A phase 2 cooperative group adjuvant trial using a biomarker-based decision algorithm in patients with stage I non-small cell lung cancer (SWOG-0720, NCT00792701).

BACKGROUND: This cooperative group adjuvant phase 2 trial in patients with completely resected stage I non-small cell lung cancer with tumor diameters measuring ≥ 2 cm was designed to assess the feasibility and preliminary efficacy of assigning patients to therapy or observation using a molecularly based decision algorithm. METHODS: At least a lobectomy and sampling of recommended mediastinal lymph node stations, good Zubrod performance status, adequate organ function, and a formalin-fixed and paraffin-embedded tumor specimen were required. Excision repair cross-complementing group 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were analyzed using immunofluorescence-based in situ automated quantitative image analysis and categorized as high or low using prespecified cutoff values. Patients with high ERCC1 and RRM1 were assigned to observation and all others to 4 cycles of cisplatin and gemcitabine. Feasibility was defined as treatment assignment within 84 days from surgery in > 85% of patients. Secondary objectives were to estimate the 2-year survival. RESULTS: Treatment assignment met the feasibility criteria in 88% of eligible patients (71 of 81 patients). The collective 2-year disease-free and overall survival rates were 80% and 96%, respectively. Protein levels for RRM1 fell within the previously established range, ERCC1 levels were slightly lower than expected, and they were significantly correlated (correlation coefficient, 0.4). The rates of assignment of patients to observation (22%) and chemotherapy (78%) were as expected. CONCLUSIONS: Gene expression analysis for treatment assignment is feasible. Survival results are encouraging and require future validation. Real-time performance of quantitative in situ ERCC1 and RRM1 analysis requires further development.

Overcoming barriers to lung cancer screening using a systemwide approach with additional focus on the non-screened.

BACKGROUND: The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility. METHODS: Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria. RESULTS: The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented. CONCLUSION: Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community.

Social Distancing to Avoid SARS-CoV-2 Infection in Cancer and Noncancer Patients.

BACKGROUND: Social distancing has been recommended by the Centers for Disease Control and Prevention to avoid exposure to SARS-CoV-2 ( Epidemiol Prev 2020;44:353-362).Cancer patients on or after active therapy seem to be more prone to COVID being symptomatic and life-threatening. When evaluating cancer patients' risk of acquiring COVID, it is essential to know the behavior of cancer patients that will affect their risk of exposure. However, it is not known to what degree social distancing is practiced by cancer patients compared with noncancer patients and what factors lead to the decision to distance oneself. METHOD: After a pilot phase using patients' MyChart messaging, links to the electronic questionnaires were texted to patients using Twillio. Responses were stored on REDCap (Vanderbilt University, Nashville, TN). Six questions about their social distancing behavior and mask wearing were posed and responses were compared between cancer and noncancer patients. Demographics, comorbidities, and a questionnaire about anxiety (Generalized Anxiety Disorder 7-item scale) were recorded. To assess differences between cancer and noncancer groups, Bonferroni-corrected χ 2 tests and proportions confidence intervals were used. RESULTS: The pilot survey was sent in mid-2020 and the full survey followed in January 2021 during a high community COVID incidence. Three hundred eighty-seven cancer patients (32.4% responded) and 503 noncancer patients (22.9% responded) completed the survey. Questions about leaving their houses, driving, shopping, friends, and family indicated that patients with cancer are more cautious ( P < 0.001). Cancer patients were up to 20% more likely to distance themselves. No difference was seen in wearing a mask-both groups wore approximately 90% of the time. Most respondents were female (63% versus 71%). Cancer patients were older (>60 y, 69% versus 45%) and less likely to work (52% versus 31%) or less likely to be White collar workers (21% versus 38%). In both groups, 54% marked "not at all anxious." CONCLUSIONS: Cancer patients' responses revealed a distancing behavior that would likely lower the risk exposure to SARS-CoV-2. It is unclear which of the demographic differences would account for this behavior, although remarkably anxiety was not a clear motivating factor. The high acceptance of masks is encouraging. Early publications during the pandemic and patient education suggesting a higher COVID risk for cancer patients may have reduced risk prone behavior. Considering COVID's impact on the vulnerable cancer population and uncertainty in immunosuppressed patients about clearing the virus or adequately responding to a vaccine, further studies about health behavior and health promotion during the pandemic are needed.

Adjuvant treatment of stage IB NSCLC: the problem of stage subset heterogeneity.

