Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
目的： 探讨高脂低碳水化合物饮食联合放疗对肺移植瘤小鼠肿瘤微环境的影响。 方法： 选用C57BL/6J小鼠建立Lewis肺癌模型，分为普通饮食组、高脂低碳水化合物饮食组、普通饮食+放疗组和高脂低碳水化合物饮食+放疗组，每组18只。普通饮食组和普通饮食+放疗组小鼠予以普通饮食（脂肪供能比例为12.11%）饲养，高脂低碳水化合物饮食组和高脂低碳水化合物饮食+放疗组小鼠予以高脂低碳水化合物饮食（脂肪供能比例为45.00%）饲养。第12～14天对普通饮食+放疗组和高脂低碳水化合物饮食+放疗组小鼠的肿瘤部位进行放射治疗，照射剂量为24 Gy/3f，观察和监测小鼠体重、肿瘤体积、血糖和血酮值、肝肾功能、生存情况。采用免疫组织化学染色检测CD34和淋巴管内皮透明质酸受体1（LYVE-1），采用天狼星染色检测胶原纤维，采用多重免疫荧光检测CD8和程序性死亡蛋白1（PD-1），采用流式细胞术检测免疫细胞表型。 结果： 接种后第27天，普通饮食组小鼠的体重为（24.78±2.22）g，高于普通饮食+放疗组［（22.15±0.48）g，P=0.030］和高脂低碳水化合物饮食+放疗组［（22.02±0.77）g，P=0.031）］。在接种后第15天，高脂低碳水化合物饮食+放疗组的肿瘤体积为（220.88±130.05）mm3，小于普通饮食组［（504.37±328.48）㎜3，P=0.042）］和高脂低碳水化合物饮食组［（534.26±230.42）mm3，P=0.016］，但与普通饮食+放疗组［（274.64±160.97）mm3］差异无统计学意义（P＞0.05）。第4周高脂低碳水化合物饮食组小鼠的血糖值为（8.00±0.36）mmol/L，低于普通饮食组［（9.57±0.40）mmol/L，P＜0.05］。第2周和第3周高脂低碳水化合物饮食组小鼠的血酮值分别为（1.00±0.20）mmol/L和（0.90±0.17）mmol/L，均高于普通饮食组［分别为（0.63±0.06）mmol/L和（0.70±0.10）mmol/L，均P＜0.05］。接种后第30天，普通饮食组与高脂低碳水化合物饮食组小鼠的天冬氨酸氨基转移酶、丙氨酸氨基转移酶、肌酐和尿素等指标差异均无统计学意义（均P＞0.05），各组小鼠的心、肝、脾、肺、肾均未见明显毒性改变及肿瘤转移。普通饮食组、高脂低碳水化合物饮食组和普通饮食+放疗组小鼠的中位生存时间分别为38、41和55 d，高脂低碳水化合物饮食+放疗组小鼠的中位生存时间未达到。高脂低碳水化合物饮食+放疗组小鼠肿瘤组织中CD8表达上调，PD-1、CD34、LYVE-1和胶原纤维表达下调。高脂低碳水化合物饮食+放疗组的肿瘤旁淋巴结中CD8+ T细胞比例［（25.13±0.97）%］高于普通饮食组［（20.60±2.23）%，P＜0.05］和普通饮食+放疗组［（19.26±3.07）%，P＜0.05］，但与高脂低碳水化合物饮食组［（22.03±1.75）%］差异无统计学意义（P＞0.05）。普通饮食+放疗组肿瘤旁淋巴结中CD4+ T细胞比例［（31.33±5.16）%］和高脂低碳水化合物饮食+放疗组肿瘤旁淋巴结中CD4+ T细胞比例［（30.63±1.70）%］高于普通饮食组［（20.27±2.15）%，P＜0.05］和高脂低碳水化合物饮食组（23.70±2.62，P＜0.05）。普通饮食+放疗组的肿瘤旁淋巴结中Treg细胞在T细胞中占比最高［（16.58±5.10）%］，但与普通饮食组、高脂低碳水化合物饮食组和高脂低碳水化合物饮食+放疗组比较，差异均无统计学意义（均P＞0.05）。 结论： 高脂低碳水化合物饮食联合放疗可促进肺癌肿瘤微环境中免疫效应细胞的募集并增强其功能，抑制肿瘤微血管生成，从而抑制肿瘤生长。.

