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ObjectivesNeoadjuvant chemoimmunotherapy is the optimal choice in the treatment of NSCLC; however, the optimal number of therapeutic cycles remains unclear. The primary aim of this study was to determine the optimal number of neoadjuvant therapeutic cycles in NSCLC.MethodsThis study was a real-world clinical analysis that included patients who received neoadjuvant chemoimmunotherapy followed by surgery from January 2020 to August 2022. Patients were divided into two groups based on the number of therapeutic cycles: 2-cycle group and 3-4-cycles group. The primary endpoint was the major pathological response (MPR) rate.ResultsA total of 251 patients were included: 150 in the 2-cycle group and 101 in the 3-4-cycles group. Baseline characteristics were well-balanced between the groups. The MPR in the 2-cycle group was 57.3% and not significantly different from that of 57.4% in the 3-4-cycles group (p=0.529). Thirty-two patients (31.7%) in the 3-4-cycles group underwent surgery > 42 days after the final cycle of neoadjuvant therapy, significantly more than the 24 patients (16.0%) in the 2-cycle group (p=0.003). The incidence of adverse events related to neoadjuvant therapy was higher in the 3-4-cycles vs 2-cycle groups (72.3% versus 58.0%, respectively; p=0.021), while the 2-cycle group had a higher rate of postoperative morbidities (28.0% versus 12.9%, respectively; p=0.004). Additionally, for patients with ≤ 44.2% regression in diameter on computed tomography after two cycles of treatment, the MPR rate was higher in the 3-4-cycles vs 2-cycle group (47.3% versus 29.9%, respectively; p=0.048). For cases with programmed death-ligand 1 expression, regarding tumor proportion score ≤ 10%, 3-4 cycles of neoadjuvant treatment increased the MPR rate compared with 2 cycles (37.5% versus 9.5%, respectively; p=0.041).ConclusionOur data support the positive role of chemoimmunotherapy in the neoadjuvant treatment of NSCLC. Extending to 3–4 cycles instead of 2 cycles of neoadjuvant chemoimmunotherapy may improve the safety of surgery and result in a lower incidence of postoperative morbidities; however, the MPR rate may not increase significantly. CT re-evaluation during treatment and PD-L1 expression at initial diagnosis are potential indicators to guide the choice of the number of therapeutic cycles.

PurposeWe evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated.Materials and methodsThe Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients.ResultsIn the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%).ConclusionThe Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

BackgroundChemotherapy combined with immunotherapy or anti-vascular therapy is both recommended by guidelines for first-line treatment of lung adenocarcinoma. However, no head-to-head clinical trial has ever compared which strategy is the optimal choice. This real-world retrospective study was done to compare the efficacy and treatment-related adverse events of immunotherapy and bevacizumab in combination with chemotherapy.Patients and methodsFrom January 2018 to March 2021, we retrospectively collected 276 patients with advanced lung adenocarcinoma managed with chemotherapy combined with bevacizumab or PD-1 inhibitors at our center. Among them, 139 patients were treated with chemotherapy combined with bevacizumab, while 137 patients were treated with chemotherapy combined with PD-1 inhibitors. After receiving four cycles of combination therapy, all patients received maintenance therapy until disease progression. Progression‐free survival (PFS), overall response rate (ORR), overall survival (OS), disease control rate (DCR), and adverse events (AE) were analyzed between the two groups.ResultsCompared to patients who received anti-vascular therapy, patients who underwent immunotherapy achieved better PFS (7.3 months vs. 10 months, p = 0.002) while ORR (40.9% vs. 51.1%, p = 0.093), as well as OS (18 months vs. 24 months, p = 0.060), had no statistical difference between the two groups. In the PD-L1-negative population, there was no statistical difference in PFS and OS between the two groups. (8.0 months VS. 6.0 months, p = 0.738; and 19 months vs. 13 months, p = 0.274). In the PD-L1-positive population, there was a significant benefit in PFS in the population receiving immunotherapy (7.0 months vs. 10.0 months, p = 0.009). Proteinuria and hypertension occurred more frequently in the bevacizumab-treated group (p = 0.001 and p = 0.002), whereas immune-related pneumonia and hypothyroidism occurred more frequently in the immunotherapy-treated group (p = 0.007 and p = 0.030).ConclusionsThe addition of a PD-1 inhibitor was superior to bevacizumab in terms of PFS among patients with advanced lung adenocarcinoma. PD-L1-positive patients appeared to exhibit better PFS, OS, and ORR. Toxic reactions were manageable in both groups.

