Effects of repetitive transcranial magnetic stimulation on fear of cancer recurrence and its underlying neuromechanism.

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism. Methods and analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment. Discussion: Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated. Ethics and dissemination: Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. Trial registration: NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023.

Preoperative chemoradiation-induced hematological toxicity and related vertebral dosimetry evaluations in patients with locally advanced gastric cancer: data from a phase III clinical trial.

BACKGROUND: To explore the hematological toxicity (HT) induced by neoadjuvant chemoradiotherapy (nCRT) compared with neoadjuvant chemotherapy (nCT) and to identify the appropriate vertebral body (VB) dosimetric parameters for predicting HT in patients with locally advanced gastric cancer (GC). METHODS: In the phase III study, 302 patients with GC from an ongoing multi-center randomized clinical trial (NCT01815853) were included. Patients from two major centers were grouped into training and external validation cohorts. The nCT group received three cycles of XELOX chemotherapy, while the nCRT received the same dose-reduced chemotherapy plus 45 Gy radiotherapy. The complete blood counts at baseline, during neoadjuvant treatment, and in the preoperative period were compared between the nCT and nCRT groups. The VB was retrospectively contoured and the dose-volume parameters were extracted in the nCRT group. Patients' clinical characteristics, VB dosimetric parameters, and HTs were statistically analyzed. Instances of HT were graded according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The receiver operating characteristic (ROC) curves were generated to identify the optimal cut-off points for dosimetric variables and verify the prediction efficiency of the dosimetric index in both training and external validation cohorts. RESULTS: In the training cohort, 27.4% Grade 3 + HTs were noted in the nCRT group and 16.2% in the nCT group (P = 0.042). A similar result was exhibited in the validation cohort, with 35.0% Grade 3 + HTs in the nCRT group and 13.2% in the nCT group (P = 0.025). The multivariate analysis of the training cohort revealed that V5 was associated with Grade 3 + leukopenia (P = 0.000), Grade 3 + thrombocytopenia (P = 0.001), and Grade 3 + total HTs (P = 0.042). The Spearman correlation analysis identified a significant correlation of V5 with the white blood cell nadir (P = 0.0001) and platelet nadir (P = 0.0002). The ROC curve identified the optimal cut-off points for V5 and showed that V5 < 88.75% could indicate a decreased risk of Grade 3 + leukopenia, thrombocytopenia, and total HTs in the training as well as the external validation cohorts. CONCLUSIONS: Compared with nCT, nCRT could increase the risk of Grade 3 + HT in patients with locally advanced GC. Dose constraints of V5 < 88.75% in irradiated VB could reduce the incidence of Grade 3 + HT.

Neoadjuvant chemoradiotherapy induced lymphopenia in gastric cancer and associations with spleen dosimetry and survival outcomes.

Background: Few studies concentrate on spleen dosimetry of radiotherapy for gastric cancer (GC). Although there is no consensus on the spleen dose-volume threshold for lymphopenia, several studies indicated that the higher the spleen dose, the higher the risk of lymphopenia. This study aimed to identify the appropriate spleen dosimetric parameters for predicting grade 4 + lymphopenia in patients with locally advanced GC. Material and methods: A total of 295 patients treated with nCRT and nChT from June 2013 to December 2021 at two major centers were included, of whom 220 were assigned to the training cohort and 75 to the external validation cohort. Results: Grade 4 + lymphopenia was more common in the nCRT than in the nChT group (49.5% vs. 0, P < 0.001 in the training cohort; 25.0% vs. 0, P = 0.001 in the external validation cohort). Age ≥ 60 years (P = 0.006), lower pretreatment absolute lymphocyte count (P = 0.001), higher spleen volume (SPV) (P = 0.001), and higher V20 (P = 0.003) were significant risk factors of grade 4 + lymphopenia for patients treated with nCRT. Patients with grade 4 + lymphopenia had significantly worse PFS (P = 0.043) and showed a negative correlation trend with OS (P = 0.07). Limiting V20 to < 84.5% could decrease the incidence of grade 4 + lymphopenia by 35.7%. The predictive effectiveness of the multivariable model in the training and external validation cohorts was 0.880 and 0.737, respectively. Conclusion: Grade 4 + lymphopenia during nCRT was more common than nChT, and was associated with a worse PFS in GC patients. Constraining the spleen V20 to < 84.5% may indirectly improve outcomes through lymphocyte preservation.

