Efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of recurrent cervical cancer: a prospective cohort.

OBJECTIVE: This study aimed to investigate the efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted computed tomography (CT)-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of pelvic recurrent cervical carcinoma after external beam radiotherapy. METHODS: From January 2019 to August 2023, 45 eligible patients were enrolled in this prospective cohort. All patients underwent 3D-PNCT-assisted CT-guided HDR-ISBT with a prescribed dose of 4-7 Gy/fraction to the high-risk clinical target volume (HR-CTV) over 3-8 fractions, either for curative or palliative purposes. The primary endpoints were local progression-free survival (LPFS) and tumor response rate (TRR). The secondary outcome measures included overall survival (OS), toxicities, and symptom resolution. RESULTS: Forty-five patients received 261 fractions of 3D-PNCT-assisted HDR-ISBT. Twenty-nine patients had isolated pelvic recurrence, and 16 patients had simultaneous extra-pelvic or distant recurrences. The TRR was 66.7%. The 2- and 5-year LPFS rates were 30.0% and 25.7%, respectively. The median OS was 23.2 months, and 2- and 5-year OS rates were 49.5% and 34.0%, respectively. The multivariate analysis indicated that squamous cell carcinoma, radical surgery, recurrence-free interval≥12 months, tumor diameter, pelvic recurrence type, and HR-CTV D90≥45 Gy were independent factors influencing LPFS (all p<0.05). D100≥21 Gy, V100≥83%, and V150≥45% were associated with better LPFS (all p<0.05). Tumor diameter and metastasis were independent predictive factors for OS (all p<0.05). The pain relief rate was 66.7% (10/15). Grade 3-4 toxicities occurred in 20.0% of patients. CONCLUSION: 3D-PNCT-assisted HDR-ISBT for reirradiation of recurrent cervical cancer proved to be an effective and safe alternative to radical surgery.

Effects of Gene Alternative Splicing Events on Resistance to Cryptocaryonosis of Large Yellow Croaker (Larimichthys crocea).

Large yellow croaker (L. crocea) is a productive species in marine aquaculture with great economic value in China. However, the sustainable development of large yellow croaker is hampered by various diseases including cryptocaryonosis caused by Cryptocaryon irritans. The genetic regulation processes for cryptocaryonosis in large yellow croaker are still unclear. In this present study, we analyzed differential alternative splicing events between a C. irritans resistance strain (RS) and a commercial strain (CS). We identified 678 differential alternative splicing (DAS) events from 453 genes in RS and 719 DAS events from 500 genes in CS. A set of genes that are specifically alternatively spliced in RS was identified including mfap5, emp1, and trim33. Further pathway analysis revealed that the specifically alternative spliced genes in RS were involved in innate immune responses through the PRR pathway and the Toll and Imd pathway, suggesting their important roles in the genetic regulation processes for cryptocaryonosis in large yellow croaker. This study would be helpful for the studies of the pathogenesis of cryptocaryonosis and dissection of C. irritans resistance for L. crocea.

The safety and efficacy of volumetric modulated Arc therapy combined with computer tomography-guided adaptive brachytherapy for locally advanced cervical cancer: a single institution experience.

BACKGROUND: Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer. METHODS AND MATERIALS: This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS. RESULTS: Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities. CONCLUSION: VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.

High-dose rate endorectal brachytherapy for rectal cancer: A state-of-the-art review.

Rectal cancer is a common malignancy that requires multidisciplinary treatment. By utilizing the dose-response relationship in rectal cancer radiotherapy, increasing the radiotherapy dose can improve clinical complete remission rates. High-dose rate endorectal brachytherapy (HDREBT) is a novel technique that delivers high doses of radiotherapy directly to the tumor via an endorectal applicator, sparing the adjacent normal tissues from excessive radiation exposure. HDREBT includes contact X-ray brachytherapy and high-dose-rate intracavitary brachytherapy. We introduce the latest developments in applicators and imaging techniques for HDREBT in rectal cancer and summarize the current evidence on the efficacy, safety, and feasibility of HDREBT as a neoadjuvant, definitive, or palliative treatment option for all stages of rectal cancer patients. We also discuss the potential advantages and challenges of HDREBT in achieving organ preservation and improving the quality of life of rectal cancer patients. HDREBT has shown promising results in achieving high complete response rates, enabling nonoperative management, improving organ preservation rates, and providing effective palliation in rectal cancer patients. More studies are needed to optimize its dose and fractionation schemes in different clinical scenarios.

