Impact of individualized treatment on recovery from fatigue and return to work in survivors of advanced-stage Hodgkin's lymphoma: results from the randomized international GHSG HD18 trial.

BACKGROUND: Persisting cancer-related fatigue impairs health-related quality of life (HRQoL) and social reintegration in patients with Hodgkin's lymphoma (HL). The GHSG HD18 trial established treatment de-escalation for advanced-stage HL guided by positron emission tomography after two cycles (PET-2) as new standard. Here, we investigate the impact of treatment de-escalation on long-term HRQoL, time to recovery from fatigue (TTR-F), and time to return to work (TTR-W). PATIENTS AND METHODS: Patients received European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and life situation questionnaires at baseline, interim, end of treatment, and yearly follow-up. TTR-F was defined as time from the end of chemotherapy until the first fatigue score <30. TTR-W was analyzed in previously working or studying patients and measured from the end of treatment until the first documented work or education. We compared duration of treatment on TTR-F and TTR-W using Cox proportional hazards regression adjusted for confounding variables. RESULTS: HRQoL questionnaires at baseline were available in 1632 (83.9%) of all randomized patients. Overall, higher baseline fatigue and age were significantly associated with longer TTR-F and TTR-W and male sex with shorter TTR-W. Treatment reduction from eight to four chemotherapy cycles led to a significantly shorter TTR-F [hazard ratio (HR) 1.41, P = 0.008] and descriptively shorter TTR-W (HR 1.24, P = 0.084) in PET-2-negative patients. Reduction from six to four cycles led to non-significant but plausible intermediate accelerations. The addition of rituximab caused significantly slower TTR-F (HR 0.70, P = 0.0163) and TTR-W (HR 0.64, P = 0.0017) in PET-2-positive patients. HRQoL at baseline and age were the main determinants of 2-year HRQoL. CONCLUSIONS: Individualized first-line treatment in patients with advanced-stage HL considerably shortens TTR-F and TTR-W in PET-2-negative patients. Our results support the use of response-adapted shortened treatment duration for patients with HL.

Adherence and health literacy as related to outcome of patients treated for rheumatoid arthritis : Analyses of a large-scale observational study.

BACKGROUND: Disabilities in daily living and quality of life are key endpoints for evaluating the treatment outcome for rheumatoid arthritis (RA). Factors possibly contributing to good outcome are adherence and health literacy. METHODS: The survey included a representative nationwide sample of German rheumatologists and their patients with RA. The physician questionnaire included the disease activity score (DAS28) and medical prescriptions. The patient questionnaire included fatigue (EORTC QLQ-FA13), health assessment questionnaire (HAQ), quality of life (SF-12), health literacy (HELP), and patients' listings of their medications. Adherence was operationalized as follows: patient-reported (CQR5), behavioral (concordance between physicians' and patients' listings of medications), physician-assessed, and a combined measure of physician rating (1 = very adherent, 0 = less adherent) and the match between physicians' prescriptions and patients' accounts of their medications (1 = perfect match, 0 = no perfect match) that yielded three categories of adherence: high, medium, and low. Simple and multiple linear regressions (controlling for age, sex, smoking, drinking alcohol, and sport) were calculated using adherence and health literacy as predictor variables, and disease activity and patient-reported outcomes as dependent variables. RESULTS: 708 pairs of patient and physician questionnaires were analyzed. The mean patient age (73% women) was 60 years (SD = 12). Multiple regression analyses showed that high adherence was significantly associated with 5/7 outcome variables and health literacy with 7/7 outcome variables. CONCLUSION: Adherence and health literacy had weak but consistent effects on most outcomes. Thus, enhancing adherence and understanding of medical information could improve outcome, which should be investigated in future interventional studies.

A multi-institutional analysis of intraoperative radiotherapy for early breast cancer: Does age matter?

BACKGROUND: Single-session intraoperative radiation therapy (IORT) minimizes treatment demands associated with traditional whole breast radiation therapy (WBRT) but outcomes on local disease control and morbidity among the elderly is limited. METHODS: A multi-institutional retrospective registry was established from 19 centers utilizing IORT from 2007 to 2013. Patient, tumor, and treatment variables were analyzed for ages <70 and ≥70. RESULTS: We evaluated 686 patients (<70 = 424; ≥70 = 262) who were margin and lymph node negative. Patients <70 were more likely to have longer operative time, oncoplastic closure, higher rates of IORT used as planned boost, and receive chemotherapy and post-operative WBRT. Wound complication rates were low and not significantly different between age groups. Median follow-up was 1.06 (range 0.51-1.9) years for < 70 and 1.01 (range 0.5-1.68) years for ≥ 70. There were 5 (0.73%) breast recurrences (4 in <70 and 1 ≥ 70, p = 0.65) and no axillary recurrences during follow-up. CONCLUSIONS: IORT was associated with a low rate of wound complication and local recurrence on short-term follow-up in this cohort.

