Tumor Histology Research Articles

Anlotinib versus placebo as adjuvant therapy for localized high-grade soft tissue sarcomas: a phase 2, double-blinded, randomized controlled trial.

We aimed to investigate the efficacy and safety of anlotinib as adjuvant targeted therapy for completely resected localized high-grade soft tissue sarcomas (STS). Patients with localized high-grade STS after complete resection were randomly assigned in a 1:1 ratio to receive either oral 12 mg anlotinib or placebo once daily on days 1-14 every 21 days as a cycle, with up to 6 cycles until disease relapse, unmanageable toxicity or death. The efficacy and safety were analyzed. This trial was the first trial exploring adjuvant targeted therapy for STS (NCT03951571). Between June 2019 and November 2023, 88 patients were randomly assigned to receive anlotinib (n=44) or placebo (n=44). With a median follow-up of 30.95 months, the 1-year and 2-year disease-free survival (DFS) rates were 88% and 77% in the anlotinib group, compared to 64% and 58% in the placebo group. Compared to patients treated with surgery alone, patients receiving adjuvant anlotinib combined with surgery had a reduced risk of disease recurrence (HR 0.47 [95% CI 0.22~1.00, P=0.0445]). Based on the tumor histology, the reduced risk of disease recurrence with anlotinib versus placebo was observed in patients with myxofibrosarcoma (HR 0.54 [95% CI 0.17~1.65], P=0.2698) and undifferentiated pleomorphic sarcoma (HR 0.58 [95% CI 0.12~2.87], P=0.4971). Four patients discontinued anlotinib, including two for proteinuria/hematuria (2/44, 5%) and two for poor healing of surgical wound (2/44, 5%). Compared to surgery alone, adjuvant anlotinib following surgery reduces the incidence of disease relapse in localized high-grade STS, with acceptable toxicity.

En-bloc resection of scapular chondrosarcoma with intraoperative computer navigation

Background: Surgical removal of scapular tumours presents a complex problem due to the vicinity of major nerves and blood vessels and its functional importance. Planning such a procedure presents a significant challenge, further complicated by varia-bles such as histological findings, tumour location, and size. In recent years, the development of 3-D imaging, modelling, and printing has proven to be helpful in planning and improving the safety and accuracy regarding major anatomical structures and minimalisation of healthy tissue resection. With modern modalities, we can more readily adhere to the recommendation of limb-salvage surgery. So far, computer-navigated surgery has been used for chondrosarcoma resections of long bones, pelvis, sacrum, and spine, but very few reports provide insight into scapular chondrosarcoma resections using computer navigation. Case presentation: We present a case of a 36-year-old male with a secondary chondrosarcoma grade 1, where “en bloc” resection was successfully performed by using MR- and CT-based intraoperative computer navigation. Discussion: Surgery remains the sole treatment for chondrosarcomas, aiming for complete tumour resection with negative margins while preserving limb function. Successful use of surgical navigation has been documented in various bones, yielding precise bony resection but not soft tissue margins. Conclusion: We applied principles of chondrosarcoma treatment to scapular chondrosarcoma, achieving functional shoulder preservation. Combining navigation with PSI could enhance surgical outcomes, though challenges include technology availability and variability in patient cases.

Sex differences in the impact of multimorbidity on long-term mortality for patients with colorectal cancer: a population registry-based cohort study.

Women have better survival than men patients with colorectal cancer (CRC), but the extent to which this is due to multimorbidity is unclear. A population-based study of 1843 patients diagnosed with CRC in Australia. Data included patient's demographics, multimorbidity, tumour histology, cancer stage, and treatment. We estimated the risks of all-cause mortality and cause-specific mortality due to cancer or non-cancer causes. Men had lower survival than women (P≤0.010) amongst those diagnosed at Stages I-III (15-year survival: 56.0% vs 68.0%, 48.5% vs 60.7%, 34.8% vs 47.5%, respectively), excepting Stage IV (14.4% vs 12.6%; P=0.18). Married men exhibit better survival than those who were never married (P=0.006). Heart attacks (9.9% vs 4.3%, P<0.001) and emphysema (4.8% vs 2.1%, P=0.004) were more prevalent in men than women. Comorbid stroke and high cholesterol (adjusted hazard ratio, AHR=2.22, 95% confidence interval, CI=1.17-4.21, P=0.014) and leukaemia (AHR=6.36, 95% CI=3.08-13.1, P<0.001) increased the risk of cancer death for men only. For women, diabetes increased the risk of all-cause death (AHR=1.38, 95% CI=1.02-1.86, P=0.039) and high blood pressure increased the risk of death due to non-cancer causes (AHR=2.00, 95% CI=1.36-2.94, P<0.001). Separate models of CRC care are needed for men and women with consideration of multimorbidity and social factors.