The Efficacy of Volumetric Modulated Arc Therapy Combined With Chemotherapy, Brachytherapy, and Local Hyperthermia on Patients with Locally Advanced Cervical Cancer: A Retrospective Study.

OBJECTIVE: To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). METHODS: In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4 Gy/1.8 Gy/28 f) concurrent with cisplatin-based chemotherapy (40 mg/m2, q1w, 6 cycles) and local HT (40.5-41°C for 60 min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. RESULTS: The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. CONCLUSION: VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.

Integrated mRNA and miRNA expression analyses for Cryptocaryon irritans resistance in large yellow croaker (Larimichthys crocea).

Large yellow croaker (Larimichthys crocea) is one of the most important mariculture fish in China. However, cryptocaryonosis caused by Cryptocryon irritans infection has brought huge economic losses and threatened the healthy and sustainable development of L. crocea industry. Recently, a new C. irritans resistance strain of L. crocea (RS) has been bred using genomic selection technology in our laboratory work. However, the molecular mechanisms for C. irritans resistance of RS have not been fully understood. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that are post-transcriptional regulators, and they play vital roles in immune process of bony fish. Identification of anti-C.irritans relevant miRNA signatures could, therefore, be of tremendous translational value. In the present study, integrated mRNA and miRNA expression analysis was used to explore C. irritans resistance mechanisms of the L. crocea. RS as well as a control strain (CS) of L. crocea, were artificially infected with C. irritans for 100 h, and their gill was collected at 0 h (pre-infection), 24 h (initial infection), and 72 h (peak infection) time points. The total RNA from gill tissues was extracted and used for transcriptome sequencing and small RNA sequencing. After sequencing, 23,172 known mRNAs and 289 known miRNAs were identified. The differential expression was analyzed in these mRNAs and mRNAs and the interactions of miRNA-mRNA pairs were constructed. KEGG pathway enrichment analyses showed that these putative target mRNAs of differentially expressed miRNAs (DEMs) were enriched in different immune-related pathways after C. irritans infection in RS and CS. Among them, necroptosis was the immune-related pathway that was only significantly enriched at two infection stages of RS group (RS-24 h/RS-0h and RS-72 h/RS-0h). Further investigation indicates that necroptosis may be activated by DEMs such as miR-133a-3p, miR-142a-3p and miR-135c, this promotes inflammation responses and pathogen elimination. These DEMs were selected as miRNAs that could potentially regulate the C. irritans resistance of L. crocea. Though these inferences need to be further verified, these findings will be helpful for the research of the molecular mechanism of C. irritans resistance of L. crocea and miRNA-assisted molecular breeding of aquatic animals.

Identification and Expression Analysis of LncRNAs Reveal the Immune Mechanism of Visceral White-Nodules Disease Resistance in Large Yellow Croaker.

