Challenges and limitation of MTAP immunohistochemistry in diagnosing desmoplastic mesothelioma/sarcomatoid pleural mesothelioma with desmoplastic features

AimGenomic-based ancillary assays including immunohistochemistry (IHC) for BRCA-1 associated protein-1 (BAP1) and methylthioadenosine phosphorylase (MTAP), and fluorescence in situ hybridization (FISH) for CDKN2A are effective for differentiating pleural mesothelioma (PM) from reactive mesothelial proliferations. We previously reported a combination of MTAP and BAP1 IHC effectively distinguishes sarcomatoid PM from fibrous pleuritis (FP). Nevertheless, cases of sarcomatoid PM with desmoplastic features (desmoPM) are encountered where the IHC assessment is unclear.Methods and resultsWe evaluated assessment of MTAP IHC, BAP1 IHC, and CDKN2A FISH in 20 desmoPM compared to 24 FP. MTAP and BAP1 IHC could not be assessed in 11 (55 %) and 10 (50 %) cases, respectively, due to loss or faint immunoreactivity of internal positive control cells, while CDKN2A FISH could be evaluated in all cases. The sensitivities for MTAP loss, BAP1 loss, and CDKN2A homozygous deletion in desmoPM were 40 %, 10 %, and 100 %. A combination of MTAP loss and BAP1 loss yielded 45 % of sensitivity.ConclusionsMTAP IHC is a useful surrogate diagnostic marker in differentiating ordinary sarcomatoid PM from FP, but its effectiveness is limited in desmoPM. CDKN2A FISH is the most effective diagnostic assays with 100 % sensitivity and specificity in discriminating desmoPM from FP in the facilities where the FISH assay is available.     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

Tongue cancer treatment and oncological outcomes: The role of glossectomy classification

BackgroundNowadays surgery remains the gold standard of treatment for tongue cancer. Via a more clear and precise terminology, the glossectomy classification by Ansarin et al. facilitates shared communication between surgeons, allowing comparison between published research and improving surgical practice and patient care. To establish the association of glossectomies, according to their classification by Ansarin et al. with overall survival (OS), disease-free survival (DSF), and cause-specific survival (CSS) in tongue cancer, we conducted a systemic retrospective study on 300 consecutive patients affected by primary oral tongue cancer and treated with surgery at the European Institute of Oncology, IRCCS (IEO).MethodsThree hundred patients with tongue squamous cell carcinoma and treated at the Division of Otorhinolaryngology and Head and Neck Surgery of the European Institute of Oncology, IRCCS were cataloged according to the glossectomy classification. OS, DFS, and CSS were compared by surgical treatments.ResultsOS-5yrs was 80% for the type I glossectomy group, 75% for type II, 65% for type III, and 35% for type IV-V. DFS-5yrs was 74%, 60%, 55%, and 27%, respectively for I, II, III, and IV-V glossectomy group; CSS-5yrs was 82%, 80%, 72%, and 48%, respectively for I, II, III, and IV-V glossectomy group (p < 0.01).ConclusionsThis study confirmed that the application of the glossectomy classification was statistically correlated with patients' oncological outcomes.     

Analysis of Progression Patterns and Failure Sites of Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations Receiving First-line Treatment of Tyrosine Kinase Inhibitors

BackgroundReliable prediction of progression patterns and failure sites for patients with stage IV lung adenocarcinoma is valuable for physicians to deliver personalized tyrosine kinase inhibitor (TKI) treatment.Patients and MethodsWe retrospectively enrolled 266 patients who had stage IV lung adenocarcinoma and received first-line TKI treatment from 2013 to 2017 in Shanghai Chest Hospital. The clinical characteristics at initial diagnosis, progression patterns, and failure sites were analyzed with the attempt to identify some predictive factors for progression patterns and failure sites.ResultsAmong all patients, 62.4% developed systemic progression, and 37.6% developed oligoprogression. Both cohorts had a median progression-free survival (PFS) of 9 months. The percentage of patients who developed original and distant failure was 39.1% and 60.9%, respectively. Patients with oligometastasis at initial diagnosis were more prone to develop oligoprogression (odds ratio [OR], 4.370; 95% confidence interval [CI], 1.881-10.151; P = .001), whereas pulmonary metastasis was negatively correlated with oligoprogression (OR, 0.567; 95% CI, 0.330-0.974; P = .04). Both oligometastasis diagnosis (OR, 2.959; 95% CI, 1.347-6.500; P = .007) and the maximum diameter of the primary lung lesion (threshold 3.25 cm: OR, 3.646; 95% CI, 2.041-6.515; P = .0001) were strong predictive factors for original failures. Osseous metastasis at initial diagnosis might be an indication for distant failure (OR, 0.536; 95% CI, 0.316-0.909; P = .021).ConclusionOver one-half of patients with stage IV lung adenocarcinoma receiving first-line TKI treatment developed systemic progression and distant failure. Metastasis patterns at initial diagnosis was the most important predictive factor for progression patterns and failure sites. The maximum diameter of the primary lung lesion and evidence of osseous metastasis were also found to be significant indicative factors for failure sites.     

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H₀: 55% and H₁= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.     

