant irradiation and chemotherapy for carcinoma of the cervix between December 1988 and April 1991, with a view to identifying predictive factors. METHODS AND MATERIALS: The biologically effective dose received by each patient to the rectal reference point defined by the International Commission of Radiation Units and Measurements, Report 38, were calculated. Radiotherapy consisted of 46 Gy external beam irradiation plus three high dose-rate intracavitary treatments of 10 Gy each prescribed to point A. Cisplatin 30 mg/m2 was given weekly throughout the duration of the irradiation. The results have been compared to data from 119 patients treated with irradiation alone to assess the confounding effect of the cisplatin. RESULTS: The relationship between the biologically effective dose delivered to the rectal reference point and the development of late complications shows a strong dose-response with a threshold for complications occurring at approximately 125 Gy3 corresponding to a brachytherapy dose of approximately 8 Gy per fraction. This value is approximately the same biologically effective dose threshold as that found for external beam irradiation in the head and neck region. The data from the group of patients treated without cisplatin is comparable to the data from the first group of patients in the lower dose ranges; the higher doses were not used and thus are not available for comparison. CONCLUSION: Using the linear quadratic model applied to our clinical results, we have established a threshold for late rectal complications for patients treated with external beam irradiation and high dose-rate brachytherapy for carcinoma of the cervix. This threshold is consistent with similar data for external beam irradiation in the head and neck region.

Antineoplastic Agents↗
PubMed1997

Biologically effective doses in medium dose rate brachytherapy of cancer of the cervix.

The amount of dose reduction on changing from low dose rate (LDR) brachytherapy to medium dose rate (MDR) or high dose rate (HDR) afterloading has been the subject of much debate. The magnitude of reduction depends, together with other possible factors, on two radiobiological parameters: the alpha/beta ratio and the half-time of repair of the relevant tissues. In an attempt to extract these radiobiological parameters for the late rectal complications observed in our previously published clinical results four different schedules using MDR and one using LDR are analyzed. The percentage incidence of complications was a function of increasing biologically effective dose (BED), but would yield nonsense scattergrams if plotted against raw total dose. In addition, for three other published MDR series, three LDR series, and two HDR series, the incidence of rectal complications is plotted against BED to examine the predictive potential of using BED as the surrogate of total dose. Our own results were published in 1996, consisting of 102 patients treated at the LDR of 0.44 Gy/hr and 88 patients treated by four different schedules using an MDR of 1.6-1.7 Gy/hr. Follow-up is at least 3 years in all schedules. The linear quadratic formula including the "g" dose rate factor was used to analyze them, assuming exponential repair of the repairable beta term. First, multivariate and profile likelihood analyses were carried out to obtain estimates of alpha/beta and T1/2 for rectal late responding tissues. Then graphs of incidence of rectal complications vs. BED were constructed, assuming alpha/beta = 3 Gy and T1/2 = 1.5 hr, values which had not been contradicted by the multivariate analysis. Graphs were drawn both for "all grades including mild reactions" (grades 1 + 2 + 3) and for "serious" complications (grade 3 in our system). In addition, other published cervical brachytherapy series were reviewed, with calculation of their BEDs if not published by the authors. It was necessary to review and compare their grading systems, so that "mild and moderate" (grades 1 and 2) could be contrasted with "serious" (grades 3 and 4 or 5 in various systems). Comparisons were made with other published results, including three LDR, three MDR, and two HDR series spanning from 1982 to 1997. The BEDs at which the incidence of rectal complications rose above the arbitrary level of 10% were compared for all three ranges of dose rate. The multivariate analysis gave estimates of alpha/beta and T1/2 which were not significantly different from 3 Gy and 1.5 hr, respectively, so these values were used to compute the BEDs for the subsequent comparisons. It was found that the graphs of incidence of rectal complications for "all grades including mild" agreed rather better between all series than might have been expected, within a provisional (10%) threshold BED of range 100-123 Gy3 (60-74 Gy given as 2 Gy fractionated external beam or as LDR). The dose-response curves diverged above these values, as expected until common grading systems such as SOMA/ LENT become more widely used. For "serious" complications the 10% incidence occurred at a median BED of 140 Gy3 (84 Gy given as 2 Gy fractionated external beam or as LDR), range 124-155 Gy3. The use of BED (or extrapolated response dose), assuming alpha/beta = 3 Gy and T1/2 = 1.5 hr, instead of total dose, enabled incidence of late rectal complications in cervical brachytherapy with LDR, MDR, and HDR to be plotted in a reasonably consistent way. This does not mean that those parameter values have been definitively determined, but they appear to be provisional values that may be of use in comparing the expected effects of new schedules until better values are obtained from greater use of common grading systems.

