SOHO State of the Art Updates and Next Questions: BTK inhibitors combined with chemoimmunotherapy in CLL, the best of both worlds?

Chemoimmunotherapy (CIT) remains a standard-of-care in many regions for first line (1L) therapy of CLL. In fit patients, fludarabine, cyclophosphamide, and rituximab (FCR) has the advantage of achieving undetectable measurable residual disease (MRD) with time-limited treatment and prolonged treatment-free remissions with a plateau on the PFS curve, but have several limitations, most notably the inferior PFS and survival outcomes for patients with unmutated IGHV compared to ibrutinib + rituximab seen in the E1912 study and a risk for long-term toxicities such as therapy-related myeloid neoplasms. Given the nonoverlapping toxicity profile with CIT and its efficacy in patients with high risk genomics, ibrutinib is a potentially useful agent to combine with CIT, with the aim of achieving deep and durable remissions, with time-limited treatment.

Engineering of New Pneumocandin Side-Chain Analogues from Glarea lozoyensis by Mutasynthesis and Evaluation of Their Antifungal Activity.

Pneumocandins are lipohexapeptides of the echinocandin family that inhibit fungal 1,3-β-glucan synthase. Most of the pathway steps have been identified previously. However, the lipoinitiation reaction has not yet been experimentally verified.

A Video Game Promoting Cancer Risk Perception and Information Seeking Behavior Among Young-Adult College Students: A Randomized Controlled Trial.

Background: Risky behaviors tend to increase drastically during the transition into young adulthood. This increase may ultimately facilitate the initiation of carcinogenic processes at a young age, highlighting a serious public health problem. By promoting information seeking behavior (ISB), young adults may become aware of cancer risks and potentially take preventive measures.

Assessment of patients' and caregivers' informational and decisional needs for left ventricular assist device placement: Implications for informed consent and shared decision-making.

Background: Several organizations have underscored the crucial need for patient-centered decision tools to enhance shared decision-making in advanced heart failure. The purpose of this study was to investigate the decision-making process and informational and decisional needs of patients and their caregivers regarding left ventricular assist device (LVAD) placement.

Methods: In-depth, structured interviews with LVAD patients, candidates and caregivers (spouse, family members) (n = 45) were conducted.

Impact of enhanced detection on the increase in thyroid cancer incidence in the United States: review of incidence trends by socioeconomic status within the surveillance, epidemiology, and end results registry, 1980-2008.

Background: In the past 3 decades, the incidence of thyroid cancer in the United States has been increasing. There has been debate on whether the increase is real or an artifact of improved diagnostic scrutiny. Our hypothesis is that both improved detection and a real increase have contributed to the increase.

Phase II, multicenter, uncontrolled trial of single-agent sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer.

Purpose: Sorafenib is an oral multikinase inhibitor that targets the Ras/Raf/MEK/ERK mitogenic signaling pathway and the angiogenic receptor tyrosine kinases, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor beta. We evaluated the antitumor response and tolerability of sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer (NSCLC), most of whom had received prior platinum-based chemotherapy.

Patients And Methods: This was a phase II, single-arm, multicenter study.

Multiple roles for MRE11 at uncapped telomeres.

Progressive telomere attrition or uncapping of the shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. Telomere deprotection activates both ataxia telangiectasia mutated (ATM) and telangiectasia and Rad3-related (ATR) kinase-dependent DNA damage response pathways, and promotes efficient non-homologous end-joining (NHEJ) of dysfunctional telomeres. The mammalian MRE11-RAD50-NBS1 (MRN; NBS1 is also known as NBN) complex interacts with ATM to sense chromosomal double-strand breaks and coordinate global DNA damage responses.

Association between imatinib-resistant BCR-ABL mutation-negative leukemia and persistent activation of LYN kinase.

Background: Imatinib is a tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). BCR-ABL mutations are associated with failure of imatinib treatment in many CML patients. LYN kinase regulates survival and responsiveness of CML cells to inhibition of BCR-ABL kinase, and differences in LYN regulation have been found between imatinib-sensitive and -resistant CML cell lines.

Epidermal overgrafting improves coloration in remote flaps and grafts applied to the face for reconstruction.

Background: Flaps and grafts applied to the face from sites below the clavicles are mismatched with regard to their coloration compared with normal facial skin. The color can be improved by removing the epidermis and overgrafting with a thin, split-thickness skin graft of scalp epidermis. This report reviews the authors' clinical experience using this technique.

Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis.

Human carcinomas arise through the acquisition of genetic changes that endow precursor cancer cells with a critical threshold of cancer-relevant genetic lesions. This complex genomic alterations confer upon precursor cancer cells the ability to grow indefinitely and to metastasize to distant sites. One important mechanism underlying a cell's tumorigenic potential is the status of its telomere.

Stenotrophomonas maltophilia: changing spectrum of a serious bacterial pathogen in patients with cancer.

