The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis.
Patients diagnosed with ...clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments.
From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group.
Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.
e23540 Background: Epithelioidhemangioendothelioma is a rare vascular soft tissue sarcoma, 90% of which contains WWTR1-CAMTA1 fusion gene. Studies have shown that mTOR inhibitors may have a certain ...effect on EHE patients. Methods: A retrospective analysis of the efficacy and safety of mTOR inhibitor everolimus in the treatment of advanced unresectable epithelioidhemangioendothelioma in our hospital in the past one year. Patients with advanced epithelioidhemangioendothelioma (EHE) confirmed by consultation in the pathological center received this regimen, everolimus 10mg, once a day orally for 28 days, every 4 weeks as a treatment cycle until the disease progressed or showed intolerable toxicity. Results: There were 3 females and 5 males, and their average age was 41.8 years old. All of them were unresectable with liver, lung, and shoulder primary lesions, and lungs, liver, pleura and bone metastasis. Ki67 is from 2% to 10%. 3 patients who received molecular pathological examination were all identified the WWTR1-CAMTA1 fusion gene, and one of them also had EWSR1 chromosome translocation. Previous antineoplastic treatments included gemcitabine, cisplatin, albumin paclitaxel, epirubicin, dacarbazine chemotherapy, anlotinib targeting, and toripalimab immune therapy. 5 patients were treated with first-line drugs, 2 cases with second-line and 1 case with third-line. In terms of overall efficacy, 1 case was not evaluated, 2 cases lost follow-up due to poor tolerance and economic factors, 2 cases were included in the clinical trails after reaching tumor control for 3 months, and the other 3 cases achieved tumor remission with a median PFS of 11.0 months, and the best curative effect was SDa. Severe oral mucositis can greatly affect the medication experience of patients, which can be relieved after symptomatic medication, or when interstitial pneumonia and hemogram decrease significantly, we can consider the oral administration of everolimus 5mg. Conclusions: At present, there is no standard treatment for EHE, we can roughly see the efficacy of mTOR inhibitor everolimus in some EHE patients, mainly disease stability. Emphasis on side effect management, improve tolerance, and systematic treatment of EHE needs to be further explored.
e16341 Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor with low-grade malignancy. However, a small proportion of cases still exhibit more aggressive behavior and ...emerge as distant metastases. Limited data exist on systemic therapy for these entities. Methods: A retrospective analysis was performed on patients diagnosed with SPN of the pancreas who underwent medical treatment in our hospital between January 2020 and December 2023. The clinicopathological characteristics and therapeutic regimens of the patients were collected. The primary outcomes were disease control rate (DCR) and progression free survival (PFS). SPSS software V27.0 was used for data analysis. Results: Five patients were identified and 60.0% of patients were female . The median age was 34 years (range 16-53). All patients first underwent surgical resection. Four individuals had metachronous distant metastasis and one had synchronous distant metastasis. The most common metastatic site was peritoneum (3/5) and liver (3/5), followed by the distant lymph node (2/5). Progesterone receptor positive expression was found in four cases. Four patients received targeted therapy as first-line treatment (3 receiving anlotinib 12mg once daily on days 1-14 every 3 weeks and 1 receiving everolimus 10mg per day). All patients receiving targeted therapy had stable disease, with a DCR of 100%. The median PFS in the targeted therapy group was 8.1 months (95% CI, 6.7-9.5). Only one patient underwent first-line chemotherapy (gemcitabine plus S-1) and experienced disease progression at the initial efficacy evaluation. Data for second-line treatment was available for three patients. One patient got progressive disease (PD) after etoposide administration. Two individuals received everolimus 10mg daily, one of whom showed PD and the other achieved a partial response (PR). All treatment-related adverse events (AEs) were manageable. Conclusions: Metastatic SPN of the pancreas may be not chemosensitive. Targeted therapy, such as anlotinib and everolimus, appears to be a potential therapeutic option.
We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center ...randomized phase II trial.
Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate.
We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively.
S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT.
ClinicalTrial.gov NCT02301481.
The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic ...neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.
Background： Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair （MMR） status may ...relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis. Methods： The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, Chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method. Results： The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type （7/19）. Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor （P = 0.02）. Conclusions： Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage Ⅲ/Ⅳdisease with signet ring cell carcinoma. The prognosis was relatively poor.