Brachytherapy↗
PubMed1996

Analysis of the retinohypothalamic tract in congenic albino and pigmented rats.

To determine whether differences in the retinohypothalamic tract (RHT) were related specifically to albinism, we analyzed the distribution and trajectory of this pathway in congenic F344-c/+ albino and pigmented rats using the inactive subunit of cholera toxin conjugated to horseradish peroxidase as an anterograde tracer. We found that the overall volume of the tract in the albino rats was greater than in the pigmented rats (P < 0.05). We also noted shape differences.

Albinism↗
PubMed1996

Fractionation in medium dose rate brachytherapy of cancer of the cervix.

PURPOSE: To establish an optimum fractionation for medium dose rate (MDR) brachytherapy from retrospective data of patients treated with different MDR schedules in comparison with a low dose rate (LDR) schedule. METHODS AND MATERIALS: The study population consists of consecutive Stage IB-IIA-IIB patients who received radiotherapy alone with full dose brachytherapy plus external beam pelvic and parametrial irradiation from 1986-1993. Patients also receiving surgery or chemotherapy were excluded. The LDR group (n = 102, median follow-up: 80 months) received a median dose to Point A of two 32.5 Gy fractions at 0.44 Gy/h plus 18 Gy of external whole pelvic irradiation. The MDR1 group (n = 30, median follow-up: 45 months) received a mean dose of two 32 Gy fractions at 1.68 Gy/h. An individual dose reduction of 12.5% was planned for this group according to the Manchester experience, but only a 4.8% dose reduction was achieved. The MDR2 group (n = 10, median follow-up: 36 months) received a dose of two 24 Gy fractions at 1.65 Gy/h. The MDR3 group (n = 10, median follow-up 33 months) received a mean dose of three 15.3 Gy fractions at 1.64 Gy/h. And finally, the MDR4 group (n = 38, median follow-up: 24 months) received six 7.7 Gy fractions from two pulses 6 h apart in each of three insertions at 1.61 Gy/h. The median external pelvic dose to MDR schedules was between 12 and 20 Gy. The linear quadratic (LQ) formula was used to calculate the biologically effective dose (BED) to tumor (Gy10) and rectum (Gy3), assuming T1/2 for repair = 1.5 h. RESULTS: The crude central recurrence rate was 6% for LDR (mean BED = 95.4 Gy10) and 10% for MDR4 (mean BED = 77.0 Gy10) (p = NS). The remaining MDR groups had no recurrences. Grade 2 and 3 rectal or bladder complications were 0% for LDR (rectal BED = 109 Gy3) 83% for MDR1 (BED = 206 Gy3), and 30% for MDR3 (BED = 127 Gy3). The MDR2 and MDR4 groups presented no complications (BED, 123 Gy3, and 105 Gy3, respectively). The LQ formula appears to correlate with late complications of the different MDR regimens. A BED above 125 Gy3 was associated with Grade 2 + 3 rectal complications. Adequate central tumor control may be compromised with a tumor BED below 90-95 Gy10. CONCLUSIONS: Medium dose rate brachytherapy at 1.6 Gy/h to Point A has a marked dose rate effect. Increased fractionation is the cost of overcoming the less favorable therapeutic ratio for MDR than for LDR. A larger (25%) reduction of brachytherapy dose than previously reported is also necessary. Our most recently developed schedule for Stage I-II patients is three insertions on three treatment days with six 8.0 Gy brachytherapy fractionations, two on each treatment day, following or preceding an external whole pelvis dose of 18 Gy, and followed by additional external parametrial dose.

Adult↗
PubMed1996

A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis.