Mechanistic mathematical models (MMs) are a powerful tool to help us understand and predict the dynamics of tumour growth under various conditions. In this work, we use 5 MMs with an increasing number of parameters to explore how certain (often overlooked) decisions in estimating parameters from data of experimental tumour growth affect the outcome of the analysis. In particular, we propose a framework for including tumour volume measurements that fall outside the upper and lower limits of detection, which are normally discarded. We demonstrate how excluding censored data results in an overestimation of the initial tumour volume and the MM-predicted tumour volumes prior to the first measurements, and an underestimation of the carrying capacity and the MM-predicted tumour volumes beyond the latest measurable time points. We show in which way the choice of prior for the MM parameters can impact the posterior distributions, and illustrate that reporting the most likely parameters and their 95% credible interval can lead to confusing or misleading interpretations. We hope this work will encourage others to carefully consider choices made in parameter estimation and to adopt the approaches we put forward herein.

Tumor volume doubling time (TVDT) has been shown to be a potential surrogate marker of biological tumor activity. However, its availability in clinics is strongly limited due to ethical and practical reasons, as its assessment requires at least two subsequent tumor volume measurements in untreated patients. Here, a translational modeling framework to predict TVDT distributions in untreated cancer patient populations from tumor growth data in patient-derived xenograft (PDX) mice is proposed. Eleven solid cancer types were considered. For each of them, a set of tumor growth studies in PDX mice was selected and analyzed through a mathematical model to characterize the distribution of the exponential tumor growth rate in mice. Then, assuming an exponential growth of the tumor mass in humans, the growth rates were scaled from PDX mice to humans through an allometric scaling approach and used to predict TVDTs in untreated patients. A very good agreement was found between model predicted and clinically observed TVDTs, with 91% of the predicted TVDT medians fell within 1.5-fold of observations. Further, exploiting the intrinsic relationship between tumor growth dynamics and progression free survival (PFS), the exponential growth rates in humans were used to generate the expected PFS curves in absence of anticancer treatment. Predicted curves were extremely close to published PFS data from studies involving patient cohorts treated with supportive care or low effective therapies. The proposed approach shows promise as a potential tool to increase knowledge about TVDT in humans without the need of directly measuring tumor dimensions in untreated patients, and to predict PFS curves in untreated patients, that could fill the absence of placebo-controlled arms against which to compare treaded arms during clinical trials. However, further validation and refinement are needed to fully assess its effectiveness in this regard.

BACKGROUND: Tumor burden score (TBS) based on maximum tumor diameter and number has been shown to correlate with prognosis in patients with hepatocellular carcinoma (HCC). Nevertheless, the results are conflicting. Hence, we conducted a meta-analysis to analyze the association between TBS and survival outcomes of HCC patients.
METHODS: A comprehensively search of the databases including PubMed, Embase and Web of Science was performed to retrieve studies satisfying the inclusion criteria until August 31, 2023. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. All the data analyses were carried out by STATA 12.0.
RESULTS: 10 retrospective studies containing 25073 patients were incorporated in the study. The results demonstrated that high TBS was markedly association with poor overall survival (OS) (HR: 1.79, 95% CI: 1.45-2.23) and relapse-free survival / progression-free survival(RFS/PFS) (HR: 1.71; 95% CI: 1.42-2.07). Subgroup analysis showed that the prognostic value of TBS in HCC was not affected by any subgroup.
CONCLUSIONS: TBS may be an efficient prognostic index in HCC patients.

