Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

xloma.fota13 shared this article with you from Inoreader Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer Via Cancer Medicine We developed the risk assessment based on the types of dynamic changes of bone metastasis before the use of radium‐223 dichloride (Ra‐223). This risk assessment can be used to maximize the clinical benefits of Ra‐223 treatment for bone‐predominant metastasis. Abstract Background To best employ radium‐223 dichloride (Ra‐223) for patients with castration‐resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone‐predominant status in patients treated with Ra‐223. Methods We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra‐223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra‐223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression‐free survival (PFS). Results During the median follow‐up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13‐1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04‐2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02‐2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11‐2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra‐223 treatment. This was associated with non‐bone metastasis progression, especially visceral metasta sis, and overall survival. Conclusions Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone‐predominant metastasis type to benefit from Ra‐223. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Simultaneous integrated boost of intensity‐modulated radiation therapy to Stage II‐III non‐small cell lung cancer with metastatic lymph nodes

xloma.fota13 shared this article with you from Inoreader Simultaneous integrated boost of intensity‐modulated radiation therapy to Stage II‐III non‐small cell lung cancer with metastatic lymph nodes Via Cancer Medicine The different radiation doses were simultaneously prescripted 78 Gy (PTVp）and 60‐65 Gy (PTVn). SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety and satisfactory efficacy. Abstract Local tumor failure remains a major problem after radiation‐based nonsurgical treatment for unresectable locally advanced nonsmall cell lung cancer (NSCLC）and inoperable stage II NSCLC. The aim of this study was to evaluate the feasibility of simultaneous integrated boost of intensity‐modulated radiation therapy (SIB‐IMRT) to stage II‐III NSCLC with metastatic lymph nodes (ChiCTR 2000029304). Patients were diagnosed by pathology or PET‐CT. PTV was divided into two parts as follows, the PTV of primary tumor (PTVp) and the PTV of metastatic lymph nodes (PTVn). The radiotherapy doses were simultaneously prescripted 78 Gy (BED = 101.48 Gy) for PTVp and 60‐65 Gy (BED = 73.6‐81.25 Gy) for PTVn, 26f/5.2 weeks. Response was scored according to WHO criteria. Radiotherapy toxicity was scored according to RTOG criteria. Hematology and gastrointestinal toxicity were scored according to CTCAE1.0 criteria. A total of 20 patients were enrolled. Seventeen patients were diagnosed by pathology and three patients were diagnosed by PET‐CT. All patients were treated with SIB‐IMRT. The objective response rate (ORR) was 90%, with CR 25%, PR 65%, NC 10%, and PD 0%. Although radiotherapy toxicity was common, there were no grade ≥3, with radiation pneumonitis (10 cases), esophagitis (17 cases), and dermatitis (12 cases). The local control rates at 1, 3, and 5 years were 85%, 75%, and 70%, respectively. The overall survival（OS）and local progression‐free survival (LPFS) rates at 1, 3, and 5 years were 90%, 42.6%, and 35.5% and 84.4%, 35.5%, and 28.4%, respectively. SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety, and satisfactory efficacy. However, due to the limitation of small sample, these findings are needed to confirm by future trials with a larger sample size. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Sulfiredoxin‐1 is a promising novel prognostic biomarker for hepatocellular carcinoma

xloma.fota13 shared this article with you from Inoreader Sulfiredoxin‐1 is a promising novel prognostic biomarker for hepatocellular carcinoma Via Cancer Medicine In this work, we evaluated the prognostic power of SRXN1 for hepatocellular carcinoma using clinical specimens from both the public databases and Zhongshan Hospital. We also established a prognostic nomogram based on SRXN1 expression, which was proved to be more accurate than the routine staging systems for the prediction of overall survival. Finally, functional and pathway enrichment analysis and PPI network analysis of SRXN1 and its related genes were conducted, respectively, which may shed light on the mechanism of SRXN1 as an oncogene. Abstract Identifying novel prognostic biomarkers for hepatocellular carcinoma (HCC) and then, develop an effective individualized treatment strategy remain extremely warranted. The prognostic role of sulfiredoxin‐1(SRXN1), an antioxidant enzyme, remains unknown in HCC. This study aimed to explore the prognostic implications of SRXN1 in HCC patients after partial hepatectomy. The expression of SRXN1 in HCC and normal tissue were analyzed using the patients from the public databases and Zhongshan Hospital. The Cox regression, Kaplan‐Meier survival analysis, and time‐dependent receiver operating characteristic curves were performed to identify the predictive role of SRXN1 expression on HCC patients. A prognostic nomogram based on SRXN1 expression was constructed and validated to further confirm the predictive power of SRXN1 as a prognostic biomarker. Finally, functional enrichment analysis and protein‐protein interaction network analysis of SRXN1 and its associated genes were conducte d. The results showed that SRXN1 was upregulated in HCC samples compared with the normal liver tissues. Patients with SRXN1 upregulation had shorter survival time. SRXN1 overexpression was significantly correlated with advanced clinicopathological parameters. The prognostic nomogram based on SRXN1 expression was proved to be more accurate than routine staging systems for the prediction of overall survival. Protein‐protein interaction network analysis demonstrated the first neighbor genes of SRXN1 mainly participated in response to oxidative stress. In brief, SRXN1 could be a prognostic biomarker for the management of HCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical outcomes of newly diagnosed primary CNS lymphoma treated with ibrutinib‐based combination therapy: A real‐world experience of off‐label ibrutinib use