While 5-year survival rates in patients with stage IB non-small-cell lung cancer (NSCLC) are historically modest (40% to 67%), adjuvant chemotherapy trials including this subgroup have shown little evidence of chemotherapeutic benefit. This article reviews the available data regarding adjuvant chemotherapy following surgically resected stage IB NSCLC, framed within the context of present and future proposed definitions of this diagnosis. The discussion addresses limitations of the current staging system and how this contributes to the mixed results seen with adjuvant treatment. In addition, the authors consider current treatment options for stage IB NSCLC and review planned clinical trials for stage I disease designed to exploit new pharmacogenomic findings.

A Defined Esophagectomy Perioperative Clinical Care Process Can Improve Outcomes and Costs.

Esophagectomy (EG) is a high-risk therapy for esophageal cancer and end-stage benign disease. This study compares the results of EG before and after implementation of a perioperative clinical care process including a health provider education program (EP) and institutional uncomplicated postoperative clinical pathway (POP) for purpose quality improvement. This is a single institution retrospective cohort study. The EP was provided to critical care and telemetry unit nurses and the POP was imbedded in the electronic health record. Patients undergoing elective EG with reconstruction with the stomach for benign disease or cancer were included from 2005 to 2011. Cohorts were pre- and postimplementation (PreI and PostI) of an EP and 8-day POP (August 2008). Patient, tumor and peri/postoperative-specific variables were compared between cohorts, as well as resource utilization and hospital costs. We identified 33 PreI and 41 PostI patients. Both cohorts had similar patient demographics, preoperative comorbidities, majority cancer diagnosis, and for cancer patients, majority adenocarcinoma and IIB/III pathologic stage. Both groups had one death and similar rate of discharge to home. The PostI cohort demonstrated reduced 30-day readmission rate (2.4% vs 24.2%); P < 0.05. In regard to clinical outcomes, the PostI group exhibited reduced deep venous thrombosis/pulmonary emboli (2.4% vs 18.2%); P < 0.05. The PostI group demonstrated significantly reduced radiographic test utilization and costs, as well as total overall 30-day readmission costs. A defined perioperative clinical process involving educating the patient care team and implementing a widely disseminated POP can reduce complications, 30-day readmission rates, and hospital costs after EG.

A novel operative approach to scimitar syndrome.

Scimitar syndrome is a rare congenital cardiac anomaly defined by an anomalous right pulmonary vein draining the right lung to the inferior vena cava. We describe a unique operative approach performed on 2 patients with infantile scimitar syndrome.

Bipolar radiofrequency to ablate atrial fibrillation in patients undergoing mitral valve surgery.

BACKGROUND: Atrial fibrillation (AF) affects 30% to 50% of patients undergoing mitral valve surgery. The optimum treatment of AF in these patients is unclear. The purpose of this study was to describe initial clinical experience using a bipolar radiofrequency clamp to facilitate AF ablation in patients undergoing mitral valve surgery. METHODS: From November 2001 through March 2003 a bipolar radiofrequency clamp was used to facilitate AF ablation in 108 patients undergoing mitral valve surgery. Preoperative AF was paroxysmal in 25%, persistent in 26%, and permanent in 49% of the patients. All patients underwent bilateral pulmonary vein isolation performed with the bipolar radiofrequency clamp and excision or exclusion of the left atrial appendage. Most patients had connecting lesions between the right and left pulmonary veins and between the left atrial appendage and the left pulmonary veins. Novel statistical methods were used to create a plot of the prevalence of AF versus time after surgery. RESULTS: Mean time required for AF ablation was 17+/-4 minutes (range, 9-28 minutes). All patients left the operating room with sinus rhythm or with atrial or atrioventricular pacing for an underlying nodal rhythm. Perioperative AF was common, affecting 64% of patients. At discharge, 33% of patients were in AF or atrial flutter. By 3 months postoperatively, the predicted prevalence of AF or atrial flutter was 15%. There were no device-related complications. CONCLUSIONS: Bipolar radiofrequency facilitates rapid and safe AF ablation in patients with mitral valve disease. Perioperative AF is common and should be treated aggressively. By 3 months postoperatively, 85% of patients are free of AF or atrial flutter. Continued follow-up is necessary to document late results of this strategy.

Outcomes and efficacy of thoracic surgery biopsy for tumor molecular profiling in patients with advanced lung cancer.

