Analysis of the Parotid Glands on an Energy Spectrum CT Iodine Map to Evaluate Irradiation-Induced Acute Xerostomia in Patients With Nasopharyngeal Carcinoma.

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.

Prognostic Value of Pretreatment Serum CA199 in Patients with Locally Advanced Rectal Cancer Treated with CRT Followed by TME with Normal Pretreatment Carcinoembryonic Antigen Levels.

BACKGROUND: Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial. OBJECTIVES: The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery. METHODS: A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ2 method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA < 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA < 5 ng/mL and CA199 < 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated). RESULTS: Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, p = 0.030), ypN (OR 1.622, p = 0.026), and pretreatment CA199 levels (OR 1.886, p = 0.048). CONCLUSION: Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making.

Chemotherapy-based split stereotactic body radiation therapy for borderline resectable and locally advanced pancreatic cancer: study protocol of a prospective, single-arm phase II trial.

INTRODUCTION: The question of how to administer adequate chemotherapy to synchronise stereotactic body radiation therapy (SBRT) treatment strategy to maximise the benefits of neoadjuvant therapy for the improved prognosis of patients with borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer is a challenging and debatable issue. No studies have yet evaluated the efficacy of split-course SBRT as the neoadjuvant chemoradiotherapy regimen. We aimed to study whether neoadjuvant chemotherapy plus split-course SBRT results in better outcomes in BRPC and LAPC patients. METHODS AND ANALYSIS: Treatment-naïve patients with radiographically confirmed BRPC or LAPC, supporting biopsy results and no severe comorbidities will be enrolled. They will be treated with nab-paclitaxel plus gemcitabine (nab-P+Gem) chemotherapy plus split-course SBRT, followed by an investigator's choice of continuation of treatment with nab-P+Gem or surgery. nab-P+Gem chemotherapy will commence on day 1 for each of six cycles: nab-paclitaxel 125 mg/m2 intravenous infusion over approximately 30-45 min, followed by gemcitabine 1000 mg/m2 intravenous infusion over about 30 min on days 1 and 15 of each 28-day cycle. During the first and second cycles of chemotherapy, SBRT will be given as a single irradiation of 10 Gy four times (days 2 and 16 of each 28-day cycle). The primary endpoint is progression-free survival; while the secondary outcomes are the time to treatment failure, disease control rate, overall response rate, overall survival, R0 resection rate and incidence of adverse effects. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (No. 2019YF015-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT04289792.

Combined High-Dose LATTICE Radiation Therapy and Immune Checkpoint Blockade for Advanced Bulky Tumors: The Concept and a Case Report.

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. Since only a small fraction of the tumor volume receive high dose in a SFRT treatment, even with the anticipated bystander effects, total tumor eradications are rare. Backed by the evidence of immune activation of high dose radiation, it is logical to postulate that the combination of High-Dose LATTICE radiation therapy (HDLRT) with immune checkpoint blockade would be effective and could subsequently lead to improved local tumor control without added toxicities, through augmenting the effects of radiation in-situ vaccine and T-cell priming. We herein present a case of non-small cell lung cancer (NSCLC) with multiple metastases. The patient received various types of palliative radiation treatments with combined chemotherapies and immunotherapies to multiple lesions. One of the metastatic lesions measuring 63.2 cc was treated with HDLRT combined with anti-PD1 immunotherapy. The metastatic mass regressed 77.84% over one month after the treatment, and had a complete local response (CR) five months after the treatment. No treatment-related side effects were observed during the follow-up exams. None of the other lesions receiving palliative treatments achieved CR. The dramatic differential outcome of this case lends support to the aforementioned postulate and prompts for further systemic clinical studies.

Predictive value of carcinoembryonic antigen and carbohydrate antigen 19-9 related to downstaging to stage 0-I after neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

OBJECTIVE: To explore the value of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in predicting downstaging to stage 0-I cancer after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer. MATERIALS AND METHODS: We respectively investigated pretreatment CEA, pretreatment CA19-9, posttreatment CEA, posttreatment CA19-9, pre-post-CA19-9 ratio, and pre-post-CEA ratio in 674 patients with locally advanced rectal cancer receiving nCRT and determined the patients' thresholds by using the receiver operating characteristic curve analysis. The association between downstaging (stage 0-I after nCRT), pathological complete response, and clinicopathological parameters was evaluated using the Pearson χ2 test. The clinicopathological parameters which were found to be significantly associated with downstaging were analyzed by logistic regression models and were incorporated into a scoring system. RESULTS: Multivariate analysis showed that pretreatment CA19-9 level, posttreatment CEA level, pre-post-CEA ratio, and pre-post-CA19-9 ratio were significantly correlated with downstaging. Area under the curve of the scoring system was higher than that of parameters alone. CONCLUSION: The 4-factor scoring system with CA19-9 level, posttreatment CEA level, pre- post-CEA ratio, and pre-post-CA19-9 ratio is of more value in predicting downstaging to stage 0-I patients with locally advanced rectal cancer after nCRT than using the parameters alone.