PURPOSE: Recent randomized trials of selected patients with single brain metastasis comparing resection followed by whole-brain radiotherapy (WBRT) to WBRT alone have shown a statistically significant survival advantage for surgery and WBRT. A multiinstitutional retrospective study was performed, which identified comparable patients who were treated with stereotactic radiosurgery (RS) and WBRT. METHODS AND MATERIALS: The RS databases of four institutions were reviewed to identify patients who met the following criteria: single-brain metastasis; no prior cranial surgery or WBRT; age > 18 years; surgically resectable lesion; Karnofsky Performance Status (KPS) > or = 70 at time of RS; nonradiosensitive histology. One hundred twenty-two patients were identified who met these criteria. Patients were categorized by: (a) status of the primary, (b) status of non-CNS metastasis, (c) age, (d) baseline KPS (from 70-100), (e) histology, (f) time from diagnosis of primary to the detection of the brain metastasis, (g) gender, and (h) tumor volume. RS was performed with a linear accelerator based technique (peripheral dose range was 10-27 Gy, median was 17 Gy). WBRT was performed in all but five patients who refused WBRT (dose range was 25-40 Gy, median was 37.5 Gy). RESULTS: The median follow-up for all patients was 123 weeks. The overall local control rate (defined as lack of progression in the RS volume) was 86%. Intracranial recurrence outside of the RS volume was seen in 27 patients (22%). The actuarial median survival from date of RS is 56 weeks, and the 1-year and 2-year actuarial survival rates are 53% and 30%. The median duration of functional independence (sustained KPS > or = 70) is 44 weeks. Nineteen of 77 deaths were attributed to CNS progression (25% of all deaths). Multivariate analysis revealed the following factors to be statistically significant predictors of survival: baseline KPS (p < .0001) and absence of other sites of metastasis (p = 0.008). CONCLUSION: The RS in conjunction with WBRT for single brain metastasis can produce substantial functional survival, especially in patients with good performance status and without extracranial metastasis. These results are comparable to recent randomized trials of resection and WBRT. The advantages of RS over surgery in terms of cost, hospitalization, morbidity, and wider applicability strongly suggest that a randomized trial to compare RS with surgery is warranted.

Adult↗
PubMed1996

Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3.

PURPOSE: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. METHODS AND MATERIALS: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. RESULTS: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months)> CONCLUSION: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant.

Cohort Studies↗
PubMed1996

Ploidy as a prognostic feature in colonic adenocarcinoma.

OBJECTIVE: To determine whether DNA content and cell-cycle kinetic characteristics in Dukes stage B colonic adenocarcinomas provide additional prognostic information in the context of clinicopathologic variables of known significance. DESIGN: Archival, paraffin-embedded tissue blocks from 210 Dukes B colonic adenocarcinomas were retrieved. After confirming stage, tumor cell nuclei were extracted, suspended, and stained. Cell nuclei from adjacent normal colon mucosa were used as controls. SETTING: University-based, tertiary cancer referral center. INTERVENTIONS: Samples obtained from tumors resected at our institution between 1965 and 1984 were analyzed by flow cytometry for DNA index (DI) and percentages of cells in synthesis (S) phase (%S) and in G2 and mitosis (M) phases (%G2M). The data were correlated with 5-year survival. Follow-up was complete in all patients to at least 5 years. RESULTS: Univariate analysis showed that the highest survival rates were associated with DI values near 1 and 2 (diploid and tetraploid tumors, P = .02) and the lowest %G2M values (tumors with fewer mitoses; P = .01). Five-year survival rates also differed significantly between patients with diploid (DI < 1.1) and those with aneuploid (1.1 < DI < 2) tumors (80% vs 64%, respectively; P = .02). Multivariate analysis revealed that race (P < .01), lymphatic or capillary microinvasion (P < .03), and ploidy (P < .05) were significantly associated with outcome. The influence of ploidy, race, and microinvasion on 5-year survival was estimated with logistic regression, and 8 subgroups of patients emerged with 5-year survival probabilities ranging from 39% for black patients with aneuploid tumors and microinvasion to 88% for white patients with diploid tumors and no microinvasion. CONCLUSIONS: Tumor DNA content provides additional independent information that allows further refinement of our prognostic ability in patients with Dukes B colonic adenocarcinoma. This may aid in the identification of a cohort of patients who may potentially benefit from aggressive adjuvant therapy.

