Search Results (306)

Background: Hormone receptor-positive (HR+), HER2− negative metastatic breast cancer (MBC) is the most common subtype of advanced breast cancer. Resistance to endocrine therapy often develops, particularly after CDK4/6 inhibitors. Everolimus, an mTOR inhibitor, may restore hormone sensitivity, but real-world data after CDK4/6 and chemotherapy are limited. Methods: This retrospective, single-center study included 70 patients with HR+/HER2− MBC who progressed on CDK4/6 inhibitors and at least one line of chemotherapy. All received daily oral everolimus (10 mg) plus exemestane (25 mg). Tumor response was assessed via RECIST v1.1, and survival outcomes were estimated using the Kaplan–Meier method. Results: Median progression-free survival was 6.6 months and overall survival was 22.6 months. The disease control rate was 88.6%, with 57.1% showing partial response. Fatigue (20%), skin toxicity (8.6%), and stomatitis (5.7%) were the most common adverse events. No grade 3–4 toxicities or discontinuations occurred. No clinical or pathological variables significantly influenced survival. Conclusions: Everolimus plus exemestane provided meaningful clinical benefit and manageable toxicity in heavily pretreated HR+/HER2− MBC patients. This regimen remains a valid later-line option, particularly in settings with limited access to newer targeted therapies or genomic testing. Full article

Objective: Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy, with limited treatment strategies in the recurrent or metastatic cases. Although immune checkpoint inhibitors (ICIs) have shown efficacy in head and neck cancers (HNCs), clinical data specific to SNSCC are scarce. This study aimed to evaluate the therapeutic efficacy and prognosis of ICIs in patients with SNSCC. Methods: We conducted a retrospective review of 18 patients with pathologically confirmed SNSCC treated with nivolumab or pembrolizumab at Gifu University Hospital between May 2017 and December 2024. Treatment response was assessed using RECIST v1.1 criteria. Overall response rate (ORR) and disease control rate (DCR) were evaluated as treatment effects, and overall survival (OS) and progression-free survival (PFS) were evaluated as prognoses. Subgroup analyses were performed according to treatment regimen. Results: The ORR and DCR for all patients were 43.8% and 56.3%, respectively. Pembrolizumab-treated patients showed higher response rates (ORR: 66.7%; DCR: 83.3%) compared to those treated with nivolumab (ORR: 30%; DCR: 40%). Median OS and PFS were 21.5 and 7.9 months, respectively. Long-term durable responses exceeding two years were observed in several cases. Although pembrolizumab tended to result in better outcomes, no statistically significant difference was found between groups. Immune-related adverse events were infrequent and manageable. Conclusions: This study suggests that a subset of patients with SNSCC may benefit from ICI therapy, particularly in combination with chemotherapy. Despite the rarity of SNSCC, accumulating clinical evidence—including prospective studies—is essential to establish standardized treatment strategies for this disease. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. At the time of diagnosis, many HCC patients are not candidates for surgical resection and are considered for other locoregional therapies, including transarterial radioembolization (TARE) and stereotactic body radiation therapy (SBRT). To date only a few studies have explored the safety and efficacy of combining TARE and SBRT. Therefore, we aimed to evaluate it. Patients who received both SBRT and TARE from 2016 to 2024 were retrospectively evaluated for treatment-related toxicity based on criteria for adverse events (CTCAE v4.0). Treatment response was evaluated by modified response evaluation criteria for solid tumors (m-RECIST). We identified 12 patients with median age of 66.5 (range: 40, 87) and median follow up of 12 months. The median time between TARE and SBRT was 6.5 months (range: 1.5 to 24). Following the second treatment, ALBI grade remined the same among all patients at 3-month post treatment compared to baseline. Baseline CP was A among all patients and remained unchanged during follow-up and no higher than grade 3 clinical or biochemical toxicity was seen. The objective response rate (ORR) among patients receiving treatment to the same lesion was 100%. The combination treatment was consistent with prior studies in which the combination of TARE and SBRT has been shown to have good local control with few cases of grade 3 toxicity. Our study demonstrates that treatment with TARE and SBRT was safe and effective among our small sample of patients. Full article