Predictors and trajectories of fear of cancer recurrence in Chinese breast cancer patients.

OBJECTIVE: Fear of cancer recurrence (FCR) is one of the most common and aversive psychological phenomena among cancer patients. This study explored the trajectories of FCR over the 18 months following discharge, and evaluated the associations between baseline demographic and clinical variables and FCR trajectories among Chinese women treated for breast cancer. METHODS: This is a longitudinal prospective study. All participants were asked to completed a battery of questionnaires (FCR-7, PHQ-9, GAD-7 and MPQ-VAS) at baseline, 6, 12, and 18 months after discharge. Generalized linear mixed model and group-based trajectory analyses were conducted. RESULTS: Three hundred women with breast cancer were recruited. Latent class growth modeling analysis showed that three-group trajectory solution was the best fitting (i.e., 'intermediate level-stable group' (63.3%), 'low level-increasing group' (18.3%), and 'high level-decreasing group' (18.3%). Patients reported significant higher FCR at baseline assessment compared to other time points. Significant positive associations were found between anxiety, depression and FCR. Patients who had no baseline depression (estimate = -2.14, 95% CI: -2.78-(-1.51), P < 0.001) or anxiety (estimate = -2.77, 95% CI: -3.44-(-2.10), P < 0.001) tended to report significant lower FCRs over time. Women with none/mild life stress exhibited significant lower FCRs than those with moderate/high life stress, and participants with a family history of cancer or pessimism reported higher FCRs. CONCLUSION: >60% of the breast cancer women showed intermediate level-stable FCRs over the 18 months after discharge. Baseline anxiety, depression, life stress, family cancer history and pessimism predicts higher FCR levels. Clinical teams responsible for continuing patient care following treatment should develop clearer strategies for management of FCR.

Group-based trajectory and predictors of anxiety and depression among Chinese breast cancer patients.

Background: The aim of the current study is to investigate the change in anxiety and depression amongst Chinese breast cancer patients and to identify causal associations between baseline variables and the trajectory of anxiety and depression within this identified group. Methods: This is a longitudinal prospective study. Three hundred women with breast cancer were recruited. Patient's depression and anxiety were repeatedly measured by PHQ-9 and GAD-7 at baseline, 6, 12, and 18 months after discharge. The SAS 9.4 PROC Traj procedure was used to examine the group-based trajectory of these recruited patients. Linear mixed models (LMM) were utilized to examine anxiety/depression changes over time, accounting for relevant baseline demographic and clinical factors. Results: About 26.3% of the participants reported none or very mild anxiety over time, 60.7% reported stable low-level anxiety, and the remaining 13.0% showed significantly decreasing trend in GAD total scores. Meanwhile, 10.7% of the participants reported none or very mild depressive symptoms over time, 66.0% reported stable PHQ total scores throughout the research period, and 23.3% were classified as the "high level-decreasing group". Patients reported significantly higher anxiety and depression scores in the first three assessments. Participants with no or mild life stress along with a positive personality tended to report lower anxiety and depression scores over time. Conclusion: Most of the breast cancer patients reported stable low-level anxiety and depression 18 months after discharge. Early assessment of optimism and stress levels among cancer patients might help identify people at risk of experiencing long-term anxiety and depression.

Alleviating Excessive Worries Improves Co-Occurring Depression and Pain in Adolescent and Young Adult Cancer Patients: A Network Approach.

Objective: Anxiety, depression, and pain are highly interactive with each other in adolescent and young adult (AYA) cancer patients. This study aims to map out the connectivity between anxiety, depression and pain symptoms amongst Chinese AYA cancer patients from the perspective of a network model. Methods: Two hundred and eighteen AYA patients, aged between 15 and 39 years at diagnosis; completed the Patient Health Questionnaire (PHQ), Generalized Anxiety Disorder (GAD), and McGill Pain Questionnaire-Visual Analogue Scale (MPQ-VAS). Network analyses were performed. Results: In all, 38.07% (95% CI = 31.58-44.57%) of the participants reported depression, 30.73% (95% CI = 24.56-36.91%) reported anxiety, and 14.22% (95% CI = 9.55-18.89%) reported current pain. The generated network illustrated that anxiety, depression and pain community were well connected. In the network, "having trouble relaxing" (GAD4, node strength = 1.182), "uncontrollable worry" (GAD2, node strength = 1.165), and "sad mood" (PHQ2, node strength = 1.144) were identified as the most central symptoms, while "uncontrollable worry" (GAD2, bridge strength = 0.645), "guilty" (PHQ6, bridge strength = 0.545), and "restlessness" (GAD5, bridge strength = 0.414) were the key bridging symptoms that connected different communities. Conclusion: Anxiety, depression and pain symptoms are highly interactive with each other. Alleviating AYA cancer patient's excessive worries might be helpful in improving the patient's co-occurring anxiety, depression and pain symptoms.

