Patient Selection Factors Research Articles

Image-guided resection of high-grade glioma: patient selection factors and outcome

In patients with glioma, image-guided surgery helps to define the radiographic limits of the tumor to maximize safety and the extent of resection while minimizing damage to eloquent brain tissue. The authors hypothesize that image-guided resection (IGR) techniques are associated with improved outcomes in patients with malignant glioma. Data recorded in 486 patients enrolled in the Glioma Outcomes Project were analyzed in this study. Demographic data and outcomes in patients who underwent IGR were compared with those in patients who underwent resection without IGR. Univariate analysis performed with chi-square testing was used to compare patient presentation, tumor characteristics, and death rates. Multivariate logistic regression was used to predict various outcome parameters. Patients who underwent IGR were younger and had smaller, lower-grade tumors than those in whom IGR was not performed. They were more likely to present with seizure and normal consciousness. Unexpectedly, gross-total resection was performed in significantly fewer patients with IGR than in individuals without IGR. Patients with IGR were more likely to be discharged home with the ability to live independently, and they had a shorter duration of hospital stay than patients without IGR. Survival was significantly longer in patients who underwent IGR, but multivariate analysis showed that glioblastoma multiforme (GBM) and age accounted for these observations. Selection bias occurs regarding patients who receive IGR; these biases include younger age, presentation with seizure and normal level of consciousness, tumor diameter less than 4 cm, and non-GBM on histopathological studies. Outcome appears to be improved in patients who undergo IGRs of high-grade gliomas. It is unclear if these improved outcomes are due to the selection of a more favorable patient population or to the IGR techniques themselves. It is likely that the full potential of image guidance in glioma surgery will not be realized until it is applied to a wider range of patients.

Neoadjuvant Treatment of Unresectable Liver Metastases from Colorectal Cancer

There has been increasing interest in the use of neoadjuvant treatment for downstaging and downsizing disease in patients with initially unresectable liver metastases from colorectal cancer with a view to potentially curative surgery. This has been increasingly feasible with the more active treatment combinations presently available based on oxaliplatin or irinotecan. This article reviews the evidence supporting the use of this treatment strategy and discusses the implications of advances in treatment in other metastatic disease settings for these patients and the issues of patient selection and prognostic factors.

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal

Epidermal growth factor receptor inhibitors in the treatment of non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in both men and women. Despite the introduction of the newer cytotoxic agents in NSCLC treatment during the last decade the survival rates of patients have reached a plateau. New strategies are clearly needed to improve treatment outcomes. Epidermal growth factor receptor (EGFR) has a key role in cancer development and progression and has been recognised as a target of increasing importance in NSCLC. Gefitinib, erlotinib and cetuximab are EGFR-targeting agents that are being extensively evaluated in NSCLC. EGFR inhibitors demonstrate significant clinical activity in ~ 10 – 20% of pretreated NSCLC patients. Somatic mutations in the kinase domain of the receptor have been shown to be associated with enhanced sensitivity to EGFR inhibitors. However, four large Phase III randomised, placebo-controlled trials of gefitinib and erlotinib in combination with standard platinum-based first-line chemotherapy failed to show any survival benefit in patients receiving the study drugs. Possible reasons include patient selection, drug scheduling, trial design or other factors. Active research is ongoing to improve the efficacy of EGFR inhibitors as monotherapy or in combination with other treatment modalities.

Immunohistochemical Analysis of Platelet-derived Growth Factor Receptor-α, -β, c-kit, c-abl, and Arg Proteins in Glioblastoma: Possible Implications for Patient Selection for Imatinib Mesylate Therapy

