To find a useful non-invasive biomarker for evaluating treatment response to neoadjuvant immunochemotherapy (nICT) in patients with esophageal squamous cell carcinoma (ESCC), using spectral computed tomography (CT). Spectral CT-derived parameters including the 40 keV virtual monoenergetic imaging (VMI), iodine concentration (IC), and normalized iodine concentration (NIC) were obtained before and after nICT in 87 patients with ESCC. Independent samples t-test (normality) or Mann-Whitney U test (non-normality) was used to compare the differences of spectral CT-derived parameters between responders and non-responders. Binary logistic regression analysis was performed to identify independent predictive factors for responders. Diagnostic performance of parameters in predicting response was tested with receiver operating characteristic (ROC) curve analysis. The post-area, post-40 keV VMI, post-IC, and post-NIC of the responders were significantly lower than those of the non-responders (p < 0.001, < 0.001, < 0.001, and 0.002, respectively). Post-area (odds ratio [OR], 0.980, 95
368 Background: Co-inhibition of lymphocyte activation gene-3 (LAG-3) and programmed cell death protein-1 (PD-1) may enhance antitumor responses for patients (pts) with advanced/metastatic esophageal squamous cell carcinoma (ESCC). We evaluated the efficacy and safety of LBL-007, a novel, fully human anti-LAG-3 IgG4 monoclonal antibody (mAb), with tislelizumab (TIS), a humanized IgG4 anti-PD-1 mAb, and chemotherapy (CT) in pts with unresectable, locally advanced/metastatic ESCC, regardless of baseline PD-L1 status. Methods: In this phase 2, randomized, active-controlled, open-label trial (NCT06010303), pts ≥18 years with ECOG PS ≤1 and no prior systemic therapy were randomized 2:1 to LBL-007 (600 mg IV Q3W) + TIS (200 mg IV Q3W) + CT (Arm A; A) or TIS (200 mg IV Q3W) + CT (Arm B; B); CT was 60-80 mg/m 2 cisplatin + 750-800 mg/m 2 5-FU or 175 mg/m 2 paclitaxel IV Q3W. Primary endpoint was overall response rate (ORR) per investigator-assessed RECIST v1.1. Secondary endpoints were progression-free survival (PFS), duration of response (DoR), disease control rate (DCR), and incidence and severity of treatment-emergent adverse events (TEAEs). Results: As of May 30, 2025, 118 pts were randomized (A: n=78; B: n=40). Median age (range) was 61.5 (44-80) years in A and 65.5 (46-80) in B; 85.9% of pts in A and 87.5% in B were male. Median follow-up (range) was 12.5 (0-18.5) months (mo) in A and 11.5 (0.4-18.8) in B. Confirmed ORR (95% CI) was 61.5% (49.8-72.3) in A and 60.0% (43.3-75.1) in B (Table). Median PFS (95% CI) was 8.2 (5.7-9.2) mo in A and 6.9 (5.6-8.2) in B (HR, 0.85 [95% CI, 0.54-1.34]; P =0.4753). The most common TEAEs were anemia (A: 63 [81.8%]; B: 27 [67.5%]), neutrophil count decreased (A: 53 [68.8%]; B: 24 [60.0%]) and WBC count decreased (A: 48 [62.3%]; B: 21 [52.5%]). Grade ≥3 treatment-related TEAEs occurred in 77.9% of pts in A and 65.0% in B. TEAEs led to discontinuation in 23 (29.9%) pts in A and 11 (27.5%) in B, and to death in 2 (2.6%) and 2 (5.0%) pts, respectively. Immune-mediated AEs occurred in 40 (51.9%) pts in A and 20 (50%) in B, and infusion-related reactions in 7 (9.1%) and 2 (5.0%) pts, respectively. Conclusions: In pts with advanced/metastatic ESCC, adding LBL-007 to TIS + CT did not improve ORR versus TIS + CT alone, which was consistent with historical data in this population. PFS was numerically longer with LBL-007 but not statistically significant. The safety profile of the triplet was manageable and consistent with the known profiles of the individual agents. Clinical trial information: NCT06010303 . Efficacy. Arm An=78 Arm Bn=40 ORR, n (%)95% CI 48 (61.5)49.8-72.3 24 (60.0)43.3-75.1 Complete response 2 (2.6) 1 (2.5) Partial response 46 (59.0) 23 (57.5) Stable disease 23 (29.5) 12 (30.0) Progressive disease 4 (5.1) 3 (7.5) Not evaluable (NE) 3 (3.8) 1 (2.5) DCR, n (%)95% CI 71 (91.0)82.4-96.3 36 (90.0)76.3-97.2 DoR, median, mo95% CI 7.25.7-12.3 7.34.1-NE