The effect of storage time and temperature on the proteomic analysis of FFPE tissue sections

Formalin-fixed paraffin-embedded (FFPE) tissues present an important resource for cancer proteomics. They are more readily available than fresh frozen (FF) tissues and can be stored at ambient temperature for decades. FFPE blocks are largely stable for long-term preservation of tumour histology, but the antigenicity of some proteins in FFPE sections degrades over time resulting in deteriorating performance of immunohistochemistry (IHC). It is not known whether FFPE sections that have previously been cut from blocks and used for liquid chromatography-mass spectrometry (LC–MS) analysis at a later time are affected by storage time or temperature. We determined the stability of FFPE sections stored at room temperature (RT) versus − 80 °C over 48 weeks. The stored sections were processed at different timepoints (n = 11) and compared to sections that were freshly cut from FFPE blocks at each timepoint (controls). A total of 297 sections (rat brain, kidney and liver stored at RT, − 80 °C or freshly cut) were tryptically digested and analysed on TripleTOF 6600 mass spectrometers in data-dependent acquisition (DDA) mode. Kidney and liver digests were also analysed in data-independent acquisition (DIA) mode. The number of proteins and peptides identified by DDA with ProteinPilot and some common post-translational modifications (PTMs) were unaffected by the storage time or temperature. Nine of the most common FFPE-associated modifications were quantified using DIA data and all were unaffected by storage time or temperature. Therefore, FFPE tissue sections are suitable for proteomic studies for at least 48 weeks from the time of sectioning.

An international survey of diffusion and perfusion magnetic resonance imaging implementation in the head and neck.

The goal of this international survey was to understand how diffusion (DWI) and perfusion imaging (PWI) are being applied to clinical head and neck imaging. An online questionnaire focusing on acquisition, clinical indications, analysis, and reporting of qualitative DWI (QlDWI), quantitative DWI (QnDWI) and dynamic contrast-enhanced PWI (DCE-PWI) in the head and neck was circulated to members of the American Society of Head and Neck Radiology (ASHNR) and European Society of Head and Neck Radiology (ESHNR) over a 3-month period. Descriptive statistics and group comparisons were calculated with SPSS® v27. There were 294 unique respondents (17.6% response rate) from 256 institutions (182 ESHNR, 74 ASHNR). DWI was routinely acquired for some head and neck indications at 95.7% of the respondents' institutions, with 92.5% of radiologists interpreting QlDWI but only 36.7% analysing QnDWI. QlDWI was most frequently applied to primary mucosal masses or the middle ear, whilst QnDWI was routinely used to distinguish tumour histologies, and primary or recurrent carcinoma. DCE-PWI was routinely acquired at 53.6% of institutions and used by 40.8% of respondents, however, there was no clinical scenario in which it was routinely applied by most users. DCE-PWI analysis methods varied, with time-intensity curve classifications being the most frequently reported. Lack of standardisation was identified as a key reason for not implementing QnDWI, whilst numerous factors prevented the adoption of DCE-PWI. There is widespread routine interpretation of QlDWI by head and neck radiologists, but there is considerable variation in the application and analysis of head and neck QnDWI and DCE-PWI. Question How are diffusion (DWI) and dynamic contrast-enhanced perfusion imaging (DCE-PWI) being utilised by head and neck radiologists across a wide range of practices? Findings An international survey demonstrated widespread routine interpretation of qualitativeDWI but variable application and analysis of quantitative DWI and DCE-PWI with numerous barriers to implementation. Clinical relevance The survey results will aid discussion on how to standardise and optimally disseminate these MRI techniques in day-to-day practice. More focused education and resource allocation may be required to accelerate the adoption of quantitative DWI and DCE-PWI.

Another Addition to Abdomen’s Pandora’s Box: Multi-compartment Enormous Liposarcoma

Abstract Soft tissue sarcomas constitute less than 1% of all neoplasms, with a third of malignant tumours in the retroperitoneum being sarcomas and liposarcoma being the commonest. Local aggressiveness and clinical non-specificity make treatment challenging. A 52-year-old man presented with a massive lump in the abdomen. Surgery following work-up indicated a well-differentiated retroperitoneal liposarcoma (RPLS) with intraperitoneal and scrotal extension and weighed a substantial 6.8 kg. Treatment required meticulous local resection preserving the functionality. RPLS manifests as a large, locally advanced lesion with intraperitoneal extension, but extension into the inguinal canal is unknown. Being low grade, distant metastasis is infrequent, and the challenge lies in achieving effective local control and preventing local recurrence. The preferred treatment involves radical resection incorporating en bloc resection of involved structures. Strategic neoadjuvant and adjuvant therapies, tailored to specific tumour histology, may enhance local control and overall survival. Radical resection of the tumour from the mesentery of the large and small bowel, preserving their vascularity along with retroperitoneal component, albeit in parts, was achieved and is the first-line cure in RPLS. In select cases, individualised chemotherapy and radiation therapy may offer a survival benefit.

Topical Photodynamic Therapy in a Medical Centre: The Scottish Dermatology Experience.

