Nomogram predicting overall survival after surgical resection for retroperitoneal leiomyosarcoma patients

BackgroundSurgery is the best way to cure the retroperitoneal leiomyosarcoma (RLMS), and there is currently no prediction model on RLMS after surgical resection. The objective of this study was to develop a nomogram to predict the overall survival (OS) of patients with RLMS after surgical resection.MethodsPatients who underwent surgical resection from September 2010 to December 2020 were included. The nomogram was constructed based on the COX regression model, and the discrimination was assessed using the concordance index. The predicted OS and actual OS were evaluated with the assistance of calibration plots.Results118 patients were included. The median OS for all patients was 47.8 (95% confidence interval (CI), 35.9-59.7) months. Most tumor were completely resected (n=106, 89.8%). The proportions of French National Federation of Comprehensive Cancer Centres (FNCLCC) classification were equal as grade 1, grade 2, and grade 3 (31.4%, 30.5%, and 38.1%, respectively). The tumor diameter of 73.7% (n=85) patients was greater than 5 cm, the lesions of 23.7% (n=28) were multifocal, and 55.1% (n=65) patients had more than one organ resected. The OS nomogram was constructed based on the number of resected organs, tumor diameter, FNCLCC grade, and multifocal lesions. The concordance index of the nomogram was 0.779 (95% CI, 0.659-0.898), the predicted OS and actual OS were in good fitness in calibration curves.ConclusionThe nomogram prediction model established in this study is helpful for postoperative consultation and the selection of patients for clinical trial enrollment

Case report: Pathological complete response to perioperative treatment of radiotherapy combined with angiogenesis inhibitor in a patient with pleomorphic liposarcoma

BackgroundLiposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment.Case presentationA 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1–14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months.ConclusionThis case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy

Evaluation of AJCC staging system and proposal of a novel stage grouping system in retroperitoneal liposarcoma: the Fudan Zhongshan experience

BackgroundOverall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system.MethodsThe cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell’s consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram.ResultsA total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate.ConclusionCompared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients

Does Aggressive Surgery Mean Worse Quality of Life and Functional Capacity in Retroperitoneal Sarcoma Patients?—A Retrospective Study of 161 Patients from China

The mainstay of treatment for primary retroperitoneal sarcoma (RPS) is surgery. However, whether multiple visceral resection (MVR) affects patients’ quality of life compared with simple tumor resection has not been reported. Patients with primary RPS who underwent radical resection between 2009 and 2021 were included. Patients who were alive at the last follow-up were asked to complete the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The primary endpoint of the study was the global health (GH) score. A total of 161 patients were included, including 77 in the MVR group and 84 in the non-MVR group. When comparing EORTC scores on functional domains and symptom scales between MVR and non-MVR groups, only constipation scores differed (p = 0.011). Comparing GH scores within 6 months after surgery between the two groups, GH was better in non-MVR patients (58.3 vs. 76.4, p = 0.082). However, patients with longer postoperative intervals in the MVR group had higher scores (p p = 0.522). As the postoperative interval increased, there was an improvement in all indicators in MVR patients, while there was no significant improvement in non-MVR patients. Aggressive surgical approaches impair quality of life within 6 months postoperatively, but the long-term quality of life is similar to that of patients undergoing simple tumor resection. This should be factored into RPS treatment decisions

Table_1_Nomogram predicting overall survival after surgical resection for retroperitoneal leiomyosarcoma patients.docx

BackgroundSurgery is the best way to cure the retroperitoneal leiomyosarcoma (RLMS), and there is currently no prediction model on RLMS after surgical resection. The objective of this study was to develop a nomogram to predict the overall survival (OS) of patients with RLMS after surgical resection.MethodsPatients who underwent surgical resection from September 2010 to December 2020 were included. The nomogram was constructed based on the COX regression model, and the discrimination was assessed using the concordance index. The predicted OS and actual OS were evaluated with the assistance of calibration plots.Results118 patients were included. The median OS for all patients was 47.8 (95% confidence interval (CI), 35.9-59.7) months. Most tumor were completely resected (n=106, 89.8%). The proportions of French National Federation of Comprehensive Cancer Centres (FNCLCC) classification were equal as grade 1, grade 2, and grade 3 (31.4%, 30.5%, and 38.1%, respectively). The tumor diameter of 73.7% (n=85) patients was greater than 5 cm, the lesions of 23.7% (n=28) were multifocal, and 55.1% (n=65) patients had more than one organ resected. The OS nomogram was constructed based on the number of resected organs, tumor diameter, FNCLCC grade, and multifocal lesions. The concordance index of the nomogram was 0.779 (95% CI, 0.659-0.898), the predicted OS and actual OS were in good fitness in calibration curves.ConclusionThe nomogram prediction model established in this study is helpful for postoperative consultation and the selection of patients for clinical trial enrollment.</p