Cold tumors are resistant to neoantigen vaccines (NeoVac) combined with systemic anti-PD1 (aPD1) due to unalleviated T-cell exhaustion in tumor. Here, we found the exhaustion of T cells in tumor-draining lymph nodes (TdLNs) contributed greatly to the exhaustion of T cells in tumor, which could not be improved by systemic aPD1. Therefore, we developed a novel strategy for cold tumors: NeoVac combined with intranodal aPD1 injection (NeoVac + aPD1-i.n). This approach effectively impedes T cell exhaustion in TdLNs and promotes naive T-cell differentiation into central memory T cells (TCM), which further develop into non-exhausted, tumor-specific effector memory T cells (TEM) upon neoantigen stimulation to efficiently kill tumor cells. In CT26 colon cancer and B16F10 melanoma models, NeoVac + aPD1-i.n significantly reduced intratumoral PD1+ T-cell proportions, achieving tumor growth inhibition rates of 70.7% (CT26) and 94.3% (B16F10), with prolonged survival and no obvious adverse effects. By inducing tumor-specific immune response, aPD1-i.n overcomes the drug resistance of NeoVac in cold tumors, holding great clinical translation potential.
ObjectiveDespite advances in prevention, cervical cancer remains a serious global health issue. Concurrent chemoradiation is the standard treatment for locally advanced squamous cell carcinoma, yet 20-30% of patients develop persistent cervical cancer due to incomplete response, resulting in poor outcomes. This study aims to develop a predictive model for persistent cervical cancer in patients with locally advanced cervical squamous cell carcinoma following concurrent chemoradiation therapy, leveraging pretreatment multisequence magnetic resonance imaging data and advanced deep learning techniques.MethodsThis retrospective study included 259 patients with locally advanced cervical squamous cell carcinoma who underwent concurrent chemoradiation therapy at two centres. Four magnetic resonance imaging sequences were used to generate 2.5D data. A deep learning model incorporating Crossformer was developed and compared with radiomics and clinical models. Model performance was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis.ResultsCrossFormer model outperformed the traditional convolutional neural network models in slice-level analysis across all cohorts, achieving an area under the curve of 0.775 in the test cohorts. The deep learning model achieved high predictive accuracy, with area under the curves of 0.884, 0.833, and 0.814 in the training, validation, and test cohorts, respectively, outperforming both the clinical and radiomics models. Combining clinical features with the deep learning model further improved performance, yielding area under the curves of 0.914, 0.868, and 0.839 in the respective cohorts.ConclusionThe developed model, utilizing 2.5D multi-sequence magnetic resonance imaging data and the deep learning technology that incorporated Crossformer, demonstrated strong predictive performance for persistent cervical cancer in patients with locally advanced cervical squamous cell carcinoma following concurrent chemoradiation therapy. This approach offers a promising and clinically applicable tool for treatment decision-making.