Immune checkpoint inhibitors (ICIs) are a key treatment for advanced non-small cell lung cancer (NSCLC), but most patients will ultimately experience disease progression due to acquired resistance to ICI. Clinically, it is relevant to differentiate between systemic progression (SP) and oligoprogression (OP). Following SP, ICI treatment is usually discontinued, while in OP, patients are preferably treated with local ablative treatment with continuation of the ICI treatment. However, with progressive disease, it remains difficult to differentiate between true OP or SP. Circulating tumor DNA (ctDNA) analysis provides an accurate real-time reflection of the tumor burden. It remains elusive if ctDNA abundance and/or dynamics can discriminate between OP and SP. Therefore, the aim of this exploratory cohort study is to evaluate whether the sequential molecular tumor profiling of ctDNA is suitable for discriminating between true OP and SP in advanced NSCLC. Patients with stage III/IV NSCLC showing progression after ≥3 months of ICI were included. OP was defined retrospectively by RECIST response ≥ 6 months after local treatment and continued ICIs. Serial plasma samples were analyzed using the AVENIO ctDNA Expanded NGS assay targeting 77 cancer-related genes. Twenty patients (6 OP, 14 SP) were included. Somatic alterations were detected in 16 patients (median 4 mutations). No significant differences in baseline ctDNA levels, changes at progression, or mutation patterns were observed between OP and SP. Although ctDNA levels generally decreased early after the start of ICI treatment, and were increased at disease progression, mutational profiles of the 77 genes using the AVENIO Expanded ctDNA panel did not distinguish OP from SP. Full article

Background/Aims: Predicting treatment response to immunotherapy in hepatocellular carcinoma (HCC) is essential to improve clinical outcomes with personalized treatment strategies. This study aims to develop an AI-driven prediction model using radiomic analysis from the liver and viable HCCs on pretreatment CT to differentiate responders from non-responders. Methods: HCC patients who received immunotherapy between 2016 and 2023 with pretreatment CT scans were included. Radiomic features were extracted from the whole liver and the viable HCCs on the portal venous phase CT prior to immunotherapy. Multiple machine learning models were trained for binary classification to predict treatment response, initially using liver features (Model 1), and subsequently including both liver and tumor features (Model 2). Model performance was evaluated using three-fold cross-validation. Results: Among 55 HCC patients (median age, 69; 76.4% male) who received immunotherapy, 21 (38.2%) were responders and 34 (61.8%) non-responders by mRECIST criteria. Over 5000 radiomic features were extracted from pretreatment CT scans of the liver and viable tumors, of which approximately 100 were predictive of treatment response. Model 1 (liver) achieved an average accuracy of 77%, sensitivity of 76%, and specificity of 78%. Model 2 (liver and tumor) demonstrated improved performance, with accuracy, sensitivity, and specificity of 86%, 70%, and 94%, respectively, supporting the value of combined liver–tumor radiomics in treatment response prediction. Conclusions: This pilot study developed an AI-based model using CT-derived radiomic features to predict immunotherapy response in HCC patients. The approach may offer a non-invasive strategy to support personalized treatment planning using pretreatment CT scans. Full article

Objectives: Cervical cancer remains a significant global health burden for women. While neoadjuvant chemotherapy (NACT) has emerged as a potential treatment option, the prognostic implications of early non-response to NACT remain inadequately characterized. This systematic review aims to elucidate the association between early non-response to NACT and long-term disease-free survival (DFS) in cervical cancer patients. Methods: A comprehensive systematic review was conducted following PRISMA guidelines. PubMed, Embase, Elsevier, Springer, EBSCO, and Cochrane Library were systematically searched to identify eligible studies. Pooled hazard ratios (HRs) for DFS with 95% confidence intervals (CIs) were calculated using R software (version 4.5.1). Heterogeneity was assessed via Cochran’s Q test and I² statistics. Publication bias was evaluated using funnel plots, Begg’s test, Egger’s test, and trim-and-fill methods. Sensitivity analyses further validated result robustness. Results: Eleven studies (n = 2064 patients; 1546 responders, 518 non-responders) met inclusion criteria. The pooled early non-response rate ranged from 13% to 39%. Early non-response significantly correlated with poorer DFS (HR = 3.29, 95% CI 2.35–4.62). Subgroup analyses by response criteria showed HRs of 2.94 (95% CI 1.72–5.03) for WHO criteria and 4.00 (95% CI 2.52–6.34) for RECIST criteria. No significant publication bias was detected (Begg’s p = 0.35; Egger’s p = 0.28). Sensitivity analyses and trim-and-fill adjustments confirmed result stability. Conclusions: Early non-response to NACT predicts worse DFS in women with cervical cancer. These findings proposed the need for large-scale or prospective studies to validate the prognostic value of early non-response and optimize treatment strategies for non-responders. Future prospective trials with standardized protocols are essential to validate these findings and establish criteria for optimizing patient selection for NACT-based therapeutic strategies. Full article

