Meta-Analysis of Rates and Risk Factors for Local Recurrence in Surgically Resected Patients With NSCLC and Differences Between Asian and Non-Asian Populations.

Introduction: Postoperative radiotherapy (PORT) reduces local failure in patients with NSCLC, without a clear overall survival benefit. It is unknown whether the subsets of patients benefit. Two recent large randomized controlled trials, PORT-C (People's Republic of China) and Lung ART (Europe), reported widely different locoregional recurrence (LR) rates in the control arms, at 18.3% and 28.1% (46% of which were mediastinal recurrences), respectively. We performed a meta-analysis of patients with pathologic (p) N0 to N2 disease to evaluate the risk factors for LR and to explore possible differences in recurrence risk between Asian population (AP) and non-Asian population (NAP). Methods: We identified all original studies of curative NSCLC surgical resection which reported risk of LR between January 1, 2000, and January 10, 2021, excluding studies with less than 10 LR, patients with metastatic disease, or any neoadjuvant therapy. A total of 87 studies were identified with pN0 to N2 disease; of these, 56 were of high quality (HQ) on the basis of the Newcastle-Ottawa Scale. For each risk factor, we derived pooled relative risk (RR) and 5-year rate estimates using random-effects models. Results: Overall, the three significant highest pooled RRs (95% confidence intervals) for LR were pN2 versus pN0 (3.01, 1.39-6.55), lymphovascular invasion (1.92, 1.58-2.33), and advanced pT3-4 stage versus pT1 (1.86, 1.53-2.25). For HQ studies, the highest RRs for LR were lymphovascular invasion (1.94, 1.57-2.40), sublobar versus lobar resection (1.86, 1.46-2.36), and pN1 versus pN0 (1.84, 1.37-2.47), but pN2 versus pN0 was no longer significant (3.0, 0.57-15.61), on the basis of only two eligible studies. The RRs for LR were consistent for most factors in AP and NAP, although the RR for male versus female sex was higher in AP (1.44, 1.21-1.72) than in NAP (1.09, 0.99-1.19). Where reported, the pooled rate of LR at 5 years was lower in AP (12.0%) than in NAP (22.7%), despite similar overall 5-year recurrence rates (both LR and distal) in both populations: 38.0% in AP and 37.3% in NAP. Nevertheless, a lower 5-year mortality rate was noted in AP (24.3%) than in NAP (45.9%). Conclusions: There is little high-quality evidence to support the hypothesis that pN2 disease is a risk factor for LR, but LR seems to be lower in Asians. Prospective evaluation of LR factors and rates may be necessary before further prospective evaluation of PORT, because it may not depend on nodal status alone. Recurrence rates may differ in Asians. The impact of mutational status and modern treatment including targeted therapies and immune checkpoint inhibitors is inadequately studied.

A Review of Concurrent Chemo/Radiation, Immunotherapy, Radiation Planning, and Biomarkers for Locally Advanced Non-small Cell Lung Cancer and Their Role in the Development of ECOG-ACRIN EA5181.

ECOG-ACRIN EA5181 is a current prospective, randomized trial that is investigating whether the addition of concomitant durvalumab to standard chemo/radiation followed by 1 year of consolidative durvalumab results in an overall survival benefit over standard chemo/radiation alone followed by 1 year of consolidative durvalumab in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC). Because multiple phase I/II trials have shown the relative safety of adding immunotherapy to chemo/radiation and due to the known synergism between chemotherapy and immunotherapy, it is hoped that concomitant durvalumab can reduce the relatively high incidence of local failure (38%-46%) as seen in recent prospective, randomized trials of standard chemo/radiation in this patient population. We will review the history of radiation for LA-NSCLC and discuss the role of induction, concurrent and consolidative chemotherapy as well as the concerns for late cardiac and pulmonary toxicities associated with treatment. Furthermore, we will review the potential role of next generation sequencing, PD-L1, ctDNA and tumor mutation burden and their possible impact on this trial.

