Immunotherapy Improves the Survival of Stage 4 Non-Small Cell Lung Cancer Patients at the US Population Level: The Real-World Evidence.

INTRODUCTION: Immunotherapy has revolutionized the management of lung cancer and improved lung cancer survival in trials, but its real-world impact at the population level remains unclear. METHODS: Using data obtained from eight Surveillance, Epidemiology, and End Results (SEER) registries from 2004 through 2019, we addressed the long-term trends in the incidence, incidence-based mortality (IBM), and survival of lung cancer patients in the United States. RESULTS: The incidence and IBM of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) all significantly decreased steadily from 2004 to 2019. The 1-year survival (1-YS) of both NSCLC and SCLC improved over time, with the best improvement observed for Stage 4 NSCLC. Two significant turning points of Stage 4 NSCLC 1-YS were observed over the years: 0.63% (95% confidence interval [CI]: 0.33%-0.93%) from 2004 to 2010, 0.81% (95% CI: 0.41%-1.21%) from 2010 to 2014 and a striking 2.09% (95% CI: 1.70%-2.47%) from 2014 to 2019. The same two turning points in 1-YS were pronounced for Stage 4 NSCLC in women, which were coincident with the introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immunotherapy. However, for Stage 4 NSCLC in men, only one significant turning point in the 1-YS starting in 2014 was found, which might only correspond to immunotherapy. Significant period effects in reduced IBM were also observed for both Stage 4 AD and Stage 4 SQCC during the period. CONCLUSION: This SEER analysis found that immunotherapy improved the survival of Stage 4 NSCLC patients at the population level in the United States. This real-world evidence confirms that immunotherapy has truly revolutionized the management of lung cancer.

The reduced mortality of malignant melanoma at the population level is mainly attributable to treatment advances for the past decade.

BACKGROUND: Cutaneous malignant melanoma (CMM) causes most skin cancer deaths in the United States (US). The mortality has been decreasing in the US population. We hypothesize that this population-level reduction is mainly attributable to the treatment advances, rather than the successful primary and secondary prevention. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) databases, we collected the incidence, incidence-based mortality (IBM), and 5-year survival (5-YS) rates of CMM from 1994 to 2019. Trends by stage and sex were examined by joinpoint regression analyses and age-period-cohort analyses. RESULTS: The overall incidence of CMM rose by 1.6% yearly from 1994 to 2006 (95% confidence interval [CI]: 0.9% to 2.2%) and then increased with a numerical trend. And we projected the incidence will continue to increase until 2029. In contrast, the IBM for all CMM has decreased yearly by 2.8% (95% CI: -3.9% to -1.8%) since 2010 after continuously increasing by 3.8% annually (95% CI: 3.2% to 4.4%) from 1996 to 2010. For early-stage (localized and regional) CMM, we found the incidence since 2005 plateaued without further increase, while the incidence for CMM at distant stage continuously increased by 1.4% per year (95% CI: 0.9% to 2.0%). Improvements in 5-YS were observed over the study period for all CMM and were most obvious in distant stage. And significant period effects were noted around the year 2010. CONCLUSION: This study demonstrated improved survival and reduced mortality of CMM at the US population level since 2010, which were consistent with the introduction of novel therapies. Encouraging effects of primary prevention among adolescents in the most recent cohorts were found. However, the plateaued overall incidence and early diagnosis rates indicated that advances in primary and secondary prevention are very much needed to further control the burden of CMM.

Second primary malignancies in cervical cancer and endometrial cancer survivors: a population-based analysis.

BACKGROUND: We evaluated the relative attribution and interactions of treatment and patient-related risk factors for second primary malignancies (SPMs) in cervical and endometrial cancer survivors. METHODS: Stage I-III cervical and endometrial cancer survivors' data from the Surveillance, Epidemiology, and End Results (SEER) registry between January 1988 and December 2015 were analyzed. The standardized incidence ratio (SIR), excess absolute risk (EAR), and corresponding 95% confidence interval (95% CI) values were calculated. Analyses were classified based on proxies of human papillomavirus (HPV), smoking, hormone, and radiotherapy (RT) status. Additive and multiplicative interactions were assessed. RESULTS: Cervical cancer survivors had a higher risk for developing potentially HPV and smoking-related SPMs, especially in the RT group (SIRHPV = 3.7, 95% CI: 2.9-4.6; SIRsmoking = 3.2, 95% CI: 2.8-3.6). Second vaginal cancer patients had the highest SIR (23.8, 95% CI: 14.9-36.0). There were strong synergistic interactions between RT and the proxy of smoking (Pinteraction < 0.001), accounting for 36% of potentially smoking-related SPMs in cervical cancer survivors. CONCLUSIONS: RT, HPV, and smoking promote SPMs in cervical cancer to different extents. The SPM burden in cervical cancer survivors could be mostly attributed to smoking and RT and their interactions.

