To evaluate the safety and feasibility of implantation and retrieval of a novel implantable microdevice (IMD) in NSCLC patients undergoing operative resection.
Adjuvant therapy has limited impact on ...postsurgical outcomes in NSCLC due to the inability to predict optimal treatment regimens.
An IMD measuring 6.5 mm by 0.7 mm, containing micro-reservoirs allowing for high-throughput localized drug delivery, was developed and loaded with 12 chemotherapeutic agents. Five patients with peripheral lung lesions larger than 1.0 cm were enrolled in this phase 1 clinical study. IMDs were inserted into tumors intraoperatively under direct vision, removed with the resected specimen, and retrieved in pathology. Surrounding tissues were sectioned, stained, and analyzed for tissue drug response to the IMD-delivered microdoses of these agents by a variety of pharmacodynamic markers.
A total of 14 IMDs were implanted intraoperatively with 13 (93%) successfully retrieved. After technique refinement, IMDs were reliably inserted and retrieved in open, Video-Assisted Thoracoscopic Surgery, and robotic cases. No severe adverse reactions were observed. The one retained IMD has remained in place without movement or any adverse effects. Analysis of patient blood revealed no detection of chemotherapeutic agents. We observed differential sensitivities of patient tumors to the drugs on the IMD.
A multi-drug IMD can be safely inserted and retrieved into lung tumors during a variety of surgical approaches. Future studies will encompass preoperative placement to better examine specific tumor responsiveness to therapeutic agents, allowing clinicians to tailor treatment regimens to the microenvironment of each patient.
More than half of all patients with non-small cell lung cancer (NSCLC) have metastatic disease at the time of diagnosis. A subset of these patients has oligometastatic disease, which exists in an ...intermediary state between locoregional and disseminated metastatic disease. In addition, some metastatic patients on systemic therapy may have limited disease progression, or oligoprogression. Historically, treatment of metastatic NSCLC was palliative in nature, with little expectation of long-term survival. However, an accumulation of evidence over the past 3 decades now demonstrates that local ablative therapy to sites of limited metastases or progression can improve patient outcomes for this complex disease. This review examines the evidence behind local ablative therapy in oligometastatic and oligoprogressive NSCLC, with a focus on surgery, stereotactic radiotherapy, and radiofrequency ablation.
Objective A predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1%) or diffusing capacity of the lung for carbon monoxide (DLCO%) of <40% has traditionally been considered to ...convey a high risk of lobectomy owing to elevated postoperative morbidity and mortality. These recommendations, however, were largely derived from the pre–video-assisted thoracoscopic surgical (VATS) era. We hypothesized that VATS lobectomy would be associated with acceptable morbidity and mortality at ppoFEV1% and ppoDLCO% values < 40%. Methods PpoFEV1% and ppoDLCO% were calculated for patients undergoing open or VATS lobectomy for lung cancer in the Society of Thoracic Surgeons General Thoracic database from 2009 to 2011. Univariate comparisons, multivariate analyses, and 1:1 propensity matching were performed. Results A total of 13,376 patients underwent lobectomy (50.9% open, 49.1% VATS). A decreased ppoFEV1% and ppoDLCO% were each independent predictors for both cardiopulmonary complications and mortality in the open group (all P ≤ .008). In the VATS group, ppoFEV1% was an independent predictor of complications ( P = .001) but not mortality ( P = .77), and ppoDLCO% was an independent predictor of complications ( P = .046) and mortality ( P = .008). With decreasing ppoFEV1% or ppoDLCO%, complications and mortality increased at a greater rate in the open lobectomy than in a propensity-matched VATS group (n = 4215 each). For patients with ppoFEV1% < 40%, mortality was greater in the open (4.8%) than in the matched VATS group (0.7%, P = .003). Similar results were seen for ppoDLCO% < 40% (5.2% open, 2.0% VATS, P = .003). The rate of complications was significantly greater at ppoFEV1% < 40% in the open (21.9%) than in the matched VATS (12.8%, P = .005) group and similar results were seen with ppoDLCO% < 40% (14.9% open, 10.4% VATS, P = .016). Conclusions VATS lobectomy can be performed with acceptable rates of morbidity and mortality in patients with reduced ppoFEV1% or ppoDLCO%.
•We found fair concordance between biopsies and resections of lung adenocarcinoma.•A higher nuclear grade and desmoplasia are found in resection specimens.•Presence of a high-grade growth pattern in ...biopsies is of prognostic relevance.•Survival prediction on biopsies shows an acceptable area under the curve.•Biopsy assessment may guide the extent of resection in early-stage adenocarcinoma.
