Diabetes in Trauma Patients: A Potential Gateway to a Medical Home.

BACKGROUND: Diabetes is a major determinant of health outcomes. Trauma patients are disproportionately from lower socioeconomic status, where lack of access to health care prevents timely treatment. Trauma centers could play a role in identifying patients in need of improved glucose management, but the current burden of disease is not known. We assessed the incidence of patients in need of intervention that presented to a level 1 trauma center over a 6-month period. METHODS: A retrospective chart review over 6 months of all trauma patients admitted to a level 1 trauma center was performed. Patients' past medical history (PMH), medication reconciliation, and hemoglobin A1c (HbA1c) were recorded on initial assessment; patients <18 years old, lacking an HbA1c, or missing PMH were excluded. Patients with PMH of diabetes or antihyperglycemic use were classified by HbA1c: well-controlled ≤8.0% or poorly controlled >8.0%. Patients with no history of diabetes or antihyperglycemic use were classified based on their HbA1c: non-diabetic <5.7%, pre-diabetic 5.7-6.4%, and undiagnosed diabetic ≥6.5%. RESULTS: Overall, 1377 patients were identified. After exclusion criteria, 903 patients were classified as follows: 593 (66%) non-diabetics, 160 (18%) pre-diabetics, and 150 (17%) diabetics. Fifteen diabetics were undiagnosed; 39 of the diagnosed diabetics were poorly controlled. Including pre-diabetics, a total of 214 (24%) trauma patients were in need of improved glycemic control. DISCUSSION: One in four trauma patients would benefit from improved outpatient glycemic management, representing a missed opportunity for preventative health care. Trauma centers should develop strategies to meet this need as part of their post-discharge care.

Use of lateral femoral cutaneous nerve blocks by landmark technique is ineffective in decreasing narcotic usage after skin grafts: A retrospective case-control study.

INTRODUCTION: Cutaneous burns are commonly treated with autologous skin grafts. Following skin grafting, many patients complain of pain at the donor site. Donor sites are taken most commonly from the lateral thigh, which is innervated by the lateral femoral cutaneous nerve (LFCN). Use of a LFCN blocks should decrease nociception from the donor site. METHODS: Our group began utilizing LFCN blocks in 2019. Utilizing anatomic landmarks, LFCN blocks were performed on all patients who received autologous skin grafts to reduce perioperative pain. A retrospective cohort study was performed on all patients with 10% or less total body surface areas burns who received an autologous skin graft. A similar cohort from 2016, prior to use of any local or regional analgesia, was used as a historical control. Post-operative enteral and parenteral narcotic analgesics were collected for each post-operative day up to day 5 or discharge (whichever came first) and converted to morphine milligram equivalents (MME) to quantify analgesia after surgery. RESULTS: Chart review identified 55 patients in the 2020 cohort. Fifty-five patients from the 2016 cohort were matched based upon size of skin graft, total body surface area (TBSA) burned, gender, and age. There were no statistically significant differences between the two groups in terms of size of graft, TBSA burned, age, gender, or type of burn. When examining narcotics usage in the immediate perioperative period (days 0-2), we found no difference between the two groups for total MME (113 vs 133, p = 0.28) or IV MME (38 vs 33, p = 0.45). Similar relationships existed in the extended post-operative period (days 1-5) for total MME (149 vs. 188, t = 0.22) or IV MME (37 vs. 50, t = 0.25). Examining daily narcotic usage also yielded no statistically different values. CONCLUSION: Our data shows that use of LFCN block by landmark technique did not reduce narcotic usage in patients that undergo skin grafting procedures. Future studies should consider ultrasound-guided LFCN blocks.

Diagnostic Inaccuracies Using Extended Focused Assessment With Sonography in Trauma for Traumatic Pneumothorax.