Adenocarcinoma↗
PubMed1996

Cytoreduction and prognosis in acute lymphoblastic leukemia--the importance of early marrow response: report from the Childrens Cancer Group.

PURPOSE: To quantify the residual marrow lymphoblast fraction that best defines patients at high risk for relapse, and the optimal time for assessment during remission induction. PATIENTS AND METHODS: The residual lymphoblast percentage was evaluated on day 7 (n = 220) and day 14 (n = 205) during a four- or five-drug induction in patients with poor prognostic factors. The rate of cytoreduction was related to event-free survival (EFS) and other factors. RESULTS: On the New York (NY) regimen, 68%, 14%, and 18%, and on the Berlin-Frankfurt-Munster (BFM) regimen, 56%, 15%, and 29% of patients had M1 (< 5% blasts), M2 (5-25%), or M3 (> 25%) responses on day 7 (P = .075). On day 14, the corresponding values were 87%, 6%, 7% on NY and 84%, 8%, 8% on BFM. For patients who achieved remission by day 28 and a day-7 marrow rating of M1, M2, or M3, the 6-year EFS rate was 78%, 61%, and 49% (P < .001). The day-14 ratings predicted for a 72%, 32%, or 40% EFS (P < .001). Patients with 5% to 10% blasts day 7 had three times as many events as those with less than 5% and had no better EFS than those with 11% to 25% blasts. Patients with a WBC count more than 200,000/microL at diagnosis and an M1 day 7 marrow had an EFS rate of 69%, while for those with M2 or M3, the EFS rate was 41%. Day-7 marrow had greater prognostic significance than the day-14 evaluation. For slow responders on day 7, the day-14 marrow provided additional information. EFS for patients who achieved M1 by day 14 was 65%. EFS decreased to 20% for those still M2 or M3 on day 14. Day-7 and -14 evaluations had significance for patients of all ages and WBC levels. CONCLUSION: Marrow aspiration on day 7 of therapy provided more useful information than that on day 14. However, day-14 marrow provided additional information for patients with a poor day-7 response. The rate of cytoreduction is a powerful, independent prognostic factor that can identify patients with a slow early response who are at risk for a short remission duration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Further analysis of radiobiological parameters from the First and Second British Institute of Radiology randomized studies of larynx/pharynx radiotherapy.

PURPOSE: This retrospective analysis of 1345 patients treated for cancer of the larynx or pharynx by randomization into two groups in each center in two separate trials of fractionated radiotherapy was carried out in an attempt to extract the radiobiological parameters alpha (dose), beta (fraction size), and gamma (overall time) from the data. METHODS AND MATERIALS: Details of the trials have been published previously. In the first, 734 patients were randomized to either five or three fractions per week, in centers each using their own overall time, which varied from 3 to 7 weeks in different centers. In the second trial, 611 patients were randomized to "short" (< or = 4 weeks) or "long" (4-7 weeks) overall time. We combine the data from both studies and use the linear-quadratic formula with logistic regression and maximum-likelihood methods to obtain the radiobiological factors, taking into account other variables such as stage or age, when significant. RESULTS: The parameters calculated for local tumor control showed significant estimates of alpha, very small estimates of beta, and significant values of gamma. The derived estimates of alpha/beta were large, but very variable. The time-dose tradeoff--gamma/alpha was 0.76 Gy/day for larynx and 0.3 Gy/day for pharynx tumors (not significantly different from each other). Late complications gave indeterminate alpha/beta ratios and a time-dose factor not significantly different from zero. Acute normal-tissue effects gave alpha/beta estimates of 8-9 Gy and time factors of 0.8-0.9 Gy/day. CONCLUSIONS: The results are consistent with other published values with the exception that significant time factors for late complications could not be excluded.

Age Factors↗
PubMed1995

The adverse effect of treatment prolongation in cervical carcinoma.