Long non-coding RNAs (lncRNAs) have several known functions in fish growth processes and signal transduction, but their possible roles in response to bacterial diseases remain largely unresolved. In this study, we report a comprehensive cold-water bacterial disease-responsive lncRNA expression profile for understanding the transcriptional regulatory mechanisms of visceral white-nodules disease resistance in large yellow croaker. A total of 2534 high-confidence lncRNAs were identified by a rigorous filtering pipeline as a basic sequence set for comparative transcriptional analysis. In addition, a total of 10,200 lncRNA-mRNA pairs with high correlation coefficients were identified by expressions level correlation analysis, including non-redundant 381 DE lncRNAs and 2590 differential expressed genes. MSTRG_11084_1 and MSTRG_20402_1 were linked to a large number of target genes and may be involved in important functions in immune regulation. We further revealed the conserved and idiosyncratic features of the disease response process between the technical control strain (TCS) and the resistant strain (RS). Immune-related pathways were enriched in GO terms and KEGG pathways, among which cytokine-cytokine receptor interaction, MAPK signaling pathway, and NF-kappa B signaling pathway may play a key role in VWND resistance in large yellow croaker. Protein-protein interaction network (PPI) analysis revealed that immune-related target genes such as il-10, met, acta2, myc, cav1, and ntrk1, as well as growth and metabolism-related target genes such as pik3r2, igf1, sc5d, hmgcr, and lss were considered the main hub genes. This study represents the first characterization of lncRNAs involved in VWND resistance in large yellow croaker and provides new clues for elucidating the disease response mechanism of large yellow croaker.

Image Guidance Volume-Modulated Arc Radiation Therapy Concurrently With Nab-Paclitaxel Plus Cisplatin for Patients With Locally Advanced Cervical Cancer: A Single-Arm Dose Escalation Trial.

PURPOSE: Nanoparticle albumin-bound (nab) paclitaxel has improved uptake by tumor cells in comparison to paclitaxel. The aim of this study was to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin with concurrent image guidance volume modulated arc therapy for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: This single-arm phase 1 trial followed the standard 3 + 3 dose escalation design. Patients with histologically proven stage IB2-IVA LACC were eligible. Image guidance volume modulated arc therapy included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and subsequent high-dose-rate intracavitary brachytherapy at a total dose of 30.0 Gy in 5 fractions, twice a week. Concurrent chemotherapy regimen included weekly cisplatin (40 mg/m2) and weekly nab-paclitaxel at escalating doses (10, 20, 33, 50, and 70 mg/m2 per week). Duration of the planned treatment was 8 weeks. Grade 4 hematologic toxicity and grade 3 or above nonhematologic toxicity were considered as DLT. MTD was defined as the highest dose with ≤33% DLT. RESULTS: A total of 22 patients were enrolled from September 2019 to August 2021. The most common adverse events were grade 1 to 3 leukopenia, diarrhea, and nausea/vomiting. A total of 4 patients (18.0%) experienced DLT: grade 3 hypokalemia at 33 mg/m2 (1 of 6 subjects), grade 3 deep vein thrombosis at 50 mg/m2 (1 of 6) and 70 mg/m2 (1 of 4), and grade 3 perineum edema at 70 mg/m2 (1 of 3). The estimated MTD was 50 mg/m2. Complete response was observed in 20 patients (90.9%). CONCLUSIONS: In patients undergoing concurrent IG-VAMT with nab-paclitaxel plus cisplatin for LACC, MTD of nab-paclitaxel was 50 mg/m2. Complete response rate was 90.9%.

A comparative study of dosimetric parameters of 3D-printed non-coplanar template-assisted CT-guided iodine-125 seed implantation brachytherapy in patients with inguinal lymph node metastatic carcinomas.

Purpose: To compare the pre-plan and post-plan dosimetric parameter differences of 3D-printed non-coplanar templates (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 (125I) radioactive seed implantation brachytherapy (RISI) in patients with inguinal lymph node metastasis (ILNM). Material and methods: This was a retrospective study of 15 patients with ILNM carcinomas treated with 3D-PNCT-assisted CT-guided RISI between May, 2015 and April, 2018. All patients underwent prior external beam radiotherapy (EBRT) or surgery. Dosimetric parameters included D90, D100 (dose delivered to 90% and 100% of the volume, respectively), V100, V150, V200 (percentage of target volume receiving 100%, 150%, and 200% of the prescribed dose, respectively). Quality parameters included conformal index (CI), external index (EI), and homogeneity index (HI). Paired t-test and Bland-Altman analysis were applied to compared pre-plan and post-plan parameters. Results: The median gross tumor volume (GTV) in the pre-plan was 8.7 ml (range, 0.8-185.1 ml). There were statistically significant differences in V100, V150, CI, and EI (p < 0.05). Bland-Altman analysis indicated that accidental error of RISI was small. In 1 of the 15 cases, D90 and D100 exceeded the prescribed therapeutic accuracy. In 1 of the 15 cases, V150, EI, and GTV were outside the specified accuracy range (95% confidence interval). Conclusions: 3D-PNCT-assisted CT-guided RISI is a safe, accurate, and feasible choice in ILNM treatment. The procedure of RISI has significantly improved. The pre-plan can be accurately executed by 3D-PNCT-assisted CT-guided RISI.

