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BackgroundHepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery.MethodWe retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators.ResultA total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA.ConclusionThe nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.

BackgroundCurrently, gastric cancer with positive lavage cytology without gross peritoneal dissemination (GC-CY1) is a special type of metastatic form with poor prognosis. Consensus guidelines on treatment strategies for patients with GC-CY1 have not been established. This study involves a single-arm, prospective, phase II clinical trial to examine the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) albumin-bound paclitaxel combined with Camrelizumab and S-1 in the treatment of GC-CY1 patients.Methods/designThis is a prospective single-center exploratory study, and the primary endpoints of the trial are R0 resection rate and conversion rate of abdominal free cancer cells (FCCs), with secondary endpoints of 3-year progression-free survival (PFS); 3-year overall survival (OS); objective remission rate (ORR); disease control rate (DCR); safety and TRG classification.DiscussionThis study is the first to apply NIPS albumin-bound paclitaxel combined with Camrelizumab and S-1 to the conversion therapy of GC-CY1 patients. It is speculated that this combination of regimens will increase the negative conversion rate of FCCs by 20%, which will provide innovative insights into conversion treatment ideas for GC-CY1 patients to be managed in a more comprehensive and optimized manner.Clinical trial registrationhttp://clinicaltrials.gov/, identifier NCT05410847.

ObjectiveTo quantitatively characterize the dosimetric effects of long on-couch time in prostate cancer patients treated with adaptive ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-Tesla magnetic resonance (MR)-linac.Materials and methodsSeventeen patients consecutively treated with UHF-RT on a 1.5-T MR-linac were recruited. A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate. We collected data for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan.ResultsOverall, 290 MR scans were collected (85 pre-MR, 85 PV-MR, 49 Bn-MR and 71 post-MR scans). With a median on-couch time of 49 minutes, the mean planning target volume (PTV)-V95% of all scans was 97.83 ± 0.13%. The corresponding mean clinical target volume (CTV)-V100% was 99.93 ± 0.30%, 99.32 ± 1.20%, 98.59 ± 1.84%, and 98.69 ± 1.85%. With excellent prostate-V100% dose coverage, the main reason for lower CTV-V100% was slight underdosing of seminal vesicles (SVs). The median V29 Gy change in the rectal wall was -1% (-20%–17%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow.ConclusionsThis 3D-MR–based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period with adaptive ATS workflow on 1.5-T MR-linac, albeit with a relatively long on-couch time. The 3-mm CTV-PTV margin was adequate for prostate irradiation but occasionally insufficient for SVs. More attention should be paid to restricting high-dose RT to the rectal wall when optimizing the ATS plan.

BackgroundThe use of lymph node (LN) tracers can help obtain a complete dissection of the lymph nodes and increase the detection rate of LNs and metastatic LNs. Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have been widely used in radical gastrectomy in recent years. Nevertheless, the comparison of their clinical effects has not been studied.Method/designThe FUTURE-01 trial will be the first randomized, open-label, single-center trial to compare CNSI and ICG. The study started in 2021 and enrolled 96 patients according to a prior sample size calculation. The primary outcome is the number of LNs retrieved. The secondary outcomes are LN staining rate, LN metastasis rate, stained LN metastasis rate, perioperative recovery and survival.ConclusionBy comparing the safety and efficacy of CNSI and ICG tracer-guided LN dissection in patients with gastric cancer, we can determine the most appropriate LN tracer at present. With the help of LN tracers, the operation is simplified, and the prognosis of these patients is improved. Our study is a prospective exploration of the safety, efficacy, and prognosis of CNSI and ICG.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05229874?cond=NCT05229874&draw=2&rank=1, identifier NCT05229874.

BackgroundA feasible method to detect somatic copy number deletion (SCND) of genes is still absent to date.MethodsInterstitial base-resolution deletion/fusion coordinates for CDKN2A were extracted from published articles and our whole genome sequencing (WGS) datasets. The copy number of the CDKN2A gene was measured with a quantitative multiplex PCR assay P16-Light and confirmed with whole genome sequencing (WGS).ResultsEstimated common deletion regions (CDRs) were observed in many tumor suppressor genes, such as ATM, CDKN2A, FAT1, miR31HG, PTEN, and RB1, in the SNP array-based COSMIC datasets. A 5.1 kb base-resolution CDR could be identified in >90% of cancer samples with CDKN2A deletion by sequencing. The CDKN2A CDR covers exon-2, which is essential for P16INK4A and P14ARF synthesis. Using the true CDKN2A CDR as a PCR target, a quantitative multiplex PCR assay P16-Light was programmed to detect CDKN2A gene copy number. P16-Light was further confirmed with WGS as the gold standard among cancer tissue samples from 139 patients.ConclusionThe 5.1 kb CDKN2A CDR was found in >90% of cancers containing CDKN2A deletion. The CDKN2A CDR was used as a potential target for developing the P16-Light assay to detect CDKN2A SCND and amplification for routine clinical practices.

