Additional radiation therapy to the chest wall (boost) following mastectomy for locally advanced breast cancer is associated with practice pattern variation and an undefined survival benefit. This investigation examines the influence of a chest wall boost to post-mastectomy radiation therapy (PMRT) on breast cancer survival (BCS) and overall survival (OS) in women with locally advanced breast cancer using data from the California Cancer Registry (CCR). First primary female invasive breast cancers, diagnosed 2005-2009, treated with mastectomy and PMRT were identified from the CCR (n = 5586). Patients were categorized according to whether or not they received a boost. Bivariate analyses of patient socio-demographic, tumor and clinical factors on BCS and OS were performed using the Kaplan-Meier method. Adjusting for potential confounders, we used multivariate proportional hazards models to identify predictors of BCS and OS. Risks of overall and cause specific mortality were reported as hazard ratios (HRs) with 95% confidence intervals (CIs); significance was set at p < 0.05. From 2005-2009, there were 5586 patients treated with PMRT with a median follow-up 38.9 months. A boost was given to 3104 (56%) patients. Eighty-two percent of the patients were treated with chemotherapy, and 48% were treated with antihormonal therapy. Patients more likely to receive a boost compared to those not receiving it were Her2 positive patients (p = 0.04), Hispanics (p = 0.0003), low socioeconomic status (p < 0.0001), and patients who received chemotherapy (p = 0.04). In univariate analyses radiation boost was not related to BCS (p = 0.63) or OS (p = 0.71). Patients who had not received chemotherapy had a borderline better BCS and OS (p = 0.0549). In the univariate analyses there were no differences between the boost and the no boost group in regards to molecular subtype or age. Further, there was no difference for the use of a radiation boost in inflammatory breast cancer. In multivariate analysis, where each variable was studied while controlling for all other variables, there were no differences in BCS for those who did and did not receive a radiation boost (HR, 1.053; 95% CI, 0.86-1.29; p = 0.62) or OS (HR, 1.017; 95% CI, 0.86-1.20; p = 0.84). In these models, variables related to poor survival after controlling for potential confounders were ER- vs ER+; PR- vs PR+; advanced stage vs stage 1; presence of positive nodes; and not receiving systemic chemotherapy (most significant at p < 0.0001). In an era of comparative effectiveness in oncology, we found no difference in BCS or OS with the addition of a radiation boost following PMRT in our large database. There was a trend for improved BCS and OS for those patients not treated with chemotherapy in the radiation boost group in comparison to the no boost group, suggesting an increased role of local therapy in this setting.

PURPOSE:To develop a population-based three-dimensional lymph node target volume of the head and neck. METHODS AND MATERIALS:The T2 weighted axial magnetic resonance imaging (MRI) images of 35 patients with known head and neck cancer were reviewed. An experienced head and neck radiologist marked each lymph node (LN) electronically. The images were distributed to one of 12 axial levels of the head and neck with each level representing a distinct portion of the neck based on external contours and the presence of anatomic structures. The LNs were marked with five different symbols to distinguish the superior/inferior extent of each LN within each level. With the categorization of each image into a different superior/inferior level of the neck, the registration of the images was limited to two dimensions. Nonlinear transformation accounted for inter-patient differences although no local warping was used. The co-registration used recognizable anatomic landmarks (vertebral body, mandible, maxilla, clivus as well as the sternocleidomastoid muscle, external skin contour, spinal cord) to match the patient anatomy. RESULTS:In total, 503 images were co-registered with the baseline images. The majority of the co-registrations were of good quality; 361, 122, and 20 image co-registrations scored as global, limited, and poor co-registrations respectively. One thousand and fifty seven LNs were marked, with 122 LNs marked as submandibular and submental LN. Among the levels A, B, C, D, E, F, G, H, 22, 44, 206, 199, 196, 175, 63, 35 LN were marked respectively. Noteworthy anatomic variation was observed among the different nodal groups that are summarized in the representative baseline images. CONCLUSIONS:Image registration of a series of head and neck images generates a valuable population-based lymph node map that can be used to guide the three-dimensional delineation of the elective lymph node target volume. Significant variation in the lymph node location was seen in all LN groups. The medial border of the internal jugular vein can be used as an important landmark structure in delineating the jugular LN clinical target volume and, for that reason, intravenous contrast is recommended to improve visualization. The location of the submandibular LN appear to be limited to the space anterior and lateral to the submandibular gland and are found mostly along the inferior edge of the mandible. The location of the retropharyngeal LN does vary but their location does not appear to vary with any other recognizable axial structure. The lymph node map provides another collaborating piece of evidence in defining the head and neck LN clinical target volume.