BACKGROUND: The lack of preoperative prognostic factors to accurately predict tumour aggressiveness in non-functioning pancreatic neuroendocrine tumours may result in inappropriate management decisions. This study aimed to critically evaluate the adequacy of surgical treatment in patients with resectable non-functioning pancreatic neuroendocrine tumours and investigate preoperative features of surgical appropriateness.
METHODS: A retrospective study was conducted on patients who underwent curative surgery for non-functioning pancreatic neuroendocrine tumours at San Raffaele Hospital (2002-2022). The appropriateness of surgical treatment was categorized as appropriate, potential overtreatment and potential undertreatment based on histologic features of aggressiveness and disease relapse within 1 year from surgery (early relapse).
RESULTS: A total of 384 patients were included. Among them, 230 (60%) received appropriate surgical treatment, whereas the remaining 154 (40%) underwent potentially inadequate treatment: 129 (34%) experienced potential overtreatment and 25 (6%) received potential undertreatment. The appropriateness of surgical treatment was significantly associated with radiological tumour size (P < 0.001), tumour site (P = 0.012), surgical technique (P < 0.001) and year of surgical resection (P < 0.001). Surgery performed before 2015 (OR 2.580, 95% c.i. 1.570 to 4.242; P < 0.001), radiological tumour diameter < 25.5 mm (OR 6.566, 95% c.i. 4.010 to 10.751; P < 0.001) and pancreatic body/tail localization (OR 1.908, 95% c.i. 1.119 to 3.253; P = 0.018) were identified as independent predictors of potential overtreatment. Radiological tumour size was the only independent determinant of potential undertreatment (OR 0.291, 95% c.i. 0.107 to 0.791; P = 0.016). Patients subjected to potential undertreatment exhibited significantly poorer disease-free survival (P < 0.001), overall survival (P < 0.001) and disease-specific survival (P < 0.001).
CONCLUSIONS: Potential overtreatment occurs in nearly one-third of patients undergoing surgery for non-functioning pancreatic neuroendocrine tumours. Tumour diameter emerges as the sole variable capable of predicting the risk of both potential surgical overtreatment and undertreatment.

OBJECTIVE: Various methods exist to perform and post-process perfusion weighted MR imaging in the post-treatment imaging of glioma patients to differentiate tumor progression from tumor-related abnormalities. One of these post-processing methods produces \'fractional tumor burden\' maps. This multi-reader study investigated the clinical feasibility of fractional tumor burden maps on real world data from radiological follow-up of high-grade astrocytoma patients.
METHODS: Five readers with background in radiology and varying levels of experience were tasked with assessing 30 astrocytoma and glioblastoma patients during one reader session. First, they were provided with a dataset of conventional MRI sequences, including perfusion MRI with regional cerebral blood volume maps. Then the dataset was expanded with a corresponding fractional tumor burden maps. Diagnostic accuracy, duration of post-processing, duration of the assessment of the fractional tumor burden maps, the diagnostic confidence reported by the readers and their diagnoses were recorded. Final diagnosis was determined by clinical and radiological follow-up and/or histopathological data used as gold standard.
RESULTS: A mean sensitivity of 83.3 % and mean specificity of 55.1 % was obtained without the use of fractional tumor burden maps, whereas their additional of fractional tumor burden maps resulted in a mean sensitivity and specificity of 79.5 % and 54.2 %, respectively. Diagnostic accuracies with and without fractional tumor burden maps were not significantly different (Z = 0.76, p = 0.450). The median time spent post-processing was 313 s, while the median duration of the assessment of the FTB maps was 19 s. Interestingly, reader confidence increased significantly after adding the fractional tumor burden-maps to the assessment (Z = 454, p < 0.01).
CONCLUSIONS: While the use of fractional tumor burden maps does not carry additional value in the radiological follow-up of post-operative high-grade astrocytoma and glioblastoma patients, it does give readers more confidence in their diagnosis.