BACKGROUND: Traumatic pneumothorax (PTX) can be deadly, and rapid diagnosis is vital. Ultrasound (US) is rapidly gaining acceptance as an accurate bedside diagnostic tool. While making the diagnosis is important, not all PTX require tube thoracostomy. Our goal was to evaluate the predictive ability of ultrasound in identifying clinically significant PTX. METHODS: Over 13 months, data was collected on patients undergoing evaluation for trauma. Patients were included if they underwent US, radiograph chest X-ray (CXR), and computed tomography of the chest. Predictive ability of ultrasound was evaluated in identifying clinically significant PTX. RESULTS: Ninety-four patients received evaluation by all 3 modalities. Of these, 32% were diagnosed with PTX. Sixteen patients (17%) had a clinically significant PTX. Chest X-ray and US both had a sensitivity of 75%; however, US had more than twice as many false positives, resulting in a much lower positive predictive value (63% vs 80%). CONCLUSIONS: While US can reliably rule out PTX, it may be overly sensitive diagnosing clinically significant PTX. Ultrasound alone should not be used in determining the need for tube thoracostomy as many patients will not require acute intervention.

Association Between Adverse Childhood Experiences and Posttraumatic Stress Disorder Symptoms in Adults With Injury.

This case-control study examines the risk factors associated with acute stress disorder in patients with severe injury.

Cryoablation for Chest Wall Trauma: A Brief Report.

Respiratory failure secondary to rib fractures is a major source of morbidity and mortality in trauma patients, particularly in older populations. Management of pain in these patients is complex due to the nature of the injuries. We present 3 patients who underwent a video-assisted thoracoscopic cryoablation of intercostal nerves for pain control after chest trauma. None of the patients developed post-operative complications related to poor respiratory status such as pneumonia or atelectasis. At one-month clinic follow-up, all patients reported no chest pain and were not using opiate analgesics. In patients for whom there is a contraindication to rib fixation in the setting of unstable rib fractures, cryoablation may be a method by which to improve respiratory status and decrease ventilator dependency due to pain. Cryoablation of intercostal nerves may provide a more durable and clinically feasible solution to aid in the healing process of these patients.

Unexpected Diaphragmatic Hernia Among Patients Undergoing Video-Assisted Thoracic Surgery for Internal Fixation of Rib Fractures.

Traumatic blunt diaphragm injuries are a diagnostic challenge in trauma. They may be missed due to the increasing trend of non-operative management of patients. The purpose of this study was to review the rate of occult blunt diaphragm injuries in patients who underwent video assisted thoracic surgery (VATS) for rib fixation. This retrospective study included patients that received VATS as part of our institutional protocol for rib fracture management. This includes utilizing incentive spirometry, multimodal analgesia, and early consideration for VATS. Data was abstracted from the electronic medical record and included demographics, operative findings, and outcomes. Thirty patients received VATS per our rib fracture protocol. No patients had any identified diaphragm injury on pre-operative imaging. A concomitant diaphragm injury was identified in 20% (6/30) of the study population. All patients were alive at 30 days. For all patients, total hospital length of stay was 14.5 days, ICU length of stay was 8.9 days, and average ventilator days was 4.2 days. When comparing patients with and without concomitant diaphragm injuries, hospital length of stay was 16.8 days vs. 14.5 (P = 0.59), ICU length of stay was 11.8 days vs. 8.2 (P = 0.54), and ventilator days was 4.5 days vs. 4.2 (P = 0.93). This study revealed that 20% of patients undergoing VATS for rib fracture fixation had a concomitant diaphragm injury. This higher-than-expected prevalence suggests that groups of patients sustaining blunt trauma may have occult diaphragmatic injuries that are otherwise unidentified. This raises the need for improved diagnostic modalities to identify these injuries.

Reducing Health Care Burden of Emergency General Surgery with a 24-Hour Dedicated Emergency General Surgery Service.