Sensitivity and specificity of waveform analysis for assessing postoperative epidural function

Study objectivesTo characterize the accuracy of epidural waveform analysis (EWA) in assessing the functionality of thoracic epidural catheters in the immediate postoperative period (primary objective), and to determine the inter-rater reliability between EWA waveform observers (secondary outcome).DesignSingle center, prospective diagnostic accuracy cohort study.SettingPost-anesthetic care unit of a university teaching hospital.Patients84 adult patients undergoing elective thoracic, gynecologic, vascular, urologic, or general surgery with preoperative placement of a thoracic epidural catheter for perioperative analgesia.InterventionsEWA tracings were video recorded in the immediate postoperative period through the epidural catheter in the post-anesthetic care unit.MeasurementsPostoperative EWA tracings were compared with clinical assessments of the sensory block to ice produced by epidural local anesthetic in the immediate postoperative period. Additionally, intra-class correlation analysis of agreement between 3 independent (and blinded) EWA waveform observers was carried out.ResultsAmong 80 patients with thoracic epidurals who completed the study protocol, 73 demonstrated postoperative functional epidurals with sensory block to ice and 7 demonstrated non-functional epidurals. EWA yielded 65 true positives, 6 true negatives, 8 false negatives, and 1 false positive. Postoperative EWA sensitivity, specificity, positive predictive value and negative predictive value, along with the 95% confidence intervals (CI) were 89% (79–95%), 86% (42–100%), 98% (92–100%), and 43% (18–71%) respectively. Intra-class correlation between waveform assessors was 0.870 (95% CI 0.818–0.910, p < 0.001).ConclusionsEWA is useful in assessing the position of thoracic epidural catheters in the immediate postoperative period, demonstrating high sensitivity and specificity as well as robust inter-rater reliability. For patients in whom sensory block to ice cannot be reliably assessed postoperatively, EWA may provide a useful adjunct for assessing epidural functionality.     

健脾温肾软坚解毒方、康艾注射液联合低剂量化疗治疗老年脾肾两虚型晚期非小细胞肺癌的临床研究

目的观察健脾温肾软坚解毒方、康艾注射液联合低剂量化疗对老年脾肾两虚型晚期非小细胞肺癌患者瘤灶、免疫功能及无进展生存期的影响。方法将80例老年脾肾两虚型晚期非小细胞肺癌患者随机分为治疗组和对照组,每组40例。对照组予常规剂量化疗,治疗组予健脾温肾软坚解毒方、康艾注射液联合低剂量化疗。化疗2个周期后,观察两组患者瘤灶、免疫功能的变化情况,随访患者的无进展生存期。结果①试验期间,对照组脱落2例,试验组无脱落,最终完成试验者78例,其中治疗组40例,对照组38例。②两组实体瘤疗效比较,差异无统计学意义(P0.05)。③化疗1个周期与化疗前组内比较,两组血清NK、CD3~+、CD4~+、CD8~+水平差异无统计学意义(P0.05);化疗2个周期与化疗前组内比较,治疗组血清CD8~+水平升高(P0.05),对照组血清NK、CD3~+、CD4~+水平降低(P0.05)。化疗1个周期后组间比较,治疗组血清CD3~+、CD4~+水平高于对照组(P0.05);化疗2个周期后组间比较,治疗组血清NK、CD3~+、CD4~+水平高于对照组(P0.05)。④两组患者中位无进展生存时间均为4.5个月,差异无统计学意义(P0.05)。结论健脾温肾软坚解毒方、康艾注射液联合低剂量化疗能有效控制老年肺肾两虚型晚期非小细胞肺癌患者的瘤灶变化,并有利于稳定血清NK、CD3~+和CD4~+水平,保护患者的免疫功能。     

局部晚期非小细胞肺癌外科治疗中的气道重建

背景与目的部分局部晚期非小细胞肺癌患者需要采取不同的气道重建方式，以彻底切除病变并最大限度保存肺功能。本研究旨在探讨气道重建中的外科相关问题。方法回顾分析研究2003年1月～2005年6月2206例肺癌手术中100例气道重建患者的临床资料，其中鳞癌42例，腺鳞癌23例，腺癌11例，粘液表皮样癌5例，腺样囊性癌4例，类癌3例及其它混合散在分布类型12例。ⅠB期34例，ⅡB期23例，ⅢA期23例，ⅢB期20例。主要手术方式包括：右上叶袖状切除42例，右下叶袖状切除1例，左上叶袖状切除24例，左下叶袖状切除4例。两叶袖状切除8例，隆凸成形重建17例，肺叶袖状切除合并肺动脉成形4例。结果97例患者为完全性切除（R0），3例为不完全性切除（R1）。术后5例出现并发症，分别为肺部感染2例，胸腔感染1例，支气管胸膜瘘1例，肺泡胸膜瘘1例，并发症发生率为5％。术后住院日为4～27日（中位11日）。99例治愈出院，肺部感染导致死亡1例，手术死亡率为1％。结论对局部晚期非小细胞肺癌采取适当的气道重建方式，符合外科手术原则，可取得较满意的治疗效果。对血管、气管、支气管的处理技巧是手术获得成功的关键。