PurposeIn principle, intensity-modulated electron therapy (IMET) can be delivered through mechanical scanning, with a robotic arm mounting a linac.Materials and methodsHere is a scanning algorithm to identify the back-and-forth, top-to-bottom (zigzag) pattern scan sequence. The algorithm includes generating beam positions with a uniform resolution according to the applicator size; adopting discrete energies to achieve the depth of 90% dose by compositing energies; selecting energy by locating the target’s distal edge; and employing the energy-by-energy scan strategy for step-and-shoot discrete scanning. After a zigzag scan sequence is obtained, the delivery order of the scan spots is optimized by fast simulated annealing (FSA) to minimize the path length. For algorithm evaluation, scan sequences were generated using the computed tomography data of 10 patients with pancreatic cancer undergoing intraoperative radiotherapy, and the results were compared between the zigzag path and an optimized path. A simple calculation of the treatment delivery time, which comprises the irradiation time, the total robotic arm moving time, the time for energy switch, and the time to stop and restart the beam, was also made.ResultsIn these clinical cases, FSA optimization shortened the path lengths by 12%–43%. Assuming the prescribed dose was 15 Gy, machine dose rate was 15 Gy/s, energy switch time was 2 s, stop and restart beam time was 20 ms, and robotic arm move speed was 50 mm/s, the average delivery time was 124±38 s. The largest reduction in path length yielded an approximately 10% reduction in the delivery time, which can be further reduced by increasing the machine dose rate and the robotic arm speed, decreasing the time for energy switch, and/or developing more efficient algorithms.ConclusionMechanically scanning IMET is potentially feasible and worthy of further exploration.

Circular RNAs (circRNAs) are a class of closed circular non-coding RNAs widely exist in eukaryotes, with high stability and species conservation. A large number of studies have shown that circRNAs are abnormally expressed in various tumor tissues, and are abundant in plasma with long half-life and high specificity, which may be served as potential tumor biomarkers for early diagnosis, treatment and prognosis of malignant tumors. However, the role of circRNAs is still poorly understood in gastric cancer. This article reviews the research progress of circRNAs in gastric cancer in recent years so as to explore the relationship between circRNAs and the occurrence and the development of gastric cancer, and provide new ideas for the diagnosis and treatment of gastric cancer.

Chemotherapy resistance exposes patients to side effects and delays the effect of therapy in patients. So far, there are no predictive tools to predict resistance to chemotherapy and select sensitive chemotherapeutic drugs for the patient. Here, we aim to develop an in-vitro primary cell culture model from breast cancer patients to predict sensitivity to chemotherapy. We created the primary breast cancer cell medium BCMI and culture system with higher efficiency of the model establishment. Immunofluorescence staining of ERa, PR and HER2 were done to identify the primary breast cancer cell from the counterpart breast cancer patient. The killing assay showed that these primary breast cancer cells responded differently to doxorubicin and pirarubicin treatment. These results indicate that our established primary breast cancer cell model holds great promise for predicting breast cancer sensitivity to chemotherapy drugs.

