Prognostic Significance of SUVmax Combined With Lactate Dehydrogenase in Advanced Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Retrospective Study.

PURPOSE: This research aims to investigate the predictive capacity of PET/CT quantitative parameters combined with haematological parameters in advanced lung cancer patients treated with immune checkpoint inhibitor (ICI) plus chemotherapy. METHODS: A total of 120 patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were enrolled before therapy. The following parameters were calculated: the maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); total tumour volume (MTV) and total lesion glycolysis (TLG); and whole-body metabolic values (MTVwb, TLGwb, SUVmeanwb, and SUVmaxwb). Lactate dehydrogenase (LDH) levels, absolute neutrophil count, absolute platelet count, albumin levels and derived neutrophil to lymphocyte ratio (dNLR) were also computed. The associations between the variables and therapy outcome (evaluated by iRECIST) were analyzed. RESULTS: Based on iRECIST, 32 of 120 patients showed iPD, 43 iSD, 36 iPR and 9 iCR. Multivariate analysis found that SUVmax, MTVwb, LDH and absolute platelet count were associated with treatment response (P =0.015, P =0.005, P <0.001 and P =0.015, respectively). Kaplan-Meier survival analyses showed that SUVmax ≥11.42 and LDH ≥245 U/L were associated with shorter OS (P = 0.001 and P = 0.004, respectively). Multivariate Cox regression revealed that SUVmax and LDH alone were not correlated with survival prognosis (p>0.05), but the combination of SUVmax and LDH was independently associated with OS (P=0.015, P=0.001, respectively). The median survival time (MST) for the low (LDH<245 and SUVmax<11.42), intermediate(LDH<245 or SUVmax<11.42), and high(SUVmax≥11.42 and LDH≥245) groups was 24.10 months (95% CI: 19.43 to 28.77), 17.41 months (95% CI: 15.83 to 18.99), and 13.76 months (95% CI: 12.51 to 15.02), respectively. CONCLUSION: This study identified that SUVmax plus LDH correlated with the survival outcome in patients with advanced lung cancer receiving PD-1/PD-L1 blockade plus chemotherapy.

Feasibility of semiquantitative 18F-fluorodeoxyglucose PET/computed tomography in patients with advanced lung cancer for interim treatment evaluation of combining immunotherapy and chemotherapy.

OBJECTIVE: This study aimed to investigate the prognosis value of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in advanced lung cancer patients with immunotherapy combined with chemotherapy. METHODS: Fifty-one advanced lung cancer patients were included in this retrospective study, who underwent 18F-FDG PET/CT imaging before four cycles of immunotherapy combined with chemotherapy at our institution between January 2018 and January 2020. The following PET/CT parameters were calculated: standardized uptake value SUVmax, SUVmean, SUVpeak, SUVsd, metabolic tumor volume (MTV), total lesion glycolysis (TLG), MTV25%, MTV42%, MTV50%, MTV75%, global lung glycolysis (GLG), target-to-background ratio (TBR), SUVpeakwb, MTVwb, TLGwb, SUVmeanwb, SUVmaxwb. Logistics regression analyses were used for assessing the association between baseline metabolic parameters and response to treatment. Kaplan-Meier estimator curves and the log-rank test were constructed for survival analyses. RESULTS: According to RECIST, nine patients (18%) showed partial response, 25 (49%) had SD, and 17 (33%) had progressive disease. The mean ± SD of SUVmax, SUVpeak, MTV were lower in clinical benefit (CB) group than no-clinical benefit (no-CB) group (all P < 0.05). Median PFS was 3.7 months in no-CB group and 9.9 months in CB group (P < 0.001). Multivariate logistic analysis indicated that SUVmax and histology were independent factors significantly related to the evaluation of therapeutic efficiency. Furthermore, SUVmax is an independent predictor of efficacy in non-small cell lung cancer. CONCLUSION: SUVmax can be used to predict interim treatment response of immunotherapy combination with chemotherapy for advanced lung cancer. Moreover, the combination of SUVmax and histology may predict treatment response with acceptable reliability. However, a large prospective multicenter trial is still needed to examine the above finding for lacking limited evidence.

Next Generation Sequencing in the Management of Leptomeningeal Metastases of Non-Small Cell Lung Cancer: A Case Report and Literature Review.

