The Hospitalist Model and Oncology: Oncologist Opinions About Inpatient Cancer Care Delivery.

Hospitalists, rather than oncologists, are increasingly providing inpatient medical care to hospitalized patients with cancer, yet the opinions of oncologists regarding this model of care delivery are unknown. A survey was conducted assessing these opinions and experiences with inpatient cancer care delivery at a tertiary cancer center. Only 30% of oncologists agreed that caring for hospitalized patients with cancer was an efficient use of their time, and most believed a hospitalist service allowed them to pursue other interests. Most had a positive experience with hospitalists, agreeing that hospitalists can diagnose and manage toxicities of cancer therapy, exhibit professionalism, and communicate with them and their patients appropriately. Hematologic malignancy specialists were more likely to value inpatient service time and had less confidence in the ability of hospitalists. Overall, the hospitalist model was generally accepted by oncologists and will continue to be an important part of oncologic care delivery.

Current Therapeutic Interventions in Lower Extremity Venous Insufficiency: a Comprehensive Review.

PURPOSE OF REVIEW: Chronic venous disease (CVD), although affecting up to 40% of the US population, is often underdiagnosed by healthcare professionals due to an incomplete understanding of the presenting symptoms. CVD is a common cause of lower extremity pain and discomfort, including aching, cramping, tingling, burning, swelling, heaviness, restlessness, and fatigue, and may lead to significant morbidity if left untreated. The negative impact of CVD on quality of life is well established and the optimization of management strategies is an important area of evolving research. RECENT FINDINGS: Management of CVD has rapidly evolved over the last two decades with the development of minimally invasive endovenous ablative techniques, now the mainstay of treatment. We discuss the data supporting various methods of CVD treatment with an emphasis on the impact on patient comfort and quality of life. Both radiofrequency ablation (RFA) and endovenous laser therapy (EVLA) are excellent options for treatment of lower extremity venous disease, but RFA is associated with less post-procedure discomfort. Ultrasound-guided foam therapy is best reserved for the adjuvant setting or for patients ineligible for RFA or EVLA.

Cigarette smoking during external beam radiation therapy for prostate cancer is associated with an increased risk of prostate cancer-specific mortality and treatment-related toxicity.

OBJECTIVE: To evaluate whether a history of smoking or smoking during therapy after external beam radiotherapy (EBRT) for clinically localised prostate cancer is associated with increased treatment-related toxicity or disease progression. PATIENTS AND METHODS: Of 2358 patients receiving EBRT for prostate cancer between 1988 and 2005, 2156 had chart-recorded smoking histories. Patients were classified as 'never smokers', 'current smokers', 'former smokers', and 'current smoking unknown'. Variables considered included quantity of tobacco use in pack-years, duration of smoking, and, for former smokers, how long before initiation of RT the patient quit smoking, when available. The median EBRT dose was 8100 Gy and the median follow-up was 95 months. Toxicity was graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. RESULTS: Current smoking significantly increased the risks of both prostate-specific antigen relapse [hazard ratio (HR) 1.4, P = 0.02] and distant metastases (HR 2.37, P < 0.001), as well as prostate cancer-specific death (HR 2.25, P < 0.001). Multivariate analysis showed that smoking was also associated with increased risk of EBRT-related genitourinary toxicities (current smoker, HR 1.8, P = 0.02; former smoker, HR 1.45, P = 0.01). Smoking did not increase gastrointestinal toxicity. CONCLUSIONS: Current smokers with prostate cancer are at increased risk of biochemical recurrence, distant metastasis, and prostate cancer-related mortality after definitive RT to the prostate. Current and former smokers, regardless of duration and quantity of exposure, are at an increased risk of long-term genitourinary toxicity after EBRT. Oncologists should encourage patients to participate in smoking-cessation programmes before therapy to potentially lower their risk of relapsing disease and post-treatment toxicities.

Low-Dose-Rate Brachytherapy Boosting Concurrent Chemoradiation as a Definitive Treatment Modality for Cervical Cancer: Long-term Clinical Results of Outcomes and Associated Toxicity.

PURPOSE: To review and report the long-term treatment-induced adverse events (AEs) and outcomes of concomitant chemoradiotherapy boosted by low-dose-rate (LDR) conventional brachytherapy (BT) planning in patients with locoregionally advanced cervical cancer. PATIENTS AND METHODS: After obtaining institutional review board approval, we reviewed the records of patients with stage IB1 to IVA, intact cervical cancer who were treated at our institution between 1983 and 2009. Eligible patients underwent definitive radiotherapy with external-beam radiation concomitant with cisplatin-based chemotherapy and boosted by LDR BT. Patient, tumor, and treatment characteristics; treatment-induced AEs, namely, gastrointestinal and genitourinary toxicities, as well as treatment outcomes; locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were reviewed and reported. RESULTS: The study included 129 eligible cervical cancer patients; the median age was 46 years (mean, 47 ± 11 y; range, 28 to 81 y), consisting of stages I, II, III, and IV (29.5%, 48.1%, 17.8%, and 4.6%, respectively). The median follow-up was 37 months (mean, 58 ± 59 mo; range, 3 to 275 mo). The 3-year OS, PFS, LRC, and DC were 75.9%, 71.6%, 84.7%, and 80.2%, respectively. The 5-year OS, PFS, LRC, and DC were 70.7%, 68.7%, 84.7%, and 78.3%, respectively. The 10-year OS, PFS, LRC, and DC were 68.7%, 62.3%, 82.5%, and 73.2%, respectively. Gastrointestinal and genitourinary grade 3 and 4 acute AEs were reported in 3.9% and 0%, and chronic grade 3 and 4 AEs were reported in 20.9% and 12.4% of all patients, respectively. CONCLUSIONS: Definitive chemoradiotherapy followed by conventional LDR BT boost is effective, feasible, and tolerable treatment modality for cervical cancer. A comparison with MRI image-guided BT shows comparable treatment outcomes with superior OS in favor of LDR BT but inferior LC with a relatively worse toxicity profile.

