Hypopharyngeal squamous cell carcinoma (HPSCC) has a poor prognosis. Although neoadjuvant chemoimmunotherapy (nCIT) is promising, responses are heterogeneous and PD-L1 combined positive score (CPS) inadequately stratifies benefit. We sought biomarkers to guide patient selection. In this prospective, single-center, single-arm phase II trial, patients with resectable locally advanced HPSCC received two cycles of neoadjuvant toripalimab, albumin-bound paclitaxel, and nedaplatin. The primary endpoint was the pathological complete response (pCR) rate. Pre-treatment tumor biopsies from a subset of patients (n=13) were analyzed by single-cell RNA sequencing (scRNA-seq) to identify determinants of response. Findings were validated in a larger cohort (n=60) using bulk RNA sequencing and immunohistochemistry. Among 70 evaluable patients, the objective response rate was 82.7%. Of the 64 patients who underwent surgery, the pCR rate was 29.7% (95% CI, 18.9%-42.7%). Baseline PD-L1 CPS was not associated with pathological response (P=0.313). Single-cell analysis revealed that the pre-treatment tumor microenvironment of responders was significantly enriched with a pro-inflammatory neutrophil subset characterized by high expression of CCL3 (Neu_CCL3). A gene signature score derived from this subset was a strong and independent predictor of pCR (AUC = 0.788), significantly outperforming PD-L1 CPS (AUC = 0.621). The efficacy of nCIT in HPSCC is predetermined by a baseline immune architecture orchestrated by a CCL3+ neutrophil subset. The Neu_CCL3 gene signature is a promising, clinically translatable biomarker that can fill a critical gap in precision immunotherapy for HPSCC.

Response assessment in rectal cancer undergoing total neoadjuvant therapy: decision tree analysis integrating contrast enhanced T1-weighted MRI.

Introduction Breast cancer patients face several physical and psychological problems, such as anxiety, depression, and cognitive dysfunction. The disease and treatments can also impact the microbiota, which is associated with cognitive and psychological issues and, consequently, affected quality-of-life (QoL). This study aimed to correlate the initial gut microbiota of newly diagnosed HR+ (Hormone Receptor)/HER2- breast cancer patients with their mental health, cognitive function, and QoL at baseline and after 3 months of neoadjuvant chemotherapy. Materials and methods This is a prospective, longitudinal, observational, exploratory study. Newly diagnosed HR+/HER2- breast cancer patients undergoing neoadjuvant chemotherapy were recruited upon diagnosis. At baseline (before neoadjuvant chemotherapy), general and lifestyle information, adherence to the Mediterranean diet, biochemical analysis, gut microbiota profile, the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core-30 (EORTC QLQ-C30), the Montreal Cognitive Assessment (MoCA) and the Hospital Anxiety and Depression Scale (HADS), were collected. The EORTC QLQ-C30, MoCA, and HADS were repeated 3 months later. Results From the 11 participants, most showed mild cognitive impairment at baseline, and there was no clear trend of improvement or deterioration at 3 months. Participants had borderline anxiety at baseline, which improved to a normal range, while depression remained stable. QoL declined for most women, with over 70% experiencing problems at 3 months. The association of these parameters with microbiota profile suggested that women with poorer cognitive function over time had lower Shannon index and microbial richness. Women with improved scores in the depression subscale of the HADS appear to have higher Shannon index and lower richness. Contrarily, Shannon index was lower and richness was higher for improved anxiety and global QoL scores. The results also suggest that changes in the abundance of various genera and phyla may be linked to the evolution of scores for the 3 questionnaires. Conclusion Our study suggests a link between the microbiota profile at diagnosis and the psychological symptoms that develop at 3 months of breast cancer treatment. These findings shed light on potential strategies for positively modulating the microbiota to help enhance the body's resilience, particularly mental health, throughout the disease and treatments.

