Case Report: Termination of unplanned pregnancy led to rapid deterioration of non-small-cell lung cancer during osimertinib treatment.

We present a case of a woman with non-small-cell lung cancer (NSCLC) who experienced disease progression during treatment with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) osimertinib due to an unplanned pregnancy. Given the risk of tumor progression, the patient underwent an artificial abortion. However, disease deterioration occurred shortly after termination of the pregnancy, with severe chest pain, increased dyspnea, and pleural effusion. After positive rescue measures, including emergency thoracic drainage, thoracentesis, and oxygen uptake, her symptoms improved. Considering pregnancy as an immune escape physiological process, the patient continued treatment with osimertinib, and a partial response (PR) lasting 16 months was observed. Therefore, this case highlights the importance of being vigilant about the rapid development of the tumor after delivery in pregnant patients with EGFR-mutation lung cancer and taking preventive measures to cope with various emergencies.

Th17-inducing dendritic cell vaccines stimulate effective CD4 T cell-dependent antitumor immunity in ovarian cancer that overcomes resistance to immune checkpoint blockade.

BACKGROUND: Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing. METHODS: ID8 tumor cells were injected intraperitoneally into mice. Mice were treated with Th17-DC or conventional DC (cDC) vaccine alone or with immune checkpoint blockade (ICB). Systemic immunity, tumor associated immunity, tumor size and survival were examined using a variety of experimental strategies. RESULTS: Th17-DC vaccines increased Th17 T cells in the tumor microenvironment, reshaped the myeloid microenvironment, and improved mouse survival compared with cDC vaccines. ICB had limited efficacy in OC, but Th17-inducing DC vaccination sensitized it to anti-PD-1 ICB, resulting in durable progression-free survival by overcoming IL-10-mediated resistance. Th17-DC vaccine efficacy, alone or with ICB, was mediated by CD4 T cells, but not CD8 T cells. CONCLUSIONS: These findings emphasize using biologically relevant immune modifiers, like Th17-DC vaccines, in OC treatment to reshape the tumor microenvironment and enhance clinical responses to ICB therapy.

Dramatic response and acquired resistance to savolitinib in advanced intrahepatic cholangiocarcinoma with MET amplification: a case report and literature review.

Background: Cholangiocarcinoma (CCA) is an aggressive disease with limited treatment options. Despite substantial efforts to explore better regimens, gemcitabine-based chemotherapy has been the standard first-line treatment for decades. With the growing field of precision medicine, biomarker-guided treatments are gaining popularity. MET alteration is a frequent occurrence in various cancer types, making it a promising target. Case presentation: A 53-year-old man visited our hospital with a complaint of upper abdominal pain. Advanced CCA was diagnosed based on the biopsy of the metastatic lymph nodes and immunohistochemistry. Next-generation sequencing revealed MET amplification. As the patient was intolerant to traditional chemotherapy, savolitinib (a c-MET inhibitor) was administered. Partial response was achieved, and the treatment was well tolerated. After 1 year, the patient developed progressive disease, to which the emergence of epidermal growth factor receptor amplification may have contributed. Conclusion: Our study verified the therapeutic value of a c-MET inhibitor in advanced CCA-harboring MET amplification and provides an alternative strategy for patients who are intolerant to chemotherapy.

Signalling in pancreatic cancer: from pathways to therapy.

Pancreatic cancer (PC) is a common malignant tumour in the digestive system. Due to the lack of sensitive diagnostic markers, strong metastasis ability, and resistance to anti-cancer drugs, the prognosis of PC is inferior. In the past decades, increasing evidence has indicated that the development of PC is closely related to various signalling pathways. With the exploration of RAS-driven, epidermal growth factor receptor, Hedgehog, NF-κB, TGF-ß, and NOTCH signalling pathways, breakthroughs have been made to explore the mechanism of pancreatic carcinogenesis, as well as the novel therapies. In this review, we discussed the signalling pathways involved in PC and summarised current targeted agents in the treatment of PC. Furthermore, opportunities and challenges in the exploration of potential therapies targeting signalling pathways were also highlighted.

Cost-effectiveness analysis of toripalimab plus chemotherapy as the first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) without EGFR or ALK driver mutations from the Chinese perspective.