Purpose: This study was an open-label, randomized Phase III trial in newly diagnosed patients with anaplastic glioma other than glioblastoma multiforme comparing external beam radiotherapy (EBRT) plus adjuvant procarbazine, cyclohexylchloroethylnitrosurea (lomustine), and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-h infusion each week of RT.Methods and Materials: Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible. A central pathology review was accomplished for most patients, but was not mandated before registration. The study had initially opened as a Northern California Oncology Group trial in 1991, becoming an Intergroup Radiation Therapy Oncology Group (RTOG), Southwestern Oncology Group and the North Central Cancer Treatment Group study in July 1994. A total accrual of 293 patients was planned for the sample size, using survival as the primary end point. The experimental arm (RT/BUdR + PCV) was to be compared with the control arm (RT + PCV) using a one-sided alpha = 0.05, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after enrollment completion.Results: Between July 1994 and August 1996, 134 patients were randomized to EBRT + PCV (non-BUdR patients) and 134 to EBRT/BUdR + PCV (BUdR patients). The study was closed before the full-anticipated accrual on the basis of an interim analysis that predicted no survival benefit for the BUdR arm. Of the 268 patients, 41 and 37, respectively, were ineligible or canceled primarily on the basis of the central pathology review findings. Thus, 93 patients and 97 patients were eligible/analyzable in the non-BUdR and BUdR arms, respectively. Patient characteristics were well balanced in both arms, with most <50 years old and in the RTOG recursive partitioning analysis (RPA) Class I category. The minimal potential follow-up was 4.6 years. The median survival for non-BUdR patients was 4.1 years compared with 4.6 years for the BUdR patients (p = 0.61). The 4-year overall survival rate was 51% in both arms. For RPA Class I patients (the best prognostic class), the median survival had not been reached for non-BUdR patients (4-year survival rate 61%) and was 5.6 years for BUdR patients (4-year survival rate 64%; p = 0.91). Each arm was also compared with the RTOG historical database for RPA Class I patients with no statistically significant difference found in overall survival (BUdR vs. historical, p = 0.31 and non-BUdR vs. historical, p = 0.48). Grade 4 toxicity occurred in 15 and 17 patients in the non-BUdR and BUdR arms, respectively, with one treatment-related death in the BUdR group.Conclusion: No survival advantage was noted by adding BUdR to EBRT and PCV in this patient population (C) 2004 Elsevier Inc.