Background/Objectives: Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. The tumor microenvironment, particularly tumor-associated macrophages (TAMs), plays a key role in tumor progression and angiogenesis. M2-polarized TAMs are considered pro-tumorigenic; however, their prognostic significance and relationship with microvessel density (MVD) at the invasive front of GC remain unclear. This study evaluated the prognostic significance of CD163+ M2 TAMs and MVD at the invasive front of gastric adenocarcinoma. Methods: A retrospective analysis was performed on 106 patients who underwent radical R0 surgery for GC without neoadjuvant therapy. Immunohistochemistry using CD163 and CD34 antibodies was applied to quantify M2 TAMs and MVD at the invasive front. Median values were used as cut-offs. Associations with clinicopathological features were analyzed, and survival was assessed using Kaplan–Meier and Cox regression models. Results: The mean number of CD163+ M2 TAMs was 70, and the mean MVD was 33. A significant positive correlation between M2 TAMs and MVD was observed (p = 0.001). Higher M2 TAMs infiltration was associated with deeper tumor invasion (pT) and showed a trend toward advanced pTNM stage. In univariate analysis, neither M2 TAMs nor MVD was associated with survival. Multivariate analysis identified pT (p = 0.02) and MVD (p = 0.03) as independent prognostic factors, with increased MVD associated with improved overall survival. Conclusions: CD163+ M2 TAMs are linked to angiogenesis at the invasive front of gastric cancer and correlate with tumor invasiveness. Increased MVD may represent an independent favorable prognostic marker, highlighting the biological importance of the invasive tumor front.

Background. In unresectable hepatoblastoma (HB), particularly “pre-treatment extent of tumor” (PRETEXT) IV tumors or those with positive annotation factors, standard management consists of intensive chemotherapy followed by surgical resection or orthotopic liver transplantation (OLT). Radiotherapy has traditionally been avoided because of the liver’s radiosensitivity and the risk of radiation-induced liver disease. Proton beam therapy (PBT), owing to its dosimetric advantage and ability to spare uninvolved liver parenchyma, may represent a potential local control strategy in selected pediatric patients for whom curative surgery or OLT is not feasible. Case Presentation. We describe five pediatric patients with advanced hepatoblastoma treated with proton beam therapy at our institution between February 2022 and January 2024. The cohort included three girls and two boys, with a median age of 3.0 years (interquartile range [IQR], 1.6–4.0) and a median alpha-fetoprotein level of 435,453 ng/mL (IQR: 7,668–1,276,681) at diagnosis. All patients were initially considered inoperable because of extensive hepatic involvement, inadequate future liver remnant, or multifocal disease, and OLT was not feasible owing to donor limitations or medical comorbidities. All received neoadjuvant chemotherapy using SIOPEL-based regimens, achieving partial tumor response. Tumors ranged from 5 to 12 cm and involved central hepatic segments, the portal region, or both lobes. PBT was delivered at a total dose of 50 GyE in 10–25 fractions as definitive or consolidative therapy, followed by surgical resection in three patients. Two patients additionally received targeted therapy and immunotherapy. At last follow-up, four patients were alive with no evidence of disease, while one patient died from tumor progression. Conclusions. These cases suggest that proton beam therapy may serve as a feasible liver-sparing local treatment option for selected pediatric patients with unresectable or residual hepatoblastoma when surgery or OLT is not possible. While limited by availability and cost, PBT may facilitate multimodal therapy and preserve future treatment options.