Radiotherapy (RT) is a widely used treatment with strong therapeutic effects, but overcoming challenges related to hypoxia-induced tumor resistance and ineffective antitumor immune responses is crucial for optimal outcomes. In this study, we developed a versatile nanosystem using mesoporous silica nanoparticles (MSNs), R837, and a small quantity of manganese peroxide (Mn/ZnO2). The synthesized MSN@R837-Mn/ZnO2 nanoparticles exhibited precise tumor targeting and accumulation, controlled drug release under acidic conditions, and increased sensitivity in magnetic resonance imaging. These attributes collectively augmented the therapeutic efficacy of RT by alleviating hypoxia and immunosuppression. Tumor cells treated with RT combined with these nanoparticles displayed reduced oxidative stress, alleviated hypoxia, and normalized blood vessel formation. Notably, all mice in the RT + PD-1 + MSN@R837-Mn/ZnO2 group achieved complete tumor regression with extended survival. Safety assessments confirmed the absence of MSN@R837-Mn/ZnO2 toxicity, highlighting its potential as a promising approach with dual functionality for the diagnostic imaging and treatment of cancer. Radiotherapy (RT) faces challenges like hypoxia-induced tumor resistance and weak antitumor immune responses. This study developed a nanosystem using mesoporous silica nanoparticles (MSNs), R837, and manganese peroxide (Mn/ZnO2). The MSN@R837-Mn/ZnO2 nanoparticles showed precise tumor targeting, controlled drug release in acidic conditions, and enhanced MRI sensitivity, boosting RT efficacy by reducing hypoxia and immunosuppression. Tumor cells treated with RT and these nanoparticles had less oxidative stress, improved hypoxia, and normalized blood vessels. Remarkably, all mice in the RT+PD-1+MSN@R837-Mn/ZnO2 group achieved complete tumor regression and extended survival, with no toxicity observed, indicating its potential for cancer imaging and treatment.
BACKGROUND:The introduction of the anti-PD-1 antibody has greatly improved the clinical outcomes of patients with non-small cell lung cancer (NSCLC). In this study, we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced inoperable or metastatic NSCLC and reported an association between peripheral blood biomarkers and clinical response in these patients. METHODS:This single-center study included medical record data of patients with NSCLC treated with the PD-1 antibody as a first-line or subsequent line of treatment, either as monotherapy or in combination with chemotherapy. The patients were enrolled from 2020 to 2022. We dynamically evaluated multiple Th1 and Th2 cytokines in the blood serum and analyzed the phenotype of T cells from the peripheral blood to explore the correlation between cytokine levels, T cell phenotypes, and clinical response. RESULTS:A total of 88 patients with stage IIIA-IV NSCLC were enrolled, out of which 60 (68.18%) achieved a partial response (PR), 13 (14.77%) had stable disease (SD), and 15 (17.05%) experienced disease progression (PD). The disease control rate was 82.95%. Our results suggested a significant reduction (P = 0.002, P < 0.005) in lymphocyte absolute counts after treatment in patients with PD. Higher levels of IFN-γ (P = 0.023, P < 0.05), TNF-α (P = 0.00098, P < 0.005), IL-4 (P = 0.0031, P < 0.005), IL-5 (P = 0.0015, P < 0.005), and IL-10 (P = 0.036, P < 0.05) were detected in the peripheral blood before treatment in the PR group compared to the PD group. Moreover, patients with high levels of IL-5, IL-13, IL-4, IL-6, IFN-γ, and TNF-α (> 10 ng/mL) had superior progression-free survival compared to those with low levels (< 10 ng/mL). Furthermore, PD-1 expression on CD8+ T cells was higher in patients who showed a PR than in those who did not show a response (SD + PD; P = 0.042, P < 0.05). CONCLUSIONS:The findings of this study imply that the decrease in absolute blood lymphocyte counts after treatment is correlated with disease progression. Serum cytokine levels may predict the effectiveness and survival rates of anti-PD-1 blockade therapy in patients with NSCLC. In addition, PD-1 expression on CD8+ T cells was positively associated with better clinical response. Our findings highlight the potential of peripheral blood biomarkers to predict the effectiveness of PD-1-targeted treatments in patients with NSCLC. Larger prospective studies are warranted to further clarify the value of these biomarkers.