BEACOPP and COPP/ABVD as salvage treatment after primary extended field radiation therapy of early stage Hodgkins disease - results of the German Hodgkin Study Group.

Patients with early stage favorable Hodgkin's disease who relapse after extended field radiotherapy have satisfactory results. We retrospectively analysed patients with relapsed HD after initial radiation therapy alone to determine treatment outcome and prognostic factors. Nine-hundred and forty five patients in localized stages without risk factors received either 40 Gy extended field RT or 30 Gy EF RT followed by an additional 10 Gy to involved lymph node regions. 107 patients relapsed and received salvage therapy. Characteristics of the 107 patients at relapse were as follows: median age was 34 years (range 18--75) with relapse occuring at a median of 19 months (range 4--98 months), 31% were female. The majority of patients (93%) were treated with conventional chemotherapy. Sixty-nine percent were treated with COPP/ABVD like regimens, 21% with BEACOPP, and 3% received various other regimens. Seven percent were treated with radiotherapy alone. Complete remission was achieved in 87% of all salvaged patients. The median follow-up after relapse was 45 months. FF2F (freedom from second treatment failure) and OS (overall survival) were 81% and 89%, respectively. In multivariate analysis age was the major prognostic factor for FF2F and OS (p<0.0001, for both). Further independent prognostic factors were B symptoms (p=0.05) and salvage chemotherapy (p=0.03) for FF2F, and B symptoms (p=0.03) and extranodal involvement (p=0.02) for OS. The long-term outcome of patients relapsing after EF RT is excellent. Age, B symptoms, extranodal involvement and salvage chemotherapy were identified as prognostic factors for second relapse and survival.

A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly).

In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.

Fatigue in long-term survivors of Hodgkin's lymphoma; a report from the German Hodgkin Lymphoma Study Group (GHSG).

Although treatment regimens for Hodgkin's lymphoma have become more sophisticated, little is known about the prevalence of fatigue in long-term survivors. Therefore, we investigated the fatigue status of long-term survivors of Hodgkin's lymphoma and a control group using a pre-validated questionnaire. In 1995/1996, we contacted 1981 patients, who were enrolled in the German Hodgkin Studies HD 1-6. All patients were treated according to the treatment protocols HD1-3 (1981-1988) and HD 4-6 (1988-1993). The patients with a current status of complete remission were asked to complete a quality-of-life (QoL) questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ C-30)) and a fatigue questionnaire (Multidimensional Fatigue Inventory (MFI)). The results were compared with the data from 935 controls, matched for age, gender and living area. Eight-hundred and eighteen questionnaires from the patients were available for analysis. The median time between the end of treatment and completing the questionnaire is 5.2 years. Fatigue levels of patients with Hodgkin's lymphoma are high, even years after treatment. Fatigue dimensions are significantly influenced by several clinical and non-clinical factors. Fatigue levels of Hodgkin's lymphoma patients are significantly higher than those of the control group. Further investigations are warranted to explore the effectiveness of treatment strategies for fatigue.

[Cancer fatigue syndrome]. / Das Krebs-Fatigue-Syndrom.

Tumour-related fatigue, which occurs in almost all tumour patients under therapy--very often even years after a successful therapy--has a considerable impact not only on the quality of life, but apparently also on the course and outcome of treatment. There is little known about where cancer fatigue syndrome comes from. Medical research is required particularly for the continuous states of tiredness persisting for years. The questionnaires currently in use permit an accurate evaluation of the existence and the course of tumour-related fatigue. The treatment of the cancer fatigue syndrome includes the correction of underlying metabolic disorders as well as--even more importantly--physical training and psycho-oncological measures in order to better cope with the disease. Many questions, however, are left open, for instance the impact of cancer fatigue syndrome on disability pensions of tumour patients. The German Fatigue Society (DfaG) was therefore founded in March 2002 in order to find out the correlations between these questions and the cancer fatigue syndrome.