BACKGROUND: Molecular testing of patients with advanced non-small cell lung cancer for personalized therapy often is limited by insufficient specimen from nonsurgical biopsies. We measured the feasibility, patient safety, and clinical impact of thoracic surgical tumor biopsy in patients with stage IV non-small cell lung cancer. METHODS: This is a single institution retrospective analysis. Patients with stage IV non-small cell lung cancer undergoing elective surgical tissue biopsy for molecular analysis were evaluated from March 2011 to November 2012. Perioperative specific variables were measured. RESULTS: Twenty-five patients with known or suspected stage IV non-small cell lung cancer undergoing surgical biopsy were identified. All cases were discussed at a multidisciplinary thoracic oncology conference or a multidisciplinary thoracic oncology clinic. Preoperative histologies included adenocarcinoma in 20 patients (80.0%) and squamous cell carcinoma in 2 patients (8.0%). Surgical procedures consisted of video-assisted thoracic surgery wedge biopsy (16, 64%), video-assisted thoracic surgery pleural biopsy (4, 16.0%), mediastinoscopy (2, 8.0%), supraclavicular/cervical lymph node excisional biopsy (3, 12.0%), and rib/chest wall resection (2, 8.0%). There were no deaths and 5 postoperative complications (20.0%). Surgery identified potentially targetable molecular information in 19 of the total patients undergoing operation (76.0%) and changed the treatment strategy in 14 patients (56.0%); 10 of the total cohort (40.0%) were enrolled into therapeutic targeted clinical trials. CONCLUSIONS: These data suggest that thoracic surgical biopsy can be safely performed in appropriately selected patients with stage IV non-small cell lung cancer and direct personalized therapy and enrollment into relevant clinical trials. Patients with advanced-stage non-small cell lung cancer should be discussed in a multidisciplinary setting to determine the need and strategy for thoracic surgical biopsy for molecular analysis.

Size of Stage IIIA primary lung cancers and survival: a surveillance, epidemiology and end results database analysis.

Size of early-stage lung cancer is important in the prognosis of patients. We examined the large population-based Surveillance, Epidemiology and End Results database to determine if tumor size was an independent risk factor of survival in patients undergoing lobectomy for N2 positive Stage IIIA nonsmall cell lung cancer (NSCLC). This study identified 1971 patients diagnosed with N2 positive Stage IIIA NSCLC, from 1998 to 2007, and who underwent lobectomy. Five tumor groups based on the seventh edition TNM lung cancer staging system (pathologic T1a 2 cm or less; T1b greater than 2 cm and 3 cm or less; T2a greater than 3 cm and 5 cm or less; T2b greater than 5 cm and 7 cm or less; T3 greater than 7 cm) were analyzed. Survival was reduced in patients with T3, T2a, and T2b tumors compared with patients with T1a and T1b (P < 0.001). Survival estimates correlated with tumor size with poorer survival in T3 followed by T2b, T2a, and then T1b and T1a. Cohorts with T1a (hazard ratio [HR], 0.53; P = 0.01) and T1b (HR, 0.54; P = 0.01) were both found to have decreased hazard of death. Negative predictors of survival, in addition to increasing tumor size, included age and male gender, whereas positive predictors included tumor Grade I and upper lobe location. Increasing size of tumor is an independent negative risk factor for survival in patients undergoing lobectomy for N2 positive Stage IIIA NSCLC.

Repair of nonmalignant postlaryngectomy pharyngotracheal fistula.

The repair of nonmalignant postlaryngectomy pharyngotracheal fistulae is not commonly encountered in medical literature. This rare complication can occur years after laryngectomy for cancer and reconstruction of a neopharynx, and is often associated with adjuvant radiation to the area, making the choice of method for surgical repair critical for success. Optimally, a pedicled myofascial flap from the pectoralis major muscle, from outside the field of radiation, is used to reinforce the repair of the fistula. We present 2 rare cases.

Video assisted thoracic surgery sublobar resection of intralobar pulmonary sequestration after preoperative embolization of systemic blood supply.

Intralobar pulmonary sequestration is abnormal lung tissue of embryonic origin that receives arterial blood supply from the systemic arterial circulation from the abdominal aorta. The arterial blood supply traverses the diaphragm and courses through the inferior pulmonary ligament. Intralobar pulmonary sequestrations are usually treated by anatomic lobar or sublobar resections via an open thoracotomy. Recent reports suggest the utility of a video assisted thoracic surgery (VATS) pulmonary resection. However, the presence of the feeding systemic artery often makes VATS resection difficult or impossible, due to the risk of injury to the feeding vessel, and subsequent retraction below the diaphragm. We present procedural video recordings describing a multidisciplinary procedure, where precedent coil embolization of the feeding systemic vessel allows for relative risk-free VATS sublobar resection of the intralobar pulmonary sequestration.