Outcomes of Surgical Treatment for Graves&rsquo; Disease: A Single-Center Experience of 216 Cases

Background: The role of surgery in the treatment of Graves&rsquo; disease (GD) needs to be revisited. The aims of the present retrospective study were to evaluate the outcomes of the current surgical strategy as a definitive treatment of GD at our center and to explore the clinical association between GD and thyroid cancer. Methods: A patient cohort of 216 cases from 2013 to 2020 was involved in this retrospective study. The data of the clinical characteristics and follow-up results were collected and analyzed. Results: There were 182 female and 34 male patients. The mean age was 43.9 &plusmn; 15.0 years old. The mean duration of GD reached 72.2 &plusmn; 92.7 months. Of the 216 cases, 211 had been treated with antithyroid drugs (ATDs) and hyperthyroidism had been completely controlled in 198 cases. A total (75%) or near-total (23.6%) thyroidectomy was performed. Intraoperative neural monitoring (IONM) was applied to 37 patients. The failure of ATD therapy (52.3%) was the most common surgical indication, followed by suspicion of a malignant nodule (45.8%). A total of 24 (11.1%) patients had hoarseness after the operation and 15 (6.9%) patients had transient vocal cord paralysis; 3 (1.4%) had this problem permanently. No bilateral RLN paralysis occurred. A total of 45 patients had hypoparathyroidism and 42 of them recovered within 6 months. Sex showed a correlation with hypoparathyroidism through a univariate analysis. A total of 2 (0.9%) patients underwent a reoperation because of hematomas. A total of 104 (48.1%) cases were diagnosed as thyroid cancer. In most cases (72.1%), the malignant nodules were microcarcinomas. A total of 38 patients had a central compartment node metastasis. A lateral lymph node metastasis occurred in 10 patients. Thyroid carcinomas were incidentally discovered in the specimens of 7 cases. The patients with concomitant thyroid cancer had a significant difference in body mass index, duration of GD, gland size, thyrotropin receptor antibodies and nodule(s) detected. Conclusion: Surgical treatments for GD were effective, with a relatively low incidence of complications at this high-volume center. Concomitant thyroid cancer is one of the most important surgical indications for GD patients. Careful ultrasonic screening is necessary to exclude the presence of malignancies and to determine the therapeutic plan

Genetic Polymorphisms Contribute to the Individual Variations of Imatinib Mesylate Plasma Levels and Adverse Reactions in Chinese GIST Patients

Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300–600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method. There were statistically significant variances in the steady-state IM trough plasma concentrations (from 272.22 to 4365.96 ng/mL). Subjects of GG in rs2242480, T allele carriers in rs1045642 and CC in rs3814055 had significantly higher steady-state IM dose-adjusted trough plasma concentrations. Subjects of CC in rs3814055 had significantly higher incidence rate of edema. The genetic polymorphisms of rs2242480, rs1045642, rs3814055 were significantly associated with IM plasma levels, and the genetic variations of rs3814055 were significantly associated with the incidence rate of edema in Chinese GIST patients. The current results may serve as valuable fundamental knowledge for IM therapy in Chinese GIST patients

Outcomes of Surgical Treatment for Graves’ Disease: A Single-Center Experience of 216 Cases

