Pakistan faces an escalating cancer burden, with approximately 185,748 new cases and 118,631 deaths annually. According to GLOBOCAN data, breast cancer (16.5%), lip/oral cavity cancer (8.6%), and lung cancer (5.1%) are the most prevalent, with breast cancer alone accounting for 31.3% of female cases. The country's limited healthcare resources, including severe shortages of oncologists and radiotherapy facilities, exacerbate this crisis, requiring urgent intervention. The delta Mortality-to-Incidence Ratio (dMIR) metric identifies cancers with the largest outcome gaps between Pakistan and top-performing countries, highlighting where improvements could yield the greatest impact. For instance, stomach cancer (dMIR = 0.60), Kaposi sarcoma (0.58), and oral cavity cancer (0.49) represent critical priorities. By focusing resources on high-dMIR cancers through early detection, treatment access, and prevention programs, Pakistan can significantly reduce preventable mortality. To address these challenges, Pakistan must implement a comprehensive National Cancer Control Plan. Key steps include expanding screening programs for breast, cervical, and oral cancers; training healthcare workers; upgrading radiotherapy infrastructure; and launching public awareness campaigns targeting tobacco use and lifestyle risks. Strategic investments in these areas, coupled with policy reforms and public-private partnerships, could transform cancer outcomes in Pakistan. Key Words: Pakistan, Cancer burden, Delta mortality-to-incidence ratio, Cancer disparities, Low- and middle-income countries.

To evaluate the expression of Fascin-1 in colorectal carcinoma and analyse its association with clinicopathological parameters and pathological stage.

A cross-sectional Study. Place and Duration of the Study: Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, from July 2022 to June 2023.

Surgical resection specimens of colorectal carcinoma underwent histopathological processing for the preparation of haematoxylin and eosin-stained slides. Immunohistochemical evaluation for the biomarker Fascin-1 was then performed, and its expression was evaluated according to standard criteria.

There was a total of 73 cases of colorectal cancer in this study. The mean age of patients was 44.76 ± 15.83 years (13-75 years). Histopathological subtype adenocarcinoma NOS was the most common finding on microscopic examination. Moderately differentiated tumours were the most frequent finding (63%, n = 46). In this study, most tumours were of the rectosigmoid region (26%, n = 19). Fascin-1 had positive expression in 46.6% (n = 34) cases. In histopathologic subtype, poorly differentiated tumours had a statistically significant expression of Fascin-1 (p = 0.001). ROC curve analysis of the continuous Fascin-1 product score against pathological stage demonstrated excellent predictive performance (AUC = 0.859, p <0.001). Multivariate analysis demonstrated higher expression of Fascin-1 to be a significant predictor of advanced stage (OR = 6.131, 95% CI: 1.197-31.410; p = 0.030). However, lymphovascular invasion (p = 0.082), tumour deposits (p = 0.798), and tumour grade (p = 0.315) did not show a significant association with advanced stage.

Fascin-1 expression is significantly associated with advanced tumour stage in colorectal carcinoma. Independent association of Fascin-1 with staging in multivariate analysis suggests its potential role as a biomarker for tumour progression. Its higher expression in poorly differentiated tumours and signet ring cell carcinoma also supports its role in tumour aggressiveness.

Colorectal neoplasms, Fascin-1, Immunohistochemistry, Neoplasm grading, Neoplasm staging.

To evaluate the distribution of cancers across different age groups among residents of Balochistan from 2021 to 2024 and compare these patterns with those observed in other provinces of Pakistan.

An observational study. Place and Duration of the Study: Pathology-based cancer registry at the Section of Histopathology, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan, and Department of Pathology, Aria Institute of Medical Sciences, Quetta, Pakistan, from January 2021 to December 2024.

