Citations

Key Points Deep sequencing identifies a significant reservoir of subclonal mutations affecting key genes in CLL pathogenesis. Convergent evolution of genetic lesions in tumor subclonal populations is recurrently found in CLL.

ABSTRACT We report a case of a 62-year-old female with seizures and encephalitis. Molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (HSV-1 and HSV-2). To our knowledge, this is the first report of simultaneous detection of HSV-1 and HSV-2 in cerebrospinal fluid.

Objective (1) To characterize long‐term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium‐sized vestibular schwannoma (VS) using a validated self‐assessment inventory; and (2) to identify clinical variables associated with long‐term dizziness handicap. Study Design Cross‐sectional observational study. Setting Two independent tertiary academic referral centers: one located in the United States and one in Norway. Subjects and Methods All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. Results The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long‐term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long‐term dizziness handicap. Conclusion At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long‐term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship.

Background: We examined patient interest in a telehealth model in which the patient supplies the hardware and Internet connectivity to meet with a healthcare provider from his or her home via video call (video appointment). We hoped to understand prospectively the desirability, feasibility, and viability from the patient perspective. Materials and Methods: A phone survey was conducted of a random sample of patients who had been seen in the outpatient setting at a single institution. The sample was stratified by proximity to the local institution with oversampling for patients living outside a 120-mile radius. Results: Out of 500 total patients, 301 patients responded, and 263 met the inclusion criteria. Of those 263 respondents, 38% indicated “very likely” to accept an invitation to see their provider via video, 28.1% “somewhat likely,” and 33.8% “not at all likely.” Of respondents, 75% have broadband, although only 36% reported having a Web camera. The primary factors affecting willingness to participate in a video appointment include comfort in setting up a video call, age, and distance participants would have traveled for an in-clinic appointment. Conclusions: Patient survey data indicate that most patients are likely to be accepting of telehealth care to the home using video call and that most have the required technology. Nevertheless, there are still significant hurdles to effectively implement this adaptation of telehealth care as part of mainstream practice.

Abstract Background: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is the most common adult leukemia in the United States. Prior studies in Olmsted County, Minnesota, showed a CLL age and sex adjusted incidence rate of 6.6 per 100,000 during 1985-89. Subsequently, the definition of CLL is now based on the 2008 International Workshop on CLL (IWCLL) Guidelines. Individuals having a CLL immunophenotype by flow cytometry are classified as CLL if the absolute B-cell count (ABC) is >5 x 109/L or classified as monoclonal B-cell lymphocytosis (MBL) if ABC is <5 x 109/L. To assess the impact of these changes on the incidence of CLL and clinically discovered MBL, we conducted an incidence study in Olmsted County for the years 2000-2010. Methods Using diagnostic indexes available through the Rochester Epidemiology Project and the Mayo CLL database, we identified all CLL and clinically identified MBL cases from 2000-2010. Incidence rates and demographics were compared between the older National Cancer Institute-Working Groups 1996 guidelines (NCI-WG 96) defined as absolute lymphocyte count (ALC)> 5 x 109/L and the IWCLL 2008 guidelines defined as ABC > 5 x 109/L. Incidence rates were age and sex adjusted using the 2010 US white population. Time to treatment (TTT) survival analyses was from time of diagnosis to date of first treatment or last follow-up and Cox regression analysis was used. Results Using the NCI-WG 96 classification, there were 8 MBL cases and 115 CLLs in whom 61% were Rai stage 0, 34% were Rai stage 1-2, and 5% were Rai stage 3-4. Using the IWCLL 2008 classification, there were 44 MBL cases and 79 CLLs in whom 43% Rai stage 0, 49% were Rai stage 1-2 and 8% Rai stage 3-4. Median ALC at diagnosis was 8.1 x 109/L for CLL and 5.9 x 109/L for MBL. Median ABC count at diagnosis was 7.1 x 109/L for CLL and 2.8 x 109/L for MBL. The age and sex adjusted incidence rate (per 100,000) for CLL for 2000-2010 was 10.0 using NCI-WG 96 and 6.8 using IWCLL 2008. Rates for MBL were 0.66 using NCI-WG 96 and 3.5 using IWCLL 2008. The median TTT for CLL was 9.2 years using NCI-WG 96 and 6.5 years by IWCLL 2008. Discussion This study demonstrates that reclassification of CLL using the IWCLL 2008 guidelines decreases CLL incidence relative to the NCI-WG 96 criteria. For the first time, this population based study also establishes an incidence rate for clinically identified MBL. Approximately 50% of previously labeled Rai 0 CLL are now reclassified as MBL. Re-classification increases the percent of Rai stage 1-2 and decreases the percent of Rai 0 cases at diagnosis. Reclassification also substantially shortens the median TTT for newly diagnosed CLL cases classified by the 2008 criteria relative to the NCI-WG 96 criteria. In summary, the IWCLL 2008 reclassification has significant implications for incidence studies, staging, and prognosis of CLL and MBL. Citation Format: Aaron D. Norman, Timothy G. Call, Curtis A. Hanson, Neil E. Kay, Clive S. Zent, Wei Ding, James R. Cerhan, Sara J. Achenbach, Kari G. Rabe, Celine M. Vachon, Emily J. Hallberg, Tait D. Shanafelt, Susan L. Slager. Incidence of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis in Olmsted county, 2000-2010: impact of the 2008 International Workshop on CLL Guidelines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2287. doi:10.1158/1538-7445.AM2013-2287