Background: This study aimed to investigate the effects of multidisciplinary whole-course nutrition management on the nutritional status and complications during the course of treatment in patients with esophageal cancer (EC) undergoing chemoradiotherapy. Methods: A total of 36 EC patients undergoing chemoradiotherapy were divided into a control group (n = 18) and an intervention group (n = 18). Participants in the control group were given routine nutritional support, whereas those in the intervention group were provided whole-course nutrition management from the nutrition support team. Nutrition-related indicators, that is, serum albumin level (ALB), hemoglobin (Hb), and C reactive protein were assessed before, during, and after treatment in both groups. The incidence of complications (e.g., lymphocytopenia, radiation esophagitis, and myelosuppression), clinical outcomes, length of hospital stay, and hospital costs were also recorded. Differences between the 2 groups were tested using the Mann–Whitney U and chi-square tests. Results: The ALB and Hb levels of the patients in the control group decreased significantly [ALB: −2.6 (−5.6, 0), P = .01; Hb: −12.0 (−27.0, −2.0), P = .04] and C reactive protein increased [8.9 (2.9, 14.9), P = .02] compared to those before treatment, while the indicators of participants in the intervention group did not change (P > .05). The incidence of grade ≥ II lymphocytopenia was higher in the control group than that in the intervention group (33.3% vs 61.1%, P = .03). Moreover, compared with the control group, the average length of hospital stay decreased by 12 days [47 (40, 50) vs 35 (23, 40), P = .001], and in-patient expenses decreased by 20,504 CNY in the intervention group (P = .004). Conclusion: Multidisciplinary whole-course nutrition management can maintain the nutritional status of patients with EC undergoing chemoradiotherapy. This may lower the incidence of complications, shorten hospital stays, and reduce in-patient expenses.
OBJECTIVE:To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy. METHODS:EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups. RESULTS:The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05). CONCLUSIONS:EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..
e16010 Background: Preoperative therapy of esophageal squamous cell carcinoma (ESCC) is stepping into the era of combined therapy with PD-1 inhibitor after the success of PD-1 antibodies in the first-line and second-line treatment for advanced ESCC. This single center study retrospectively analyzed the efficacy and safety of preoperative chemotherapy combined with PD-1 antibody in patients with locally advanced operable or potentially resectable ESCC in the real world. Methods: The study enrolled operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in our center from April 2020 to December 2020. The treatment regimen were 2 to 4 cycles of paclitaxel liposome (135̃175 mg/m 2 ) or albumin paclitaxel (180mg/m 2 ) plus nedaplatin (75mg/m 2 ) or lobaplatin (30mg/m 2 ) combined with PD-1 inhibitors (toripalimab 13/20, sintilimab 3/20, pembrolizumab 2/20, camrelizumab 1/20, tislelizumab 1/20) with standard therapeutic dose followed by tumor response assessment and surgery. The primary end point were safety, tumor response and complete pathological response (pCR) rate. Results: A total of 20 patients including 17 males and 3 females, of which median age was 65 and 85% were stage III-IVA (AJCC 8 th ), were included in the study. Of all the patients, 18 patients accomplished 2 cycles of therapy and had safety assessment, 13 patients underwent surgery, 2 patients were waiting for operations and 2 patients achieving partial response rejected surgery and were prepared for radical chemoradiotherapy. Treatment-related adverse events exceeding grade 3 levels included leukopenia 5.6% (1/18), neutropenia 16.7% (3/18), thrombocytopenia 5.6% (1/18), and immune hepatitis 5.6% (1/18). There was no severe surgery-related complication. Objective response rate (ORR) was 70.6% (12/17), and disease control rate (DCR) was 100% (17/17). R0 resection rate was 92.3% (12/13), the pCR rate was 15.4% (2/13), and 61.5% (8/13) of the patients had downstaged to the ypT1-2N0M0 I stage. One patient finally reached a pCR after switching to preoperative chemoradiotherapy because of progression after treatment of chemotherapy and PD-1 inhibitor. Conclusions: Preoperative chemotherapy combined PD-1 inhibitor treatment was well tolerated and had high efficacy in locally advanced operable and potential resectable ESCC. Since the study included some potentially resectable patients with late staging, the pCR rate may be lowered. The further study aims to find the efficient biomarker including PD-L1 expression and CD8 + T cell infiltration. Moreover, well-designed randomized prospective trials for better evidence are required.