Objectives: The results of a CHOICE-1 study demonstrated the superior efficacy of toripalimab (anti-PD-1 antibody) plus chemotherapy for patients with advanced non-small cell lung cancer (NSCLC), with a manageable safety profile. This study was performed to evaluate the economic value of this treatment for this patient population from the Chinese payer's perspective. Materials and methods: Basic data were derived from the CHOICE-1 study. Markov models were developed to simulate the process of advanced NSCLC, including the progression-free survival (PFS), progressive disease (PD), and death in intention-to-treat (ITT) populations, as well as patients with squamous or non-squamous NSCLC. The cost was obtained from the local institution, and the value of utilities referred to previous studies. Monte Carlo simulations were performed to depict the probabilistic scatter plots of the incremental cost-effectiveness ratio (ICER) and acceptability curves, aiming to address the uncertainty of model inputs. Results: Compared with standard chemotherapy, toripalimab plus chemotherapy yields an ICER of $21,563 per quality-adjusted life year (QALY) in the ITT population. For patients with squamous NSCLC, comparing the combined therapy with chemotherapy led to an ICER of $18,369 per QALY, while the ICER was $24,754 per QALY in patients with non-squamous NSCLC. With the threshold of willingness to pay we set ($37,653 per QALY), toripalimab plus chemotherapy was cost-effective in these patient populations. Conclusion: For patients with advanced NSCLC, toripalimab plus chemotherapy was an optimal choice as first-line treatment, regardless of histology.

Optimized CAR-T therapy based on spatiotemporal changes and chemotactic mechanisms of MDSCs induced by hypofractionated radiotherapy.

Poor intratumoral infiltration is the major challenge for chimeric antigen receptor (CAR)-T cell therapy in solid tumors. Hypofractionated radiotherapy (HFRT) has been reported to induce immune cell infiltration and reshape the tumor immune microenvironment. Here, we showed that HFRT (5 × 5 Gy) mediated an early accumulation of intratumoral myeloid-derived suppressor cells (MDSCs) and decreased infiltration of T cells in the tumor microenvironment (TME) of immunocompetent mice bearing triple-negative breast cancer (TNBC) or colon cancer, which was further confirmed in tumors from patients. RNA sequencing (RNA-seq) and cytokine profiling analysis revealed that HFRT induced the activation and proliferation of tumor-infiltrated MDSCs, which was mediated by the interactions of multiple chemokines and chemokine receptors. Further investigation showed that when combined with HFRT, CXCR2 blockade significantly inhibited MDSCs trafficking to tumors and effectively enhanced the intratumoral infiltration and treatment efficacy of CAR-T cells. Our study demonstrates that MDSCs blockade combined with HFRT is promising for CAR-T cell therapy optimization in solid tumors.

Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer.

Immune checkpoint inhibitors (ICIs) in the form of anti-CTLA-4 and anti-PD-1/PD-L1 have become the frontier of cancer treatment and successfully prolonged the survival of patients with advanced non-small cell lung cancer (NSCLC). But the efficacy varies among different patient population, and many patients succumb to disease progression after an initial response to ICIs. Current research highlights the heterogeneity of resistance mechanisms and the critical role of tumor microenvironment (TME) in ICIs resistance. In this review, we discussed the mechanisms of ICIs resistance in NSCLC, and proposed strategies to overcome resistance.

A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis.

Pleural and peritoneal metastasis accompanied by malignant pleural effusion (MPE) or malignant ascites (MA) is frequent in patients with advanced solid tumors that originate from the lung, breast, gastrointestinal tract and ovary. Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities. However, malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction. Here, we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA, which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment. Interestingly, we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells. Based on this feature, a novel PD-L1-targeting chimeric switch receptor (PD-L1.BB CSR) was designed, which can bind to PD-L1, switching the inhibitory signal into an additional 4-1BB signal. When co-expressed with a 2nd-generation CAR, PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment, causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models. Further investigations revealed elevated expressions of T-cell activation, proliferation, and cytotoxicity-related genes, and we confirmed that PD-L1 scFv and 4-1BB intracellular domain, the two important components of PD-L1.BB CSR, were both necessary for the functional improvements of CAR-T cells. Overall, our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells. Based on this study, a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis (NCT04684459).

Genomic landscape of lung adenocarcinomas in different races.