Topical photodynamic therapy (PDT) is widely used in dermatology for treating superficial non-melanoma skin cancer (NMSC) and dysplasia. This study aims to assess real-world outcomes of PDT in a Scottish dermatology service. We retrospectively reviewed patients with superficial NMSC and dysplasia who underwent conventional and daylight PDT at the Photobiology Unit, Dundee, Scotland. A total of 705 patients with 2108 NMSC and precancerous skin lesions underwent conventional PDT. Clearance at 12 months was achieved in 53.4% of actinic keratoses (AK), 71.3% of Bowenoid AK, 86.4% of Bowen's disease (BD), 89.0% of superficial basal cell carcinoma (BCC), and 89.7% of nodular BCC. On multivariate analysis, small lesion size and thin histological tumour thickness of superficial BCC were features, which were associated with likelihood of achieving clearance after PDT. Female sex, head/neck sites, larger lesion size, strong pre-treatment fluorescence intensity, fluorescence specificity, prominent treatment-induced erythema and an urticarial reaction were associated with moderate to severe pain during PDT. Daylight PDT for 77 AK patients (158 treatments) showed excellent or good outcomes in 63.3% of lesions. Higher visible light exposure is correlated with better treatment outcomes. In real-life settings, whilst the PDT response rates of BD and selected BCC are high and consistent with clinical trial outcomes, the efficacy rates for AK appear lower than expected. This emphasizes the need for realistic expectations in chronic disease management. Through review over a prolonged period, factors associated with PDT tolerability and outcomes were identified, allowing predictive utilisation for optimizing patient-centred PDT regimens.

The presenting symptoms of patients with appendiceal malignant tumors.

824 Background: Timely detection of appendiceal malignant tumors is a clinical priority because of the propensity for this malignancy to metastasize to the peritoneal cavity. Up to one in every 2 patients with this rare tumor type will present with distant metastatic disease, owing to there being no standardized screening tests for early detection of primary appendiceal cancers. Case reports have pointed to broad/non-specific symptoms of patients diagnosed with appendiceal malignant tumors, yet information is needed from large cohorts to support prompt/accurate clinical diagnoses. Methods: We analyzed data from patients with a pathologically-confirmed first primary appendiceal malignant tumor (AC) who prospectively enrolled in the nation-wide Genetics of Appendix Cancer [GAP] clinical cohort study (Clinicaltrials.gov, NCT05734430) between November 2022 and May 2024. The primary outcome was presenting symptoms that led to AC diagnosis. Symptom effects and interactions with diagnosis age/year, sex, body mass index (BMI), and tumor histology, were quantified with negative binomial regression models and presented as incidence rate ratios (IRRs) and 95% confidence intervals. Results: Of the 352 patients included in our analyses (median [IQR] age, 51.0 [42-59] yr), 77.6% were female and 96.6% had an adenocarcinoma histology. Seventy-seven percent of patients (n=270) reported one or more presenting symptoms, of whom 55.2% (n=149) experienced these symptoms for 3+ months prior to diagnosis. On average, patients reported 3 symptoms (mean: 2.9, SD 3.0). The most prevalent symptoms among males and females were abdominal pain (57.1%), bloating/distension (32.1%), pelvic pain (18.5%), and abdominal/pelvic mass (18.2%). Overall, patients with early-onset AC [age&lt;50] more commonly presented with symptoms versus cases with late-onset AC (82.9% vs 71.7%, p =0.01). This finding persisted in adjusted models—the number of symptoms was highest among younger patients, rapidly decreased and plateaued around age 50 (IRR 0.97, 95%CI 0.95-0.99, p =0.002), and slowly increased again with older age (IRR 1.03, 95%CI 1.00-1.05, p =0.037). Patient sex was also significantly associated with symptom number, as males had a lower rate of symptoms versus females (IRR 0.63, 95%CI 0.48-0.83, p =0.001). In contrast, histology (IRR 1.03, 95%CI 0.53-2.02), diagnosis year (IRR 1.01, 95%CI 0.99-1.04, p =0.35) and BMI (IRR 1.01, 95%CI 0.99-1.02) were not associated with symptom number in adjusted models. Conclusions: In a large nation-wide cohort, three of every 4 patients were symptomatic prior to primary AC diagnosis. Compared to the rapid time course of acute appendicitis, over 40% of this population presented with symptoms for 3+ months prior to AC diagnosis. The higher symptom burden among young patients and females supports the need for clinical providers to keep occult appendiceal tumors in the differential diagnosis of patients presenting in this manner.

Efficacy of PD-1 inhibitor plus chemotherapy versus chemotherapy in advanced esophageal carcinoma: A meta-analysis of phase III clinical trials.

