Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

Development and Validation of a Novel Prognostic Model for Overall Survival in Newly Diagnosed Multiple Myeloma Integrating Tumor Burden and Comorbidities.

Background: Multiple myeloma (MM) is a highly heterogeneous disease with enormously variable outcomes. It remains to be a major challenge to conduct a more precise estimation of the survival of MM patients. The existing stratifications attached less importance to the prognostic significance of comorbidities. In the present study, we aimed to develop and validate a novel and simple prognostic stratification integrating tumor burden and comorbidities measured by HCT-CI. Method: We retrospectively enrolled 385 consecutive newly diagnosed multiple myeloma (NDMM) patients in Xijing Hospital from January 2013 to December 2020. The cohort between January 2016 and December 2020 was selected as development cohort (N = 233), and the cohort between January 2013 and December 2015 was determined as validation cohort (N = 152). By using LASSO analysis and univariate and multivariable Cox regression analyses, we developed the MM-BHAP model in the way of nomogram composed of ß2-MG, HCT-CI, ALB, and PBPC. We internally and externally validated the MM-BHAP model and compared it with ISS stage and R-ISS stage. Results: The MM-BHAP model was superior to the ISS stage and partially better than the R-ISS stage according to time-dependent AUC, time-dependent C-index, DCA, IDI, and continuous NRI analyses. In predicting OS, only the MM-BHAP stratification clearly divided patients into three groups while both the ISS stage and R-ISS stage had poor classifications in patients with stage I and stage II. Moreover, the MM-BHAP stratification and the R-ISS stage performed well in predicting PFS, but not for the ISS stage. Besides, the MM-BHAP model was also applied to the patients with age ≤65 or age >65 and with or without HRCA and could enhance R-ISS or ISS classifications. Conclusions: Our study offered a novel simple MM-BHAP stratification containing tumor burden and comorbidities to predict outcomes in the real-world unselected NDMM population.

Genomic characteristics of driver genes in Chinese patients with non-small cell lung cancer.

BACKGROUND: The aim of this study was to determine the demographic profile of driver gene alterations, especially low-frequency gene alterations in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 7395 Chinese patients with NSCLC were enrolled in the study. Next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded specimens collected via either surgical resection or biopsy. RESULTS: The frequent genomic alterations found in the study were EGFR mutations (51.7%), KRAS mutations (13.1%), MET alterations (5.6%; 3.2% copy number gains and 0.5% exon 14 skipping mutation), HER2 alterations (7.0%; 2.0% copy number gains and 5.4% mutations), ALK alterations (7.2%; 3.9% rearrangements), RET rearrangements (1.4%), ROS1 rearrangements (0.9%), and NTRK rearrangements (0.6%). The EGFR mutation rate was found to be significantly higher in women than in men (69.1% vs. 38.5%, P < 0.001), while the KRAS mutation (17.5% vs. 7.3%, P < 0.001) and MET alteration rates (6.5% vs. 4.5%, P < 0.001) were significantly higher in men than in women. The EGFR mutation rate tended to decrease with age in the group aged >40 years, while the KRAS mutation rate tended to increase with age. The HER2 mutation (13.9% vs. 6.7%, P < 0.001) and ALK alteration rates (14.3% vs. 6.9%, P < 0.001) were significantly higher in the group aged <40 years than in groups aged 40 years or older. CONCLUSIONS: The frequency of different driver genes was diverse in different age-gender groups, and the results of this study may assist clinicians in clinical decision-making and the development of public healthcare strategies in the future. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This study demonstrated that the frequency of different driver genes was diverse in different age-gender groups. What this study adds It may enable clinicians to make clinical decisions, and assist government, pharmaceutical researchers and insurance companies develop public healthcare strategies.

Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

AIMS: The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. MAIN METHODS: A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. KEY FINDINGS: The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. SIGNIFICANCE: The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area.

Association Between Use of Traditional Chinese Medicine Herbal Therapy and Survival Outcomes in Patients With Stage II and III Colorectal Cancer: A Multicenter Prospective Cohort Study.