Newly diagnosed, biopsy-confirmed malignant cases received from Quetta and other cities of Balochistan through the Aga Khan University Hospital laboratory network and the collaborating Institute over four years from the cancer registry and one year from the other institute were analysed. Patients were grouped by age and gender into children (0-14 years), adolescents (15-19 years), and adults (≥20 years). Duplicate records were removed through systematic verification. Categorical variables were evaluated using frequencies and percentages.

Out of 16,342 biopsy specimens, 5,145 (31.5%) were malignant. There were 52% (n = 2,659) male and 48% (n = 2,486) female cases. Adults accounted for 93% of cases, while children and adolescents accounted for 7%. Among a total of 2,438 adult males, oesophageal cancer was most frequent (425, 17.4%), followed by stomach (351, 14.4%) and colorectal cancers (225, 9.2%). Out of the total 2,351 adult females, breast cancer was the leading malignancy (526, 22.4%), followed by oesophageal (434, 18.5%) and colorectal cancers (133, 5.7%). In younger groups, brain tumours and lymphomas predominated.

Marked predominance of oesophageal cancer in both genders highlights substantial regional variation. Overall, the predominance of gastrointestinal cancers suggests the presence of region-specific environmental risk factors.

Cancer registry, Balochistan, Oesophageal cancer, Colorectal cancer.

Patient-reported outcome measures (PROMs) are fundamental in evaluating cancer treatments within clinical research and practice. The existence of various PROMs that assess similar health domains presents challenges for comparing or aggregating study results and data. Score linking is a well-established method for addressing this issue by converting scores from the metric of one PROM to another.

To provide equipercentile equating of psychosocial scales from commonly used PROMs in cancer patients to facilitate data pooling and comparisons.

Cancer patients with diverse diagnoses from five European countries completed the EORTC CAT Core, EORTC QLQ-C30, FACT-G, SF-36, and HADS Emotional, Role, and Social functioning (EF; RF; SF) scales. For scales with Spearman correlations exceeding 0.70, scores were linked using equipercentile equating as provided by the R package "equate". To evaluate linking precision, Standardized Mean Absolute Errors (SMAEs) were calculated.

A total of 945 cancer patients were included in the analysis (mean age 58.4 years; 54.7% male). Bidirectional conversion tables were established for three pairs of SF/RF scales and 10 pairs of EF scales. Overall, linking was possible for most scales from the EORTC Measures, SF-36, and HADS, whereas the FACT-G allowed linking only for its Emotional Well-Being (EWB) scale.

The findings suggest greater linking ability for EF scales compared to RF and SF scales, which seem to be more heterogeneous in terms of content. The established crosswalks support the combined evaluation of data from different PROMs.

Frozen section (FS) is the most widely used method to assess resected pulmonary lesions intraoperatively, although it also prolongs the operation time. We aimed to evaluate the accuracy of intraoperative rapid on-site evaluation (ROSE) and evaluate whether it can serve as a faster auxiliary judgment alongside FS.

A prospective study was conducted on patients undergoing complete resection. Rapid Romanowsky (DiffQuik) staining was used for ROSE. The results of intraoperative ROSE were compared with those of frozen section and final pathological diagnosis.

A total of 75 patients were enrolled in the study, and 81 samples were taken for ROSE, which could assess biopsied samples within a few minutes. The time required for ROSE is significantly shorter than that for intraoperative frozen section analysis, and the mean time to diagnosis was significantly shorter for ROSE (by surgeon) than for FS (9.75 min vs. 29.70 min, p < 0.001). The diagnostic accuracy of ROSE was 90.1% for surgeons, 95.6% for experienced pathologists, and 81.5% for junior pathologists, respectively.

ROSE can serve as an auxiliary judgment tool, enabling frozen sections to make intraoperative decisions more rapidly. It is a valuable technique for diagnosing lung tumor intraoperatively.

This post hoc analysis of the phase 3b JUMP trial evaluated addition of anemia-supporting medications to ruxolitinib in patients with myelofibrosis and anemia.