Declining disease burden of HCC in the United States, 1992-2017: A population-based analysis.

BACKGROUND AND AIMS: The incidence of HCC has recently been consistently reported to decline in the United States. However, decreased overall mortality of HCC has just been suggested and needs further examination. APPROACH AND RESULTS: Using data from the Surveillance, Epidemiology, and End Results databases, we assessed HCC incidence, incidence-based mortality (IBM), and 1-year survival rates from 1992 through 2017 in the United States. These secular trends were analyzed using the National Cancer Institute's Joinpoint Regression Program. Age-period-cohort analyses were performed to address underlying reasons for the observed temporal trends. The incidence and mortality of liver cancer in the United States by different etiologies were acquired from the Global Burden of Disease study (1990-2019) as a likely validation set. Joinpoint and age-period-cohort analyses were performed by etiologies. The incidence rates of HCC increased during 1992-2011 and sharply decreased thereafter by -2.3% annually (95% CI: -3.5% to -1.1%). IBM peaked in 2013 (age-standardized mortality rate: 6.98 per 100,000 person-years) in the US population. IBM started to decrease significantly in 2013 by -3.2%/year (95% CI: -5.4% to -1.1% per year) after a continuous increase of 3.5% annually during 1993-2013. Overall, the 1-year survival of HCC improved from 21.4% to 56.6% over the study period. However, the highest HCC incidence and mortality risk for patients aged 60-69 and born between 1952-1957 were found. CONCLUSIONS: We found significantly decreased overall HCC-specific mortality since 2013 in the US population, along with decreased incidence and continuously improved survival. The changing etiologies, advances in screening and diagnosis, and improved treatment modality and allocation might all contribute to the downward trends of the disease burden of HCC in the United States.

The stage-specific roles of radiotherapy and chemotherapy in nodular lymphocyte predominant Hodgkin lymphoma patients: a propensity score-matched analysis of the SEER database.

BACKGROUND: The stage-specific roles of radiotherapy (RT) alone, chemotherapy alone, and combined RT and chemotherapy (CRT) for patients with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) have not been adequately evaluated. METHODS: We analyzed patients with all stages of NLPHL enrolled in the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2015. Propensity score (PS) analysis with 1:1 matching (PSM) was performed to ensure the well-balanced characteristics of the comparison groups. Kaplan-Meier and Cox proportional-hazards models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), hazard ratios (HRs), and corresponding 95% confidence intervals (95% CI). Restricted mean survival times (RMST) were also used for the survival analyses. RESULTS: For early-stage patients, CRT was associated with the best survival, the mean OS was significantly improved by approximately 20 months (20 m), and the risk of death was reduced by more than 80%, both before and after PSM (p < 0.05). For advanced-stage patients, none of RT alone, chemotherapy alone, or CRT had a significant effect on survival. Chemotherapy alone and CRT might be more beneficial for long-term survival (RMST120 m : neither RT nor chemotherapy vs. chemotherapy alone vs. CRT = 104 m vs. 111 m vs. 108 m). Subgroup analysis of patients with early-stage NLPHL showed that CRT was associated with better survival of elderly patients (improved OS = 43.8 m, HR = 0.14, p < 0.05). However, the survival benefits of treatments for young patients were not statistically significant. The efficacy of RT was significantly different between the age groups (pfor interaction  = 0.020). CONCLUSIONS: These results from SEER data suggest that CRT may be considered for early-stage NLPHL, especially for elderly patients. Further studies are needed to identify effective treatments in patients with advanced-stage NLPHL.

Radiotherapy for patients with stage IV classical Hodgkin lymphoma: a propensity-matched analysis of the surveillance, epidemiology, and end results database.

