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Considerable differences of treatment response and pattern of failure may exist between definitive chemoradiation (CRT) treated locally advanced non-small cell lung cancer (LA-NSCLC) patients. The clinical value of additional tyrosine kinase inhibitors (TKIs) before disease recurrence and salvage local therapy after initial recurrent disease remain controversial.Consecutive LA-NSCLC patients receiving definitive CRT and having definite results about driver mutations (EGFR, ALK and ROS1) were retrospectively reviewed. Initial recurrent disease was classified as in-field recurrence, out-of-field recurrence and distant metastasis. Recurrent disease occurred only in the brain or limited to ≤3 extra-cranial organs and ≤5 extra-cranial lesions, was defined as oligo-recurrence. Progression free survival and overall survival (OS) were calculated from diagnosis to disease progression or death, and to death, respectively. OS2 was measured from initial disease recurrence to death among patients who had recurrent disease.Of the 153 enrolled patients, 39 had driver mutations and 13 received additional TKI therapy besides definitive CRT. Patients harboring driver mutations but without additional TKI therapy had a similar PFS and significantly longer OS (p = 0.032) than those without driver mutations. Additional TKI therapy prolonged PFS (p = 0.021) but not OS among patients with driver mutations. No significant difference of pattern of failure was observed between patient subgroups stratified by the status of driver mutations and the usage of additional TKI therapy. Furthermore, 57 of the 95 patients with initial recurrent disease developed oligo-recurrence and salvage local therapy significantly improved OS2 (p = 0.01) among patients with oligo-recurrence disease.LA-NSCLC patients receiving definitive CRT generally had similar PFS and pattern of treatment failure, regardless of driver mutation status. Additional TKI therapy besides definitive CRT could prolong PFS but not OS. The majority of recurrent disease after definitive CRT belongs to oligo-recurrence and salvage local therapy may provide survival benefit.

Deubiquitinating enzyme OTU domain‐containing ubiquitin aldehyde‐binding proteins 1 (OTUB1) has been shown to have an essential role in multiple carcinomas. However, the function of OTUB1 in papillary thyroid cancer (PTC) and the underlying mechanisms regulating PTC cells proliferation remain poorly understood. In this study, OTUB1 was significantly upregulated in papillary thyroid carcinoma tissues and cells. Through in vitro and in vivo experiments, knockdown of OTUB1 suppressed PTC cells growth whereas OTUB1 overexpression enhanced the proliferation ability of PTC cells. Moreover, the eyes absent homologue 1 (EYA1) was recognized as a potential target of OTUB1 through mass spectrometry analysis, and we further verified that EYA1 protein level was positively correlated with OTUB1 expression in PTC cells and clinical samples. Mechanistically, OTUB1 could interact with EYA1 directly and deubiquitinate EYA1 to stabilize it. At last, EYA1 was found to play an essential role in OTUB1‐derived PTC cells growth. Overall, our investigation reveals that OTUB1 is a previously unrecognized oncogenic factor in PTC cells proliferation and suggests that OTUB1 might be a novel therapeutic target in PTC.

Purpose: To explore the clinical characteristics, management, and survival outcomes of advanced NSCLC patients treated with PD-1/PD-L1 inhibitors who presented with an atypical response (AR). Methods: A total of 926 PD-1/PD-L1-inhibitor-treated patients with metastatic NSCLC from three academic centers were retrospectively reviewed. All measurable lesions were evaluated by RECIST version 1.1. Results: Fifty-six (6.1%) patients developed AR. The median time to the occurrence of AR was 2.0 months. Patients with no fewer than 3 metastatic organs at baseline were more prone to develop AR in advanced NSCLC (p = 0.038). The common sites of progressive lesions were lymph nodes (33.8%) and lungs (29.7%). The majority (78.2%) of patients with AR had only 1–2 progressive tumor lesions, and most (89.1%) of the progressive lesions developed from originally existing tumor sites. There was no significance in terms of survival between patients with AR and those with typical response (TR). Local therapy was an independent predictor for PFS of patients with AR (p = 0.025). Conclusions: AR was not an uncommon event in patients with metastatic NSCLC treated with PD-1/PD-L1 inhibitors, and it had a comparable prognosis to those with TR. Proper local therapy targeting progressive lesions without discontinuing original PD-1/PD-L1 inhibitors may improve patient survival.

Objective: Local therapy (LT) could potentially prolong the survival of patient with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) receiving tyrosine kinase inhibitors (TKIs) and harboring oligometastatic/oligoprogressive disease (OMD/OPD). However, the optimal imaging method for identifying patients with OMD/OPD remains controversial. The objective of this study was to investigate the clinical value of incorporating PET/CT in detecting patients with OMD/OPD. Methods: Consecutive cases with metastatic EGFR-mutant NSCLC undergoing first-line EGFR-TKI treatment were retrospectively screened and those receiving baseline PET/CT and brain magnetic resonance imaging (MRI) or complete conventional imaging (CIM), including brain MRI, chest computed tomography (CT), abdomen ultrasound or CT and bone scintigraphy were included. OMD/OPD was defined as metastases/progressions documented at a maximum of five lesions and three organs, otherwise was defined as multiple metastatic/progressive disease (MMD/MPD). Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Of the 392 patients evaluated, baseline OMD was detected in 22.7% (53/233) of patients by PET/CT and in 18.2% (29/159) of patients by CIM (p = 0.171). Among the patients evaluated with baseline PET/CT, patients with OMD had longer PFS (p = 0.016) and tendency of improved OS (p = 0.058) than those with MMD. However, this result was not observed with patients evaluated using baseline CIM. With a median follow-up of 24.2 (range, 1.1–124.6) months, 297 patients had their first disease progression (FPD), of whom 164 (55.2%) had adequate imaging scans to analyze the tumor distributions at FPD comprehensively. OPD was detected in 63.0% (34/54) and 35.0% (39/110) of patients among the PET/CT and CIM assessed group (p = 0.003), respectively. Among the PET/CT assessed group, patients with OPD had significantly longer post-progressive overall survival (OS2) than those with MPD (p = 0.011). However, no significant difference of OS2 in the CIM assessed group was found. Conclusion: Patients with OMD/OPD, evaluated by PET/CT but not CIM, generally had more favorable survival outcomes than those with MMD/MPD among patients with metastatic NSCLC undergoing first-line EGFR-TKI treatment. Advances in knowledge: PET/CT seems to affect the survival of patients under first-line EGFR-TKI treated metastatic NSCLC with OMD/OPD.