BACKGROUND: Emergency general surgery (EGS) diagnoses account for 11% of surgical admissions and 50% of surgical mortality. In this population, 7 specific operations are associated with 80.3% of deaths, 78.9% of complications, and 80.2% of hospital costs. In 2016, our institution established a comprehensive in-house EGS service. Herein, we hypothesize that formation of a dedicated EGS service is associated with a significant reduction in morbidity for patients undergoing the most common EGS procedures. METHODS: All patients undergoing one of the most common EGS procedures within 2 days of admission were identified from 1/1/2013 to 5/9/2019 via a retrospective chart review. Patients were cohorted as pre- and post-EGS implementation. The primary outcome measure was the overall complication rate. Secondary endpoints included mortality, individual complication rate, time to operation, overnight operation, and length of stay. Finally, both cohorts were benchmarked to national outcomes. RESULTS: 718 patients met inclusion criteria (pre-EGS = 409 and post-EGS = 309). Overall complication rate decreased significantly (19.8% vs 13.9%, P = .0387) and overnight operations increased significantly in the post-EGS group (7.8%-16.5%, P = .0003). Pre-EGS complications were higher than national data in all but 1 procedure group, whereas post-EGS complications rates were lower in all but 2 categories. DISCUSSION: Implementation of a dedicated EGS service line was associated with a significant decrease in complication rate among the most complication-prone EGS procedures. Number of operations within 24 hours did not increase significantly; however, overnight operations did increase. Our results indicate that establishing a service-specific EGS line is reasonable and beneficial.

Presentation, Management, and Women's Health Implications of Pilonidal Disease.

Many people think of pilonidal disease (PD) in its acute presentation, which is an abscess at the gluteal cleft that is warm and tender with purulent drainage. In this article, we describe how PD is an acute, chronic, and recurring disease that requires clinicians to be vigilant in assessments, treatments, therapies, referrals, and patient education. Because PD is more common in men than women, it is often misdiagnosed and undertreated in female patients. Its impact on an individual's life, work, and health, however, cannot be underestimated. Obtaining an accurate diagnosis and appropriate care can positively impact quality of life for people with PD.

Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective.

The ros1 kinase is an oncogenic driver in non-small-cell lung cancer (nsclc). Fusion events involving the ROS1 gene are found in 1%-2% of nsclc patients and lead to deregulation of a tyrosine kinase-mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. ROS1 fusion is a distinct molecular subtype of nsclc, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology. Targeted inhibition of the aberrant ros1 kinase with crizotinib is associated with increased progression-free survival (pfs) and improved quality-of-life measures. As the sole approved treatment for ROS1-rearranged nsclc, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the ROS1 rearrangement. Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced nsclc, regardless of clinical characteristics, be tested for ROS1 rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced nsclc. If a ROS1 rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop.

Canadian perspectives: update on inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

Background: Inhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a consensus update. Methods: Clinical trials of alk inhibitor were reviewed to assess benefits, risks, and implications relative to current Canadian guidance in patients with ALK-positive nsclc. Results: Randomized phase iii trials have demonstrated clinical benefit for single-agent alectinib and ceritinib used in treatment-naïve patients and as second-line therapy after crizotinib. Phase ii trials have demonstrated activity for single-agent brigatinib and lorlatinib in further lines of therapy. Improved responses in brain metastases were observed for all second- and next/third-generation alk tyrosine kinase inhibitors in patients progressing on crizotinib. Canadian recommendations are therefore revised as follows:■ Patients with advanced nonsquamous nsclc have to be tested for the presence of an ALK rearrangement.■ Treatment-naïve patients with ALK-positive disease should initially be offered single-agent alectinib or ceritinib, or both sequentially.■ Crizotinib-refractory patients should be treated with single-agent alectinib or ceritinib, or both sequentially.■ Further treatments could include single-agent brigatinib or lorlatinib, or both sequentially.■ Patients progressing on alk tyrosine kinase inhibitors should be considered for pemetrexed-based chemotherapy.■ Other systemic therapies should be exhausted before immunotherapy is considered. Summary: Multiple lines of alk inhibition are now recommended for patients with advanced nsclc with an ALK rearrangement.

Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer.

For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents-atezolizumab, nivolumab, and pembrolizumab-have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting. Demonstration of the significant benefits of immunotherapy in nsclc has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced nsclc and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced nsclc.

Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases.

Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

Real-world benefit of nivolumab in a Canadian non-small-cell lung cancer cohort.

Background: Nivolumab was the first immuno-oncology agent available for the treatment of lung cancer in Canada. In the present study, we evaluated the real-world benefit of nivolumab in Canadian patients with lung cancer. Methods: Patients included in the cohort were identified from a registry of patients treated through expanded access to nivolumab before and after Health Canada approval. Demographics were collected from the application forms. Outcome data for the duration of treatment and survival were collected retrospectively. Results: In contrast to the randomized clinical trial populations, our study cohort included patients who were older (median age: 66 years; range: 36-92 years) and who had an Eastern Cooperative Oncology Group performance status of 2 (8.9%). Despite the poorer-prognosis cohort, median overall survival was 12.0 months, which is comparable to the survival demonstrated in the randomized phase iii trials of nivolumab in lung cancer. Median time to treatment discontinuation was 3.45 months and was similar for all patient subgroups, including poorer-prognosis groups such as those with a performance status of 2, those 75 years of age and older, and those with brain metastases. Conclusions: Nivolumab given in a real-world clinical setting was associated with results similar to those reported in the phase iii clinical trial setting.

Management of EGFR-mutated non-small-cell lung cancer: practical implications from a clinical and pathology perspective.

Starting in the early 2000s, non-small-cell lung cancer (nsclc) subtypes have evolved from being histologically described to molecularly defined. Management of lung adenocarcinomas now generally requires multiple molecular tests at baseline to define the optimal treatment strategy. More recently, second biopsies performed at progression in patients treated with tyrosine kinase inhibitors (tkis) have further defined the continued use of molecularly targeted therapy. In the present article, we focus on one molecular subtype: EGFR-mutated nsclc. For that patient population, multiple lines of tki therapy are now available either clinically or in clinical trials. Each line of treatment is guided by the specific mutations (for example, L858R, T790M, C797S) identified in EGFR. We first describe the various mechanisms of acquired resistance to EGFR tki treatment. We then focus on strategies that clinicians and pathologists can both use during tissue acquisition and handling to optimize patient results. We also discuss future directions for the molecular characterization of lung cancers with driver mutations, including liquid biopsies. Finally, we provide an algorithm to guide treating physicians managing patients with EGFR-mutated nsclc. The same framework can also be applied to other molecularly defined nsclc subgroups as resistance patterns are elucidated and additional lines of treatment are developed.

Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model.

BACKGROUND: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). MATERIALS AND METHODS: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. RESULTS: Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CONCLUSION: CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

Controlling intraoperative hemorrhage during burn surgery: A prospective, randomized trial comparing NuStat® hemostatic dressing to the historic standard of care.

