post-RT Group Research Articles

Post-irradiation dysbiosis in patients with nasopharyngeal carcinoma having received radiotherapy – A pilot study

ObjectiveTo compare the changes in the sinonasal mucosa microbiome in patients with nasopharyngeal carcinoma (NPC) before and after radiotherapy (RT), and to explore the pathogenesis of post-irradiation chronic rhinosinusitis (PI-CRS) and its association with dysbiosis. Study DesignProspective cohort study. SettingUnicenter, Tertiary referral hospital. MethodsIncluded patients newly diagnosed with NPC. Samples of ostiomeatal complex mucosa were collected before and after RT. Microbiome analysis was conducted using 16S rRNA sequencing, and statistical analysis was performed. Subgroup analyses based on RT modality (proton therapy or photon therapy) ResultsTotal of 18 patients were enrolled in the study, with 62.1% receiving intensity-modulated proton therapy (IMPT). Corynebacterium was the most dominant genus identified in both the pre- and post-RT groups, with a visible increase in Staphylococcus and a decrease in Fusobacterium genus in post-RT group. Alpha-diversity did not significantly differ between groups, although the beta-diversity analysis revealed a dispersed microbiota in the post-RT group. The functional prediction indicated a higher relative abundance of taxonomies associated with biofilm formation in the post-RT group. The subgroup analysis revealed the above changes to be more significant in patients who received photon therapy (Intensity modulated radiation therapy, IMRT). ConclusionsThis is the first study to analyze the microbiome of patients with NPC after IMPT. We identified similarities between the post-RT microenvironment and that reported in patients with CRS, with a more apparent change noted in patients treated with IMRT. Further investigation is required to further elucidate the pathogenesis of PI-CRS and its relationship to post-RT dysbiosis, particularly IMPT.

Role of prognostic nutritional index in postoperative radiotherapy for non-small cell lung cancer.

The prognostic nutritional index (PNI) is known to be correlated with clinical outcomes in non-small cell lung cancer (NSCLC) patients. However, its role has not been studied in patients who have undergone postoperative radiotherapy (PORT). This study aimed to investigate the relationship between PNI and survival and recurrence in NSCLC patients with PORT. We reviewed 97 stage I-III NSCLC patients who received PORT between January 2006 and December 2016 at our institution. We obtained PNI values for both pre-RT (within 1 month before PORT) and post-RT (within 2 months after PORT) by using serum albumin and lymphocyte count. A cutoff value for PNI was determined by the receiver operating characteristic curve (ROC). The median follow-up period was 52.8 months. The ROC curve of post-RT PNI exhibited a higher area under the curve (AUC 0.68, cut-off: 47.1) than that of pre-RT PNI (AUC 0.55, cutoff: 50.3), so the group was divided into high post-RT PNI (> 47.1) and low post-RT PNI ( 47.1). The five-year overall survival rate (OS) was 66.2% in the high post-RT group, compared with 41.8% in the low post-RT PNI group (p = 0.018). Those with both low pre-RT and low post-RT PNI had the worst five-year OS of 31.1%. Post-RT PNI (HR 0.92, p = 0.003) was an independent risk factor for mortality. PNI after PORT was significantly associated with survival. This finding suggests that PNI can be used as a prognostic marker.

Interaction of chemotherapy and radiotherapy in altering the shape of subcortical structures in patients with nasopharyngeal carcinoma.

Neuroimaging studies have found significant structural alterations of the cerebral cortex in patients with nasopharyngeal carcinoma (NPC) following radiotherapy (RT) or concomitant chemoradiotherapy (CCRT), while their effects on the shape of subcortical structures remain largely unknown. In this study, we investigated the subcortical shape alterations between three groups: 56 untreated NPC patients (pre-RT group), 37 RT-treated NPC patients (post-RT group), and 108 CCRT-treated NPC patients (post-CCRT group). Using FSL-FIRST, we found that, compared with the pre-RT group, the post-CCRT group exhibited significant inward atrophy in the bilateral thalamus, bilateral putamen, left pallidum, and left caudate and outward inflation in the left caudate, while the post-RT group only exhibited inward atrophy in the bilateral thalamus. In addition, greater maximum dosage of RT for temporal lobes was associated with more severe inward atrophy of the bilateral thalamus in treated NPC patients. These results indicated that there may be an interaction between RT and CT that can cause subcortical damage.

Structure-Function Decoupling: A Novel Perspective for Understanding the Radiation-Induced Brain Injury in Patients With Nasopharyngeal Carcinoma.