Echinococcosis is a human-animal parasitic disease caused by Echinococcosis tapeworm larvae in humans. From a global perspective, it is mainly prevalent in the mid-high latitudes of the Northern Hemisphere, and it is a widespread infectious disease. Its form, host and release areas are slightly different. In clinical practice, Echinococcus granulosus (hepatic cystic echinococcosis) is the most common. Its growth mode is swelling growth and its metastasis is more common in implanted metastasis; However, hepatic alveolar echinococcosis (HAE) is rare. It has been reported that HAE can metastasize through the blood or lymph nodes, and its invasive growth pattern is known as “carcinoma”. At this time, it may be accompanied by invasion of the portal vein and inferior vena cava(IVC)or metastasis to distant organs outside the liver (such as lung, brain, lymph nodes). Most patients are in the middle or late stages, making treatment complicated. World Health Organization guidelines recommend radical resection of HAE; However, there is no consensus on lymph node dissection. To date, there have been no reports of cases of HAE accompanied by inferior vena cava-para-abdominal aortic suspected lymph node metastasis and infection. This article reports a clinical case of a complex HAE treated by the surgical method of “middle liver resection + abdominal enlarged lymph node resection + inferior vena cava repair”, and histological examination was performed to illustrate the differences in microscopic pathology of alveolar echinococcosis invading the liver and lymph nodes at different magnifications. This article reviews the relevant literature on HAE and derives the latest treatment methods for HAE to provide a reference for future clinical cases of similar alveolar echinococcosis and maximize the benefits of patients.

PurposeThe purpose of this study is to reveal the clinicopathological features and identify risk factors of prognosis among patients with pancreatic cancer bone metastasis (PCBM).Patients and MethodsPatients with PCBM were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Independent predictors for survival of those patients were determined by the univariate and multivariate Cox regression analysis. Forest plots were drawn by GraphPad 8.0.1 and used to visually display the results of multivariate analysis.ResultsWe identified 2072 eligible PCBM patients, of which 839 patients (40.5%) were female. Patients with age >60 years accounted for 70.6%. Multivariable Cox regression analysis indicated that age, pathological type, chemotherapy, liver metastasis, lung metastasis, and marital status were independent prognostic factors for both overall survival (OS) and cancer-specific survival (CSS). Kaplan–Meier survival curves showed that for patients with PCBM, age ≤60 years, non-ductal adenocarcinoma type, chemotherapy, no liver metastasis, no lung metastasis, and married status were correlated with increased survival. This population-based study showed that 1-year OS and CSS were 13.6% and 13.7%, respectively.ConclusionThe present study identified six independent predictors of prognosis in PCBM, including age, pathological type, chemotherapy, liver metastasis, lung metastasis, and marital status. Knowledge of these survival predictors is helpful for clinicians to accelerate clinical decision process and design personalized treatment for patients with PCBM.

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm and patients with IMT tend to have a favorable outcome after complete surgical resection. However, some tumors of IMT cases have recurred and grown rapidly after successful surgery. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a highly aggressive intra-abdominal IMT variant with epithelioid-to-round cell morphology. Currently, no standard therapy exists for recurrent or invasive IMTs and EIMS, but anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are recommended for those harboring ALK gene rearrangements. We herein report the first case of PRRC2B-ALK fusion associated IMTs with clinical and pathological manifestation matched the diagnosis criteria of EIMS and the durable clinical response of the sequential use of ALK TKIs (crizotinib, alectinib, ceritinib, and lorlatinib). A female patient with EIMS of the greater omentum was suffering from a rapid recurrence after cytoreductive surgery was done. Crizotinib was administered when PRRC2B-ALK fusion was detected, and partial response was achieved. The progression-free survival (PFS) of crizotinib was 5 months. Alectinib was administered based on the results of second next-generation sequencing (NGS) analysis, which identified the secondary mutation ALK R1192P. The best overall response of alectinib treatment was a partial response (PR) and the PFS was 5.5 months. Ceritinib was prescribed as third-line therapy after alectinib resistance with ALK L1196M mutation. PR was achieved and the PFS of ceritinib was 6 months. The patient was taking lorlatinib after ceritinib resistance and achieved a stable disease at 2 months with the PFS more than 5 months. The overall survival was more than two years as of the time of manuscript preparation. We describe an EIMS of greater omentum caused by PRRC2B-ALK fusion gene and showed durable clinical response to the sequential use of ALK TKIs.