397 Background: Programmed death cell death protein-1 (PD-1) inhibitors combined with chemotherapy have demonstrated survival benefits in patients with advanced esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). Our pooled analysis aims to analyze the efficacy of PD-1 inhibitor plus chemotherapy in advanced esophageal carcinoma (EC) in phase III randomized clinical trials (RCTs). Methods: We collected data from eligible phase III RCTs searched through PubMed, EMBASE, ClinicalTrials.gov, and meeting abstracts till July 5, 2024. Initial screening revealed 792 articles. We excluded duplicates, review articles and irrelevant studies, and we included eight RCTs that reported objective response rate (ORR), treatment-related adverse events (TRAEs), overall survival (OS) and progression-free survival (PFS). Odds ratio (OR) for ORR and TRAEs, and hazard ratio (HR) for OS and PFS were computed along with a 95% confidence interval (CI) and p-value for pooled analysis, using a random effect model in RevMan v.5.4. We performed a subgroup analysis based on a combined positive score (CPS) for programmed cell death ligand-1 (PDL-1) expression and tumor histology. Results: We included eight phase III RCTs (Jupiter-06, Checkmate 648, Keynote 590, ESCORT-1st, Orient-15, Checkmate 649, ESCORT-NEO, and ASTRUM-007), including 4131 patients with 2137 in group A (PD-1 inhibitor + chemotherapy) and 1994 in group B (placebo + chemotherapy, or chemotherapy). PD-1 inhibitors against EC included nivolumab, pembrolizumab, camrelizumab, sintilimab, toripalimab, and serplulimab. A total of 9.9% of patients were diagnosed with EAC, and 90.1% were ESCC. A pooled analysis showed significant achievement in ORR in group A compared to group B with an OR of 2.19 (CI: 1.77-2.69, p &lt; 0.05, I² = 60%). In terms of OS benefit, group A led to a 29% reduction in death risk compared to group B (HR: 0.71, CI: 0.66-0.76, p &lt; 0.05, I² = 0). Group A also showed a significantly reduced risk of disease progression compared to group B (HR: 0.62, CI: 0.54-0.70, p &lt; 0.05, I² = 60%). Safety analysis revealed more TRAEs (OR: 1.93, CI: 1.43-2.60, p &lt; 0.01, I² = 11%) and grade ≥3 AEs (OR: 1.34, CI: 1.08-1.67, p &lt; 0.05, I² = 54%) in group A compared with group B. Sub-group analysis based on CPS revealed that patients with CPS ≥10 showed more OS (pooled HR: 0.59 vs 0.75) (p = 0.04) and PFS (pooled HR: (0.59 vs 0.64) (p = 0.18) benefits as compared to patients with CPS &lt;10. Survival analysis between ESCC and EAC also exhibited statistically non-significant OS benefits (p = 0.28). Conclusions: PD-1 inhibitor plus chemotherapy as a first-line therapy in advanced EC, mainly in patients with CPS ≥10, showed improved antitumor efficacy in terms of superior ORR, OS, and PFS, with a manageable toxicity profile providing a benchmark for future studies.

Influence of data review on community physicians’ treatment preferences in frontline esophageal cancer (EC).

501 Background: EC remains a global health challenge with a rising incidence and poor prognosis despite advancements in treatment modalities. Standard therapies include surgery, chemotherapy (CT), radiation therapy, and recently, targeted and immunotherapy. The PD-L1 inhibitors pembrolizumab (pembro) and nivolumab (nivo) received FDA approval for frontline treatment in EC in March and May 2021, respectively, based in part on the KEYNOTE-590 (KN590) and CheckMate 648 trials. In this study, we aimed to uncover rationale in physician preference for PD-L1 inhibitors in EC. Methods: US-based oncologists convened at two in-person meetings in April 2024 to discuss clinical and real-world data presented at the 2024 ASCO GI Cancers Symposium. Among data discussed included the KN590 5-year update. Survey questions were fielded at the meeting to capture participants’ impressions. Demographics were captured via an online survey ahead of the meeting. Responses from participants who manage EC and responded to all survey questions were aggregated. Results: 86 participants qualified; and, collectively, are 76% community physicians with 18 years average in clinical practice, see 18 patients median on clinic days, and spend 83% of their time in direct patient care on average. ECOG PS status (50%), tumor histology (52%), and location/stage (48%) were reported as critical factors in treatment decision-making; only 14% said PD-L1 status was a major factor. Participants were queried on a hypothetical patient case of esophageal squamous cell and adenocarcinoma before and after reviewing the KN590 data. Prior to reviewing KN590, physician preferences in the squamous cell 1L setting were split between nivo+CT and pembro+CT; following data review, pembro+CT was favored nearly 3:1. In the adenocarcinoma 1L setting, preference shifted from 60/40 nivo+CT to 60/40 pembro+CT, see Table. The cohort were most impressed with the overall survival (87%) and objective response rates (40%), and 55% would consider pembro+CT for both squamous cell and adenocarcinoma disease while 37% would consider it for PD-L1 CPS&gt;10 squamous cell disease only. Conclusions: Our study showed PD-L1 status was not a major factor in clinical decisions. The shift in treatment preference toward pembro+CT for both patient cases following KN590 data review suggests an impact for data review to influence physician behavior. This highlights the importance of educational initiatives to disseminate clinical updates to providers. It is still to be determined the optimal platform and length for these initiatives, and to quantify their effectiveness. 65-year-old male patient with advanced EC;PD-L1 CPS ≥10;ECOG PS of 1 Squamous cell disease Adenocarcinoma Before After Before After Fluoropyrimidine (FP) + platinum (P)-based CT 1% 1% 1% 0% FP +P-based CT + nivo 55% 27% 60% 36% FP + P-based CT + pembro 43% 71% 38% 63% Nivo + ipilimumab 1% 1% 0% 1% None of the above 0% 0% 0% 0%

Prognostic implications and therapeutic response in GNAS-mutated colorectal adenocarcinoma: A retrospective cohort analysis.

