The study, led by Xun Jiang, Guoliang Liao, Xin Yan, and colleagues at Fujian Medical University Union Hospital and collaborating institutions, followed 167 patients with clinical stage IB to IIIB NSCLC who received neoadjuvant therapy followed by curative-intent surgical resection between 2018 and 2022. Rather than measuring distress at a single moment, the team assessed it at three critical junctures: before the start of neoadjuvant therapy, immediately before surgery, and three months after the operation. This longitudinal design is what sets the work apart, because it captures not just whether patients are distressed, but how their distress behaves across the most demanding phases of multimodality cancer treatment.

To quantify emotional distress, the researchers deployed four well-validated screening instruments: the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS-A and HADS-D), the Generalized Anxiety Disorder-7 questionnaire (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9). For the primary analyses, a patient was considered positive for emotional distress if they scored positively on any of these measures at a given time point. This broad definition deliberately casts a wide net, capturing the full spectrum of anxiety and depressive symptoms rather than requiring a formal psychiatric diagnosis. The approach reflects a growing consensus in psycho-oncology that subthreshold distress, while less visible, can still carry clinical weight.

The central analytical move was to classify each patient into one of three trajectory groups based on their pattern of distress across the three assessments. Patients who never screened positive were labeled persistently negative (ED0); those who screened positive at some but not all time points were labeled intermittently positive (ED1); and those who screened positive at every assessment were labeled persistently positive (ED2). The distribution was revealing: 47.3 percent of patients remained persistently negative, 29.9 percent were intermittently positive, and 22.8 percent — nearly one in four — carried persistent distress through the entire treatment arc. Median follow-up extended to 46 months, long enough to observe meaningful differences in survival outcomes.

The survival curves diverged dramatically. Three-year overall survival was 89.9 percent in the persistently negative group, 71.9 percent in the intermittently positive group, and just 57.9 percent in the persistently positive group, a gradient that was highly statistically significant across the cohort. In other words, patients whose emotional distress never lifted fared substantially worse than those who remained psychologically resilient throughout treatment, with the intermittent group occupying an intermediate position. This dose-response-like pattern — where worse distress trajectories correspond to progressively worse survival — strengthens the plausibility of a genuine association rather than a statistical fluke.

The association survived rigorous statistical adjustment. In multivariable Cox regression models that accounted for established clinicopathologic prognostic factors, persistent emotional distress remained independently associated with poorer overall survival, with a hazard ratio of 5.04 (95 percent confidence interval, 2.55 to 9.99) compared with persistently negative patients. The effect on progression-free survival was similarly robust, with a hazard ratio of 3.26 (95 percent confidence interval, 1.87 to 5.69). A hazard ratio of five is a large effect by oncology standards, comparable in magnitude to some of the strongest clinicopathologic predictors, which is precisely why the finding demands attention — and, the authors caution, further validation before distress screening is elevated to a formal prognostic tool.

The researchers also explored whether distress data could improve predictive performance when combined with conventional clinical variables. Models integrating the emotional distress trajectory with clinicopathologic factors achieved an area under the curve (AUC) of 0.86 for predicting overall survival and 0.80 for progression-free survival. These are respectable discrimination values, suggesting that psychological trajectories carry information that complements, rather than merely duplicates, what tumor stage, histology, and treatment response already reveal. The authors are careful, however, to note that the added prognostic value of distress assessment beyond standard variables requires confirmation in independent cohorts before it can inform clinical decision-making.

Why might persistent emotional distress be biologically linked to cancer outcomes? The study itself is observational and cannot establish causation, but the surrounding literature offers several plausible mechanisms. Chronic psychological stress activates the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, elevating cortisol and catecholamines that can reshape the tumor microenvironment, modulate immune surveillance, and potentially blunt the efficacy of treatments — including the immunotherapies and chemotherapies now standard in neoadjuvant NSCLC protocols. Recent work has even suggested that pretreatment distress may influence response to immune checkpoint inhibitors in lung cancer, hinting that the cancer-immune dialogue is sensitive to the patient’s psychological state. Persistent distress may also reflect or exacerbate behaviors that affect outcomes, from reduced adherence to follow-up care to diminished resilience during postoperative recovery.