Purpose/Objective: IMRT results in a more inhomogeneous dose within the tumor target when compared to conventional delivery. The concept of equivalent uniform dose has been proposed as a way to concisely report the inhomogeneous dose distribution based on radiobiologic response of the tumor. However, dose fractionation is not accounted for in a newly proposed generalized EUD (gEUD). In this study, we propose a modified EUD (mEUD) to account for dose fractionation without losing the simplicity of the gEUD. Materials/Methods: The gEUD, which is fitted phenomenologically from clinical data, is given as (Σvi Dia)1/a, where vi and Di are fractional volume and the dose at that volume, respectively, and a is the tissue specific parameter determined empirically from comparing treatment plans and clinical outcomes. This gEUD can be thought of as dose-domain proxy for tumor control probability (TCP) and normal tissue complication probability (NTCP). gEUD has many advantages over TCP/NTCP such as ease of calculation, robustness with imprecise parameters, and utilization of clinical experience. The mEUD is simply the gEUD with addition of the biologically effective dose (BED) and a correction factor. mEUD is given as (1/c)(Σvi BEDia)1/a. BED is the dose given in infinitely small fractions that will yield the same biologic response as the dose in question and is given as BED=nd[1+d/(α/β)], where n is the number of fraction, d is the dose per fraction, and αand β are linear and quadratic constants of the survival fraction. C is the correction factor which is given as 1+(D0/n0)/(α/β). D0and n0 are the typical prescription dose and fraction number for the particular institution. mEUD is interpreted as the uniform dose given in fractions typical of that particular institution that will yield the same TCP/NTCP as the inhomogeneous IMRT dose distribution in question. This modification also contributes to the more precise determination of the a parameter by making it account only for the functional subunit architecture. The gEUD and the mEUD were calculated for 45 nasopharyngeal cancer patients treated with IMRT. The calculations were carried out when 70 Gy is delivered to the GTV or PTV70 simultaneously with 59.4 Gy is delivered to the high-risk subclinical disease or PTV59.4. In addition, the parotid glands and the spinal cord were also calculated. Results: The calculated average gEUDs were 72.3 Gy (± 2.6 Gy) for the PTV70, 54.4 Gy (± 7.2 Gy) for the PTV59.4, 26.7 Gy (± 4.5 Gy) for the parotids, and 34.1 Gy (± 6.9 Gy) for the spinal cord. mEUD was calculated incorporating 33 fractions in the formula. The calculated average mEUDs were 71.9 Gy (± 4.0) for PTV70, 50.2 Gy (± 8.2) for PTV59.4, 27.6 Gy ( ± 5.3) for the parotid glands, and 35.1 Gy (± 8.4) for the spinal cord. Conclusions: The concept of EUD was a good starting point to incorporate radiobiologic response as a means to report and analyze inhomogeneous IMRT treatment dose distribution. Recent generalization of EUD using generalized means made it possible for the EUD concept to be applied both to tumor and normal tissue. While the gEDU has numerous advantages such as being very intuitive and convenient to manipulate for such purposes as computer optimization, one of the criticisms has been that it failed to account for fractionation. Such shortcoming has been a result of having only one parameter, a, for each tissue, ignoring the role of any other clinical variables other than the total dose. mEUD combining gEUD with BED preserves all advantages of gEUD while reflecting the fractionation effect and accounting for linear- and quadratic- survival characteristics.

Purpose/Objective: To create a population-based lymph node imaging atlas of the head and neck and to define and relate the lymph node CTV to axial imaging landmarks in head and neck cancer. Materials/Methods: The axial T2 MRI’s of 37 H+N cancer patients were used. Each lymph node (LN) was marked by a radiologist (NF). The images were separated into 8 separate levels (A-H) with distinctive bony/soft tissue landmarks. A single baseline image represented each of these levels (A-H). The LN were marked using different symbols (○ ▵ □ × +); with the symbol ○ representing the most superior slice and +the most inferior slice within that level. The Zone IA/B LN were divided into 4 separate vertical levels. Non-rigid manual affine transformation was used for inter-patient anatomical variation and scaling differences. Local non-linear deformations were not used. Results: 877 LN were marked. Only 2 of 12 representative levels are included below due to practical limitations. In fig 1 (Level B), the large majority of retropharyngeal (RP) LN are found at the B and C level. Intraparotid LN were scattered. Fig 2 (Level D) outlines Zone II and upper V LN, with most LN a substantial distance from the midline sensitive structures. A population-based CTV for H+N cancer will be presented. Conclusions: The LN bearing regions of the H+N show significant 3D variation that the conformal radiotherapist must consider. The LN atlas provides a basis to improve the accuracy of lymph node CTV delineation and should minimize geographic miss and lead to dose sparing of normal tissue. Population based atlases of other LN bearing areas are needed. View Large Image Figure ViewerDownload (PPT)

Purpose: To determine factors that effect QOL in patients with locally advanced squamous cell cancer of the head and neck randomized to standard fractionation radiotherapy (SFX), hyperfractionation (HFX), Accelerated Fractionation with Split (AFX-S) and Accelerated Fractionation with Concomitant Boost (AFX-C).