101 patients with baseline hemoglobin <12.0 g/dL initiated an erythropoiesis-stimulating agent (ESA) or danazol <3 months post-enrollment and maintained ESA/danazol ≥3 months; 97% initiated ESAs. Patients enrolled in JUMP who had hemoglobin <12.0 g/dL but did not initiate ESAs/danazol within 3 months were evaluated as an unmatched comparator. Total JUMP population data were also analyzed for spleen length (≥50% reduction from baseline) and symptom response (≥6.5-point improvement in FACT-Lym score).

Baseline characteristics were similar to comparator JUMP patients (no ESAs/danazol within 3 months, n = 1242). Mean total daily ruxolitinib dose remained >25 mg. Week 24 spleen length response was achieved by 37% of patients; 26% achieved symptom response, similar to the comparator population (28% and 26%, respectively) and comparable to the total JUMP population (N = 2233). Outcomes were similar between the hemoglobin <12.0 g/dL analysis population and patients with baseline hemoglobin <10.0 g/dL (n = 52). In all groups, hemoglobin levels increased after Week 4 following an expected initial decrease.

This analysis suggests that patients treated with ruxolitinib and anemia-supporting care continued to receive optimal ruxolitinib dosing; spleen-length and symptom response rates in these patients were comparable to the overall JUMP population, the majority of whom did not have anemia.

Results support use of anemia-supporting medications with ruxolitinib and may allow maintenance of ruxolitinib dose intensity in patients with myelofibrosis and anemia.

Brazil has substantially expanded public oncology investment over the past decade, particularly within the Brazilian Unified Health System (SUS). However, whether increased spending has translated into measurable population-level improvements in cancer outcomes remains uncertain.

We conducted a retrospective ecological time-series analysis using national data from 2008 to 2023. Public expenditures for female breast and prostate cancer were extracted from DATASUS and inflation-adjusted, while mortality data were obtained from INCA and age-standardized. Key policy milestones-RDC 55/2010, creation of Conitec in 2011, Ordinance No. 874/2013, and Constitutional Amendment 95/2016-were mapped against expenditure and mortality trends. Findings therefore represent system-level associations rather than causal estimates of patient-level therapeutic effectiveness.

Oncology expenditures increased substantially, with more pronounced growth after 2011, whereas national age-standardized mortality rates for female breast and prostate cancer changed comparatively little. This pattern represents a descriptive temporal divergence between expenditure growth and mortality trends, not evidence of therapeutic inefficacy or a quantified causal effect. Regional differences in diagnostic capacity, healthcare infrastructure, continuity of care, and treatment timeliness may influence how financial inputs translate into population-level outcomes.

Brazil's experience supports a value-oriented oncology strategy linking investment not only to technology incorporation, but also to early diagnosis, implementation capacity, regional equity, and effective care pathways. These ecological findings do not support individual-level causal inference, particularly for prostate cancer, for which mortality is a delayed and relatively insensitive medium-term endpoint. Future studies should incorporate stage at diagnosis, treatment pathways, time-to-treatment indicators, and regional survival data.

Clinicians need a reliable, noninvasive tool that can predict the risk of gastrointestinal stromal tumor (GIST) recurrence preoperatively. We aimed to develop a machine learning model based on preoperative contrast-enhanced CT (CECT) to predict recurrence-free survival (RFS) in GIST patients who underwent radical resection.

A total of 192 patients with intermediate- and high-risk GISTs who underwent radical resection and subsequently received adjuvant imatinib were included, with a minimum follow-up duration of 24 months. A machine learning model (Model_radiomic) based on preoperative CECT was built to predict RFS, which was compared with the Armed Forces Institute of Pathology (AFIP) index (Model_AFIP). The C-index and time-dependent receiver operating characteristic curves were estimated via the Kaplan-Meier method and compared via the log-rank test.