Radiation-induced functional and structural brain alterations are well documented in patients with nasopharyngeal carcinoma (NPC), followed by radiotherapy (RT); however, alterations in structure–function coupling remain largely unknown. Herein, we aimed to assess radiation-induced structure–function decoupling and its importance in predicting radiation encephalopathy (RE). We included 62 patients with NPC (22 patients in the pre-RT cohort, 18 patients in the post-RT-RE+ve cohort, and 22 patients in the post-RT-RE–ve cohort). A metric of regional homogeneity (ReHo)/voxel-based morphometry (VBM) was used to detect radiation-induced structure–function decoupling, which was then used as a feature to construct a predictive model for RE. Compared with the pre-RT group, patients in the post-RT group (which included post-RT-RE+ve and post-RT-RE–ve) showed higher ReHo/VBM coupling values in the substantia nigra (SN), the putamen, and the bilateral thalamus and lower values in the brain stem, the cerebellum, the bilateral medial temporal lobes (MTLs), the bilateral insula, the right precentral and postcentral gyri, the medial prefrontal cortex (MPFC), and the left inferior parietal lobule (IPL). In the post-RT group, negative correlations were observed between maximum dosage of RT (MDRT) to the ipsilateral temporal lobe and ReHo/VBM values in the ipsilateral middle temporal gyrus (MTG). Moreover, structure–function decoupling in the bilateral superior temporal gyrus (STG), the bilateral precentral and postcentral gyri, the paracentral lobules, the right precuneus and IPL, and the right MPFC exhibited excellent predictive performance (accuracy = 88.0%) in identifying patients likely to develop RE. These findings show that ReHo/VBM may be a novel effective imaging metric that reflects the neural mechanism underlying RE in patients with NPC.

Localization and restaging of carcinoma prostate by 68Gallium prostate-specific membrane antigen positron emission tomography computed tomography in patients with biochemical recurrence.

Introduction:Radical prostatectomy (RP) and radical radiotherapy (RT) are well established primary curative options for localized prostate cancer. Despite technical improvements, prostate-specific antigen (PSA)-recurrence after RP and RT is a common clinical scenario. We aimed to assess the role of 68Gallium (68Ga) prostate-specific membrane antigen positron emission tomography computed tomography (PSMA PET/CT) in patients with biochemical recurrence of prostate cancer after RP or RT for the detection and localization recurrent and metastatic disease.Materials and Methods:We ambispectively (70 retrospective and 100 prospective) analyzed the data of men with biochemical recurrence post-RP and post-RT who were evaluated by 68Ga PSMA PET/CT at our institute. We aimed to assess the relationship between serum PSA levels and the probability of having a positive scan in patients with recurrent prostate cancer.Results:The study included 170 men, all had adenocarcinoma of the prostate, 124/170 had previous RP and 46/170 had prior RT. The median serum PSA in the RP group was 1.8 ng/ml and 5.2 ng/ml in the RT group. In the post-RP cohort, the detection rate of 68Ga PSMA PET/CT was 39.3% for PSA 0.2 to <0.5 ng/ml, 47.3% for PSA 0.5 to <1 ng/ml, 68.4% for PSA 1 to <2 ng/ml and 93.1% for PSA ≥2 ng/ml. In the post-RT group, the detection rate was 88.8% for PSA 2 to <4 ng/ml and 100% for PSA ≥4 ng/ml.Conclusions:68Ga PSMA PET/CT provides a novel imaging modality for the detection of prostate cancer recurrence and metastases at low posttreatment PSA levels, which may help in directing appropriate salvage treatments.

Radiation-induced changes in small world network in patients with nasopharyngeal carcinoma: a three-dimensional structure MRI imaging study

Objective To investigate the radiotherapy (RT)-induced changes in the brain structural network in patients with nasopharyngeal carcinoma (NPC). Methods Three-dimensional structural magnetic resonance data (3D-T1W) was adopted to investigate the structural network in 103 patients with NPC before and after receiving RT. The structural networks were then reconstructed using 3D-T1W. The radiation-induced changes in topology properties of small world network were analyzed by using graph theoretical analysis. Results Patients showed small world properties before and after RT. Compared with the pre-RT group, the global and local efficiency were lower, the shortest path length was longer and the clustering coefficient was less in the post-RT group. In addition, the hub regions in the post-RT group were significantly different from those in the pre-RT group, mainly located in the left rolandic operculum, right inferior frontal gyrus, right parahippocampal gyrus, right lingual gyrus, bilateral supramarginal gyrus, left superior temporal gyrus and temporal pole of the right middle temporal gyrus. Conclusion It is speculated that RT leads to high efficiency of network topology and information transmission, which provides a novel perspective for exploring the RT-induced brain changes, diagnosis of RT-induced injury and evaluation of RT efficacy. Key words: Nasopharyngeal neoplasm/radiotherapy; Voxel-based morphometry; Gray matter; Small world property