BackgroundThe relationship between sarcopenia and clinical outcomes during conversion therapy in patients with lavage cytology positive gastric cancer (GC-CY1) remains unclear. This study aimed to investigate the impact of sarcopenia and skeletal muscle loss on the efficacy of conversion therapy, tumour response and survival in GC-CY1 patients.MethodsRetrospective analysis of data from a prospective trial of conversion therapy conducted between April 2018 and August 2019 in patients with GC-CY1 (NCT03718624). Skeletal muscle index (SMI) was measured at the level of the third lumbar (L3) vertebra and the sarcopenia was defined using published cut-off points in all patients. We defined ΔSMI (%)/50 days above 9.53% for men and ΔSMI (%)/50 days above 8.81% for women as significant muscle loss (SML) and analysed the changes in skeletal muscle during conversion therapy in relation to treatment efficacy, survival and tumour response.ResultsOf the 36 patients, 7 patients (19.44%) developed sarcopenia before conversion therapy, 6 (16.67%) developed new sarcopenia after conversion therapy, and 8 (22.22%) developed SML during treatment. Multivariate analysis showed that sarcopenia before treatment [Odds Ratio (OR) =8.923, 95%CI: 1.341-25.321, p=0.002] and SML during treatment (OR=7.803, 95%CI: 1.106-16.189, p=0.001) had a negative impact on the success rate of conversion therapy. Cox multifactorial analysis found that pre-treatment sarcopenia [overall survival (OS): Hazard Ratio (HR) =6.341, 95%CI: 1.269-18.943, p=0.001; progression-free survival (PFS): HR=8.212, 95%CI: 1.569-36.582, p=0.001], newly developed sarcopenia after conversion therapy (OS: HR=3.189, 95%CI: 1.023-9.811, p=0.012; PFS: HR=3.084, 95%CI: 1.042-14.236, p=0.013) and the presence of SML during treatment (OS: HR=10.234, 95%CI: 2.532-54.231, p=0.002; PFS: HR=9.562, 95%CI: 2.341-38.092, p=0.002) were independent risk factor for OS and PFS in GC-CY1 patients.ConclusionPre-treatment sarcopenia and the presence of SML during treatment are strongly correlated with the immediate and long-term outcomes of GC-CY1 patients and can be used as imaging markers to predict the treatment efficacy and prognosis of patients in clinical practice.

BackgroundNeoadjuvant chemotherapies have been widely recommended in patients with locally advanced gastric cancer (LAGC). However, the evidence of combining neoadjuvant chemotherapy with anti–programmed death 1 (anti–PD-1) antibody therapy for patients with LAGC is lacking. Thus, we conducted a single-arm phase II trial to evaluate the efficacy and safety of the anti–PD-1 antibody sintilimab plus XELOX regimen (capecitabine plus oxaliplatin) in patients with LAGC.MethodsPatients with LAGC (cT3-4 N+ M0, CY0, P0) were enrolled and received four preoperative cycles of sintilimab (200 mg, IV, Q21d) plus XELOX (oxaliplatin 130 mg/m2, IV, d1 with capecitabine 1,000 mg/m2, bid, d1–d14, Q21d) therapy. The primary endpoint was the pathological complete response (pCR) rate. This clinical trial was registered at Chictr.org.cn (trial number: ChiCTR2000030414).ResultsThirty patients were enrolled from March 2020 to July 2021, with a median age of 62 years (range, 30–72), and 18 (60.0%) were men. There were 19 (63.3%) patients with PD-L1 CPS ≥1.The pCR rate was 33.3% [95% confidence interval (CI), 17.3%–52.8%], and the major pathologic response (MPR) rate was 63.3% (95% CI, 43.9%–80.1%). All the patients underwent R0 resection. The objective response rate (ORR) and the disease control rate (DCR) were 70.0% (95% CI, 50.6%–85.3%) and 100% (95% CI, 88.4%–100%), respectively. Downstaging of the overall TNM stage was observed in 22 (73.3%) patients. The pCR rate in patients with PD-L1 CPS ≥1 and patients with PD-L1 CPS