xloma.fota13 shared this article with you from Inoreader Clinical outcomes of newly diagnosed primary CNS lymphoma treated with ibrutinib‐based combination therapy: A real‐world experience of off‐label ibrutinib use Via Cancer Medicine Our real‐world experience demonstrated the clinical benefit of the ibrutinib‐based combination therapy in treating newly diagnosed PCNSL patients, in complement to the activity of the drug combination reported for relapse/refractory PCNSL. Our data also underscored the clinical significance of liquid biopsy including cerebrospinal fluid ctDNA in tracing tumor burden and evaluating treatment response. Abstract Ibrutinib‐based combination therapy with high‐dose methotrexate (HD‐MTX) has recently shown clinical activity against relapse/refractory (R/R) primary central nervous system lymphoma (PCNSL). Herein, we report our real‐world experience of treating 11 newly diagnosed PCNSL patients with the ibrutinib/MTX combination. HD‐MTX was given at 3.5 g/m2 every 2‐week for eight doses. Ibrutinib was held upon HD‐MTX infusion until clearance and was administered daily post‐induction until disease progression, intolerable toxicity, or death. Nine out of 11 patients completed the induction phase and received ibrutinib as maintenance therapy. An objective response rate (ORR) of 82% (9/11) was observed including complete response (64%) and partial response (18%). The median progression‐free survival (PFS) was 7.4 months while the median overall survival (OS) was not reached. The ibrutinib/MTX combination was well tolerated in these treatment‐naïve PCNSL pa tients with an acceptable safety profile. Moreover, the longitudinal analysis of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) revealed that CSF ctDNA detection was closely associated with tumor response, and sustained tumor responses correlated with the clearance of ctDNA from the CSF. In sum, our data not only demonstrated the clinical benefit of the ibrutinib and HD‐MTX combination regimen in treating newly diagnosed PCNSL patients in a real‐world setting, but also highlighted the significance of liquid biopsy including CSF ctDNA in tracing tumor burden and assessing treatment response. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma

xloma.fota13 shared this article with you from Inoreader Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma Via Cancer Medicine This study provided evidences that the genetic mutation model (named as ITS) identified a melanoma population with multiple genetic patterns of sensitivity to ICIs, who might potentially benefit from ICIs therapy. Preliminary data from three independent cohorts strongly suggested better treatment outcomes from ICIs therapy in melanoma patients with high ITS. Remarkably, the combination strategy of ITS and TMB or LDH showed better prediction efficacy compared with any single biomarker. Abstract Several biomarkers such as tumor mutation burden (TMB), neoantigen load (NAL), programmed cell‐death receptor 1 ligand (PD‐L1) expression, and lactate dehydrogenase (LDH) have been developed for predicting response to immune checkpoint inhibitors (ICIs) in melanoma. However, some limitations including the undefined cut‐off value, poor uniformity of test platform, and weak reliability of prediction have restricted the broad application in clinical practice. In order to identify a clinically actionable biomarker and explore an effective strategy for prediction, we developed a genetic mutation model named as immunotherapy score (ITS) for predicting response to ICIs therapy in melanoma, based on whole‐exome sequencing data from previous studies. We observed that patients with high ITS had better durable clinical benefit and survival outcomes than patients with low ITS in three independent cohorts, as well as in the meta‐cohort. Notably, the prediction capability of ITS was m ore robust than that of TMB. Remarkably, ITS was not only an independent predictor of ICIs therapy, but also combined with TMB or LDH to better predict response to ICIs than any single biomarker. Moreover, patients with high ITS harbored the immunotherapy‐sensitive characteristics including high TMB and NAL, ultraviolet light damage, impaired DNA damage repair pathway, arrested cell cycle signaling, and frequent mutations in NF1 and SERPINB3/4. Overall, these findings deserve prospective investigation in the future and may help guide clinical decisions on ICIs therapy for patients with melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Race modifies survival benefit of guideline‐based treatment: Implications for reducing disparities in muscle invasive bladder cancer