Integrative analysis of GWAS and transcriptome reveals p53 signaling pathway mediates resistance to visceral white-nodules disease in large yellow croaker.

Visceral white-nodules disease (VWND), caused by Pseudomonas plecoglossicida, is one of the primary causes of morbidity and mortality in large yellow croaker aquaculture. Host disease resistance is a heritable trait that involves complex regulatory processes. However, the regulatory mechanism of bacterial resistance in large yellow croaker is still unclear. This study attempted to systematically evaluate the major genetic loci and transcriptional regulatory mechanisms associated with the resistance to VWND in large yellow croaker by crossover method studies. A large population of large yellow croaker was challenged with P. plecoglossicida, with survival time recorded and samples were taken for genotyping. Meanwhile, spleen samples that were used for RNA-seq to compare their transcriptomic profiles before and after infection were taken from resistant populations (RS) and susceptible control populations (CS) bred using the genomic selection (GS) technique. Genome-wide association analyses using 46 K imputed SNP genotypes highlighted that resistance is a polygenic trait. The integrative analysis results show the co-localization of the cd82a gene between disease resistance-related genetic loci and comparative transcriptional analysis. And functional enrichment analysis showed differential enrichment of the p53 signaling pathway in RS and CS groups, suggesting that there may be cd82a-mediated p53 signaling pathway activation for VWND resistance. This large-scale study provides further evidence for the heritability and transcriptional regulatory mechanisms of host inheritance of VWND resistance.

Re-Irradiation for Recurrent Cervical Cancer: A State-of-the-Art Review.

The recurrence rate of cervical cancer after primary treatment can reach 60%, and a poor prognosis is reported in most cases. Treatment options for the recurrence of cervical cancer mainly depend on the prior treatment regimen and the location of recurrent lesions. Re-irradiation is still considered as a clinical challenge, owing to a high incidence of toxicity, especially in in-field recurrence within a short period of time. Recent advances in radiotherapy have preliminarily revealed encouraging outcomes of re-irradiation. Several centers have concentrasted on stereotactic body radiation therapy (SBRT) for the treatment of well-selected cases. Meanwhile, as the image-guiding techniques become more precise, a better dose profile can also be achieved in brachytherapy, including high-dose-rate interstitial brachytherapy (HDR-ISBT) and permanent radioactive seed implantation (PRSI). These treatment modalities have shown promising efficacy with a tolerable toxicity, providing further treatment options for recurrent cervical cancer. However, it is highly unlikely to draw a definite conclusion from all of those studies due to the large heterogeneity among them and the lack of large-scale prospective studies. This study mainly reviews and summarizes the progress of re-irradiation for recurrent cervical cancer in recent years, in order to provide potential treatment regimens for the management of re-irradiation.

MRI radiomics in overall survival prediction of local advanced cervical cancer patients tread by adjuvant chemotherapy following concurrent chemoradiotherapy or concurrent chemoradiotherapy alone.