Inhibition of tyrosine kinase (TK) receptors by synthetic small molecules has become a promising new therapy option in oncology. The TK inhibitor imatinib mesylate selectively targets PDGFR-alpha, -beta, c-kit, c-abl and arg and has proven successful in the treatment of chronic myeloid leukaemia. In recurrent glioblastoma, phase II therapy trials using imatinib mesylate have been initiated. As only a fraction of patients seems to benefit from imatinib mesylate therapy and due to potential side effects and high costs of imatinib mesylate therapy, selection of the right patients is important. The goal of our study was to assess systematically immunohistochemical expression of the major TKs targeted by imatinib mesylate in glioblastoma, as expression of these factors could be used to select patients for imatinib mesylate therapy. In a cohort of 101 glioblastoma patients, anti-PDGFR-alpha, -beta, c-kit, c-abl and arg protein immunohistochemistry was performed. Expression of these proteins was assessed semi-quantitatively and correlated with patient survival.PDGFR-alpha and arg expression in tumor cells was widespread in 1/101 cases, respectively. Focal PDGFR-alpha, -beta, c-kit, c-abl and arg immunolabeling was detected in 25/101, 19/101, 4/101, 7/101 and 31/101 cases, respectively. Statistical analysis did not reveal any correlation between expression of the TKs and patient survival. We show here for the first time in a large series of glioblastomas that PDGFR-alpha, -beta, c-kit, c-abl and arg expression is immunohistochemically detectable in a fraction of cases. The value of anti-tyrosine kinase immunolabeling as predictive factor for patient selection remains to be clarified by comparative analysis of tumor tissue of therapy-responders versus non-responders.

Spontaneous Resolution of Acquired Tonsillar Herniation Caused by Isolated Cerebellar Tonsil Inflammation: Case Report

Chiari I malformation is a well-known disease involving caudal descent of the cerebellar tonsils and is generally considered to be a congenital condition. Acquired Chiari I malformations as a result of various causes are well described. An unusual case is reported in which regression of an acquired Chiari I malformation caused by isolated cerebellar tonsil inflammation in a patient with infectious mononucleosis was observed after conservative treatment. This supports the view that the cause of tonsillar herniation should be considered as an important factor in patient selection for surgical decompression. A 6-year-old boy presented with a 1-week history of progressive occipital headache, neck pain, and dysequilibrium. A neurological examination revealed hyperreflexia in all extremities; he also had a fever, pharyngitis, and cervical adenopathy. A magnetic resonance imaging study demonstrated isolated right cerebellar tonsil enhancement and herniation into the foramen magnum. Further laboratory findings disclosed Epstein-Barr virus infection. The patient underwent conservative treatment for systemic illness, and he was asymptomatic after 3 weeks. A follow-up magnetic resonance imaging study obtained 2 months after discharge demonstrated resolution of the tonsillar herniation. Because the patient presented with infectious mononucleosis and cerebellar tonsillar herniation, direct treatment of decompression was considered unnecessary. Thus, caution in patient selection for surgical treatment is suggested in such unique cases.

Association of patient autonomy with increased transplantation and survival among new dialysis patients in the United States

It is unclear whether patients with chronic kidney disease who are more autonomous in medical decision making have better outcomes than those who are not. We examined the contribution of patient autonomy to treatment selection (peritoneal dialysis versus hemodialysis) and subsequent association with transplantation and survival. Data were obtained from the Dialysis Morbidity and Mortality Study Wave 2, a national random sample of 4,025 new dialysis patients enrolled during 1996 and 1997 and followed up until October 31, 2001. Responders were asked to quantify their contribution to treatment selection and were grouped based on perceived degree of participation as patient led, team led, or patient and team led. Groups were compared and subsequent outcomes were evaluated by using Cox regression. Six hundred thirty-six patients (26.3%) reported a patient-led decision, 860 patients (35.6%) reported a team-led decision, and 922 patients (38.1%) reported a patient-and-team-led decision in treatment assignment. Unadjusted death rates were significantly lower (127 versus 159 versus 207 deaths/1,000 patient-years at risk; P < 0.0001), and transplantation rates were significantly higher (103 versus 88 versus 41 transplantations/1,000 patient-years at risk; P < 0.0001) for patients reporting the greatest contribution to modality selection. With adjustment for case mix, mortality risks were lowest (relative risk [RR], 0.84; 95% confidence interval [CI], 0.71 to 0.99) and transplantation rates were highest (RR, 1.44; 95% CI, 1.07 to 1.93) for the patient-led group. Although the contribution of patient selection factors cannot be completely ignored, this analysis supports an association of patient autonomy with transplantation and survival. Greater efforts to empower patients with chronic kidney disease during the period before end-stage renal disease may improve clinical outcomes.

