Glucocorticoid-induced adrenal insufficiency is a well-known adverse effect of glucocorticoid therapy, occurring not only with oral administration but also with intramuscular, inhaled, and other routes of administration. However, the impact of intermittent high-dose glucocorticoids used during chemotherapy on hypothalamic-pituitary-adrenal (HPA) axis function remains incompletely understood.

In this prospective pilot study, 47 women with breast cancer receiving paclitaxel-based chemotherapy with dexamethasone premedication were evaluated. Morning serum cortisol and adrenocorticotropic hormone (ACTH) concentrations were measured before dexamethasone administration at baseline and prior to subsequent weekly chemotherapy cycles. Longitudinal trends in cortisol and ACTH concentrations were analyzed using ANOVA and Spearman correlation.

Across the entire group, morning cortisol and ACTH concentrations showed an overall downward tendency during treatment. However, no statistically significant changes were observed. The results did not demonstrate significant suppression of morning cortisol or ACTH concentrations during intermittent high-dose dexamethasone administration in this group.

These findings underline the limitations of single cortisol measurements and highlight the need for a longitudinal approach when assessing adrenal function in oncology patients. Further studies incorporating dynamic testing are required to determine the optimal method for evaluating HPA axis function during intermittent glucocorticoid exposure.

Thyroid nodules are among the most common endocrine disorders and present a variable risk of malignancy. Accurate preoperative assessment using clinical, sonographic, and cytological parameters is essential for appropriate management.

A prospective cross-sectional study was conducted on 70 patients presenting with thyroid complaints at Baghdad Teaching Hospital between January and June 2024. All participants underwent clinical evaluation, thyroid function testing, ultrasonography using the TIRADS classification, fine-needle aspiration cytology using the Bethesda system, and histopathological examination following surgery.

Multinodular goiter was the most prevalent thyroid condition in both sexes. Higher TIRADS grades, particularly Grade 5, and higher Bethesda categories were significantly associated with malignancy. Papillary carcinoma was the most frequent malignant histological type. Malignancy was more common among patients requiring re-aspiration. A positive family history and presentation with neck swelling were significantly associated with malignant nodules.

The combined use of TIRADS and the Bethesda system provides reliable prediction of thyroid malignancy. Family history and neck swelling are important clinical indicators that should prompt closer surveillance and early diagnostic intervention.

To identify a distal pancreatectomy (DP) surgical procedure with a low risk for fistula.

Common use of computed tomography (CT) increases detection of pancreatic lesions early or incidentally.

We retrospectively analyzed data from 63 patients with DP between 2000 and 2021. Fifty-three patients were diagnosed with tumors and 10 without. The pancreatic thickness at the resection site was measured on CT before surgery. We compared the postoperative outcomes of patients with and without postoperative pancreatic fistula (POPF).

Twenty-six patients (41%) were male, and the mean age was 54 ± 15  years. Patients with severe POPF had poorer outcomes, including severe complications, readmission, resurgery, and longer hospital stays than did those without (P ≤ .05). The pancreas thickness cutoff for discriminating severe pancreatic fistula was 13.2  mm, with an area under the curve of 71.4% (95% confidence interval [CI], 56.0-86.7%). Multivariable analysis showed that a thickness >13.2  mm (odds ratio [OR], 11.11; 95% CI, 1.92-64.12), more recent surgery (OR, 5.86; 95% CI, 1.29-26.51), and use of suture only (OR, 5; 95% CI, 1.12-20) were significantly associated with severe POPF.

DP has a high leakage rate, with some morbidity and mortality. DP thickness >13.2 mm was associated with a higher risk of POPF. Gastrointestinal anastomosis stapling, especially using the double clamping technique, is safe and results in less POPF, as shown in both clinical and cadaveric studies.

Accurate delineation of organs of interest (OOIs, also commonly referred to as organs at risk, OARs) is crucial for safe radiotherapy. While deep learning-based segmentation using convolutional neural networks has achieved high geometric accuracy, clinical translation is hindered by overconfident, uncalibrated predictions in anatomically ambiguous regions. Uncertainty quantification and model calibration are prerequisites for safe clinical workflows. This study compared the standard nnU-Netv2 against its residual-encoding variant (ResEncM), hypothesizing that ResEncM would demonstrate superior reliability and calibration while maintaining comparable geometric accuracy. Patient/material and methods: T1-weighted contrast-enhanced MRI scans from 70 brain cancer patients were used (55 training/validation, 15 testing). Ground-truth contours for brainstem, hippocampi, chiasm, optic nerves, optic tracts, and pituitary were delineated per Danish Neuro Oncology Group guidelines. Both architectures were trained using five-fold cross-validation with identical preprocessing. Epistemic uncertainty was quantified using mutual information, and Expected Calibration Error (ECE) was computed within a 10-mm isotropic margin around reference contours.