244 Background: GNAS, a key regulator of the G-protein signaling pathway, is frequently mutated in colorectal adenocarcinomas and other malignancies. Despite its role in tumorigenesis, GNAS mutations remain understudied, with no established targeted therapies. Exploring the impact of GNAS alterations on therapeutic response and outcomes in colorectal cancer (CRC) is crucial for developing effective treatment strategies. Methods: We reviewed 531 CRC cases from our institutional Molecular Tumor Board database, identifying 8 patients with GNAS mutations. The prevalence ofGNASmutations in our cohort was 1.5%, which aligns with reported rates of 2-5% in various CRC cohorts. Comprehensive clinicopathologic data, including tumor histology, staging, treatment outcomes, and response rates, were analyzed. A detailed evaluation was conducted on stage IV patients to assess their response, progression-free survival (PFS), and overall survival (OS) in comparison to historical stage IV CRC benchmarks. Results: The cohort included 8 patients with a median age of 61 years (range: 33-73 years), with balanced gender representation (50% male, 50% female). The racial distribution was 50% Black or African American, 25% White, and 12.5% Asian or Pacific Islander. The majority of patients (62.5%) were diagnosed at stage IV, with primary tumor sites predominantly in the sigmoid colon and cecum. Among the 5 stage IV patients, while no patients achieved a complete or partial response, 3 exhibited stable disease, resulting in a 60% disease control rate (including stable disease). The median progression-free survival (mPFS) was 9 months, reflecting the duration of disease control before progression, while the median overall survival (mOS) was 15 months. These outcomes are notably lower than historical benchmarks for stage IV CRC, where response rates typically range from 40-50% with mOS of 20-24 months, highlighting the potentially adverse prognostic impact of GNAS mutations. Conclusions: Patients with GNAS-mutated colorectal adenocarcinoma appear to represent a unique subset with poorer therapeutic outcomes, even when achieving stable disease. The observed disease control in the absence of objective responses underscores the complexity of treating GNAS-mutated tumors and highlights the urgent need for targeted therapies tailored to this molecular subtype. Further research into the biological mechanisms underlying GNAS mutations and their impact on CRC treatment resistance is warranted to improve patient outcomes.

Efficacy of pembrolizumab in advanced esophageal carcinoma: A systematic review and meta-analysis.

438 Background: Pembrolizumab, a monoclonal immunoglobulin G4 antibody is a programmed cell death protein 1 inhibitor, approved for treatment of advanced (metastatic or recurrent) esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). We performed a pooled analysis to assess the efficacy of pembrolizumab in esophageal carcinoma (EC) and to compare it with chemotherapy alone. Methods: We conducted a systemic literature search, using PubMed, EMBASE, and ClinicalTrials.gov, till July 30, 2024. Initial search yielded 412 articles. We excluded duplicates and irrelevant studies and included 4 clinical trials (CT) that reported pembrolizumab’s efficacy in EC. We estimated pooled objective response rate (ORR), partial response (PR), and hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS), along with 95% confidence interval (CI) and p-value in RevMan v.5.4. Subgroup analysis, based on combined positive score (CPS) for programmed cell death ligand-1 (PDL-1) expression and tumor histology type was also performed. Results: We included four CTs in our study; their characteristics are shown in the table. The estimated pooled ORR and PR of pembrolizumab in all patients was 21% (CI: 0.10-0.41) (p &lt; 0.001) and 19% (CI: 0.08-0.37) (p &lt; 0.001), respectively. Pooled median PFS was 3.05 mo (CI: 0.92-5.17) (p = 0.004), and pooled median OS was 8.05 mo (CI: 5.21-10.88) (p &lt; 0.001). Pembrolizumab use in EC showed a reduced risk of disease progression vs chemotherapy alone [HR: 0.85 (CI: 0.75-0.96) (p &lt; 0.05)] and a 21% reduction in mortality [HR: 0.79 (CI: 0.71-0.88) (p &lt; 0.001)]. Safety analysis revealed less grade ≥3 adverse events [OR: 0.56 (CI: 0.35-0.90), p &lt; 0.05)] with pembrolizumab compared with chemotherapy alone. On subgroup analysis between ESSC and EAC, pembrolizumab exhibited statistically nonsignificant responses with ORR (OR: 1.29, CI: 0.89-1.88, p = 0.18), OS (pooled HR: 0.94, CI: 0.76-1.15, p = 0.53). Pembrolizumab in patients with CPS ≥10 vs CPS &lt;10 also showed statistically non-significant responses with ORR [OR: 1.70, CI: 0.99-2.91, p = 0.06), OS (pooled HR: 0.63 vs 1.00) (p = 0.05) and PFS (pooled HR: 0.62 vs 0.83, p = 0.08). Conclusions: Pembrolizumab alone or combined with chemotherapy compared with chemotherapy alone exhibited favorable responses in terms of ORR, OS and PFS with a manageable toxicity profile, setting a benchmark for future studies. Characteristics of included studies. Trial ID, phase Histology Line Number of patients Regimen Median follow-up (mo) ORR (%) Median PFS (mo) Median OS (mo) KEYNOTE-590, III ESCC, EAC 1 st 749 Pembro + chemo vs chemo 58.8 45 vs 29.3 6.3 vs 5.8 12.3 vs 9.8 KEYNOTE-181, III ESCC, EAC 2 nd 628 Pembro vs chemo 7.1 13.1 vs 6.7 2.1 vs 3.4 9.3 vs 6.9 KEYNOTE-180, II ESCC, EAC 3 rd or later 121 Pembro 5.8 9.9 2.0 5.8 KEYNOTE-028, 1b ESCC, EAC 3 rd or later 21 Pembro 7 30 1.8 7 Pembro: pembrolizumab, mo: month.