ObjectiveThis study aimed to develop prognostic prediction models for patients with Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG) who received neoadjuvant therapy (neoadjuvant chemoradiotherapy or neoadjuvant chemotherapy) and radical surgery. A baseline nomogram and a post-operative nomogram were constructed before neoadjuvant therapy and after surgery. The predictive performance of the constructed nomograms was internally validated and compared to the TNM staging system.Materials and MethodsA total of 245 patients diagnosed with Siewert type II/III AEG and treated with neoadjuvant therapy followed by radical surgery at The Fourth Hospital of Hebei Medical University between January 2011 and December 2017 were enrolled. The variables before neoadjuvant therapy were defined as baseline factors, while the variables of baseline factors along with the variables of treatment and postoperative pathology were defined as post-operative factors. To construct the corresponding nomograms, independent predictors of baseline and post-operative factors were identified. The C-index and a time-dependent receiver operating characteristic curve were used to evaluate the model’s discrimination ability. The calibration ability of the model was determined by comparing the probability of predicted free-recurrence to the actual free-recurrence. Decision curve analysis (DCA) was used to determine the clinical usefulness of the nomogram.ResultsAmong the baseline factors, age, cT stage, cN stage, Borrmann type, and staging laparoscopy were independent prognostic predictors. In contrast, among the post-operative factors, age, cN stage, staging laparoscopy, ypT stage, clinical response, number of positive lymph nodes, number of negative lymph nodes, laurén classification, and lymphatic, or perineural invasion (VELPI) were independent prognostic predictors. The two nomograms were constructed using the independent predictors of prognosis. The C-indexes for the baseline and post-operative nomograms were 0.690 (95% CI, 0.644-0.736) and 0.817 (95% CI, 0.782-0.853), respectively. The AUCs of the baseline nomogram at 3 and 5 years were both greater than cTNM (73.1 vs 58.8, 76.1 vs 55.7). Similarly, the AUCs of the post-operative nomogram were both greater than ypTNM (85.2 vs 69.1, 88.2 vs 71.3) at 3 and 5 years. The calibration curves indicated that both models had a high degree of calibration ability. By comparing the DCA at 3 and 5 years, we determined that the two nomograms constructed had better clinical utility than the TNM staging system.ConclusionsThe constructed nomograms have a more accurate predictive ability than the eighth edition TNM staging system, which can be useful for treatment selection and follow-up monitoring of patients.

PurposeThe current algorithms for measuring ventilation images from 4D cone-beam computed tomography (CBCT) are affected by the accuracy of deformable image registration (DIR). This study proposes a new deep learning (DL) method that does not rely on DIR to derive ventilation images from 4D-CBCT (CBCT-VI), which was validated with the gold-standard single-photon emission-computed tomography ventilation image (SPECT-VI).Materials and MethodsThis study consists of 4D-CBCT and 99mTc-Technegas SPECT/CT scans of 28 esophagus or lung cancer patients. The scans were rigidly registered for each patient. Using these data, CBCT-VI was derived using a deep learning-based model. Two types of model input data are studied, namely, (a) 10 phases of 4D-CBCT and (b) two phases of peak-exhalation and peak-inhalation of 4D-CBCT. A sevenfold cross-validation was applied to train and evaluate the model. The DIR-dependent methods (density-change-based and Jacobian-based methods) were used to measure the CBCT-VIs for comparison. The correlation was calculated between each CBCT-VI and SPECT-VI using voxel-wise Spearman’s correlation. The ventilation images were divided into high, medium, and low functional lung regions. The similarity of different functional lung regions between SPECT-VI and each CBCT-VI was evaluated using the dice similarity coefficient (DSC). One-factor ANONA model was used for statistical analysis of the averaged DSC for the different methods of generating ventilation images.ResultsThe correlation values were 0.02 ± 0.10, 0.02 ± 0.09, and 0.65 ± 0.13/0.65 ± 0.15, and the averaged DSC values were 0.34 ± 0.04, 0.34 ± 0.03, and 0.59 ± 0.08/0.58 ± 0.09 for the density change, Jacobian, and deep learning methods, respectively. The strongest correlation and the highest similarity with SPECT-VI were observed for the deep learning method compared to the density change and Jacobian methods.ConclusionThe results showed that the deep learning method improved the accuracy of correlation and similarity significantly, and the derived CBCT-VIs have the potential to monitor the lung function dynamic changes during radiotherapy.

BackgroundGastric cancer with only peritoneal lavage cytology (GC-CY1) is a special type of gastric cancer, which is defined as stage IV. The pre-treatment systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) are representative blood indexes of systemic inflammatory response and nutritional status. However, the clinical significance of combined detection of these two indexes is still unclear. This study aims to evaluate the clinical value of the new score system by combining SII and PNI (SII-PNI score) as a predictor of efficacy and prognosis after neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel combined with Apatinib conversion therapy for GC-CY1 patients.MethodsWe registered a prospective clinical study involving 36 GC-CY1 patients from April 2018 to August 2019 (NCT03718624). All patients underwent re-laparoscopic exploration after treatment. According to free cancer cells (FCCs) status, these patients were divided into FCCs group and non-FCCs group. The SII-PNI score ranged from 0 to 2 as follows: score of 2, high SII (≥512.1) and low PNI (≤52.9); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI.ResultsAll patients underwent re-laparoscopic exploration after 3 cycles of NIPS paclitaxel and Apatinib conversion therapy. Among them, 28 cases (77.78%) were in non-FCCs group, and 8 cases (22.22%) were in FCCs group. The SII-PNI score of non-FCCs patients was significantly lower than that of FCCs patients (p=0.041). The prognosis of patients with high SII-PNI score was significantly worse than that of patients with low SII-PNI score (p

