Journal of cancer research and therapeutics最新文献

Background: Patients with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options and poor outcomes.

Methods: This phase III study (NCT04236141) evaluated the efficacy and safety of polatuzumab vedotin plus bendamustine and rituximab (Pola+BR) versus BR in Chinese patients with transplant-ineligible R/R DLBCL to support regulatory submission in China. Patients were randomized 2:1 to receive Pola+BR or placebo+BR. The primary endpoint was complete response (CR) at the end of treatment (EOT) by positron emission tomography-computed tomography.

Results: Overall, 42 patients were analyzed (Pola+BR, n = 28; placebo+BR, n = 14). At data cutoff (July 12, 2021; median follow-up: 7.5 months), CR at EOT was 25.0% (7/28) with Pola+BR and 14.3% (2/14) with placebo+BR, 10.7% difference [95% confidence interval (CI): -19.0, 40.4]. The median investigator-assessed progression-free survival was 4.6 (95%CI: 3.1-6.4) months with Pola+BR and 2.0 (95% CI: 1.9-4.6) months with placebo+BR, with a 50% reduction in risk of progression or death (unstratified hazard ratio: 0.50; 95% CI: 0.24-1.05). The median overall survival was 10.6 [95% CI: 5.5-not evaluable (NE)] and 6.5 (95% CI: 6.0-NE) months, with a 45% reduction in risk of death. The incidence of Grade 3-4 adverse events was similar between Pola+BR (20/27 patients, 74.1%) and placebo+BR arms (11/14 patients, 78.6%).

Conclusions: Efficacy findings were consistent with results of the GO29365 study (NCT02257567); treatment with Pola+BR led to clinically meaningful improvements in response rates in Chinese patients with transplant-ineligible R/R DLBCL with no new safety signals.

Objective: To examine the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) with Sonazoid (Sonazoid-CEUS) for endometrial lesions.

Methods: In this prospective and multicenter study, data were collected from 84 patients with endometrial lesions from 11 hospitals in China. All the patients received a conventional US and Sonazoid-CEUS examination. The lesion characteristics based on US and Sonazoid-CEUS imaging were collected from the case report forms. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were determined using histopathologic diagnosis as the gold standard.

Results: Of the 79 patients included, 29 were diagnosed with benign lesions and 50 with endometrial carcinoma (EC). The accuracy, sensitivity, specificity, PPV, and NPV for Sonazoid-CEUS and US at differentiating EC from benign endometrial lesions were 82.2%, 94%, 62.1%, 81.0%, and 85.7%, and 79.7%, 96%, 51.7%, 92.3%, and 88.2%, respectively, with no significant differences observed for any of the values. For Sonazoid-CEUS, the best delineators of EC versus benign lesions were early enhancement and hyperenhancement (74% vs 53.3%, P = 0.029, 68% vs 45%, P < 0.001), and lesion size enlargement (76% vs 48%, P = 0.001). Despite finding no significant difference in the enhancement patterns (P = .367), a faster wash-in pattern with the contrast agent entering before the surrounding myometrium was more common in the EC vs benign cases (92% vs 48.3%).

Conclusions: Sonazoid-CEUS has higher accuracy, specificity, and comparable sensitivity for differentiating EC from benign endometrial lesions compared with conventional US. It provides complementary hemodynamics information reflective of tissue vascularization, which may improve the overall diagnostic efficiency.

Abstract: Colorectal cancer is the third most prevalent malignant tumor worldwide. Despite the advancements in surgical procedures and treatment options, CRC remains a considerable cause of cancer-related mortality. Shikonin is a naphthoquinone compound that exhibits multiple biological activities, including anti-inflammatory and anti-tumor effects as well as wound healing promotion. Recently, Shikonin has been increasingly used in basic research on colorectal malignant tumors. Therefore, we explored the mechanisms of action and structural improvements of Shikonin in colorectal cancer through a literature review to provide valuable insights for the advancement of research and development of related pharmaceuticals.

Abstract: Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has revolutionized one of the standard most efficient treatments for EGFR mutation-positive non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR-TKI, is currently one of most efficient treatments in clinical practice. However, it has a potentially fatal side effect: interstitial lung disease (ILD). When severe ILD occurs, a drug substitution is often required, and there is a rising concern about which drug to choose to inhibit the progression of NSCLC and avoid aggravating while alleviating ILD. Herein, we report an NSCLC case with osimertinib-induced ILD successfully rechallenged by almonertinib. In addition, we conducted a literature review on the clinical efficacy and adverse effects of almonertinib, hoping to provide insight into NSCLC treatment.

