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OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery. METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0. RESULTS: From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached. CONCLUSIONS: Neoadjuvant atezolizumab in resectable stage IB to IIIB non-small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non-small cell lung cancer.

Esophageal cancer is one of the deadliest cancers worldwide. It typically has a poor overall prognosis because of diagnosis in advanced stages. Sensitive biomarkers for the early detection of esophageal cancer are urgently needed to reduce the high mortality of this disease. Circulating microRNAs (miRNAs) are emerging as a novel non-invasive biomarker for cancer diagnosis due to its high stability and specificity. In this study, we profiled circulating miRNAs in serum of patients with esophageal adenocarcinoma (EAC) using the Solexa sequencing analysis. The analysis demonstrated marked differences of more than 195 circulating miRNAs including 96 of upregulated and 99 of downregulated miRNA in EAC patients compared with healthy subjects. Quantitative reverse transcription PCR verified that the concentrations of circulating miR-25-3p and miR-151a-3p were significantly elevated, while the concentrations of miR-100-5p and miR-375 were significantly decreased in EAC patients compared with healthy controls. These data indicate the profile of these 4 miRNAs may potentially serve as a serum biomarker to identify patients with EAC, and circulating miRNA profiling may be clinically useful for early detection or treatment response in EAC patients.

This paper reports the results of a collaborative lung cancer study between City of Hope Cancer Center (Duarte, California) and CIRECA, LLC (Cambridge, Massachusetts), comprising 328 samples from 249 patients, that used an optical technique known as spectral histopathology (SHP) for tissue classification. Because SHP is based on a physical measurement, it renders diagnoses on a more objective and reproducible basis than methods based on assessing cell morphology and tissue architecture. This report demonstrates that SHP provides distinction of adenocarcinomas from squamous cell carcinomas of the lung with an accuracy comparable to that of immunohistochemistry and highly reliable classification of adenosquamous carcinoma. Furthermore, this report shows that SHP can be used to resolve interobserver differences in lung pathology. Spectral histopathology is based on the detection of changes in biochemical composition, rather than morphologic features, and is therefore more akin to methods such as matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging. Both matrix-assisted laser desorption ionization time-of-flight mass spectrometry and SHP imaging modalities demonstrate that changes in tissue morphologic features observed in classical pathology are accompanied by, and may be correlated to, changes in the biochemical composition at the cellular level. Thus, these imaging methods provide novel insight into biochemical changes due to disease. doi: 10.5858/arpa.2017-0476-SA, In the following publication, we report results of a study carried out jointly between CIRECA, LLC (Cambridge, Massachusetts), and the City of Hope (COH) Cancer Center (Duarte, California) designed to [...]

Analysis of gene expression patterns in normal tissues and their perturbations in tumours can help to identify the functional roles of oncogenes or tumour suppressors and identify potential new therapeutic targets. Here, gene expression correlation networks were derived from 92 normal human lung samples and patient-matched adenocarcinomas. The networks from normal lung show that NKX2-1 is linked to the alveolar type 2 lineage, and identify PEBP4 as a novel marker expressed in alveolar type 2 cells. Differential correlation analysis shows that the NKX2-1 network in tumours includes pathways associated with glutamate metabolism, and identifies Vaccinia-related kinase (VRK1) as a potential drug target in a tumour-specific mitotic network. We show that VRK1 inhibition cooperates with inhibition of poly (ADP-ribose) polymerase signalling to inhibit growth of lung tumour cells. Targeting of genes that are recruited into tumour mitotic networks may provide a wider therapeutic window than that seen by inhibition of known mitotic genes.

IntroductionAdenocarcinoma in situ (AIS), formerly bronchioloalveolar carcinoma, is an uncommon subtype of lung adenocarcinoma and accounts for approximately 3% to 4% of lung cancers. Compared with other lung cancer histologies, AIS patients are less likely to be smokers, yet associations with other lung cancer risk factors and differences by sex have not been determined.MethodsA total of 338 AIS patients and frequency-matched controls from the parent study (cases = 6039, controls = 2073) were included in these analyses. Odds ratios and 95% confidence intervals as estimates of the relative risk were obtained from multivariable unconditional logistic regression analyses.ResultsRisk of AIS was associated with ever smoking (OR = 2.7, 95% confidence intervals: 2.1, 3.6), increased 20% to 30% for each 10-year increase in pack-years of smoking and decreased with increased years since quitting (p for trend