Radiation dose ≥54 Gy and CA 19-9 response are associated with improved survival for unresectable, non-metastatic pancreatic cancer treated with chemoradiation.

BACKGROUND: Unresectable pancreatic cancer (UPC) has low survival. With improving staging techniques and systemic therapy, local control in patients without metastatic disease may have increasing importance. We investigated whether the radiation dose used in chemoradiation (CRT) as definitive treatment for UPC and the CA 19-9 response to therapy have an impact on overall survival (OS). METHODS: From 1997-2009 46 patients were treated with CRT for non-metastatic UPC. Median prescribed RT dose was 54 Gy (range 50.4-59.4 Gy). All patients received concurrent chemotherapy (41: 5-fluorouracil, 5: other) and 24 received adjuvant chemotherapy. RESULTS: 41 patients were inoperable due to T4 disease and 5 patients with T3 disease were medically inoperable. Five patients did not complete CRT due to progressive disease or treatment-related toxicity (median RT dose 43.2 Gy). Overall, 42 patients were dead of disease at the time of last follow-up. The median and 12 month OS were 8.8 months and 35%, respectively. By univariate analysis, minimum CA 19-9 post-CRT <90 U/mL was favorably associated with OS (12.3 versus 8.8 months, p = 0.012). Radiotherapy dose ≥54 Gy trended towards improved OS (11.3 versus 6.8 months, p = 0.089). By multivariable analysis, a delivered RT dose of ≥54 Gy (HR 0.47, p = 0.028) and minimum CA 19-9 post-CRT of <90 U/mL (HR 0.35, p = 0.008) were associated with OS. CONCLUSIONS: CRT as definitive treatment for UPC had low survival. However, our retrospective data suggest that patients treated to ≥54 Gy or observed to have a minimum post-CRT CA 19-9 <90 U/mL had improved likelihood of long-term survival.

Gastrointestinal stromal tumors: a paradigm for therapeutic options in solid organ tumors.

Although a relatively rare malignancy with a national incidence of 3500-4000 annually, Gastrointestinal Stromal Tumor (GIST) is of significance in the realm of clinical and pharmacological research. GIST exhibits remarkable uniformity in its pathogenesis and ultrastructure as 95% of cases are linked to constitutive activation and overexpression of a membrane tyrosine kinase, c-KIT (CD117). Although previously refractory to any course of action but surgery, GIST heralded a triumph in targeted cancer therapy when administration of a specific first-generation tyrosine-kinase inhibitor Imatinib mesylate (STI571) was shown to inhibit c-Kit and demonstrated a significant increase in patient survival. Over the subsequent decade, GIST has become a paradigm for the potency of Imatinib in adjuvant or neoadjuvant therapy, showcasing the clinical relevance and rapidity of translational research in the field of targeted molecular therapy. Subsequent to demonstrating the efficacy of Imatinib as a therapeutic agent, GIST has also exposed the limitations of current targeted therapies. Within two years, 50% of GISTs develop secondary mutations that allow resistance to Imatinib. However, extensive research regarding both primary and secondary c-KIT mutations has illuminated the mechanisms of Imatinib resistance and has the potential to ameliorate this therapeutic setback. Current research to this end lies in two primary directions: the development of tyrosine kinase inhibitors (some of which also inhibit other oncogenic agents such as PDGFR, bcr-abl, and VEGF) that are either generally more potent than Imatinib or less susceptible to specific mechanisms of resistance; and drugs that target the downstream effectors of the mutant c-KIT kinase, including PKC and mTOR. This paper will systematically review current research on second-generation targeted molecular therapy in the treatment of GIST, and expand upon its value as a model for treatment of other solid organ tumors.

Temperature-based extrinsic reproductive isolation in two species of Drosophila.

Drosophila santomea and D. yakuba are sister species that live on the African volcanic island of São Tomé, where they are ecologically isolated: D. yakuba inhabits low-altitude open and semiopen habitats while D. santomea lives in higher-elevation rain and mist forest. To determine whether this spatial isolation reflected differential preference for and tolerance of temperature, we estimated fitness components of both species at different temperatures as well as their behavioral preference for certain temperatures. At higher temperatures, especially 28 degrees C, D. santomea was markedly inferior to D. yakuba in larval survival, egg hatchability, and longevity. Moreover, D. santomea females, unlike those of D. yakuba, become almost completely sterile after exposure to a temperature of 28 degrees C, and conspecific males become semisterile. Drosophila santomea adults prefer temperatures 2-3 degrees C lower than do adults of D. yakuba. Drosophila santomea, then, is poorly adapted to high temperature, partially explaining its restriction to cool, high habitats, which leads to extrinsic premating isolation and immigrant inviability. Rudimentary genetic analysis of the interspecific difference in egg hatchability and larval survival showed that these differences are due largely to cytoplasmic effects and to autosomal genes, with sex chromosomes playing little or no role.