PURPOSE: Proliferation of surviving tumor clonogens during a course of protracted radiation therapy may be a cause of local failure in cervical carcinoma. The effect of total treatment time was analyzed retrospectively in relation to pelvic control and overall survival for squamous cell carcinomas of the uterine cervix. METHODS AND MATERIALS: Two hundred and nine patients (Stage IB-IIIB) treated with a combination of external beam and low dose rate intracavitary irradiation were evaluable for study. Multivariate analysis and Kaplan-Meier statistical methods were used to determine the effect of treatment time on pelvic control and survival at 5 years. RESULTS: The median treatment duration was 55 days. For all stages combined, the 5-year survival and pelvic control rates were significantly different with treatment times < 55 days vs. > or = 55 days: 65 and 54% (p = 0.03), 87 and 72% (p = 0.006), respectively. By stage, a shorter treatment duration (i.e., < 55 days vs. > or = 55 days) was significant for 5-year overall survival and pelvic control for Stages IB/IIA and III, but not for Stage IIB: Stage IB/IIA (81 and 67%, 96 and 84%), Stage III disease (52 and 42%, 76 and 55%) and Stage IIB (43 and 50%, 74 and 80%, respectively). Survival decreased 0.6%/day and pelvic control decreased 0.7%/day for each additional day of treatment beyond 55 days for all stages of disease. Additionally, significant late complications were not influenced by treatment time. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients with cervical carcinoma. This is consistent with emerging data from other institutions. Therapeutic implications include avoidance of unnecessary treatment breaks, the design of fractionation schemes that decrease treatment duration, and possibly the use of tumor cytostatic drugs during conventional radiation.

Brachytherapy↗
PubMed1995

Effect of time, dose and fractionation on local control of nasopharyngeal carcinoma.

To study the effect of radiation factors on local control of nasopharyngeal carcinoma, 1008 patients with similarly staged T1N03M0 disease (Ho's classification) were retrospectively analyzed. All patients were treated by megavoltage irradiation alone using the same technique. Four different fractionation schedules had been used sequentially during 1976-1985: with total dose ranging from 45.6 to 60 Gy and fractional dose from 2.5 to 4.2 Gy. The median overall time was 39 days (range = 38-75 days). Both for the whole series and 763 patients with nodal control, total dose was the most important radiation factor. The hazard of local failure decreased by 9% per additional Gy (p < 0.01). Biological equivalents expressed in terms of Biologically Effective Dose or Nominal Standard Dose also showed strong correlation. Fractional dose had no significant impact. The effect of overall treatment time was insignificant for the whole series, but almost reached statistical significance for those with nodal control (p = 0.06). Further study is required for elucidation, as 85% of patients completed treatment within a very narrow range (38-42 days), and the possible hazard is clinically too significant to be ignored.

Actuarial Analysis↗
PubMed1995

Self-reported health and survival in the Longitudinal Study of Aging, 1984-1986.

Changing and often declining health among elderly individuals makes interpreting the long-standing association between self-reported health (SRH) and mortality potentially problematic. This analysis of the Longitudinal Study of Aging from 1984 through 1986 explores changes over time in the association between a single self-report of health and survival among 4380 noninstitutionalized individuals aged 70 and older. Health was reported as excellent or very good (excellent/very good), good, fair or poor. The association between SRH and survival was modeled controlling for age, race, education, marital status, body mass index, difficulty performing activities of daily living, social contacts, self-reported stroke, heart disease, cancer, diabetes and recent hospitalization. Among women, SRH and survival were associated in a nonproportional model, with relative hazard declining over time. Women with poor vs excellent/very good SRH had adjusted relative hazards at 5, 14, 23 and 32 months of 3.8 [95% confidence interval (CI) 2.0-7.1], 2.7 (95% CI: 1.8-4.1), 2.0 (95% CI: 1.3-3.0), and 1.4 (95% CI: 0.7-2.7). The declining relative hazard was due to an increasing mortality rate over time among women initially reporting excellent/very good health. SRH was associated with survival among men in a proportional model (constant relative hazard over time). Men with poor vs excellent/very good SRH had an adjusted relative hazard of 1.7 (95% CI: 1.1-2.6) over the entire follow-up. The relative hazard of lesser magnitude among men reflects the weaker SRH-survival association, possibly too weak for any interaction with time to be detected. The constant relative hazard is also consistent with a rapid decline in health before death among men. The diminishing SRH-survival association among women is consistent with their longer period of declining health before death.