Impact of the National Lung Screening Trial (NLST) publication and Medicare Lung cancer screening payment on lung cancer incidence rates: An interrupted time series analysis.

INTRODUCTION: Explore the impact of the Lung Cancer Screening Trial (NLST-September-2011) and the Medicare approval for CT-screening (CT-LCS-AP-February-2015) on lung cancer incidence rates, mortality, and the percentage of early-stage lung cancer diagnosis (ESLCD-T1-T2N0M0). METHODS: Retrospective interrupted time series analysis using SEER-18 database. All individuals with lung cancer (LC) diagnosis from 2006 to 2016 were included. The effect of NLST and CT-AP-2015 on the monthly percentage of early-stage ESLCD was the primary outcome, additionally LC incidence and mortality rates were calculated. The analysis was performed by age, sex, race, marital status, insurance status, and household income. Bivariate and multivariate models were used to identify predictors of ESLCD. RESULTS: The study cohort was composed by 388,207 individuals, 69 years old in average, 46.6 % female, and 81.1 % white. LC incidence and mortality rates declined from 2006 to 2016 without association with NLST-September-2011 and CT-LCS-AP-February-2015. The percentage of ESLCD increased over time for all groups. Overall rates of ESLCD started at 18 % in January-2006 and increased to 25 % by December-2016. The intervention NLST-2011 did not show an impact in the ESLCD while the CT-AP-2015 showed a significant impact in the ESLCD trend (p < 0.001). ESLCD was associated with female, white, insurance, and household incomes above median. Medicare expansion was a significant factor for insured group, married patients and those from households under the median income level. CONCLUSION: Medicare approval for CT screening was found to have a statistically significant effect on the diagnosis of early-stage lung cancer and neither NLST-September-2011 nor CT-AP-2015-February-2015 impacted the incidence nor mortality rates. POLICY SUMMARY: To improve early-stage lung cancer diagnosis, it is vital to invest in health policies to increase Lung Cancer Screening implementation and to reduce disparities in access to diagnosis. Furthermore, policies that facilitate access to diagnosis and treatment are crucial to reduce lung cancer mortality.

Bevacizumab's Association With a Decreased Risk of Brain Metastases in ECOG-ACRIN E1505, a Phase 3 Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab in Surgically Resected NSCLC.

Introduction: ECOG-ACRIN E1505 was a phase 3 randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with stages IB (>4 cm) to IIIA NSCLC. We sought to estimate the incidence and risk factors for brain recurrence as compared with extracranial recurrences (ECRs). Methods: ECOG-ACRIN E1505 noted that bevacizumab failed to improve overall survival (OS) (OS hazard ratio [HR] = 0.99 [0·82-1·19], p = 0.90) or recurrence-free survival when added to chemotherapy in the adjuvant setting. The cumulative incidence of brain/ECR was estimated after adjusting for recurrence at other sites and death as competing events. A multivariable regression model was fitted using competing risk analysis to evaluate the effect of covariates on brain recurrence incidence. Results: Median follow-up was 50.4 months. Among the 1501 patients enrolled, 472 developed ECR. There were 122 patients who had recurrence in the brain with or without simultaneous ECR as the first recurrence site (all-brain recurrences [ABRs]), and 84 of those with ABRs had recurrence in the brain only (isolated-brain recurrence [IBR]). The incidence of ABR, IBR, and ECR at 6 years was 9.9%, 5.9%, and 38.8%, respectively. Chemotherapy plus bevacizumab was associated with a decreased incidence of ABR (HR = 0.64, p = 0.02) and IBR (HR = 0.62, p = 0.032), but there was no significant trend for an OS decrement in the bevacizumab arm versus the control arm for both ABR and IBR. Median survivals associated with IBR, ABR, and ECR were 9.5, 9.5, and 14.1 months, respectively. Nonsquamous histology (HR = 1.87, p = 0.003) was also associated with ABR. ECR was associated with nonsquamous NSCLC histology (HR = 1.79, p < 0.01) and stage/N2 involvement (HR = 1.13/1.37, both p < 0.01). Conclusions: The addition of bevacizumab to chemotherapy was associated with reduction in brain recurrences, but not ECR. Brain metastases whether isolated or not are associated with a lower median survival than ECR and unlike ECR are not associated with traditional staging variables.

