What is the predictive value of RECIST criteria following stereotactic lung radiation?

PURPOSE: Response EvaluationCriteriain Solid Tumors (RECIST) is commonly used to assess response to anti-cancer therapies. However, its application after lung stereotactic ablative radiotherapy (SABR) is complicated by radiation-induced lung changes. This study assesses the frequency of progressive disease (PD) by RECIST following lung SABR and correlates this with actual treatment outcomes as determined by longitudinal follow-up. METHODS AND MATERIALS: We reviewed patients treated with lung SABR for primary lung tumors or oligometastases between 2010 and 2015. Patients were treated with SABR doses of 54-60 Gy in 3-8 fractions. All follow-up scans were assessed and the treated lesion was serially measured over time, with the maximum diameter on axial CT slices used for RECIST calculations. Lesions demonstrating PD by RECIST criteria were identified and subsequently followed for long-term outcomes. The final 'gold-standard' assessment of response was based on size changes after PD and, as available, positron emission tomography scan and/or biopsy. RESULTS: Eighty-eight lesions met inclusion criteria. Seventy-five were lung primaries and thirteen were lung metastases. Median follow-up was 52 months (interquartile range: 33-68). Two-thirds (66 %, 58/88) of treated lesions met RECIST criteria for PD; however, local recurrence was only confirmed in 16 % (9/58) of cases. Most lesions that triggered PD by RECIST (47/58, 81 %) were ultimately found not to represent recurrence, while a minority (2/58, 3 %) had an uncertain response. The positive predictive value [PPV] of a RECIST defined PD event was 0.16. If PD was triggered within 12-months post-treatment, PPV was 0.08, compared to 0.21 for lesions triggering PD after 12-months. CONCLUSION: Using RECIST criteria, two-thirds of patients treated with lung SABR met criteria for PD. However, only a minority had recurrence, leading to a poor PPV of RECIST. This highlights the limitations of RECIST in this setting and provides context for physicians when interpreting post-lung SABR imaging.

A Rare Association of Mixed Autoimmune Hemolytic Anemia with Gastric Carcinoma.

This case report outlines a 70-year-old female patient who presented with a concurrent mixed autoimmune hemolytic anemia (AIHA) and a gastric adenocarcinoma. Her treatment course of these two diseases is summarized, which included supportive care, neoadjuvant chemotherapy for her gastric adenocarcinoma, steroids, rituximab, and surgical resection of the tumor. This approach ultimately led to the stabilization of her AIHA and primary cure for her solid malignancy. We briefly review both AIHA and gastric adenocarcinoma as clinical entities, propose working causes of hemolytic anemia including gastric adenocarcinoma, and outline a successful treatment pathway for these two concurrent conditions.

Stereotactic ablative radiotherapy before resection to avoid delay for early-stage lung cancer or oligometastases during the COVID-19 pandemic: Pathologic outcomes from the SABR-BRIDGE protocol.

BACKGROUND: During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. METHODS: Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. RESULTS: Seventy-two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3-4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well-tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5 months post-SABR (range, 2-17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months; p = .069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. CONCLUSIONS: The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.

Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial.

BACKGROUND: Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. METHODS: We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. RESULTS: CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001). CONCLUSION: The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

The quality of life in neoadjuvant versus adjuvant therapy of esophageal cancer treatment trial (QUINTETT): Randomized parallel clinical superiority trial.

BACKGROUND: We compared the health-related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I-III esophageal cancer. METHODS: A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5-fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5-fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. RESULTS: There was no significant difference in the functional assessment of cancer therapy-esophageal (FACT-E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre-treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT-E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-OG25), and EuroQol 5-D-3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30-day mortalities and 2% vs. 10% 90-day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5-year: 35% vs. 32%, p = 0.409) or disease-free survival (DFS) (5-year: 31% vs. 30%, p = 0.710). CONCLUSION: Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed.

Surgery crisis simulation during the COVID-19 pandemic.