The microdamage of " morphologically normal white matter" in patients with nasopharyngeal carcinoma after radiotherapy and its correlation with the irradiation dose

Objective To explore the correlation between microdamage in white matter and radiotherapy dose at early stage after radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). Methods Thirty-three patients who were initially diagnosed with NPC were recruited and received diffusion tensor imaging (DTI) scan and neuro-cognitive scale test within 1 week before RT and the first day after RT. DTI-related characteristic parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ‖), and radial diffusivity (λ⊥) were calculated based on whole-brain voxel analysis method. Paired t-test was conducted to evaluate statistical significance between pre-RT and post-RT groups. In the subgroup analysis, all the subjects were divided into 3 groups according to the average dose of temporal lobe, and each group was set with an equal dose interval range. The DTI-related parameters of whole brain pre-RT and post-RT in each group were statistically compared. All the statistical results were corrected by FDR with a threshold of P 100. Results FA, MD, λ‖ and λ⊥in the post-RT group significantly differed compared with those in the pre-RT group (P<0.05). The values of FA, MD, λ‖ and λ⊥were 0.455±0.016, (9.893±0.403)×10-4, (13.441±0.412)×10-4 and (8.231±0.429)×10-4, respectively. Subgroup analysis showed that the extent and degree of λ‖ and λ⊥ changes were exacerbated with the increase of the average dose of temporal lobe after RT. Particularly in high-dose group, the average dose range was 25-35 Gy and the extent of regions with significant changes was significantly larger than those in the medium-dose (15-25 Gy) and low-dose groups (5-15 Gy)(P<0.05). Conclusions DTI can be utilized to detect brain tissue microdamage in NPC patients at early stage after RT. The average radiation dose of temporal lobe may be one of the reasons for the severity of cerebral microdamage. In the future, DTI technique may be useful for guiding exposure dose of organs at risk during RT planning and to evaluate the cohort with a high risk of cerebral microdamage at early stage after RT, thereby protecting normal cerebral tissues to the maximum extent. Key words: Diffusion tensor imaging; Nasopharyngeal neoplasm/radiotherapy; Radiation-induced brain injury; Dosimetry

Chemotherapy Potentially Facilitates the Occurrence of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma Following Radiotherapy: A Multiparametric Magnetic Resonance Imaging Study

Radiation encephalopathy (RE) is deemed to be a disease induced only by radiotherapy (RT), with the effects of chemotherapeutic agents on the brains of nasopharyngeal carcinoma (NPC) patients being largely overlooked. In this study, we investigated structural and functional brain alterations in NPC patients following RT with or without chemotherapy. Fifty-six pre-RT, 37 post-RT, and 108 post-CCRT (concomitant chemo-radiotherapy) NPC patients were enrolled in this study. A surface-based local gyrification index (LGI) was obtained from high resolution MRI and was used to evaluate between-group differences in cortical folding. Seed-based functional connectivity (FC) analysis of resting-state fMRI data was also conducted to investigate the functional significance of the cortical folding alterations. Compared with the Pre-RT group, patients in the Post-CCRT group showed LGI reductions in widespread brain regions including the bilateral temporal lobes, insula, frontal lobes, and parietal lobes. Compared with the Post-RT group, patients in the Post-CCRT group showed LGI reductions in the right insula, which extended to the adjacent frontal lobe. Seed-based FC analysis showed that patients in the Post-CCRT group had lower FC between the insula and the left middle frontal gyrus than patients in the Pre-RT group. The follow-up results showed that patients in the Post-CCRT group had a much higher RE incidence rate (20.4%) than patients in the Post-RT group (2.7%; P = 0.01). These findings indicate that chemotherapy potentially facilitated the occurrence of RE in NPC patients who underwent radiotherapy.

Radiation-Induced Changes in Structural Network in Patients with Nasopharyngeal Carcinoma

Radiation therapy (RT) is the standard radical treatment for nasopharyngeal carcinoma (NPC), and has produced excellent effects in terms of survival rate [1, 2]. However, one of the serious complications gave rise by the RT is brain injury. Previous studies have found that RT could cause brain structural abnormalities on gray matter and white matter. Nevertheless, the RT effects on the network level should be further investigated. Herein, we explored changes on the structural network for patients with NPC induced by RT. The structural magnetic resonance data (sMRI) were used to investigate the structural network in 20 NPC patients after and before radiotherapy. After constructing the structural network, we examined the radiation-induced changes in topology properties of small world network using graph theoretical analysis. Our results found that both the before and after radiotherapy groups showed small world properties. Compared with the before radiotherapy (pre-RT) group, the after radiotherapy (post-RT) group had lower global and local efficiency, longer shortest path length, and less clustering coefficient. In addition, the hub regions in the post-RT group were significantly different from the pre-RT group. Our findings exhibited the architecture of network topology and information transfer efficiency became poor in post-RT group. We speculated radiation therapy might induce the differences. The results can provide a new perspective to explore and diagnose radiation-induced brain injury and evaluate the effect of radiotherapy.