Since lung adenocarcinoma (LUAD) biopsies are usually small, it is questionable if their prognostic and predictive information is comparable to what is offered by large resection specimens. This study compares LUAD biopsies and resection specimens for their ability to provide prognostic and predictive parameters.
We selected 187 biopsy specimens with stage I and II LUAD. In 123 cases, subsequent resection specimens were also available. All specimens were evaluated for growth pattern, nuclear grade, fibrosis, inflammation, and genomic alterations. Findings were compared using non-parametric testing for categorical variables. Model performance was assessed using the area under the curve for both biopsies and resection specimens, and overall (OS) and disease-free survival (DFS) was calculated.
The overall growth pattern concordance between biopsies and resections was 73.9%. The dominant growth pattern correlated with OS and DFS in resected adenocarcinomas and for high-grade growth pattern in biopsies. Multivariate analysis of biopsy specimens revealed that T2-tumors, N1-status, KRAS mutations and a lack of other driver mutations were associated with poorer survival. Model performance using clinical, histological and genetic data from biopsy specimens for predicting OS and DSF demonstrated an AUC of 0.72 and 0.69, respectively.
Our data demonstrated the prognostic relevance of a high-grade growth pattern in biopsy specimens of LUAD. Combining clinical, histological and genetic information in one model demonstrated a suboptimal performance for DFS prediction and good performance for OS prediction. However, for daily practice, more robust (bio)markers are required to predict prognosis and stratify patients for therapy and follow-up.
Summary Background The frequent recurrence of early-stage non-small-cell lung cancer (NSCLC) is generally attributable to metastatic disease undetected at complete resection. Management of such ...patients depends on prognostic staging to identify the individuals most likely to have occult disease. We aimed to develop and validate a practical, reliable assay that improves risk stratification compared with conventional staging. Methods A 14-gene expression assay that uses quantitative PCR, runs on formalin-fixed paraffin-embedded tissue samples, and differentiates patients with heterogeneous statistical prognoses was developed in a cohort of 361 patients with non-squamous NSCLC resected at the University of California, San Francisco. The assay was then independently validated by the Kaiser Permanente Division of Research in a masked cohort of 433 patients with stage I non-squamous NSCLC resected at Kaiser Permanente Northern California hospitals, and on a cohort of 1006 patients with stage I–III non-squamous NSCLC resected in several leading Chinese cancer centres that are part of the China Clinical Trials Consortium (CCTC). Findings Kaplan-Meier analysis of the Kaiser validation cohort showed 5 year overall survival of 71·4% (95% CI 60·5–80·0) in low-risk, 58·3% (48·9–66·6) in intermediate-risk, and 49·2% (42·2–55·8) in high-risk patients (ptrend =0·0003). Similar analysis of the CCTC cohort indicated 5 year overall survivals of 74·1% (66·0–80·6) in low-risk, 57·4% (48·3–65·5) in intermediate-risk, and 44·6% (40·2–48·9) in high-risk patients (ptrend <0·0001). Multivariate analysis in both cohorts indicated that no standard clinical risk factors could account for, or provide, the prognostic information derived from tumour gene expression. The assay improved prognostic accuracy beyond National Comprehensive Cancer Network criteria for stage I high-risk tumours (p<0·0001), and differentiated low-risk, intermediate-risk, and high-risk patients within all disease stages. Interpretation Our practical, quantitative-PCR-based assay reliably identified patients with early-stage non-squamous NSCLC at high risk for mortality after surgical resection. Funding UCSF Thoracic Oncology Laboratory and Pinpoint Genomics.
Several medical systems have adopted minimum volume standards for surgical procedures, including lung and esophageal resection. We sought to determine whether these proposed hospital cutoffs are ...associated with differences in outcomes.
Analyzing the State Inpatient Databases and Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, we evaluated all patients (aged ≥ 18 years) who underwent lobectomy/pneumonectomy or esophagectomy for cancer in California, Florida, and New York (2009-2011). Hospitals were defined as low volume for each procedure per proposed minimum volume standards by year: <40 lung resections and <20 esophagectomies. We compared demographic data and determined the incidence of complications and mortality between patients operated on at low- versus high-volume hospitals. Propensity matching (of demographic characteristics, income, payer, and comorbidities) was performed to balance the cohorts for analysis.
