The management of locally advanced rectal cancer is rapidly evolving and is adapted according to the response to neoadjuvant therapy (NAT). This allows clinicians to tailor strategies for patients with favourable responses, including the possibility of preserving the rectum or of reducing complications associated with a surgery that carries a high-risk for morbidity. Radiologists can have a key influence on decision making through MRI, which characterises patterns of response and post-treatment changes to the tumour as well as other prognostic elements such as lymph nodes, extramural vascular invasion, tumour deposits and mesorectal fascia involvement. However, imaging findings can be difficult to interpret, requiring a thorough understanding of both the findings and the current limitations of MRI. In this review, we address the rationale supporting the paradigm shift towards organ preservation strategies, and the role and current challenges of MRI in the restaging of rectal cancer after NAT.

Diffusion-weighted imaging (DWI) is an advanced technique that plays a key role in the evaluation of uterine tumours. This pictorial review explores key aspects of DWI acquisition and application, emphasising its role in diagnosing endometrial cancer and in identifying prognostic factors that influence staging as well as clinical and surgical patient management. It specifically highlights the new 2023 FIGO classification. Additionally, it examines the use of diffusion in the characterisation of myometrial mesenchymal lesions, applying the acronym BET1T2ER as a memory aid to distinguish between benign and malignant lesions. It draws particular attention to findings that could lead to misinterpretations.

Sarcomas, malignant neoplasms of mesenchymal origin, comprise more than 100 entities and numerous histologic subtypes. Their relative rarity compared with carcinomas, interpatient diversity, and pronounced intratumor heterogeneity (ITH) make sarcomas clinically challenging. Yet, they also provide excellent models for studying the molecular and cellular underpinnings of ITH and how it translates into diverse clinical outcomes. New single-cell and spatial omics technologies have revealed the complex architecture of sarcomas with unprecedented resolution. In this review, we use five representative entities - two genomically complex (osteosarcoma, dedifferentiated liposarcoma) and three fusion-driven, genomically "quieter" (Ewing sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma) sarcomas - to showcase recent advances in the field of ITH and the temporal evolution of sarcomas. Specifically, we review how clonal and subclonal molecular alterations, fluctuations in oncogene activity and other forms of cellular plasticity, as well as the formation of complex intratumor ecosystems, drive sarcoma progression and shape therapy resistance. We also provide an overview of recent advances in modeling ITH in sarcomas, as well as in evaluating functional diversity and assessing patient-specific treatment responses. Finally, we outline future directions in ITH research and its clinical implications.

Hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) is an established cure, but mixed donor chimerism is common even with myeloablative conditioning regimens. With many North American centers using less intensive conditioning regiments, rates of mixed donor chimerism may increase. The clinical long-term outcomes of these patients are not well described in combination with laboratory markers of hemolysis and hemoglobin S percentage.

The objective of this study was to describe long-term graft integrity and clinical outcomes in survivors of HCT for SCD with mixed donor chimerism at 1-year post-HCT.

A retrospective multi-center observational analysis of 33 children and adolescents with sickle cell disease and mixed donor chimerism at 1-year post-HCT and at least 2 years of follow-up. Descriptive statistics and a linear mixed-effects model (LMM) were used.

Longer time to follow-up was predictive of lower myeloid chimerism but not lymphoid chimerism. Higher chimerism at 1-year post-HCT were associated with higher chimerism at last follow-up (myeloid and lymphoid). Hemolysis was noted when donor myeloid chimerism was 25% or less. No secondary neoplasms were noted.

In this cohort of children and adolescents who have undergone HCT for SCD with reduced intensity or nonmyeloablative conditioning, lower myeloid chimerism was seen with longer follow-up, highlighting the need for lifetime surveillance of chimerism and clinical outcomes. A higher donor myeloid chimerism at one year is preferable and associated with higher long-term values. No secondary malignancies were observed.

