Patient-Centered Medicine: Transforming the Clinical Method

Purpose Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. Patients and Methods Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. Results The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. Conclusion CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT. J Clin Oncol 31:3061-3068. © 2013 by American Society of Clinical Oncology

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Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202)

CNS lymphoma consists of 2 major subtypes: secondary CNS involvement by systemic lymphoma and PCNSL. Contrast-enhanced MR imaging is the method of choice for detecting CNS lymphoma. In leptomeningeal CNS lymphoma, representing two-thirds of secondary CNS lymphomas, imaging typically shows leptomeningeal, subependymal, dural, or cranial nerve enhancement. Single or multiple periventricular and/or superficial contrast-enhancing lesions are characteristic of parenchymal CNS lymphoma, representing one-third of secondary CNS lymphomas and almost 100% of PCNSLs. New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions. Advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis. Furthermore, these imaging techniques may play a pivotal role in planning targeted therapies, prognostication, and monitoring treatment response.

http://www.ajnr.org/content/ajnr/32/6/984.full.pdf

Central Nervous System Lymphoma: Characteristic Findings on Traditional and Advanced Imaging

OBJECTIVE:Subdural hematomas and hygromas are infrequently encountered complications of arachnoid cysts of the middle cranial fossa and are particularly rare with cysts of other regions. Reports in the literature focus on casuistic observations. Therapeutic recommendations often include fenestration

Arachnoid cysts associated with subdural hematomas and hygromas: analysis of 16 cases, long-term follow-up, and review of the literature.

▪ Abstract Cascade effect refers to a process that proceeds in stepwise fashion from an initiating event to a seemingly inevitable conclusion. With regard to medical technology, the term refers to a chain of events initiated by an unnecessary test, an unexpected result, or patient or physician anxiety, which results in ill-advised tests or treatments that may cause avoidable adverse effects and/or morbidity. Examples include discovery of endocrine incidentalomas on head and body scans; irrelevant abnormalities on spinal imaging; tampering with random fluctuations in clinical measures; and unwanted aggressive care at the end of life. Common triggers include failing to understand the likelihood of false-positive results; errors in data interpretation; overestimating benefits or underestimating risks; and low tolerance of ambiguity. Excess capacity and perverse financial incentives may contribute to cascade effects as well. Preventing cascade effects may require better education of physicians and patients; r...

Cascade Effects of Medical Technology

Study Design. Quantitative and qualitative cross-sectional interview study. Objectives. To investigate how patients who are referred for plain radiography because of low back pain perceive the importance and usefulness of the examination. Summary of Background Data. Up to 50% of plain radiography examinations for low back pain may be unnecessary based on clinical criteria. However, many patients have great confidence in these examinations. A further exploration of the patients’ views may indicate how their needs can be met without unnecessary use of radiography. Methods. Ninety-nine patients (65 women, 34 men) 14–91 years of age who were referred from Norwegian general practitioners for plain radiography of the lumbosacral spine were asked to rate the examination as slightly/fairly or very important (93 responded). Chi-squared tests were used to evaluate differences in rating according to age, gender, clinical history, and clinical appropriateness of the examination, as determined by comparing information in the referral form with Norwegian (NR) and British (BR) recommendations for use of radiography. Each of the 99 patients also underwent a semistructured interview that was based on questions about importance, usefulness, and reasons for the radiography referral. Answers were categorized and described using a qualitative method (template analysis). Results. Seventy-two percent (68 of 93) of patients rated radiography as very important. The proportion was higher for men than women (85%vs. 65%, P = 0.04), higher for those with worsening than those with improving/unchanged symptoms (86%vs. 65%, P = 0.03), and higher for inappropriately than appropriately referred patients (NR: 76%vs. 61%, P = 0.17; BR: 81%vs. 56%, P = 0.01). The qualitative analysis showed that the patients related their views on the importance and usefulness of receiving radiography to seven different issues: symptoms and clinical history, information and advice (especially from health care providers), need for emotional support from the physician, need for certainty and reassurance, need for symptom explanation and diagnosis, reliability of radiography compared with clinical evaluation, and expected practical consequences of the radiologic examination. Conclusions. The finding that inappropriately referred patients tended to rate their radiography referral as more important than appropriately referred patients indicates that the patient’s view may be a substantial barrier to appropriate use of radiography. The study identified seven issues underlying the patients’ views on importance and usefulness of receiving radiography. Strategies to prevent unnecessary use of plain radiography for low back pain that address these issues are suggested.