Purpose: The objective of this trial was to compare the efficacy of treatment with XRT and PCV chemotherapy versus XRT plus BudR and PCV chemotherapy for newly diagnosed patients with anaplastic glioma. The primary endpoint was survival, measured from the first day of treatment. Eligibility required surgical confirmation of a grade-3 malignant glioma; no prior XRT or chemotherapy; age > 18; KPS > 70; acceptable laboratory values (WBC > 4000, platelets > 125,000, BUN < 30, SGOT and Alk P04 < 2 x maximal normal) with treatment to begin no later than 6 weeks from surgery. Central review of pathology was not done prior to registration.Material and methods: Treatment for the control arm included focal XRT to 59.4 Gy (1.8 Gy x 33 fractions) and PCV chemotherapy given adjuvantly for 6 treatment cycles every 6 weeks beginning 2 weeks after completion of XRT; patients randomized to the experimental arm were treated as above, plus a 96 hour continuous infusion of BudR at a dose of 0.8 g/m2 beginning on Thursday or Friday before the first Monday of XRT. BudR treatment continued for a total of 6 infusion during XRT.Results: Between July 1994 and August 1996, a total of 134 patients were randomized to XRT/PCV ("non-BudR pts") and 134 to XRT +BudR/PCV ("BudR pts"). The study was closed prior to full-anticipated accrual based upon interim analyses that predicted no potential survival benefit for the BudR arm. Of the 268 pts, 41 and 37, respectively, were ineligible or canceled primarily based on central pathology review. Thus, 93 pts and 97 pts were eligible/analyzable on the non-BudR and BudR arms. Patients were well balanced in both arms, the majority being under 50 yrs of age in the RPA class 1.0 category. Minimum follow-up is 4.6 years. Median survival for non-BudR pts is 4.1 yrs compared to 4.6 yrs for BudR pts [p=0.61]; 4-year survival is 51% in both arms. For RPA class 1.0 patients, median survival has not been reached for non-BudR pts (4-year survival 61%) and is 5.6 yrs for BudR pts (4-year survival 64%) [p=0.91]. Both arms were also compared to the RTOG historical database for RPA Class 1.0 pts with no significant difference in median or 4-year survival [p=0.54]. Grade 4 toxicity occurred in 15 and 17 pts in the non-BudR and BudR arms respective with one treatment related death in the BudR group.Conclusion: No survival advantage was noted by adding BudR to XRT and PCV in this patient population. Purpose: The objective of this trial was to compare the efficacy of treatment with XRT and PCV chemotherapy versus XRT plus BudR and PCV chemotherapy for newly diagnosed patients with anaplastic glioma. The primary endpoint was survival, measured from the first day of treatment. Eligibility required surgical confirmation of a grade-3 malignant glioma; no prior XRT or chemotherapy; age > 18; KPS > 70; acceptable laboratory values (WBC > 4000, platelets > 125,000, BUN < 30, SGOT and Alk P04 < 2 x maximal normal) with treatment to begin no later than 6 weeks from surgery. Central review of pathology was not done prior to registration. Material and methods: Treatment for the control arm included focal XRT to 59.4 Gy (1.8 Gy x 33 fractions) and PCV chemotherapy given adjuvantly for 6 treatment cycles every 6 weeks beginning 2 weeks after completion of XRT; patients randomized to the experimental arm were treated as above, plus a 96 hour continuous infusion of BudR at a dose of 0.8 g/m2 beginning on Thursday or Friday before the first Monday of XRT. BudR treatment continued for a total of 6 infusion during XRT. Results: Between July 1994 and August 1996, a total of 134 patients were randomized to XRT/PCV ("non-BudR pts") and 134 to XRT +BudR/PCV ("BudR pts"). The study was closed prior to full-anticipated accrual based upon interim analyses that predicted no potential survival benefit for the BudR arm. Of the 268 pts, 41 and 37, respectively, were ineligible or canceled primarily based on central pathology review. Thus, 93 pts and 97 pts were eligible/analyzable on the non-BudR and BudR arms. Patients were well balanced in both arms, the majority being under 50 yrs of age in the RPA class 1.0 category. Minimum follow-up is 4.6 years. Median survival for non-BudR pts is 4.1 yrs compared to 4.6 yrs for BudR pts [p=0.61]; 4-year survival is 51% in both arms. For RPA class 1.0 patients, median survival has not been reached for non-BudR pts (4-year survival 61%) and is 5.6 yrs for BudR pts (4-year survival 64%) [p=0.91]. Both arms were also compared to the RTOG historical database for RPA Class 1.0 pts with no significant difference in median or 4-year survival [p=0.54]. Grade 4 toxicity occurred in 15 and 17 pts in the non-BudR and BudR arms respective with one treatment related death in the BudR group. Conclusion: No survival advantage was noted by adding BudR to XRT and PCV in this patient population.