Comparisons of Metastatic Patterns, Survival Outcomes and Tumor Immune Microenvironment Between Young and Non-Young Breast Cancer Patients.

Background: Metastases are the main cause of breast cancer-related deaths. Breast cancer has a more aggressive phenotype and less favorable prognosis in young females than in older females. In this study, we aimed to compare the metastatic patterns, survival outcomes and tumor immune microenvironment of young and non-young breast cancer patients. Methods: Patients with a diagnosis of breast cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The significance of young age (≤40 years) in the metastatic profile and prognosis of breast cancer was investigated. The transciptome expression data were acquired from The Cancer Genome Atlas (TCGA) database. And the differentially expressed genes (DEGs) and primarily enriched function pathways were identified by comparing between young and non-young breast cancer samples, and tumor immune infiltrating cell types in the tumor microenvironment were compared. Results: A total of 281,829 female breast cancer patients were included in SEER: 18,331 young (6.5%) and 263,498 non-young (93.5%) women. The metastatic rates of bone, liver and distant lymph nodes (DLNs) in the young cohort were significantly higher than those in the non-young cohort. The most frequent two-site metastatic combination was bone and liver (0.61%) in the young cohort, whereas it was bone and lung (0.32%) in the non-young cohort. Breast cancer-specific survival (BCSS) was significantly shortened among those in the young cohort compared with those in the non-young cohort (p < 0.001). Young age was associated with significantly shorter BCSS only among patients with HR+/HER2- tumors (p < 0.001). The enriched biological pathways based on DEGs between two cohorts were related to the regulation of immune response and several metabolic processes. M2 macrophages were significantly abundant in non-young breast cancer than young breast cancer. Conclusion: Young and non-young breast cancer patients present with different metastatic patterns. Young age is a negative prognostic factor, particularly for HR+/HER2- breast cancer. The differences in metastatic patterns between young and non-young cohorts should be taken into account in the clinical management of metastatic breast cancer. The young breast cancer patients may gain better response to immunotherapy due to immune activated TME than non-young breast cancer.

Integrative Dissection of Novel Lactate Metabolism-Related Signature in the Tumor Immune Microenvironment and Prognostic Prediction in Breast Cancer.

The outcomes of some breast cancer patients remain poor due to being susceptible to recurrence, metastasis and drug resistance, and lactate metabolism has been described as a hallmark of cancer and a contributor to cancer progression and immune escape. Hence, it is worthy of seeking potentially novel biomarkers from lactate metabolism relevant perspectives for this particular cohort of patients. In this context, 205 available lactate metabolism-related genes (LMGs) were obtained by a search of multiple genesets, and the landscape of somatic mutation, copy number variation, and mRNA expression levels was investigated among these genes. Crucially, 9 overall survival-related LMGs were identified through univariate Cox regression analysis in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature, defined as Lactate Metabolism Index (LMI), was established with 5 OS-related LMGs using Least Absolute Shrinkage and Selection Operator (LASSO) Cox hazard regression analysis in TCGA training set, and then validated in two external cohorts (METABRIC and GSE96058). From the comprehensive results, breast cancer patients with high LMI had considerably poorer survival probability across all cohorts, and the degree of clinical features tended to be more severe as the LMI value increased. Furthermore, a prognostic nomogram incorporating LMI, age, and AJCC stage was constructed and demonstrated great prediction performance for OS of breast cancer patients, which was evaluated by the calibration plot and the decision curve analysis. Moreover, the potential effect of different LMI values on levels of immune checkpoints, tumor-infiltrating immune cells, and cytokines were explored ultimately, and patients with higher LMI values might gain an immunosuppressive tumor microenvironment that contributed to immune escape of breast cancer and inferior prognosis. Collectively, all findings in the study indicated the potential prognostic value of LMI in breast cancer, providing further implications for the role of lactate metabolism in breast cancer prognosis, tumor immune microenvironment, and immunotherapy.