Survival comparison of adenosquamous, squamous cell, and adenocarcinoma of the lung after lobectomy.

BACKGROUND: Primary adenosquamous carcinoma (ASC) of the lung is a rare tumor that may carry a poor prognosis. We examined a national database to see if ASC exhibited distinct clinical behavior from squamous cell (SC) and adenocarcinoma (AC) of the lung. METHODS: This is a retrospective study querying the Surveillance, Epidemiology, and End Results database to identify 872 surgical patients diagnosed with ASC, 7888 with SC, and 12,601 with AC of the lung from 1998 to 2002. Analysis characterized clinical variables to determine patterns of presentation and compared survival among the above three histologic groups after lobectomy for stage I and II disease. RESULTS: ASC represented 4.1% of the 21,361 patients examined. ASC tended toward right side (56.9%) laterality and upper lobe (60.0%) location. Compared with AC, patients with ASC and SC were more likely to be male (p < 0.0001), and ASC patients had worse histologic grade (p< 0.0001). Survival after lobectomy for stage I and II disease was significantly reduced in ASC and SC compared with AC (p < 0.0001). ASC had a significantly increased hazard ratio of 1.35 and 1.27 relative to AC and SC, respectively. Other significant negative predictors of survival included tumor grade of III and IV, stage II, age, and black ethnicity. CONCLUSIONS: This large review demonstrates that ASC is an uncommon tumor with distinct clinical behavior and worse prognosis than AC and SC. Further insight into the molecular profile of ASC is needed to determine the cause of its biologic aggressiveness.

Racial disparities on the use of invasive and noninvasive staging in patients with non-small cell lung cancer.

INTRODUCTION: Racial disparities have been reported in non-small cell lung cancer (NSCLC) staging and therapeutic outcomes. We investigated whether such disparities exist in the era of modern noninvasive staging modalities, including positron emission tomography scan use. METHODS: NSCLC patients from the California Cancer Registry diagnosed between January 1, 1994, and December 31, 2004, were included. The likelihood of obtaining invasive (thoracoscopy, bronchoscopy, and mediastinoscopy) and noninvasive staging procedures (computed tomography, magnetic resonance imaging, and positron emission tomography scans), along with surgical resection, were analyzed using logistic regression adjusted for known confounders. RESULTS: Of 13,762 NSCLC patients, 12,395 with adequate staging information were included. 10,217 patients (82%) were classified as white, 2178 patients (18%) were non-white, and 738 were black patients (6%). No association was seen between race and the use of either noninvasive (odds ratio [OR] = 1.02; p = 0.76) or invasive staging procedures (OR = 0.96; p = 0.44). However, compared with white patients, black patients had a lower likelihood of undergoing surgery, regardless of noninvasive (OR = 0.6; p <0.001) or invasive staging use (OR = 0.63; p = 0.02). There was no survival difference for those who underwent surgery between white and non-white patients, regardless of noninvasive (hazard ratio = 0.95; p = 0.45) or invasive staging (hazard ratio = 1.03; p = 0.79). CONCLUSIONS: In contrast to prior published work, we found no difference in rates of both invasive and noninvasive staging between white and non-white patients. However, non-white patients-particularly blacks-were less likely to receive surgery. The reason for the apparent difference in surgical rates could not be explained by the variables we evaluated. Thus, other factors such as personal preference or access to care require further investigation.

Induction chemoradiotherapy increases pleural and pericardial complications after esophagectomy for cancer.

HYPOTHESIS: Limited information is available on late complications of multimodality therapy for locally advanced esophageal cancer. This study focuses on postesophagectomy benign pleural and pericardial complications to determine their prevalence, temporal pattern, and treatment, and their association with induction chemoradiotherapy and influence on survival. METHODS: Between March 1987 and November 2001, 291 patients with clinical stage > or = IIA esophageal cancer underwent esophagectomy; 106 received induction chemoradiotherapy. A propensity score incorporating clinical stage and histopathology was used to identify 100 matched pairs of induction chemoradiotherapy and surgery-only patients. Among these, occurrence of pleural effusion, pericardial effusion, and pericarditis was ascertained by follow-up. Time-related occurrence, risk factors, and association with survival were assessed by repeated-events analyses. RESULTS: During follow-up, 61 induction chemoradiotherapy patients experienced at least one pleural or pericardial complication, as did 46 propensity-matched surgery-only patients. Most occurred within 1 year, with 1-year freedom from occurrence only 34% after induction chemoradiotherapy and 59% after surgery only (p = 0.02). Risk of pleural effusion was nearly twice as great (hazard ratio 1.7, p = 0.0004) and pericardial complications 5 times greater (hazard ratio 5.3, p = 0.0005) after induction chemoradiotherapy than after surgery alone. Complications after induction chemoradiotherapy required intervention somewhat more frequently (58% versus 47%, p = 0.18), although they did not diminish subsequent survival (p > 0.8). CONCLUSIONS: Benign pleural and pericardial complications occur surprisingly frequently after esophagectomy, particularly when induction chemoradiotherapy is employed. This must be factored into discussions of morbidity for multimodality treatment strategies for locally advanced esophageal cancer and should be considered distinct from acute toxicity of induction chemoradiotherapy reported.