Noninvasive evaluation of vaginal fibrosis following radiotherapy for gynecologic malignancies: A feasibility study with ultrasound B-mode and Nakagami parameter imaging

This study's purpose is to develop a quantitative ultrasound technology to evaluate radiation-induced vaginal fibrosis. Radiation therapy (RT) is an important treatment modality for most gynecologic (GYN) malignancies. However, vaginal fibrosis is a common chronic side-effect, affecting 80% of women post vaginal or pelvic RT. Vaginal fibrosis leads to pain, sexual dysfunction, and poor quality of life. The authors propose a novel ultrasound approach that combines conventional B-mode imaging with Nakagami parameter imaging to quantitatively evaluate post-RT vaginal injury. From the B-mode image, vaginal wall thickness and echo intensity were calculated to capture the anatomy and echogenicity of the vaginal wall. From Nakagami imaging, two statistical parameters, Nakagami probability density function (PDF) and Nakagami shape, were computed to measure the concentration and arrangement of vaginal tissue microstructures. This novel ultrasound imaging concept was investigated in a pilot study of 12 patients, who were previously diagnosed and treated for endometrial cancer. The 12 participants were stratified into two groups: (1) the control group consisted of 6 patients who received surgery (hysterectomy) alone and (2) the post-RT group consisted of 6 patients who received surgery plus radiotherapy, with a follow-up time of 12-38 months. Each participant underwent one transvaginal ultrasound study (6 MHz). Three transverse images of the anterior vaginal wall were acquired in a 2 cm step from the apex (vaginal cuff) to the introitus (vagina opening). The vaginal wall thickness, echo intensity, Nakagami PDF, and Nakagami parameter were calculated to evaluate radiation-induced vaginal fibrosis. Both B-mode and Nakagami methods showed significant differences in parameters between the post-RT and nonirradiated vaginal walls. Compared with the control group, the vaginal wall thickness of the post-RT group increased by 153.2% (p = 0.002), the echo intensity increased by 11.6% (p = 0.017), the Nakagami PDF increased by 72.3% (p < 0.001), and the Nakagami shape valued increased by 33.0% (p = 0.028). Vaginal fibrosis appears to be associated with a thickened vaginal wall, higher echogenicity, as well as increased Nakagami PDF and shape parameters. This pilot study shows the authors' quantitative ultrasound approach combining B-mode and Nakagami imaging is a promising imaging method to evaluate vaginal fibrosis. This imaging method may be useful as physicians try to address vaginal toxicities and sexual dysfunction in women after radiotherapy for GYN malignancies.

How reliable is contact endoscopy of the nasopharynx in patients with nasopharyngeal cancer?

To evaluate diagnostic reliability of contact rhinoscopy in patients with nasopharyngeal carcinoma. A cross-sectional randomized single-blinded study was carried out to evaluate the reliability of the findings of contact rhinoscopy in patients with nasopharyngeal carcinoma assessed by different observers. Random images of contact endoscopy of 157 subjects including normal patients and patients with nasopharyngeal carcinoma, both prior to external beam radiation therapy (RT), the non-RT group, and after external beam radiation therapy, the post-RT group, were available for analysis. Three independent observers of varying clinical experience and histopathologic knowledge viewed the images and made a diagnosis for each image. The diagnosis of each image was correlated with the histology of the biopsy from the corresponding patient. In the non-RT group, Kappa values for inter- and intraobserver reliability to differentiate normal epithelium from primary nasopharyngeal carcinoma were 0.894, 1.000, 0.794 and 0.694, 1.000, 0.776 for the house officer, radiologist, and pathologist, respectively. There were no significant differences in interobserver and intraobserver reliabilities between the assessors. In the post-RT group, Kappa values for the inter- and intraobserver reliability to diagnose recurrent carcinoma or atypia, squamous metaplasia, and radiation change for the three observers were 0.820, 0.718, 0.775 and 0.731, 0.622, 0.734, respectively. There were no significant differences in interobserver and intraobserver reliabilities between the assessors. The clinical diagnosis of nasopharyngeal carcinoma by contact endoscopy is highly reliable and is not dependent on the clinical experience or knowledge of histopathology of the observers.