There is also the possibility of reverse causation — that persistent distress is a marker, not a driver, of underlying disease severity. Patients whose cancer is biologically more aggressive may feel worse, respond less well to neoadjuvant therapy, and experience more complications, generating distress that merely mirrors their prognosis. The multivariable adjustment for clinicopathologic factors partially addresses this concern, and the fact that distress was measured before treatment outcomes were known helps with temporality, but only prospective interventional studies — for example, trials testing whether effective psychological treatment improves survival — could settle the question of causality. Such trials would be ambitious but not unprecedented, given prior evidence that psychological interventions can influence immune parameters and quality of life in cancer patients.

The practical implications are nonetheless immediate. Clinical guidelines from the National Comprehensive Cancer Network and the American Society of Clinical Oncology already recommend routine distress screening in cancer care, yet screening is often performed once, at diagnosis, and its results rarely feed into prognostic discussions. This study suggests that a single snapshot may miss the patients who matter most: the roughly one in five whose distress persists across the treatment journey. Repeated, brief screening with instruments like the HADS, GAD-7, or PHQ-9 at each treatment milestone is feasible in busy thoracic oncology clinics, and patients flagged with persistent positivity could be prioritized for psycho-oncology referral, pharmacologic treatment, or intensified supportive care. As neoadjuvant immunotherapy transforms the standard of care for resectable NSCLC, the patients undergoing this demanding treatment sequence may represent a group in whom psychological monitoring is not just compassionate care, but a potential component of prognostic evaluation — one that costs little to implement and could meaningfully change how clinicians see the whole patient.

Subject of Research: Longitudinal emotional distress trajectories and survival outcomes in patients with resectable non–small cell lung cancer treated with neoadjuvant therapy and surgery

Article Title: Prognostic significance of dynamic emotional distress during neoadjuvant therapy and surgery for resectable non–small cell lung cancer

Article References: Jiang, X., Liao, G., Yan, X., Lin, Y., Huang, R., Cheng, L., Xu, G., Zheng, B., Chen, C., & Yang, Z. (2026). Prognostic significance of dynamic emotional distress during neoadjuvant therapy and surgery for resectable non–small cell lung cancer. Supportive Care in Cancer, 34(10), Article 1027. https://doi.org/10.1007/s00520-026-11260-2

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11260-2

Keywords: non-small cell lung cancer, emotional distress, neoadjuvant therapy, prognosis, overall survival, progression-free survival, HADS, GAD-7, PHQ-9, psycho-oncology, distress screening, supportive care

The research team recruited 332 adults with a mean age of 34.85 years, who completed a battery of validated online questionnaires. Participants reported on their history of childhood sexual abuse, their symptoms of complex PTSD as measured by the International Trauma Questionnaire, their binge eating severity on the Binge Eating Scale, their night eating behaviors on the Night Eating Questionnaire, and their general emotional distress on the Brief Symptom Inventory-18, which captures depression, anxiety, and somatization. A Satisfaction with Life Scale rounded out the survey, allowing the researchers to situate eating pathology within a broader picture of well-being. The sample was predominantly female, predominantly Jewish, and non-clinical, meaning participants were recruited from the community rather than from treatment settings.

Complex PTSD is a diagnostic construct that extends beyond the classic features of post-traumatic stress disorder. In addition to re-experiencing, avoidance, and a persistent sense of threat, CPTSD encompasses disturbances in self-organization: profound difficulties with emotion regulation, a negative self-concept, and problems in relationships. These additional features are thought to arise particularly after prolonged or repeated interpersonal trauma, such as childhood sexual abuse, which betrays the child’s trust in caregivers or familiar adults and disrupts the development of a stable sense of self. The researchers hypothesized that this broader trauma syndrome, rather than trauma exposure alone, would be the proximal driver of disordered eating, and that the emotional distress dimensions of depression, anxiety, and somatization would carry the signal from trauma to eating behavior.