BackgroundConcern has been raised that early detection of lung cancer may lead to the treatment of clinically indolent cancers. No population-based study has examined the natural history of patients with stage I NSCLC who receive no surgery, chemotherapy, or radiation therapy. Our hypothesis is that long-term survival in patients with untreated stage I non-small cell lung cancer (NSCLC) is uncommon.MethodsA total of 101,844 incident cases of NSCLC in the California Cancer Center registry between 1989 and 2003 were analyzed; 19,702 patients had stage I disease, of whom 1,432 did not undergo surgical resection or receive treatment with chemotherapy or radiation. Five-year overall survival (OS) and lung cancer-specific survival were determined for this untreated group, for subsets of patients who were recommended but refused surgical resection, and for T1 tumors.ResultsOnly 42 patients with untreated stage I NSCLC were alive 5 years after diagnosis. Five-year OS for untreated stage I NSCLC was 6% overall, 9% for T1 tumors, and 11% for patients who refused surgical resection. Five-year lung cancer-specific survival rates were 16%, 23%, and 22%, respectively. Among these untreated patients, median survival was 9 months overall, 13 months for patients with T1 disease, and 14 months for patients who refused surgical resection.ConclusionLong-term survival with untreated stage I NSCLC is uncommon, and the vast majority of untreated patients die of lung cancer. Given that median survival is only 13 months in patients with T1 disease, surgical resection or other ablative therapies should not be delayed even in patients with small lung cancers.

IntroductionCytology is commonly used to diagnose non-small cell lung cancer (NSCLC) but is an inaccurate means of diagnosis of bronchioloalveolar carcinoma (BAC). The aims of this study were to calculate the sensitivity and specificity of cytologic diagnosis of BAC and to estimate the misclassification of BAC as other subtypes of NSCLC.MethodsPreoperative fine-needle aspiration cytology diagnoses were compared to histology diagnoses in 222 patients, including 51 patients with pure or mixed BAC, who underwent lung resection for NSCLC at our institution since 1999.ResultsThe sensitivity and specificity of a cytologic diagnosis of BAC were 12% and 99%, respectively. Based on cytologic diagnosis, 63% of BAC was misclassified as adenocarcinoma, and 18% was misclassified as undifferentiated NSCLC. In this cohort, 35% of adenocarcinomas and 12% of undifferentiated NSCLC diagnosed by cytology had BAC histology.ConclusionsDiagnosis of NSCLC by cytology alone results in significant misclassification of BAC, most commonly as adenocarcinoma or undifferentiated NSCLC. Because patients with BAC respond differently to certain treatments such as endothelial growth factor receptor inhibitors and surgical resection of multifocal lung cancer, misclassification of BAC may have important therapeutic implications.

BackgroundIn patients undergoing intraperitoneal (IP) photodynamic therapy (PDT), the combination of aggressive surgical debulking and light therapy causes an apparent systemic capillary-leak syndrome that necessitates significant intensive care unit (ICU) management after surgery.MethodsFrom May 1997 to May 2001, 65 patients underwent surgical debulking and PDT as part of an ongoing phase II trial for disseminated IP cancer. Perioperative data were reviewed retrospectively, and statistical analyses were performed to determine whether any identifiable factors were associated with the need for mechanical ventilation for longer than 1 day and with the occurrence of postoperative complications.ResultsForty-three women and 22 men (mean age, 49 years) were treated. Operative time averaged 9.8 hours, and mean estimated blood loss was 1450 mL. The mean crystalloid requirement for the first 48 hours after surgery was 29.3 L, and 49 patients required blood products. Twenty-four patients were intubated for longer than 24 hours, with a mean of 8.3 days for those intubated longer than 1 day. The median ICU stay was 4 days. Overall, 110 complications developed in 45 (69%) of the 65 patients. Significant complications included 6 patients with acute respiratory distress syndrome, 28 patients with infectious complications, and 4 patients with anastomotic complications. Statistical analyses revealed that surgery-related factors were significantly associated with these complication outcomes.ConclusionsPatients who undergo surgical debulking and IP PDT develop a significant capillary-leak syndrome after surgery that necessitates massive volume resuscitation, careful ICU monitoring, and, frequently, prolonged ventilatory support.