Abstract Background: Hsp90 is a molecular chaperone protein required for the stabilization and activation of many proteins, referred to as Hsp90 ‘clients’, such as HER2, HIF1-a, EGFR, ER, PI3K, AKT, P53 and VEGFR. The drug candidate, ganetespib is a novel triazolone inhibitor of Hsp90, with over 700 patients treated to date. Ganetespib has shown activity in preclinical models of HER2+, ER+/PR+ and TNBC. Early clinical trials documented ganetespib single agent activity in heavily pretreated HER2+ and TNBC patients. Ganetespib has been well tolerated in clinical trials with a favorable safety profile. This efficacy-screening study is designed to provide further evidence of ganetespib activity and identify potentially predictive biomarkers in metastatic breast cancer (BC). Methods: The ENCHANT-1 Trial is an international, first-line 2-cohort Phase 2 study in BC patients: Cohort A, HER2 amplified (n = 35), and Cohort B, TNBC (n = 35). Patients who present with previously untreated metastatic disease are eligible for treatment with ganetespib at 150 mg/m2 twice weekly on 3 out of 4 wks, for a total of up to 12 wks. Primary endpoint: ORR assessed using RECIST1.1 criteria. Key secondary endpoints include metabolic response as assessed by PET/CT at wk 3 utilizing modified EORTC criteria. Disease progression (PD) at wk 3 by PET imaging indicates discontinuation of study therapy, and is performed to quickly offer patients with metabolic PD a standard of care treatment. The study is designed as Simon 2-stage requiring at least one OR in 15 patients for the respective cohort to expand to 35 patients. A Steering Committee is established to oversee the overall study and review the interim results. Results: The study was initiated in 23 centers globally. At the time of submission, a total of 17 patients had been enrolled; TNBC (n = 15) and HER2 (n = 2). Here we report the interim analysis in the TNBC cohort. The median age was 54 years (range 30 -77) with ECOG PS 0 (n = 7/15). Most patients (n = 9) presented with de novo metastatic disease. 5 patients were not evaluable for PET assessment (3 had not yet reached wk 3 and 2 withdrawn before wk 3 for clinical progression), and 9 patients were not evaluable for objective response at wk 6 (3 withdrawn before or at wk 3 for clinical progression and 6 had not yet reached wk 6 evaluation). In the 10 patients with evaluable PET imaging, 9 patients achieved metabolic (m) response (2 mPR, 4 mSD with dominant tumor shrinkage and 3 SD) and one patient with mPD. In the 6 patients evaluable for OR at wk 6, one patient achieved PR, 2 SD and 3 PD. Treatment with ganetespib was well tolerated; the most common AEs were mild or moderate diarrhea (8/15, 53%), fatigue (5/15, 33%), decreased appetite (4/15, 27%), insomnia (4/15, 27%), and nausea (4/15, 27%). Conclusion: Ganetespib single agent was generally well tolerated and showed anti-tumor activity TNBC patients as early as 3 weeks following treatment. PET seems to be a good tool to screen antitumor activity of new agents in early settings rather that in heavily pretreated patients. The TNBC cohort has met the protocol criteria for proceeding to stage 2. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-23.