There are currently limited systemic treatment options for patients with advanced neuroendocrine tumours (NETS) and the efficacy of existing treatments is sub-optimal. We evaluated the efficacy and ...safety of Tegafur/gimeracil/oteracil/potassium capsules (S-1)/Temozolomide with or without thalidomide for the treatment of NETS (STEM trial).
A randomised, controlled, open-label, phase 2 trial conducted at eight hospitals in China. Adults (≥18 years) with unresectable/metastatic, pancreatic or non-pancreatic NETS, with an Eastern Cooperative Oncology Group (ECOG) PS of 0–1, and progression on ≤2 previous therapies were randomised (1:1, using hierarchical block randomization with block length 4, stratified by pancreatic/non-pancreatic disease to receive S-1 40–60 mg orally twice daily on days 1–14 plus temozolomide 200 mg orally daily on days 10–14 in a 21-day cycle OR S-1 and temozolomide plus thalidomide orally nightly (100 mg on days 1–7, 200 mg on days 8–14, and 300 mg from day 15), until disease progression, death, intolerable toxicity, withdrawal of informed consent or at the investigator's discretion. The primary endpoint was objective response rate (ORR) by RECIST 1.1 in an intention-to-treat population. Safety was assessed in all patients who received treatment. The study was registered at ClinicalTrials.gov: NCT03204019 (pancreatic group) and NCT03204032 (non-pancreatic group).
Between March 23, 2017 and November 16, 2020, 187 patients were screened and 140 were randomly assigned to S-1/temozolomide plus thalidomide (n = 69) or S-1/temozolomide (n =71). After a median follow-up of 12·1 months (IQR: 8·4–16·6), the ORR was comparable in the S-1/temozolomide plus thalidomide and S-1/temozolomide groups 26·1% 95% CI 17·2–37·5 versus 25·4% 95% CI 16·7–36·6; odds ratio: 1·03 95% CI 0·48–2·22; P = 0·9381). In the S-1/temozolomide plus thalidomide group, the most common grade 3–4 treatment-related adverse event was fatigue (2/68, 3%), and in the control group were thrombocytopenia and diarrhea (both 1/71, 2%). There were no treatment-related deaths in either group.
S-1/temozolomide with or without thalidomide leads to a comparable treatment response in patients with advanced/metastatic NETS.
This work was supported by CAMS Innovation Fund for Medical Sciences (CIFMS,2021-I2M-1-066, 2017-I2M-4-002, 2021-I2M-1-019, 2017-I2M-1-001), the National Natural Science Foundation of China (81972311, 82141127, 31970794,), the State Key Project on Infection Diseases of China (2017ZX10201021-007-003), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310026), Sanming Project of Medicine in Shenzhen (SZSM202011010), and the State Key Laboratory Special fund from the Ministry of Science (2060204).
Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases. However, a lack of biological, molecular, and genomic information and an absence of data from ...rigorous trials limit the validity of these strategies. This review presents the viewpoints from an international conference consisting of several expert working groups. The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature, evaluating the evidence on which management decisions were based, developing internationally acceptable recommendations for clinical practice, and making recommendations for clinical and research endeavors. The review for each question will be followed by recommendations from the panel.
The predictive effect of preoperative chemoradiotherapy (CRT) is low and difficult in guiding individualized treatment. We examined a surrogate endpoint for long-term outcomes in locally advanced ...gastric cancer patients after preoperative CRT.
From April 2012 to April 2019, 95 patients with locally advanced gastric cancer who received preoperative concurrent CRT and who were enrolled in three prospective studies were included. All patients were stage T
N
. Local control, distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were evaluated. Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses. The down-staging depth score (DDS), which is a novel method of evaluating CRT response, was used to predict long-term outcomes.
The median follow-up period for survivors was 30 months. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve predicted by the DDS was 0.728, which was better than the pathological complete response (pCR), histological response and ypN0. Decision curve analysis further affirmed that DDS had the largest net benefit. The DDS cut-off value was 4. pCR and ypN0 were associated with OS (P=0.026 and 0.049). Surgery and DDS are correlated with DMFS, DFS and OS (surgery: P=0.001, <0.001 and <0.001, respectively; and DDS: P=0.009, 0.013 and 0.032, respectively). Multivariate analysis showed that DDS was an independent prognostic factor of DFS (P=0.021).
DDS is a simple, short-term indicator that was a better surrogate endpoint than pCR, histological response and ypN0 for DFS.
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