First-in-Human Intrathoracic Implantation of Multidrug-Eluting Microdevices for In Situ Chemotherapeutic Sensitivity Testing as Proof of Concept in Nonsmall Cell Lung Cancer.

OBJECTIVE: To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection. BACKGROUND: Adjuvant therapy has limited impact on postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens. METHODS: An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers. RESULTS: A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD. CONCLUSIONS: A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.

Added Value of Magnetic Resonance Over Computed Tomography in Distinguishing Nonneoplastic Complex Thymic Cysts From Malignant Cystic Thymic Neoplasms.

PURPOSE: The aim of the study was to evaluate cystic thymic masses by using computed tomography (CT) and magnetic resonance (MR) scoring systems to differentiate nonneoplastic thymic cysts from cystic thymic neoplasms. METHODS: This retrospective multisite study included adult patients who underwent CT and MR imaging of the chest between 2007 and 2020 with any of the following impressions on cross-sectional imaging studies: "thymic mass with cystic component," "unilocular or multilocular cystic thymic lesion," "complex thymic cyst," "thymic cyst with hemorrhage." Two blinded radiologists reviewed and recorded specific imaging features as well as overall impressions on both CT and MR using a Likert scale scoring system. Data were analyzed, and diagnostic accuracy of CT and MR was compared using areas under the receiver operating characteristic curves (AUC). RESULTS: Fifty-six patients were included, of which 45 (80%) had benign masses. Total of 21 patients (38%) had indeterminate scores on CT of which 3 (14%) were malignant, while only 6 (11%) had indeterminate scores on MR and 1 was malignant. Magnetic resonance scoring system (AUC, 0.95) performed better than CT scoring system (AUC, 0.86) in distinguishing benign versus malignant lesions (P = 0.06). Lack of enhancement within the mass was completely predictive of benign etiology (P < 0.001). Wall thickness of an enhancing cyst was predictive of malignancy, with AUC 0.93. CONCLUSIONS: Magnetic resonance yielded higher specificity allowing a larger number of lesions to be confidently assigned a benign diagnosis. This could help in averting unnecessary follow-up, biopsies, or surgery. The authors recommend follow-up imaging with MR for prevascular masses, even those appearing "solid" on CT.

Lung Cancer Strategist Program: A novel care delivery model to improve timeliness of diagnosis and treatment in high-risk patients.

INTRODUCTION: The diagnosis and treatment of lung cancer is challenged by complex diagnostic pathways and fragmented care that can lead to care disparities for vulnerable patients. METHODS: A multi-institutional, multidisciplinary conference was convened to address the complexity of lung cancer care particularly in patients at high-risk for treatment delay. The resulting care delivery model, called the Lung Cancer Strategist Program (LCSP), was led by a thoracic-trained advanced practice provider (APP) with emphasis on expedited surgery and early oncologic consultation in the assessment of a newly diagnosed suspicious lung nodule. We performed a retrospective review to evaluate care efficiency and oncologic outcomes in the first 100 LCSP patients compared to 100 concurrent patients managed via routine surgical referral. RESULTS: In the 78 LCSP and 41 routine referral patients managed via nodule surveillance, LCSP patients had a shorter time from suspicious finding to work-up (3 vs. 26 days, p < 0.001) and to surveillance decision (12.5 vs. 39 days, p < 0.001). In the 22 LCSP and 59 routine referral patients treated for intrathoracic malignancy, LCSP patients had fewer hospital visits (4 vs 6, p < 0.001), clinicians seen (1.5 vs. 2, p = 0.08), and diagnostic studies (4 vs 5, p = 0.01) with a shorter time to diagnosis (30.5 vs. 48 days, p = 0.02) and treatment (40.5 vs. 68.5 days, p = 0.02). CONCLUSIONS: Patient triage through a thoracic-trained APP in consultation with surgical, medical, and radiation oncology facilitates rapid assessment of benign versus malignant lesions with reduced time to diagnosis and treatment, even among patients at high-risk for treatment delay.

Impact of Nodule Density in Women With Sublobar Resection for Stage IA Adenocarcinoma.

BACKGROUND: This study sought to examine the impact of nodule density on recurrence and survival in female patients with lung adenocarcinoma treated by lobectomy or sublobar resection. METHODS: In this retrospective study of female patients who underwent surgical resection for pathologic stage IA adenocarcinoma, patients with preoperative imaging were included for analysis if the consolidation-to-tumor ratio was 0.5 (solid-predominant ground-glass opacity [GGO]) to 1.0 (solid). Kaplan-Meier curves were generated to estimate overall survival (OS) and disease-free survival (DFS). Risk estimates were calculated using multivariable Cox proportional hazards models. RESULTS: For all 357 patients sublobar resection demonstrated worse 5-year DFS compared with lobectomy (76.4% vs 67.9%, P = .05). Multivariable modeling showed worse DFS with sublobar resection (hazard ratio, 1.55; P = .06) and tumors ≥ 2 cm (hazard ratio, 2.32; P = .05). On radiologic evaluation the solid-predominant GGO group (n = 81) demonstrated a smaller solid component compared with the solid nodule group (n = 163; 1.49 cm vs. 1.84 cm, respectively; P < .001) yet comparable total size. The solid-predominant GGO group showed improved 5-year OS (90.8 vs 76.8, P = .01) and DFS (79.3 vs 67.2, P = .05) compared with the solid nodule group. Additionally the solid-predominant GGO group demonstrated equivalent OS (90.8% vs 90.8%, P = .93) and DFS (76.0% vs 81.7%, P = .60) with sublobar resection compared with lobectomy. CONCLUSIONS: In this report of female patients with stage IA adenocarcinoma, sublobar resection was associated with worse DFS compared with lobectomy in whole-group analysis. However patients with solid-predominant GGOs demonstrated improved 5-year OS and DFS compared with patients with solid nodules with equivalent outcomes regardless of resection type.