Association between muscle mass, visceral adiposity, and histologic tumor stromal features in colon cancer.

Sarcopenia and obesity are indicators for poor outcomes in colon cancer. Additionally, aggressive histopathologic tumor stromal features, such as a low tumor-stroma ratio (TSR) and low tumor-infiltrating lymphocytes (TILs) predict survival and treatment response. As their relationship remains underexplored, we studied the association between skeletal muscle mass, visceral adipose tissue (VAT), TSR, and TILs in patients with colon cancer. We studied 194 stage II/III colon carcinoma patients who underwent elective surgery. Preoperative computed tomography (CT) scans classified patients into four groups based on skeletal muscle index (normal/low) and visceral adipose tissue index (normal/high). Tumor tissues were assessed for TSR and TILs, and five-year disease recurrence and relative hazard were evaluated. Among the patients, 56 (28.9%) were classified as Normal Muscle, Normal VAT, 26 (13.4%) as Normal Muscle, High VAT, 75 (38.7%) as Low Muscle, Normal VAT, and 37 (19.1%) as Low Muscle, High VAT. Patients with low skeletal muscle mass were more often male (62.5% vs. 39%, P=0.005). Stroma-high tumors were less common in Low Muscle, Normal VAT patients (24%) compared to Normal Muscle, High VAT (50%), Low Muscle, High VAT (48.6%), and Normal Muscle, Normal VAT (41.1%) patients (P=0.020). Tumors with low TILs were similarly distributed across groups (P=0.679). Low Muscle, Normal VAT patients had a lower recurrence hazard compared to both Low Muscle, High VAT (hazard ratio [HR] 0.34, 95% CI 0.12-0.98, P=0.048) and Normal Muscle, Normal VAT (HR 0.31, 95% CI 0.11-0.87, P=0.027) patients. Low Muscle, Normal VAT colon cancer patients exhibited fewer aggressive tumor features and a lower recurrence risk compared to Low Muscle, High VAT patients. These findings highlight the importance of body composition in tumor biology and prognosis.

Tumor-to-tumor metastases: systematic review and meta-analysis of 685 reported cases.

Tumor-to-tumor metastasis is an exceedingly rare phenomenon where secondary deposits of a tumor develops in another one. Our systematic review and meta-analysis aims to uncover and analyze reported cases to enhance our understanding and improve patients' care. A comprehensive search of the literature was conducted to identify 685 cases of tumor-to-tumor metastasis from 543 articles. Key information, including the donor and recipient organs, tumor histology, primary to metastasis time interval, presence of distant metastases and overall survival was extracted and analyzed. The highest incidence of tumor-to-tumor metastasis was observed in breast cancer and lung cancer metastasizing to meningioma (n = 52, 7.6%; n = 49, 6.2%; respectively). There were 131 (19.2%) autopsy cases, 477 (69.6%) cases diagnosed in vivo, and in 77 cases (11.2%), the timing of diagnosis was unavailable. Death of the patient (including autopsy cases) was reported in 256 (37.4%) cases. In 160 (23.35%) patients, the primary of the metastasis (POM) was occult at the time of metastasis, and in 385 (56.2%) cases, the POM was already known. The median period between clinically overt primary cancer diagnosis and tumor-to-tumor metastasis was 2.0years. Donor metastases to other sites were observed in 328 (47.9%) cases. In multivariate Cox regression analysis, the primary-to-metastasis interval (< 3 vs > 3years, HR 2.01, 95% CI 1.18-3.43, p = 0.01) and the presence of donor metastases to other sites (present vs absent; HR 0.37, 95% CI 0.23-0.59, p < 0.001) were significantly associated with survival. In summary, our findings emphasize the necessity for heightened clinical vigilance, early detection, and tailored management to effectively address this unique and challenging clinical scenario.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited. We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment. Predicted superpopulations included African (AFR, N=153), Admixed American (AMR, N=222), East Asian (EAS, N=67), European (EUR, N=968), and South Asian (SAS, N=42). Reported race and ethnicity and ancestry-based genetic superpopulations were non-randomly associated (p<0.001). Patients with an atypical teratoid rhabdoid tumor or meningioma were enriched for AFR ancestry (OR=2.6, FDR=0.01; OR=2.9, FDR=0.01, respectively). Among KIAA1549::BRAF fusion-positive low-grade glioma (LGG) diagnoses, EAS and SAS patients disproportionately harbored exon 15:09 breakpoints (FDR<0.05), and AMR patients demonstrated rare breakpoints, which were associated with lesser degree of surgical resection and worse event free survival (EFS) versus other breakpoints (HR=4.6, p=0.03). Non-EUR and AMR patients with germ cell tumors and SHH-activated medulloblastoma, respectively, exhibited worse EFS relative to EUR patients (HR=12.1, p<0.01; HR=5.2, p=0.03) and AFR patients with LGG (HR=16.4, p<0.01) or ependymoma (HR=5.5, p=0.02) had worse overall survival compared to EUR patients. We observed higher frequency of clinical trial enrollment among AMR patients across tumor histologies (OR=2.0, p=<0.01), but increased utilization of photon versus proton radiation relative to other superpopulations (OR=0.55, p=0.04). Genetic ancestry-associated differences exist across pediatric CNS tumor histological and molecular subtypes from PBTA and PNOC. Further investigation into genetic and socioeconomic factors contributing to these observed inequities is needed.