Network connectivity between fear of cancer recurrence, anxiety, and depression in breast cancer patients.

BACKGROUND: Fear of cancer recurrence (FCR), anxiety, and depression are common psychological disturbances that frequently occur together among cancer patients. This study investigated network connectivity between FCR, anxiety, and depressive symptoms in a large representative sample of breast cancer patients. METHODS: This was a multicenter, cross-sectional study of 803 women with breast cancer. All participants completed the 4-item FCR scale, Generalized Anxiety Disorder Scale (GAD-7), and Patient Health Questionnaire (PHQ-9). Network analysis was conducted to investigate the network structure, central symptoms, bridge symptoms, and network stability of these disturbances. RESULTS: The generated network model indicated that anxiety and depression symptom communities were well-connected with each other, while FCR emerged as a distinct cluster with only a few weak links to anxiety and depression communities. Depressive and anxiety symptoms were more central than FCR symptoms were in the model. 'Having trouble relaxing' (#GAD4, strength = 1.147) was the most central node within the whole network, and 'strong feelings about recurrence' (#FCR4, strength = 0.531) was the least central node. Several anxiety symptoms (e.g., 'feeling afraid', 'uncontrollable worry', and 'restlessness') acted as important bridging symptoms connecting FCR, depression and anxiety communities. 'Uncontrollable worry' (#GAD2) had the highest node-specific predictive betweenness value. The network stability of this model was high. CONCLUSION: Depression and anxiety symptoms are highly interactive with each other among women with breast cancer. Conversely, FCR may have attenuated relations with anxiety and depression communities and emerged as a relatively independent, unique experience. Anxiety symptoms, particularly 'uncontrollable worry', acted as important trans-diagnostic symptoms that connected different communities. Findings suggested interventions to alleviate excessive worries and enhance feelings of personal control might be helpful in preventing or reducing related symptoms of FCR, anxiety and depression.

Fear of Recurrence in Chinese Cancer Patients: Prevalence, Correlates, and Network Analysis.

BACKGROUND: Fear of cancer recurrence (FCR) is a significant issue for most cancer patients. Until now, a detailed investigation of the structure of FCR and the interaction among its constituent elements is lacking. This study aims to investigate the phenomenon of FCR by means of network analysis in Chinese cancer patients. METHODS: This is a multi-center, cross-sectional study that included 996 cancer patients from southern China. All participants were assessed by the 7-item Chinese version Fear of Cancer Recurrence Scale (FCR-7). Multivariate logistic regression, and network analyses were conducted. Central symptoms (nodes) in the FCR network were identified. RESULTS: Among the 996 patients, 543 (54.52%) reported moderate FCR, and 137 (13.76%) reported high FCR. Chemotherapy (OR = 2.954, P = 0.016), and childhood severe illness experience (OR = 2.331, P = 0.016) were positively associated with high FCR, while higher monthly income (OR = 0.403, P = 0.046) was negative associated with high FCR. The node #FCR2 (Worried/anxious about recurrence) was the most central node within the FCR network (Strength = 1.190), while node #FCR6 (Examining for physical signs) was the least central node (Strength = 0.373). The edge FCR1-FCR2 ("Afraid"-"Worried/anxious") was the thickest and most saturated edge in the network. After controlling for age and gender, an almost identical network was obtained with respect to edges magnitude and strength. CONCLUSION: Fear of recurrence is a frequently reported issue among Chinese cancer patients. Patients with chemotherapy and childhood severe illness experience were more vulnerable and should be particularly monitored. Compared to behavioral component (i.e., body checking, overscreening and overtreatment) and cognitive component (i.e., intrusions), emotional component (i.e., worry/anxious) is more central to identify FCR and might be potential targets for further interventions.

Maternal and Paternal Depression During Pregnancy in China: Prevalence, Correlates, and Network Analysis.