Supraclavicular Approach for Neurogenic Thoracic Outlet Syndrome: Description of a Learning Curve.

BACKGROUND: The supraclavicular exposure represents an alternative approach for thoracic outlet decompression in neurogenic thoracic outlet syndrome with unique access to neurovascular structures. We aimed to evaluate the learning curve for this approach and associated patient outcomes. METHODS: Patients undergoing first-time, unilateral, supraclavicular thoracic outlet decompression for neurogenic thoracic outlet syndrome were included. Cumulative-sum and linear-spline-regression analyses were used to determine the operative time learning curve. Patients were consecutively organized into early (learning phase) and late (competency) cohorts. Primary endpoints were the operative time learning curve operation number and association of this learning curve on differences in self-reported postoperative symptomatic improvement between early and late cohorts, adjusting for American Society of Anesthesiology classification, body mass index, previous treatment (opioid/neuropathic medication/botulinum-injection), and length of stay. RESULTS: Among 114 patients, learning curve analyses showed decreasing operative times, plateauing at the 51st operation (ß = -1.63, 95% confidence interval [-2.30, -0.95], P < .001). No periprocedural differences existed between early (operations 1-50) and late (operations 51-114) cohorts. Self-reported 90-day outcomes were similar in early and late cohorts (odds ratio [OR]: 1.60 [0.65, 3.95], P = .31). Mediators of poor self-reported outcomes included increasing American Society of Anesthesiology classification (OR 0.21 [0.08, 0.54], P = .001), failed preoperative botulinum injection (OR 0.15 [0.03, 0.65], P = .01), and increased length of stay (OR 0.40 [0.22, 0.73], P = .003). CONCLUSIONS: The learning curve for supraclavicular thoracic outlet decompression in neurogenic thoracic outlet syndrome occurred after 51 operations with a trend towards improved 90-day self-reported outcomes from the early to late phases. These findings, along with mediators of poorer outcomes, may aid surgeons in adopting a new approach and counseling patients on expected outcomes.

Reoperation for Persistent or Recurrent Neurogenic Thoracic Outlet Syndrome.

Identifying the exact cause for persistent and recurrent neurogenic thoracic outlet syndrome (NTOS) is challenging even with high-resolution imaging of the thoracic outlet. Improvement can be achieved with redo first rib resection, although the posterior first rib remnant is one of several potential points of brachial plexus compression. In approaching reoperative surgery for NTOS, the aim is to provide complete thoracic outlet decompression as guided by the patient's history, physical examination, and adjunctive imaging. This may involve resection of the posterior first rib remnant, scar tissue encasing the brachial plexus, elongated C7 transverse process, cervical rib, and/or pectoralis minor tendon.

Finding the "True" N0 Cohort: Technical Aspects of Near-infrared Sentinel Lymph Node Mapping in Non-small Cell Lung Cancer.

OBJECTIVE: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification. BACKGROUND: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease. METHODS: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC. RESULTS: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1 mg compared to <1 mg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22). CONCLUSIONS: SLN(s) are more reliably identified with ICG dose ≥1 mg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.

Value of circulating insulin-like growth factor-associated proteins for the detection of stage I non-small cell lung cancer.

OBJECTIVE: Circulating biomarkers related to insulin-like growth factor (IGF) signaling are associated with disease progression in multiple carcinomas, but their potential diagnostic value for lung cancer screening has been inadequately examined. We evaluated 9 circulating IGF-related factors for their ability to assign clinical significance to indeterminate pulmonary nodules identified via computed tomography-based radiologic studies. METHODS: Patients (n = 224 stage I non-small cell lung cancer; n = 123 benign) were enrolled by Rush University and the Mayo Clinic and had pretreatment serum evaluated for levels of IGF-1, IGF-2, and insulin-like growth factor binding proteins (IGFBPs) 1-7. The Mann-Whitney rank-sum test and receiver-operator characteristics curves were used to assess differences in biomarker concentrations relevant to malignant versus benign pathology. These targets were used to help refine our companion blood test for assigning clinical significance to computed tomography-detected solitary nodules (discovery cohort, n = 94) and were validated against an independent cohort from the Mayo Clinic (n = 81). RESULTS: Patients with benign pulmonary nodules were found to have serum concentrations of IGFBP-3, IGFBP-5, IGF-1, and IGF-2 that were higher (P = .001, P < .001, P = .002, and P = .011, respectively) than those with non-small cell lung cancer, with distinct associations with histologic subtypes observed. Refinement of our multianalyte classification algorithm using IGF-related factors provided a new panel consisting of interleukin-6, interleukin-1 receptor antagonist, interleukin-10, stromal cell-derived factor-1(α + ß), IGFBP-4, IGFBP-5, and IGF-2 with improved assay performance-achieving a (validated) negative predictive value of 100%. CONCLUSIONS: Our findings suggest a divergent role for IGF signaling in the biology of benign and malignant pulmonary nodules. Upon further validation, these observations may help identify cases of false positives resulting from computed tomography-based screening studies.