To investigate MRI-based breast edema patterns as biomarkers of tumor aggressiveness and their predictive value for pathological response to neoadjuvant chemotherapy (NAC) in invasive breast cancer. This retrospective study evaluated 235 female patients (mean age, 52 ± 12 years) with biopsy-proven invasive breast cancer who underwent pre-NAC breast MRI. After excluding 19 patients (10 for inadequate image quality, 9 for post-biopsy imaging), 216 patients were analyzed. Breast edema score (BES) was independently assessed by two radiology residents to evaluate interobserver agreement. Subsequently, a breast radiologist reviewed all cases to establish the definitive dataset. The differences in clinicopathological characteristics between the two groups and between different BES were compared. Interobserver agreement for BES classification was very high (92.6% concordance). Edema presence correlated significantly with larger tumor size (p = 0.001), higher histological grade (p = 0.001), axillary lymph node metastasis (p = 0.015), hormone receptor negativity (p < 0.001), lymphovascular invasion (p = 0.031), and elevated Ki-67 (p = 0.001). Higher BES groups (BES 2-4) showed stronger associations with aggressive features: tumor size (p < 0.001), grade (p = 0.022), hormone receptor negativity (p = 0.001), non-luminal subtypes (p = 0.001), and intratumoral necrosis (p = 0.002). Neither edema nor BES predicted pathological response to NAC (p = 0.999, p = 0.299). BES and edema are robust imaging biomarkers of tumor aggressiveness but demonstrate no predictive value for NAC response. MRI-based edema scoring holds clinical relevance for noninvasive tumor phenotyping and risk stratification in breast cancer management. Question Can MRI-based breast edema patterns predict tumor aggressiveness and pathological response to neoadjuvant chemotherapy in invasive breast cancer patients, aiding noninvasive risk stratification? Findings BES correlates with aggressive tumor features (larger size, higher grade, hormone negativity; all p < 0.050 but shows no predictive value for NAC response (p = 0.299). Clinical relevance BES serves as a practical imaging biomarker for risk stratification and tumor phenotyping, guiding individualized therapy. However, it shows no utility in predicting NAC response, emphasizing the need for complementary predictive tools in treatment planning.

The Peritoneal Cancer Index recorded at laparotomy is based on visual and palpable inspection of peritoneal surfaces for disease. This study aimed to analyze interobserver variation in assigning the lesion score (LS) and morphologic term (MT) to characterize peritoneal lesions (PL) and predict the probability of malignancy (POM) among surgeons with expertise in cytoreductive surgery (CRS) for peritoneal malignancies. The study selected 80 intraoperative images of PLs depicting different morphologic appearances of PLs arising from different primary tumors in various peritoneal regions. In the study, 50 expert peritoneal malignancy surgeons were asked to assign an LS to the region in question, select the MT or MTs to describe the PL, and predict the POM. Information on the presence of disease on histopathology was not provided at this point. Inter-observer reliability was evaluated using Krippendorff's alpha (α). A consensus was reached if any option received more than 75% of the votes. The study participants comprised 41 (82%) of 50 experts. Consensus on LS was achieved for 18 images (22.5%), with low agreement (α = 0.174). For MTs, a consensus was reached for 21 images (26.5%; α = 0.0902, denoting low and unreliable agreement. Of these 21 images, the MT used was "tumor nodule" for 90.4% of the images (p < 0.001). The POM was accurately predicted in 52.5% of the cases (α = 0.155). Administration of neoadjuvant chemotherapy had no impact on the surgeons' assessment of the three parameters. Even the most experienced CRS surgeons showed high interobserver variation and unreliable agreement in the description and accurate characterization of PLs on pictorial records. A Delphi consensus to standardize the MT used and scoring of PL could reduce discordance.

Achieving a margin-negative (R0) resection in borderline resectable pancreatic cancer (BRPC) is a critical prognostic determinant. The optimal clinical strategy-neoadjuvant therapy (NAT) versus upfront surgery (UFS)-remains a key clinical question. This narrative review synthesized contemporary evidence from studies published between 2009 and 2025, encompassing a total of 5598 patients with BRPC. The analysis compared oncological outcomes between NAT and UFS, specifically focusing on resection rates, R0 resection frequency, and median overall survival (OS). Mixed-cohort studies lacking BRPC subgroup analysis were excluded. Evidence from both comparative and single-arm studies indicated that the majority of cohorts achieved significantly higher R0 resection rates and improved median OS following NAT. Resection rates after NAT ranged from 29% to 90%, whereas UFS cohorts reported rates between 62% and 92%. Although resection was more frequent in UFS groups, NAT cohorts demonstrated superior oncological margins; R0 rates in NAT groups ranged from 23% to 100% compared to 14% to 90% in UFS groups. This translated into a survival benefit, with NAT groups achieving a median OS of 11.0 to 43.9 months versus 11.6 to 27.8 months for UFS. NAT also facilitated superior pathological downstaging and reduced lymph node positivity. Neoadjuvant therapy, utilizing potent multi-agent regimens, significantly improves R0 resection rates and overall survival in BRPC and is increasingly recognized as the preferred clinical strategy. Currently, this survival benefit is not clearly established for patients with upfront resectable disease.