xloma.fota13 shared this article with you from Inoreader Race modifies survival benefit of guideline‐based treatment: Implications for reducing disparities in muscle invasive bladder cancer Via Cancer Medicine Receipt of guideline‐based treatment nearly eliminated survival disparities between Latino and white individuals with bladder cancer but the benefit was not the same for black individuals, highlighting several potential targets for intervention. Abstract Background Black individuals with muscle‐invasive bladder cancer (MIBC) experienced 21% lower odds of guideline‐based treatment (GBT) and differences in treatment explain 35% of observed Black‐White differences in survival. Yet little is known of how interactions between race/ethnicity and receipt of GBT drive within‐ and between‐race survival differences. Methods Black, White, and Latino individuals diagnosed with nonmetastatic, locally advanced MIBC from 2004 to 2013 within the National Cancer Database were included. Guideline‐based treatment was defined as the receipt including one or more of the following treatment modalities: radical cystectomy (RC), neoadjuvant chemotherapy with RC, RC with adjuvant chemotherapy, and/or chemoradiation based on American Urological Association guidelines. Cox proportional hazards model of mortality estimated effects of GBT status, race/ethnicity, and the GBT‐by‐race/ethnicity interaction, adjusting for covariates. Results Of the 54 910 MIBC individuals with 125 821 person‐years of posttreatment observation (max = 11 years), 6.9% were Black, and 3.0% were Latino. Overall, 51.4%, 45.3%, and 48.5% of White, Black, and Latino individuals received GBT. Latino individuals had lower hazard of death compared to Black (HR 0.81, 95% CI 0.75‐0.87) and White individuals (HR 0.92, 95% 0.86‐0.98). With GBT, Latino and White individuals had similar outcomes (HR = 1.00, 95% 0.91‐1.10) and both fared better than Black individuals (HR = 0.88, 95% 0.79‐0.99 and HR = 0.88, 95% 0.83‐0.94, respectively). Without GBT, Latino individuals fared better than White (HR = 0.85, 95% 0.77‐0.93) and Black individuals (HR = 0.74, 95% 0.67‐0.82) while White individuals fared better than Black individuals (HR = 0.87, 95% 0.83‐0.92). Black individuals with GBT fared worse than Latinos without GBT (HR = 1.02, 95% 0.92‐1.1 4), although not statistically significant. Conclusion Low GBT levels demonstrated an "under‐allocation" of GBT to those who needed it most—Black individuals. Interventions to improve GBT allocation may mitigate race‐based survival differences observed in MIBC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next‐generation sequencing technique

xloma.fota13 shared this article with you from Inoreader Characteristics and prognostic significance of genetic mutations in acute myeloid leukemia based on a targeted next‐generation sequencing technique Via Cancer Medicine Genetic mutations can predict favorable or unfavorable prognosis of AML patients. Allo stem cell transplantation can provide benefits for AML patients with bad genetic mutations. Abstract To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next‐generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3‐internal tandem duplication (FLT3‐ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPA double mutation. In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse‐free survival (RFS), DNMT3A, FLT3‐ITD, or RUNX1 mutation predicted a higher likelihood of remission‐induction failure, whereas NRAS mutation or CEBPA double mutation predicted longer OS. Concurrent DNMT3A, FLT3‐ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation‐related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next‐generation sequencing screening. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trimodal therapy in T2‐4aN0M0 bladder cancer––How to select the best candidate?

xloma.fota13 shared this article with you from Inoreader Trimodal therapy in T2‐4aN0M0 bladder cancer––How to select the best candidate? Via Cancer Medicine Bladder tumor diameter on pretreatment CT is the single best predictor of tumor volume and of response to trimodal therapy. In cisplatin‐eligible patients with a tumor diameter ≤3 cm, trimodal treatment provides 5‐year disease‐specific survival of 80% Abstract The reported results of trimodal treatment (TMT) in muscle‐invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2‐4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre‐TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow‐up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease‐specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p < 0.0001 for overall, disease‐specific and recurrence‐free survivals. For every 1 cm increase in tumor diameter, the risk of disease‐specific mortality increased by 1.57. Age, cisplatin eligibility and the Charlson Comorbidity Index were significant predictors of overall survival but not of disease‐specific or recurrence‐free survival. Patients who were cisplatin‐eligible with a tumor diameter ≤3 cm had a 5‐year disease‐specific survival rate of 79.2% as opposed to 33.9% in patients without one of these features (p < 0.001). When tumor diameter exceeded 5 cm (irrelevant of all other parameters), 5‐year disease‐specific survival rate was only 28.2%. Patient profiles can accurately predict response to TMT. In cisplatin‐eligible patients with a tumor diameter ≤3 cm, TMT provides an excellent disease‐specific survival rate. In patients with a tumor diameter >5 cm TMT renders unacceptably poor treatment outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non‐high‐incidence area