Skin rash and good performance status (PS) predict improved survival with gefitinib for patients with advanced non-small cell lung cancer (NSCLC)

7097 Background: Gefitinib (Iressa®) is active as a single agent for the treatment of advanced NSCLC patients who have failed prior chemotherapy. For optimal utilization of gefitinib, effective methods to identify sub-sets of patients likely to benefit from treatment are necessary. We analyzed patients treated with gefitinib on an Expanded Access Program at our institutions to detect possible predictive factors for patient selection to future studies. Methods: Patients (N=178) with advanced NSCLC were treated with gefitinib (250 mg PO QD) upon progression from chemotherapy. Patients with ECOG PS of ≤ 2, adequate bone marrow, hepatic and renal function were eligible. Results: Baseline patient characteristics were: Median age: 68 years (range 29–100); males - 56%; Adenocarcinoma –49%, squamous –21%, bronchioloalveolar-6%, other –24%. Objective partial responses were noted in 4 (2.4%) and disease stabilization in 28 (17%) patients. The median survival (MS) was 6.1 months (95% CI 4.42–7.21) and median time to progression was 3 months (95% CI 2.0–3.0). The predictive factors analyzed were gender, skin rash, diarrhea and PS. Patients who developed a skin rash (any grade) had a MS of 11 months compared to 4.5 months for patients without a rash (P < 0.0001, log rank test). Patients with PS 0/1 and 2 had a MS of 5.8 months and 2.9 months respectively (P < 0.0001). Other factors did not impact survival. Conclusions: Occurence of skin rash and baseline PS of 0/1were associated with significantly improved survival for advanced NSCLC patients who failed prior chemotherapy, upon treatment with gefitinib. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca

Skin rash and good performance status (PS) predict improved survival with gefitinib for patients with advanced non-small cell lung cancer (NSCLC)

7097 Background: Gefitinib (Iressa®) is active as a single agent for the treatment of advanced NSCLC patients who have failed prior chemotherapy. For optimal utilization of gefitinib, effective methods to identify sub-sets of patients likely to benefit from treatment are necessary. We analyzed patients treated with gefitinib on an Expanded Access Program at our institutions to detect possible predictive factors for patient selection to future studies. Methods: Patients (N=178) with advanced NSCLC were treated with gefitinib (250 mg PO QD) upon progression from chemotherapy. Patients with ECOG PS of ≤ 2, adequate bone marrow, hepatic and renal function were eligible. Results: Baseline patient characteristics were: Median age: 68 years (range 29–100); males - 56%; Adenocarcinoma –49%, squamous –21%, bronchioloalveolar-6%, other –24%. Objective partial responses were noted in 4 (2.4%) and disease stabilization in 28 (17%) patients. The median survival (MS) was 6.1 months (95% CI 4.42–7.21) and median time to progression was 3 months (95% CI 2.0–3.0). The predictive factors analyzed were gender, skin rash, diarrhea and PS. Patients who developed a skin rash (any grade) had a MS of 11 months compared to 4.5 months for patients without a rash (P < 0.0001, log rank test). Patients with PS 0/1 and 2 had a MS of 5.8 months and 2.9 months respectively (P < 0.0001). Other factors did not impact survival. Conclusions: Occurence of skin rash and baseline PS of 0/1were associated with significantly improved survival for advanced NSCLC patients who failed prior chemotherapy, upon treatment with gefitinib. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca

Use of emergency medical services in acute myocardial infarction and subsequent quality of care: Observations from the national registry of myocardial infarction 2

Use of emergency medical services in acute myocardial infarction and subsequent quality of care: Observations from the national registry of myocardial infarction 2

Prophylactic pancreatic duct stenting: a panacea?

Prophylactic pancreatic duct stenting: a panacea?

Transurethral hot water balloon thermotherapy for benign prostatic hyperplasia.

For many years the transurethral prostatectomy has been the standard therapy for benign prostatic hyperplasia (BPH). In the past 10 to 15 years, a number of competing minimally invasive technologies (MIT) have been used to treat patients with symptomatic BPH. These heat-based treatments include transurethral microwave thermotherapy, interstitial devices (eg, interstitial laser coagulation and transurethral needle ablation), high-intensity focused ultrasound, and water-induced thermotherapy (WIT). This article reviews the evidence supporting the efficacy and safety of transurethral hot water balloon thermotherapy for BPH. Appropriate patient selection factors for WIT versus other MITs are reviewed. A novel combination therapy for adenocarcinoma of the prostate also is proposed.

Treatment of advanced gastric cancer by palliative gastrectomy, cytoreductive therapy and postoperative intraperitoneal chemotherapy.