The aim of the study was to evaluate the concordance between radiological imaging modalities and pathological findings and to test whether neoadjuvant therapy (NAT) is included in surgical planning, especially in the appropriateness of breast-conserving surgery (BCS). We conducted a retrospective observational study in 280 patients diagnosed with nonmetastatic breast cancer, including [NAT(+): 75 and NAT(−): 205]. Radiological examinations included ultrasonography, mammography, and magnetic resonance imaging before and after NAT. We compared the surgical outcomes, with pathological findings between these groups. In our statistical analyses, we examined the agreement of radiological, surgical, and pathological findings using Pearson chi-square test, Fisher exact test, and the Kappa coefficient. In addition, the data were analyzed using the Python artificial intelligence program and the results were presented. In the study, it was observed that compliance was higher in patients who received NAT compared with those who did not, BCS compliance increased significantly, patients who were not suitable for BCS after NAT became suitable, and there was inconsistency between radiological and pathological findings. Neoadjuvant therapy improves radiological compliance and increases the feasibility of BCS in patients with nonmetastatic breast cancer by effectively reducing tumor size and facilitating more precise surgical planning. Future studies should focus on integrating advanced imaging techniques and molecular profiling to improve treatment strategies and patient outcomes.

Magnetic resonance imaging (MRI) is the standard diagnostic technique for the locoregional assessment of rectal cancer. The pertinent guidelines recommend neoadjuvant therapy depending on cT and cN categories. In this experimental study, we examined the accuracy of pretreatment MRI staging. MRIs of 50 patients from the OCUM study (non-pretreated, 24 women, histologically confirmed rectal adenocarcinoma, located ≤12cm from the anal verge, stages I-III) were re-assessed by 74 radiologists affiliated with certified colorectal cancer centers. The radiologically determined Union for International Cancer Control (UICC) stages were compared with the histopathological findings, which were unknown to the radiologists. The degree of agreement between the radiologists' assessments and the histopathology was analyzed with κGold, a weighted average of Brennan-Prediger agreement coefficients. 2915 complete assessments were performed for cTcN (UICC stages); 740 cases (25.4%) were not classifiable because of cTX (0.1%) or cNX (25.3%). The UICC stage accorded with the histopathology in 979 cases (33.6%); there was overstaging in 737 cases (25.3%) and understaging in 459 (15.7%). The κGold for agreement was 0.114 (95% confidence interval, [0.032-0.20]). Agreement was also low for T- and N-categories (κGold=0.354 and κGold=0.235, respectively), but was better for distance to the mesorectal fascia (MRF) (κGold=0.736) and extramural vascular invasion (EMVI) (κGold=0.579). Although MRI remains the standard diagnostic technique for the locoregional assessment of rectal cancer, its accuracy for T- and N-staging in rectal cancer is low, particularly with regard to the distinction of T2 from T3a/b and the assessment of lymph nodes. The assessment of MRF and EMVI is much more reliable.