OBJECTIVES: To build radiomics based OS prediction tools for local advanced cervical cancer (LACC) patients treated by concurrent chemoradiotherapy (CCRT) alone or followed by adjuvant chemotherapy (ACT). And, to construct adjuvant chemotherapy decision aid. METHODS: 83 patients treated by ACT following CCRT and 47 patients treated by CCRT were included in the ACT cohort and non-ACT cohort. Radiomics features extracted from primary tumor area of T2-weighted MRI. Two radiomics models were built for ACT and non-ACT cohort in prediction of 3 years overall survival (OS). Elastic Net Regression was applied to the the ACT cohort, meanwhile least absolute shrinkage and selection operator plus support vector machine was applied to the non-ACT cohort. Cox regression models was used in clinical features selection and OS predicting nomograms building. RESULT: The two radiomics models predicted the 3 years OS of two cohorts. The receiver operator characteristics analysis was used to evaluate the 3 years OS prediction performance of the two radiomics models. The area under the curve of ACT and non-ACT cohort model were 0.832 and 0.879, respectively. Patients were stratified into low-risk group and high-risk group determined by radiomics models and nomograms, respectively. And, the low-risk group patients present significantly increased OS, progression-free survival, local regional control, and metastasis free survival compare with high-risk group (P < 0.05). Meanwhile the prognosis prediction performance of radiomics model and nomogram is superior to the prognosis prediction performance of Figo stage. CONCLUSION: The two radiomics model and the two nomograms is a prognosis predictor of LACC patients treated by CCRT alone or followed by ACT.

Tissue-Specific Analysis of Alternative Splicing Events and Differential Isoform Expression in Large Yellow Croaker (Larimichthys crocea) After Cryptocaryon irritans Infection.

The large yellow croaker (Larimichthys crocea) is one of the most important mariculture fish in China. Recently, cryptocaryonosis caused by Cryptocryon irritans infection has brought huge economic losses and threatens the healthy and sustainable development of the L. crocea industry. However, the molecular mechanism and regulation process for L. crocea resistance to C. irritans infection has not been fully researched. Alternative splicing (AS) is an important post-transcriptional regulatory mechanism that allows cells to produce transcriptional and proteomic diversity. The results of AS are tissue dependent, and the expression of tissue-specific transcription subtype genes is determined by AS and transcriptional regulation. However, studies on the tissue specificity of AS events in L. crocea following infection with C. irritans have not been performed. In this study, the L. crocea were artificially infected with C. irritans; their skin and gill were collected at 0 h, 24 h, 48 h, 72 h, and 96 h post infection. After sequencing and differential expression analysis, a set of 452, 692, 934, 711, 534, and 297 differential alternative splicing (DAS) events were identified in 0 h, 12 h, 24 h, 48 h, 72 h, and 96 h post infection respectively. Furthermore, 4160 differentially expressed isoforms (DEIs) and 4209 DEI genes were identified from all time point groups. GO enrichment and pathway analysis indicated that many genes of DAS and DEIs were rich in immune-related GO terms and KEGG pathways, such as the Toll and Imd signaling pathway, NOD-like receptor signaling pathway, TNF signaling pathway, and TNF signaling pathway. Among hub DEI genes, alternative splicing-related genes (cwc25, prpf8, and sf3a3), skin function-related gene (fa2h), and oxygen deprivation-related gene (hyo1) were found in DEI genes. This study provided insight into the temporal change of DAS and DEIs between skin and gill of L. crocea against C. irritans infection and revealed that these differences might play immune-related roles in the infection process.

Comparative transcriptome analysis reveals immunoregulation mechanism of lncRNA-mRNA in gill and skin of large yellow croaker (Larimichthys crocea) in response to Cryptocaryon irritans infection.