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In this review, we summarize the findings of recent clinical research studies on biomarkers detected in samples obtained from patients with lung cancer bone metastasis. These markers include the following: (1) bone resorption-associated markers, such as N-terminal telopeptide (NTx)/C-terminal telopeptide (CTx), C-terminal telopeptide of type I collagen (CTx-I), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), pyridinoline (PYD), and parathyroid hormone related peptide (PTHrP); (2) bone formation-associated markers, including total serum alkaline phosphatase (ALP)/bone specific alkaline phosphatase(BAP), osteopontin (OP), osteocalcin (OS), amino-terminal extension propeptide of type I procollagen/carboxy-terminal extension propeptide of type I procollagen (PICP/PINP); (3) signaling markers, including epidermal growth factor receptor/Kirsten rat sarcoma/anaplastic lymphoma kinase (EGFR/KRAS/ALK), receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB/osteoprotegerin (RANKL/RANK/OPG), C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4), complement component 5a receptor (C5AR); and (4) other potential markers, such as calcium sensing receptor (CASR), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), cytokeratin 19 fragment/carcinoembryonic antigen (CYFRA/CEA), tissue factor, cell-free DNA, long non-coding RNA, and microRNA. The prognostic value of these markers is also investigated. Furthermore, we listed some clinical trials targeting hotspot biomarkers in advanced lung cancer referring for their therapeutic effects.

BackgroundSurgical therapy of breast cancer and bone metastasis can effectively improve the prognosis of breast cancer. However, after the first operation, the relationship between preoperative indicators and outcomes in patients who underwent metastatic bone surgery remained to be studied. Purpose 1. Recognize clinical and laboratory prognosis factors available to clinical doctors before the operation for bone metastatic breast cancer patients. 2. Develop a risk prediction model for 3-year postoperative survival in patients with breast cancer bone metastasis.MethodsFrom 2014 to 2020, patients who suffered from breast cancer bone metastasis and received therapeutic procedures in our institution were included for analyses (n=145). For patients who underwent both breast cancer radical surgery and bone metastasis surgery, comprehensive datasets of the parameters of interest (clinical features, laboratory factors, and patient prognoses) were collected (n=69). We performed Multivariate Cox regression to identify factors that were associated with postoperative outcome. 3-year survival prediction model and nomograms were established by 100 bootstrapping. Its benefit was evaluated by calibration plot, C-index, and decision curve analysis. The Surveillance, Epidemiology, and End Results database was also used for external validation.ResultsRadiotherapy for primary cancer, pathological type of metastatic breast cancer, lymph node metastasis, elevated serum alkaline phosphatase, lactate dehydrogenase were associated with postoperative prognosis. Pathological types of metastatic breast cancer, multiple bone metastasis, organ metastases, and elevated serum lactate dehydrogenase were associated with 3-year survival. Then those significant variables and serum alkaline phosphatase counts were integrated to construct nomograms for 3-year survival. The C-statistic of the established predictive model was 0.83. The calibration plot presents a graphical representation of calibration. In the decision curve analysis, the benefits are higher than those of the extreme curve. The receiver operating characteristic of the external validation of the model was 0.82, indicating a favored fitting degree of the two models.ConclusionOur study suggests that several clinical features and serological markers can predict the overall survival among the patients who are about to receive bone metastasis surgery after breast cancer surgery. The model can guide the preoperative evaluation and clinical decision-making for patients. Level of evidence Level III, prognostic study.