BackgroundBruton’s tyrosine kinase (BTK) is a downstream mediator in B-cell receptor (BCR) signaling and is essential for B-cell differentiation and proliferation. BTK inhibitors are approved and in clinical use for hematological cancers such as lymphoma and leukemia, with testing underway in solid tumors. Because BTK is expressed in myeloid-derived suppressor cells (MDSCs) known to worsen breast cancer (BC) outcomes, we investigated the clinical relevance of BTK expression in multiple BC subtypes as a predictor of progression and/or response to treatment.MethodsWe performed an integrative transcriptomic analysis of tumor BTK expression across three large BC cohorts (The Cancer Genome Atlas (TCGA), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), and Sweden Cancerome Analysis Network-Breast (SCAN-B); total n = 5,240), 10 neoadjuvant chemotherapy (NAC) datasets, and the I-SPY2 neoadjuvant immunotherapy trial cohort. Gene set enrichment analysis (GSEA) and xCell deconvolution were used to evaluate associations with cell proliferation, immune infiltration, and tumor microenvironment (TME) composition while single-cell sequencing datasets (SCP1039, SCP1106) were used to identify BTK-expressing cell populations. Survival analyses were performed using Kaplan-Meier and log-rank tests.ResultsBTK levels were the highest in triple-negative BC (TNBC) among the subtypes and unexpectedly drove stronger proliferation gene set enrichment in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2–) tumors (e.g., MITOTIC_SPINDLE, G2M_CHECKPOINT). However, BTK expression did not correlate with American Joint Committee on Cancer (AJCC) stage or overall, disease-free, or disease-specific survival across cohorts or molecular subtypes. Notably, BTK-high tumors showed robust enrichment of immune pathways (interferon gamma (IFN-γ) response, interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor-α (TNF-α) signaling) and exhibited elevated tumor-infiltrating leukocyte and lymphocyte fractions, increased cytolytic activity, and greater abundance of myeloid and lymphoid cell populations. BTK expression was not consistently associated with NAC response as only one of 10 datasets (GSE25066) showed a weak association within ER+ and HER2-positive subtypes. Similarly, BTK levels did not predict response in I-SPY2 patients receiving durvalumab plus olaparib, despite strong correlations with programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) expression. Single-cell analysis localized BTK transcripts primarily to myeloid and B cells.ConclusionBTK expression in BC reflects a proliferative and immune-active TME, particularly in TNBC and HER2-positive subtypes, but lacks prognostic or predictive value for NAC or PD-L1-based immunotherapy response.

Low-dose nivolumab with neoadjuvant chemotherapy and oral metronomic therapy in borderline resectable oral cavity squamous cell carcinoma: a phase II trial

Neoadjuvant immune checkpoint blockade (ICB) and radiation therapy (RT) improve disease-free survival in select patients with soft tissue sarcoma (STS). However, most STS are myeloid-rich and lack pre-existing T cells associated with ICB response. In preclinical models, we observed that intratumoral BO-112 (nanoplexed polyinosinic: polycytidylic acid (poly I:C)) engages myeloid cells that persist after RT, ultimately enhancing T cell-dependent tumor control. We evaluated BO-112 and hypofractionated RT, with or without nivolumab, in fourteen patients with high-risk STS in a phase 1 neoadjuvant trial. Consistent with its immunologic potency, the triple combination induced rare immune-related adverse events (myositis-myocarditis-myasthenia gravis spectrum), mitigated by BO-112 and nivolumab dose adjustment. BO-112 and RT reprogrammed tumor-associated myeloid cells toward antigen-presenting states, promoted clonal replacement by less exhausted T cells, and enhanced malignant cell depletion compared to standard RT. These immunologic changes coincided with encouraging disease control in a small, high-risk cohort, supporting further clinical development.

BackgroundRadiological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemoradiation therapy (CRT) is challenging to assess.PurposeTo evaluate whether computed tomography (CT) and biological features can predict tumor regression grade (TRG), recurrence-free survival (RFS), and overall survival (OS) of patients who undergo surgery after CRT for PDAC.Material and MethodsThis retrospective study included 125 patients who underwent surgery after CRT for non-metastatic PDAC between January 2013 and March 2021. Two board-certified radiologists independently reviewed initial and post-CRT CT images and assessed the primary tumor extent and regional lymph node metastasis. Another board-certified radiologist quantitatively assessed the primary tumor on pre- and post-CRT diffusion-weighted and positron emission tomography images. Logistic regression and Cox regression analyses were performed to identify predictors of TRG 0/1, RFS, and OS.ResultsIn total, 44 (35.2%) patients had a TRG of 0/1. The normalized post-CRT carbohydrate antigen (CA) 19-9 level (<37 IU) (odds ratio [OR] = 3.69; P = 0.024) and adjacent organ invasion on post-CRT CT images (OR = 0.24; P = 0.042) were independent predictors of TRG 0/1. During follow-up (mean = 33.6 months), 68 (54.4%) patients experienced tumor recurrence and 65 (52.0%) died. The normalized post-CRT CA 19-9 level (<37 IU) (hazard ratio [HR] = 0.51; P = 0.028) was a significant predictor of RFS, and size change (%) after CRT (HR = 0.24; P = 0.044) was an independent predictor of OS.ConclusionThe normalized post-CRT CA 19-9 level and adjacent organ invasion on post-CRT CT images predicted TRG. The normalized post-CRT CA 19-9 level was associated with RFS, whereas size change was an independent predictor of OS.