Aim: The tumor microenvironment in pancreatic cancer, characterized by abundant desmoplastic stroma, has been implicated in the failure of chemotherapy. Therefore, developing therapeutic strategies targeting tumor and stromal cells is essential. Triptolide, a natural compound derived from the plant Tripterygium wilfordii, has shown antitumor activity in various cancers, including pancreatic cancer. However, its effects on pancreatic cancer cells and the microenvironment remain unclear. This study aimed to explore the effect of triptolide on tumor cells and the tumor microenvironment in pancreatic cancer.

Methods: Cell Counting Kit-8, colony formation, apoptosis, and cell cycle assays were performed to determine the effect of triptolide on tumor cells. Additionally, co-culture assays were performed to explore the effects of the compound on cancer-associated fibroblasts (CAFs) in vitro. Orthotopic xenograft and subcutaneous tumor models were used to explore the antitumor and antistromal activation effects of triptolide in vivo. RNA sequencing was performed to identify the pathways involved in these processes in pancreatic cancer cells.

Results: Triptolide inhibited the proliferation of pancreatic cancer cells and attenuated stromal activation in vitro and in vivo. Furthermore, it suppressed autophagy and induced apoptosis in pancreatic cancer cells by inhibiting the secretion of CXCL1. Extracellular matrix formation in CAFs was disrupted by suppressing the paracrine secretion of TGF-β from tumor cells.

Conclusion: These findings indicate that triptolide plays a dual antitumor role against tumor cells and CAFs, thus providing new insights into treating pancreatic cancer in the future.

Background: To evaluate the association of demographic and clinicopathological characteristics with the survival of patients with testicular mixed teratoma and seminoma (TMTS).

Methods: The data of 3296 eligible patients with TMTS who underwent surgery between 2010 and 2015 were obtained from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier survival curves. The association of demographic and clinicopathological characteristics with the OS and CSS of patients with TMTS was assessed using the Cox proportional hazard regression model.

Results: The number of patients with TMTS increased annually. In Kaplan-Meier analyses, TMTS patients with advanced T stage (P < 0.001 for OS and P < 0.001 for CSS), lymph node metastasis (P < 0.001 for OS and P < 0.001 for CSS), distant metastasis (P < 0.001 for OS and P < 0.001 for CSS), no regional lymph node resection (P = 0.003 for OS and P = 0.002 for CSS), large tumor size (P = 0.001 for OS and P = 0.001 for CSS), and LVI (P < 0.001 for OS and P < 0.001 for CSS) exhibited inferior OS and CSS. Moreover, distant metastasis (HR 11.224, P < 0.001; HR 15.817, P < 0.001) and regional lymph node resection (HR 0.425, P = 0.003; HR 0.366, P = 0.004) were identified as independent prognostic factors for OS and CSS in patients with TMTS through multivariable analyses.

Conclusions: Distant metastasis and lymph node metastasis were deemed important prognostic factors for OS and CSS in patients with TMTS. Therefore, a comprehensive understanding and clinical assessments of these prognostic factors are necessary before tailoring clinical management and treatment plan specified for patients with TMTS.

Purpose: To investigate and compare the feasibility, safety, and clinical outcomes of antegrade and retrograde laparoscopic bilateral inguinal lymphadenectomy for penile cancer.

Methods: We retrospectively analyzed the clinical data of 32 patients with penile cancer admitted between 2018 and 2022. Among them, 17 patients underwent antegrade laparoscopic inguinal lymphadenectomy (ALIL group) and 15 underwent retrograde laparoscopic inguinal lymphadenectomy (RLIL group). The key surgical procedures and techniques are described. Operative time, intraoperative blood loss, hospital stay, drainage duration, postoperative complications, and follow-up data in both groups were statistically analyzed.

Results: Surgery in both groups was successfully completed without the need for intraoperative conversion to open surgery. The operative time was significantly shorter for ALIL than for RLIL (P < 0.001). Significantly less intraoperative blood loss was reported with ALIL than with RLIL (P < 0.001). The ALIL group had a significantly shorter hospital stay than the RLIL group (P = 0.027). The number of removed lymph nodes in the ALIL group differed insignificantly from that in the RLIL group (P = 0.360). Postoperative drainage duration, recurrence, short-term survival, and postoperative complications were similar between both groups.

Conclusion: In the patients with penile cancer, ALIL and RLIL yielded similar perioperative outcomes. However, ALIL was associated with shorter operative time, less blood loss, and shorter hospital stays. ALIL did not require repositioning of the laparoscopic instruments, thereby simplifying the procedure and minimizing patient trauma. Additionally, if needed, pelvic lymphadenectomy could be performed simultaneously from the same trocar position used in ALIL.

Aim: Toripalimab is the first antitumor programmed cell death protein 1 (PD-1) antibody approved in China. For better patient management, it is important to understand the real-world outcomes of toripalimab in treating patients with lung cancer in the real world outside of clinical trials to improve patient care.