SummaryCOVID-19 puts health care providers at risk for infection with SARS-CoV-2. Personal protective equipment (PPE) can reduce viral transmission if used properly. We used simulation of an intraoperative crisis involving an infectious outbreak to assess PPE adherence and confidence in PPE use. Simulation of an intraoperative crisis with a patient with COVID-19 revealed gaps in PPE adherence; however, simulation training successfully increased confidence in PPE use and received positive feedback.

Predicting pathological complete response (pCR) after stereotactic ablative radiation therapy (SABR) of lung cancer using quantitative dynamic [18F]FDG PET and CT perfusion: a prospective exploratory clinical study.

BACKGROUND: Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [18F]FDG-PET and CT Perfusion (CTP). METHODS: Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [18F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [18F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria. RESULTS: RPA identified three response groups based on tumour blood volume before SABR (BVpre-SABR) and change in SUVmax (ΔSUVmax), the thresholds being BVpre-SABR = 9.3 mL/100 g and ΔSUVmax = - 48.9%. The highest true pCR rate of 92% was observed in the group with BVpre-SABR < 9.3 mL/100 g and ΔSUVmax < - 48.9% after SABR while the worst was observed in the group with BVpre-SABR ≥ 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively). CONCLUSIONS: In this study, we developed a predictive model based on dynamic [18F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BVpre-SABR and ΔSUVmax which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies. TRIAL REGISTRATION: MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, https://clinicaltrials.gov/ct2/show/NCT02136355.

Idiopathic Subglottic Stenosis: An Institutional Review of Outcomes With a Multimodality Surgical Approach.

OBJECTIVES: This article reports on a unique cohort of patients with idiopathic subglottic stenosis spilt fairly equally between endoscopic and open surgical approaches. Patients' sequence of operations and reinterventions over time are outlined, offering insight to improve surgical counseling and allow for informative, autonomous patient decision making. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic center. METHODS: Cases of consecutive adults with idiopathic subglottic stenosis managed surgically over a 12-year period (January 2006-December 2017) were retrospectively reviewed. Surgical workflow, complications, and outcomes, including reinterventions and tracheotomy dependence, are reported. RESULTS: Seventy-two patients (71 women; mean age, 50.4 years) with idiopathic subglottic stenosis requiring surgical airway intervention were identified. Six patients underwent tracheotomy prior to attempt at airway stenosis surgery. Initial surgical approach thereafter included endoscopic (73.5%, n = 53) and open (26.4%, n = 19) procedures. Thirty-one patients underwent cricotracheal resection; the reintervention rate was 22.5%. Sixty patients underwent 147 endoscopic procedures; the reintervention rate was 75.5%, and the mean time between dilations was 83 weeks (range, 5-402). Two (2.8%) patients remain tracheotomy dependent. Adverse events were significantly higher in the cricotracheal group, especially with respect to dysphonia and temporary gastrostomy tube placement (P < .01). CONCLUSIONS: Endoscopic and open surgical airway intervention can be employed successfully to avoid tracheotomy dependence and maintain airway patency; however, multiple procedures are usually required, regardless of surgical approach. Cricotracheal reintervention rates are lower than endoscopic dilation but with increased morbidity. Quality-of-life outcomes should be clearly discussed with patients before deciding on a surgical management strategy.

Measuring the Integration of Stereotactic Ablative Radiotherapy Plus Surgery for Early-Stage Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial.