The statistical engine of the study was structural equation modeling, a technique that allows researchers to test an entire network of hypothesized relationships simultaneously rather than examining correlations one pair at a time. The fitted model showed excellent fit to the data, with a comparative fit index of 0.99, a root mean square error of approximation of 0.079, and a standardized root mean square residual of 0.05, values that fall within or near conventional thresholds for a well-fitting model. Within that model, childhood sexual abuse strongly predicted CPTSD symptoms, with a standardized path coefficient of 0.39, indicating a substantial association. CPTSD, in turn, was linked to both binge eating and night eating symptoms, but the routes connecting them diverged in ways the authors had not fully anticipated.

The pathway to night eating syndrome ran almost entirely through anxiety. Night eating syndrome is characterized by recurrent episodes of eating after the evening meal or during the night, often with full awareness and frequently without the compensatory behaviors seen in bulimia. In the model, anxiety fully mediated the path from CPTSD to night eating, with a standardized indirect effect of 0.45 that was highly significant. In practical terms, this suggests that among people with complex trauma symptoms, it is the anxious arousal, the chronic vigilance and worry that often accompany trauma, that appears to channel distress into nighttime eating, rather than depressed mood or bodily complaints. Full mediation means that once anxiety was accounted for, the direct link between CPTSD and night eating was no longer statistically meaningful.

The road to binge eating was different. Somatization, the propensity to manifest emotional pain as headaches, gastrointestinal complaints, fatigue, and other physical symptoms, partially mediated the association between CPTSD and binge eating, with a standardized coefficient of 0.20. Partial mediation implies that somatization carries part of the relationship, but that a direct path from CPTSD to binge eating also remains. This pattern is consistent with theoretical accounts in which binge eating functions as a bodily regulation strategy, a way of numbing or soothing distress that is experienced physically rather than verbally. For survivors whose trauma is somatically encoded, the drive to eat may be less about anxious rumination and more about quieting a body that has learned to hold its pain in flesh rather than words.

Perhaps the most surprising result concerned depression. CPTSD and depression were almost inseparable in the data, with a path coefficient of 0.82, one of the strongest associations in the entire model. Yet depression did not significantly mediate either the pathway to binge eating or the pathway to night eating. The authors highlight this dissociation as a key contribution of the study. It suggests that although depression is a near-constant companion of complex trauma, it may be a relatively nonspecific one, whereas anxiety and somatization carry more diagnostic information about which form of disordered eating a survivor is most likely to develop. If replicated, this specificity could sharpen clinical assessment: a trauma survivor presenting with high anxiety might be screened for night eating, while one reporting prominent physical symptoms might be evaluated for binge eating.

The authors are careful to frame these findings as preliminary rather than definitive, and their cautions deserve emphasis. The study used a cross-sectional design, meaning all data were collected at a single point in time, so the direction of the pathways is a statistical inference rather than a demonstrated causal sequence. Childhood sexual abuse was measured by retrospective self-report, which can be affected by memory and disclosure biases. Participants were not clinically diagnosed; eating pathology was assessed by questionnaire symptom scales rather than structured diagnostic interviews. And the sample, drawn largely from Jewish female adults online, limits generalizability to men, other populations, and clinical settings. The model fit statistics, while good, describe how well the hypothesized network matches the observed correlations, not proof that the mechanisms operate as drawn.

Even with those limits, the study opens a promising line of investigation. It positions binge eating and night eating not as isolated problems with food, but as potential expressions of a wider trauma-related syndrome in which the body becomes the site of regulation and repair. The plain-language summary accompanying the paper makes this point directly: in people with a history of childhood sexual abuse, disordered eating may be connected with broader trauma-related difficulties, not only with eating itself. Understanding anxiety, somatization, and complex PTSD may therefore be essential when assessing these eating problems, rather than focusing on eating behavior alone.