xloma.fota13 shared this article with you from Inoreader Development and external validation of a nomogram to predict the risk of Upper gastrointestinal precancerous lesions in a non‐high‐incidence area Via Cancer Medicine We performed a cross‐sectional study from October 2012 with the major national public health project—Early Screening Program in Urban China (CanSPUC) in Hunan province. In this study, we analyze the results of upper gastrointestinal cancer (UGC) screening conducted in the first 7 year of CanSPUC. And for the firstly time, we aim to develop and externally validate a nomogram for predicting the risk of UGPL, so as to provide a simple and accurate tool for risk questionnaire evaluation of UGC screening in non‐high‐incidence area. Abstract Background Upper gastrointestinal precancerous lesions (UGPL) is the major preventable disease in non‐high‐incidence area. A prognostic nomogram was constructed to predict and identity susceptible population of UGPL before endoscope screening. Methods We recruited 300 ,016 eligible participants for upper gastrointestinal cancer (UGC) screening aged 40‐74 years from two cities in Hunan province from 2012 to 2019. Individuals at high risk of UGC on basis of questionnaire estimation underwent endoscopic screening. Participants in two cities accepting endoscopy were used as training and external validation cohorts, respectively. A nomogram was developed based on independent prognostic factors of UGPL determined in multivariable logistic regression analysis. Results Of 35, 621 with high risk for UGC, 10, 364 subjects undertook endoscopy (participation rate of 29.1%). The detection rate for UGPL was 4.55%. The nomogram showed that age, gender, mental trama, picked food, and atrophic gastritis history in a descending order were significant contributors to UGPL risk. The C‐index value of internal and external validation of the model is 0.612 and 0.670, respectively. The calibration data for UGPL showed optimal agreement between the nomogram prediction and actual observation. Furthermore, high‐risk and low‐risk group divided based on score from the nomogram predicted a significantly distinct detection rate. Conclusion The nomogram provides screening workers a simple and accurate tool for identifying individuals at a higher risk of UGPL as primary screening before endoscopy among Chinese population in non‐high‐risk areas, thus reducing the incidence of UGC by improving the UGPL detection. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Convalescent Plasma for the Treatment of Severe COVID‐19 Infection in Cancer Patients

xloma.fota13 shared this article with you from Inoreader Convalescent Plasma for the Treatment of Severe COVID‐19 Infection in Cancer Patients Via Cancer Medicine Patients with cancer are particularly vulnerable to infection with COVID‐19 given immunodeficiency secondary to their underlying disease and cancer‐directed therapy. Here, we report a case series of 24 cancer patients with COVID‐19 treated with convalescent plasma. Non‐intubated patients, particularly those on nasal cannula alone, had favorable outcomes, suggesting convalescent plasma may be a viable treatment options for cancer patients with COVID‐19, particularly if utilized early in the disease course. Abstract Background Patients with malignancy are particularly vulnerable to infection with Severe Acute Respiratory Disease‐Coronavirus‐2 (SARS‐CoV‐2) given their immunodeficiency secondary to their underlying disease and cancer‐directed therapy. We report a case series of patients with cancer who received convalescent plasma, an investigational therapy for severe Coronavirus Disease 2019 (COVID‐19). Methods Patients with cancer were identified who received convalescent plasma. Enrolled patients had confirmed COVID‐19 with severe or life‐threatening disease and were transfused with convalescent plasma from donors with a SARS‐CoV‐2 anti‐spike antibody titer of ≥ 1:320 dilution. Oxygen requirements and clinical outcomes of interests were captured as well as laboratory parameters at baseline and 3 days after treatment. Results We identified 24 patients with cancer, 14 of whom had a hematological malignancy, who were treated with convalescent plasma. Fifteen patients (62.5%) were on cancer‐directed treatment at the time of COVID‐19 infection. After a median of hospital duration of 9 days, 13 patients (54.2%) had been discharged home, 1 patient (4.2%) was still hospitalized, and 10 patients had died (41.7%). Non‐intubated patients, particularly those on nasal cannula alone, had favorable outcomes. Three mild febrile non‐hemolytic transfusion reactions were observed. C‐reactive protein significantly decreased after 3 days of treatment, while other laboratory parameters including ferritin and D‐dimer remained unchanged. Conclusions Convalescent plasma may be a promising therapy in cancer patients with COVID‐19. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer

xloma.fota13 shared this article with you from Inoreader Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer Via Cancer Medicine In this clinical trial, patients with resectable early stage non‐small cell lung cancer received a combination of neoadjuvant chemotherapy with avelumab, an anti‐PD‐L1 monoclonal antibody. The study found that there were no increased surgical complications. Also, the benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint. Abstract Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.