Phase II radiation therapy oncology group trial of weekly paclitaxel and conventional external beam radiation therapy for supratentorial glioblastoma multiforme.

PURPOSE: Fractionated external beam radiotherapy (EBRT) +/- carmustine (BCNU) is the standard of care for patients with glioblastoma multiforme (GBM), but survival results remain poor. Preclinical studies indicate synergy between RT and paclitaxel (TAX) in astrocytoma cell lines. Phase I studies in GBM have demonstrated a maximum tolerated dose for TAX of 225 mg/m(2)/3 h/week x 6, during EBRT, with no exacerbation of typical RT-induced toxicities. The Radiation Therapy Oncology Group (RTOG) therefore mounted a Phase II study to determine the feasibility and efficacy of conventional EBRT and concurrent weekly TAX at its MTD. PATIENTS AND METHODS: Sixty-two patients with histologic diagnosis of GBM were enrolled from 8/16/96 through 3/21/97 in a multi-institutional Phase II trial of EBRT and TAX 225 mg/m(2)/3 h (1-3 h before EBRT), administered the first treatment day of each RT week. Total EBRT dose was 60 Gy (200 cGy/fraction), 5 days per week. A smaller treatment field, to include gross disease plus a margin only, was used after 46 Gy. RESULTS: Sixty-one patients (98%) were evaluable. Median age was 55 years (range, 28-78). Seventy-four percent were > or = 50 years. Recursive partitioning analysis (RPA) Classes III, IV, V, VI included 10 (17%), 21 (34%), 25 (41%), and 5 (8%) patients, respectively. Gross total resection was performed in only 16%. There was no Grade 3 or 4 neutropenia or thrombocytopenia. Hypersensitivity reactions precluding further use of TAX occurred in 4 patients. There were 2 instances of late neurotoxicity (4% Grade 3 or 4). Ninety-one percent of patients received treatment per protocol. Seventy-seven percent completed prescribed treatment (6 weeks). Of 35 patients with measurable disease, CR/PR was observed in 23%, MR in 17%, and SD in 43%. Seventeen percent demonstrated progression at first follow-up. Median potential follow-up time is 20 months. Median survival is 9.7 months, with median survivals for RPA classes III, IV, V, and VI of 16.3, 10.2, 9.5, 2.5 months, respectively. Ten patients remain alive. CONCLUSION: Concurrent full-dose EBRT and weekly high-dose TAX is feasible in the majority of GBM patients. Acute toxicity is acceptable; myelosuppression and peripheral sensory neuropathy are surprisingly modest, despite considerably higher overall dose intensity, compared to that achievable in other disease sites. Median survival by RPA class without prolonged adjuvant therapy is comparable to RTOG controls treated with standard EBRT and BCNU (1 year of BCNU).

Radiotherapeutic effects on brain function: double dissociation of memory systems.

OBJECTIVE: The neurocognitive sequelae of therapeutic cranial irradiation are not well characterized in adults with primary brain tumors. To address this problem, we prospectively examined neuropsychological findings during two phases of radiation effects. BACKGROUND: Investigations of radiation effects have revealed variable outcomes that range from no radiation-associated morbidity to severe cognitive impairment, but have relied on case reports or retrospective studies of late-delayed changes in white matter or in cognition. No reliable radiographic or neurocognitive tools exist to describe the multiple phases of radiation effects. METHOD: Twenty adult patients (median age, 39 years) from a university hospital were treated with radiotherapy (RT) for low-grade primary brain tumors. Prospective longitudinal neuropsychological studies were compared at baseline (after surgery and before irradiation) and at 3, 6, and 12 months after RT to examine early-delayed effects, including verbal memory changes in 20 patients and visual memory changes in 11 patients. We also examined cognitive changes during the late-delayed phase for up to 3 years after RT and determined whether early-delayed memory deficit predicted late-delayed memory deficit in a small subset of patients. A comprehensive neuropsychological battery was used, including verbal and visual memory tests designed to compare learning, storage, and retrieval. RESULTS: Patients demonstrated normal verbal memory at baseline, decrement, and then rebound in verbal retrieval. Deficit at baseline and recovery up to 1 year after RT defined visual memory. Together, these observations constitute a double dissociation of memory functions. No changes over time were observed in other neurocognitive tests or in fatigue or mood measures. Time-dependent patterns of each long-term memory test were examined in relation to lesion site in individual patients. CONCLUSIONS: The double dissociation of memory functions after RT may provide markers for the damaging and facilitative early-delayed effects of RT. Late-delayed effects were not predicted based on early-delayed changes in a small sample.