Introduction: Occult breast cancer (OBC) is defined as axillary lymph node metastasis without an identifiable primary breast tumor. Although advances in imaging have reduced the incidence of “true” OBC, long-term outcomes extending beyond a decade remain rarely reported. Recent literature has also suggested that a subset of OBC may originate from ectopic breast tissue located within axillary lymph nodes, suggesting biological heterogeneity within this rare entity. Case Presentation: A 54-year-old woman presented with right axillary lymphadenopathy. Comprehensive imaging showed no intramammary lesion, and surgical biopsy confirmed metastatic breast cancer, consistent with OBC. Axillary lymph node dissection revealed seven metastatic nodes (ER 50%, PR 0%, HER2 3+). She received adjuvant chemotherapy and a non-steroidal aromatase inhibitor for ten years without recurrence. Twenty years later, screening mammography identified a new spiculated mass in the ipsilateral breast. Core needle biopsy revealed HER2-positive invasive ductal carcinoma (ER &lt;5%, PR 15%, HER2 3+, MIB-1 51%). Neoadjuvant chemotherapy with trastuzumab resulted in a clinical complete response, and total mastectomy yielded a pathological complete response. Conclusion: This case illustrates an exceptionally rare occurrence of an ipsilateral HER2-positive breast tumor appearing 20 years after treatment for OBC. The absence of MRI at the initial diagnosis, the long disease-free interval, and the discordant tumor biology highlight the diagnostic challenge of distinguishing a new primary cancer from a delayed manifestation of occult disease. Furthermore, considering emerging evidence that some OBC may arise from axillary ectopic breast tissue, the present case—lacking any pathological features of ectopic tissue—supports a metastatic origin rather than an ectopic primary. Lifelong surveillance is essential for patients with OBC, even after prolonged remission.

Stage IA pancreatic ductal adenocarcinoma (PDAC) is an early-stage disease where curative resection is feasible. While minimally invasive surgery (MIS) is increasingly used and adjuvant chemotherapy is standard for resected PDAC, their roles in stage IA patients remain unclear. This study evaluated the oncologic and perioperative outcomes of surgical approach and adjuvant chemotherapy in stage IA PDAC patients. We retrospectively analyzed patients with histologically confirmed stage IA PDAC who underwent curative-intent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) at Severance Hospital (2005-2022). Those receiving neoadjuvant therapy or other procedures were excluded. Survival was assessed with Kaplan-Meier estimates and Cox models. Among 102 patients, 48 (47.1%) underwent MIS and 78 (76.5%) received adjuvant chemotherapy. The mean tumor size was 1.62cm; 49 patients had right-sided tumors and 53 had left-sided tumors. MIS was more common in the DP group than the PD group (67.9 vs. 24.5%, p < 0.001). 12 patients (11.8%) had pathologic margin involvement of the tumor in final pathology. 59 patients (57.8%) experienced complications postoperatively and 78 patients (76.5%) received adjuvant chemotherapy. The 5-year overall and disease-free survival rates were 58.2% and 48.6%, respectively. On multivariable analysis, age (HR 1.05, p = 0.027), female sex (HR 0.32, p = 0.006), and adjuvant chemotherapy (HR 0.24, p = 0.001) were independently associated with overall survival. Age and adjuvant chemotherapy were also independently associated with recurrence-free survival. Adjuvant chemotherapy was associated with improved outcomes in stage IA PDAC overall, but did not confer an overall survival benefit in left-sided tumors, underscoring the need for larger studies to define its role in this subgroup.