Patients' views on importance and usefulness of plain radiography for low back pain.

This study investigates delay in diagnosing primary central nervous system lymphoma (PCNSL), which has a variable clinical and radiological presentation. Early diagnosis and treatment may improve survival and cause less sequela in PCNSL. Medical records of all new cases of PCNSL morphologically verified while alive or by autopsy in Norway in 1989-1998 were reviewed (n = 74). The time from initial symptom to final morphological diagnosis of PCNSL had a median (mean, range) of 70 (106, 22-330) days in 16 AIDS patients and 75 (157, 8-1285) days in 58 non-AIDS patients. Among non-AIDS patients, the time to diagnosis was longer in patients with no tumour in the first neuroimaging report after initial symptom (p = 0.001). Median (mean, range) time from initial symptom to neuroimaging was 14 (25, 1-60) days in AIDS patients and 21 (88, 1-1095) days in non-AIDS patients. In the non-AIDS group, those presenting with personality change or visual disturbance had more delayed imaging than the others. The time from first neuroimaging examination to final diagnosis in non-AIDS patients had a median (mean, range) of 28 (69, 1-845) days, and was longer when no tumour was indicated in the imaging report (p = 0.005) and if first biopsy did not confirm the diagnosis (p = 0.02). All AIDS patients had their diagnosis of PCNSL first established by autopsy. The time from first neuroimaging to autopsy had a median (mean, range) of 48 (81, 10-270) days. There is a considerable delay in the diagnosis of PCNSL and strategies for earlier diagnosis are thus needed. Physicians should consider early neuroimaging in patients with personality changes or visual disturbance, early renewed imaging in patients with persistent neurological symptoms but no tumour on initial imaging, and early/repeated biopsy of focal brain lesions in both AIDS patients and non-AIDS patients.

https://www.tandfonline.com/doi/pdf/10.1080/02841860500256272

Diagnostic delay in primary central nervous system lymphoma

Spontaneous disappearance of an arachnoid cyst in the middle intracranial fossa.

In a 32-year-old woman, cerebral angiography showed fibromuscular dysplasia of the left anterior and middle cerebral arteries. She had had epilepsy and subarachnoid hemorrhages with subsequent hemiplegia. Since she also had multiple enchondromas (Ollier disease), this may represent a case of Maffucci syndrome.

Fibromuscular dysplasia of intracranial arteries in a patient with multiple enchondromas (Ollier disease).

The incidence of primary central nervous system lymphoma (PCNSL) has been reported to increase in some parts of the world, while being stable in other regions. In an attempt to characterize the incidence rate, clinical features, treatment, outcome, and prognostic factors of PCNSL in Norway, we report our experience in a large unselected series of patients. Clinical features, histological diagnosis, radiological findings, treatment, and outcome of all patients diagnosed with PCNSL in Norway in the years 1989 � /1998 were registered. During the 10-year period 58 new cases of histologically verified PCNSL were registered in Norway. The annual incidence rate of PCNSL was on average 1.34 cases per million people with a non-significant increasing trend (p� /0.069). For patients diagnosed before death (n� /45) the estimated survival following histological diagnosis was 55%, 47%, and 23% at 1, 2, and 5 years, respectively. In Cox-regression analysis age, WHO performance status and treatment had independent prognostic impact on survival. In the studied decade, there was a non-significant trend towards increased incidence of PCNSL, perhaps due to increased availability of diagnostic imaging, especially magnetic resonance imaging.

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John Ludvig Larsen

Papers

Patients' views on importance and usefulness of plain radiography for low back pain.

Diagnostic delay in primary central nervous system lymphoma

Spontaneous disappearance of an arachnoid cyst in the middle intracranial fossa.

Fibromuscular dysplasia of intracranial arteries in a patient with multiple enchondromas (Ollier disease).

Incidence, Clinical Features, Treatment and Outcome of Primary Central Nervous System Lymphoma in Norway A Ten-year National Survey