Bone marrow metastasis of ovarian cancer: A two‑center retrospective study and literature review.

Bone marrow metastasis (BMM) causes pancytopenia and disseminated intravascular coagulation (DIC), resulting in rapid mortality. The incidence of this disease is likely underestimated, with confirmed BMM occurring at approximately twice the rates expected clinically. The present study describes two detailed cases and includes a literature review of BMM caused by ovarian cancer. The existing medical records of patients admitted to Oita University Hospital (Yufu, Japan) and Saitama Medical University International Medical Center (Hidaka, Japan) were retrospectively analyzed and a literature review regarding BMM associated with ovarian cancer was conducted. The literature review of BMM of ovarian cancer, including the present cases, revealed that patient ages ranged between 37 and 71 years, with tumor histology described in 5 out of 8 cases. Notably, 3 previous cases involved rare histological types (small cell carcinoma, carcinosarcoma and mucinous carcinoid), whereas the present identified cases involved common types. The first case involved a patient who developed isolated BMM/carcinomatosis during maintenance therapy with olaparib for recurrent high-grade ovarian serous carcinoma. The patient initially presented with elevated cancer antigen 125 levels and decreased blood counts. Following the onset of BMM, the patient's lactate dehydrogenase level was elevated to 2,712 U/l. The second patient was diagnosed with BMM/carcinomatosis, concurrent with an initial diagnosis of ovarian clear cell carcinoma. Both patients subsequently developed pancytopenia and DIC, resulting in mortality. To the best of our knowledge, the present study is the first retrospective study of BMM of ovarian cancer. For early diagnosis, BMM should be considered in the differential diagnosis when a reduction in blood counts is accompanied by an elevation in serum tumor markers, regardless of histological type.

Profiling Sociodemographic Risk Factors and Clinical Outcomes of Women with Endometrial Cancer in Puerto Rico: The Central Role of Obesity and Obstetric Features.

Incidence of endometrial cancer (EC) in Hispanic/Latina (H/L) women are higher compared to other race/ethnicities in the United States. EC is the third most common cancer and the fourth cause of cancer-related deaths in Puerto Rican women, yet demographic and clinical information is limited. High rates of EC risk factors such as obesity, diabetes mellitus type 2 (DM2) and hypertension (HTN) have been documented in the Puerto Rican population. To describe the demographic, clinical history, lifestyle, obstetrical-gynecological, pathologic, and molecular profiles of women with EC predominantly from Southern/Central Puerto Rico. We conducted a retrospective secondary analysis of data abstracted from the Puerto Rico Central Cancer Registry (PRCCR), self-administered questionnaires and medical records of EC cases. Descriptive statistics were conducted using SPSS V28 and RStudio. We identified 105 EC cases aged 28-82. The major risk factors were BMI ≥ 30 (72%), HTN (33%), and DM2 (20%). Endometrioid adenocarcinoma was the main histological tumor type (80%), of which 74% were Type I. Obesity and nulliparity were associated with younger age at diagnosis. Older age at diagnosis (> 65 y/o) was associated with more advanced disease. This study defined the clinical-demographic profile of women with EC from Puerto Rico and identified risks factors that are associated with younger or older age at diagnosis. Profiling the risk factors for EC may help improve diagnostic accuracy and clinical management and result in better outcomes for this under-served, under-researched cancer patient population.

Treatment of focal anaplastic Wilms tumor: A report from the Children's Oncology Group AREN0321 and AREN03B2 studies.