IntroductionSomatic copy number deletion (SCND) of CDKN2A gene is the most frequent event in cancer genomes. Whether CDKN2A SCND drives human cancer metastasis is far from clear. Hematogenous metastasis is the main reason of human gastric carcinoma (GC) death. Thus, prediction GC metastasis is eagerly awaited.MethodGC patients (n=408) enrolled in both a cross-sectional and a prospective cohorts were analysed. CDKN2A SCND was detected with a quantitative PCR assay (P16-Light). Association of CDKN2A SCND and GC metastasis was evaluated. Effect of CDKN2A SCND by CRISPR/Cas9 on biological behaviors of cancer cells was also studied.ResultsCDKN2A SCND was detected in 38.9% of GCs from patients (n=234) enrolled in the cross-sectional cohort. Association analysis showed that more CDKN2A SCND was recognized in GCs with hematogenous metastasis than those without (66.7% vs. 35.7%, p=0.014). CDKN2A SCND was detected in 36.8% of baseline pN0M0 GCs from patients (n=174) enrolled in the prospective study, the relationship between CDKN2A SCND and hematogenous metastasis throughout the follow-up period (62.7 months in median) was also significant (66.7% vs. 34.6%, p=0.016). Using CDKN2A SCND as a biomarker for predicting hematogenous metastasis of GCs, the prediction sensitivity and specificity were 66.7% and 65.4%. The results of functional experiments indicated that CDKN2A SCND could obviously downregulate P53 expression that consequently inhibited the apoptosis of MGC803 GC and HEK293T cells. This may account for hematogenous metastasis of GCs by CDKN2A SCND.ConclusionCDKN2A SCND may drive GC metastasis and could be used as a predictor for hematogenous metastasis of GCs.

BackgroundReports have shown that neoadjuvant concurrent chemoradiotherapy (nCRT) increases the R0 resection rate for patients with Siewert type II or III adenocarcinoma of the gastroesophageal junction (AEG). However, the long-term efficacy of nCRT for AEG patients remains unclear. In this multicenter study, we investigated the long-term results of AEG patients treated with nCRT.MethodsA total of 149 patients with potentially resectable advanced AEG (T3/4, Nany, M0) were randomly divided into two groups: the nCRT-treated group (treated group) (n = 76) and the surgery group (control group) (n = 73). The primary endpoint was disease-free survival (DFS), and the secondary outcome indexes included the R0 resection rate, HER-2 expression, tumor regression grade (TRG), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events.ResultsIn the treated group, the overall therapeutic efficacy rate was 40.8%, and the pathological complete response (pCR) rate was 16.9%. The rates of patients who underwent R0 resection in the treated and control groups were 97.0% and 87.7%, respectively (p < 0.05). The toxic effects were mainly graded 1–2 in the treated group. The median DFS times in the treated and control groups were 33 and 27 months, respectively (p = 0.08), whereas the median OS times were 39 and 30 months, respectively (p = 0.01). The median DFS times of patients with positive and negative HER-2 expression in the treated group were 13 and 43 months, respectively (p = 0.01), and the median OS times were 27 and 41 months, respectively (p = 0.01).ConclusionSurgery after nCRT improved the efficacy of treatment for AEG patients and thus provided a better prognosis.Clinical Trial RegistrationThe trial is registered with ClinicalTrials.gov (number NCT01962246).

