Palliative radiotherapy tailored to life expectancy in end-stage cancer patients: reality or myth?

BACKGROUND: The purpose of the study was to investigate the adequacy of palliative radiation treatment in end-stage cancer patients. METHODS: Of 216 patients referred for palliative radiotherapy, 33 died within 30 days and constitute the population of the study. Symptoms, Karnofsky Performance Status (KPS), laboratory tests, and survival estimates were obtained. Treatment course was evaluated by medical records. Univariate analyses were performed by using the 2-sided chi-square test. With significant variables, multiple regression analysis was performed. RESULTS: Median age was 65 years, and median survival was 15 days. Prevailing primary cancer types were lung (39%) and breast (18%). Metastases were present in 94% of patients, brain (36%), bone (24%) and lung (18%). In 91%, KPS was < 0%. KPS, lactate dehydrogenase, dyspnea, leucocytosis, and brain metastases conveyed a poor prognosis. From 85 survival estimates, only 16% were correct, but 21% expected more than 6 months. Radiotherapy was delivered to 91% of patients. In 90% of radiation treatments, regimens of at least 30 Gy with fractions of 2-3 Gy were applied. Half of the patients spent greater than 60% of their remaining lifespan on therapy. In only 58% of patients was radiotherapy completed. Progressive complaints were noted in 52% and palliation in 26%. CONCLUSIONS: Radiotherapy was not appropriately customized to these patients considering the median treatment time, which resembles the median survival time. About half of the patients did not benefit despite spending most of their remaining lives on therapy. Prolonged irradiation schedules probably reflect overly optimistic prognoses and unrealistic concerns about late radiation damage. Single-fraction radiotherapy was too seldom used.

PSA after incidental irradiation of the nonmalignant prostate: long-term changes.

BACKGROUND: Incidental irradiation of the prostate may affect serum prostate-specific antigen (PSA). However, scarce data exist on PSA changes after irradiation of noncancerous prostatic tissue. This is an update of a study on PSA after pelvic irradiation. MATERIAL AND METHODS: From 1997 to 2007, blood samples of 33 men were examined who had undergone pelvic irradiation for rectal or anal cancer. The planning target volume included the prostate in all cases. No patient had clinical evidence of prostatic disease. Radiotherapy was applied in fractions of 1.8-2 Gy up to 40-50 Gy (n = 3), 50-60 Gy (n = 21), and 60-65 Gy (n = 2). Seven patients received 5 x 5 Gy. Serum PSA was measured before, during, and after radiotherapy periodically. Median log (PSA) changes were calculated according to elapsed time from starting radiotherapy. The significance was tested with chi(2)-test. RESULTS: 18 patients died during follow-up. For 15 patients, long-term PSA data with a median follow-up of 9 years (2,546-3,528 days) are available. PSA levels rose during the first weeks of irradiation peaking at 2-4 weeks with a significant 2.7-fold increase (p < 0.01). 1 year after radiation therapy, PSA declined below (90%) the preirradiation level, but this difference was not significant (p = 0.36). On further follow-up PSA did not change up to 8.9 years after radiotherapy (p = 0.36). CONCLUSION: Irradiation of the prostate causes transient increase of serum PSA. By 1 year, PSA has returned near the preirradiation value and stays there for at least 9 years. A major interference with prostate cancer screening or surveillance after radiotherapy is therefore unlikely.

C-reactive protein levels and clinical symptoms following gadolinium administration in hemodialysis patients.