A Review of Immunotherapy for Stage III and Metastatic Non-Small Cell Lung Cancer and the Rationale for the ECOG-ACRIN EA5181 Study.

ECOG-ACRIN EA5181 is a phase III prospective, randomized trial that randomizes patients undergoing chemo/radiation for locally advanced non-small cell lung cancer (LA-NSCLC) to concomitant durvalumab or no additional therapy, with both arms receiving 1 year of consolidative durvalumab. Radiation dose escalation failed to improve overall survival in RTOG 0617. However, conventionally fractionated radiation to 60 Gy with concomitant chemotherapy is associated with a high risk of local failure (38%-46%). It is hoped that concomitant immunotherapy during chemo/radiation can help decrease the risk of local failure, thereby improving overall survival and progression-free survival with acceptable toxicity. In this article, we review conventional chemo/radiation therapy for LA-NSCLC, as well as the quickly evolving world of immunotherapy in the treatment of non-small cell lung cancer and discuss the rationale and study design of EA5181. IMPLICATIONS FOR PRACTICE: This article provides an up-to-date assessment of how immunotherapy is reshaping the landscape of metastatic non-small cell lung cancer (NSCLC) and how the impact of this therapy is now rapidly moving into the treatment of patients with locally advanced NSCLC who are presenting for curative treatment. This article reviews the recent publications of chemo/radiation as well as those combining immunotherapy with chemotherapy and chemo/radiation, and provides a strategy for improving overall survival of patients with locally advanced NSCLC by using concomitant immunotherapy with standard concurrent chemo/radiation.

The Incidence of Node-Positive Non-small-Cell Lung Cancer Undergoing Sublobar Resection and the Role of Radiation in Its Management.

Purpose: To identify the incidence, preoperative risk factors, and prognosis associated with pathologically positive lymph node (pN+) in patients undergoing a sub-lobar resection (SLR). Methods: This is a retrospective study using the National Cancer Database (NCDB) from 2004 to 2014 analyzing SLR excluding those with any preoperative chemotherapy and/or radiation, follow-up <3 months, stage IV disease, or >1 tumor nodule. Multivariable modeling (MVA) was used to determine factors associated with overall survival (OS). Propensity score matching (PSM) was used to determine preoperative risk factors for pN+ in patients having at least one node examined to assess radiation's effect on OS in those patients with pN+ and to determine whether SLR was associated with inferior OS as compared to lobectomy for each nodal stage. Results: A total of 40,202 patients underwent SLR, but only 58.3% had one lymph node examined. Then, 2,615 individuals had pN+ which decreased progressively from 15.1% in 2004 to 8.9% in 2014 (N1, from 6.3 to 3.0%, and N2, from 8.4 to 5.9%). A lower risk of pN+ was noted for squamous cell carcinomas, bronchioloalveolar adenocarcinoma (BAC), adenocarcinomas, and right upper lobe locations. In the pN+ group, OS was worse without chemotherapy or radiation. Radiation was associated with a strong trend for OS in the entire pN+ group (p = 0.0647) which was largely due to the effects on those having N2 disease (p = 0.009) or R1 resections (p = 0.03), but not N1 involvement (p = 0.87). PSM noted that SLR was associated with an inferior OS as compared to lobectomy by nodal stage in the overall patient population and even for those with tumors <2 cm. Conclusion: pN+ incidence in SLRs has decreased over time. SLR was associated with inferior OS as compared to lobectomy by nodal stage. Radiation appears to improve the OS in patients undergoing SLR with pN+, especially in those with N2 nodal involvement and/or positive margins.

Diabetes mellitus type 2 is associated with increased tumor expression of programmed death-ligand 1 (PD-L1) in surgically resected non-small cell lung cancer-A matched case-control study.

OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression is a biomarker for cancer immunotherapy. Diabetes mellitus type-2 is a comorbid disease associated with adverse outcomes in Non-Small Cell Lung Cancer (NSCLC). We aimed to investigate the differences in PD-L1 expression in diabetics. METHODS: A matched case-control cohort of surgically-resected NSCLC was assembled from an early multicenter study (PMID: 19152440). PD-L1 immunohistochemistry (Clone 22C3) was graded by a tumor positive score (TPS) system (TPS0: no staining; TPS1: <1%; TPS2: 1-49%; TPS3: ≥50%). Variables showing significance at univariate survival analysis were fit in a Cox regression survival model. RESULTS: Diabetics (n=40) and nondiabetics (n=39) showed no differences in age, gender, cancer stage, and follow-up. NSCLCs were more likely PD-L1 positive in diabetics but with tumor positivity <50% (TPS0: 7.5 vs. 20.5%, TPS1: 35 vs. 25.6%, TPS2: 45 vs.23.1%, TPS3: 12.5 vs. 30.8%, respectively; P<0.05). In diabetics, squamous cell carcinomas (SCC) and adenocarcinomas were mainly TPS2 (65% vs. 20%) and TPS1 (50% vs. 26%), respectively. Peritumoral inflammation correlated with TPS (r=0.228), a relationship accentuated in diabetics (r=0.377, P<0.05) but diminished and non-significant in nondiabetics (r=0.136, P≥0.05). This association was stronger in SCC (r=0.424). Diabetes was associated with increased tumor recurrence (HR: 3.08; 95%CI: 1.027-9.23). CONCLUSION: Diabetes is associated with an increase in peritumoral inflammation, PD-L1 positivity, and recurrence in NSCLC, more pronounced in SCC, suggesting the possibility of metabolic reprogramming and upregulation of PD-L1 by inducible pathways.

The Role of Race and Economic Characteristics in the Presentation and Survival of Patients With Surgically Resected Non-Small Cell Lung Cancer.

BACKGROUND: Little is understood regarding the inter-relation between economic, marital, and racial/ethnic differences in presentation and survival of surgically resected lung cancer patients. Our investigation will assess these differences in addition to known therapeutic, patient, and histopathologic factors. METHODS: A retrospective review of the Surveillance Epidemiology and End Reporting database was conducted through the years 2007-2012. The population was split into nine different ethnic groups. Population differences were assessed via chi-square testing. Multivariable analysis (MVA) were used to detect overall survival (OS) differences in the total surgical population (TS, N = 35,689) in an ear (T1-T2 < 4 cm N0) surgical population [early-stage resectable (ESR), N = 17,931]. Lung cancer-specific survival (LCSS) was assessed in the ESR. RESULTS: In the TS population, as compared to Whites, Blacks, and Hispanics presented with younger age, more adenocarcinomas, lower rates of marriage, lower rates of insurance, less stage I tumors, and had less nodes examined, but their type of surgical procedures and OS/LCSS were the same. MVA demonstrated that lower OS and LCSS were associated with males, single/divorced/widowed partnership, lower income (TS only), and Medicaid insurance. MVA also found that Blacks and Hispanics had a similar OS/LCSS to Whites and that all ethnic groups were associated with a similar or better outcomes. The 90-day mortality and positive nodes were correlated with not having insurance and not being married, but they were not associated with ethnicity. CONCLUSION: In TS and ESR groups, OS was not different in the two largest ethnic groups (Black and Hispanic) as compared to Whites, but was related to single/widowed/divorced status, Medicaid insurance, and income (TS group only). Nodal positivity was associated with patients who did not have a married partner or insurance suggesting that these factors may impact disease biology. Economic and psychosocial variables may play a role in survival of ear lung cancer in addition to standard histopathologic and treatment variables.

Population-based differences in the outcome and presentation of lung cancer patients based upon racial, histologic, and economic factors in all lung patients and those with metastatic disease.

