Effect of collagen vascular disease-associated interstitial lung disease on the outcomes of lung cancer surgery

Abstract

              <span> 
                </span><h3>Purpose</h3> 
                <p>This study compared the effect of collagen vascular disease-associated interstitial lung disease (CVD-ILD) with that of idiopathic interstitial pneumonias (IIPs) on the outcomes of lung cancer surgery.</p> 

              <span> 
                </span><h3>Methods</h3> 
                <p>This study retrospectively reviewed the medical records of patients who underwent surgery for non-small cell lung cancer (NSCLC) and compared the data of 16 patients with CVD-ILD with those of 70 patients with IIPs. The patterns of interstitial lung disease (ILD) on chest computed tomography were classified into usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) patterns.</p> 

              <span> 
                </span><h3>Results</h3> 
                <p>The numbers of UIP and NSIP patterns were 10 (62.5%) and 6 (37.5%) patients in CVD-ILD group, and 62 (88.6%) and 8 (11.4%) patients in IIPs group, respectively. A postoperative acute exacerbation (AE) appeared in 1 patient (6.3%) in the CVD-ILD group and 6 patients (8.6%) in the IIPs group. No significant differences in the incidence of postoperative AE and mortalities were observed between the two groups. The five-year overall survival rates of the CVD-ILD and IIPs groups were 37.5 and 49.2%, respectively.</p> 

              <span> 
                </span><h3>Conclusions</h3> 
                <p>Surgery for NSCLC in CVD-ILD patients appear to cause no increase in postoperative AE and mortality in comparison to that seen in IIPs patients. Similar to IIPs, CVD-ILD might therefore affect the prognosis of resected NSCLC.</p> 
              <br /><br />

http://ift.tt/2m5030m

Morphology of the region anterior to the anal canal in males: visualization of the anterior bundle of the longitudinal muscle by transanal ultrasonography

Abstract

              <span> 
                </span><h3>Purpose</h3> 
                <p>The anterior bundle of the longitudinal muscle in the region anterior to the anal canal in males has been described, although the anatomical details remain unclear. The present study was undertaken to clarify the precise morphology of the anterior bundle of the longitudinal muscle and its relationship to the surrounding structures, and to visualize the anterior bundle of the longitudinal muscle via transanal ultrasonography.</p> 

              <span> 
                </span><h3>Methods</h3> 
                <p>Histological examination was carried out using seven male cadavers; an additional three male cadavers were used for transanal ultrasonography, and the ultrasonography images were compared with the actual sagittal sections. In addition, transanal ultrasonography images of 50 male patients at Tokatsu-Tsujinaka Hospital were studied.</p> 

              <span> 
                </span><h3>Results</h3> 
                <p>The region anterior to the anal canal consisted of smooth muscles and skeletal muscles. The anterior bundle of the longitudinal muscle was situated between the bulbospongiosus and the external anal sphincter, and consisted of smooth muscle. The bundle was identified in the transanal ultrasonography of cadavers by comparison with the actual sections. Transanal ultrasonography images of living bodies showed the anterior bundle of the longitudinal muscle as a hypoechoic layer of approximately 17.7 mm in length.</p> 

              <span> 
                </span><h3>Conclusions</h3> 
                <p>The detailed anatomical findings of the anterior bundle of the longitudinal muscle suggested “an alternate arrangement of smooth muscles and skeletal muscles” in the region anterior to the anal canal and facilitated the visualization of the anterior bundle of the longitudinal muscle in transanal ultrasonography.</p> 
              <br /><br />

http://ift.tt/2lvY0za

Anatomy of the sacral hiatus and its clinical relevance in caudal epidural block

Abstract

              <span> 
                </span><h3>Purpose</h3> 
                <p>Caudal epidural anesthesia (CEB) is widely used for the prevention of chronic lower back pain, the control of intraoperative analgesia such as genitourinary surgery and labor pain cases in sacral epidural space approach for the implementation of analgesia. CEB is an anesthetic solution used into the sacral canal via sacral hiatus (SH). For optimal access into the sacral epidural space, detailed anatomical landmarks of SH are required. This study aims at exploring the anatomical structures and differences of the SH by using the sacral bone as a guide point to failure criteria for reviewing the caudal epidural anesthesia and improving the criteria for success in practice.</p> 