Both models achieved high geometric accuracy (brainstem dice similarity coefficient [DSC] > 0.93, hippocampi DSC > 0.81). No significant geometric differences were found for large structures. ResEncM showed significantly lower DSC for the pituitary (p = 0.003) and chiasm (p = 0.018). However, ResEncM demonstrated significantly lower epistemic uncertainty and ensemble variance across all structures (p < 0.05), and significantly reduced ECE for the optic chiasm, optic tracts, and pituitary.

Integrating a deep residual encoder into the standard U-Net framework significantly improves reliability and calibration of automated brain OOI contours while maintaining strong geometric performance. The ResEncM architecture provides a more trustworthy tool for clinical radiotherapy by reliably flagging high-uncertainty voxels, supporting confidence-aware clinical workflows.

Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy with limited treatment options for advanced or metastatic disease. Immune checkpoint inhibitors (ICIs) have shown durable responses in clinical trials, but evidence derives from small and highly selected populations. This study investigates the effectiveness and tolerability of pembrolizumab in an unselected real-world cohort. Patient/material and methods: This retrospective, multicenter cohort study evaluated the real-world efficacy, durability, and safety of pembrolizumab in Danish patients with advanced or metastatic SCCA treated between September 2018 and September 2023. A total of 37 patients, who received at least one dose of pembrolizumab for non-resectable, recurrent or metastatic disease, were included (89% ≥ 2nd line). Median age was 64 years, the majority were female (64.9%), and most tumours were human papillomavirus (HPV) (p16) positive (73.0%).

The objective response rate (ORR) was 13.5%, with two complete and three partial responses. The clinical benefit rate (CBR) was 48.6%, and two patients had durable responses exceeding 24 months. Median progression-free survival (PFS) and overall survival (OS) were 4.0 months 95% confidence interval (CI) (2.6-5.5) and 12.1 months 95% CI (7.6-15.2), respectively. Patients with good performance status and HPV-positive disease had significantly improved survival outcomes. Treatment was well tolerated, and no treatment-related deaths were reported.

In this real-world cohort, pembrolizumab demonstrated durable responses in a subset of patients with advanced SCCA and an acceptable safety profile. Outcomes were comparable to clinical trial data, indicating modest activity. Findings support using pembrolizumab as a treatment option in selected patients, but further evidence is needed to refine its role.

Lung cancer continues to be the leading cause of morbidity and mortality associated with malignancies. Identifying prognostic factors is vital for improving survival outcomes. This study assessed the impact of clinical, demographic, and genetic factors on overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). A prospective cohort of 70 NSCLC patients was analyzed. Demographic and clinical data, including epidermal growth factor receptor (EGFR) mutation status and clinical response by RECIST 1.1 criteria, were assessed. Survival outcomes were estimated using the Kaplan-Meier method with log-rank test. The median PFS and OS were 15 and 24 months, respectively. EGFR-positive patients showed significantly longer survival than EGFR-negative patients (PFS: 17 vs. 11 months, OS: not reached [NA] vs. 24 months). Brain metastases indicated poor OS (OS: 15 months vs. NA) but did not affect PFS. Patients with a partial response after one year exhibited improved overall survival (24-month OS probability of 77.8%). EGFR mutation status, brain metastases, and clinical response are key predictors of survival in NSCLC patients. Integrating genetic screening, timely management of brain metastases, and early assessment may enhance personalized treatment and improve prognosis.

To evaluate the long-term efficacy, safety, and cosmetic outcomes of carbon-ion radiation therapy (C-ion RT) as a nonsurgical treatment option for patients with early-stage breast cancer.

This single-center, prospective phase 1/2 trial enrolled women aged ≥60 years with stage I (cT1N0M0), estrogen receptor-positive, human epidermal growth factor receptor type 2-negative invasive ductal carcinoma, ≤2 cm in diameter. Patients received C-ion RT at a total dose of 60 Gy (relative biological effectiveness) in 4 fractions, followed by adjuvant aromatase inhibitors. The primary endpoint was 5-year local control. Secondary endpoints included complete response (CR) rate, adverse events (AEs), cosmetic outcomes, disease-free survival, and overall survival. Imaging was used for evaluating tumor response, and follow-up was conducted for a median of 73 months.

Twelve patients were treated in the phase 2 component of the trial. The CR rate was 100%, with a median time to CR of 12 months (range, 4-36 months). The 5-year local control and disease-free survival rates were both 92%, and the overall survival rate was 100%. One case of in-field recurrence occurred in a patient with a high Ki-67 index. Acute grade 1 dermatitis was observed in 6 patients. No grade ≥2 acute AEs were reported. Regarding late AEs, grade 1 rib fractures (n = 2) and grade 1 mastitis-related pain (n = 3) were managed conservatively. Magnetic resonance imaging revealed subclinical pectoral muscle inflammation in 7 cases. All patients except one (who underwent mastectomy due to recurrence) maintained excellent cosmetic outcomes.