The C-index values of the Model_radiomic in the training, testing and validation cohorts ranged from 0.678 to 0.763, whereas the areas under the curves (AUCs) at 3 and 5 years were 0.744-0.790 and 0.703-0.833, respectively. The C-index values of Model_AFIP in the above datasets were 0.539-0.660, and the AUCs at 3 and 5 years were 0.497-0.649 and 0.503-0.630. Model_radiomic demonstrated a higher C-index than Model_AFIP did in the training and external validation cohorts (p = 0.010 and 0.042, respectively). Model_radiomic presented a greater AUC value than Model_AFIP did at the 5th year in the training cohort (p = 0.009).

We found the machine learning-based preoperative CECT performed better than the AFIP index in prediction of RFS of GIST patients, especially at the 5th year, predicting recurrence risk in patients who underwent radical resection and receiving adjuvant therapy. This model may serve as a non-invasive tool to identify high-risk individuals who require more intensive surveillance and personalized management following radical resection.

N6-methyladenosine (m⁶A) modification has emerged as a critical regulator in gastric cancer progression. Fragile X messenger ribonucleoprotein 1 (FMRP), an RNA-binding protein with tumorigenic potential, remains poorly characterized in gastric cancer.

FMRP expression in gastric cancer was assessed through bioinformatic analyses and tissue microarray-based immunohistochemistry. Its biological functions were examined through loss-of-function experiments in vitro and in vivo. Mechanistic investigations, including RNA interaction, m⁶A site mutation, and RNA stability analyses, were performed to identify downstream targets and pathways regulated by FMRP.

Bioinformatic analyses and tissue microarray-based immunohistochemistry showed that FMRP was significantly upregulated in gastric cancer tissues. FMRP depletion suppressed tumor growth and metastasis. Subsequently, Dishevelled segment polarity protein 2 (DVL2) was identified as a candidate downstream target of FMRP. DVL2 was also significantly upregulated in gastric cancer tissues, and its expression positively correlated with FMRP expression. Mechanistically, FMRP bound to DVL2 mRNA and enhanced its stability in an m⁶A-dependent manner. Among the candidate sites tested, mutation of 1271A attenuated FMRP-mediated regulation of DVL2 reporter activity, supporting the involvement of this site. Functionally, FMRP promoted activation of the noncanonical Wnt/planar cell polarity (PCP) signaling pathway and enhanced the proliferative, migratory, and invasive capacities of gastric cancer cells via DVL2.

These results define FMRP as an oncogenic driver in gastric cancer that operates via the DVL2/Wnt/PCP axis. Targeting this pathway may provide a potential therapeutic strategy for gastric cancer.

Deep inspiration breath hold (DIBH) is widely used to reduce cardiac dose in left-sided breast radiotherapy. However, the reliability of DIBH at CT simulation, has not been systematically evaluated despite the importance of CT simulation as the basis for treatment planning. We investigated the clinical impact of surface-guided breathing training on DIBH reliability and cardiac dose sparing.

In this retrospective cohort study, 115 breast cancer patients undergoing DIBH CT simulation were analyzed before and after implementation of surface-guided breathing training using an SGRT system. DIBH performance was quantified by partial lung volume increase (PLVI) and breath-hold variability. Correlations between external surface motion and internal DIBH depth were assessed. Cardiac dose metrics were compared, with a subgroup analysis for patients receiving lymphatic drainage area (LDA) irradiation.

Prior to training, insufficient DIBH CTs-including negative PLVI cases-were observed. After training implementation, all CT scans were acquired in intended breath-hold states, eliminating insufficient DIBH acquisitions. Mean PLVI increased by ~ 9%, and breath-hold variability decreased by ~ 26%. Sternum motion correlated most strongly with PLVI, with multiregion surface monitoring yielding the highest internal correlation. These improvements were reflected in significant reductions in cardiac dose, particularly in the LDA subgroup, with selected heart dose metrics reduced up to 96%, while maintaining target coverage.

DIBH at CT simulation with surface-guided breathing training proves to be reliable. The training prevents planning CTs in wrong breathing states and thus enables clinically meaningful cardiac dose reduction in breast radiotherapy.