ObjectiveThis study aimed to develop a dual-energy spectral computed tomography (DESCT) nomogram that incorporated both clinical factors and DESCT parameters for individual preoperative prediction of lymph node metastasis (LNM) in patients with colorectal cancer (CRC).Material and MethodsWe retrospectively reviewed 167 pathologically confirmed patients with CRC who underwent enhanced DESCT preoperatively, and these patients were categorized into training (n = 117) and validation cohorts (n = 50). The monochromatic CT value, iodine concentration value (IC), and effective atomic number (Eff-Z) of the primary tumors were measured independently in the arterial phase (AP) and venous phase (VP) by two radiologists. DESCT parameters together with clinical factors were input into the prediction model for predicting LNM in patients with CRC. Logistic regression analyses were performed to screen for significant predictors of LNM, and these predictors were presented as an easy-to-use nomogram. The receiver operating characteristic curve and decision curve analysis (DCA) were used to evaluate the clinical usefulness of the nomogram.ResultsThe logistic regression analysis showed that carcinoembryonic antigen, carbohydrate antigen 199, pericolorectal fat invasion, ICAP, ICVP, and Eff-ZVP were independent predictors in the predictive model. Based on these predictors, a quantitative nomogram was developed to predict individual LNM probability. The area under the curve (AUC) values of the nomogram were 0.876 in the training cohort and 0.852 in the validation cohort, respectively. DCA showed that our nomogram has outstanding clinical utility.ConclusionsThis study presents a clinical nomogram that incorporates clinical factors and DESCT parameters and can potentially be used as a clinical tool for individual preoperative prediction of LNM in patients with CRC.

PurposeBone metastasis from endometrial cancer (EC) is rare and poorly described. The purpose of the present study was to investigate the correlation between the clinically accessible factors and survival time among EC patients with bone metastasis.Patients and MethodsWe retrospectively identified and reviewed EC patients with bone metastasis from 2010 to 2016, based on the Surveillance, Epidemiology and End Results (SEER) database. Univariable and multivariable Cox regressions were applied to evaluate the effects of clinical variables on survival. Kaplan–Meier plots were used to visually demonstrate the correlation between independent risk factors and survival.ResultsClinical data of 584 EC patients with bone metastasis from the SEER database were analyzed. EC patients with bone metastasis experienced extremely poor survival, with 1-year overall survival (OS) and cancer-specific survival (CSS) rates 33.8 and 35.8%, respectively. Variables associated with OS and CSS in the univariable analysis included race, tumor grade, tumor subtype, tumor size, lung, liver and brain metastases, surgery, radiotherapy, and chemotherapy. In the multivariable analysis, tumor grade, tumor subtype, liver and brain metastases, local surgery, and systemic chemotherapy remained independent risk factors for OS and CSS. However, local radiotherapy was an independent predictor of OS, not CSS.ConclusionsWe identified several factors affect the survival of EC patients with bone metastasis, which is useful for clinicians to assess patients’ outcomes. Our study supports surgery and radiotherapy of primary EC, and systemic chemotherapy for prolonging survival among EC patients with bone metastasis, which lays a solid foundation for defining optimal treatment strategy in this specific cohort.

BackgroundThis study aimed to develop and validate a computed tomography (CT)-based radiomics model to predict microsatellite instability (MSI) status in colorectal cancer patients and to identify the radiomics signature with the most robust and high performance from one of the three phases of triphasic enhanced CT.MethodsIn total, 502 colorectal cancer patients with preoperative contrast-enhanced CT images and available MSI status (441 in the training cohort and 61 in the external validation cohort) were enrolled from two centers in our retrospective study. Radiomics features of the entire primary tumor were extracted from arterial-, delayed-, and venous-phase CT images. The least absolute shrinkage and selection operator method was used to retain the features closely associated with MSI status. Radiomics, clinical, and combined Clinical Radiomics models were built to predict MSI status. Model performance was evaluated by receiver operating characteristic curve analysis.ResultsThirty-two radiomics features showed significant correlation with MSI status. Delayed-phase models showed superior predictive performance compared to arterial- or venous-phase models. Additionally, age, location, and carcinoembryonic antigen were considered useful predictors of MSI status. The Clinical Radiomics nomogram that incorporated both clinical risk factors and radiomics parameters showed excellent performance, with an AUC, accuracy, and sensitivity of 0.898, 0.837, and 0.821 in the training cohort and 0.964, 0.918, and 1.000 in the validation cohort, respectively.ConclusionsThe proposed CT-based radiomics signature has excellent performance in predicting MSI status and could potentially guide individualized therapy.

Plasma metabolomics and lipidomics have been commonly used for biomarker discovery. Studies in white and Japanese populations suggested that gender and age can affect circulating plasma metabolite profiles; however, the metabolomics characteristics in Chinese population has not been surveyed. In our study, we applied liquid chromatography-mass spectrometry-based approach to analyze Chinese plasma metabolome and lipidome in a cohort of 534 healthy adults (aging from 15 to 79). Fatty-acid metabolism was found to be gender- and age-dependent in Chinese, similar with metabolomics characteristics in Japanese and white populations. Differently, lipids, such as TGs and DGs, were found to be gender-independent in Chinese population. Moreover, nicotinate and nicotinamide metabolism was found to be specifically age-related in Chinese. The application of plasma metabolome and lipidome for renal cell carcinoma diagnosis (143 RCC patients and 34 benign kidney tumor patients) showed good accuracy, with an area under the curve (AUC) of 0.971 for distinction from healthy control, and 0.839 for distinction from the benign. Bile acid metabolism was found to be related to RCC probably combination with intestinal microflora. Definition of the variation and characteristics of Chinese normal plasma metabolome and lipidome might provide a basis for disease biomarker analysis.