The treatment options for the 10-20 per cent of patients with gastric cancer who present with peritoneal dissemination are extremely limited and no standard approach exists. The feasibility of using intraperitoneal chemotherapy to treat gastric cancer with intra-abdominal gross residual lesions after palliative gastrectomy with maximal cytoreduction was investigated. Early postoperative intraperitoneal chemotherapy started on the day of operation with 5-fluorouracil 500 mg/m2 and cisplatin 40 mg/m2 (days 1-3) over a 4-week interval. Of the 53 patients enrolled between July 1994 and December 1998, 49 were eligible. The progression-free survival (PFS) was 7 months and the overall survival was 12 months. In multivariate analysis, performance status was the only significant defining factor for PFS (P = 0.009). The predominant toxicity was neutropenia and nausea/vomiting. The relative dose intensity of 5-fluorouracil and cisplatin was 89 and 63 per cent respectively. Performance status emerged as a major determining factor for prognosis and patient selection for early postoperative intraperitoneal chemotherapy in patients with advanced gastric cancer after maximally cytoreductive surgery.

Rationale and feasibility of combined radiotherapy and Anti-CD20 immunotherapy in CD20+ B cell NHL

Purpose/Objective: “Zevalin” (Ibritumomab Tiuxetan incorporating the beta emitter Y-90) recently became the first radiolabeled antibody compound to receive FDA approval for clinical use against relapsed and refractory low grade CD20+ B cell lymphoma. Dose limiting toxicity for “Zevalin” involves hemopoietic suppression and thrombocytopenia, making depressed marrow reserves an important factor in appropriate patient selection. Mechanisms by which antibody targeting and CD20 surface antigen expression could be further amplified would be of great interest and would potentially allow groups of currently ineligible patients to receive this treatment at lower but still effective doses. Our laboratory group recently reported that relatively low doses of ionizing radiation appear to upregulate CD20 surface antigen expression in a variety of human B cell lines. This observation suggests a possible role for adjunctive low dose radiation targeted to lymphoma deposits using either external beam radiotherapy or low dose RIT delivered in a time-frame calculated to promote targeting efficiency of subsequent CD20+ NHL immunotherapy. In order to establish baseline data on clinical safety and effectiveness of combinations of ionizing radiation and RIT, we have utilized database information on patients registered on “Zevalin” clinical trials who had previously received external beam radiotherapy.

NovaSure Impedance-Controlled System for Endometrial Ablation

Study Objective To assess the efficacy and safety of the NovaSure endometrial ablation system in women with severe dysfunctional uterine bleeding (DUB). Study Design Prospective, single-arm, controlled, observational pilot study (Canadian Task Force classification II-1). Setting Free-standing center for gynecologic endoscopy. Patients One hundred seven premenopausal women whose menorrhagia was unresponsive to medical therapy, who had completed childbearing, and who had undistorted uterine cavities. Intervention Endometrial ablation with the NovaSure system. Measurements and Main Results Diaries were used to qualify patients for the study, as well as for posttreatment evaluation of menstrual blood loss and bleeding pattern (amenorrhea, spotting, hypomenorrhea, eumenorrhea, menorrhagia). No drug or mechanical endometrial pretreatment was administered. Position of the uterus was not a factor in patient selection. No intraoperative or postoperative complications occurred. Treatment time averaged 94 seconds. Of 107 women, 106 completed 6 months of follow-up and 105 had 12 months. Amenorrhea was 46% and 58%, respectively. Conclusion The NovaSure System is safe and is effective in treating women with DUB. Endometrial pretreatment is not necessary, and presence of blood in the uterine cavity during treatment is not a limiting factor.

A Retrospective, Long-term, Third-Party Follow-up of Patients Considered for Spinal Cord Stimulation