Background: Lung adenocarcinoma is a molecularly heterogeneous disease. Several studies, including The Cancer Genome Atlas Research Network (TCGA) and Lung Cancer Mutation Consortium (LCMC), explored the genetic alterations among different ethnic groups. However, minority groups are often under-represented in these relevant studies and the genomic alterations among racial groups are not fully understood. Methods: We analyze genomic characteristics among racial groups to understand the diversities and their impact on clinical outcomes. Results: Native Americans had significantly higher rates of insertions and deletions than other races (P<0.001). Among patients with lung adenocarcinomas, EGFR and KRAS were the highest discrepancy genes in the different racial groups (P<0.001). The EGFR exon 21 L858R point mutation was three times higher in Asians than in all other races (P<0.001). Asians, Whites, and Blacks had 4.7%, 3.1%, and 1.8% ALK rearrangement, respectively (P<0.001). White patients had the highest rates of reported KRAS G12C (15.51%) than other races (P<0.001). Whites (17.2%), Blacks (15.1%), and Other (15.7%) had higher rates of STK11 mutation than Asians (3.94%) (P<0.001). RET rearrangement and ERBB2 amplification were more common in Asian patients than in Other racial groups. Apart from point mutations, structural variations, and fusion genes, we identified a significant amount of copy number alterations in each race. Conclusions: The tumor genomic landscape is significantly distinct in different races. This data would shed light on the understanding of molecular alterations and their impacts on clinical management in different lung cancer patients.

Identification pyroptosis-related gene signature to predict prognosis and associated regulation axis in colon cancer.

Background: Pyroptosis is an important component of the tumor microenvironment and associated with the occurrence and progression of cancer. As the expression of pyroptosis-related genes and its impact on the prognosis of colon cancer (CC) remains unclear, we constructed and validated a pyroptosis-related genes signature to predict the prognosis of patients with CC. Methods: Microarray datasets and the follow-up clinical information of CC patients were obtained from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Candidate genes were screened out for further analysis. Various methods were combined to construct a robust pyroptosis-related genes signature for predicting the prognosis of patients with CC. Based on the gene signature and clinical features, a decision tree and nomogram were developed to improve risk stratification and quantify risk assessment for individual patients. Results: The pyroptosis-related genes signature successfully discriminated CC patients with high-risk in the training cohorts. The prognostic value of this signature was further confirmed in independent validation cohort. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CC patients. The decision tree identified risk subgroups powerfully, and the nomogram incorporating the gene signature and clinical risk factors performed well in the calibration plots. Conclusion: Pyroptosis-related genes signature was an independent prognostic factor, and can be used to predict the prognosis of patients with CC.

Response to chemotherapy combined with anlotinib plus anlotinib maintenance in intra-abdominal desmoplastic small round cell tumors (IADSRCT): a case report and literature review.

BACKGROUND: Intra-abdominal desmoplastic small round cell tumors (IADSRCT) are rare and aggressive neoplasia that are resistant to chemotherapy. Anlotinib is an oral multi-target tyrosine kinase inhibitor that also has anti-angiogenic and anti-proliferative properties. In this article, we report on a case showing effective and durable responses to chemotherapy combined with anlotinib in a young man with IADSRCT. CASE PRESENTATION: A 27-year-old man was admitted to our hospital complaining of a palpable periumbilical mass that had been present for longer than 4 months. The diagnosis of IADSRCT was confirmed by biopsy and immunohistochemistry. An extensive unresectable metastasis was found on the initial diagnosis. The patient received six cycles of chemotherapy combined with anlotinib, and maintenance therapy with anlotinib was recommended. Hematochezia, proteinuria and hypertension were observed, however, long-term maintenance therapy was well tolerated. A partial response was observed after two cycles of combined therapy and the patient was still alive with stable disease at the time of reporting. CONCLUSIONS: Chemotherapy combined with anlotinib plus anlotinib maintenance showed promising efficacy and manageable toxicity in the treatment of advanced IADSRCT.

Integratively Genomic Analysis Reveals the Prognostic and Immunological Characteristics of Pyroptosis and Ferroptosis in Pancreatic Cancer for Precision Immunotherapy.