Background: The role of surgery in the treatment of Graves’ disease (GD) needs to be revisited. The aims of the present retrospective study were to evaluate the outcomes of the current surgical strategy as a definitive treatment of GD at our center and to explore the clinical association between GD and thyroid cancer. Methods: A patient cohort of 216 cases from 2013 to 2020 was involved in this retrospective study. The data of the clinical characteristics and follow-up results were collected and analyzed. Results: There were 182 female and 34 male patients. The mean age was 43.9 ± 15.0 years old. The mean duration of GD reached 72.2 ± 92.7 months. Of the 216 cases, 211 had been treated with antithyroid drugs (ATDs) and hyperthyroidism had been completely controlled in 198 cases. A total (75%) or near-total (23.6%) thyroidectomy was performed. Intraoperative neural monitoring (IONM) was applied to 37 patients. The failure of ATD therapy (52.3%) was the most common surgical indication, followed by suspicion of a malignant nodule (45.8%). A total of 24 (11.1%) patients had hoarseness after the operation and 15 (6.9%) patients had transient vocal cord paralysis; 3 (1.4%) had this problem permanently. No bilateral RLN paralysis occurred. A total of 45 patients had hypoparathyroidism and 42 of them recovered within 6 months. Sex showed a correlation with hypoparathyroidism through a univariate analysis. A total of 2 (0.9%) patients underwent a reoperation because of hematomas. A total of 104 (48.1%) cases were diagnosed as thyroid cancer. In most cases (72.1%), the malignant nodules were microcarcinomas. A total of 38 patients had a central compartment node metastasis. A lateral lymph node metastasis occurred in 10 patients. Thyroid carcinomas were incidentally discovered in the specimens of 7 cases. The patients with concomitant thyroid cancer had a significant difference in body mass index, duration of GD, gland size, thyrotropin receptor antibodies and nodule(s) detected. Conclusion: Surgical treatments for GD were effective, with a relatively low incidence of complications at this high-volume center. Concomitant thyroid cancer is one of the most important surgical indications for GD patients. Careful ultrasonic screening is necessary to exclude the presence of malignancies and to determine the therapeutic plan

Novel near-infrared II aggregation-induced emission dots for in vivo bioimaging.

Near-infrared II fluorescence imaging holds great promise for in vivo imaging and imaging-guided surgery with deep penetration and high spatiotemporal resolution. However, most NIR-II aromatic luminophores suffer from the notorious aggregation-caused quenching (ACQ) effect in the aqueous solution, which largely hinders their biomedical application in vivo. In this study, the first NIR-II organic aggregation-induced emission (AIE) fluorophore (HLZ-BTED), encapsulated as nanoparticles (HLZ-BTED dots) for in vivo biomedical imaging, was designed and synthesized. The NIR-II AIE HLZ-BTED dots showed high temporal resolution, high photostability, outstanding water-solubility and biocompatibility in vitro and in vivo. The HLZ-BTED dots were further used for long-term breast tumor imaging and visualizing tumor-feeding blood vessels, long-term hind limb vasculature and incomplete hind limb ischemia. More importantly, as a proof-of-concept, this is the first time that non-invasive and real-time NIR-II imaging of the gastrointestinal tract in health and disease has been performed, making the AIE dots a promising tool for gastrointestinal (GI) tract research, such as understanding the healthy status of GI peristalsis, diagnosing and evaluating intestinal motility dysfunction, and assessing drug effects on intestinal obstruction

Tumor-associated tertiary lymphoid structure predicts postoperative outcomes in patients with primary gastrointestinal stromal tumors

Tumor-infiltrating tertiary lymphoid structures (TLS) are thought to have anti-tumor activity and are believed to indicate a favorable prognosis in cancer patients. However, the prognostic value of TLS in gastrointestinal stromal tumors (GIST) is unknown. We evaluated the prognostic value of TLS using two independent GIST cohorts. Pathological examinations identified TLS in 44.9% of patients in our discovery cohort (DC). TLS was significantly associated with smaller tumor size (P = .011), relatively well morphological classification (P < .001), lower NIH classification (P < .001), lower recurrence (P = .005), longer survival time (P < .001) and lower imatinib resistance (P = .006). Kaplan-Meier curves showed that TLS was remarkably associated with favorable survival (P = .0002) and recurrence (P = .0015) time. In addition, the presence of KIT mutations and the absence of TLS suggested worst prognosis both in terms of overall survival (OS) (P = .0029) and time to recurrence (TTR) (P = .0150), while the presence of PDGFRA mutations and TLS suggested optimal prognosis for OS and TTR. Multivariate analyzes demonstrated that TLS was an independent prognostic factor for OS (HR:0.180, P = .002) and TTR (HR:0.412, P = .023). These results were confirmed using our validation cohort. Multiplexed immunohistochemistry staining was used to determine the composition of TLS. Therapies designed to target TLS may be a novel therapeutic strategy for GIST patients with imatinib resistance