Methods: We retrospectively examined the clinical data of 80 patients with lung cancer who received the PD-1 inhibitor (toripalimab). The Chi-square test was performed to identify clinical factors associated with the advancement of the disease. Multivariate Cox regression analysis was used to screen prognostic variables linked to real-world progression-free survival (PFS) and overall survival (OS). OS and PFS were calculated using the Kaplan-Meier method, and the comparisons were determined using the log-rank test, and continuous and categorical variables were explained using median and percentage, respectively.

Result: The median OS of the estimated 80 patients was 15.85 months (95% confidence interval [CI]: 14.103-17.949 months), and the estimated PFS was 5.650 months (95% CI: 7.226-11.264 months). The longer OS and PFS correlate with the patient's staging and number of treatment lines. The PD-1 drug gave stage III patients a significantly longer PFS and OS compared to stage IV patients (PFS: 14.65 vs. 6.68, P = 0.004; OS: 21.1 vs. 13.7, P = 0.003). First- or second-line immunotherapy patients have significantly longer PFS and OS than third- or fourth-line (PFS: 6.4 vs. 3.6, P = 0.009; OS: 20.0 vs. 10.5, P = 0.003). In patients with stage IV (n = 60) with extensive metastasis, the site of metastasis is mostly 1-3 sites after receiving toripalimab. The duration of PD-1 inhibitor OS in progressive patients (n = 56) was significantly prolonged (P = 0.038).

Conclusion: For patients with lung cancer, toripalimab can considerably extend PFS and OS in the first or second line and in stage III. PD-1 inhibitors are administered to patients with stage IV extensively metastatic lung cancer, which indicates an oligometastatic progression pattern, primarily in 1-3 locations, who are treated with PD-1 inhibitors. Continuing toripalimab beyond disease progression significantly prolonged OS.

Purpose: To evaluate the risk factors that may delay enhanced recovery in the ablation of liver tumors.

Methods: A total of 310 patients who underwent ultrasound-guided ablation of liver tumors under general anesthesia were prospectively enrolled. Baseline data, intraoperative parameters, and postoperative events were evaluated. Postoperative pain was scored using the visual analog scale (VAS). Logistic regression analysis was conducted for univariate and multivariate analyses.

Results: The study included 42 females (13.5%) and 268 males (86.5%). The mean age of the sample was 57 ± 11 years old. The average length of stay (LOS) was 4.3 ± 2.4 days. A total of 199 out of 310 patients (64.2%) experienced moderate to severe pain (VAS score > 3). Seventy out of 310 patients (22.6%) experienced other complications. In the multivariable analysis, the number of lesions [odds ratio (95% confidence interval): 3.23 (2.15-4.84); P < 0.001], maximum diameter of lesions [1.12 (1.07-1.17), P < 0.001], and smallest distance between the lesions and the liver capsule [0.91 (0.89-0.94), P < 0.001] were risk factors for postoperative pain (VAS > 3). A history of alcohol consumption [2.62 (1.33-5.19), P = 0.005] was a risk factor for other complications. Surgical history [0.40 (0.24-0.67), P = 0.001] was a protective factor against LOS. Total operation time [1.01, 1.00-1.01, P = 0.009] was a mild risk factor for LOS.

Conclusion: The number of lesions, maximum diameter of the lesions, smallest distance between the lesions and the liver capsule, total operation time, and a history of alcohol use were risk factors that may delay enhanced recovery in patients undergoing ablation of liver tumors. These findings may provide evidence to promote the use of the enhanced recovery after surgery protocol.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade fibrohistiocytic tumor with malignant potential. It is considered to have a high local recurrence rate due to the characteristic invasion of the finger-like lesion into the soft tissues.

Method: This retrospective study presents details of 20 DFSP patients with a history of surgery and a long follow-up period. All patients were followed up for 10 years to assess the relationship between the surgical margin and the recurrence rate. Seventeen patients provided informed consent for detailed pathological examinations.

Results: Twenty Asian patients with a mean age of 42.55 years were included in this study. The location of the DFSP varied among the individuals; seven were closed by sutures, four were full-thickness skin grafts, and nine were closed using a pedicled flap. The average follow-up period was 4.185 ± 3.09 years. Recurrence was observed in 8 out of the 20 patients 1-8 years after surgery (recurrence group). A significant (P = 0.04) difference in the average surgical margin was observed between the recurrence group (1.62 ± 0.74 cm) and the remaining patients (heal group; 2.83 ± 1.43 cm). The median Ki-67 value was 12%.

Conclusion: Local control of DFSP after surgery is challenging. The first choice of DFSP treatment is surgery to clear the margins and reconstruct the area. Enhancing the diagnosis rate of DFSP during the initial visit is important for the proper management and operation opportunity.