C-ion RT demonstrated excellent long-term tumor control with minimal toxicity and favorable cosmetic outcomes in selected patients with early-stage breast cancer. These findings support its potential as a nonsurgical alternative for patients who are medically inoperable or decline surgery, warranting further investigation in larger, controlled trials.

A recent meta-analysis reported that patients with ovarian cancer have a 3-fold increase in the risk of diagnosis of depression compared to the general population. However, the role of disease-related processes in depressive symptoms-particularly at diagnosis versus after treatment-remains unclear. This study aimed to examine the contribution of somatic symptoms to the assessment of depression severity in patients with ovarian cancer, both at diagnosis and 1 year later, compared to healthy controls.

A total of 428 patients with ovarian cancer completed psychosocial assessments at 1-2 weeks before surgical intervention or initiation of neoadjuvant chemotherapy and at a 1-year follow-up visit. A comparison sample from the Midlife in the United States study was included. Item factor analysis was used to examine the functioning of somatic items in a common depression symptom index in both samples.

Somatic items demonstrated differential functioning between groups. Specifically, patients with ovarian cancer were more likely to endorse somatic symptoms at lower levels of depression as compared to healthy aging adults; they additionally required a lower level of depression to endorse somatic items as compared to nonsomatic items. These differences between patients with cancer and healthy aging adults were no longer present at 1 year postdiagnosis.

These findings support the conclusion that somatic symptoms may disproportionately inflate depression scores among patients with ovarian cancer at diagnosis, which may potentially lead to misclassification or overestimation of depression severity. This highlights the need for refined measurement approaches that account for the somatic burden of cancer in assessing depression during active disease.

Trastuzumab Rezetecan (SHR-A1811) is an antibody-drug conjugate (ADC) targeting the human epidermal growth factor receptor 2 (HER2). It features a novel enzyme-cleavable linker and delivers the topoisomerase I inhibitor payload, rezetecan, with a drug-to-antibody ratio of approximately 6.0. Its population pharmacokinetics (PopPK) were characterized using a nonlinear mixed-effects model based on data from 645 patients with HER2-expressing or HER2-mutated advanced solid tumors with 18,671 samples across three phase 1 trials. A two-analyte PopPK model was developed to describe the intact ADC and released payload. The intact ADC followed a two-compartment model with linear elimination, while the payload rezetecan was best described by a one-compartment model with first-order release and linear elimination. Stepwise covariate modeling identified several baseline factors-body weight, tumor size, albumin, aspartate aminotransferase, age, and cancer type-as statistically significant parameters-covariates' relationships. However, their effects on the AUC of both intact ADC and payload were limited (< 20% change). No clinically relevant impacts were observed for race, sex, formulation, or renal/hepatic function on ADC or payload exposure. In conclusion, the developed PopPK model adequately characterizes the pharmacokinetics of Trastuzumab Rezetecan and its released payload. Based on the covariate analysis, no dose adjustments are warranted for the studied patient population. This model can further support dose selection in future clinical trials through exposure-response analyses.

Ki-67 index and mitotic count form the basis of grading of small intestinal neuroendocrine tumours (siNET). We hypothesized that the mitosis-specific marker phosphohistone H3 (PHH3) might better correlate with cancer-specific survival (CSS) and with response to treatment. We evaluated the association between Ki-67 index, PHH3-estimated mitotic count, and survival outcomes in a retrospective cohort of 73 consecutive patients with metastatic siNET. Additionally, we estimated the optimal cut-off for PHH3 and cross-validated the outcome. Both markers adequately distinguished CCS when comparing lower and higher proliferation groups (Ki-67: 128 vs. 95 m; PHH3: 149 vs. 88 m). They were strongly associated with CSS as continuous (HR 1.18 [1.08-1.28] and 1.16 [1.09-1.25]), and dichotomous variables (HR 2.96 [1.31-6.67] and 3.11 [1.50-6.46]). The Cox model based on PHH3 displayed slightly better optimism-corrected Harrell's c-index (0.71 vs. 0.68) and Akaike information criterion (219 vs. 223). Additionally, PHH3 showed significant association with PFS after treatment with somatostatin analogues (HR 1.12 [1.03-1.21]), and borderline significant association with PFS after treatment with peptide receptor radionuclide therapy (HR 1.11 [1.00-1.24]). A cut-off of >2 mitoses per 10 high-power fields estimated by PHH3 seemed to have better discrimination power compared to the standard WHO cut-off (<2). Mitotic count based on PHH3 is associated with CSS and with PFS after treatment with first-line SSA and possibly with PRRT for metastatic siNET. It may be an alternative to Ki-67 for estimation of proliferation and grading. A cut-off of >2 mitoses per 10 HPF might better distinguish G1 and G2 tumours.