              <span> 
                </span><h3>Materials and methods</h3> 
                <p>Detailed morphometric measurements of orientation points of the SH were taken in 87 sacral bones. The measurements were taken using digital calipers and calculated with photogrammetric methods using Image J program.</p> 

              <span> 
                </span><h3>Results</h3> 
                <p>Most commonly encountered shape of the SH was inverted U (33.33%), while 6.9% 3.45% often lack SH and bifida shape were found. The average length of the SH was 28.7 ± 7.1 mm, the average distance of the intercornual distance was 13.48 ± 2.69 mm, the average of the apex of SH and S2 sacral foramen was 34.68 ± 7.09 mm. There was no statistically significant difference determined in bilateral measurements (<em>p</em> &gt; 0.05). Apex and base of SH were most commonly observed against S4 and S5 vertebrae, respectively. The level of maximum curvature of sacrum was S3 in 62.07% and S4 in 28.78%. Findings of spina bifida level were found 16.13% often in L5–S1 segment. Sacral cornua were marked by their bilateral presence in 55.26% and impalpable in 21.05% cases. Minimum distance between the S2 and the apex of the SH was 7.25 mm which suggested that it would not be safe to push the needle beyond 7 mm into the sacral canal so as to avoid dural puncture. In 8.77% cases, the depth of hiatus was less than 3 mm.</p> 

              <span> 
                </span><h3>Conclusions</h3> 
                <p>Single bony landmark may not help in locating the SH because of the anatomical variations. Important anatomical landmarks of the CEB are the sacral cornu, lateral sacral crests, the apex of the SH, the base of the SH, the top portion of the median sacral crest, anteroposterior distance of the sacral canal, intercornual distance, distance of the apex of the SH to the S2 foramina. Depth of hiatus less than 3 mm may be one of the causes for the failure of needle insertion. Surrounding bony irregularities, different shapes of hiatus and defects in dorsal wall of sacral canal should be taken into consideration before undertaking CEB so as to avoid its failure. This guide can be done by considering the points and securing a successful venture.</p> 
              <br /><br />

http://ift.tt/2lQMGjR

Population pharmacokinetics of ABT-767 in BRCA1 or BRCA2 mutation carriers with advanced solid tumors or in subjects with high grade serous ovarian, primary peritoneal or fallopian tube cancer

Abstract

              <span> 
                </span><h3>Purpose</h3> 
                <p>The objective of the manuscript is to describe the development of a population pharmacokinetic model for ABT-767, a potent and orally bioavailable inhibitor of poly (ADP-ribose) polymerase enzyme, and to evaluate the potential influence of patient demographics and baseline covariates on the pharmacokinetics of ABT-767.</p> 

              <span> 
                </span><h3>Methods</h3> 
                <p>A total of 1809 plasma ABT-767 concentrations from 90 subjects were used for population pharmacokinetic modeling. Covariates screened for influence on pharmacokinetic parameters were body weight, lean body weight, body surface area, albumin, creatinine clearance, serum creatinine, liver function tests, and age. The effect of food on absorption and bioavailability were also evaluated. Model validation was performed using bootstrap analysis and visual predictive check.</p> 

              <span> 
                </span><h3>Results</h3> 
                <p>A two-compartment model with firstorder absorption adequately described the pharmacokinetics of ABT-767. The population estimates of apparent clearance from central compartment (CL/<em>F</em>), volume of central compartment (<em>V</em> 
                          <sub>c</sub>/<em>F</em>), and absorption rate constant (<em>k</em> 
                          <sub>a</sub>) were 7.34 L/h, 25.8 L, 1.45 h<sup>−1</sup>, respectively. The estimates of interindividual variabilities (%CV) in CL/<em>F, V</em> 
                          <sub>c</sub>/<em>F</em>, and <em>k</em> 
                          <sub>a</sub> were 40.4, 40.5, and 53.8%, respectively. The <em>k</em> 
                          <sub>a</sub> was influenced by food. Albumin on CL/<em>F</em> was a statistically significant covariate; however, it explained only 8% of the variability in the pharmacokinetics of ABT-767.</p> 