Purpose: To compare the dose and volume of bladder and rectum treated using high-dose-rate (HDR) prostate implant boost versus conformal external beam radiotherapy boost, and to use the dose-volume information to perform a critical volume tolerance (CVT) analysis and then estimate the potential for further dose escalation using HDR brachytherapy boost.Methods and Materials: Using CT scan data collected before and after patients underwent HDR prostate implant, a 7-field conformal prostate-only external beam treatment plan and HDR brachytherapy treatment plan were constructed for each patient. Doses to the normal structures were calculated. Dose-volume histograms (DVH) were plotted for comparison of the two techniques. Wilcoxon signed rank test was performed at four dose levels to compare the dose to normal structures between the two treatment techniques. The acute and late effects of HDR brachytherapy were calculated based on the linear-quadratic (LQ) model. CVT analyses were performed to calculate the potential dose gain (PDG) using HDR brachytherapy boost.Results: The volume of bladder and rectum receiving high dose was significantly less from implant boost. On the average, 0.19 cc of the bladder received 100% of the brachytherapy prescription dose, compared with 5.1 cc of the bladder receiving 100% of the prescription dose in the 7-field conformal external beam radiotherapy boost. Similarly, 0.25 cc of the rectum received 100% of the dose with the implant boost, as compared to 2.9 cc in the conformal external beam treatment. The implant also delivered higher doses inside the prostate volume. On average, 47% of the prostate received greater than or equal to 150% of the prescription dose. The CVT analysis revealed a range of PDG using the HDR brachytherapy boast which depended on the following variables: critical volume (CV), critical volume tolerance dose (CVTD), number of HDR fractions (N), and the dose of external beam radiotherapy (XRT) delivered with brachytherapy boost. The PDG varied from -3.45% to 10.53% for tumor with an alpha-beta ratio of 10 and 7.14% to 64.6% for tumor with an alpha-beta ratio of 1.5 based on the parameters used for calculation in this study.Conclusions: HDR brachytherapy can provide better sparing of rectum and bladder while delivering a higher dose to the prostate. Even with the increased late effects of high dose per fraction, there is still a potential for dose escalation beyond external radiotherapy limits using HDR brachytherapy. (C) 2000 Elsevier Science Inc.

PURPOSE:This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy.METHODS AND MATERIALS:Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment.RESULTS:As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment.CONCLUSIONS:Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years.