Background: In spite of the wide use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or conventional chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of giving patients programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination (PD-1/L1 + CTLA-4) versus simply applying chemotherapy in patients with advanced or metastatic NSCLC.Methods: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials (RCTs). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). Results: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both overall survival (OS) [HR=0.75, 95%CI (0.70-0.80), P<0.001] and progression-free survival (PFS) [HR=0.83, 95%CI (0.73-0.95), P<0.001]. Sex is another vital factor that affects the efficacy of ICIs. Male [HR=0.71, 95%CI (0.63-0.81)] benefits more from ICIs than the female [HR 0.80, 95%CI (0.68-0.94)] in OS. Besides, ICIs were associated with fewer AEs compared to chemotherapy.Conclusion: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in treatment of advanced or metastatic NSCLC.
The prognosis of the small cell esophageal cancer (SCEC) patient in our study was poor due to lack of treatment options which were limited to surgery and chemotherapies, with a median overall survival (OS) of only 11.1 months according to previous studies. Herein, we adopted the regimen of immunotherapy plus chemotherapy, which exerted superior and durable benefit (OS > 19 months) in the patient in our study. Immunotherapy plus chemotherapy might therefore be a reasonable option for selected SCEC patients. In addition, well‐designed trials for better evidence are required to verify the findings in this study.
e15130 Background: Immune checkpoint inhibitor(ICI) -associated myocarditis is rare, but it could account for a very high mortality rate. This study reviewed the occurrence of ICI-associated myocarditis in Chinese cancer patients. Methods: A retrospective analysis was made on the occurrence of ICI-associated myocarditis in cancer centers of 12 3A-grade hospitals in China from January 1, 2018 to December 31, 2019. More than 100 patients were treated with ICIs in each center. Results: A total of 2373 patients were treated with ICI alone or in combination. The incidence of ICI-associated myocarditis was 1.05% (25/2373). Of all the data elicited from 16 patients in this study, the tumor types were listed, including: melanoma, lung cancer, renal cancer, urothelial cancer, liver cancer, gastric cancer, colorectal cancer, etc. The 16 patients included 8 male and 8 female with a median age of 65 (36-80). 3 of them had coronary heart disease. The ICI drugs included nivolumab, pembrolizumab and toripalimab, camrelizumab, sintilimab, tislelizumab, atezolizumab. Among them, there were 10 cases of PD-1 inhibitor, 1 case of PD-L1 inhibitor, 5 cases of PD-1 inhibitor combined with chemotherapy or molecular targeted drug. ICI-associated myocarditis occurred in a median of 38 days (2-420) after treatment during which 81.2% (13/16) of them received ICI 1-2 infusions. The common clinical symptoms were palpitation, chest distress and dyspnea, in addition to 8 cases with asthenia, 4 cases with respiratory failure, 2 cases without symptoms. ECG abnormality accounted for 87.5% (14/16). The common abnormalities included: 6 cases of atrial premature contraction, 4 cases of ventricular premature contraction, 3 cases of sinus tachycardia, 1 case of Grade 3 atrioventricular, 1 case of complete right bundle block, and 1 case of acute myocardial infarction. 15 cases of abnormal troponin I or T were observed, followed by CK, CK-MB, MYO and BNP increased. 14 patients were treated with glucocorticoid. 6 patients died with the mortality rate 37.5%(6/16) and 66.7% (4/6) were over 70 years old. Conclusions: The incidence of ICI-associated myocarditis in Chinese patients is low, but the mortality rate is high. Regular monitoring of cardiac biomarkers and ECG is helpful for early diagnosis.