To investigate the interrelation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of patients with lung cancer in nine different ethnic groups. A retrospective review of the SEER database was conducted through the years 2007-2012. Population differences were assessed via chi-square testing. Multivariable analyses (MVA) were used to detect overall survival (OS) differences in the total population (TP, N = 153,027) and for those patients presenting with Stage IV (N = 70,968). Compared to Whites, Blacks were more likely to present with younger age, male sex, lower income, no insurance, single/widowed partnership, less squamous cell carcinomas, and advanced stage; and experience less definitive surgery, lower OS, and lung cancer-specific (LCSS) survival. White Hispanics presented with younger age, higher income, lower rates of insurance, single/widowed partnership status, advanced stage, more adenocarcinomas, and lower rates of definitive surgery, but no difference in OS and LCSS than Whites. In the TP and Stage IV populations, MVAs revealed that OS was better or equivalent to Whites for all other ethnic groups and was positively associated with insurance, marriage, and higher income. Blacks presented with more advanced disease and were more likely to succumb to lung cancer, but when adjusted for prognostic factors, they had a better OS in the TP compared to Whites. Disparities in income, marital status, and insurance rather than race affect OS of patients with lung cancer. Because of their presentation with advanced disease, Black and Hispanics are likely to have increased benefit from lung cancer screening.

Compliance and safety of a novel home exercise program for patients with high-grade brain tumors, a prospective observational study.

PURPOSE: The purpose of this study is to evaluate compliance with and safety of a novel independent home exercise program for patients with high-grade brain tumors. We designed this program around the preferences and individual capabilities of this population as well as the potential barriers to exercise in cancer patients. Demographics were collected to better understand those that persisted with exercise. METHODS: Subjects with high-grade brain tumor received one-time training that included watching an exercise video and live demonstration of resistance band exercises, a balance exercise, and recommendations for walking. Subjects were instructed to do the exercises every day for 1 month. Main outcome measures were percentage of subjects who exercised throughout the month, frequency of exercising, demographic factors, quality of life scores (assessed by FACT-BR), and self report of adverse events. RESULTS: Fourteen of the 15 (93%) subjects started the exercises during the course of the month. Nine of the fifteen (60%) continued the exercises throughout the month. Three additional subjects would have continued to exercise if formal or supervised rehabilitation had been offered. Among the subjects who continued the exercises regularly, higher frequency of exercising was significantly associated with living as married (p = 0.033), annual income >$50,000 (p = 0.047), scores of physical well-being (p = 0.047), and brain cancer specific well-being (p = 0.054) subscales. Among those who exercised frequently, there was also a trend towards increase in total FACT-BR scores (p = 0.059). The subjects who scored higher on the social well-being subscale of the FACT-BR at baseline self-reported a higher likelihood to continue the exercises after 1 month of participation in the study (p = 0.018). No adverse events were reported. CONCLUSIONS: Our small group of subjects with high-grade brain tumors demonstrated compliance with and safety of a novel independent strength and balance exercise program in the home setting. Higher frequency of exercising was associated with life quality parameters as well as marriage and income.

Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer.

A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study. These patients were classified into 4 groups: 39 with adenocarcinoma with (n = 19) and without (n = 20) diabetes, and 40 with squamous cell carcinoma with (n = 20) and without (n = 20) diabetes. Immunohistochemical expression of eight EMT markers was analyzed, including transforming growth factor-beta (TGF-ß), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), vimentin, E-cadherin, N-cadherin, HtrA1, and beta-catenin. Five markers (E-cadherin, HtrA1, TGF-ß, IGF-1R and vimentin) demonstrated significantly higher expression in diabetics than in non-diabetics in both histology types. N-cadherin had higher expression in diabetics, though the difference did not reach statistical significance. EGFR showed a higher expression in diabetics in squamous cell carcinoma only. Beta-catenin was the only marker with no difference in expression between diabetics versus non-diabetics. Our findings suggest that diabetes is associated with enhanced EMT in NSCLC, which may contribute to growth and invasiveness of NSCLC.

Multi-modality management of craniopharyngioma: a review of various treatments and their outcomes.