BACKGROUND: Until recently, gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) has increasingly replaced iodinated contrast agent examinations in dialysis patients, although only limited data existed about the clinical safety of Gd contrast agents in these patients. Specific clinical adverse events (AEs), including nephrogenic systemic fibrosis, were linked to Gd exposure in dialysis patients. An inflammatory reaction or transmetallation may be involved. STUDY DESIGN: Secondary analysis of a 5-day observational study in a parent cardiovascular study with repetitive cardiac MRI (32 patients) and patients undergoing Gd-enhanced MRI for clinical indications (6 patients). Clinical information and samples were obtained according to parent protocol. SETTING & PARTICIPANTS: Dialysis patients at a university-based dialysis unit. PREDICTOR: Gd-chelate complex. 37 of 38 patients underwent 64 MRI studies with Gd-diethylenetriamine penta-acetic acid (Gd-DTPA). 25 of these patients underwent additional MRI studies with gadobutrol (n = 10), 0.9% saline (n = 7), or both (n = 8), and 1 patient received gadobutrol only. OUTCOMES: Clinical adverse events; C-reactive protein (CRP) levels on days 1, 3, and 5 after MRI; Gd levels in blood and urine after MRI. RESULTS: CRP levels increased 10-fold on day 3 after MRI in 87% of MRI studies with Gd-DTPA (+59.3 +/- 57.9 mg/L [P < 0.001] versus -0.9 +/- 3.7 mg/L with gadobutrol versus -0.9 +/- 8.5 mg/L with 0.9% saline). 77 mild to moderate and 3 serious AEs were observed in 24 patients. CRP levels and adverse events did not correlate with Gd blood concentrations. CRP level increase or AEs were not observed after MRI with gadobutrol or 0.9% saline. LIMITATIONS: Observational study without randomization, risk of bias because of multiple MRI studies in a limited patient cohort. CONCLUSION: Gd-DTPA, but not gadobutrol, induces an acute-phase reaction and clinical AEs in dialysis patients. Additional investigations have to analyze the underlying pathomechanism.

[RheumaCheck: development and evaluation of a German language screening instrument for rheumatic diseases]. / RheumaCheck: Entwicklung und Evaluation eines deutschsprachigen Rheuma-Screening Instruments.

OBJECTIVE: Early diagnosis of inflammatory rheumatic diseases is important for patients' prognosis and outcome. The mean time delay of 1 to 5 years in Germany between the initial symptoms and the first rheumatologist contact should be reduced. Efficiency of patient questionnaires for the identification of inflammatory rheumatic diseases has been demonstrated in other countries. The aim of our study was to develop a patient questionnaire in German identifying inflammatory rheumatic diseases with a high sensitivity and specificity as well as a high positive predictive value. PATIENTS AND METHODS: The RheumaCheck questionnaire was developed by adoption of the FDA-approved Connective Tissue Disease Screening Questionnaire. 1448 patients (195 controls, 437 patients suspicious for and 816 patients with known inflammatory rheumatic diseases) recruited by rheumatologists and general practitioners answered the questionnaire that additionally assessed comorbidities and sociodemographic data. A predictive algorithm was calculated. RESULTS: Mean age of the complete group (73.1% female) was 52.5 +/- 15.1 years. 53.1% had no comorbidity. Application of the algorithm yields a high sensitivity (77.6%) and specificity (79.9%). The area under the ROC curve was 0.85 (p < 0.0001). CONCLUSION: Being aware of a possible high rate of false true results RheumaCheck is a simple, efficient instrument easily filled out by patients. It can identify the group of patients that needs further investigation, care and assessment by a rheumatologist leading to earlier diagnosis and therapy. A web version of RheumaCheck is provided on www.rheuma-check.de .

Survival prediction in terminally ill cancer patients by clinical estimates, laboratory tests, and self-rated anxiety and depression.