IMPORTANCE: Stereotactic ablative radiotherapy (SABR) is a standard treatment option in patients with medically inoperable early-stage non-small cell lung cancer (NSCLC), yet the pathologic complete response (pCR) rate after SABR is unknown. Neoadjuvant SABR in patients with cancer who are fit for resection has been hypothesized to improve local control and induce antitumor immune activity, potentially leading to better outcomes. OBJECTIVES: To determine the pCR rate after SABR and to assess oncologic and toxicity outcomes after a combined approach of neoadjuvant SABR followed by surgery. DESIGN, SETTING, AND PARTICIPANTS: A phase 2, single-arm trial, with patient accrual from September 30, 2014, to August 15, 2017 (median follow-up, 19 months), was performed at a tertiary academic cancer center. Patients 18 years or older with T1T2N0M0 NSCLC and good performance status, with adequate pulmonary reserve to undergo surgical resection, were studied. INTERVENTIONS: Patients underwent neoadjuvant SABR using a risk-adapted fractionation scheme followed by surgery 10 weeks later. MAIN OUTCOMES AND MEASURES: The pCR rate as determined by hematoxylin-eosin staining. RESULTS: Forty patients (mean [SD] age, 68 [8] years; 23 [58%] female) were enrolled. Thirty-five patients underwent surgery and were evaluable for the primary end point. The pCR rate was 60% (95% CI, 44%-76%). The 30- and 90-day postoperative mortality rates were both 0%. Grade 3 or 4 toxic effects occurred in 7 patients (18%). In patients receiving surgery, 2-year overall survival was 77% (95% CI, 48%-91%), local control was 100% (95% CI, not defined), regional control was 53% (95% CI, 22%-76%), and distant control was 76% (95% CI, 45%-91%). Quality of life did not decline after treatment, with no significant changes in mean Functional Assessment of Cancer Therapy for Lung-Trial Outcome Index score during the first year of follow-up. CONCLUSIONS AND RELEVANCE: The pCR rate after SABR for early-stage NSCLC was 60%, lower than hypothesized. The combined approach had toxic effects comparable to series of surgery alone, and there was no perioperative mortality. Further studies are needed to evaluate this combined approach compared with surgical resection alone. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02136355.

Assessment of tumour response after stereotactic ablative radiation therapy for lung cancer: A prospective quantitative hybrid 18 F-fluorodeoxyglucose-positron emission tomography and CT perfusion study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) is a guideline-recommended treatment for inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. The goal of this study was to evaluate imaging-based biomarkers of tumour response using dynamic 18 F-FDG-PET and CT perfusion (CTP). METHODS: Thirty-one patients with early-stage NSCLC participated in this prospective correlative study. Each underwent dynamic 18 F-FDG-PET/CTP studies on a PET/CT scanner pre- and 8 weeks post-SABR. The dynamic 18 F-FDG-PET measured the tumour SUVmax , SUVmean and the following parameters: K1 , k2 , k3 , k4 and Ki , all using the Johnson-Wilson-Lee kinetic model. CTP quantitatively mapped BF, BV, MTT and PS in tumours and measured largest tumour diameter. Since free-breathing was allowed during CTP scanning, non-rigid image registration of CT images was applied to minimize misregistration before generating the CTP functional maps. Differences between pre- and post-SABR imaging-based parameters were compared. RESULTS: Tumour size changed only slightly after SABR (median 26 mm pre-SABR vs. 23 mm post-SABR; P = 0.01). However, dynamic 18 F-FDG-PET and CTP study showed substantial and significant changes in SUVmax , SUVmean , k3 , k4 and Ki . Significant decreases were evident in SUVmax (median 6.1 vs. 2.6; P < 0.001), SUVmean (median 2.5 vs. 1.5; P < 0.001), k3 (relative decrease of 52%; P = 0.002), Ki (relative decrease of 27%; P = 0.03), whereas there was an increase in k4 (+367%; P < 0.001). CONCLUSIONS: Hybrid 18 F-FDG-PET/CTP allowed the response of NSCLC to SABR to be assessed regarding metabolic and functional parameters. Future studies are needed, with correlation with long-term outcomes, to evaluate these findings as potential imaging biomarkers of response.

The Potential Dangers of Recruitment Maneuvers During One Lung Ventilation Surgery.

BACKGROUND: Existing evidence regarding lung-protective ventilation (LPV) during one-lung ventilation (OLV) focuses on surrogate outcomes. Our objective was to assess whether an LPV protocol during OLV surgery is associated with reduced respiratory complications. MATERIALS AND METHODS: This was a matched control retrospective cohort study of patients undergoing pulmonary resection at a tertiary Canadian hospital. The experimental group (n = 50) was derived from primary data of two crossover RCTs, which utilized protocolized LPV strategies with varying levels of positive end-expiratory pressure and recruitment maneuvers. The control group was drawn from a prospectively maintained database; these patients received conventional nonprotocolized ventilation (2000-2010). Each experimental group patient was matched 1:1 with a control group patient with respect to clinically relevant variables (age, sex, diagnosis, smoking status, cardiovascular disease status, comorbidity, BMI, preoperative forced expiratory volume in 1 s, surgery type). Major respiratory complications were defined as composite of acute respiratory distress syndrome, need for new positive-pressure ventilation, and atelectasis requiring bronchoscopy. Paired and unpaired statistical tests were used. RESULTS: Patients appeared well matched. Major respiratory complications occurred in 8% (n = 4) and 2% (n = 1) of patients in experimental and control groups, respectively (P = 0.50). There was a trend toward increased mortality (4 versus 0, P = 0.06) with protocolized LPV. The patients who died had respiratory complications; one had acute respiratory distress syndrome and two had profound hypoxemia. CONCLUSIONS: There was a nonsignificant trend toward increased mortality with LPV during OLV. Although limited by a small sample size, our findings identify a potential danger to excessive recruitment maneuvers. Larger studies, with clinically important outcomes are needed to better define the risk/benefit trade-offs for LPV during OLV.

Use of lung-protective strategies during one-lung ventilation surgery: a multi-institutional survey.

BACKGROUND: Limited evidence suggests that intraoperative lung-protective ventilation (LPV) during one-lung ventilation (OLV) may reduce respiratory complications after thoracic surgery. Little is known about LPV practices during OLV. Our purpose was to assess the state of practice/perspectives of anesthesiologists regarding LPV during elective OLV. METHODS: We conducted a multi-institutional cross-sectional survey of anesthesiologists performing OLV at high-volume Canadian tertiary/university centers. The survey was designed, refined and distributed by a multi-disciplinary team using the Dillman method. Univariable and multivariable analyses were used. RESULTS: Seventy-five (63%) of 120 eligible respondents completed the survey. Although the critical care literature focuses on minimizing tidal volume (TV) as the central strategy of LPV, most respondents (89%, n=50/56) focused on minimizing peak airway pressure (PAP) as their primary strategy of intraoperative LPV. Only 64% (n=37/58) reported actively trying to minimize TV. While 32% (n=17/54) were unsure about the current evidence regarding LPV, 67% (n=36/54) believed that the evidence favoured their use during OLV. Perceived clinical and institutional barriers were the only predictors of reduced attempts to minimize TV on univariate analyses. In multivariable/adjusted analyses, perceived institutional barriers were the only predictors of reduced attempts to minimize TV with adjusted odds ratio of 0.1 (95% CI: 0.03-0.6). CONCLUSIONS: Most anesthesiologists defined low PAP as the primary strategy of LPV during OLV and attempted to minimize it. This study is the first to assess the practice/perspectives of anesthesiologists regarding LPV during OLV and also the first to explore predictors of LPV use. Randomized trials are currently ongoing. However, this study suggests that institutional barriers may subvert future knowledge translation and need to be addressed.

Development of an In Situ Thoracic Surgery Crisis Simulation Focused on Nontechnical Skill Training.

BACKGROUND: Our vision was to develop an inexpensive training simulation in a functional operating room (in situ) that included surgical trainees and nursing and anesthesia staff to focus on effective interprofessional communication and teamwork skills. METHODS: The simulation scenario revolved around an airway obstruction by residual tumor after pneumonectomy. This model included our thoracic operating room with patient status displayed by an open access vital sign simulator and a reversibly modified Laerdal airway mannequin (Shavanger, Norway). The simulation scenario was run seven times. Simulations were video recorded and scored with the use of Non-Technical Skills for Surgeons (NOTSS) and TeamSTEPPS2. Latent safety threats (LSTs) and feedback were obtained during the debriefing after the simulation. Feedback was captured with the Method Material Member Overall (MMMO) questionnaire. RESULTS: Several LSTs were identified, which included missing and redundant equipment and knowledge gaps in participants' roles. Consultant surgeons received a higher overall score than thoracic surgery fellows on both NOTSS (3.8 versus 3.3) and TeamSTEPPS2 (4.1 versus 3.2) evaluations, suggesting that the scenario effectively differentiated learners from experts with regards to nontechnical skills. The MMMO overall simulation experience score was 4.7 of 5, confirming a high-fidelity model and useful experiential learning model. At the Canadian Thoracic Bootcamp, the MMMO overall experience score was 4.8 of 5, further supporting this simulation as a robust model. CONCLUSIONS: An inexpensive in situ intraoperative crisis simulation model for thoracic surgical emergencies was created, implemented, and demonstrated to be effective as a proof of concept at identifying latent threats to patient safety and differentiating the nontechnical skills of trainees and consultant surgeons.

Transarterial embolization of intralobar pulmonary sequestration in a young adult with hemoptysis.

Intralobar pulmonary sequestration is a rare congenital malformation characterized by the presence of dysplastic lung that does not communicate with the tracheobronchial tree, and has aberrant systemic arterial supply. While most are asymptomatic, they rarely can present with hemoptysis, which has been traditionally managed with surgical resection of the sequestration. We report a case of an 18-year-old male who presented with acute large-volume hemoptysis on a background of recurrent minor episodes of hemoptysis, due to intralobar sequestration. He was successfully treated with transarterial embolization with a combination of polyvinyl alcohol (PVA) particles, gelfoam and coils. Transarterial embolization can be effective in managing emergent hemoptysis from pulmonary sequestration.

RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy.

BACKGROUND AND OBJECTIVES: Pneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy. METHODS: Retrospective cohort study of consecutive pneumonectomies undertaken at a tertiary hospital (2003-2013). Multivariable logistic regression was performed to adjust for confounding factors. RESULTS: ARDS and respiratory failure occurred in 12.4% (n = 20) and 19.2% (n = 31) of 161 pneumonectomy patients, respectively, and were more likely to occur in transfused patients (P = 0.03, P < 0.001). pRBCs, FFP and platelets were transfused in 27% (n = 43), 6% (n = 9), and 2% (n = 3), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBC use was the only independent predictor of ARDS with odds ratio (OR) = 1.23 (95%CI:1.08-1.39, P = 0.002) and OR = 2.45 (95%CI:1.10-5.49, P = 0.03), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBCs were the only independent predictor of respiratory failure with OR = 1.37 (95%CI:1.16-1.60, P < 0.001) and OR = 3.17 (95%CI:1.25-8.02, P = 0.02), respectively. CONCLUSIONS: Peri-operative pRBC use appears to be an independent risk factor for ARDS and respiratory failure after pneumonectomy. There is a significant dose-response relationship. Platelets and FFP did not appear to increase ARDS risk but this may be due to low utilization.

Short report: interim safety results for a phase II trial measuring the integration of stereotactic ablative radiotherapy (SABR) plus surgery for early stage non-small cell lung cancer (MISSILE-NSCLC).

A phase II trial was launched to evaluate if neoadjuvant stereotactic ablative radiotherapy (SABR) before surgery improves oncologic outcomes in patients with stage I non-small cell lung cancer (NSCLC). We report a mandated interim safety analysis for the first 10 patients who completed protocol treatment. Operable patients with biopsy-proven T1-2 N0 NSCLC were eligible. SABR was delivered using a risk-adapted fractionation (54Gy/3 fractions, 55/5 or 60/8). Surgical resection was planned 10 weeks later at a high-volume center (>200 lung cancer resections annually). Patients were imaged with dynamic positron emission tomography-computed tomography scans using 18F-fludeoxyglucose (18F-FDG-PET CT) and dynamic contrast-enhanced CT before SABR and again before surgery. Toxicity was recorded using CTCAE version 4.0. Twelve patients were enrolled between 09/2014 and 09/2015. Two did not undergo surgery, due to patient or surgeon preference; neither patient has developed toxicity or recurrence. For the 10 patients completing both treatments, median age was 70 (range: 54-76), 60% had T1 disease, and 60% had adenocarcinoma. Median FEV1 was 73% predicted (range: 54-87%). Median time to surgery post-SABR was 10.1 weeks (range: 9.3-15.6 weeks). Surgery consisted of lobectomy (n = 8) or wedge resection (n = 2). Median follow-up post-SABR was 6.3 months. After combined treatment, the rate of acute grade 3-4 toxicity was 10%. There was no post-operative mortality at 90 days. The small sample size included herein precludes any definitive conclusions regarding overall toxicity rates until larger datasets are available. However, these data may inform others who are designing or conducting similar trials. TRIAL REGISTRATION: NCT02136355 . Registered 8 May 2014.

Is it safe to wait? The effect of surgical wait time on survival in patients with non-small cell lung cancer.

BACKGROUND: The effect of surgical wait times on survival in patients with non-small cell lung cancer (NSCLC) remains largely unknown. Our objective was to determine the effect of surgical wait time on survival and incidence of upstaging in patients with stage I and II NSCLC. METHODS: All patients with clinical stage I and II NSCLC who underwent surgical resection in a single centre between January 2010 and December 2011 were reviewed. Analysis was stratified based on preoperative clinical stage. We assessed the effect of wait time on survival using a Cox proportional hazard model with wait time in months as a categorical variable. Incidence of upstaging at least 1 stage was assessed using logistic regression. RESULTS: We identified 222 patients: 180 were stage I and 42 were stage II. For stage I, wait times up to 4 months had no significant effect on survival or incidence of upstaging. For stage II, patients waiting between 2 and 3 months had significantly decreased survival (hazard ratio 3.6, p = 0.036) and increased incidence of upstaging (odds ratio 2.0, p = 0.020) than those waiting 0 to 1 month. For those waiting between 1 and 2 months, there was no significant difference in survival or upstaging. CONCLUSION: We did not identify an effect of wait time up to 4 months on survival or upstaging for patients with stage I NSCLC. For patients with stage II disease, wait times greater than 2 months adversely affected survival and upstaging.

CONTEXTE: En chirurgie, l'effet des temps d'attente sur la survie des patients atteints d'un cancer du poumon non à petites cellules (CPNPC) demeure pour une bonne part inconnu. Notre objectif était de déterminer l'effet des temps d'attente sur la survie et sur l'incidence de la restadification à un niveau plus élevé chez les patients atteints d'un CPNPC de stade I et II. MÉTHODES: Tous les patients présentant un CPNPC clinique de stade I et II ayant subi une résection chirurgicale dans un seul centre entre janvier 2010 et décembre 2011 ont été passés en revue. L'analyse a été stratifiée selon le stade clinique préopératoire. Nous avons évalué l'effet des temps d'attente sur la survie à l'aide d'un modèle de risques proportionnels de Cox, les temps d'attente en mois ayant servi de variable catégorielle. L'incidence de la restadification à la hausse d'au moins un stade a été évaluée par régression logistique. RÉSULTATS: Nous avons recensé 222 patients : 180 de stade I et 42 de stade II. Pour le stade I, les temps d'attente allant jusqu'à 4 mois n'ont eu aucun effet significatif sur la survie ou sur l'incidence de la restadification. Pour les stades II, les patients ayant attendu de 2 à trois 3 mois ont présenté une réduction significative de la survie (risque relatif 3,6, p = 0,036) et une incidence accrue de restadification (rapport des cotes 2,0, p = 0,02) comparativement à ceux qui avaient attendu 1 mois et moins. Chez les patients ayant attendu 1 ou 2 mois, on n'a noté aucune différence significative sur la survie ou la restadification. CONCLUSION: Nous n'avons observé aucun effet d'une attente allant jusqu'à 4 mois sur la survie ou la restadification chez les patients atteints d'un CPNPC de stade I. Pour les patients atteints d'une maladie de stade II, les temps d'attente de plus de 2 mois ont eu un impact négatif sur la survie et la restadification.

Management of necrotizing pneumonia and pulmonary gangrene: a case series and review of the literature.

BACKGROUND: Necrotizing pneumonia is an uncommon but severe complication of bacterial pneumonia, associated with high morbidity and mortality. The availability of current data regarding the management of necrotizing pneumonia is limited to case reports and small retrospective observational cohort studies. Consequently, appropriate management for these patients remains unclear. OBJECTIVE: To describe five cases and review the available literature to help guide management of necrotizing pneumonia. METHODS: Cases involving five adults with respiratory failure due to necrotizing pneumonia admitted to a tertiary care centre and infected with Streptococcus pneumoniae (n=3), Klebsiella pneumoniae (n=1) and methicillin-resistant Staphylococcus aureus (n=1) were reviewed. All available literature was reviewed and encompassed case reports and retrospective reviews dating from 1975 to the present. RESULTS: All five patients received aggressive medical management and consultation by thoracic surgery. Three patients underwent surgical procedures to debride necrotic lung parenchyma. Two of the five patients died in hospital. CONCLUSIONS: Necrotizing pneumonia often leads to pulmonary gangrene. Computed tomography of the thorax with contrast is recommended to evaluate the pulmonary vascular supply. Further study is necessary to determine whether surgical intervention, in the absence of pulmonary gangrene, results in better outcomes.

Management of tumors involving the chest wall including pancoast tumors and tumors invading the spine.

Bronchogenic carcinomas involving the chest wall include tumors invading the ribs and spine, as well as Pancoast tumors. In the past, such neoplasms were considered to be incurable, but with new multimodality regimens, including induction chemoradiation followed by surgery, they can now be completely resected and patients can benefit from prolonged survival. The most important prognostic factors are the completeness of resection and the pathologic nodal status.

Human alveolar epithelial cells attenuate pulmonary microvascular endothelial cell permeability under septic conditions.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are characterised by high-protein pulmonary edema and severe hypoxaemic respiratory failure due to increased permeability of pulmonary microvascular endothelial cells (PMVEC). Alveolar epithelial cells (AEC) contribute importantly to normal alveolar function, and AEC dysfunction in ALI/ARDS is associated with worse outcomes. We hypothesized that AEC can modulate human PMVEC barrier function, and investigated the effects of AEC presence on human PMVEC barrier under septic conditions in vitro. PMVEC isolated from human lung were treated in vitro with septic stimulation (lipopolysaccharide [LPS], a mixture of clinically-relevant cytokines [cytomix], or plasma from patients with severe sepsis), and the trans-PMVEC leak of Evans Blue dye-labeled albumin assessed. PMVEC septic responses were compared in the presence/absence of co-cultured A549 epithelial cell line or primary human AEC. Septic stimulation with LPS, cytomix, or septic plasma induced marked PMVEC hyper-permeability (10.2±1.8, 8.9±2.2, and 3.7±0.2 fold-increase vs. control, respectively, p<0.01 for all). The presence of A549 cells or primary human AEC in a non-contact co-culture model attenuated septic PMVEC hyper-permeability by 39±4% to 100±3%, depending on the septic stimulation (p<0.05). Septic PMVEC hyper-permeability was also attenuated following treatment with culture medium conditioned by previous incubation with either naïve or cytomix-treated A549 cells (p<0.05), and this protective effect of A549 cell-conditioned medium was both heat-stable and transferable following lipid extraction. Cytomix-stimulated PMN-dependent PMVEC hyper-permeability and trans-PMVEC PMN migration were also inhibited in the presence of A549 cells or A549 cell-conditioned medium (p<0.05). Human AEC appear to protect human PMVEC barrier function under septic conditions in vitro, through release of a soluble mediator(s), which are at least partly lipid in nature. This study suggests a scientific and potential clinical therapeutic importance of epithelial-endothelial cross talk in maintaining alveolar integrity in ALI/ARDS.