BACKGROUND:To investigate the capability of radiomic analysis using T2-weighted (T2W) and spectral attenuated inversion-recovery T2-weighted (SPAIR T2W) magnetic resonance imaging (MRI) for predicting the therapeutic response of esophageal squamous cell carcinoma (ESCC) to chemoradiotherapy (CRT).METHODS:Pretreatment T2W- and SPAIR T2W-MRI of 68 ESCC patients (37 responders, 31 nonresponders) were analyzed. A number of 138 radiomic features were extracted from each image sequence respectively. Kruskal-Wallis test were performed to evaluate the capability of each feature on treatment response classification. Sensitivity and specificity for each of the studied features were derived using receiver operating characteristic (ROC) analysis. Support vector machine (SVM) and artificial neural network (ANN) models were constructed based on the training set (23 responders, 20 nonresponders) for the prediction of treatment response, and then the testing set (14 responders, 11 nonresponders) validated the reliability of the models. Comparison between the performances of the models was performed by using McNemar's test.RESULTS:Radiomic analysis showed significance in the prediction of treatment response. The analyses showed that complete responses (CRs) versus stable diseases (SDs), partial responses (PRs) versus SDs, and responders (CRs and PRs) versus nonresponders (SDs) could be differentiated by 26, 17, and 33 features (T2W: 11/11/15, SPAIR T2W: 15/6/18), respectively. The prediction models (ANN and SVM) based on features extracted from SPAIR T2W sequence (SVM: 0.929, ANN: 0.883) showed higher accuracy than those derived from T2W (SVM: 0.893, ANN: 0.861). No statistical difference was observed in the performance of the two classifiers (P=0.999).CONCLUSIONS:Radiomic analysis based on pretreatment T2W- and SPAIR T2W-MRI can be served as imaging biomarkers to predict treatment response to CRT in ESCC patients.
BACKGROUND: Most tumor cell lines exhibited low-dose hyperradiosensitivity (LDHRS) to radiation doses lower than 0.3 Gy. Pulsed low–dose rate radiotherapy (PLDR) took advantage of LDHRS and maximized the tumor control process. In this study, we retrospectively analyzed patients receiving PLDR for refractory malignancies. PATIENTS AND METHODS: In total, 22 patients were included in our study: 9 females and 13 males. The median age was 61 years old. All the patients previously received multiline treatments and failed with an estimated survival less than 6 months. Thus, palliative PLDR was given. The PLDR was delivered using 10 fractions of 2 Gy/day, with an interval of 3 minutes, for 5 days per week. The dose rate was 6.67 cGy/min. The median follow-up was 1 year (range 8-30 months). Nine patients underwent PLDR for reirradiation due to locally recurrent diseases. The time interval from last irradiation was 11 to 168 months. Ten patients received PLDR due to poor performance status. Three patients were given PLDR for bulky tumor. The irradiated sites included primary disease (seven patients), locally recurrent disease (nine patients), and retroperitoneal adenopathy (six patients). RESULTS: Five patients developed grade 3 or 4 toxicities. No grade 5 toxicities occurred. All the toxicities recovered after treatments. In general, the 1-year local-regional control rate was approximately 40%, and almost all the patients developed progression at the second year after PLDR. The 6-month survival rate was 76%, and the 1-year survival rate was 69%. For the three patients given PLDR for bulky tumor, all of them achieved partial remission 1 month after the PLDR, and one patient achieved complete response at the fourth month. CONCLUSION: PLDR is an effective and safe option not only for reirradiation but also for patients with poor performance status or bulky tumors. A prospective clinical trial (NCT03061162) is ongoing to validate our results.
影像组学作为一种非侵入性的图像分析方法,大量研究证实其在肿瘤诊断、分期、治疗反应预测和预后中的研究价值.本文从影像组学的概念、分析流程、国内外研究现状,以及最常用图像分割、特征提取、分析和建模预测软件方面进行综述.通过本文可快速熟悉和了解不同软件的特点,为影像组学在临床上的进一步应用提供良好的契机和实践基础.随着医学影像数据的进一步积累和标准化,以及人工智能和深度学习的发展,将为影像组学指引新的方向.