Background and Objective: Colorectal cancer (CRC) most commonly metastasizes to the liver and lungs; however, synchronous metastases to pelvic structures such as the vagina and urethra are extremely rare, posing a significant diagnostic and therapeutic challenge. This report describes an unusual case of sigmoid colon adenocarcinoma with synchronous metastases to the vagina and urethra, highlighting its diagnostic evaluation and the value of a multidisciplinary approach. Methods: A 59-year-old woman with a history of deep vein thrombosis treated with apixaban presented with chronic constipation and pelvic bleeding. A gynecological evaluation revealed a vaginal lesion. A colonoscopy, biopsy, pelvic magnetic resonance imaging, and molecular profiling were performed. Treatment included chemotherapy (capecitabine and oxaliplatin), panitumumab, and pelvic radiotherapy. Results: The biopsy confirmed a moderately differentiated invasive adenocarcinoma in the sigmoid colon with synchronous metastases to the vagina and urethra. Molecular profiling identified a rat sarcoma virus oncogene and BRAF (B-Raf proto-oncogene), allowing for the use of targeted therapy. The patient achieved a complete response according to RECIST 1.1 criteria and significant symptomatic improvement, including pain reduction, although dosages were adjusted for thrombocytopenia. She is currently continuing palliative treatment with good tolerance and durable symptomatic improvement. Conclusions: This case underscores the need to consider unusual metastatic sites in patients with colorectal cancer presenting with gynecological symptoms. Early diagnosis, based on imaging and histology, alongside molecular characterization, is crucial for effective personalized therapy. Multidisciplinary coordination is key to optimizing clinical outcomes in these rare metastatic presentations. Full article

Purpose: Neuroendocrine carcinomas (NECs) are aggressive tumors treated with cisplatin-based chemotherapy, though responses vary. As DNA damage response (DDR) pathways influence cisplatin sensitivity, this single-center retrospective study evaluates the efficacy of first-line cisplatin in recurrent or metastatic NEC based on DDR mutation status. Materials and Methods: This study analyzed patients with grade 3 recurrent or metastatic NEC treated with first-line etoposide plus cisplatin at Samsung Medical Center between January 2019 and September 2023. All patients underwent next-generation sequencing to determine DDR mutation status, defined by pathogenic alterations in major DNA repair pathways. Clinical outcomes were assessed per RECIST v1.1. Survival analyses were conducted using Kaplan–Meier methods and Cox regression models, with significance set at p ≤ 0.05. Results: A total of 40 patients with NEC were included in this study. There were 16 patients with DDR wild-type (WT) and 24 patients with DDR mutant type (MT). The most common primary tumor sites were the pancreas (25.0%), stomach (20.0%), and gallbladder/duct (12.5%). Among 40 patients, those with DDR mutations (n = 24) showed significantly higher objective response (58.3% vs. 12.5%) and disease control rates (91.7% vs. 50.0%) compared to patients with DDR WT (n = 16). The median progression-free survival (PFS) showed the favorable trend in the DDR mutant group (8.0 vs. 4.3 months; p = 0.15), with similar trends observed across homologous recombination repair (HRR), Fanconi anemia (FA), and mismatch repair (MMR) subgroups. Conclusions: This study revealed that patients with DDR mutations had significantly higher response to first-line etoposide–cisplatin, suggesting DDR mutation status as a potential predictive marker to guide treatment and improve outcomes in recurrent or metastatic NEC. Full article