              <span> 
                </span><h3>Conclusions</h3> 
                <p>Albumin on CL/<em>F</em> was the only statistically significant baseline covariate affecting ABT-767 pharmacokinetics, but it only explained a fraction of the pharmacokinetic variability. Dosage adjustments based on body size, age, or mild renal impairment are not needed for ABT-767. The developed model will be used to evaluate ABT-767 exposure–response analyses and to perform simulations for different dose and dosing regimens.</p> 
              <br /><br />

http://ift.tt/2l9jg1F

Use of Systemic Therapy Concurrent With Cranial Radiotherapy for Cerebral Metastases of Solid Tumors

The incidence of brain metastases of solid tumors is increasing. Local treatment of brain metastases is generally straightforward: cranial radiotherapy (e.g., whole-brain radiotherapy or stereotactic radiosurgery) or resection when feasible. However, treatment becomes more complex when brain metastases occur while other metastases, outside of the central nervous system, are being controlled with systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies). It is known that some anticancer agents can increase the risk for neurotoxicity when used concurrently with radiotherapy. Increased neurotoxicity decreases quality of life, which is undesirable in this predominantly palliative patient group. Therefore, it is of utmost importance to identify the compounds that should be temporarily discontinued when cranial radiotherapy is needed.

This review summarizes the (neuro)toxicity data for combining systemic therapy (chemotherapeutics, molecular targeted agents, or monoclonal antibodies) with concurrent radiotherapy of brain metastases. Because only a limited amount of high-level data has been published, a risk assessment of each agent was done, taking into account the characteristics of each compound (e.g., lipophilicity) and the microenvironment of brain metastasis. The available trials suggest that only gemcitabine, erlotinib, and vemurafenib induce significant neurotoxicity when used concurrently with cranial radiotherapy. We conclude that for most systemic therapies, the currently available literature does not show an increase in neurotoxicity when these therapies are used concurrently with cranial radiotherapy. However, further studies are needed to confirm safety because there is no high-level evidence to permit definitive conclusions. The Oncologist 2017;22:222–235

Implications for Practice: The treatment of symptomatic brain metastases diagnosed while patients are receiving systemic therapy continues to pose a dilemma to clinicians. Will concurrent treatment with cranial radiotherapy and systemic therapy (chemotherapeutics, molecular targeted agents, and monoclonal antibodies), used to control intra- and extracranial tumor load, increase the risk for neurotoxicity? This review addresses this clinically relevant question and evaluates the toxicity of combining systemic therapies with cranial radiotherapy, based on currently available literature, in order to determine the need to and interval to interrupt systemic treatment.

http://ift.tt/2m504Bo

Validation of Progression-Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials

Purpose.

The aim of this study was to investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma.

Materials and Methods.

Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual-level surrogacy was assessed by Kendall’s tau through a Clayton bivariate Copula survival (CBCS) model. Summary-level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least-square (WLS) regression model and the CBCS model.

Results.

The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall’s tau ranging from 0.46 to 0.47. The summary-level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age.

Conclusions.

The analyses demonstrated low to moderate individual-level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. The Oncologist 2017;22:189–198

Implications for Practice: For better disease management and for more efficient clinical trial designs, it is important to know if progression-free survival (PFS) is a good surrogate endpoint for overall survival in malignant mesothelioma. With a relatively large database of 17 phase II trials and 716 patients from Cancer and Leukemia Group B and North Central Cancer Treatment Group, we conducted statistical analyses and found that there is no evidence to suggest that PFS is a valid surrogate endpoint for OS for malignant mesothelioma. Future research work is needed to find alternative surrogate endpoints for OS.

http://ift.tt/2m55qfL

A Phase I/IIa Study of DHP107, a Novel Oral Paclitaxel Formulation, in Patients with Advanced Solid Tumors or Gastric Cancer

Lessons Learned.

Ideally, patients should have access to an oral formulation of paclitaxel, as well as an intravenous formulation, to allow development of regimens exploring alternate schedules and to avoid reactions to Cremophor EL (BASF Corp., Ludwigshafen, Germany, https://www.basf.com).

DHP107 is a novel oral paclitaxel formulation that is a tolerable and feasible regimen for patients with gastric cancer, with data suggesting efficacy similar to that of intravenous paclitaxel.