BACKGROUND: Depression is a commonly seen mental health concern for mothers and fathers during their transition to parenthood. This study aims to provide new insights into the prevalence of maternal and paternal depression, its demographic and clinical correlates, and its symptom network among Chinese pregnant women and their partners. METHODS: In this multicenter, cross-sectional study, 769 pregnant women and their partners were assessed by Edinburgh Postnatal Depression Scale (EPDS) from June 15th to Sep 15th, 2020 in southern China. Convenient sampling method was used. Univariate analyses, multivariate logistic regression, and network analyses were conducted. Networks of maternal and paternal depression were compared. RESULTS: In total, 60 (EPDS total score ≥13, 7.80%, 95% CI: 5.90-9.70%) women and 23 (2.99%, 95% CI: 1.78-4.20%) of these women's partners reported depression. Physical comorbidities (OR=2.664, P=0.003) was the only factor that was found to significantly correlate with maternal depression. Network analyses showed that the resulting networks were well connected and that there was significant difference of network structure between maternal and paternal depression (M=0.330, P<0.001). Centrality plot indicated that "sad or miserable" (strength=1.097) was the most central symptom in the maternal depression network, while "scared or panicky" (strength=1.091) was the most central node in the paternal network. The edge between "things have been getting on top of me" - "able to laugh and see the funny side of things" (difference: 0.153, P=0.020), and "scared or panicky" - "the thought of harming myself" (difference: 0.084, P<0.001) was significantly stronger in women's partners than that in pregnant women. CONCLUSION: Maternal and paternal depression during pregnancy could result in significant negative consequences. Symptoms like "sad or miserable" and "scared or panicky" are critical and might be potential targets for further interventions. Evidence-based treatments, such as pharmacology, psychotherapy, community reinforcement and family training, might be beneficial for parents with depression during and after the pregnancy.

Mental Health Outcomes in Perinatal Women During the Remission Phase of COVID-19 in China.

BACKGROUND: Since the middle of March, the COVID-19 outbreak has been well contained in China. The prevention and control measures for the outbreak have been downgraded to a normalized level. However, until now, the change in level of psychological health amongst perinatal women during the remission phase of the COVID-19 outbreak has not been investigated in China. The aim of this current study was to assess the symptoms of anxiety, depression, insomnia and quality of life (QOL) in perinatal women and to identify potential risk factors associated with these symptoms. METHODS: This was a cross-sectional, hospital-based survey conducted between March 25th till June 5th, 2020 in southern China. Convenient sampling method was adopted. Women's anxiety, depression, insomnia symptoms and QOL was examined through standardized measurements. Multivariate logistic regression and Analysis of Covariance (ANCOVA) was conducted for the same. RESULTS: A total of 625 perinatal women completed the study; of them, 195 women (31.2%, 95%CI=27.56%-34.84%) reported anxiety, 120 (19.2%, 95%CI=16.10%-22.30%) reported depression, and 87 (13.9%, 95%CI=11.20%-16.64%) experienced symptoms of insomnia. Previous adverse experiences during pregnancy was a significant risk factor for anxiety (OR=1.628, 95%CI=1.069-2.480, P=0.023), depression (OR=1.853, 95%CI=1.153-2.977, P=0.011), and insomnia (OR=2.160, 95%CI=1.290-3.616, P=0.003). Participants having infected friends/families/colleagues were more likely to report anxiety (OR=2.195, 95%CI=1.245-3.871, P=0.007) and depression (OR=2.666, 95%CI=1.482-4.794, P=0.001). Those women whose regular check-ups were severely interrupted by the COVID-19 were also more likely to experience symptoms of anxiety (OR=2.935, 95%CI=1.701-5.062, P<0.001) and insomnia (OR=2.195, 95%CI=1.098-4.390, P=0.026). CONCLUSION: The COVID-19 pandemic does affect the mental health and well being of perinatal women. Increased attention should be paid to women who have infected friends/families/colleagues and those with previous adverse experiences during pregnancy. Coping strategies that relieve psychological stress during the COVID-19 outbreak should be provided to prevent adverse outcomes for women and their infants.

Suicidal Ideation in Newly-Diagnosed Chinese Cancer Patients.

OBJECTIVE: Suicide is one of the main reasons cited behind the death rate of cancer, and suicidal ideation (SI) is the first step toward it. This study aimed to investigate the prevalence and associates of suicidal ideation in newly-diagnosed Chinese cancer patients. METHODS: This multicenter study was conducted from January 2018 to September 2019. Eligible participants were asked to complete a Case Record Form (CRF), the Patient Health Questionnaire (PHQ-9), General Anxiety Disorder Questionnaire (GAD-7), Fear of Cancer Recurrence Questionnaire (FCRQ-7), and McGill Pain Questionnaire-Visual Analogue Scale (MPQ-VAS). Univariate analyses and multivariate logistic regression analyses were conducted for assessment. RESULTS: Out of 603 patients, 91 (15.1%, 95%CI: 12.23%-17.96%) reported suicidal ideation in the last 2 weeks. Physical comorbidities (OR=1.808, P=0.039), childhood adversity experience (OR=5.999, P=0.001), cancer pain (OR=1.828, P=0.047), depression (OR=2.811, P=0.013), and anxiety (OR=6.532, P<0.001) were significantly associated with suicidal ideation. It was also found that patients who regularly exercised were less likely to report suicidal thoughts (OR=0.172, P=0.007). CONCLUSION: Physical comorbidities, body ache, and mood disturbances are possible risk factors for suicidal ideation that warrant further attention in clinical practice. Preventive measures, such as systematic screening and arrangement for regular check-ups, could be beneficial to lower the risk of suicide.