BackgroundThyroid dysfunction is common for cancer patients receiving PD-1/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1/PD-L1 inhibitors.MethodsPD-1/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials.ResultsForty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I2 = 40%, Z=9.91(P

BackgroundUnderstanding the safety and adverse event profiles of PD-1/PD-L1 inhibitors is important in guiding cancer immunotherapy. Consequently, we designed this meta-analysis to evaluate the safety of PD-1/PD-L1 inhibitors in clinical trials involving cancer patients.MethodsFour safety indicators comprising treatment-related adverse events, death, discontinuation of therapy and grades 3–5 adverse events were evaluated using the random effect model. The quality of enrolled trials was assessed using the Newcastle Ottawa Scale (NOS).ResultsForty-four clinical trials were included in the final meta-analysis. Compared with chemotherapy, the risk of death due to the use of PD-1/PD-L1 inhibitors was much lower than that experienced in the control group (OR = 0.65, 95%CI: [0.47, 0.91], I2 = 0%, Z = 2.52 (P = 0.01)). Similar observations were apparent regarding the other three indicators of safety and also when the use of PD-1/PD-L1 inhibitors alone is compared with the combined use of PD-1/PD-L1 and CTLA-4. When used together with chemotherapy, PD-1/PD-L1 inhibitors increased the incidence of the adverse events as compared to the use of chemotherapy alone. Increased risks for adverse events were also noticed with the use of PD-1/PD-L1 inhibitors over the use of a placebo.ConclusionThe use of PD-1/PD-L1 inhibitors alone is associated with a better safety profile compared to either the use of chemotherapy or the use of PD-1/PD-L1 inhibitors with other anticancer regimens.

BackgroundCervical cancer is one of the most common types of gynecological malignancies worldwide. This study aims to develop an immune signature to predict survival in cervical cancer.MethodThe gene expression data of 296 patients with cervical cancer from The Cancer Genome Atlas database (TCGA) and immune-related genes from the Immunology Database and Analysis Portal (ImmPort) database were included in this study. The immune signature was developed based on prognostic genes. The validation dataset was downloaded from the Gene Expression Omnibus (GEO) database.ResultThe immune signature namely immune-based prognostic score (IPRS) was developed with 229 genes. Multivariate analysis revealed that the IPRS was an independent prognostic factor for overall survival (OS) and progression-free survival (PFS) in patients with cervical cancer. Patients were stratified into high IPRS and low IPRS groups, and those in the high IPRS group were associated with better survival, which was validated in the validation set. A nomogram with IPRS and stage was constructed to predict mortality in cervical cancer.ConclusionsWe developed a robust prognostic signature IPRS that could be used to predict patients’ survival outcome.

This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081–0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16–0.34), olaparib (HR = 0.27 with 95% CrI: 0.20–0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17–0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24–0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24–0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34–0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30–0.45), olaparib (HR = 0.35 with 95% CrI: 0.25–0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30–0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable.

PurposeThe aim of this work is to introduce the 2019 International Planning Competition and to analyze its results.Methods and materialsA locally advanced non-small cell lung cancer (LA-NSCLC) case using the simultaneous integrated boost approach was selected. The plan quality was evaluated by using a ranking system in accordance with practice guidelines. Planners used their clinical Treatment Planning System (TPS) to generate the best possible plan along with a survey, designed to obtain medical physics aspects information. We investigated the quality of the large population of plans designed by worldwide planners using different planning and delivery systems. The correlations of plan quality with relevant planner characteristics (work experience, department scale, and competition experience) and with technological parameters (TPS and modality) were examined.ResultsThe number of the qualified plans was 287 with a wide range of scores (38.61–97.99). The scores showed statistically significant differences by the following factors: 1) department scale: the mean score (89.76 ± 8.36) for planners from the departments treating >2,000 patients annually was the highest of all; 2) competition experience: the mean score for the 107 planners with previous competition experience was 88.92 ± 9.59, statistically significantly from first-time participants (p = .001); 3) techniques: the mean scores for planners using VMAT (89.18 ± 6.43) and TOMO (90.62 ± 7.60) were higher than those using IMRT (82.28 ± 12.47), with statistical differences (p