Activities of Daily Living↗
PubMed1994

Stereotactic radiosurgery for glioblastoma multiforme: report of a prospective study evaluating prognostic factors and analyzing long-term survival advantage.

PURPOSE: Prospective evaluation of the toxicity and efficacy of radiosurgery with external beam radiotherapy in the management of newly diagnosed glioblastoma. METHODS AND MATERIALS: From 5/89 to 12/92, 31 out of 51 patients with glioblastoma multiforme underwent radiosurgery, in addition to 54 Gy in 1.8 Gy/fraction following biopsy (n = 12) or resection (n = 19). Eligibility required supratentorial glioblastoma, tumor not > 4 cm in > 1 axis, age > 18 years, and location > 1 cm from optic chiasm. Patient characteristics were: age 20-78 years (median = 57); 22 male, 9 female; Karnofsky score 20-90 (m = 70), and volume of 2.3-59.7 c.c. (m = 17.4). Eighteen patients were treated with 1 collimator, 5 with 2, 7 with 3, and 1 with 4; peripheral isodoses were 40-90% (m = 72.5) and minimum and maximum tumor dose ranges were 10-20 (m = 12) and 15-35 Gy (m = 18.75). Patients were followed clinically and radiographically every 8-12 weeks to analyze survival, quality of life, and toxicity. RESULTS: With a follow-up of 12-171 weeks, 8 out of 31 (26%) patients are alive. Median survival is 42 weeks. Twelve and 24-month actuarial survival are 38 and 28%. Comparison of the 2-year survival with previous Radiation Therapy Oncology Group patients was carried out using a nonparametric recursive partitioning technique and the observed vs. expected values are 28 vs. 9.7% (p < 0.05). Extent of resection and performance status were associated with improved survival in a multivariate analysis. No significant acute toxicity was encountered. Four patients (13%) developed clinically significant necrosis verified by biopsy or positron emission tomography scan at 9-59 weeks after radiosurgery. CONCLUSION: The improvement in median survival in broadly selected glioblastoma patients treated with radiosurgery is difficult to determine, but the 2-year survival may be superior. Future randomized trials of radiosurgery are recommended, and ad hoc use of this modality should be discouraged.

Adult↗
PubMed1994

A comparison of the efficacy and complication rates of low dose-rate versus high dose-rate brachytherapy in the treatment of uterine cervical carcinoma.

PURPOSE: To compare the outcome and complication rates for treatment of uterine cervical carcinoma with low dose-rate (LDR) vs. high dose-rate (HDR) brachytherapy at the University of Wisconsin Comprehensive Cancer Center (UWCCC). METHODS AND MATERIALS: One-hundred ninety-eight evaluable patients with cervical carcinoma, Stages IB to IIIB, treated with curative intent with a combination of megavoltage teletherapy and LDR brachytherapy from 1977 to 1988 were the subject of an initial review. In 1989, a HDR treatment program was initiated where all patients with cervical carcinoma were subsequently treated with a combination of HDR brachytherapy and teletherapy. Using the linear-quadratic model (LQ), the dose and schedule of HDR brachytherapy and teletherapy were designed to give similar tumor control and late effects as LDR therapy. Technically, the HDR schedule required meticulous attention to treatment geometry to limit severe late effects. Forty patients treated with the HDR program with 2-4 year follow-up were reviewed and compared to the previous LDR patient group. The LDR and HDR treatment groups were comparable with regards to age, weight, stage distribution, bulk of disease, and histology. RESULTS: No significant difference in survival was found between the LDR and HDR groups with 3-year actuarial overall survival being 66% and 77%, respectively. Three-year actuarial pelvic control rates were similar at 80% and 77% for the LDR and HDR groups, respectively. No significant difference in late treatment complications requiring hospitalization or surgery was found between the two treatment groups with a complication rate of 10% (20/198) for the LDR patients and 2.5% (1/40) for the HDR patients. CONCLUSION: As predicted by our LQ calculations, treatment results for LDR and HDR brachytherapy were similar with respect to survival, pelvic control and late complications in the treatment of cervical carcinoma. The HDR brachytherapy program at the UWCCC appears to be a safe and effective alternative to LDR therapy in the treatment of cervical carcinoma.

Adolescent↗