Background The survival advantage of radiotherapy for patients with stage IV classic Hodgkin lymphoma (HL) has not been adequately evaluated. Methods We analyzed patients with stage IV HL enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry from January 2000 to December 2012. Propensity score (PS) analysis with 1:2 matching was performed to ensure well-balanced characteristics of the comparison groups. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), the hazards ratio (HR) and corresponding 95% confidence intervals (95% CI). Results Overall, for all patients with stage IV HL, receiving radiotherapy was associated with both significantly improved OS and CSS. Radiotherapy to any lesions could independently improve the OS and CSS by 30% to 36% in the multivariate analyses before and after PS matching (PSM), with the best improvement of 33% to 40% observed for patients with nodular sclerosis (P < 0.05) among all HL pathological types. In particular, radiotherapy, most likely to the residual site, was more pronouncedly associated with the improvement in survival for patients with stage IV HL who were young (age<45, P < .05) or without B symptoms (PInteraction for OS = 0.099, PInteraction for CSS = 0.255). For those patients without B symptoms, after PSM, the OS was improved by 65% (P = .021). Conclusions The large SEER results support that radiotherapy is associated with better survival of patients with stage IV HL.

Comparison of Treatment Modalities for Locally Advanced Gastric Cancer: A Propensity Score Matching Analysis.

Background: A consensus regarding optimum treatment strategies for locally advanced gastric cancer (LAGC) has not yet been reached. We aimed to evaluate the efficacy of various treatment modalities for LAGC and provided clinicians salvage options under real-world situation. Methods: Medical charts of patients with LAGC who underwent radical resection plus adjuvant chemotherapy or chemoradiotherapy from July 2003 to December 2014 were included. Validation cohort were selected from SEER database between 2004 and 2014. Kaplan-Meier and Cox proportional hazardous models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Propensity score matching (PSM) was used to adjust for potential baseline confounding. Results: A total of 350 patients were included and divided into D1 dissection plus chemotherapy group (D1CT, n = 74), D1 dissection plus adjuvant chemoradiotherapy group (D1CRT, n = 69), D2 dissection plus adjuvant chemotherapy group (D2CT, n = 134), and D2 dissection plus adjuvant chemoradiotherapy group (D2CRT, n = 73). PSM identified 50 patients in each group. After PSM, better DFS (P for D2CRT vs. D1CT, D1CRT, and D2CT was 0.001, 0.006, and 0.001, respectively) and OS (P for D2CRT vs. D1CT, D1CRT, and D2CT was 0.001, 0.011, and 0.022, respectively) were found for the D2CRT group (mean, OS = 110.7months, DFS = 95.2 months) than the other groups. Similar findings were further validated in the Surveillance, Epidemiology, and End Results database (SEER) cohort. In addition, patients in the D1CRT group achieved similar survival outcomes to those in the D2CT group (mean OS, 72.8 vs. 59.1 months, P = 0.86; mean DFS, 54.4 vs. 34.1 months, P = 0.460). Conclusions: The results of the study indicated the better role for D2CRT in treating the LAGC, meanwhile, the patients treated with D1CRT might achieve similar survival as that of D2CT patients.

Reassessment of American Joint Committee on Cancer Staging for Stage III Renal Cell Carcinoma With Nodal Involvement: Propensity Score Matched Analyses of a Large Population-Based Study.

Background: To assess the role of nodal involvement in stage III renal cell carcinoma (RCC) according to the American Joint Committee on Cancer (AJCC) 8th staging system. We compared the survival outcomes of RCC patients with pT1-3N1M0 disease and those with pT3N0M0 or stage IV (stratified as pT4NanyM0 and pTanyNanyM1) disease in a large population-based cohort. Methods: A cohort of 3,112 eligible patients with RCC was identified from the Surveillance, Epidemiology, and End Results (SEER) database, registered between January 2004 and December 2015. Kaplan-Meier and Cox proportional hazards models were used to evaluate the overall survival (OS), and cancer-specific survival (CSS). The prognostic value of the modified stage for pT1-3N1M0 disease was assessed by nomogram-based analyses. Propensity score matching (PSM) was used to adjust for potential baseline confounding. Results: Patients with pT1-3N1M0 disease showed similar survival outcomes (median OS 41.0 vs. 38.0 months, P = 0.77; CSS 45.0 vs. 39.0 months, P = 0.59) to pT4NanyM0 patients, whereas the significantly better survival outcome was found for pT3N0M0 patients. After PSM, comparable survival rates were observed between pT1-3N1M0 group and pT4NanyM0 group, which were still significantly worse than the survival of pT3N0M0 patients. The modified stage IIIA (pT3N0M0), IIIB (pT1-3N1M0, pT4NanyM0), and IV (pTanyNanyM1) showed higher predictive accuracy than AJCC stage system in the nomogram-based analyses (concordance index: 0.70 vs. 0.68, P < 0.001 for OS; 0.71 vs. 0.69, P < 0.001 for CSS). Conclusions: The pT1-3N1M0 RCC might be reclassified as stage IIIB together with pT4NanyM0 disease for better prediction of prognosis, further examination and validation are warranted.