BACKGROUND: Cryptocaryonosis caused by Cryptocaryon irritans is one of the major diseases of large yellow croaker (Larimichthys crocea), which lead to massive economic losses annually to the aquaculture industry of L. crocea. Although there have been some studies on the pathogenesis for cryptocaryonosis, little is known about the innate defense mechanism of different immune organs of large yellow croaker. RESULTS: In order to analyze the roles of long non-coding RNAs and genes specifically expressed between immune organs during the infection of C. irritans, in this study, by comparing transcriptome data from different tissues of L. crocea, we identified tissue-specific transcripts in the gills and skin, including 507 DE lncRNAs and 1592 DEGs identified in the gills, and 110 DE lncRNAs and 1160 DEGs identified in the skin. Furthermore, we constructed transcriptome co-expression profiles of L. crocea gill and skin, including 7,503 long noncoding RNAs (lncRNAs) and 23,172 protein-coding genes. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of the DE lncRNAs in the gill were specifically enriched in several pathways related to immune such as HIF-1 signaling pathway. The target genes of DE lncRNAs and DEGs in the skin are specifically enriched in the complement and coagulation cascade pathways. Protein-protein interaction (PPI) network analysis identified 3 hub genes including NFKBIA, TNFAIP3 and CEBPB, and 5 important DE lncRNAs including MSTRG.24134.4, MSTRG.3038.5, MSTRG.27019.3, MSTRG.26559.1, and MSTRG.10983.1. The expression patterns of 6 randomly selected differentially expressed immune-related genes were validated using the quantitative real-time PCR method. CONCLUSIONS: In short, our study is helpful to explore the potential interplay between lncRNAs and protein coding genes in different tissues of L. crocea post C. irritans and the molecular mechanism of pathogenesis for cryptocaryonosis. HIGHLIGHTS: Skin and gills are important sources of pro-inflammatory molecules, and their gene expression patterns are tissue-specific after C. irritans infection. 15 DEGs and 5 DE lncRNAs were identified as hub regulatory elements after C. irritans infection The HIF-1 signaling pathway and the complement and coagulation cascade pathway may be key tissue-specific regulatory pathways in gills and skin, respectively.

Detection of setup errors with a body-surface laser-scanning system for whole-breast irradiation after breast-conserving surgery.

PURPOSE: We compared the setup errors determined by an optical imaging system (OSIS) in women who received breast-conserving surgery (BCS) followed by whole-breast radiotherapy (WBRT) with those from cone-beam computed tomography (CBCT) carried out routinely. METHODS: We compared 130 setup errors in 10 patients undergoing WBRT following BCS by analyzing the translational and rotational couch shifts via CBCT and OSIS. Patients were treated with intensity-modulated radiotherapy (IMRT). The patient outline extracted from the planning reference Computed tomography (CT) was used as the reference for OSIS and CBCT alignment during treatment. We detected the setup uncertainty using CBCT and OSIS at the first five fractionations of RT and then twice a week. RESULTS: The absolute translational setup error (mean ± Standard deviation (SD)) in x (lateral), y (longitudinal), and z (vertical) axes detected by the OSIS was 0.14 ± 0.18, 0.15 ± 0.14, and 0.13 ± 0.13 cm, respectively. The rotational setup error (mean ± SD) in Rx (pitch), Ry (roll), and Rz (yaw) axes was 0.77 ± 0.54, 0.76 ± 0.61, and 1.23 ± 0.95, respectively. Significant difference is observed only in one direction (Rx, p = 0.03) in the paired setup errors obtaining from OSIS and CBCT, without significant differences in five directions. CONCLUSION: OSIS is a repeatable and reliable system that can be used to detect misalignments with accuracy, which is capable of supplementing CBCT for WBRT after BCS. We believe that an OSIS may be easier to use, quicker, and reduce overall dose as this method of patient alignment does not require ionizing radiation.

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report.

Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.

Chinese Expert Consensus on Iodine125 Seed Implantation for Recurrent Cervical Cancer in 2021.

The treatment modality for recurrent cervical cancer (rCC) is limited, and the prognosis of these patients is poor. Seed implantation could be an important component of rCC management in the context of dose boost or salvage therapy after surgery or radiotherapy, which is characterized by a minimally invasive, high local dose, and rapidly does fall, sparing normal tissue. For patients with good performance status and lateral pelvic wall recurrence with an available puncture path, seed implantation was recommended, as well as for selected central pelvic recurrence and extra-pelvic recurrence. The combination of brachytherapy treatment planning system and CT guidance was needed, and three-dimensional printing templates could greatly improve the accuracy, efficiency, and quality of seed implantation to achieve a potential ablative effect and provide an efficient treatment for rCC. However, the recommendations of seed implantation were mainly based on retrospective articles and lack high-quality evidence, and multicenter prospective randomized studies are needed. In this consensus on iodine125 seed implantation for rCC, indication selection, technical process and requirements, dosimetry criteria, radiation protection, combined systemic therapy, and outcomes of seed implantation for rCC are discussed.

