Wigle, Dennis

Abstract Objectives Society guidelines discourage biopsy of thymic epithelial tumours (TETs) due to the perceived risk of local seeding or pleural dissemination. However, few studies have evaluated this concern, and the true risk of preoperative biopsy remains unknown. Methods We queried the United States’ National Cancer Database for adults with localized TETs who underwent upfront R0 thymectomy 2004-2015. Use of preoperative biopsy over time was assessed with the Cochran-Armitage test. Postoperative outcomes were compared with chi-square and Wilcoxon rank sum tests. Overall survival (OS) was analysed with Kaplan-Meier and Cox proportional hazard methods. Results We identified 1056 patients. The median age was 61 years; 47% (492) were male. Use of preoperative percutaneous biopsy increased 2006-2015 from 18% to 33% (P < .001). Patients who underwent biopsy had larger tumours [median 6.6 vs 5.0 cm], more open operations [72% (150) vs 62% (331)] and regional lymphadenectomies [44% (118) vs 33% (250)], and a longer length of hospitalization (median 4 vs 3 days). Thirty-day mortality was similar between the groups. There was no difference in 10-year OS between the biopsy and no-biopsy groups [75% (95% CI 69%-82%) vs 76% (95% CI 73%-80%), P = .8]. After adjusting for age, sex, primary payor, histology, and tumour size, OS was similar between the biopsy and no-biopsy groups [AHR 0.97 (95% CI 0.72-1.29), P = .9]. Conclusions In this analysis of patients with localized TETs undergoing upfront R0 thymectomy, preoperative biopsy is not associated with worse OS. More study is needed to further explore whether biopsy increases risk of recurrence.

ABSTRACT Background Functional lumen imaging probe (FLIP) utility is established in treatment‐naïve achalasia but less clear following lower esophageal sphincter (LES) directed therapy. Methods Achalasia patients with LES directed therapy across three tertiary care centers between 2017 and 2024 with post‐treatment FLIP and timed barium esophagram (TBE) were retrospectively identified. Reduced esophagogastric junction (EGJ) opening was defined by distensibility index (DI) < 2 mm 2 /mmHg and diameter < 12 mm. Abnormal emptying on TBE was defined as column height ≥ 5 cm at 5 min and/or retained tablet. Eckardt scores ≤ 3 defined clinical response. Key Results The study included 222 patients (46% peroral endoscopic myotomy, 46% laparoscopic Heller myotomy, 8% pneumatic dilation) with a median of 1.4 years to post‐treatment TBE/FLIP. Abnormal emptying on TBE was associated with a narrower median EGJ diameter (13.2 vs. 14.8 mm, p = 0.008), a greater frequency of EGJ diameter < 12 mm (36% vs. 21%, p = 0.012), and a smaller change in EGJ diameter (+4.6 vs. +8.6 mm, p = 0.002). Abnormal emptying on TBE occurred more frequently in patients with EGJ DI < 2 mm 2 /mmHg (8.5% vs. 2.6%, p = 0.052), but was not associated with median EGJ DI (4.5 vs. 5.1 mm 2 /mmHg, p = 0.29) nor median change in EGJ DI (+2.9 vs. +3.9 mm 2 /mmHg, p = 0.25). Patients with reduced EGJ DI or EGJ diameter more often had abnormal TBE (37% vs. 22%, p = 0.012). Only the change in DI (+3.8 vs. +1.5 mm 2 /mmHg, p = 0.012) and diameter (+8.2 vs. +1.6 mm, p = 0.002) on FLIP was associated with a clinical response based on Eckardt ≤ 3. Conclusions and Inferences FLIP following achalasia therapy generally correlates with TBE, although discrepant findings are not uncommon. In particular, FLIP EGJ‐diameter has a strong association with esophageal emptying on TBE. Both TBE and FLIP have limited association with clinical response based on Eckardt, with change in DI and diameter on FLIP most strongly associated. Consequently, FLIP as part of multimodal assessment appears useful in the longitudinal follow‐up of treated achalasia.

Background Our study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC. Methods This is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers. Results 30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%–91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%–94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively. Conclusions Perioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.