CT features of SARS-CoV-2 pneumonia according to clinical presentation: a retrospective analysis of 120 consecutive patients from Wuhan city.

OBJECTIVES: To characterize the chest computed tomography (CT) findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) according to clinical severity. We compared the CT features of common cases and severe cases, symptomatic patients and asymptomatic patients, and febrile and afebrile patients. METHODS: This was a retrospective analysis of the clinical and thoracic CT features of 120 consecutive patients with confirmed SARS-CoV-2 pneumonia admitted to a tertiary university hospital between January 10 and February 10, 2020, in Wuhan city, China. RESULTS: On admission, the patients generally complained of fever, cough, shortness of breath, and myalgia or fatigue, with diarrhea often present in severe cases. Severe patients were 20 years older on average and had comorbidities and an elevated lactate dehydrogenase (LDH) level. There were no differences in the CT findings between asymptomatic and symptomatic common type patients or between afebrile and febrile patients, defined according to Chinese National Health Commission guidelines. CONCLUSIONS: The clinical and CT features at admission may enable clinicians to promptly evaluate the prognosis of patients with SARS-CoV-2 pneumonia. Clinicians should be aware that clinically silent cases may present with CT features similar to those of symptomatic common patients. KEY POINTS: • The clinical features and predominant patterns of abnormalities on CT for asymptomatic, typic common, and severe cases were summarized. These findings may help clinicians to identify severe patients quickly at admission. • Clinicians should be cautious that CT findings of afebrile/asymptomatic patients are not better than the findings of other types of patients. These patients should also be quarantined. • The use of chest CT as the main screening method in epidemic areas is recommended.

Surgery to the primary tumor is associated with improved survival of patients with metastatic esophageal cancer: propensity score-matched analyses of a large retrospective cohort.

The survival advantage of surgery to the primary tumor for patients with distant metastatic esophageal cancer has not been adequately evaluated. This study aims to investigate the role of surgery to the primary tumor in distant metastatic esophageal cancer and to evaluate possible different effects of surgery on survival of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). This study included a cohort of 4,367 metastatic esophageal cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, registered from January 2004 to December 2014. Kaplan-Meier and Cox proportional hazardous models were used to evaluate the overall survival (OS) and corresponding 95% confidence interval (CI). Propensity score matching (PSM) was used to adjust for potential baseline confounding. Both EAC (median OS for surgery group vs. no-surgery group-14.0 vs. 9.0 months, P < 0.001) and ESCC (median OS for surgery vs. no-surgery group-11.0 vs. 7.0 months, P = 0.002) experienced survival benefits from surgery. We found that surgery to the primary tumor, when combined with chemotherapy, was associated with improved survival for patients with M1b disease, both EAC and ESCC, with a greater benefit observed in younger patients, and those with EAC. While the present data indicate a potential survival benefit from surgery for some patients with metastatic esophageal cancer, it is possible that performance status and metastatic disease burden impacted patient selection, influencing these results. Further studies are needed to determine the role of surgery for patients with metastatic esophageal cancer.

Palliative Gastrectomy and Survival in Patients With Metastatic Gastric Cancer: A Propensity Score-Matched Analysis of a Large Population-Based Study.

OBJECTIVES: The role of palliative gastrectomy in the management of metastatic gastric cancer remains inadequately clarified. METHODS: We analyzed patients with metastatic gastric cancer enrolled in the Surveillance, Epidemiology, and End Results registry from January 2004 to December 2012. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method was performed to ensure well-balanced characteristics of the groups of patients who undergone gastrectomy and those without gastrectomy. Data were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate the overall survival and cancer-specific survival rates with corresponding 95% confidence intervals (CIs). RESULTS: In general, receiving any kind of gastrectomy was associated with an improvement in survival in the multivariate analyses (hazard ratio [HR]os = 0.64, 95% CI = 0.59-0.70, HRcss = 0.63, 95% CI = 0.57-0.68) and PS matching (PSM) analyses (HRos = 0.63, 95% CI = 0.56-0.70, HRcss = 0.62, 95% CI = 0.55-0.70). After PSM, palliative gastrectomy was found to be associated with remarkably improved survival for patients with stage M1 with only 1 metastasis but not associated with survival of patients with stage M1 with extensive metastasis (≥2 metastatic sites). DISCUSSION: The results obtained from the Surveillance, Epidemiology, and End Results database suggest that patients with metastatic gastric cancer might benefit from palliative gastrectomy on the basis of chemotherapy. However, a PSM cohort study of this kind still has a strong selection bias and cannot replace a properly conducted randomized controlled trial.