Purpose: Drug-induced fever is frequently reported in cancer patients treated with anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1), and stoppage of the offending agent is the management of choice. However, given the complex management of cancer patients, this needs to be carefully studied. Therefore, we conducted a meta-analysis to estimate the risk of fever associated with anti-PD-1/PD-L1 in cancer patients.Methods: From May 2010 to 2020, an electronic search was conducted through PubMed for relevant studies. All clinical trials reporting fever in cancer patients treated with PD-1/PD-L1 inhibitors were included, while other designs were excluded. A manual search was also conducted to search for relevant articles. Outcomes included the risk of pyrexia and febrile neutropenia in the overall population and based on the grade of fever (all grades vs. grades 3–5). The Newcastle–Ottawa Scale was used to assess the quality of included studies.Results: Thirty-one articles, involving 27 clinical trials and 15,867 participants, were included. The increased risk of pyrexia for all grades is only found when PD-1/PD-L1 plus cytotoxic T lymphocyte-associated protein 4 (CTLA-4) was compared to CTLA-4 [odds ratio (OR) = 2.48, 95% CI: 1.17, 5.23]. The risk of febrile neutropenia for all-grade fever was significantly lower in the PD-1/PD-L1 group compared to that of chemotherapy alone (OR = 0.02, 95% CI: 0.01, 0.05). A similar trend in the risk of febrile neutropenia was also found for grades 3–5 (OR = 0.02, 95% CI: 0.01, 0.05).Conclusion: The increased risk of pyrexia for all grades could only be found when PD-1/PD-L1 plus CTLA-4 was compared with CTLA-4. Meanwhile, compared to chemotherapy, PD-1/PD-L1 inhibitors reduced the risk of febrile neutropenia.

PurposeThis study investigates the impact of the magnetic field on plan quality and dose at the tissue–air interface in MR-guided radiotherapy of head and neck cancer.Materials and MethodsThe charts of 10 patients with hypopharyngeal carcinoma who were treated with conventional fractionated radiotherapy were collected and reviewed. The skin and tissues containing air cavities were contoured. Three plans using 9 fields of intensity-modulated radiation therapy were generated for each patient in the Monaco treatment planning system of an Elekta Unity MR-linac. The first plan was optimized without the magnetic field (plan0T). The second plan was recalculated in the presence of a 1.5-T magnetic field (plan1.5T_reCal) using the same segment shape and monitor units as the first plan. The third plan was reoptimized in the presence of a 1.5-T magnetic field (plan1.5T_reOpt) using the same cost function as the first plan. The dose to the skin and tissues containing air cavities were compared across the three types of plans. A plan-quality metric method was used to evaluate the plan quality according to the clinical requirements.ResultsThe skin dose was increased in the presence of the 1.5-T magnetic field, and the amplitude increase of plan1.5T_reOpt (ΔDmean 1.30 ± 0.42 Gy, ΔDmax 1.68 ± 1.36 Gy) was smaller than that of plan1.5T_reCal (ΔDmean 1.81 ± 0.79 Gy, ΔDmax 5.43 ± 2.26 Gy). There were no significant differences in terms of the metrics of interfaces of tissues containing air cavities except for an increased maximum dose to the larynx and trachea. The plan quality of plan1.5T_reCal (68.0 ± 9.2) was significantly worse than that of plan0T (82.2 ± 7.0), and the plan quality of plan1.5T_reOpt (80.0 ± 7.0) was similar to that of plan0T.ConclusionThe presence of a 1.5-T magnetic field had an apparent impact on the dose distribution, in particular, a significant increase in the skin dose. The plan quality of plan1.5T_reOpt was similar to that of the original plan0T when the same cost function was used.

Purpose: The meta-analysis was put into practice in evaluating the risk ratio of immune-related digestive system inflammation in patients with solid tumors caused by PD-1/PD-L1 inhibitors.Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Results: After screening and eligibility assessment, a total of 26 clinical trials involving 16,409 patients were selected for the final quantitative synthesis. Immune-related digestive system inflammations, including colitis, hepatitis, pancreatitis, were evaluated separately. Compared with chemotherapy, PD-1/PD-L1 inhibitors led to an increase in the incidence risk of all grade colitis (RR = 2.43, 95% CI: [1.23, 4.82], P = 0.01). Similar incidence trend could also be seen when PD-1/PD-L1 inhibitors were combined with chemotherapy (RR = 2.62, 95% CI: [1.25, 5.48], P = 0.01). Whether compared with Nivolumab plus Ipilimumab or Ipilimumab alone, the incidence risk of colitis in the Nivolumab group was significantly lower than that of the control group. Similar analysis results could also be seen in the incidence risk of hepatitis. We did not find a statistically significant effect on the incidence of immune-related pancreatitis after the use of PD-1/PD-L1 inhibitors.Conclusion: The use of PD-1/PD-L1 inhibitors increased the incidence risk of immune-related colitis and hepatitis, but this potential to increase the incidence risk of the disease was weaker than Ipilimumab.