PURPOSE: To study how survival of palliative cancer patients relates to subjective prediction of survival, objective prognostic factors (PFs), and individual psychological coping. PATIENTS AND METHODS: Survival was estimated according to three categories (< 1 month, 1 to 6 months, and > 6 months) by two physicians (A and B) and the institutional tumor board (C) for 216 patients recently referred for palliative radiotherapy. After 6 months, the accuracy of these estimates was assessed. The prognostic relevance of clinical symptoms, performance status, laboratory tests, and self-reported emotional distress (Hospital Anxiety and Depression Scale) was investigated. RESULTS: In 61%, 55%, and 63% of the patients, prognoses were correctly estimated by A, B, and C, respectively. kappa statistic showed fair agreement of the estimates, which proved to be overly optimistic. Accuracy of the three estimates did not improve with increasing professional experience. In particular, the survival of 96%, 71%, and 87% of patients who died in less than 1 month was overestimated by A, B, and C, respectively. On univariate analysis, 11 of 27 parameters significantly affected survival, namely performance status, primary cancer, fatigue, dyspnea, use of strong analgesics, brain metastases, leukocytosis, lactate dehydrogenase (LDH), depression, and anxiety. On multivariate analysis, colorectal and breast cancer had a favorable prognosis, whereas brain metastases, Karnofsky performance status less than 50%, strong analgesics, dyspnea, LDH, and leukocytosis were associated with a poor prognosis. CONCLUSION: This study revealed that physicians' survival estimates were unreliable, especially in the case of patients near death. Self-reported emotional distress and objective PFs may improve the accuracy of survival estimates.

Survivin and its prognostic significance in pediatric acute B-cell precursor lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Impaired apoptosis, mediated by members of the inhibitor of apoptosis proteins (IAP) family such as survivin, is thought to contribute to leukemic cell survival. In contrast to low expression of survivin in normal differentiated adult tissues, very high levels of survivin have been described in a number of different tumors. Overexpression of survivin was found to correlate with poor prognosis in a variety of cancers including hematologic malignancies. To date, however, there is no information available on the prognostic role of survivin in pediatric precursor B-cell acute lymphocytic leukemia (BCP-ALL), the most frequent malignancy in childhood. DESIGN AND METHODS: In a retrospective study including 66 pediatric patients we analyzed the impact of survivin protein levels on outcome in BCP-ALL. RESULTS: Survivin overexpression, with an up to ten-fold increase of the normal level, was detected in 65% of the leukemic samples in contrast to negligible expression in non-malignant hematopoietic cells. Despite considerable variety of expression levels in ALL cells, there was no association of survivin levels with established risk factors. However, patients suffering relapse of disease or death had significantly higher survivin expression than those with a favorable outcome. Overexpression of survivin is a significant prognostic marker for 3 year relapse free, event-free and overall survival, again independent of the established prognostic factors in ALL, such as age and leukocyte count at diagnosis as assessed in multivariate analysis. INTERPRETATION AND CONCLUSIONS: Overexpression of survivin in BCP-ALL identifies patients with a high risk of early relapse. Upon confirmation in a prospective analysis, survivin expression may, in the future, serve to further refine treatment stratification with intensification of therapy in those patients prone to relapse.

Does interscalene catheter placement with stimulating catheters improve postoperative pain or functional outcome after shoulder surgery? A prospective, randomized and double-blinded trial.

BACKGROUND: In this prospective, randomized, double-blind trial we investigated the use of stimulating catheters in patients during and after shoulder surgery; functional improvement being the primary outcome measurement. METHODS: After eliciting an adequate muscular twitch at < or =0.5 mA nerve stimulation output, the perineural catheter was advanced either blindly (conventional catheter = CC group, n = 20) or guided by stimulation via the catheter (stimulating catheter = SC group, n = 20). A bolus of 40 mL prilocaine 1% and 10 mL ropivacaine 0.75% was injected, followed by a patient-controlled infusion of ropivacaine 0.2% (8 mL/h infusion rate, bolus 2 mL, lockout time 20 min). RESULTS: Onset of motor block was faster in the SC group, whereas sensory block did not differ between groups. Median pain scores on two postoperative days were equal. Improvement of the objective shoulder function score (Constant Murley Score) 6 wk postoperatively was enhanced to a clinically relevant extent in the SC group compared to the CC group (P < 0.01). CONCLUSIONS: We conclude that the use of a stimulating catheter results in a faster onset of motor block, unaltered postoperative pain, and a significantly improved functional outcome 6 wk after shoulder surgery.