BACKGROUND: Diagnosis of Leptomeningeal Metastases (LM) from Non-Small Cell Lung Cancer (NSCLC) is usually based on clinical symptoms, Cerebral-Spinal Fluid (CSF) cytology, and neuro-imaging. However, early diagnosis of LM in NSCLC is challenging due to the low sensitivity of these approaches. The Next-Generation Sequencing (NGS) using CSF could help improve the diagnosis of LM and guide its treatment options. CASE PRESENTATION: We report a 39-year-old male NSCLC patient with negative molecular testing results in the lung cancer tissue sample. The patient developed symptoms of LM with the negative CSF cytology and MRI; however, the NGS analysis of CSF revealed an EGFR exon 19 del mutation. The patient attained 6 months of Progression-Free Survival (PFS) by treating with erlotinib and anlotinib before the neurological symptoms appeared again. EGFR Thr790Met was positive in the CSF but negative in his plasma. The patient was then treated with osimertinib therapy and the response was maintained for more than 1 year. RESULTS & DISCUSSION: This case is the first study reporting the clinical benefit of using the combination of erlotinib and anlotinib for the treatment of LM with the EGFR 19 del, osimertinib with EGFR T790M mutation in CSF, but negative gene mutation in the blood or lung tumor biopsy specimens. Our results support that genetic analysis should be performed with CSF samples in all cases of suspected LM when the results of testing for EGFR/ALK/ROS1 mutation in blood samples or tumor biopsy specimens are negative, as these patients could benefit from treatment of TKIs in a poor prognostic setting. CONCLUSION: In parallel to current patents, NGS could be applied as a novel strategy in the managing of NSCLC patients with LM.

Timing of Adjuvant Chemoradiation in pT1-3N1-2 or pT4aN1 Esophageal Squamous Cell Carcinoma After R0 Esophagectomy.

INTRODUCTION: Postoperative adjuvant radiation therapy (RT) and chemotherapy (aCRT) have been supposed to improve prognosis and outcomes in patients with node-positive thoracic esophageal squamous cell carcinoma (TESCC). Our aim was to analyze the impacts of interval between surgery and aCRT on prognosis, determining the optimal time interval. METHODS: We retrospectively reviewed 520 patients with TESCC between 2007 and 2015 treated with aCRT following radical esophagectomy without neoadjuvant chemotherapy and RT. These patients underwent RT (50-60 Gy) combined with 2-6 cycles chemotherapy after surgery. The time intervals were from 17 days to 145 days and divided into three groups: short interval group (≤28 days, S-Int group), medial interval group (≥29 and ≤ 56 days, M-Int group) and long interval group (≥57 days, L-Int group). RESULTS: Median follow-up was 35.6 months and the 3-, 5-year survival rates and median survival were 49.5%, 36.6% and 35.9 months. The duration of postoperative interval was a predictor of survival outcomes. The median survival and 5-year survival rates in S-Int, M-Int and L-Int groups were 23.6 (32.1%), 44.2 (43.3%) and 32.0 (31.5%) months (P=0.007). The difference was statistically significant between the M-Int and S-Int or L-Int group but was not between the S-Int and L-Int group. Besides, toxic reactions including early, late and adverse events (grade ≥3) in M-Int group were significantly less than S-Int and show no significant differences with L-Int group. CONCLUSION: The optimal time interval was from 29 days to 56 days (5-8 weeks) both in terms of survival outcomes and toxic reactions.

Development of EGFR TKIs and Options to Manage Resistance of Third-Generation EGFR TKI Osimertinib: Conventional Ways and Immune Checkpoint Inhibitors.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have been first-line therapy in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Progression inevitably happens after 10-14 months of first- or second-generation EGFR TKIs treatment for acquired resistance. Owing to the successful identification of EGFR T790M, third-generation EGFR TKIs such as osimertinib were developed to target such resistance mutation. Nowadays, osimertinib has shown its efficacy both in first-line and second-line after resistance to previous generations of TKI treatment of EGFR-mutant NSCLC. However, drug resistance also emerges on third-generation EGFR TKIs. Multiple mechanisms of acquired resistance have been identified, and some novel strategies were reported to overcome third-generation TKI resistance. Immune checkpoint inhibitors (ICIs) have dramatically changed the prognosis of selected patients. For patients with EGFR-addicted metastatic NSCLC, ICIs have also revealed a potential role. In this review, we will take stock of mechanisms of acquired resistance to third-generation TKIs and discuss current challenges and future perspectives in clinical practice.