The objective of this study was to follow up patients considered for spinal cord stimulation and assess outcomes and patient selection factors associated with outcome. A retrospective study of patients considered for spinal cord stimulation was performed. This included three groups: A) those who did not have a temporary trial of stimulation, B) those who did not go on to have long-term stimulation after a trial, and C) those who did go on to have long-term stimulation after a trial. Patient notes were obtained, a structured telephone interview conducted, and patients returned a questionnaire. VAS scores, percentage pain reduction reported, quality of life reports, Oswestry Disability Index and Hospital Anxiety and Depression Indices were recorded. Fifty-two percent of patients who had long-term stimulation reported 50% or greater pain reduction. In the subset of these patients with the diagnosis of failed back surgical syndrome, 51% reported 50% or greater pain reduction. Significant improvements in VAS, Oswestry Disability Index, and depression were reported pre and post long-term stimulation. There were significant differences in the quality-of-life reports between the patients who received long-term stimulation (who showed a positive outcome) and those who did not (who showed a negative outcome); 80% of patients receiving long-term stimulation reported an improvement in their quality of life. Follow-up of a cohort of patients receiving long-term stimulation demonstrated some reduction of treatment efficacy. Use of a psychological interview aided patient selection, but no other factors showed a correlation with reported pain reduction. No serious adverse effects were demonstrated. A revision rate of 23.5% occured in long-term stimulated patients. We conclude that spinal cord stimulation is an efficacious therapy which is not associated with serious side effects. There is some reduction in therapeutic efficacy over time. Patients deteriorate without treatment.

Pancreas after kidney transplantation.

After three decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for patients with insulin-dependent diabetes mellitus (IDDM) and advanced diabetic nephropathy with end-stage renal disease (ESRD) and for

Varicella Pneumonia: Another ‘Steroid Responsive’ Pneumonia?

Varicella-zoster virus (VZV) pneumonitis remains an often-fatal complication of VZV infection. Antiviral agents and supportive care are widely accepted therapies. Cautious use of corticosteroids in life-threatening VZV pneumonitis may be justified. Appropriate patient selection factors are as yet unidentified and the decision to commence corticosteroid therapy in this setting is clinical.

Carboplatin Based Chemotherapy in the Treatment of Advanced Urothelial Cancer with Poor Prognostic Features

Objective : Multiagent cisplatin based chemotherapy improves survival and quality of life in patients with good performance status (PS) and adequate renal function. This treatment has considerable toxicity and many patients are not suitable for this treatment by virtue of age/PS or poor renal function. Materials and methods : In this study, we report a review of 45 such patients treated by carboplatin based chemotherapy. Chemonaive patients with metastatic or locally advanced bladder cancer were treated with a combination of carboplatin (AUC 6) and methotrexate (60 mg/m 2 ) alone (MC, n =16 ) or with vincristine (1.4 mg/m 2 ) (JMO, n =29 ). Median age was 69 (range 45-90) and 24 (53%) patients had visceral metastases, PS S 2 in 26 patients (58%) and 35 (78%) patients had a GFR h 50 ml/min. Results : Forty four patients were evaluable for response. There was one complete response (2%) and eight partial responses (18%) for an overall response rate (ORR) of 20.5% (95% confidence interval (CI) 10-35%). Response rates were higher for JMO, (ORR 25%: 95% CI 11-45%) than for MC, ORR 12.5% (95% CI 2-38%), p =0.021. Eighteen out of 38 symptomatic patients had improvement in symptoms following chemotherapy. Median survival was 4.4 months for all patients, with 29.1% (CI 15.8-43.8%) alive at 1 year. Median survival for JMO was 4.7 months [with 37% (95% CI 19.2-55%) patients alive at 1 year] and 3 months for MC. The main toxicity was haematological (CTC grades 3-4 leucopenia in 29% of patients and thrombocytopaenia in 15.5%) which was similar for both regimes. Peripheral neuropathy was documented in 21 patients who received JMO and 2 receiving MC. Conclusion : Carboplatin and Methotrexate - Vincristine exhibit modest activity and are tolerable when used as first line treatment in patients with poor risk features. In this retrospective review, JMO seemed to be more active than MC but an effect due to differences in patient selection and prognostic factors cannot be excluded. Improvement in patient symptoms were documented but the overall palliative benefit of such activity remains to be determined.

Current perspectives in muscle invasive bladder cancer

Muscle-infiltrating bladder cancer should be dealt with in a multimodality approch with collaboration between the urologist, medical oncologist and radiotherapist. Neo-adjuvant chemotherapy has not been proven to improve survival, but may be useful in programs of bladder preservation. Response to M-VAC neo-adjuvant chemotherapy is an important prognostic factor, but may represent patient selection factors. It is not known whether it is better to administer chemotherapy in the neo-adjuvant or in the adjuvant setting, that may spare some patients unnecessary chemotherapy. The international adjuvant chemotherapy trial coordinated by the EORTC (protocol 30994) will hopefully clarify some of the unanswered questions concerning whether or not adjuvant chemotheraphy immediately following cystectomy improves survival.