Background.

We evaluated the maximum tolerated dose (MTD) of DHP107, a novel oral paclitaxel formulation, and the efficacy and safety of the agent in patients with advanced solid tumors.

Patients and Methods.

Phase I study: cohorts of 3–6 patients with advanced solid tumors received escalating DHP107 doses. Phase IIa study: patients with measurable advanced gastric cancer received DHP107, 200 mg/m2 b.i.d., on days 1, 8, and 15 every 4 weeks. Pharmacokinetics, safety, and efficacy were analyzed.

Results.

Phase I: 17 patients received a dose-escalating regimen of DHP107, 150–250 mg/m2 b.i.d. Dose-limiting toxicities were neutropenia and febrile neutropenia. The MTD (recommended dose) for phase IIa was 200 mg/m2 b.i.d. Phase IIa: 11 patients with measurable advanced gastric cancer in whom first-line therapy failed received DHP107 (MTD). Three confirmed partial responses were observed. Median progression-free survival of gastric cancer patients (n = 16) treated at the MTD was 2.97 (95% confidence interval, 1.67–5.40) months (Fig. 1). The most frequent grade 3/4 adverse events were neutropenia (35.3%) and leukopenia (17.6%) at the MTD (phase I and IIa combined; n = 17).

Conclusion.

DHP107 showed good antitumor efficacy and was tolerable. The MTD (200 mg/m2 b.i.d.) is recommended for use in further studies comparing DHP107 with standard intravenous paclitaxel therapy. The Oncologist 2017;22:129–e8

http://ift.tt/2mC62r5

Environmental and Psychosocial Barriers to and Benefits of Cervical Cancer Screening in Kenya

Background.

Cervical cancer is the second most commonly diagnosed cancer in females and is a leading cause of cancer-related mortality in Kenya; limited cervical cancer screening services may be a factor. Few studies have examined men’s and women’s perceptions on environmental and psychosocial barriers and benefits related to screening.

Materials and Methods.

In 2014, 60 women aged 25–49 years and 40 male partners participated in 10 focus groups (6 female and 4 male), in both rural and urban settings (Nairobi and Nyanza, Kenya), to explore perceptions about barriers to and benefits of cervical cancer screening. Focus groups were segmented by sex, language, geographic location, and screening status. Data were transcribed, translated into English, and analyzed by using qualitative software.

Results.

Participants identified screening as beneficial for initiating provider discussions about cancer but did not report it as a beneficial method for detecting precancers. Perceived screening barriers included access (transportation, cost), spousal approval, stigma, embarrassment during screening, concerns about speculum use causing infertility, fear of residual effects of test results, lack of knowledge, and religious or cultural beliefs. All participants reported concerns with having a male doctor perform screening tests; however, men uniquely reported the young age of a doctor as a barrier.

Conclusion.

Identifying perceived barriers and benefits among people in low- and middle-income countries is important to successfully implementing emerging screening programs. The novel findings on barriers and benefits from this study can inform the development of targeted community outreach activities, communication strategies, and educational messages for patients, families, and providers. The Oncologist 2017;22: 173–181

Implications for Practice: This article provides important information for stakeholders in clinical practice and research when assessing knowledge, beliefs, and acceptability of cervical cancer screening and treatment services in low- and middle-resourced countries. Formative research findings provide information that could be used in the development of health interventions, community education messages, and materials. Additionally, this study illuminates the importance of understanding psychosocial barriers and facilitators to cervical cancer screening, community education, and reduction of stigma as important methods of improving prevention programs and increasing rates of screening among women.

http://ift.tt/2m4HtoS

Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Results of a Prospective, Noninterventional Study on Routine Treatment Between 2006 and 2012 in Germany

Purpose.

Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies.

Patients and Methods.

Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature.

Results.

Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%–91.1%) and 82.8% (95% CI, 81.2%–84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%–97.6%) and 90.0% (95% CI, 88.6%–91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade ≥2 and ≥3 was observed in 2.5% and less than 1% of patients, respectively.

Conclusion.

The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). The Oncologist 2017;22:131–138

Implications for Practice: On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany.

http://ift.tt/2mCbJFG