Neoadjuvant chemotherapy may not benefit esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

BACKGROUND: To assess the efficacy of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (CRT). METHODS: The clinical data of patients with ESCC treated with chemoradiotherapy with or without NAC were collected and retrospectively reviewed. The overall survival, locoregional failure-free survival, and distant failure-free survival were analyzed statistically. RESULTS: A total of 60 patients fulfilled the inclusion criteria, of which 41 were treated with NAC-CRT and 19 were treated with CRT-alone. Patient characteristics were well balanced between the NAC-CRT and CRT-alone groups, except for the ECOG scores. The tumor response to NAC included 11 patients (26.8%) with partial response (PR), 25 patients (61.0%) with stable disease (SD), 5 patients (12.2%) with progression disease (PD), and no patients with complete response (CR). After CRT, 21 patients achieved CR (14 after NAC-CRT and 7 after CRT-alone), 30 had PR (19 and 11, respectively), 6 maintained SD (5 and 1, respectively), and 3 patients (all in the NAC-CRT group) developed PD. Twenty-nine patients (18 in NAC-CRT and 11 in CRT-alone) succumbed to the disease from locoregional or distant failure, one patient in the NAC-CRT group died of radiation pneumonitis, one patient in the CRT-alone group died from unknown reasons, and 29 patients remained alive. The overall survival, locoregional failure-free survival, and distant failure-free survival at 1 and 2 years in all the patients were 64.9% and 40.5%, 58.6% and 52.0%, and 85.7% and 79.3%, respectively. The overall survival, locoregional failure-free survival, and distant failure-free survival between the NAC-CRT group and the CRT-alone group were not significantly different. CONCLUSION: In patients with ESCC treated with definitive CRT, NAC treatment using the current regimen does not prolong overall survival, locoregional failure-free survival or distant failure-free survival. Further development of NAC treatment is urgently needed.

A sugarcane R2R3-MYB transcription factor gene is alternatively spliced during drought stress.

MYB transcription factors of the R2R3-MYB family have been shown to play important roles in many plant processes. A sugarcane R2R3-MYB gene (ScMYB2) and its two alternative forms of transcript (ScMYB2S1 and ScMYB2S2) were identified in this study. The deduced protein of ScMYB2S1 is a typical plant R2R3-MYB protein, while ScMYB2S2 encodes a truncated protein. Real-time qPCR analysis revealed that ScMYB2S1 is suppressed under PEG-simulated drought stress in sugarcane, while ScMYB2S2 is induced at later treatment stage. A senescence symptom was observed when ScMYB2S1 was injected into tobacco leaves mediated by Agrobacterium, but no symptom for ScMYB2S2. Further investigation showed that the expression levels of 4 senescence-associated genes, NtPR-1a, NtNYC1, NtCAT3 and NtABRE, were markedly induced in tobacco leaves after ScMYB2S1-injection, while they were not sensitive to ScMYB2S2-injection. Moreover, MDA and proline were also investigated after injection. Similarly, MDA and proline levels were induced by ABA and ScMYB2S1, while inhibited by ScMYB2S2. We propose that ScMYB2, by alternatively splicing two transcripts (ScMYB2S1 and ScMYB2S2), is involved in an ABA-mediated leaf senescence signaling pathway and play positive role in respond to drought-induced senescence in sugarcane. The results of this study provide information for further research in sugarcane stress processes.

Establishment and application of a loop-mediated isothermal amplification (LAMP) system for detection of cry1Ac transgenic sugarcane.

To meet the demand for detection of foreign genes in genetically modified (GM) sugarcane necessary for regulation of gene technology, an efficient method with high specificity and rapidity was developed for the cry1Ac gene, based on loop-mediated isothermal amplification (LAMP). A set of four primers was designed using the sequence of cry1Ac along with optimized reaction conditions: 5.25 mM of Mg(2+), 4:1 ratio of inner primer to outer primer, 2.0 U of Bst DNA polymerase in a reaction volume of 25.0 µL. Three post-LAMP detection methods (precipitation, calcein (0.60 mM) with Mn(2+) (0.05 mM) complex and SYBR Green I visualization), were shown to be effective. The sensitivity of the LAMP method was tenfold higher than that of conventional PCR when using templates of the recombinant cry1Ac plasmid or genomic DNA from cry1Ac transgenic sugarcane plants. More importantly, this system allowed detection of the foreign gene on-site when screening GM sugarcane without complex and expensive instruments, using the naked eye. This method can not only provide technological support for detection of cry1Ac, but can also further facilitate the use of this detection technique for other transgenes in GM sugarcane.