INTRODUCTION: One of the primary intraoperative challenges during burn surgery is to adequately excise the burn while avoiding massive hemorrhage. This has become increasingly important, as we see more burn patients that are older and with more medical comorbidities. While adequate excision down to healthy tissues for deep burns is essential for skin graft to take, it also leads to active bleeding that can be a challenge to control. Good hemostasis is imperative as a hematoma is the most common cause of graft loss. Several new products have become available to help control intraoperative hemorrhage. A new hemostatic dressing, NuStat®, is available and approved by FDA in United States. METHODS: A single institution prospective randomized control trial was completed at Regional Burn Center of the University of South Alabama comparing NuStat® with the institutional historic standard of care. Twenty such patients were included in our study. A cost analysis was also completed as part of the study retrospectively. RESULTS: For dressings used to treat the burn site, blood loss on the side treated with NuStat® was on average less (27g/100cm2) than the side treated with our historic standard of care (31g/100cm2), though it was not statistically significant (p=0.81). Similarly, on the donor site, blood loss on the side treated with NuStat® was on average less (14g/100cm2) than the side treated with our historic standard of care (15g/100cm2), but it was also not statistically significant (p=0.92). Average total blood loss from both excision and donor sites was also less with NuStat® (10g/100cm2) compared to the historic standard of care (12g/100cm2), but it was also not significant (p=0.77). There was no difference in the number of cycles required to achieve hemostasis for either the burn (1.15 NuStat® vs. 1.1 for historic standard of care, p=0.70) or the donor site (1 vs. 1, p=1.0). When comparing the cost of NuStat® versus the historic standard of care, the actual costs incurred for the wounds was less for the portion treated with NuStat® ($148.43) when compared to the historic standard of care ($186.45) (p<0.001). CONCLUSIONS: Based on these findings, NuStat® hemostatic action should be comparable to the historic standard of care, and these newer hemostatic agents evaluated further in burn surgery and bleeding during other procedures such as trauma surgery.

Waiting Time Intervals for Non-small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays.

AIMS: Very little is known regarding the time required to diagnose and treat patients with non-small cell lung cancer (NSCLC) in Canada. We sought to quantify diagnostic and treatment intervals for NSCLC care in Alberta and identify risk factors for delays. MATERIALS AND METHODS: The Alberta Cancer Registry identified all cases of stage I-III NSCLC diagnosed and treated in Alberta, Canada from 2004 to 2011. Diagnostic data were obtained from physician billing, inpatient/outpatient hospital data and electronic medical records to quantify the duration of diagnostic and treatment intervals and their sum (system interval). Multivariable logistic regression was carried out to identify factors associated with delays. RESULTS: Of the 3009 eligible patients included, the median and 90th percentile system interval was 78 (95% confidence interval 76-80) and 185 days (95% confidence interval 178-195), respectively. The treatment interval was longer than the diagnostic interval, with medians of 51 (95% confidence interval 49-53) and 38 (95% confidence interval 36-40) days, respectively. After adjustment, age > 60 years and treatment by modalities other than supportive care (especially surgery) were associated with delays. Factors associated with prompt care included high acuity presentations and stage III disease. CONCLUSION: The majority of Albertans with potentially curable NSCLC exceeded guidelines for the timeliness of their care.

Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered.

Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses.

BACKGROUND: Tecemotide is a MUC1-antigen-specific cancer immunotherapy. The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy. Here, we attempted to gain further insight into the effects of tecemotide in START. PATIENTS AND METHODS: START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer. We present updated overall survival (OS) data and exploratory analyses of OS for baseline biomarkers: soluble MUC1 (sMUC1), antinuclear antibodies (ANA), neutrophil/lymphocyte ratio (NLR), lymphocyte count, and HLA type. RESULTS: Updated OS data are consistent with the primary analysis: median 25.8 months (tecemotide) versus 22.4 months (placebo) (HR 0.89, 95% CI 0.77-1.03, P = 0.111), with ∼20 months additional median follow-up time compared with the primary analysis. Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinically relevant prolonged OS with tecemotide versus placebo (29.4 versus 20.8 months; HR 0.81, 95% CI 0.68-0.98, P = 0.026). No improvement was seen with sequential chemoradiotherapy. High sMUC1 and ANA correlated with a possible survival benefit with tecemotide (interaction P = 0.0085 and 0.0022) and might have future value as biomarkers. Interactions between lymphocyte count, NLR, or prespecified HLA alleles and treatment effect were not observed. CONCLUSION: Updated OS data support potential treatment benefit with tecemotide in patients treated with concurrent chemoradiotherapy. Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit. CLINICALTRIALSGOV NUMBER: NCT00409188.

Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations.

Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in medline, embase, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations.