[Acquired thrombotic thrombocytopenic purpura during durvalumab monotherapy for non-small cell lung cancer].

Immune checkpoint inhibitor (ICI)-induced thrombocytopenias are rare immune-related adverse events (irAE), but ICI-related thrombotic thrombocytopenic purpura (TTP) is extremely rare. A 79-year-old woman with non-small cell lung cancer received maintenance therapy with the anti-human PD-L1 monoclonal antibody durvalumab. Four weeks after the last infusion, she developed overt TTP. Remission was achieved by plasma exchange and prednisolone, and the patient has now been recurrence-free for over 12 months. To our knowledge, this is the first report of TTP occurring as an irAE of durvalumab.

Prophylactic pegfilgrastim reduces febrile neutropenia in ramucirumab plus docetaxel after chemoimmunotherapy in advanced NSCLC: post hoc analysis from NEJ051.

Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.

Real-world safety of first-line immuno-oncology combination therapies for advanced non-small-cell lung cancer.

Aim: Real-world adverse event (AE) data are limited for first-line (1L) treatments in advanced non-small-cell lung cancer (NSCLC). Methods: Using Flatiron Health Spotlight data, information for a pre-specified list of AEs was abstracted and described among patients with advanced NSCLC receiving 1L nivolumab + ipilimumab (NIVO + IPI), NIVO + IPI + chemotherapy and other approved immuno-oncology (IO) therapy + chemotherapy combination therapies. Results: Fatigue, pain, dyspnea, weight loss, decreased appetite, diarrhea, nausea/vomiting, cough, constipation and rash were the most common AEs. Rates of AEs were generally numerically similar across the three cohorts. The majority of patients received treatment for AEs and approximately one fourth of the patients had hospitalization due to their AEs. Conclusion: The real-world safety experiences of patients treated with 1L NIVO + IPI-based regimens were in general similar to those treated with other approved IO + chemotherapy combination therapies.

Immuno-oncology (IO) therapies boost the immune system to fight cancer cells and have been approved to treat non-small-cell lung cancer (NSCLC). The IO combination of nivolumab + ipilimumab (NIVO + IPI) is approved to treat NSCLC that has spread to other parts of the body or come back and at least 1% of the tumor cells express a protein called PD-L1; NIVO + IPI is also approved in combination with a short course chemotherapy, independent of tumor PD-L1 expression. While NIVO + IPI-based regimens are generally safe, some patients experienced side effects during the clinical trial. However, there is limited information on the side effects of these treatments in a real-world setting. This study analyzed data on side effects from a de-identified database of patients with advanced NSCLC who were treated with NIVO + IPI, NIVO + IPI + chemotherapy, or other approved IO + chemotherapy combinations based on information obtained from physicians' notes in clinical practice settings. The most common side effects among patients in all groups were tiredness, pain, shortness of breath, weight loss, decreased appetite, diarrhea, nausea/vomiting, cough, constipation and rash. The rates at which the side effects occurred were numerically similar regardless of the specific treatment that patients received. Approximately one-quarter of patients in each treatment group were hospitalized because of a side effect. These results show that in a real-world setting, NIVO + IPI-based regimens have similar safety to other IO + chemotherapy combinations when used as a first treatment for NSCLC that has spread or come back.

Rapid Discharge After Anatomic Lung Resection: Is Ambulatory Surgery for Early Lung Cancer Possible?

BACKGROUND: Given resource constraints during the coronavirus disease 2019 pandemic, we explored whether minimally invasive anatomic lung resections for early-stage lung cancer could undergo rapid discharge. METHODS: All patients with clinical stage I-II non-small cell lung cancer from September 2019 to June 2022 who underwent minimally invasive anatomic lung resection at a single institution were included. Patients discharged without a chest tube <18 hours after operation, meeting preset criteria, were considered rapid discharge. Demographics, comorbidities, operative details, and 30-day outcomes were compared between rapid discharge patients and nonrapid discharge "control" patients. Multivariable logistic regression was performed for predictors of nonrapid discharge. RESULTS: Overall, 430 patients underwent resection (200 lobectomies and 230 segmentectomies); 162 patients (37%) underwent rapid discharge and 268 patients (63%) were controls. The rapid discharge group was younger (66.5 vs 70.0 years; P < .001), was assigned to lower American Society of Anesthesiologists class (P = .02), had more segmentectomies than lobectomies (P = .003), and had smaller tumors (P < .001). There were no differences between groups in distance from home to hospital (P = .335) or readmission rates (P = .39). Increasing age had higher odds for nonrapid discharge (odds ratio, 1.04; 95% CI, 1.02-1.07), whereas segmentectomy had decreased odds (odds ratio, 0.46; 95% CI, 0.28-0.75). CONCLUSIONS: Approximately 37% of the patients underwent rapid discharge after operation with similar readmission rate to controls. Increasing age had higher odds for nonrapid discharge; segmentectomy was likely to lead to rapid discharge. Consideration of rapid discharge minimally invasive lung resection for early-stage lung cancer can result in significant reduction in inpatient resources without adverse patient outcomes.

Metformin in Conjunction With Stereotactic Radiotherapy for Early-stage Non-small Cell Lung Cancer: Long-term Results of a Prospective Phase II Clinical Trial.

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is increasingly detected in early stages and there is interest in improving outcomes with stereotactic body radiotherapy (SBRT). As metformin affects NSCLC signaling pathways, it might alter the metabolism of NSCLC treated with SBRT. This study investigated the long-term outcomes of a phase II clinical trial evaluating metformin in conjunction with SBRT for early-stage NSCLC. PATIENTS AND METHODS: The trial evaluated patients with American Joint Commission on Cancer (AJCC) 7th edition Stage I-II, cT1-T2N0M0 NSCLC who were randomized 6:1 to receive metformin versus placebo in conjunction with SBRT. The outcomes analyzed included local failure (LF), progression-free survival (PFS), overall survival (OS), and Common Terminology Criteria for Adverse Events (CTCAE) version 4 toxicities. RESULTS: There were 14 patients randomized to the metformin arm and one to the placebo. Median follow-up was four years. In the metformin group, the median PFS was 4.65 years [95% confidence interval (CI)=0.31-5.93] and median survival was 4.97 years (95%CI=3.05-4.61). Five year PFS was 27.8% (95%CI=5.3-57.3%) and OS was 46.0% (95%CI=16.0-71.9%). The one patient randomized to placebo was alive and without progression at five years. There were no LFs in the primary SBRT treatment volumes and no CTCAE version 4 Grade ≥3 adverse events. CONCLUSION: Outcomes of SBRT and metformin for early-stage NSCLC were similar to historic controls. These findings along with the results of the NRG-LU001 and OCOG randomized trials do not support the therapeutic use of metformin for NSCLC.

Dosimetric comparison of five different radiotherapy treatment planning approaches for locally advanced non-small cell lung cancer with sequential plan changes.

BACKGROUND: The purpose of this study was to compare the dosimetric characteristics of five different treatment planning techniques for locally advanced non-small cell lung cancer (LA-NSCLC) with sequential plan changes. METHODS: A total of 13 stage III NSCLC patients were enrolled in this study. These patients had both computed tomography (CT) images for initial and boost treatment plans. The latter CT images were taken if tumor shrinkage was observed after 2 weeks of treatment. The prescription dose was 60 Gy/30 Fr (initial: 40 Gy/20 Fr, and boost: 20 Gy/10 Fr). Five techniques (forward-planed 3-dimensional conformal radiotherapy [F-3DCRT] on both CT images, inverse-planned 3DCRT [I-3DCRT] on both CT images, volumetric modulated arc therapy [VMAT] on both CT images, F-3DCRT on initial CT plus VMAT on boost CT [bVMAT], and hybrid of fixed intensity-modulated radiotherapy [IMRT] beams and VMAT beams on both CT images [hybrid]) were recalculated for all patients. The accumulated doses between initial and boost plans were compared among all treatment techniques. RESULTS: The conformity indexes (CI) of the planning target volume (PTV) of the five planning techniques were 0.34 ± 0.10, 0.57 ± 0.10, 0.86 ± 0.08, 0.61 ± 0.12, and 0.83 ± 0.11 for F-3DCRT, I-3DCRT, VMAT, bVMAT, and hybrid, respectively. In the same manner, lung volumes receiving >20 Gy (V20Gy ) were 21.05 ± 10.56%, 20.86 ± 6.45, 19.50 ± 7.38%, 19.98 ± 10.04%, and 17.74 ± 7.86%. There was significant improvement about CI and V20Gy for hybrid compared with F-3DCRT (p < 0.05). CONCLUSION: The IMRT/VMAT hybrid technique for LA-NSCLC patients improved target CI and reduced lung doses. Furthermore, if IMRT was not available initially, starting with 3DCRT might be beneficial as demonstrated in the bVMAT procedure of this study.

A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer.

BACKGROUND: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab. METHODS: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor ß receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive. RESULTS: This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available. CONCLUSIONS: The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort. TRIAL REGISTRATION: Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

Cryoablation is superior to radiofrequency ablation for the treatment of non-small cell lung cancer: A meta-analysis.

This meta-analytical study compared the efficacy of cryoablation and radiofrequency ablation (RFA) in treating non-small cell lung cancer (NSCLC). We searched PubMed, Cochrane, Embase, and Web of Science™ for all relevant articles published until April 2022 that compared the efficacy of RFA and cryoablation in treating NSCLC. We used the Cochrane evaluation tool to assess the risk of bias. The fixed- or random-effects models were used, when appropriate. The primary outcome was a 3-year disease-free survival, whereas recurrence rate and complication rates were secondary outcomes. There were 340 patients divided across the seven studies we included in our meta-analysis. Based on the continuous-type variable analysis, cryoablation was superior to RFA in terms of 3-year disease-free survival (P = 0.003) and complication (P ＜ 0.00001) rates. Similarly, significant reductions in cryoablation were found for recurrence rates (P = 0.05) compared with RFA. Overall, cryoablation was superior to RFA in terms of prognosis and lifespan, regardless of whether systemic metastases occurred in non-small cell lung cancer.

Impact of Environmental Exposures on Lung Cancer in Patients Who Never Smoked.

BACKGROUND: Despite the rising incidence of lung cancer in patients who never smoked, environmental risk factors such as ambient air pollution in this group are poorly described. Our objective was to identify the relationship of environmental exposures with lung cancer in patients who never smoked. METHODS: A prospectively collected database was reviewed for all patients with non-small cell lung carcinoma (NSCLC) who underwent resection from 2006 to 2021. Environmental exposures were estimated using the geocoded home address of patients. Logistic regression was used to determine the association of clinical and environmental variables with smoking status. Kaplan-Meier and Cox proportional hazards analyses were used to assess survival. RESULTS: A total of 665 patients underwent resection for NSCLC, of which 67 (10.1%) were patients who never smoked and 598 (89.9%) were current/former smokers. Patients who never smoked were more likely of white race (p = 0.001) and had well-differentiated tumors with carcinoid or adenocarcinoma histology (p < 0.001). Environmental exposures were similar between groups, but patients who never smoked had less community material deprivation (p = 0.002) measured by household income, education, health insurance, and vacancies. They had improved overall survival (p = 0.012) but equivalent cancer recurrence (p = 0.818) as those who smoked. In univariable Cox analyses, fine particulate matter (HR: 1.447 [95% CI 1.197-1.750], p < 0.001), distance to nearest major roadway (HR: 1.067 [1.024-1.111], p = 0.002), and greenspace (HR: 0.253 [0.087-0.737], p = 0.012) were associated with overall survival in patients who never smoked. CONCLUSIONS: Lung cancer patients who never smoked have unique clinical and pathologic characteristics, including higher socioeconomic status. Interventions to reduce environmental exposures may improve lung cancer survival in this population.

Targeted Toxicities: Protocols for Monitoring the Adverse Events of Targeted Therapies Used in the Treatment of Non-Small Cell Lung Cancer.

Targeted therapies have revolutionized the treatment for many patients with non-small cell lung cancer (NSCLC). Multiple new oral targeted therapies have been approved in the last decade; however, their overall efficacy may be reduced by poor adherence, treatment interruptions, or dose reductions due to adverse events. Most institutions lack standard monitoring protocols for toxicities from these targeted agents. This review describes important adverse events observed in clinical trials and reported by the U.S. Food and Drug Administration for both currently approved and upcoming promising therapies in the treatment of NSCLC. These agents cause a range of toxicities, including dermatologic, gastroenteric, pulmonary, and cardiac toxicities. This review proposes protocols for routine monitoring of these adverse events, both prior to initiation of therapy and while on treatment.

Platinum-combination chemotherapy with or without immune-checkpoint inhibitor in patients with postoperative recurrent non-small cell lung cancer previously treated with adjuvant platinum-doublet chemotherapy: A multicenter retrospective study.

BACKGROUND: Rechallenge with platinum-combination chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) after disease progression on platinum-combination chemotherapy occasionally leads to a favorable response. The efficacy and safety of platinum-combination chemotherapy with or without immune-checkpoint inhibitor (ICI) for patients with recurrent NSCLC after surgery followed by adjuvant platinum-doublet chemotherapy remains uncertain. METHODS: Patients who relapsed after surgery plus adjuvant platinum-doublet chemotherapy and received platinum-combination chemotherapy with or without ICI between April 2011 and March 2021 at four Nippon Medical School hospitals were retrospectively analyzed. RESULTS: Among 177 patients who received adjuvant platinum-doublet chemotherapy after surgery, a total of 30 patients who received platinum-combination rechemotherapy with or without ICI after relapse were included in this study. Seven patients received ICI-combined chemotherapy. The median disease-free survival (DFS) after surgery was 13.6 months. The objective response rate and disease-control rate were 46.7% and 80.0%, respectively. The median progression-free survival and overall survival were 10.2 and 37.5 months, respectively. Patients with longer DFS (≥12 months) had a better prognosis than others. The most common grade ≥3 toxicity associated with this treatment was neutropenia (33%). Grade ≥3 immune-related adverse events were pneumonitis (14%) and colitis (14%). Treatment-related deaths did not occur in this study. CONCLUSION: Platinum-combination chemotherapy with or without ICI for patients with postoperative recurrent NSCLC who previously received adjuvant platinum-doublet chemotherapy was effective and safe. In particular, this therapy may be promising for patients with longer DFS.

Current knowledge of small cell lung cancer transformation from non-small cell lung cancer.

Lung cancer is the leading cause of cancer related death, and is divided into two major histological subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Histological transformation from NSCLC to SCLC has been reported as a mechanism of treatment resistance in patients who received tyrosine kinase inhibitors (TKIs) targeting EGFR, ALK and ROS1 or immunotherapies. The transformed histology could be due to therapy-induced lineage plasticity or clonal selection of pre-existing SCLC cells. Evidence supporting either mechanism exist in the literature. Here, we discuss potential mechanisms of transformation and review the current knowledge about cell of origin of NSCLC and SCLC. In addition, we summarize genomic alterations that are frequently observed in both "de novo" and transformed SCLC, such as TP53, RB1 and PIK3CA. We also discuss treatment options for transformed SCLC, including chemotherapy, radiotherapy, TKIs, immunotherapy and anti-angiogenic agents.

The evolution of lung cancer and impact of subclonal selection in TRACERx.

Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource.

Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I.

BACKGROUND: An important issue for patients with cancer treated with novel therapeutics is how they weigh the effects of treatment on survival and quality of life (QOL). We compared QOL in patients enrolled to SWOG S1400I, a substudy of the LungMAP biomarker-driven master protocol. METHODS: SWOG S1400I was a randomized phase III trial comparing nivolumab plus ipilimumab vs nivolumab for treatment of immunotherapy-naïve disease in advanced squamous cell lung cancer. The primary endpoint was the MD Anderson Symptom Inventory-Lung Cancer severity score at week 7 and week 13 with a target difference of 1.0 points, assessed using multivariable linear regression. A composite risk model for progression-free and overall survival was derived using best-subset selection. RESULTS: Among 158 evaluable patients, median age was 67.6 years and most were male (66.5%). The adjusted MD Anderson Symptom Inventory-Lung Cancer severity score was 0.04 points (95% confidence interval [CI] = -0.44 to 0.51 points; P = .89) at week 7 and 0.12 points (95% CI = -0.41 to 0.65; P = .66) at week 13. A composite risk model showed that patients with high levels of appetite loss and shortness of breath had a threefold increased risk of progression or death (hazard ratio [HR] = 3.06, 95% CI = 1.88 to 4.98; P < .001) and that those with high levels of both appetite loss and work limitations had a fivefold increased risk of death (HR = 5.60, 95% CI = 3.27 to 9.57; P < .001)-compared with those with neither risk category. CONCLUSIONS: We found no evidence of a benefit of ipilimumab added to nivolumab compared with nivolumab alone for QOL in S1400I. A risk model identified patients at high risk of poor survival, demonstrating the prognostic relevance of baseline patient-reported outcomes even in those with previously treated advanced cancer.

Non-small cell lung cancer disparities in stage at presentation and treatment for Asian American, Native Hawaiian, and Pacific Islander women.

BACKGROUND AND OBJECTIVES: Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) represent the fastest-growing group in the United States. While described in aggregate, great variations exist within the community. We aimed to determine whether there were differences in stage at presentation and treatment status among AANHPI women with non-small cell lung cancer (NSCLC). METHODS: Between 2004 and 2016, we identified 522 361 female patients with newly diagnosed NSCLC from the National Cancer Database. Multivariable logistic regression models were used to define adjusted odds ratios (aORs) of presenting with stage IV disease and not receiving treatment. RESULTS: AANHPI women were more likely to present with stage IV disease compared to White (54.32% vs. 40.28%, p < 0.001). Aside from Hawaiian, Pakistani, and Hmong women, all other ethnic groups had greater odds of presenting with stage IV disease than White women. AANHPI women <65 years were more likely to present with stage IV disease (p = 0.030). Only Vietnamese women showed a significant difference (aOR = 1.30 [1.06-1.58], p = 0.010) for likelihood of receiving treatment compared to White. CONCLUSIONS: Differences in stage at presentation and treatment status in women with NSCLC were observed among AANHPI ethnic groups when populations were disaggregated.

Prevalence and Predictability of Occult Satellite Nodules in Clinical Stage Ia Non-small Cell Lung Cancer following Lobectomy.

INTRODUCTION: We sought to assess the prevalence and clinical predictors of satellite nodules in patients undergoing lobectomy for clinical stage Ia disease. PATIENTS AND METHODS: The National Cancer Database was queried for patients who underwent lobectomy for clinical stage cT1N0 NSCLC. Collaborative staging information was used to identify patients who were pathologically upstaged based on having separate tumor nodules in the same lobe as the primary tumor. Multivariable logistic regression was used to assess the association of clinical factors with the detection of separate nodules. RESULTS: A separate tumor nodule was recorded in 2.8% (n = 1284) of 45,842 clinical stage Ia patients treated with lobectomy or bilobectomy. Female gender (3.1% vs. male 2.5%; P = .002) and non-squamous histology (adenocarcinoma 3.2% and large cell neuroendocrine 3.0% vs. squamous cell 1.9% tumors; P < .001) were associated with the presence of separate nodules. The frequency increased for tumors larger than 3 cm (≤ 3cm, 2.7% vs. > 3cm, 3.8%; P < .001). Other factors associated with separate nodules were upper lobe location, pleural and/or lymphovascular invasion and occult lymph node disease. The best predictive model for separate nodules based on the available clinical variables resulted in an area under the curve of 0.645 (95% CI 0.629-0.660). CONCLUSION: Separate tumor nodules may be detected with a low but relatively consistent frequency across the spectrum of patients with clinical stage Ia NSCLC. The predictive ability using basic clinical factors in the database is limited.

Neoaortoiliac system and cryopreserved human allograft for the treatment of aortic graft infections.

OBJECTIVE: To report and compare neoaortoiliac system reconstruction and cryopreserved human allograft in treating aortic graft infections. METHODS: We retrospectively analysed the data of the patients treated for aorto graft infections between January 2015 and May 2021 in our hospital. The clinical data, diagnostic procedures, and surgical options were evaluated. The primary endpoint of this study was the 30-day and 1-year mortality; secondary endpoints were major postoperative complications. RESULTS: We retrospectively reviewed a series of 31 consecutive patients (28 males; median age 72 years, range, 50-87 years) with aortic graft infection treated with NAIS (n = 20, 65%) or cryopreserved allograft (n = 11, 36%). The clinical presentation included fever attacks in 18 (58%) patients, abdominal pain in 15 (48%) patients, haemodynamic instability in 6 (19%) patients, and haematemesis in 2 (7%) patients. The median operative time of the NAIS was longer than CHA without a statistically significant difference (458 min vs. 359 min, p = .505). The postoperative morbidity for all patients was 81%, with no significant difference between NAIS and CHA groups (85% vs. 73%, p = .638). There was no limb thrombosis of the new reconstructions. Limb loss occurred in 4 (13%) patients, including 2 (10%) NAIS patients and 2 (18%) CHA patients. One NAIS patient developed complications in the form of a distal (femoral) disruption of the vein 15 days after surgery. There were no significant differences between NAIS and CHA groups in ICU stay (12 vs 8 days, .984) but in hospitalization (22 vs 33, p = .033). The most common bacteria isolated were staphylococci strains in 15 (48%). In 13 (36%) patients, candida was positive. The in-hospital 30-day and 1-year mortality for all patients was 16% (5/31) and 29% (9/31), with no significant differences between NAIS and CHA at 30 days (25% vs. 0, p = .133) or 1 year (35% vs. 18%, .429). Five NAIS patients died during the hospital stay; three of them had end-of-life decisions. After a median follow-up of 16 months (1-66 months), 12 (39%) patients died, including 9 patients with NAIS and 3 with CHA reconstructions. The causes of death included overwhelming sepsis in 5 (42%) patients, graft disruption in one (8%) NAIS patient, non-small cell lung cancer in one (8%) patient, COVID-19 in one (8%) patient and unknown causes (8%) in one. CONCLUSIONS: Non-staged neoaortoiliac system reconstruction and cryopreserved human allografts show comparable short- and midterm results for treating aortic graft infections. However, both procedures remain challenging with high morbidity and mortality rates.

A Pragmatic Cluster-Randomized Trial of a Standing Order Entry Intervention for Colony-Stimulating Factor Use Among Patients at Intermediate Risk for Febrile Neutropenia.

PURPOSE: Primary prophylactic colony-stimulating factors (PP-CSFs) are prescribed to reduce febrile neutropenia (FN) but their benefit for intermediate FN risk regimens is uncertain. Within a pragmatic, randomized trial of a standing order entry (SOE) PP-CSF intervention, we conducted a substudy to evaluate the effectiveness of SOE for patients receiving intermediate-risk regimens. METHODS: TrACER was a cluster randomized trial where practices were randomized to usual care or a guideline-based SOE intervention. In the primary study, sites were randomized 3:1 to SOE of automated PP-CSF orders for high FN risk regimens and alerts against PP-CSF use for low-risk regimens versus usual care. A secondary 1:1 randomization assigned 24 intervention sites to either SOE to prescribe or an alert to not prescribe PP-CSF for intermediate-risk regimens. Clinicians were allowed to over-ride the SOE. Patients with breast, colorectal, or non-small-cell lung cancer were enrolled. Mixed-effect logistic regression models were used to test differences between randomized sites. RESULTS: Between January 2016 and April 2020, 846 eligible patients receiving intermediate-risk regimens were registered to either SOE to prescribe (12 sites: n = 542) or an alert to not prescribe PP-CSF (12 sites: n = 304). Rates of PP-CSF use were higher among sites randomized to SOE (37.1% v 9.9%, odds ratio, 5.91; 95% CI, 1.77 to 19.70; P = .0038). Rates of FN were low and identical between arms (3.7% v 3.7%). CONCLUSION: Although implementation of a SOE intervention for PP-CSF significantly increased PP-CSF use among patients receiving first-line intermediate-risk regimens, FN rates were low and did not differ between arms. Although this guideline-informed SOE influenced prescribing, the results suggest that neither SOE nor PP-CSF provides sufficient benefit to justify their use for all patients receiving first-line intermediate-risk regimens.