Bladder cancer (BC) and Renal cell carcinoma(RCC) are the two most frequent genitourinary cancers in China. In this study, a comprehensive liquid chromatography—mass spectrometry (LC-MS) based method, which utilizes both plasma metabolomics and lipidomics platform, has been carried out to discriminate the global plasma profiles of 64 patients with BC, 74 patients with RCC, and 141 healthy controls. Apparent separation was observed between cancer (BC and RCC) plasma samples and controls. The area under the receiving operator characteristic curve (AUC) was 0.985 and 0.993 by plasma metabolomics and lipidomics, respectively (external validation group: AUC was 0.944 and 0.976, respectively). Combined plasma metabolomics and lipidomics showed good predictive ability with an AUC of 1 (external validation group: AUC = 0.99). Then, separation was observed between the BC and RCC samples. The AUC was 0.862, 0.853 and 0.939, respectively, by plasma metabolomics, lipidomics and combined metabolomics and lipidomics (external validation group: AUC was 0.802, 0.898, and 0.942, respectively). Furthermore, we also found eight metabolites that showed good predictive ability for BC, RCC and control discrimination. This study indicated that plasma metabolomics and lipidomics may be effective for BC, RCC and control discrimination, and combined plasma metabolomics and lipidomics showed better predictive performance. This study would provide a reference for BC and RCC biomarker discovery, not only for early detection and screening, but also for differential diagnosis.

Renal cell carcinoma (RCC) is the second most lethal urinary cancer. RCC is frequently asymptomatic and it is already metastatic at diagnosis. There is an urgent necessity for RCC specific biomarkers selection for diagnostic and prognostic purposes. In present study, we applied liquid chromatography—mass spectrometry (LC-MS) based metabolomics to analyze urine samples of 100 RCC, 34 benign kidney tumors and 129 healthy controls. Differential metabolites were analyzed to investigate if urine metabolites could differentiate RCC from non-RCC. A panel consisting of 9 metabolites showed the best predictive ability for RCC from the health controls with an area under the curve (AUC) values of 0.905 for the training dataset and 0.885 for the validation dataset. Separation was observed between the RCC and benign samples with an AUC of 0.816. RCC clinical stages (T1 and T2 vs. T3 and T4) could be separated using a panel of urine metabolites with an AUC of 0.813. One metabolite, N-formylkynurenine, was discovered to have potential value for RCC diagnosis from non-RCC subjects with an AUC of 0.808. Pathway enrichment analysis indicated that tryptophan metabolism was an important pathway in RCC. Our data concluded that urine metabolomics could be used for RCC diagnosis and would provide candidates for further targeted metabolomics analysis of RCC.

Currently, genomic characterization has become standard of care for tumor types such as non-small cell lung cancer, breast cancer, melanoma, and colorectal cancer. A deep understanding of genomic alterations in different tumor types would help identify potentially actionable genomic changes which occur across a wide variety of tumor types. A basket trial is a new type of clinical trial for which eligibility is based on the presence of a specific genomic alteration, irrespective of histology. Basket trials are phase II screening trials for the off-label use of a targeted drug in patients with the same genomic alterations for which it was approved. Intractable cancer refers to a type or condition of cancer which is unresponsive or resistant to treatment; intractable cancers may be classified into five subtypes as follows: hard-to-treat condition of common advanced cancer after multiple-line therapy, rare cancer in which no standard of care has been recommended, advanced cancer in which standard of care does not work well, cancer accompanied with organ dysfunction, and cancers in older or younger cancer patients. Previous studies have demonstrated that in basket trials, genomic-guided therapy yields clinical benefits in intractable cancer, thereby providing novel insights into the optimal clinical management of such cancers. In this review, we describe a novel way to classify intractable cancer, and summarize the current knowledge on such cancers. We additionally provide information on the role of basket trials in intractable cancer.