Object Tracking Algorithm Based on Dual Color Feature Fusion with Dimension Reduction.

Aiming at the problem of poor robustness and the low effectiveness of target tracking in complex scenes by using single color features, an object-tracking algorithm based on dual color feature fusion via dimension reduction is proposed, according to the Correlation Filter (CF)-based tracking framework. First, Color Name (CN) feature and Color Histogram (CH) feature extraction are respectively performed on the input image, and then the template and the candidate region are correlated by the CF-based methods, and the CH response and CN response of the target region are obtained, respectively. A self-adaptive feature fusion strategy is proposed to linearly fuse the CH response and the CN response to obtain a dual color feature response with global color distribution information and main color information. Finally, the position of the target is estimated, based on the fused response map, with the maximum of the fused response map corresponding to the estimated target position. The proposed method is based on fusion in the framework of the Staple algorithm, and dimension reduction by Principal Component Analysis (PCA) on the scale; the complexity of the algorithm is reduced, and the tracking performance is further improved. Experimental results on quantitative and qualitative evaluations on challenging benchmark sequences show that the proposed algorithm has better tracking accuracy and robustness than other state-of-the-art tracking algorithms in complex scenarios.

Radiotherapy Improves the Survival of Patients With Metastatic Cervical Cancer: A Propensity-Matched Analysis of SEER Database.

OBJECTIVE: To demonstrate whether radiotherapy has an effect on the survival of patients with stage IVb (M1) cervical cancer, as it has not been adequately clarified. METHODS: We analyzed International Federation of Gynecology and Obstetrics (FIGO) stage M1 cervical cancer diagnosed in patients between 1992 and 2013 using population-based data from the Surveillance, Epidemiology, and End Results registry. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method was performed to ensure well-balanced characteristics of comparison groups. Data were analyzed by Kaplan-Meier and Cox proportional hazards regression models to evaluate the overall survival (OS) and cancer-specific survival (CSS) months with corresponding 95% confidence intervals (95% CIs). RESULTS: In general, receiving radiotherapy significantly improved OS and CSS both before and after PS matching (PSM) (P < 0.001), with significantly improved OS (hazard ratio, 0.69; 95% CI, 0.62-0.76) and CSS (hazard ratio, 0.79; 95% CI, 0.70-0.89) after PSM in patients with stage M1 cervical cancer. Before PSM, radiotherapy was found to be associated with improved survival even for the patients with stage M1 cervical cancer with extensive metastasis (≥2 metastatic sites) (P < 0.001). Although P value was not significant for brain metastasis, the survival month was numerically improved before PSM (OS and CSS, 1 month vs 4 months). Overall, radiotherapy still significantly improved survival for patients with one metastatic site (ie, oligometastases) either before or after PSM (P < 0.05), with the survival month improved more than 6 months. CONCLUSIONS: The large Surveillance, Epidemiology, and End Results results support that radiotherapy might improve the survival of patients with metastatic cervical cancer. It might be prudent to carefully select suitable patients for radiation therapy for metastatic cervical cancer.

Phenolic resin surface restructuring upon exposure to humid air: a sum frequency generation vibrational spectroscopic study.

Epoxy and phenolic resins are extensively used for modern microelectronics, for example, as packaging materials. Humidity may greatly alter or degrade their function and application, leading to failure of the device. A nonlinear optical laser technique, sum frequency generation (SFG) vibrational spectroscopy, was used to investigate the molecular surface structures of the epoxy and phenolic resins after exposure to humid air. It was found that the adsorbed water molecules at the phenolic resin surface can induce substantial surface restructuring. The surface phenyl groups were reoriented closer to a perpendicular position to the surface after exposure to humid air from a more parallel position in air. Epoxide group surface restructuring was not observed.