The standard treatment for patients with locally advanced non-small cell lung cancer (NSCLC) is concurrent chemoradiation. However, clinical responses are heterogeneous and generally not known until after the completion of therapy. Multiple studies have investigated imaging predictors (radiomics) for different cancer histologies, but little exists for NSCLC. The objective of this study was to develop a multivariate CT-based radiomics model to a priori predict responses to definitive chemoradiation in patients with lung adenocarcinoma. Methods: Patients diagnosed with locally advanced unresectable lung adenocarcinoma who had undergone chemoradiotherapy followed by at least one dose of maintenance durvalumab were included. The PyRadiomics Python library was used to determine statistical, morphological, and textural features from normalized patient pre-treatment CT images and their wavelet-filtered versions. A nested leave-one-out cross-validation was used for model building and evaluation. Results: Fifty-seven patients formed the study cohort. The clinical stage was IIIA-C in 98% of patients. All but one received 6000–6600 cGy of radiation in 30–33 fractions. All received concurrent platinum-based chemotherapy. Based on RECIST 1.1, 20 (35%) patients were classified as responders (R) to chemoradiation and 37 (65%) patients as non-responders (NR). A three-feature model based on a KNN k = 1 machine learning classifier was found to have the best performance, achieving a recall, specificity, accuracy, balanced accuracy, precision, negative predictive value, F1-score, and area under the curve of 84%, 70%, 80%, 77%, 84%, 70%, 84%, and 0.77, respectively. Conclusions: Our results suggest that a CT-based radiomics model may be able to predict chemoradiation response for lung adenocarcinoma patients with estimated accuracies of 77–84%. Full article

Background: Transarterial radioembolization (TARE) with Yttrium-90 microspheres is an established therapy for unresectable hepatocellular carcinoma (HCC). However, its clinical efficacy compared to transarterial chemoembolization (TACE) remains unclear. Methods: We retrospectively reviewed 279 consecutive patients undergoing TARE (n = 104) or TACE (n = 175) at four tertiary centers. Patients with metastatic disease, locally advanced HCC, or Child–Pugh (CP) C were excluded. Data on treatment, adverse events, survival outcomes (median overall survival [mOS], and objective response rates [by modified Response Evaluation Criteria in Solid Tumors; mRECIST]) were collected. Results: The median follow-up of the cohort was 27 months (IQR 13–50), the mean age was 67.6 ± 10.1 years, and 207 (74.2%) were male. The cohort was balanced in age, performance status, CP class, and HCC etiology. Maximum tumor diameter was significantly larger in the TARE cohort compared to the TACE cohort (4.4 vs. 3.1 cm, p < 0.001), including within the BCLC 0/A (4.2 vs. 2.7 cm, p = 0.001) and BCLC B (5.0 vs. 4.0 cm, p = 0.049) subgroups. The mOS was longer with TACE (37 vs. 22 months; hazard ratio [HR] 1.65, 95% CI: 1.19–2.29, p = 0.002). In BCLC 0/A patients, TACE yielded longer mOS (60 vs. 25 months; HR 2.35, 95% CI: 1.17–4.69; p = 0.016). In BCLC B, mOS was longer with TACE (32 vs. 20 months), but was not statistically significant (HR 1.39, 95% CI: 0.96–2.03, p = 0.080). In BCLC 0/A, complete response rates were higher with TACE (43.2% vs. 34.3%, p = 0.012). Hepatic decompensation was more frequent with TARE- (26.0%) than with TACE-treated patients (13.7%, p = 0.010). Conclusions: TACE demonstrated superior survival outcomes over TARE, particularly in early-stage disease. These results advocate for a more nuanced selection of embolization therapies in these patients. Full article