Diagnosis and management of subclavian artery stenosis prior to coronary artery bypass grafting in the current era.

There are several approaches to managing subclavian artery stenosis (SAS) prior to coronary artery bypass grafting (CABG) with an intended internal thoracic artery (ITA) graft to the left anterior descending (LAD) artery. We herein review the incidence of and various diagnostic modalities for detecting SAS. Published relevant clinical studies from the interventional cardiovascular and cardiac surgical literature are summarized. Particular emphasis is placed on the efficacy of various approaches to the patient diagnosed with SAS prior to CABG. Stenting the subclavian artery prior to bypass surgery and using an in situ ITA is compared to using the ITA as a "free" graft. The incidence of restenosis after subclavian artery angioplasty or stenting is not trivial and has been reported to occur at a rate of 6% to 21%; however, the average rate of restenosis with stenting appears to be in the mid-teens. Subacute subclavian stent thrombosis or occlusion is exceptionally rare, suggesting that a percutaneous approach to SAS is reasonable prior to CABG. For patients requiring emergent revascularization, placement of a free ITA graft to the LAD appears to be a safe and durable treatment as patency rates are comparable to that of an in situ LITA to the LAD. In summary, although no randomized clinical trials address the optimal management of SAS prior to CABG, both percutaneous and surgical options appear to be safe and reasonably durable.

Adjuvant chemotherapy of stage I non-small cell lung cancer in North America.

The utility of adjuvant chemotherapy after surgical resection for early-stage non-small cell lung cancer (NSCLC) is now well established. Although a number of randomized clinical trials have demonstrated the efficacy of platinum-based chemotherapy in the overall population treated, subset analysis, excepting Japanese studies, has uniformly shown the greatest efficacy for patients with stage II and III disease and the least benefit for patient with stage I disease. We review data regarding adjuvant therapy of stage I NSCLC from clinical trials performed in North America and Europe. Pertinent trials from Japan are discussed elsewhere in this issue.

Advances in positron emission tomography technology have increased the need for surgical staging in non-small cell lung cancer.

OBJECTIVES: Pretreatment staging of patients with non-small cell lung cancer is critically important in determining an appropriate treatment plan. As positron emission tomography (PET) and computed tomography (CT) are proven complementary modalities in clinical staging, recent advances in PET technology have brought forth integrated PET/CT as the new standard. We tested the hypothesis that improvements in PET technology have not increased the sensitivity or specificity of PET in the staging of non-small cell lung cancer to an extent that surgical staging is no longer required. METHODS: This is a retrospective, single-institution review of 336 patients from 1995 to 2005 with biopsy-proven non-small cell lung cancer who underwent [18F] fluoro-2-deoxy-D-glucose-PET before mediastinal lymph node sampling by cervical mediastinoscopy or thoracotomy. Clinical records, histopathologic reports, and PET findings were reviewed. Data were analyzed by the Pearson chi2 test. RESULTS: Within the study population, 210 patients had routine PET and 126 had integrated PET/CT. For detecting mediastinal metastases the sensitivities of PET versus integrated PET/CT were 61.1% versus 85.7% (P < .05), specificities were 94.3% versus 80.6% (P < .001), positive predictive values were 68.8% versus 55.8%, negative predictive values were 92.1% versus 95.2%, and overall accuracy was 88.6% versus 81.7%. CONCLUSIONS: Improvements in PET technology have increased integrated PET/CT sensitivity at the cost of significantly decreased specificity. Although it may appear that integrated PET/CT incurs fewer false negative results, the dramatic increase in false positive results reinforces the notion that integrated PET/CT should be used only as an adjunct to clinical staging and that surgical staging remains the gold standard in non-small cell lung cancer.