The search continues for a favorable subgroup of patients with brain metastases in whom testing of new modalities might show a benefit in overall survival. Complete pre- and post-treatment CT evaluation of the brain was performed in 779 of the 859 patients entered into RTOG protocol 7916, a phase III study of the role of misonidazole combined with radiation therapy in the treatment of brain metastases. Pretreatment scan findings of mass effect, midline shift, massive edema, central necrosis, location of sentinel lesion, and number of lesions were correlated with length of survival for all patients as well as for each treatment group. The only characteristics that showed a statistically significant difference in survival in the overall group were the presence of < or = 3 lesions and the presence of a midline shift. The actual benefit in overall survival, however, was found to be only 3 weeks. The volume of the largest lesion prior to treatment did not correlate well with survival, nor did location of lesions. The time to response, number of responders and absolute decrease in number of lesions were similar for the four treatment arms. Patients who responded to cranial treatment had a significantly prolonged survival over those who did not respond. No CT characteristic evaluated in this study showed value as a clinically relevant prognosticator for patients with brain metastases for the overall group. Patients who fulfilled three of the four favorable clinical characteristics previously described by Diener-West (age < or = 60, KPS > or = 70, primary lesion absent or controlled and brain as sole site of metastasis), were analyzed separately. Those with < or = three lesions had a statistically significantly prolonged survival over those with four or more lesions.

Following the completion of a phase I study of etanidazole (SR 2508), a new hypoxic cell sensitizer, the RTOG, began a phase II/III trial. The objectives of the study were to determine the toxicity and efficacy of SR 2508, combined with conventional radiotherapy for the management of unresectable stage III and IV head and neck squamous carcinomas.During the first step (or the Phase II portion) of the study, 33 patients received radiotherapy plus SR 2508 (RT + SR 2508). The incidence of drug toxicities was modest; including 24% grade I peripheral neuropathy (PN), 6% grade II PN, 27% grade I or II nausea and vomiting, 9% allergy and 15% reversible neutropenia. Because observed toxicities were deemed acceptable, the second step (or phase III portion) was then activated. Patients were randomized to receive either RT or RT + SR 2508. As of November 20, 1989, a total of 242 patients have been entered onto the Phase III portion of the study. One hundred twenty-two patients were randomized to the RT + SR 2508 arm and 120 patients were randomized to the RT alone arm. The analyses presented in this report are based on data available [11]. The incidence of drug toxicities has been low, with 18% grade I or II PN, 26% nausea and vomiting (including one grade III), 14% allergy (including one grade III) and 13% reversible neutropenia. Blood samples were obtained at 0, 15 and 60 min, and 2, 4, and 20-24 hours following the administration of the first or second dose of SR 2508, for the measurement of serum drug concentration, and determination of the area under the curve (AUC). The average single drug dose AUC for 110 patients with data presently available, was 2.55 +/- 0.86 mM-hr.The observed incidences of radiotherapy related toxicities in RT + SR 2508 group were not different from those in RT alone group.Preliminary analysis of the treatment results, showed that the 33 patients from the phase II part had achieved an initial complete response rate of 58%. Considering the fact that 61% of the patients had T4 and 49% had N3, this result is encouraging.With an accrual rate of 15 cases per month, this study will meet its patient accrual goal in 1990, and the results concerning the SR 2508 efficacy will be available after another year of follow up.

Brachytherapy has proven the treatment of choice for selected recurrences of malignant gliomas. We tested the use of brachytherapy in the adjuvant treatment of these tumors when between Jan. 3, 1983 and Nov. 1 1989 we treated patients after biopsy or surgical resection of unifocal, supratentorial, and radiographically-circumscribed (eimplantable) glioblastoma multiforme (GM) or non-glioblastoma anaplastic astrocytoma (NOM) with external irradiation to the tumor volume (6000 rad), with concomitant hydroxyurea, followed by a stereotaxically-placed temporary implant with high-activity iodine-125 (5000 rad). Patients were then placed on a regimen of procarbazine, CCNU, and vincristine for 6 courses. Eighty-eight patients were entered into this NC00 protocol , with 4 dying during or immediately after external irradiation and 29 (22 GM , 7 NGM) not receiving an implant for various other reasons, the majority (62%) because the tumor had grown during irradiation. Twenty-five patients with NOM and 30 patients with GM received implants and are considered evaluable. At the time of analysis 56% of evaluable patients with NGU were alive with a median survival of 157 weeks while 43% of GM patients were alive with a median survival of 88 weeks. Twenty-five of the evaluable patients (45%) underwent reoperation after implant because of clinical deterioration and increasing steroid dependency. Other patients were treated with the same adjuvant brachytherapy regimen but were not registered with the NCOG because of geographic considerations. The median survival for the additional 27 patients with NGM was 142 weeks, and for the 50 with GM it was 83 weeks, both values close to those of patients registered with NCOG. Thirty-five patients with NGM and 33 with GM were uimplantablel~ but for various reasons were treated on another NCOG protocol of external beam irradiation given with bromodeoxyuridine (BUdR) infusion. Since these uimplantablee patients were treated concurrently with the brachytherapy patients, the two groups were compared. The median survival for the BUdR-treated patients with NGM was 199 weeks and that for those with GMwas 60 weeks. We conclude that for selected patients with GM, but not NGM, an interstitial eboostw is an advantage. Hyperthermia with brachytherapy is already being used at our center for selected recurrences of both GM _and NOM, and a trial integrating hyperthermia and brachytherapy into the adjuvant treatment of GM is being designed.