During the time period, 20,138 patients underwent lobectomy/pneumonectomy of which 12,432 operations (61.7%) were performed at low-volume hospitals (n = 456) and 7706 operations were performed at high-volume hospitals (n = 48). Of 1324 patients undergoing esophagectomy, 1087 operations (82.1%) were performed at low-volume hospitals (n = 184), whereas only 237 operations were at high-volume hospitals (n = 6). After propensity matching (lung 1:1 and esophagus 2:1), no major differences were apparent for in-hospital mortality nor major complications for either lung or esophageal resection. Length of stay was longer in low-volume hospitals after lung resection (median 6 vs 5 days; P < .001), but not after esophageal resection.
Although several groups have publicly called for minimum volume requirements for surgical procedures, the majority of patients undergo lung and esophageal resection at hospitals below the proposed cutoffs. The proposed standards for lung and esophageal resection are not associated with a difference in outcomes in this large administrative database. Efforts should be made to determine more meaningful minimum volume requirements and to determine whether such standards are appropriate.
Tracheoesophageal fistula results in persistent leakage of saliva into the trachea, prevents oral feeding, and predisposes to aspiration pneumonia. Large fistula closure may require a free flap to ...cover the defect. When the defect involves the tracheal area between the neck and the mediastinum, a tubeless field for optimal exposure can be advantageous. This article reports the use of veno-venous extracorporeal lung support, a known safe and efficient technique to support the patient’s respiratory function, for this purpose. The typical veno-venous extracorporeal lung support setting includes a femoro-jugular bypass. The patient cases reported here had characteristics that precluded the use of the jugular vein, such as neck radiation dermatitis, previous radical neck dissection, and poor accessibility. Therefore a more rarely described femoro-femoral approach was used. The cases of three patients with persistent tracheoesophageal fistula who had free flap surgeries (two bi-paddled radial forearm free flap and one latissimus dorsi muscle free flap) assisted by femoro-femoral veno-venous extracorporeal lung support are reported.
Abstract
OBJECTIVES: Early clinical stage (T1 and T2) non-small cell lung cancer (NSCLC) is commonly treated with anatomic lung resection and lymph node sampling or dissection. The aims of this study ...were to evaluate the incidence and the distribution of occult N2 disease according to tumour location and the short- and long-term outcomes.
METHODS: We performed a retrospective review of patients with clinical stage I NSCLC who underwent anatomic lung resection and lymphadenectomy. Mediastinal lymphadenectomy (ML) was defined as resection of at least 2 mediastinal stations, always including station 7 lymph nodes. Patients who had a lobe-specific lymphadenectomy were excluded.
RESULTS: One thousand six hundred and sixty-seven consecutive patients met inclusion criteria and were included. Overall, 9% (146/1667) of the patients had occult pN2 disease. At multivariable analysis, adenocarcinoma histology and vascular invasion were independently associated with greater risk of occult pN2 disease. In left and right upper lobe tumours, station 7 nodes were involved in 5 and 13% of pN2 positive cases, respectively. Station 5 and station 2/4 nodes were involved in 29 and 18% of left and right lower lobe pN2 tumours, respectively. There was no postoperative mortality, and postoperative morbidity was 28%. The median overall survival was 77.4 months. N0 patients had a median overall survival of 83.7 months vs 48.0 months and 37.9 months in N1 and N2 populations, respectively (P < 0.001).
CONCLUSIONS: Sixteen percent of pN2 patients had mediastinal lymph node metastasis beyond the lobe-specific lymphatic drainage. We recommend a complete lymphadenectomy be performed, even in clinical stage I NSCLC.
Mortal obligate RNA transcript (MORT), a long noncoding RNA, has been reported as a potential tumor suppressor in many types of cancer. The functions of MORT involved in lung adenocarcinoma (LUAD) ...were investigated in this study.
A total of 67 patients with LUAD (adenocarcinoma) were recruited in this study. Quantitative reverse transcription-polymerase chain reaction was used to assess gene expression. Cell transfections were used to analyze gene interactions. Transwell migration and invasion assay were carried out to analyze cell migration and invasion.
MORT was downregulated, whereas miRNA-223 was upregulated in LUAD. Expression of MORT was significantly affected by tumor metastasis but not by the size of tumors. Expression of miRNA-223 and MORT was inversely correlated in LUAD tissue samples. LUAD cells overexpressing MORT showed downregulated miRNA-223, whereas the expression of MORT was not significantly affected by overexpression of miRNA-223. Besides, overexpression of MORT inhibited, whereas overexpression of miRNA-223 promoted the invasion and migration of LUAD cells. Overexpression of miRNA-223 inhibited the effects of overexpressing MORT on cell invasion and migration.
Therefore, MORT may inhibit cancer cell invasion and migration in LUAD by downregulating miRNA-223.
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