Stenotrophomonas maltophilia colonization/infection in patients with cancer has significantly increased over the past 2 decades. Patients with prolonged neutropenia, exposure to broad-spectrum antibiotics, and those requiring mechanical ventilation have higher risk of infection. These micro-organisms are intrinsically resistant to carbapenems, and exposure to these agents has been linked to selection of S.

Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer.

Purpose: Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, and erlotinib, a reversible, orally available epidermal growth factor receptor tyrosine kinase inhibitor, have demonstrated evidence of a survival benefit in the treatment of non-small-cell lung cancer (NSCLC). A single-arm phase I and II study of bevacizumab plus erlotinib demonstrated encouraging efficacy, with a favorable safety profile.

Patients And Methods: A multicenter, randomized phase II trial evaluated the safety of combining bevacizumab with either chemotherapy (docetaxel or pemetrexed) or erlotinib and preliminarily assessed these combinations versus chemotherapy alone, as measured by progression-free survival (PFS).

Daily variations in delivered doses in patients treated with radiotherapy for localized prostate cancer.

Purpose: The aim of this work was to study the variations in delivered doses to the prostate, rectum, and bladder during a full course of image-guided external beam radiotherapy.

Methods And Materials: Ten patients with localized prostate cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39 fractions. Daily target localization was performed using intraprostatic fiducials and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total of 390 CT scans.

Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions.

Background: Conventional amphotericin B-based antifungal therapy for invasive fusariosis in patients with a hematologic malignancy results in a > or = 70% failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and in vivo activity against Fusarium species.

Methods: In this retrospective analysis of patients from 3 open-label clinical trials, we evaluated posaconazole for the treatment of invasive fusariosis.

Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway.

Werner Syndrome (WS) is characterized by premature aging, genomic instability, and cancer. The combined impact of WRN helicase deficiency and limiting telomere reserves is central to disease pathogenesis. Here, we report that cells doubly deficient for telomerase and WRN helicase show chromosomal aberrations and elevated recombination rates between telomeres of sister chromatids.

Multi-institutional phase 2 study of TLK286 (TELCYTA, a glutathione S-transferase P1-1 activated glutathione analog prodrug) in patients with platinum and paclitaxel refractory or resistant ovarian cancer.

The purpose of this study was to determine the safety and efficacy of TLK286 (TELCYTA(TM)), a glutathione analog prodrug, in patients with platinum and paclitaxel refractory or resistant ovarian carcinoma. Thirty-six patients with measurable disease were enrolled. TLK286 was administered at 1000 mg/m2 intravenously every 3 weeks.

In vitro model of normal, immortalized ovarian surface epithelial and ovarian cancer cells for chemoprevention of ovarian cancer.

Background: Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers. The synthetic retinoid, N-(4-hydroxyphenyl) retinamide (4-HPR), has been used in the chemoprevention of ovarian cancer. However, the effectiveness of its application for different populations has been questioned because of the genetic differences among normal, high risk, and women with cancer.

A mouse model of Werner Syndrome: what can it tell us about aging and cancer?

The molecular mechanisms involved in mammalian aging and the consequent organ dysfunction/degeneration pathologies are not well understood. Studies of progeroid syndromes such as Werner Syndrome have advanced our understanding of how certain genetic pathways can influence the aging process on both cellular and molecular levels. In addition, improper maintenance of telomere length and the consequent cellular responses to dysfunctional telomeres have been proposed to promote replicative senescence that impact upon the onset of premature aging and cancer.

Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens.

Background: Catheter-related bloodstream infections (CR-BSIs) are associated with substantial mortality, prolongation of hospital stay, and increased cost of care. Dalbavancin, a new glycopeptide antibiotic with unique pharmacokinetic properties that have allowed clinical development of a weekly dosing regimen, possesses excellent activity against clinically important gram-positive bacteria, suggesting utility in the treatment of patients with CR-BSIs.

Methods: A phase 2, open-label, randomized, controlled, multicenter study of 75 adult patients with CR-BSIs compared treatment with intravenous dalbavancin, administered as a single 1000-mg dose followed by a 500-mg dose 1 week later, with intravenous vancomycin, administered twice daily for 14 days.

Ovarian cancer identified through screening with serum markers but not by pelvic imaging.

Woolas RP, Oram DH, Jeyarajah AR, Bast RC Jr, Jacobs IJ. Ovarian cancer identified through screening with serum markers but not by pelvic imaging. This study evaluated the possible role of 3 additional tumor markers to CA 125 among postmenopausal volunteers participating in a sequential multimodal ovarian cancer screening study.

Small cell carcinoma of the esophagus: the University of Texas M. D. Anderson Cancer Center experience and literature review.

Background: Small cell carcinoma of the esophagus is a rare disease with aggressive behavior and poor prognosis. Multidrug chemotherapy remains the treatment of choice given the systemic nature of the disease. Radiotherapy has been used concurrently with chemotherapy to enhance local control.