The most recent (eighth) edition of the American Joint Committee on Cancer (AJCC) staging system divides invasive cutaneous melanoma into two broad groups: \"low-risk\" (stage IA-IIA) and \"high-risk\" (stage IIB-IV). While surveillance imaging for high-risk melanoma patients makes intuitive sense, supporting data are limited in that they are mostly respective and used varying methods, schedules, and endpoints. As a result, there is a lack of uniformity across different dermatologic and oncologic organizations regarding recommendations for follow-up, especially regarding imaging. That said, the bulk of retrospective and prospective data support imaging follow-up for high-risk patients. Currently, it seems that either positron emission tomography (PET) or whole-body computerized tomography (CT) are reasonable options for follow-up, with brain magnetic resonance imaging (MRI) preferred for the detection of brain metastases in patients who can undergo it. The current era of effective systemic therapies (ESTs), which can improve disease-free survival (DFS) and overall survival (OS) beyond lead-time bias, has emphasized the role of imaging in detecting various patterns of EST response and treatment relapse, as well as the importance of radiologic tumor burden.

BACKGROUND: Fractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis.
METHODS: This retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30-35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7-66 months).
RESULTS: GTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01).
CONCLUSIONS: GTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required.

BACKGROUND: The metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens.
METHODS: A total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via Kaplan‒Meier curves and compared via the log-rank test.
RESULTS: Univariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P < 0.0001 for all). Multivariate analysis indicated that MTA remained an independent predictor of PFS and OS [hazard ratio (HR), 2.506; 95% confidence interval (CI), 1.337-4.696; P = 0.004; and HR, 1.823; 95% CI, 1.005-3.310; P = 0.048], whereas TMTV was not. Further analysis using the NCCN-IPI model as a covariate revealed that MTA and NCCN-IPI were still independent predictors of PFS (HR, 2.617; 95% CI, 1.494-4.586; P = 0.001; and HR, 2.633; 95% CI, 1.650-4.203; P < 0.0001) and OS (HR, 2.021; 95% CI, 1.201-3.401; P = 0.008; and HR, 3.869; 95% CI, 1.959-7.640; P < 0.0001; respectively). Furthermore, MTA was used to separate patients with high NCCN-IPI risk scores into two groups with significantly different outcomes.
CONCLUSIONS: Pre-treatment MTA based on 18F-FDG PET/CT and NCCN-IPI were independent predictor of PFS and OS in DLBCL patients treated with R-CHOP. MTA has additional predictive value for the prognosis of patients with DLBCL, especially in high-risk patients with NCCN-IPI ≥ 4. In addition, the combination of MTA and NCCN-IPI may be helpful in further improving risk stratification and guiding individualised treatment options.
BACKGROUND: This research was retrospectively registered with the Ethics Committee of the Third Affiliated Hospital of Soochow University, and the registration number was approval No. 155 (approved date: 31 May 2022).

BACKGROUND: Accurate tumor volume estimation is important for evaluating the response to radionuclide therapy and external beam radiotherapy as well as to other pharmaceuticals. A common method for monitoring the growth of subcutaneous tumors in pre-clinical models and assessing the treatment response is to measure the tumor length and width by external calipers to estimate its volume. This procedure relies on an assumption of a spheroidal tumor shape wherein the tumor depth equals the width and can yield considerably inaccuracies. Ultrasound imaging is a non-invasive technique that can measure all three axes of the tumor and might be an alternative to caliper measurement with potentially greater accuracy and comparable ease-of-use and throughput. Both 2D and 3D ultrasound imaging are possible, the former offering short scan times without the need for anesthesia and heating-valuable factors for longitudinal studies in large animal cohorts. Nevertheless, tumor volume estimation accuracy by 2D ultrasound imaging has seen limited investigation. In this study we have evaluated the accuracy of tumor volume estimation by caliper and 2D ultrasound with comparisons to reference measurements by magnetic resonance imaging (MRI) in a pre-clinical model of prostate cancer treated with either external beam radiotherapy, radionuclide therapy, or no treatment.
RESULTS: Tumor volumes were measured longitudinally in 29 mice by caliper, ultrasound, and MRI before and after external beam radiotherapy, [177Lu]Lu-PSMA-617 radionuclide therapy, or no treatment. Caliper measurements had a marked bias, overestimating the tumor volumes by a median of 150% compared to MRI. Ultrasound measurements were markedly more accurate, with a median bias of -21% compared to MRI.
CONCLUSIONS: Ultrasound imaging is a reliable and accurate method for tumor volume estimation in pre-clinical models of radiotherapy, whereas caliper measurements are prone to overestimation.