Primary endometrial carcinomas with somatically derived yolk sac tumor (YST) components are rare. We analyzed 23 such cases using detailed clinicopathologic, immunohistochemical, and molecular methods. The median patient age was 68 years. Elevated serum alpha-fetoprotein (AFP) was detected in 76.9% (10/13) of tested cases. FIGO (2009) stages were I (n = 12, 55%), II (n = 1, 5%), III (n = 5, 23%), IV (n = 4, 18%), and unknown in one. Histologic YST patterns included glandular (87%), papillary (52%), solid (48%), endodermal sinus (17%), hepatoid (17%), and reticular (13%) architectures. The associated Müllerian-type neoplasms were endometrioid carcinoma (n=17), carcinosarcoma (n=3), serous carcinoma (n=2), and clear cell carcinoma (n=1). Immunohistochemically, 17 cases (74%) exhibited mutation-type p53 staining, and two (9%) were mismatch repair-deficient (MMRd). YST components uniformly expressed glypican-3 and spalt-like transcription factor, while 17 (74%) also expressed AFP. HER2 positivity was seen in 13 of 21 tested (62%; four 3+, three 2+, six 1+). Molecular analysis revealed TP53 variants in 16 of 22 cases (73%) without POLE hotspot mutations. According to The Cancer Genome Atlas molecular classification, 17 tumors were p53-abnormal (74%), two (9%) MMRd, four (17%) were no specific molecular profile (NSMP), and none were POLE-ultramutated. Recurrent copy number gains involved CCNE1 (9/22, 41%), 1q44 (12/14, 86%), and 3q26.32 (8/14, 57%). Features reminiscent of germ cell tumours included amplifications at 7p21.2 (8/14, 57%) and 9p21.3 (11/14, 79%), polysomy or amplification of chromosome 12p (6/22, 27%), deletion at 11q24.3 (8/14, 57%), and a high frequency of T>C nucleotide substitutions. Follow-up showed 15 patients (75%) had died of disease or were alive with disease; 12 of these 15 cases were p53-abnormal. Overall survival was significantly poorer than in other molecular subtypes of endometrial carcinoma. These tumors should therefore be regarded high-grade (grade 3) by definition. In summary, endometrial carcinomas with a somatically derived yolk sac tumor component are highly aggressive, predominantly p53-abnormal, with smaller subsets classified as MMRd or NSMP. Recognition of the YST component is crucial, and biomarker profiling may reveal therapeutic targets.

ELOC: mutated renal cell carcinoma (RCC) is a recently recognized, molecularly defined entity incorporated into the 2022 World Health Organization classification of genitourinary tumors. Approximately 50 cases of ELOC-mutated RCC have been reported, and the clinicopathologic and molecular features of this rare tumor require further clarification. Herein, we report the pathologic and molecular characteristics of 35 cases of ELOC-mutated RCC, representing the largest series from a single medical center to date. This cohort demonstrated an overwhelming male predominance (34/35), with a median age of 48.8 years, and low stage (predominantly T1aN0M0). Macroscopically, the tumors were well-circumscribed, measuring 1.0-5.0 cm in diameter (median, 2.5 cm), and were either solid (20/35, 57.1%) or mixed solid and cystic (15/35, 42.9%). Microscopically, the tumors showed acinar, branching tubular, papillary, or solid growth patterns and were composed of tumor cells with voluminous, clear cytoplasm and variable fibromuscular stroma. Uncommon patterns included markedly dilated cysts with small papillary tufts, myxoid areas, lymphocyte-rich stroma, and a thyroid follicle-like architecture. The nuclear grade was low. A minority of cases (5/35, 14.3%) exhibited focal areas with nuclei arranged linearly away from the basal aspect. Immunohistochemically, all tumors showed diffuse strong CAIX positivity and moderate or weak CK7 positivity. Variable CD10 expression (32/34, 94.1%), weak reactivity for AMACR (18/24, 63.2%), and negativity for GPNMB (28/28, 100%) were also observed. ELOC mutations were identified in all 35 patients by Sanger sequencing and/or next-generation sequencing (NGS). The mutated amino acid sites included Y79C (30/35, 85.7%), Y79S (2/35, 5.7%), I95N (1/35, 2.8%), E92K (1/35, 2.8%), and C112fs (1/35, 2.8%). All NGS-analyzed cases harbored ELOC mutations (28/28). Other recurrent mutations included CDH23 (6/28), ELP1 (4/28), POLE (4/28), and KMT2C (4/28). Among the 26 specimens evaluated for copy number analysis, all showed deletion of chromosome 8q, and 12/26 (46.2%) exhibited loss of 8p, consistent with biallelic ELOC inactivation. None showed 3p loss by fluorescence in situ hybridization. All patients with follow-up data were alive without evidence of disease progression. Our findings expand the clinical, histologic, immunohistochemical, and molecular spectrum of ELOC-mutated RCC and further support its classification as a distinct renal neoplasm.

The choice between radical prostatectomy (RP) and radiotherapy (RT) for localized prostate cancer depends on multiple factors. The aim of this study was to describe how urologists and radiation oncologists weigh these variables when recommending primary treatment, and to develop clinical decision support algorithms.

An online cross-sectional survey was designed for specialists in Urology and Radiation Oncology in Spain. The questionnaire was developed ad hoc and reviewed by an expert panel. Demographic data and treatment preferences were collected using a Likert scale (1-2 RP; 3 neutral; 4-5 RT) across hypothetical clinical scenarios. Clinical consensus was defined as agreement ≥75%.

The mean age of respondents was 41.3 years (SD 10.3), with 68.5% urologists and 31.5% radiation oncologists. Overall, in young patients (<50 years) with high IPSS (≥20), intravesical prostatic protrusion, Qmax < 10 mL/sec, and elevated post-void residual (PVR), the preference for surgery was high (>75%) (p < 0.001). In contrast, in patients older than 70 years with multiple comorbidities and body mass index (BMI) >35, a preference for radiotherapy (4-5) was observed in more than 75% of cases (p < 0.001).

Treatment preferences for localized PCa depend primarily on age, comorbidity, and urinary symptoms, with consistent differences between specialties. These findings reinforce the need to integrate shared decision-making tools and to develop clinical decision support algorithms.

Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs), which can be severe if not promptly identified and managed. The therapeutic education tool Immuno'Act© has been created to teach cancer patients how to handle irAEs. This study aimed to assess: (1) the preliminary effects of the therapeutic patient education (TPE) session using Immuno'Act© on perceived self-efficacy (PSE), (2) the association between PSE and patients' decision-making to cope with health events, and (3) patients' acceptance of the tool.

This pre-experimental study included cancer patients treated with ICIs at the CHU of Liège, recruited by convenience. PSE was measured using an adapted self-administered questionnaire at least three weeks before the TPE session (T0), immediately afterwards (T1) and at least three weeks after T1 (T2). Decision-making was evaluated through patients' action choices in real-life scenarios presented in Immuno'Act©. Acceptance was assessed with brief scales covering perceived utility, ease of use, aesthetic aspects and overall judgment. Sociodemographic and clinical data were collected. Adjusted general linear mixed model evaluated PSE over time; adjusted linear and logistic regression models assessed associations with PSE changes and decision-making. Descriptive statistics summarised acceptance.

Eighty patients participated. The PSE total score remained high throughout the study, with no effect from a single use of Immuno'Act© (p = 0.91). Up to 25 % of patients never chose the recommended action in coping with urgent and non-urgent irAEs. No association was observed between global PSE level and decision-making. Acceptance was rated positively by over 95 % of participants, with an overall judgment of 8.61 ± 0.96/10.

The positive acceptance of Immuno'Act©, combined with concerning findings, underscores the need to integrate such tools into clinical practice to support patients in managing irAEs.

Healthcare professionals should integrate tools like Immuno'Act© in routine care, with optimal implementation strategy to be determined.

The NAUTILUS trial randomized cT1-2/N0 breast cancer patients to evaluate the non-inferiority of omitting SLNB. We report the clinicopathologic characteristics and axillary lymph node (ALN) status of the patients enrolled in the NAUTILUS trial and suggest expectations based on the results of this trial, which are relevant in the context of the SOUND and INSEMA trials, where the majority of participants were aged 50 years or older.

The NAUTILUS trial randomized 1734 subjects into SLNB or no-SLNB arms. Axillary ultrasonography was mandatory to determine clinical N0. Clinicopathologic variables and ALN status in the SLNB arm were analyzed to determine expectations for the NAUTILUS trial results compared to other clinical trials.

Among 1734 patients, 1664 subjects were available for clinicopathologic analysis; 50.4% were in the SLNB arm and 49.6% were in the no-SLNB arm. Median age was 55 (range, 29-92) years, and 40.1% were premenopausal. Overall, 1.7%, 83.9%, and 14.0% subjects were pTmic, pT1, and pT2, respectively, with a median tumor size of 1.3 cm (range, 0.1-6.0). In the SLNB arm, 11.2% had ALN metastasis, comprising 1.1%, 9.4%, and 0.6% with pN1mic, pN1, and pN2-3, respectively. ALN metastasis rates according to tumor size were 7.0%, 12.8%, and 17.2% for sizes ≤1.0 cm, >1.0 cm & ≤ 2.0 cm, and >2.0 cm & ≤ 5.0 cm, respectively.

The NAUTILUS trial completed enrollment, with included 14.0% pT2 and 40.1% premenopausal subjects and is expected to show the impact of SLNB omission in these subgroups.

ClinicalTrials.gov Identifier: NCT04303715.

Many older adults undergo gastrointestinal (GI) cancer surgery, yet the relative impacts of advanced age, comorbidity, and frailty on postoperative mortality and failure to rescue (FTR) remain unclear. We aimed to compare the impacts of these factors on postoperative outcomes in a large population-based cohort.

We conducted a national retrospective linked database study of patients aged ≥ 65 years who underwent resection for GI or hepatobiliary cancer in Aotearoa New Zealand between 2005 and 2020. Age, comorbidity (C3 Comorbidity Score), and frailty (Hospital Frailty Risk Score) were examined as independent predictors of 90-day mortality, complications, and FTR (death following a complication). Logistic regression models were adjusted for demographic and clinical covariates.

Among 21,729 patients (mean age 75.8 ± 6.8 years), 49.3% experienced one or more complications and 6.1% died within 90 days (FTR rate of 12.3%). In adjusted models, each additional 5 years of age increased 90-day mortality odds by 40% (adjusted odds ratio [aOR] 1.40 and 95% CI 1.34-1.46). Although higher comorbidity (C3 > 3) and frailty (Hospital Frailty Risk Score > 15) also independently raised mortality risk (aOR 1.98 and 2.04, respectively), age exerted the largest effect on mortality and FTR.

Chronological age, comorbidity, and frailty each predict worse outcomes following GI cancer surgery, but advanced age remains the dominant driver of 90-day mortality and FTR. These findings underscore the need for risk stratification, shared decision-making, and preoperative optimization as wells as intense surveillance for complications and early definitive care of older adults undergoing major oncologic operations.