Background: Chinese cancer patients often use Traditional Chinese Medicine (TCM) herbal medicine during or after active cancer treatments. However, little is known about how TCM herbal medicine impacts cancer outcomes. This study aimed to evaluate the association between TCM herbal therapy and survival outcomes in patients with stage II or III colorectal cancer. Methods: We conducted an eight-center prospective cohort study in China among patients who had undergone radical resection for stage II and III colorectal cancer. All patients received comprehensive conventional treatments according to National Comprehensive Cancer Network (NCCN) guidelines, and follow-up visits were conducted over five years. We defined high exposure as a patient's use of TCM individualized herbs for more than one year, ascertained via clinical interviews. The primary outcome was disease-free survival (DFS), with overall survival (OS) as a secondary outcome. Results: Between April 2007 and February 2009, we enrolled 312 patients into the cohort; 166 (53.2%) met the definition of high exposure to TCM herbs. Adjusting for covariates, high exposure to TCM was associated with both better DFS (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.39 to 0.98) and OS (HR = 0.31, 95% CI = 0.14 to 0.68). In subgroup exploratory analysis, the effects demonstrated that the differences in outcomes were statistically significant in patients who had received chemotherapy. Conclusion: Longer duration of TCM herbal use is associated with improved survival outcomes in stage II and III colorectal cancer patients in China. More research is needed to evaluate the effects and underlying mechanisms of herbal medicine on colorectal cancer outcomes.

[Treatment of EGFRIs-related Skin Adverse Reactions by Zhiyang Pingfu Lotion].

Objective To observe the curative effect of Zhiyang Pingfu Lotion (ZPL) for its ex- ternal application in treatment of epidermal growth factor receptor inhibitors (EGFRIs)-related acneiform rash, cutaneous pruritus , xerosis cutis , and nail changes , as well as to evaluate its safety and patients' satisfaction. Methods Recruited were 201 patients with confirmed pathological diagnosis, who had acne- iform rash after using EGFRIs. They were assigned to the treatment group (131 cases) and the control group (70 cases) by random digit table. Patients in the treatment group were externally applied with self- formulated ZPL based on principles of Western medical standards, while those in the control group were externally applied with blank drugs plus conventional Western medicine standard. The therapeutic course for all was 14 days. Changes in rash degree, cutaneous pruritus, xerosis cutis, and nails were observed in both groups before and after treatment. Blood routines as well as liver and kidney function tests were performed in both groups before and after treatment. Follow-up visit was also conducted during progression-free survival (PFS). Results A total of 185 patients finished this clinical trial. Ten dropped out in the treatment group and 6 in the control group. The effective rates of rash degree, cutaneous pruritus, xerosis cutis, and nail changes were 90.1 % (109/121 ), 57.9% (70/121 ), 57. 9% (70/121 ), and 16. 5% (20/121) in the treatment group, respectively. They were 14. 1% (9/64), 6. 3% (4/64), 1. 6% (1164), and 0 (0/64) in the control group, respectively. Significant difference existed in all these indices between the two groups (X² = 105. 1022, 51. 3312, 59. 1777; P <0. 05). No serious drug-related adverse events occurred during clinical observation, with relatively better safety. The satisfaction was 95. 40% (125/131) in the treatment group and 57. 1 % (40/70) in the control group. No statistical difference in PFS was observed between the two groups (X² = 2. 006, P > 0. 05). Conclusions ZPL had significantly curative effect in treatment of EGFRIs-related skin adverse reactions, with no obvious adverse reactions. Howev- er, more randomized control trials are needed to verify these findings.

A phase II study of triweekly paclitaxel and capecitabine combination therapy in patients with fluoropyrimidine-platinum-resistant metastatic gastric adenocarcinoma.

BACKGROUND: Although randomized trials have shown a survival benefit of second-line chemotherapy (SLC) in metastatic gastric adenocarcinoma (MGA), no standard regimen has yet been established. Paclitaxel acts synergistically with capecitabine. In this phase II study, we evaluated the efficacy and safety of paclitaxel/capecitabine (PX) as an SLC regimen for patients with fluoropyrimidine-resistant MGA. MATERIALS AND METHODS: Patients were eligible if the tumor progressed to fluoropyrimidine-based regimens or relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of paclitaxel (80 mg/m 2 , days 1 and 8) and capecitabine (1000 mg/m 2 , bid, days 1-14), called PX, every 3 weeks. The primary endpoint was the objective response rate (ORR). Thirty-five patients were required according to the statistical design, and PX combination would be rejected if fewer than five patients responded. RESULTS: From November 2004 to May 2007, 36 eligible patients were enrolled. Among them, 35 (97.2%) had previously received platinum/fluoropyrimidine as first-line therapy. Response was assessed in 35 patients; 10 partial responses were obtained, resulting in an ORR of 28.5%. The median progression-free survival was 5.0 months, and the median overall survival was 11.1 months. The most frequent grade 3/4 toxicity was neutropenia, observed in 11.1% of the patients. CONCLUSIONS: PX regimen was clearly demonstrated to be active and safe for fluoropyrimidine-platinum-resistant MGA, and further evaluation in future phase III trials is warranted.