The non-apoptotic cell death processes including pyroptosis and ferroptosis have been implicated in the progression and therapeutic responses of pancreatic adenocarcinoma (PAAD). However, the extent to which pyroptosis and ferroptosis influence tumor biology remains ambiguous, especially in PAAD, which is characterized with "cold" immunity. Considering the heterogeneity among different patients, it was more practical to quantify distinct cell death profiles in an individual tumor sample. Herein, we developed a pyroptosis-ferroptosis (P-F) score for PAAD patients in The Cancer Genome Atlas (TCGA) database. A high P-F score was associated with active immune phenotype, decreased genomic alterations, and significantly longer survival. Good accuracy of the P-F score in predicting overall survival (OS) was further confirmed in the TCGA-PAAD, ICGC-PACA-CA, and E-MTAB-6134 cohorts. Besides, one immunotherapy cohort (IMvigor210 dataset) has verified that patients with high P-F scores exhibited significant advantages in therapeutic responses and clinical benefits. The sensitivity to chemotherapeutics was analyzed through the Genomics of Drug Sensitivity in Cancer (GDSC), and patients with low P-F score might be more sensitive to paclitaxel and 5-fluorouracil. Collectively, the P-F score based on the systematic evaluation of cell death profiles could serve as an effective biomarker in predicting the outcomes and responses of PAAD patients to treatments with chemotherapeutic agents or immunotherapies.

Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors.

BACKGROUND: The INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors. METHOD: We used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient's lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses. RESULTS: The base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000. CONCLUSION: As the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.

Survival of Black and White Patients With Stage IV Small Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) is associated with aggressive biology and limited treatment options, making this disease a historical challenge. The influence of race and socioeconomic status on the survival of stage IV SCLC remains mostly unknown. Our study is designed to investigate the clinical survival outcomes in Black and White patients with stage IV SCLC and study the demographic, socioeconomic, clinical features, and treatment patterns of the disease and their impact on survival in Blacks and Whites. METHODS AND RESULTS: Stage IV SCLC cases from the National Cancer Database (NCDB) diagnosed between 2004 and 2014 were obtained. The follow-up endpoint is defined as death or the date of the last contact. Patients were divided into two groups by white and black. Features including demographic, socioeconomic, clinical, treatments and survival outcomes in Blacks and Whites were collected. Mortality hazard ratios of Blacks and Whites stage IV SCLC patients were analyzed. Survival of stage IV SCLC Black and White patients was also analyzed. Adjusted hazard ratios were analyzed by Cox proportional hazards regression models. Patients' median follow-up time was 8.18 (2.37-15.84) months. Overall survival at 6, 12, 18 and 24 months were 52.4%, 25.7%, 13.2% and 7.9% in Blacks in compared to 51.0%, 23.6%, 11.5% and 6.9% in Whites. White patients had significantly higher socioeconomic status than Black patients. By contrast, Blacks were found associated with younger age at diagnosis, a significantly higher chance of receiving radiation therapy and treatments at an academic/research program. Compared to Whites, Blacks had a 9% decreased risk of death. CONCLUSION: Our study demonstrated that Blacks have significant socioeconomic disadvantages compared to Whites. However, despite these unfavorable factors, survival for Blacks was significantly improved compared to Whites after covariable adjustment. This may be due to Blacks with Stage IV SCLC having a higher chance of receiving radiation therapy and treatments at an academic/research program. Identifying and removing the barriers to obtaining treatments at academic/research programs or improving the management in non-academic centers could improve the overall survival of stage IV SCLC.

Cost-Effectiveness Analysis of First-Line Nivolumab Plus Cabozantinib for Advanced Renal Cell Carcinoma in the United States.

INTRODUCTION: Nivolumab plus cabozantinib improved progression-free survival and overall survival compared with sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC) according to CheckMate 9ER study. METHODS: A Markov model was developed to compare the costs and effectiveness of nivolumab plus cabozantinib with those of sunitinib in the first-line treatment of advanced RCC. Primary outcomes were costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model uncertainty was assessed in univariable and probabilistic sensitivity analyses. RESULTS: The total cost per patient was $681,425 for nivolumab plus cabozantinib and $256,302 for sunitinib. The incremental QALY for nivolumab plus cabozantinib was 0.49 compared with sunitinib. The ICER for nivolumab plus cabozantinib was $863,720 per QALY gained versus sunitinib. The results remained robust in univariable and probabilistic sensitivity analyses. CONCLUSIONS: On the basis of a willingness-to-pay threshold of $150,000, nivolumab plus cabozantinib was not cost-effective under current drug pricing in the first-line treatment of advanced RCC from a US payer's perspective.

Comprehensive analysis of EMT-related genes and lncRNAs in the prognosis, immunity, and drug treatment of colorectal cancer.

BACKGROUND: EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking. METHODS: All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity. RESULTS: We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC. CONCLUSIONS: Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.

The role of non-apoptotic cell death in the treatment and drug-resistance of digestive tumors.