Accuracy and dosimetric parameters comparison of 3D-printed non-coplanar template-assisted computed tomography-guided iodine-125 seed ablative brachytherapy in pelvic lateral recurrence of gynecological carcinomas.

PURPOSE: To investigate the accuracy of needle distribution and dosimetric parameter differences of 3D-printing non-coplanar template (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 seed ablative brachytherapy (125I-SAB) in gynecological cancer patients with non-central pelvic recurrence between pre-operative plan and post-operative plan. MATERIAL AND METHODS: Thirty-eight patients with forty-one non-central pelvic recurrent gynecological carcinomas after radiotherapy were enrolled in this study. All patients received 3D-PNCT-assisted CT-guided 125I-SAB from January 2016 to January 2019. The position, angle, and depth of seed needles were measured in both pre-operative plan and intra-operative real-time plan in brachytherapy treatment planning system (B-TPS). Dosimetric parameters of D90, D100, V100, V150, and V200 as well as quality parameters of conformal index (CI), external index (EI), and homogeneity index (HI) were compared between pre-operative plan and post-operative plan. Peri-operation complications and radiation-related toxicity were assessed. RESULTS: Median follow-up time was 12 months (range, 5-34 months). Prescribed dose was 100-170 Gy (median, 120 Gy). Radioactivity of 125I seed was 0.4-0.7 mCi (median, 0.55 mCi). Mean depth deviation for 499 needles was 0.8 ±1.0 cm. Mean angular deviation was 2.2 ±2.1 degrees. Mean tip distance deviation of needles was 0.4 ±0.3 cm. There were significant differences between pre-operative and post-operative plans in CI (p = 0.001) and EI (p = 0.005). No significant differences were shown in D90, D100, V100, V150, V200, and HI between pre-operative and post-operative plans. Only few patients suffered from ≤ grade 2 toxicities. CONCLUSIONS: 3D-PNCT-assisted CT-guided 125I-SAB is safe and feasible for non-central pelvic recurrence of gynecological cancer. All complications are tolerable and mild.

The Preliminary Results of 3-Dimensional Printed Individual Template Assisted 192Ir High-Dose Rate Interstitial Brachytherapy for Central Recurrent Gynecologic Cancer.

OBJECTIVE: To evaluate the feasibility and safety of high dose rate interstitial brachytherapy (HDR-IB) assisted with 3-dimensional printing individual template (3D-PIT) for central pelvic recurrent gynecologic cancer (CR-GYN). METHODS: Totally 32 patients diagnosed with CR-GYN received iridium-192(192Ir) HDR-IB assisted with 3D-PIT that was classified in 2 types(Type I: transvaginal template/ applicator, and Type II: transvaginal combined transperineal template). The prescribed dose to gross tumor volume (GTV) was 10-36 Gy in 2-6 fractions. We rely on a few dosimetric parameters for quality control. The short-term efficacy was evaluated by RECIST v1.1, and the adverse event was evaluated by CTCAE V4.0. RESULTS: The median V100, D100 and D90 of per fraction among all the patients were 88.9%±9.8%, 3.45Gy±0.54 Gy, and 5.79Gy±0.32 Gy, respectively. Dosimetric comparison between preplan and treatment plan of 20/32 patients with Type II 3D-PIT showed no significant difference in GTV volume, V100, D100, D90, conformation index (CI) and homogeneity index (HI). No severe treatment complications occurred. Grade 3 or 4 late toxicities (fistula) were observed in 3 patients (9%). The local response rate (complete remission, CR + partial remission, PR) was 84.4% (27/32) 1 month after completion of treatment. The median time to progression (TTP) was 15.4 months (95% CI 11.3- 19.6 months), 1-year local control (LC) rate were 51.7%. CONCLUSIONS: HDR-IB assisted by 3D-PIT was a reliable modality for CR-GYN due to the clinical feasibility and accepted complications.