Introduction: Neoadjuvant systemic and immunotherapy strategies in non-metastatic colon cancer have demonstrated high pathological response rates, raising interest in surgery-sparing approaches. Circulating tumour DNA (ctDNA) is an emerging biomarker for treatment response and minimal residual disease, but its role in guiding surgical omission in colon cancer remains unclear. This systematic review evaluates the diagnostic and prognostic accuracy of ctDNA in predicting pathological response following neoadjuvant therapy in non-metastatic colon cancer. Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed, Embase/MEDLINE, Scopus, and the Cochrane Register were searched from inception to 21 October 2025. Eligible studies included adults with non-metastatic colon cancer treated with neoadjuvant therapy who had serial ctDNA assessment prior to surgery. Results: Three cohort studies comprising 100 patients met inclusion criteria. Baseline ctDNA detection ranged from 42% to 84%. Across studies, ctDNA clearance following neoadjuvant therapy was consistently associated with major pathological response or pathological complete response, whereas persistent ctDNA strongly predicted residual viable tumour at resection. In the largest prospective cohort, 5 of 26 patients (19%) achieved ctDNA clearance prior to surgery; all were pathological responders, while 19 of 26 patients (73%) with persistent ctDNA demonstrated no pathological response. No study reported pathological complete response in the presence of persistently positive ctDNA. No prospective trial formally evaluated ctDNA-guided surgical omission. Conclusions: Current evidence does not support the use of ctDNA alone to guide omission of surgery after neoadjuvant therapy in non-metastatic colon cancer—even in patients who show complete pathological response. While persistent ctDNA reliably identifies patients with residual disease, ctDNA clearance lacks sufficient positive predictive value to safely forego surgery. Prospective trials with standardised ctDNA platforms and predefined non-operative management protocols are required before ctDNA-guided organ preservation can be recommended.

The KEYNOTE-522 regimen is the standard of care for stage II-III triple-negative breast cancer (TNBC). However, older patients were underrepresented in the pivotal trial. We evaluated the effectiveness and safety of this regimen in patients aged ≥65 years enrolled in the Neo-Real/GBECAM-0123 multicenter real-world study conducted across institutions in Brazil and Argentina. Among 724 patients, 80 (11%) were aged ≥65 years and presented distinct baseline characteristics, including lower frequencies of grade 3 tumors, Ki67 ≥ 50%, and germline BRCA1/2 mutations, alongside a higher prevalence of impaired performance status. The pathologic complete response (pCR) rate in older patients was 54.9% in comparison with 64.5% in younger patients, although age was not independently associated with pCR in multivariable analysis, including other relevant baseline variables. Older patients experienced a significantly higher toxicity burden, with increased rates of treatment discontinuation, dose reductions, treatment delays, hospitalizations, and grade ≥3 neutropenia. Taken together, these data indicate that older patients with TNBC harbor distinct biological and clinical features with numerically lower pCR rates, and that the increased toxicity burden underscores the need for personalized treatment strategies and dedicated research in this population.

Background Immune dysregulation and excessive inflammatory responses can lead to hemophagocytic syndrome (HPS) involving autologous blood cell phagocytosis, with fatal outcomes occurring in some cases. This case report describes an 80-year-old man who was simultaneously diagnosed with diffuse large B-cell lymphoma (DLBCL) and rectal cancer and developed HPS during neoadjuvant chemotherapy for the latter. Case description Treatment for DLBCL was initiated first, and six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were administered, which led to a clinical complete response of the lymphoma lesions. Following the completion of DLBCL treatment, preoperative chemoradiotherapy with tegafur–uracil/leucovorin (UFT/UZEL) was initiated for rectal cancer. On Day 18, a fever of 38.3 °C developed. Blood tests conducted on Day 24 revealed Grade 4 neutropenia and Grade 4 thrombocytopenia. Granulocyte colony-stimulating factor (G-CSF) preparation, antibiotic therapy, and recombinant human soluble thrombomodulin (rTM) were initiated as disseminated intravascular coagulopathy (DIC) therapy. A poor therapeutic response was achieved, and acute respiratory distress syndrome (ARDS) developed on Day 34. Imaging of the biopsied bone marrow confirmed that hemophagocytosis by macrophages was occurring. The patient was ultimately diagnosed with HPS. Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections were identified, and treatment to combat the infections was initiated; however, the patient passed away on Day 37. Conclusion It is important to consider the possibility of HPS, and diagnosis and treatment initiation should occur in a timely manner when fever of an unknown origin and decreased blood cell counts are observed during malignant disease treatment.

Obstructive rectal cancer incidentally diagnosed after a barium meal study: a case report of sequential endoscopic stenting and elective laparoscopic resection