High Fear of Cancer Recurrence in Chinese Newly Diagnosed Cancer Patients.

BACKGROUND: Fear of cancer recurrence (FCR) is common among cancer patients and of high clinical relevance. This study explores the prevalence and correlates of FCR in Chinese newly diagnosed cancer population. METHODS: This is a multicentre, cross-sectional study that includes 996 patients with mixed cancer diagnosis. All recently diagnosed patients completed a questionnaire consisting of the following: Fear of Progression Questionnaire-Short Form (FoP-Q-SF), General Anxiety Disorder Questionnaire (GAD-7), and Patient Health Questionnaire (PHQ-9). Univariate analyses, multivariate logistic regression analyses, and structural equation modeling (SEM) was performed to examine the association between tested variables and FCR. RESULTS: Of the 996 patients, 643 (64.6%) reported high FCR (scored ≥ 34 in the FoP-Q-SF). Chemotherapy (OR = 1.941), Childhood severe illness experience (OR = 2.802), depressive (OR = 1.153), and anxiety (OR = 1.249) symptoms were positively associated with high FCR, while higher monthly income (OR = 0.592) was negatively associated with high FCR. SEM indicated that emotional disturbances (anxiety and depression) directly influenced FCR, while emotional disturbances partly mediated the association between personal monthly income and FCR. CONCLUSION: High FCR is a frequently reported problem among newly diagnosed cancer patients. Various factors increased the likelihood of the development of FCR. Flexible psychological interventions are needed for patients with high FCR.

Self-Perceived Pain in Chinese Patients With Cancer.

BACKGROUND: Pain is one of the most burdensome and prevalent symptoms cancer patient report and it has severe negative impact on patient's quality of life. The aim of this study is to estimate the prevalence of pain and to test the association between demographic, clinical, psychological factors, and self-assessed pain in Chinese cancer population. METHODS: A total of 553 cancer patients were recruited in this cross-sectional study. Patient's basic demographic data was collected by a study-designed information sheet, and patient's pain, sleep disturbance and psychological distress were assessed by several validated measurements (MPQ-SF, AIS, FoP-Q-SF, PHQ-9, and GAD-7). Descriptive statistics and hierarchical multiple regression analyses were performed. RESULTS: Of the 553 patients, 411 (74.32%) patients reported that they experience some degree of pain. Fear of progression, anxiety, insomnia, and depressive symptoms were significantly associated with different subscales and the overall pain score in bivariate correlation matrix. Insomnia, depressive symptoms, and fear of cancer progression were significant independent factors of cancer pain on multivariate analyses. CONCLUSION: Psychological factors play a great role in the relationship between objective pathophysiology and patient's subjective experience of pain. It is important to evaluate each individual in detail with respect to psychological distress and pain severity when planning treatment and rehabilitation.

Fear of cancer recurrence, anxiety and depressive symptoms in adolescent and young adult cancer patients.

Background: Previous studies have indicated that younger age is consistently associated with high levels of fear of cancer recurrence (FCR), anxiety and depression. However, the associations among these variables in adolescent and young adult (AYA) cancer patients are not clear. This study explores the prevalence and correlates of FCR, anxiety and depressive symptoms in Chinese AYA cancer population. Methods: This is a cross-sectional study that includes 249 patients aged between 15 and 39 yrs at the time of cancer diagnosis. Patient's sociodemographic, clinical as well as psychological characteristics were collected by an information sheet, the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), General Anxiety Disorder Questionnaire (GAD-7) and Patient Health Questionnaire (PHQ-9). Descriptive statistics and multivariate analyses were conducted. Results: Eighty-nine (35.74%) patients experienced dysfunctional level of FCR, eighty-two (32.93%) patients experienced anxiety symptoms and ninety-six (38.55%) reported depressive symptoms. In multivariate analyses, being single, pessimistic, having more concurrent stressful life events and physical comorbidity were independently associated with higher FCR, anxiety and depressive symptoms. Patients who were not engaging in radiotherapy were more likely to report higher anxiety level. Conclusion: FCR, anxiety and depressive symptoms are frequently reported problems among AYA cancer patients. Age-appropriate and flexible psychological interventions are needed for this high-risk population.