Craniopharyngioma is a rare tumor that is expected to occur in ∼400 patients/year in the United States. While surgical resection is considered to be the primary treatment when a patient presents with a craniopharyngioma, only 30% of such tumors present in locations that permit complete resection. Radiotherapy has been used as both primary and adjuvant therapy in the treatment of craniopharyngiomas for over 50 years. Modern radiotherapeutic techniques, via the use of CT-based treatment planning and MRI fusion, have permitted tighter treatment volumes that allow for better tumor control while limiting complications. Modern radiotherapeutic series have shown high control rates with lower doses than traditionally used in the two-dimensional treatment era. Intracavitary radiotherapy with radio-isotopes and stereotactic radiosurgery may have a role in the treatment of recurrent cystic and solid recurrences, respectively. Recently, due to the exclusive expression of the Beta-catenin clonal mutations and the exclusive expression of BRAF V600E clonal mutations in the overwhelming majority of adamantinomatous and papillary tumors respectively, it is felt that inhibitors of each pathway may play a role in the future treatment of these rare tumors.

Distinguishing grade I meningioma from higher grade meningiomas without biopsy.

BACKGROUND: Many meningiomas are identified by imaging and followed, with an assumption that they are WHO Grade I tumors. The purpose of our investigation is to find clinical or imaging predictors of WHO Grade II/III tumors to distinguish them from Grade I meningiomas. METHODS: Patients with a pathologic diagnosis of meningioma from 2002-2009 were included if they had pre-operative MRI studies and pathology for review. A Neuro-Pathologist reviewed and classified all tumors by WHO 2007. All Brain MRI imaging was reviewed by a Neuro-radiologist. Pathology and Radiology reviews were blinded from each other and clinical course. Recursive partitioning was used to create predictive models for identifying meningioma grades. RESULTS: Factors significantly correlating with a diagnosis of WHO Grade II-III tumors in univariate analysis: prior CVA (p = 0.005), CABG (p = 0.010), paresis (p = 0.008), vascularity index = 4/4: (p = 0.009), convexity vs other (p = 0.014), metabolic syndrome (p = 0.025), non-skull base (p = 0.041) and non-postmenopausal female (p = 0.045). Recursive partitioning analysis identified four categories: 1. prior CVA, 2. vascular index (vi) = 4 (no CVA), 3. premenopausal or male, vi < 4, no CVA. 4. Postmenopausal, vi < 4, no CVA with corresponding rates of 73, 54, 35 and 10% of being Grade II-III meningiomas. CONCLUSIONS: Meningioma patients with prior CVA and those grade 4/4 vascularity are the most likely to have WHO Grade II-III tumors while post-menopausal women without these features are the most likely to have Grade I meningiomas. Further study of the associations of clinical and imaging factors with grade and clinical behavior are needed to better predict behavior of these tumors without biopsy.

Optimal Frequency of Psychosocial Distress Screening in Radiation Oncology.

PURPOSE: To accurately hypothesize the optimal frequency of psychosocial distress screening in patients undergoing radiation therapy using exploratory modeling of prospective data. MATERIALS AND METHODS: Between October 2010 and May 2011, 71 RT patients underwent daily screening with the Distress Thermometer. Prevalences of Distress Thermometer scores ≥ 4 were recorded. Optimal screening frequency was evaluated by planned post hoc comparison of prevalence rates and required screening events estimated by numerical modeling, consisting of data point omission to mimic weekly, every-other-week, monthly, and one-time screening intervals. Dependence on clinical variables and chronologic trends were assessed as secondary end points. RESULTS: A total of 2,028 daily screening events identified that 37% of patients reported distress at least once during the course of treatment. Weekly, every-other-week, monthly, and one-time screening models estimated distress prevalences of 32%, 31%, 23%, and 17%, respectively, but required only 21%, 12%, 7%, and 4% of the assessments required for daily screening. No clinical parameter significantly predicted distress in univariable analysis, but "alone" living situation trended toward significance (P = .06). Physician-reported grade 3 toxicity predicted distress with 98% specificity, but only 19% sensitivity. CONCLUSION: Thirty-seven percent of radiation oncology patients reported distress at least once during treatment. Screening at every-other-week intervals optimized efficiency and frequency, identifying nearly 90% of distressed patients with 12% of the screening events compared with daily screening.