Radiation pneumonitis (RP) is one of the major side effects of thoracic radiotherapy. The aim of this study is to build a dose distribution based prediction model, and investigate the correlation of RP incidence and high-order features of dose distribution. A convolution 3D (C3D) neural network was used to construct the prediction model. The C3D network was pre-trained for action recognition. The dose distribution was used as input of the prediction model. With the C3D network, the convolution operation was performed in 3D space. The guided gradient-weighted class activation map (grad-CAM) was utilized to locate the regions of dose distribution which were strongly correlated with grade≥2 and grade

Purpose: We conducted this study to determine the relationship between PD-1/PD-L1 inhibitors and the incidence risk of peripheral neuropathy in patients with solid tumors.Method: The process of the meta-analysis was performed by us according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Incidence of all-grade and grade 3–5 treatment-related peripheral neuropathy in patients with solid tumors were taken into account.Results: After screening and eligibility assessment, a total of 17 clinical trials involving 10,500 patients were selected for the final meta-analysis. The incidence risk of peripheral neuropathy for all grade was significantly lower in the PD-1/PD-L1 inhibitor group than that of the control group, either monotherapy (OR = 0.08, 95%CI:[0.03, 0.19]) or chemotherapy (OR = 0.05, 95%CI:[0.03, 0.11]). Similar incidence trend could also be seen for the incidence risk of grade 3–5 peripheral neuropathy. When PD-1/PD-L1 inhibitors were used in combination with chemotherapy, the incidence risk of peripheral neuropathy was higher than in the control chemotherapy group, whether it was all-grade (OR = 1.22, 95%CI:[1.00, 1.49]) or grade 3–5 degree (OR = 1.74, 95%CI:[1.03, 2.92]).Conclusion: Compared with chemotherapy, incidence risk of peripheral neuropathy related to PD-1/PD-L1 inhibitor was significantly lower than that of the chemotherapy group, while PD-1/PD-L1 inhibitor increased the incidence risk of peripheral neuropathy when it was combined with chemotherapy.

Radiation pneumonitis (RP) is one of the major toxicities of thoracic radiation therapy. RP incidence has been proven to be closely associated with the dosimetric factors and normal tissue control possibility (NTCP) factors. However, because these factors only utilize limited information of the dose distribution, the prediction abilities of these factors are modest. We adopted the dosiomics method for RP prediction. The dosiomics method first extracts spatial features of the dose distribution within ipsilateral, contralateral, and total lungs, and then uses these extracted features to construct prediction model via univariate and multivariate logistic regression (LR). The dosiomics method is validated using 70 non-small cell lung cancer (NSCLC) patients treated with volumetric modulated arc therapy (VMAT) radiotherapy. Dosimetric and NTCP factors based prediction models are also constructed to compare with the dosiomics features based prediction model. For the dosimetric, NTCP and dosiomics factors/features, the most significant single factors/features are the mean dose, parallel/serial (PS) NTCP and gray level co-occurrence matrix (GLCM) contrast of ipsilateral lung, respectively. And the area under curve (AUC) of univariate LR is 0.665, 0.710 and 0.709, respectively. The second significant factors are V5 of contralateral lung, equivalent uniform dose (EUD) derived from PS NTCP of contralateral lung and the low gray level run emphasis of gray level run length matrix (GLRLM) of total lungs. The AUC of multivariate LR is improved to 0.676, 0.744, and 0.782, respectively. The results demonstrate that the univariate LR of dosiomics features has approximate predictive ability with NTCP factors, and the multivariate LR outperforms both the dosimetric and NTCP factors. In conclusion, the spatial features of dose distribution extracted by the dosiomics method effectively improves the prediction ability.

Circular RNAs (circRNAs) are a class of closed circular non-coding RNAs widely exist in eukaryotes, with high stability and species conservation. A large number of studies have shown that circRNAs are abnormally expressed in various tumor tissues, and are abundant in plasma with long half-life and high specificity, which may be served as potential tumor biomarkers for early diagnosis, treatment and prognosis of malignant tumors. However, the role of circRNAs is still poorly understood in gastric cancer. This article reviews the research progress of circRNAs in gastric cancer in recent years so as to explore the relationship between circRNAs and the occurrence and the development of gastric cancer, and provide new ideas for the diagnosis and treatment of gastric cancer. [ABSTRACT FROM AUTHOR]