A computer program has been developed at the University of California, San Francisco, as an aid in planning and evaluating stereotactic brain implants made with 125I seeds. The program allows images of seeds and catheters to be positioned in the target volume revealed by CT. It then generates and displays the resulting isodose distributions. Catheters may be changed interactively until an optimum implant is achieved. From the geometry of a stereotactic implant frame as measured by CT, the program calculates the approach angles of the catheters in the frame coordinate system. After the seeds are implanted, films made with a fiducial marker box can be used to generate true seed positions and hence true isodoses. This paper describe's mathematically the geometrical transformations used by the program, and also outlines its many features and options. In its first 2 years of use the program has proved to be a valuable contributor to improved patient care.

The authors retrospectively reviewed the diagnosis and management of 20 intraocular lymphoma patients who initially presented with either ocular or central nervous system (CNS) disease. As the ophthalmic community has become more aware of this entity, the interval between symptoms and diagnosis has significantly shortened. Diagnosis can usually be made on cytopathologic examination of vitreous cells. However, in three cases more than one vitreous biopsy was necessary. Results of cytologic examination appeared to be more accurate than those of conventional lymphocyte surface marker studies in the diagnosis of an intraocular lymphoma. Long-term survival occurred in some patients treated with a combination of intrathecal chemotherapy and ocular/CNS irradiation.

This paper provides an introduction into the clinical activities of the RTOG (Radiation Therapy Oncology Group), its goals, its organization, its format for protocol development, and presents major areas of achievement. It provides an organizational chart of the group, a disease site modality cross-reference for protocols, and appendices which provide the key published results of the Group's clinical activities. This paper presents an important overview of the RTOG clinical research activities, which are designed to improve the role of radiation therapy.

I-125 sources are being used in temporary interstitial implants of various sites. Radiation safety considerations favor its use over other available radioisotopes. Cost containment is achieved by using the same sources for a number of patients. Loading I-125 seeds into implant catheters at our institutions permit customized source arrangement to optimize the implant dose patterns. Clinical examples are given for which the dose distributions achieved with customized source loading are superior to those achievable with standard Ir-192 ribbons.

The effect of giving buthionine sulfoximine (BSO), 0.0265 g/mouse (6 mM), at 12 and 6 hr before treatment with melphalan--0.0 mg, 3 mg, 6 mg, and 9 mg/kg, was studied in C3H mice, and was compared with control groups that received normal saline 12 and 6 hr before identical melphalan treatment. BSO treatment resulted in depletion of GSH levels in bone marrow, liver, and muscle to 65, 13, and 41% of control levels, respectively. Hematological toxicity was assessed by measurement of CFU-S survival and peripheral white cell counts. CFU-S survival decreased with increasing doses of melphalan, but no difference was observed with BSO pre-treatment. Likewise, WBC counts following melphalan 9 mg/kg, were similar irrespective of BSO pre-treatment. These data suggest that the marrow toxicity seen with melphalan is not worsened by pre-treatment with BSO and that if tumors can be pre-sensitized with BSO, there may be a clinical role for melphalan/BSO drug combination.