XIAP expression is an independent prognostic marker in clear-cell renal carcinomas.

Deregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. XIAP is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. To explore the relevance of XIAP for progression and prognosis in renal cell carcinomas (RCCs) of the clear-cell type, we analyzed XIAP protein expression in formalin-fixed tissue from 145 clear-cell RCCs by immunohistochemistry. XIAP protein expression was found in 95% of clear-cell RCCs. A significant increase of XIAP expression became evident from well (G1) to poorly (G3) differentiated clear-cell RCCs (P < 0.0001) and from low (pT1) to advanced (pT3) tumor stages (P = 0.0016). Log-rank test showed a significant inverse correlation (P = 0.0174) between XIAP expression and tumor aggressiveness as indicated by patients' survival. Most important, multivariate Cox regression analysis revealed that XIAP expression is an independent prognostic parameter (P = 0.018) in clear-cell RCCs. Our results suggest an important role for XIAP-mediated inhibition of apoptosis during progression of clear-cell RCCs and introduce XIAP expression as a new independent prognostic marker in this tumor type.

Coverage of anterior fossa in whole-brain irradiation.

PURPOSE: Whole-brain irradiation is indispensable in the treatment of several brain tumors and requires coverage of the entire subarachnoid space. Retrospective studies have revealed frequent recurrences in the frontobasal fossa above the cribriform plate (CP). We sought to determine how accurately the latter could actually be identified on lateral radiographs such as those used for radiotherapy planning. METHODS AND MATERIALS: The CP was localized by five radiation oncologists and five radiologists on lateral radiographs of 30 human skulls from an anatomic collection. Reference radiographs were acquired under identical conditions except for lead markers pointing to the CP and the ethmoid cells. The targeting accuracy was analyzed. RESULTS: In 39% (n = 116), the location of the CP was correctly estimated within 2 mm. Mislocations of 2-5, 5-10, and >10 mm were noted in 34% (n = 102), 20% (n = 61), and 7% (n = 21), respectively. Neither specialty nor experience (years of training) exerted a significant influence on targeting accuracy. If the roofs of the ethmoid cells formed prominent bony edges, they were mistaken for the CP in 37%. CONCLUSION: Lateral radiographs provide insufficient information to locate the CP accurately in whole brain irradiation. Additionally, localization was significantly impaired by prominent ethmoid cells.

Prognostic implications of CD95 receptor expression in clear cell renal carcinomas.

The CD95 (Apo-1/Fas) receptor-ligand system is a key regulator of apoptosis. Down-regulation of CD95 receptor and up-regulation of CD95 ligand has been reported in a variety of human tumors and is thought to confer a selective survival advantage. To explore the relevance of the CD95 system for tumor progression and prognosis in clear cell renal cell carcinomas (RCCs), we analyzed CD95 receptor and ligand expression in formalin-fixed tissue from 149 clear cell RCCs by immunohistochemistry. CD95 ligand expression could not be detected in nonneoplastic tubule epithelia and in clear cell RCCs. In contrast, CD95 receptor expression was found in the great majority of clear cell RCCs, and no down-regulation of CD95 receptor protein was evident when compared with nonneoplastic tubule epithelia. Although a significant increase (P = 0.004) of CD95 receptor expression was evident from well-differentiated (G1) to poorly differentiated (G3) RCCs, CD95 receptor expression was not correlated with tumor stage or survival of RCC patients. In conclusion, clear cell RCCs differ from other types of human cancer by their failure to down-regulate CD95 receptor expression or up-regulate CD95 ligand expression during tumor progression. These ex vivo observations suggest that down-regulation of CD95 receptor expression may not provide an additional selective growth advantage to RCC cells and thus further confirm our previous in vitro observations on a functional impairment of CD95-mediated apoptosis in RCC.