In the fifth National Wilms Tumor Study, patients received vincristine and dactinomycin (VA) without radiation for stage I focal anaplastic Wilms tumor (FAWT) and VA plus doxorubicin (DD4A) and radiation for stage II-IV FAWT. Four-year event-free survival (EFS) and overall survival (OS) for stage I FAWT were 67.5% and 88.9% and for stage IV FAWT were 61.4% and 71.6%, respectively. Therapy intensification for stage I and IV FAWT was evaluated as secondary objectives in AREN0321. Central review in the AREN03B2 Renal Tumors Classification, Biology, and Banking Study confirmed patient stage and tumor histology. Patients were then enrolled in AREN0321 and received DD4A with radiation for stage I-III FAWT and vincristine, doxorubicin, cyclophosphamide, carboplatin, and etoposide (UH-1/revised UH-1) with radiation for stage IV FAWT. Outcomes of patients with FAWT who were treated in AREN0321 (n=25) and in AREN03B2 (n=20) treated as per AREN0321 were analyzed. In the pooled data analysis from AREN0321 and AREN03B2, 4-year EFS and OS were both 100% for stage I-II FAWT (n=21), 82.4% (95% CI, 66.1%-100%) and 87.8% (95% CI, 73.4%-100%) for stage III FAWT (n=17), respectively, and both 85.7% (95% CI, 63.3%-100%) for stage IV FAWT (n=7). Four patients enrolled in AREN0321 had events: treatment failure occurred in three patients with stage III FAWT, and one treatment-related death was observed in a patient with stage IV FAWT following revised UH-1. No EFS or OS events occurred in patients with FAWT enrolled in AREN03B2 only. Patients with stage I and II FAWT have outstanding survival when treated with DD4A and radiation. Intensification of therapy may have improved survival for stage IV FAWT, albeit with an increased toxicity risk.

Incidence, characteristics, and comorbidities of a complete unselected Danish cohort of patients with thymic epithelial tumors.

We report the incidence, characteristics, and comorbidities of the complete unselected Danish cohort of patients with thymic epitheliums (TETs), which may serve as evidence for guiding treatment, surveillance, and counselling of TET patients. All patients diagnosed with TETs from January 1st, 2015, to December 31st, 2020, were identified using the Danish Pathology Data Registry. Data on patient characteristics, comorbidities, and tumor histology were collected from electronic medical records available for all patients. The cohort consisted of 283 patients with a mean age of 64 years (SD: 12). The crude rate was 8.2/1,000,000 TETs annually, thus higher than the age-standardized rates of 4.8/1,000,000 in the WHO World Standard Population and 6.1/1,000,000 in the European Standard Population. Thymomas were diagnosed in 240 patients (85%) (9% type A, 31% AB, 18% B1, 26% B2, 6% B3, 5% micronodular, 0.4% metaplastic, and 5% of unspecified subtype), thymic carcinomas in 39 patients (14%), and thymic neuroendocrine tumors in 4 patients (1.4%). Tumors in Tumour, Node, Metastasis (TNM) stage I were diagnosed in 181 patients (64%) and were mostly thymomas (72%). Prior to TET diagnosis, 91 (32%) patients presented with autoimmune disorders (19% myasthenia gravis) and 82 patients (29%) had at least one cancer diagnosis. We found a higher incidence of TETs in Denmark than in previous European population-based studies, while reporting a similar distribution of histological types and tumor stages. Furthermore, we found an increased prevalence of autoimmune disorders and cancers in the cohort before TET diagnosis compared to the general population.

Impact of Psychological Factors on Survival in Metastatic Esophagogastric Cancer: Secondary Analysis of a Randomized Controlled Trial.

Early interdisciplinary supportive care (ESC), including psychological interventions, can improve the survival of patients with metastatic esophagogastric cancer (EGC). The purpose of the study was to evaluate the association between psychological factors and survival in patients with metastatic EGC. A secondary analysis was conducted for an open-label randomized controlled trial of ESC, in which 246 patients with EGC completed a distress measure (the distress thermometer) and a depression symptom measure (the Patient Health Questionnaire-9 [PHQ-9]) at baseline before cancer treatments. Cox regression was applied to explore the influence of psychological distress and depressive symptoms on overall survival (OS) and progression-free survival (PFS). Patients with moderate depressive symptoms (PHQ-9 ≥8) had shorter PFS (3.5 v 6.0 months, P < .001) and shorter OS (10.7 v 15.0 months, P = .001) than those without. Patients with significant psychological distress had worse PFS (4.8 v 6.3 months, P = .035) and worse OS (13.4 v 15.5 months, P = .039) than those without. After controlling for performance status, group, sex, primary tumor site, tumor histology, and age, only depressive symptoms remained associated with worse PFS (adjusted hazard ratio [HR], 2.02 [95% CI, 1.41 to 2.91]; P < .001) and worse OS (adjusted HR, 1.70 [95% CI, 1.17 to 2.47]; P = .006). This study shows that depressive symptoms at baseline were associated with poor survival in patients with newly diagnosed metastatic EGC. Therefore, screening and preventive intervention for depression should be integrated into routine cancer care for this population.