Importance The randomized clinical trial Cancer and Leukemia Group B (CALGB) 140503 showed that for patients with clinically staged T1N0 non–small cell lung cancer (NSCLC; ≤2 cm), sublobar resections were associated with similar oncological outcomes to those after lobar resection. The association of the extent of parenchymal resection with recurrence and survival in patients with tumors pathologically upstaged to T2 based on visceral pleural invasion (VPI) is controversial. Objective To determine survival and recurrence rates in patients with small peripheral pT2 NSCLC (≤2 cm) that was treated by either lobar or sublobar resection in CALGB 140503. Design, Participants, and Setting CALGB 140503, a randomized multicenter noninferiority trial, included 697 patients with small peripheral NSCLC that was clinically staged as T1N0. Enrollment was from June 2007 through March 2017 at 83 participating institutions, and after a median follow-up of 7 years, the primary outcome of disease-free survival after sublobar resection was noninferior to that after lobar resection. Intervention Lobar or sublobar resection. Main Outcomes and Measures Survival end points were estimated by the Kaplan-Meier estimator. Hazard ratios and 95% CIs were estimated using stratified Cox proportional hazard models. Results Of 679 participants, 390 (57.4%) were female, and the median (range) age was 67.8 (37.8-89.7) years. Among 697 patients randomized, 566 (81.2%) had pT1 tumors (no VPI) and 113 (16.2%) had pT2 tumors (VPI). Five-year disease-free survival was 65.9% (95% CI, 61.9%-70.2%) in patients with pT1 compared with 53.3% (95% CI, 44.3%-64.1%) in patients with pT2 tumors (stratified log-rank: P = .02). Disease recurrence developed in 27.6% of patients with pT1 (locoregional only: 60 [10.8%]; distant only: 81 [14.6%]) and 41.6% of those with pT2 (locoregional only: 17 [15.0%]; distant only: 27 [23.9%]). Five-year recurrence-free survival was 73.1% (95% CI, 69.2%-77.1%) for pT1 tumors and 58.2% (95% CI, 49.2%-68.8%) for pT2 tumors (stratified log-rank: P = .01). There were no intergroup differences in disease-free or recurrence-free survival based on the extent of parenchymal resection. Conclusions and Relevance The results of this secondary analysis suggest that compared with patients with tumors without VPI, patients who had tumors with VPI had worse disease-free and recurrence-free survival and a higher rate of local and distant disease recurrence. These high rates of recurrence were independent of the extent of parenchymal resection, and these data support the inclusion of these patients in adjuvant therapy trials. Trial Registration ClinicalTrials.gov Identifier: NCT0049933

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Patients with early-stage non–small-cell lung cancer (NSCLC) who undergo curative surgical resection are at risk for developing second primary lung cancer (SPLC). Cancer and Leukemia Group B 140503 (Alliance) was a multicenter, international, randomized, phase III trial in patients with stage T1aN0 NSCLC (using the TNM staging system seventh edition) and demonstrated the noninferiority for disease-free survival between sublobar resection (SLR) and lobar resection (LR). After surgery, patients underwent computed tomography surveillance as defined by the protocol. The determination of a SPLC was done by the treating physician and recorded in the study database. We performed an analysis of the rate of SPLC (per patient per year) and the 5-year cumulative incidence in the study population and within the SLR and LR arms. Median follow-up was 7 years. The rate per patient per year in the study population, in the SLR arm, and in the LR arm was 3.4% (95% CI, 2.9 to 4.1), 3.8% (95% CI, 2.9 to 4.9), and 3.1% (95% CI, 2.4 to 4.1), respectively. The estimated 5-year cumulative incidence of SPLC in the study population, SLR arm, and LR arm was 15.9% (95% CI, 12.9 to 18.9), 17.2% (95% CI, 12.7 to 21.5), and 14.7% (95% CI, 10.6 to 18.7), respectively.

AbstractBackgroundWe hypothesized full‐thickness chest wall resection (FTCWR) with advanced surgical techniques and modern systemic therapy is safe, provides local control, and good overall survival.MethodsRetrospective review of FTCWR (including rib or part of sternum) for breast cancer between 2000 and 2020. Primary endpoints included 90‐day morbidities and all‐cause mortality. Secondary endpoints were loco‐regional and distant recurrence, DFS and overall survival (OS).ResultsA total of 35 patients met the criteria. 34 FTCWR were for recurrence and the median time to chest wall recurrence was 6 years. Tumor subtype was triple‐negative in 51% and the remainder HR+ Her2−. 58% were palliative resections. FTCWR included rib(s) in 89% and portion of sternum in 57%; 94% required reconstruction and 80% were R0 resections. There were no 90‐day mortalities. Overall morbidity was 10/35(28%). 17(49%) patients received neoadjuvant systemic therapy for their recurrence and three received neoadjuvant radiation. Adjuvant treatment included chemotherapy (8), endocrine therapy (3), and both (8). Ten patients (28%) received adjuvant radiation. The Median follow‐up was 31 months and there were 6 (17%) loco‐regional and 7 (20%) distant recurrences. OS was 86% and 67% at 1 and 3 years, respectively.ConclusionFTCWR was associated with low morbidity, mortality, recurrence rates, and good OS. Selective FTCWR is safe and has acceptable short‐term survival rates.

Abstract Purpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods: Patients with GEJ adenocarcinoma (cT1–3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS &lt; 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1–expressing EVs was significantly associated with higher pCR. Conclusions: Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.