BackgroundSince definitive concurrent chemoradiotherapy (CRT) is standard therapy for inoperable esophageal squamous cell carcinoma (ESCC), early evaluation of treatment response is crucial for patients and would be useful in assessing response, especially in patients with severe side effects.PurposeTo explore the feasibility of intravoxel incoherent motion (IVIM) MRI in the early assessment of treatment response to CRT.Study TypeProspective.PopulationTwenty‐three inoperable ESCC patients.SequenceIVIM 3T MRI of nine b values (0, 25, 50, 75, 100, 150, 200, 500 and 800 s/mm2) was performed at four timepoints: pre‐CRT (within 5 days before CRT), mid‐CRT (2–3 weeks after the start of CRT), end‐CRT (within 5 days after the end of CRT), and post‐CRT (1 month after the end of CRT).AssessmentIVIM‐based parameters and ADC were analyzed independently by two radiologists and treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST).Statistical TestsAnalyses of variance for repeated measurements were conducted to observe dynamic changes of IVIM‐based parameters (D, f, and D*) and ADC during CRT. The parameters and their change percentages (Δ%) were compared between complete response (CR) and partial response (PR) by Mann–Whitney U‐test. Diagnostic performance of parameters in predicting response was tested with receiver‐operating characteristic curve analysis.ResultsADC, D, and f increased significantly during CRT (P < 0.001, < 0.001, and 0.001, respectively). ADC, f, Δ%ADC, and Δ%D at mid‐CRT in CR group were significantly higher than those in the PR group (P = 0.002, 0.013, 0.005, and 0.011, respectively). D combined with f and ADC had highest area under curve (0.917) in identifying CR from PR.Data ConclusionIVIM parameters proved useful in assessing response to definitive concurrent CRT for inoperable ESCC and combined with ADC at an early stage of treatment was a good predictor of response.Level of Evidence: 2Technical Efficacy: Stage 4J. MAGN. RESON. IMAGING 2018;48:349–358.
Objective: Intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) could improve local control rates at different anatomic sites. However, little is known for its use in metastatic gastric cancer. Our study aimed to compare the treatment response rates of IMRI-SIB and conformal radiotherapy (CRT) in patients with metastatic gastric cancer. Materials and Methods: We retrospectively identified twenty patients with metastatic gastric cancer from 2013 to 2015, 12 given IMRT-SIB, and eight given CRT. Treatment response and toxicities were evaluated for all patients. The radiation target included peritoneal lymph nodes. RECIST criteria were used to assess the treatment response. Three patients of eight in the CRT group died before the end of treatment due to the progression of diseases in the field. Results: For the IMRT-SIB group, the median dose of high dose field was 60.8 Gy (50-64.4 Gy), and the median dose of low-dose field was 45 Gy (36-50.4 Gy). For the CRT group, the median dose of the total dose was 50 Gy (41.4-60 Gy). IMRT-SIB could elevate local dose significantly, compared to the CRT group. One patient of 12 in the IMRT-SIB group achieved complete response, and nine patients achieved partial response (PR), whereas no patient achieved CR in the CRT group. Two of five patients achieved PR (40%) in the CRT group. IMRT-SIB improved the treatment response rate significantly (odds ratio 8.33, 95% confidence interval: 1.03-67.14, P = 0.046). Two patients of 12 in the IMRT-SIB group developed enteritis, whereas two patients of five developed enteritis in the CRT group. Conclusions: IMRT-SIB could escalate the local dose and improve the treatment response rates in patients with metastatic gastric cancer and with acceptable toxicities. Further study with a larger population to validate our data is underway.