Tumor cell apoptosis evasion is one of the main reasons for easy metastasis occurrence, chemotherapy resistance, and the low five-year survival rate of digestive system tumors. Current research has shown that non-apoptotic cell death plays an important role in tumors of the digestive system. Therefore, increasing the proportion of non-apoptotic tumor cells is one of the effective methods of improving therapeutic efficacies for digestive system tumors. Non-apoptotic cell death modes mainly include autophagic cell death, pyroptosis, ferroptosis, in addition to other cell death modes. This review covers a systematic review relating to the research progress made into autophagic cell death, pyroptosis, ferroptosis, and other cell death modes in the treatment of digestive system tumors. It also highlights how treatment is a reasonable prospect based on clinical experience and provides reliable guidance for the further development of digestive system tumor treatments.

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer.

Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.

Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: A cost-effectiveness analysis in China and the United states.

BACKGROUND & AIMS: In patients with unresectable hepatocellular carcinoma (HCC), the combination of atezolizumab and bevacizumab improved progression-free survival (PFS) and overall survival compared with sorafenib in the IMbrave150 trial. However, whether the price of the combination could be affordable is unknown. The current study assessed the cost-effectiveness of the combination of atezolizumab and bevacizumab as first-line systemic therapy for patients with unresectable HCC from the Chinese and American payers' perspective. METHODS: A Markov model was built based on a global, multicentre, open-label, phase III randomized trial (IMbrave150, NCT03434379) that included three states of the patient's health: stable disease (SD), progressive disease (PD) and death. Data for all medical costs were acquired from the Red Book, published literature and West China Hospital. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were the primary outcomes. Sensitivity analyses were performed to evaluate the model uncertainty. RESULTS: The treatment consisting of a combination of atezolizumab and bevacizumab yielded an additional 0.53 QALYs compared with sorafenib alone, leading to an ICER of $145,546.21 per QALY in China and $168,030.21 per QALY in the USA, both beyond the willing-to-pay threshold ($28,527.00/QALY in China and $150,000.00 /QALY in the USA). The utility of the PD state was the most influential factor in the Chinese model, and the American model was the most sensitive to the price of sorafenib. The results of the models were robust across sensitivity analyses. CONCLUSION: The combination of atezolizumab and bevacizumab was not a cost-effective strategy for the first-line systemic treatment of unresectable HCC from the Chinese and American payers' perspective.

Association of Race, Socioeconomic Factors, and Treatment Characteristics With Overall Survival in Patients With Limited-Stage Small Cell Lung Cancer.

Importance: It has been established that disparities in race and socioeconomic status are associated with outcomes of non-small cell lung cancer. However, it remains unknown whether this extends to stage I, II, or III small cell lung cancer (SCLC), or limited-stage SCLC (L-SCLC). Objective: To investigate the associations of race, socioeconomic factors, and treatment characteristics with survival among patients with L-SCLC. Design, Setting, and Participants: Demographic information for patients with L-SCLC diagnosed between 2004 and 2014 was obtained from the National Cancer Database. The follow-up end point is death or last follow-up (date of last contact). Patients were divided into 5 mutually exclusive cohorts by race. Data analysis was performed in October 2019. Main Outcomes and Measures: Cox proportional hazards models were used to calculate univariable and multivariable models. Multivariable analyses were conducted to assess the associations of race and socioeconomic factors with risk-adjusted outcomes. Overall survival between groups was depicted by Kaplan-Meier curves. Results: Of 72 409 patients analyzed (median [range] age, 67.0 [23.0-90.0] years), 40 289 (55.6%) were women. The distribution of disease stage was 10 619 patients (14.7%) with stage I disease, 7689 patients (10.6%) with stage II disease, and 54 101 patients (74.7%) with stage III disease. The median (range) duration of follow-up was 8.2 (2.4-15.8) months. Compared with White patients, the hazard of death decreased to 0.92 (95% CI, 0.89-0.95; P < .001) for African American patients and 0.83 (95% CI, 0.77-0.91; P < .001) for Asian patients. The difference in median survival among different racial groups was significant only among those with stage III SCLC. Other factors associated with better survival were female sex, high income, high education, private insurance, diagnostic confirmation by positive cytological analysis, increase in number of sampled regional lymph nodes, and earlier stage at diagnosis. Conclusions and Relevance: This analysis highlights disparities in race and socioeconomic factors associated with outcomes of L-SCLC. Racial minorities, including African American and Asian patients, have better survival than White patients for L-SCLC after adjustment for sociodemographic factors.