Phase I trial to determine the safety, pharmacodynamics, and pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the safety, pharmacokinetics, and pharmacodynamic effect of 2-[4-(3, 5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylproprionic++ + acid (RSR13) 100 mg/kg/d with radiation therapy (RT) for glioblastoma multiforme (GBM). RSR13, a synthetic allosteric modifier of hemoglobin (HgB), is a novel radioenhancing agent that noncovalently binds to HgB, thereby reducing oxygen binding affinity and increasing tissue oxygen release to hypoxic tissues. PATIENTS AND METHODS: In this multi-institutional, dose frequency-seeking trial, 19 adult patients with newly diagnosed GBM received RSR13 100 mg/kg every other day or daily along with cranial RT (60 Gy/30 fractions). RSR13 was given over 1 hour by central venous access with 4 L/min of O(2 )by nasal cannula, followed by RT within 30 minutes. Pharmacokinetic (PK) and pharmacodynamic (PD) determinations were performed. The PD end point was shift in P50, the oxygen half-saturation pressure of HgB. RESULTS: Grade 3 dose-limiting toxicity occurred in none of the patients with every-other-day dosing and in two of the 10 patients with daily dosing. Grade 2 or greater toxicity occurred in three out of nine and six out of 10, respectively. PK and PD data demonstrate that a substantial PD effect was reliably achieved, that PD effect was related to RBC RSR13 concentration, and that there was no significant drug accumulation even with daily dosing. The mean shift in P50 was 9.24 +/- 2.6 mmHg (a 34% increase from baseline), which indicates a substantial increase in tendency toward oxygen unloading. CONCLUSION: Daily RSR13 (100 mg/kg) during cranial RT is well tolerated and achieves the desired PD end point. A phase II trial of daily RSR13 for newly diagnosed malignant glioma is currently accruing patients within the New Approaches to Brain Tumor Therapy Central Nervous System Consortium to determine survival outcome.

A dosimetric comparison of conventional vs conformal external beam irradiation of a stented coronary artery utilizing a new fluoroscopic imaging detector system.

UNLABELLED: Purpose. To determine whether conformal external photon beam irradiation may prevent or reduce the rate of restenosis of a stented coronary artery following percutaneous transluminal coronary angioplasty (PTCA). Optimal conformal external beam irradiation with limited cardiac dose requires adequate visualization of the stented vascular segment. With existing image intensifiers, identification of a coronary stent is poorly localized. We propose using an amorphous silicon panel detector to observe the movement of the stent during the cardiac cycle. BACKGROUND: Long-term radiation-induced coronary complications can be minimized by: (a) reducing the radiation field sizes, (b) fractionating the total dose over several days, and (c) applying multiple treatment beams. Localization of the movement of the stent during the cardiac cycle may allow for the design of radiation fields that conform to the stented vessel segment. This scheme may permit gating the radiation beam on or off relative to movement of the stent within or outside the radiation fields, respectively. METHODS: Using a new solid-state amorphous silicon planar detector, with a dynamic range of 12 bits, fluoroscopic images of a Palmaz-Schatz coronary stent were obtained. The stent was centered in a polystyrene phantom 20 cm thick and imaged using a 90-kVp, 3.5-ma, source-detector and source stent distances of 114 and 100 cm, respectively. With the solid-state silicon detector, the stent was identified in a single video frame (1/30 s). This fast image acquisition should allow for mapping the motion of the stent during the cardiac cycle. The stent movement during the cardiac cycle may then be correlated with the QRS complex in the electrocardiogram. CONCLUSIONS: The localization of a coronary stent during the cardiac cycle under fluoroscopy permits delivery of small conformal external radiation fields to treat stented coronary arteries, while minimizing radiation dose to surrounding normal cardiac tissue and vasculature. The best selection of treatment beam angles will be provided by high resolution fluoroscopic images of the stented region obtained from different beam directions. The three-dimensional movement of the stent, indexed in time with the QRS complex, will provide an important measure for gating radiation beams for conformal treatment delivery.

BEACOPP: a new regimen for advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group.

The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.

Quality of life assessment in Hodgkin's disease: a new comprehensive approach. First experiences from the EORTC/GELA and GHSG trials. EORTC Lymphoma Cooperative Group. Groupe D'Etude des Lymphomes de L'Adulte and German Hodgkin Study Group.