The clinical implications, if future research confirms them, could be significant. Screening for CPTSD in patients with binge eating or night eating symptoms, and conversely screening for disordered eating in trauma services, could help identify people whose difficulties currently fall between diagnostic categories. Treatments that target anxious arousal or somatic distress, alongside established eating disorder interventions, might prove more effective for trauma survivors than approaches aimed solely at food and weight. The research team, which also included Maya Levy, Iris Shachar Lavie, and Rachel Bachner-Melman of Ruppin Academic Center and Inbal Brenner of Lev-Hasharon Mental Health Center and Tel Aviv University, notes that their results provide a preliminary basis for further investigation of the trauma-related and psychological factors associated with binge- and night-eating symptoms. Longitudinal studies following survivors over time, and clinical samples with formal diagnoses, will be needed to test whether the two divergent pathways mapped here hold up as genuine mechanisms, and whether treating the anxiety behind night eating, or the bodily distress behind binge eating, can interrupt the trajectory from childhood trauma to adult eating disorder.

Subject of Research: Pathways linking childhood sexual abuse, complex PTSD, and disordered eating through anxiety and somatization

Article Title: Childhood sexual abuse and disordered eating: distinct pathways linking complex PTSD with binge eating disorder and night eating syndrome

Article References: Lev-Ari, L., Levy, M., Lavie, I. S., Bachner-Melman, R., & Brenner, I. (2026). Childhood sexual abuse and disordered eating: distinct pathways linking complex PTSD with binge eating disorder and night eating syndrome. Journal of Eating Disorders. https://doi.org/10.1186/s40337-026-01784-7

Image Credits: AI Generated

DOI: 10.1186/s40337-026-01784-7

Keywords: childhood sexual abuse, complex PTSD, binge eating disorder, night eating syndrome, anxiety, somatization, depression, trauma, eating disorders, structural equation modeling, emotional distress, mental health

The research team, led by Cheng Wu, Xunjun Li, Jiawen Chen, Chuanfa Fang and Tao Chen of Southern Medical University’s Nanfang Hospital system, examined 129 patients with locally advanced gastric cancer who received anti-PD-1 based immunotherapy before surgery between April 2022 and December 2024. Neoadjuvant therapy, given before the primary surgical treatment, has become a cornerstone approach for shrinking tumors and improving surgical outcomes in this aggressive disease. Immune checkpoint inhibitors such as anti-PD-1 antibodies work by releasing the molecular brakes that tumors place on T cells, allowing the body’s own immune defenses to attack cancer cells. But these drugs do not work for everyone, and oncologists have been searching for the factors that separate responders from non-responders.

To measure emotional distress, the researchers used two widely validated screening instruments: the Patient Health Questionnaire-9, or PHQ-9, which assesses depressive symptoms, and the Generalized Anxiety Disorder-7 scale, known as GAD-7. Patients scoring five or higher on either scale were classified as experiencing emotional distress. By this definition, 38 percent of the cohort, 49 of 129 patients, met the threshold for distress. That prevalence is consistent with what oncologists routinely observe in cancer wards, where a diagnosis of gastric cancer, often discovered at an advanced stage in populations with high disease burden, takes a substantial psychological toll.

The difference in treatment response between the two groups was striking. Among patients with emotional distress, only 36.7 percent showed a meaningful pathological response to the immunotherapy, as graded by the College of American Pathologists Tumor Regression Grade system, which pathologists use to measure how much tumor tissue has been destroyed by preoperative treatment. Among patients without distress, the response rate was 81.3 percent. The gap was statistically robust, with a P value below 0.001, meaning the probability that such a difference arose by chance alone is extremely small.

Because retrospective comparisons can be confounded by other variables, the team went further, applying multivariate logistic regression to adjust for factors that might independently influence response. Even after this statistical correction, emotional distress remained an independent negative predictor of pathological response, with an adjusted odds ratio of 0.252 and a 95 percent confidence interval of 0.076 to 0.809, and a P value of 0.021. In practical terms, distressed patients had roughly a quarter of the odds of responding to therapy compared with non-distressed patients. The authors caution, as they should, that retrospective designs cannot prove causation, but the association survived the standard statistical hurdles that such studies must clear.