Fear of cancer recurrence in adolescent and young adult cancer survivors: A systematic review of the literature.

OBJECTIVE: The current systematic review aims to provide an overview of fear of cancer recurrence (FCR) in adolescent and young adult cancer survivors (15-39 years at cancer diagnosis, AYAs). METHODS: MEDLINE, PubMed, PsycINFO, and Embase databases were independently searched to identify relevant quantitative articles. PRISMA systematic review procedures were followed with quality assessment. RESULTS: Seventeen studies were included in the current review. All were quantitative studies that utilized a cross-sectional study design. Seven articles reported results of FCR prevalence, six studied determinants related to FCR, and 11 articles provided information about consequences of FCR. Prevalence of FCR ranged from 31% to 85.2% among AYA survivors. Associations between sociodemographic/clinical variables and FCR were inconsistent. Psychological distress and higher treatment intensity were positively associated with higher FCR levels. Lower scores on levels of physical, psychological functioning, and overall health-related quality of life (QoL) were identified as consequences of increased FCR. CONCLUSION: FCR appears to be a prevalent concern among adolescent and young adult cancer populations. Adequate assessment to determine need for support and intervention is still required. Longitudinal studies in AYAs are warranted to understand the development and potential influence of FCR. Age-appropriate and flexible psychological care would be more successful potentially with this crucial background information.

Factors associated with fear of progression in chinese cancer patients: sociodemographic, clinical and psychological variables.

OBJECTIVE: Fear of progression (FoP) is a widespread problem among cancer patients and is considered to be one of the most distressing psychological consequences of cancer. The aim of this study was to investigate the association of sociodemographic, clinical, and psychological variables to FoP in Chinese cancer patients. METHODS: In this cross-sectional study, six hundred and thirty-six cancer patients were recruited. All participants were asked to complete a personal information sheet, the Chinese version of Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Questionnaire (GAD-7). Descriptive statistics and hierarchical multiple regression was conducted to analyze the data. RESULTS: Hierarchical multiple regression revealed that childhood severe illness experience (P = .011), stress (P < .001), anxiety (P < .001), depressive symptom (P < .001) and personality (P = .042) were independently predictive of higher FoP. The final regression model explained up to 40.0% (adjusted R square: 38.8%) of the observed variance. CONCLUSION: There are a number of factors that increase the likelihood of the development of FoP. The findings underline the necessity to provide effective psychological intervention for patients with high FoP in the future.

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy.

[Observation of radiobiological characteristics in a HepG2 cell line with mitochondrial DNA deletion].

OBJECTIVE: To study the radiobiological characteristics of a HepG2 cell line with mitochondrial DNA (mtDNA) deletion. METHODS: HepG2 cells were cultured in a medium containing ethidium bromide, acetylformic acid and uracil. The HepG2 cell line with mtDNA deletion (ρ(0)HepG2 cells) were acquired after 30 subcultures by limited dilution cloning. The cell survival was then observed in the absence of acetylformic acid and uracil, and the total mtDNA deletion in the cells was confirmed by PCR. The radiosensitivity of HepG2 and ρ(0)HepG2 cells was evaluated by exposure to gradient doses of 6 MV X ray irradiation. The cell apoptosis was assessed following a 2 Gy X-ray exposure with Hochest33342 staining, and the invasiveness of ρ(0)HepG2 cells was measured by Transwell assay. RESULTS: HepG2 cells could survive 30 subcultures in the presence of ethidium bromide, and massive cell death occurred after removal of acetylformic acid and uracil from the medium. PCR confirmed total mtDNA deletion from ρ(0)HepG2 cells, whose α/ß value was significantly lower than that of HepG2 cells. ρ(0)Hep-G2 cells showed an obviously lowered cell apoptosis rate following X-ray exposure with enhanced cell invasiveness. CONCLUSION: HepG2 cells can be induced by ethidium bromide into ρ(0)HepG2 cells with an increased radiation resistance, anti-apoptosis ability and cell invasiveness.