Previous reports from available trials have dealt with negative long-term sequelae in Hodgkin's disease (HD) survivors. There is, however, a lack of longitudinal data showing the correlation between outcome and various treatment-related variables and the process of re-adaptation into normal life after the end of treatment. In order to investigate the quality of life (QoL) of patients with HD in different dimensions during active treatment and follow-up and to identify longitudinal patterns of QoL dimensions during re-adaptation to normal life within the EORTC Lymphoma Cooperative Group and Groupe D'Etude des Lymphomes de L'Adulte (EORTC/GELA) and the German Hodgkin Study Group (GHSG), QoL assessment strategies were put into use over the last three to five years. Furthermore, the efforts aimed at obtaining cross-cultural comparisons between the participating countries and study groups (EORTC/GELA and GHSG). Within the randomised EORTC/GELA Trial 'H8' for clinical stage I-II HD which started in September 1993, patients receive a QoL questionnaire for completion at each follow-up visit during the first 10 years after the end of active therapy. The corresponding 'HD8' study of the GHSG employs the assessment of QoL during and after active treatment periods. Within both studies, the EORTC QLQ C30 is used for QoL assessment incorporated in the QLQ-S (quality of life questionnaire for survivors), which additionally addresses the aspects of fatigue/malaise, sexuality, specific side effects, and retrospective evaluation of treatment. In total the QLQ-S includes 45 questions on 14 functional, symptom, and fatigue scales, 15 additional single items, and 3 open questions. In addition to the longitudinal QoL assessment, the GHSG carried out cross-sectional QoL trials with all cured surviving patients from the past HD1-6 studies and a matched normal control sample employing the QLQ-S and the life situation questionnaire (LSQ), an instrument covering objective data from 45 domains of life. To date, within the trials H8 and HD8 over 3000 QoL questionnaires from more than 800 patients from ten countries are available for analysis. Replication of the psychometric properties of the scales revealed satisfactory results using factor analyses and reliability testing across languages for the QLQ-S. A feasibility analysis showed generally a good acceptance of the questionnaire by the patients and physicians. QoL assessment within international multicentre trials in HD proved feasible within the two differently organised study groups of EORTC/GELA and GHSG. The use of subjective QoL data (QLQ-S) together with objective data (LSQ) in a combined cross-sectional and longitudinal trial system will give the most comprehensive insight into the problems of the re-integration process into normal life after cure. This information will provide the basis for the development of remedies/help measures and possible modifications of treatment strategies. The current approach will be further developed in close collaboration between both trial groups, and next steps will include translation of the LSQ into other languages and adaptation to various cultural circumstances.

Palliation of AIDS-related primary lymphoma of the brain: observations from a multi-institutional database.

PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. METHODS: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha-beta value of 10. RESULTS: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS > or = 70 vs. KPS < or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management program that includes cranial irradiation. Young patients with excellent performance status are most likely to respond to treatment. The delivery of higher biologically effective doses of irradiation also may increase the probability of achieving a palliative response.

Development of prostate cancer after pituitary dysfunction: a report of 8 patients.

OBJECTIVES: Eight patients with a history of pituitary dysfunction were seen in the Department of Radiation Oncology at the Hospital of the University of Pennsylvania for evaluation of their prostate carcinoma. Because prostate cancer is a hormonally responsive cancer, hormonal abnormalities from pituitary dysfunction may have played a role in its development. In addition, many patients with pituitary dysfunction receive exogenous hormonal replacement. The histories of these 8 patients were reviewed to look for any common underlying factor in the development of their prostate cancer. METHODS: The radiation oncology charts, hospital charts, and pathology reports were reviewed. The cause and treatment of the pituitary disorder were reviewed. Hormonal dysfunction, hormonal replacement, and treatment duration were recorded. The interval to the development of prostate cancer, stage at diagnosis, prostate-specific antigen level, Gleason score, treatment, and treatment outcome were also investigated. RESULTS: We found a variety of pituitary disorders and treatments. However, all patients received testosterone replacement therapy prior to the development of their prostate cancer (median of 30 months). The time to the development of the cancer ranged from 26 to 250 months (median 98). Patients had Stage T2 or T3 tumors at diagnosis. Patients were treated either with radical prostatectomy or radiation therapy. Six of the 8 patients were alive and doing well at their last follow-up examination. CONCLUSIONS: Prostate cancer has been shown to be androgen responsive. All the patients in this series were placed on physiologic testosterone replacement for pituitary dysfunction. The role of testosterone in the initiation of prostate cancer has been debated. However, at the present time, it seems appropriate to establish close monitoring for prostate cancer in patients receiving androgen therapy for pituitary dysfunction.

Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: a multivariate analysis of a multi-institutional experience.

PURPOSE: There is limited information about the outcome of AIDS patients with primary central nervous system lymphoma treated with definitive irradiation. The purpose of this study was to determine factors associated with increased survival in such patients. METHODS: An analysis was performed of 163 patients with AIDS who were evaluated at nine urban hospitals. These patients were treated for primary central nervous system lymphoma after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (> 90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective dose according to the formula Gy10 = Total Dose x (1 + fractional dose/alpha-beta), using an alpha-beta of 10. RESULTS: Longer median survival times were associated with high Karnofsky performance status (KPS > or = 70 vs < or = 60: 181 vs 77 days), young age (< 35 vs > 35: 162 vs 61 days), and high total definitive irradiation doses (> 39 Gy10 vs < 39 Gy10: 162 vs 40 days). Tissue diagnosis, gender, race, number of lesions (solitary vs multiple), and the presence of other cancers did not influence outcome. In multivariate analysis, young age, high Karnofsky performance status, and the delivery of higher biologically effective doses of irradiation retained independent significance relative to the endpoint of survival. CONCLUSIONS: Even at urban tertiary medical centers, few AIDS patients with intracranial lesions undergo biopsies to establish a precise tissue diagnosis. Survival following definitive irradiation is strongly related to two pretreatment factors (young age, high performance status) and one treatment factor (total biologically effective dose of cranial radiotherapy). These variables should be considered in selecting patients for definitive irradiation and in designing future studies.

Report of the workshop on clinical trials. GHSG. German Hodgkin Study Group.

During the Third International Symposium, a leading panel of experts in the field discussed the current most prominent problems in the treatment of Hodgkin's disease to give recommendations for future clinical trials. Within the workshop on clinical trials the following issues were addressed: 1. Which diagnostic procedures are state of the art and to what extent are they able to contribute to a so-called response-adapted treatment (RAT)? 2. What is the optimal dose and volume of radiotherapy in different stages? 3. What is the value of chemotherapy in early stages and is it restricted to a certain subgroup? 3. Have we achieved as much as we can in intermediate stages in terms of response with now focusing future efforts on reducing toxicity and improving quality of live? 5. Is high-dose chemotherapy (HDCT) the answer to the challenge of improving treatment results in advanced stages? 6. What is the optimal schedule and dose of HDCT and consecutive autologous bone marrow transplantation (ABMT)?

Biphasic patterns of memory deficits following moderate-dose partial-brain irradiation: neuropsychologic outcome and proposed mechanisms.

PURPOSE: To identify the longitudinal neurobehavioral characteristics of the early-delayed and late-delayed effects of partial-brain radiotherapy for patients with supratentorial brain tumors with favorable histology. This study improves on previous attempts to identify radiation effects, because of the inclusion of baseline measures and the use of subjects as their own controls. PATIENTS AND METHODS: Ten neuropsychologic domains were measured in 12 patients at baseline (post-surgery and immediately before initiation of radiotherapy), and followed trimonthly for 1 year. Four to six patients were examined at 2 and 3 years postbaseline. RESULTS: Patients were impaired at baseline compared with controls only in visual memory and sentence recall, but demonstrated significant improvement in visual memory by 2 years postbaseline. Speed of processing information also showed a slope of improvement over 2 years. Retrieval from verbal long-term memory was impaired at 1.5 months postcompletion of radiotherapy, but recovered to baseline levels by 1 year. At 2 years postbaseline, long-term memory retrieval demonstrated a decline, but remained unchanged at 3 years. CONCLUSION: Long-term memory appears to be sensitive to the effects of radiotherapy. We confirmed our previous findings of a decrement with rebound during the early-delayed period, and propose that these findings are consistent with demyelination/remyelination. Decrement was observed again at 2 years postbaseline, which suggests that memory retrieval may be the earliest marker of late-delayed effects. These neurocognitive patterns are consistent with leukoencephalopathy. Confirmation of these observations will be possible if neuropsychologic testing with the same sensitivity can be incorporated into national collaborative trials.