Perhaps the most intriguing clue in the study concerns perineural invasion, or PNI, a pathological feature in which cancer cells invade and travel along nerves. PNI is recognized as an aggressive behavior in many cancers and is associated with worse prognosis. In this cohort, emotional distress correlated strongly with higher PNI prevalence: 77.8 percent of distressed patients showed perineural invasion, compared with only 26.5 percent of non-distressed patients, again with a P value below 0.001. This correlation offers a possible biological bridge between mood and treatment outcome, suggesting that distress may be linked to tumor biology that is inherently more invasive and less responsive to immune attack.

The mechanistic story that scientists have been assembling over decades makes such a link biologically plausible. Chronic psychological stress activates two major physiological systems: the hypothalamic-pituitary-adrenal axis, which drives sustained cortisol secretion, and the sympathetic nervous system, which floods tissues with catecholamines such as norepinephrine. Both pathways can suppress immune function, dampening T cell activity, reshaping the tumor microenvironment, and promoting inflammation patterns that favor cancer progression. Nerve-cancer interactions, the phenomenon underlying perineural invasion, may themselves be amplified by stress-related neural signaling, since tumors and nerves engage in a chemical dialogue that can stimulate tumor growth and dissemination. If emotional distress tilts this dialogue toward the tumor, it could simultaneously worsen invasiveness and blunt the effectiveness of drugs that depend on a vigorous immune response.

An important subgroup analysis strengthens the clinical relevance of the findings. PD-L1, a protein that tumors use to suppress immune cells, is measured by the combined positive score, or CPS, and a CPS of five or higher is a well-established biomarker predicting benefit from anti-PD-1 therapy. Patients whose tumors express high PD-L1 are expected to be the best responders to checkpoint inhibitors. Yet even within this favorable PD-L1 CPS of five or greater subgroup, patients without emotional distress maintained superior treatment response compared with distressed patients. In other words, a biomarker that normally identifies patients likely to benefit from immunotherapy did not fully protect distressed individuals from the negative association, hinting that psychological state may carry prognostic information that standard biomarkers miss.

The implications for clinical practice are significant. If the association holds up in prospective research, screening gastric cancer patients for depression and anxiety before they begin neoadjuvant immunotherapy could become as routine as measuring PD-L1 expression. Psychological support, whether through counseling, cognitive behavioral therapy, stress reduction programs or pharmacological treatment, might then be positioned not merely as an adjunct to comfort care but as a component of cancer treatment with measurable biological stakes. The study authors explicitly highlight the need for psychological support in this population and call for prospective studies to validate the underlying mechanisms and determine whether treating distress can actually improve immunotherapy outcomes.

As with all retrospective research, important caveats apply. The study included 129 patients from two Chinese hospitals, and the cohort’s characteristics may not generalize to all populations. Emotional distress was measured with screening questionnaires rather than formal psychiatric diagnosis, and the timing of the assessments relative to treatment could influence the results. Reverse causation remains possible: patients whose tumors are biologically more aggressive might feel worse, rather than the other way around, although the correlation with perineural invasion suggests a genuine biological entanglement. Still, the consistency of the findings, the strength of the statistical associations, and the plausible mechanistic framework make this one of the more compelling studies to date linking emotional state to immunotherapy efficacy in solid tumors. For the roughly one in three gastric cancer patients experiencing distress, the message is a call for integrated care, where oncologists, surgeons and mental health professionals work together, because the battle against cancer may be fought not only with antibodies and scalpels but also with the full cooperation of a patient’s mind and immune system.

Subject of Research: Association between emotional distress and pathological response to neoadjuvant immunotherapy in locally advanced gastric cancer

Article Title: Emotional distress and pathological response to neoadjuvant immunotherapy in locally advanced gastric cancer: a multicentre retrospective cohort study

Article References: Wu, C., Li, X., Chen, J., Fang, C., & Chen, T. (2026). Emotional distress and pathological response to neoadjuvant immunotherapy in locally advanced gastric cancer: a multicentre retrospective cohort study. BMC Cancer. https://doi.org/10.1186/s12885-026-17035-6

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17035-6

Keywords: gastric cancer, neoadjuvant immunotherapy, emotional distress, anti-PD-1, perineural invasion, pathological response, immune checkpoint inhibitors, PHQ-9, GAD-7, PD-L1 CPS, psychological stress, tumor microenvironment