Expression of CXCR4 and non-small cell lung cancer prognosis: a meta-analysis.

PURPOSE: The prognostic value of aberrant C-X-C chemokine receptor type 4 (CXCR4) levels in NSCLC has been described in empirical studies. This meta-analysis evaluates the value of CXCR4 as a prognostic marker for NSCLC and determines the relationship between CXCR4 and clinicopathological features of NSCLC. METHODS: A comprehensive search of the English-language literature in PubMed, Embase, Google Scholar and Web of Science was performed. Articles containing sufficient published data to determine an estimate of the hazard ratio (HR) and a 95% confidence interval (95% CI) for over survival (OS) or disease-free survival (DFS) were selected. Of 417 potentially relevant studies, 10 eligible studies (1,334 NSCLC patients) met the inclusion criteria. RESULTS: Overall, high CXCR4 expression was significantly associated with a poor OS rate (HR=1.59, 95% CI=1.36-1.87, P<0.001) while the association with DFS was not statistically significant (HR=1.00, 95% CI=0.37-2.69, P=0.993). Stratified analysis by subcellular localization found that CXCR4 overexpression in the non-nucleus predicts poor OS (HR=1.65, 95% CI=1.40-1.95, P<0.001) and DFS (HR=3.06, 95% CI=2.15-4.37, P<0.001), but elevated CXCR4 expression in the nucleus was positively associated with DFS (HR=0.44, 95% CI=0.26-0.75, P=0.002). NSCLC patients with CXCR4 expression were more likely to be diagnosed with adenocarcinoma cancer (OR=1.45, 95% CI=1.07-1.95, P=0.016), lymph node involvement (OR=0.69, 95% CI=0.50-0.96, P=0.027), and distant metastasis (OR=0.36, 95% CI=0.14-0.93, P=0.035). CONCLUSION: Aberrant overexpression of CXCR4 is associated with worse overall survival, adenocarcinoma histology, distant metastasis, lymph node involvement in NSCLC.

Current role of radiation therapy for multiple myeloma.

BACKGROUND: Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. METHODS: We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. RESULTS: Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. CONCLUSION: Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT.

Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival.

PURPOSE: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. METHODS AND MATERIALS: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. RESULTS: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. CONCLUSIONS: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

Would screening for lung cancer benefit 75- to 84-year-old residents of the United States?

BACKGROUND: The National Lung Screening Trial demonstrated that screening for lung cancer improved overall survival (OS) and reduced lung cancer mortality in the 55- to 74-year-old age group by increasing the proportion of cancers detected at an early stage. Because of the increasing life expectancy of the American population, we investigated whether screening for lung cancer might benefit men and women aged 75-84 years. MATERIALS/METHODS: Rates of non-small cell lung cancer (NSCLC) from 2000 to 2009 were calculated in both younger and older age groups using the surveillance epidemiology and end reporting database. OS and lung cancer-specific survival (LCSS) in patients with Stage I NSCLC diagnosed from 2004 to 2009 were analyzed to determine the effects of age and treatment. RESULTS: The per capita incidence of NSCLC decreased in the 55-74 cohort, but increased in the 75-84 cohort over the study period. Crude lung cancer death rates in the two age groups who had no specific treatment were 39.5 and 44.9%, respectively. These rates fell in both age groups when increasingly aggressive treatment was used. Rates of OS and LCSS improved significantly with increasingly aggressive treatment in the 75-84 age group. The survival benefits of increasingly aggressive treatment in 75- to 84-year-old females did not differ from their counterparts in the younger cohort. CONCLUSION: Screening for lung cancer might be of benefit to individuals at increased risk of lung cancer in the 75-84 age group. The survival benefits of aggressive therapy are similar in females between 55-74 and 75-84 years old.