Objective: To analyze the recurrence patterns and reasons in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and to investigate the feasibility of radiomics for analysis of radioresistance. Methods: We analyzed 306 NPC patients treated with IMRT from Jul-2009 to Aug-2016, 20 of whom developed with recurrence. For the NPCs with recurrence, CT, MR, or PET/CT images of recurrent disease were registered with the primary planning CT for dosimetry analysis. The recurrences were defined as in-field, marginal or out-of-field, according to dose-volume histogram (DVH) of the recurrence volume. To explore the predictive power of radiomics for NPCs with in-field recurrences (NPC-IFR), 16 NPCs with non-progression disease (NPC-NPD) were used for comparison. For these NPC-IFRs and NPC-NPDs, 1117 radiomic features were quantified from the tumor region using pre-treatment spectral attenuated inversion-recovery T2-weighted (SPAIR T2W) magnetic resonance imaging (MRI). Intraclass correlation coefficients (ICC) and Pearson correlation coefficient (PCC) was calculated to identify influential feature subset. Kruskal-Wallis test and receiver operating characteristic (ROC) analysis were employed to assess the capability of each feature on NPC-IFR prediction. Principal component analysis (PCA) was performed for feature reduction. Artificial neural network (ANN), k-nearest neighbor (KNN), and support vector machine (SVM) models were trained and validated by using stratified 10-fold cross validation. Results: The median follow up was 26.5 (range 8-65) months. 9/20 (45%) occurred in the primary tumor, 8/20 (40%) occurred in regional lymph nodes, and 3/20 (15%) patients developed a primary and regional failure. Dosimetric and target volume analysis of the recurrence indicated that there were 18 in-field, and 1 marginal as well as 1 out-of-field recurrence. With pre-therapeutic SPAIR T2W MRI images available, 11 NPC-IFRs (11 of 18 NPC-IFRs who had available pre-therapeutic MRI) and 16 NPC-NPDs were subsequently employed for radiomic analysis. Results showed that NPC-IFRs vs. NPC-NPDs could be differentiated by 8 features (AUCs: 0.727-0.835). The classification models showed potential in prediction of NPC-IFR with higher accuracies (ANN: 0.812, KNN: 0.775, SVM: 0.732). Conclusion: In-field and high-dose region relapse were the main recurrence patterns which may be due to the radioresistance. After integration in the clinical workflow, radiomic analysis can be served as imaging biomarkers to facilitate early salvage for NPC patients who are at risk of in-field recurrence.
RATIONALE:Follicular dendritic cell (FDC) sarcoma is a rare tumor with FDC differentiation that typically arises within lymph nodes but can also occur extranodally. To date, the primary esophageal FDC sarcoma has not been reported in the English literature.PATIENT CONCERNS:We described a 67-year-old female who foremostly presented with dysphagia, and the patient was readmitted due to a dry cough and pain of his right shoulder 2 years after initial treatment.DIAGNOSES:Primary esophageal FDC sarcoma with the right superior mediastinal lymph node metastasis.INTERVENTIONS:The esophageal tumor was removed by endoscopic submucosal dissection at the first hospitalization. At the second hospitalization 2 years after the initial visit, the tracheal stent loaded with (125) iodine radioactive seeds was placed. The profiles of genetic variations and immunotherapeutic biomarkers were also explored by next-generation sequencing protocol from the patient's blood, esophageal primary, and mediastinal metastatic tumor samples.OUTCOMES:The patient's symptom transitorily relieved, but she gave up further treatment and died 2 months after the tracheal stent was placed. As for the genomic alterations, we found 9 gene mutations in all the samples, including checkpoint kinase 2(CHEK2), FAT atypical cadherin 1 (FAT1), tumor protein 53 (TP53), DPYD, ERBB2 interacting protein (ERBB2IP), FBXW7, KMT2D, PPP2R1A, TSC2, whereas amplification of MYC was only in the metastatic example. The analysis of clonal evolution and phylogenetic tree showed the propagation and replay of polyclonal esophageal FDC sarcoma. At the same time, the detection of biomarkers for immunotherapy revealed microsatellite stable and mismatch repair-proficient (pMMR), which predicted a relatively poor anti-programmed death (PD-1)/programmed death ligand (PD-L1) immunotherapy outcome. On the contrary, the tumor mutational burdens were 10 mutations per 1 million bases in both the primary and metastatic tumor sample, which ranked the top 23.3% in solid tumors mutational burdens database of Geneseeq and might be a good predictor of the efficacy of anti-PD-1/PD-L1 immunotherapy.LESSONS:To the best of our knowledge, this case report announced the first case of extranodal primary esophageal FDC sarcoma in the world, and firstly revealed its unique genetic alterations profiles, which might contribute to further in-depth study of this rare disease.