Comparison of survival of patients receiving laparoscopic and open radical resection for stage II colon cancer.

BACKGROUND: The aim of the study was to compare the survival of patients receiving laparoscopic vs. open radical resection for stage II colon cancer. PATIENTS AND METHODS: Two hundred and twenty patients with stage II colon cancer were enrolled from Beijing Chaoyang Hospital of Capital Medical University from January 2000 to December 2009, including 61 patients in the laparoscopic radical resection group and 159 patients in the open radical resection group. The survival data in both groups were compared using the log rank test based on Kaplan-Meier survival curves. RESULTS: There was no statistically significant difference in the 3-year survival (88.5% vs. 80.5%; X(2)=1.98, P=0.159) and the 5-year survival (81.9% vs. 69.2%; X(2)=1.98, P=0.159) between both groups. However, statistically significant difference was found in median overall survival (mOS), which was 102.6 (95% CI: 76.8-122.7) months in the laparoscopic group and 90.0 (95% CI: 70.4-109.6) months in the open radical resection group (X(2)=4.183, P=0.041). mOS was 96 (95% CI: 68.6-111.4) months and 92.6 (95% CI: 56.8-107.2) months in those with and without postoperative chemotherapy, respectively (X(2)=6.389, P=0.011). For patients older than 75 years the mOS was 90.0 (95% CI: 25.3-105.0) months and 83.4 (95% CI: 13.1-96.9) months in the laparoscopic and open group, respectively. The difference between the both groups was statistically significant (X(2)=6.191, P=0.013). CONCLUSIONS: The mOS of patients receiving laparoscopic radical resection was better than open radical resection for stage II colon cancer, especially for patients over 75 years old.

[Irinotecan plus fuorouracil/leucovorin (FOLFIRI) as a second line chemotherapy for refractory or metastatic colorectal cancer].

OBJECTIVE: Irinotecan (CPT-11), a specific inhibitor of topoisomerase I, has been proven to be effective in the treatment of refractory or metastatic colorectal cancer. Furthermore, several first line phase III trials of the combination therapy (FOLFIRI) using CPT-11 and fuorouracil/leucovorin (5-Fu/LV) were reported to have significant improvement in treatment result. Therefore, we designed a multicenter clinical study to observe the overall survival (OS), time to death (TTD), time to progression (TTP), efficacy and safety of FOLFIRI regimen for patients with refractory or metastatic colorectal cancer after first line chemotherapy failure. METHODS: Patients with metastatic or refractory colorectal cancer after first line oxaliplatin-based chemotherapy failure were enrolled into this prospective, one arm and open-labeled multicenter study. Irinotecan 180 mg/m2 was administered biweekly on D1, LV 200 mg/m2 by intravenous infusion in 2 hours before bolus intravenous injection of 5-Fu 400 mg/m2, then followed immediately by intravenous infusion of 5-Fu 2.4 g/m2 in 46 hours. OS, TTD, TTP, response rate (RR) and adverse events were assessed according to RSCIST criteria and NCIC-CTG CTCAE (3.0). RESULTS: Sixty-six patients were valuable for safety assessment and and 61 for efficacy. There was no CR patient in this series. Ten patients had PR, 35 SD (57.4% ) and 16 PD (26.2%) with a response rate of 16.4% (10/61). The median TTP was 5.0 months (1-12 months), median TTD 9.9 months (5-27 months)and median OS 18.2 months (7-33 months). The adverse events including nausea,vomiting, anorexia,diarrhea, leucopenia and cholinergic syndrome were frequent, but usually in I - II degree. The rate of III/IV degree diarrhea and leucopenia was 7.6% and 22.7%, respectively. CONCLUSION: The regimen of irinotecan plus fuorouracil/leucovorin (FOLFIRI) is effective and well-tolerated as a second-line chemotherapy and may prolong the overall survival for the patient with refractory or metastatic colorectal cancer.