Background/Objectives: Pembrolizumab demonstrates a high response rate in patients with mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC), with responses often sustained even after treatment cessation. However, the pathological complete response (pCR) rate in clinically responding cases remains unknown. This study aimed to evaluate the relationship between the radiological and pathological responses in patients with dMMR mCRC who responded to pembrolizumab. Methods: This retrospective study included 27 patients with dMMR mCRC treated with pembrolizumab. The radiological response was assessed using RECIST version 1.1 criteria. The pathological response was evaluated in patients who underwent metastasectomy, with pCR defined as the absence of residual cancer cells. Results: The median progression-free survival (PFS) of the cohort was 19 months. Among the 27 patients, 3 achieved clinical complete response (cCR), and 10 had clinical partial response (cPR), resulting in a response rate of 48%. All three patients with cCR maintained their responses without metastasectomy (2-year PFS: 100%). Among patients with cPR, eight maintained their responses, while two experienced progression (2-year PFS: 75%). Five patients with cPR underwent curative-intent metastasectomy, and four of them (80%) achieved pCR. Thus, at least 40% of patients with cPR in this cohort had no residual cancer histologically. Conclusions: Our findings demonstrate the significant discordance between the radiological and pathological responses to pembrolizumab in dMMR mCRC patients, with 80% of those with cPR achieving pCR upon metastasectomy. These observations highlight the need for improved response assessment methods for precision immunotherapy. Full article

Background: Checkpoint inhibitor-associated pneumonitis (CIP) after immunotherapy has become a challenging issue in non-small cell lung cancer (NSCLC) patients. This study leverages artificial intelligence (AI) algorithms to analyze radiomic features, aiming to predict the occurrence of CIP, as well as tumor response. Methods: This study analyzed data from 159 stage III-IV NSCLC patients undergoing immunotherapy. The patients were categorized into pneumonitis and non-pneumonitis groups, and 3D radiomic features from both tumors and surrounding regions were extracted using LIFEx software. To address scanner-associated variations, a linear mixed-effect radiomics harmonization model was applied. A random forest algorithm was then used to develop models predicting CIP occurrence and tumor responses based on the pre-treatment CT radiomics. The accuracy was evaluated using the area under the curve (AUC). Results: A total of 159 patients were analyzed, of which only 31 experienced CIP. Most had grade 1 (17/31, 54.8%) or 2 (12/31, 38.7%) pneumonitis; only two (6.5%) patients had grade 3. Patients who developed pneumonitis were more likely to be male (64.5% vs. 38.3%, p = 0.014), had less adenocarcinoma histology (54.8% vs. 78.9%, p = 0.032), and exhibited a higher tumor mutational burden (57.1% vs. 24.5%, p = 0.047). Radiomics analysis reported predictability for CIP with an AUC of 0.60 (95% CI 0.55–0.66). The five-year overall and progression-free survival rates were 24.7% (95% CI 15.2–35.5%) and 9.7% (95% CI 4.4–17.4%), respectively. The radiomics features also exhibited AUCs of 0.63 (95% CI 0.59–0.67) in irRECIST and 0.66 (95% CI 0.61–0.70) in RECIST 1.1 in terms of tumor responses to immunotherapy. Conclusions: This study provides insights into the potential role of radiomic models in predicting CIP and tumor responses from pre-treatment CT images of NSCLC patients treated with immunotherapy. Full article

Background/Objectives: This systematic review and meta-analysis evaluated the effectiveness and the safety of transarterial radioembolization using Holmium-166 microspheres (Ho-166-TARE) for the treatment of primary and secondary liver tumors. The aim of the study was to offer a detailed analysis of clinical outcomes and the potential benefits of this innovative therapy. Methods: The study was conducted according to the PRISMA 2020 guidelines. The systematic search was performed in five databases in November 2023 and updated in June 2024. All 16 eligible studies were original research that evaluated Ho-166-TARE. The endpoints analyzed were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), clinical and laboratory adverse events, healthy-liver- and tumor-liver-absorbed doses. The risk of bias was assessed using the MINORS checklist. Results: The pooled overall disease control rate (DCR) was 72% (95% CI, 46–89%); by mRECIST, it was 93% (95% CI, 71–99%); and by RECIST 1.1, it was 54% (95% CI, 22–83%) at 3-month follow-up. Overall survival (OS) at 3, 6, 12, and 30 months was 98%, 89%, 74%, and 39%, respectively. Severe clinical adverse events were minimal, although some patients showed elevated GGT levels and lymphocytopenia. Tumor-absorbed doses were nearly three times higher than those in healthy liver tissue. Conclusions: These findings suggest that Ho-166-TARE is a safe and effective locoregional treatment option for liver tumors, especially in cases where systemic therapy alone is insufficient or surgical resection is not feasible. Further studies are needed to investigate tumor-specific response, optimize dosimetry strategies, and establish standardized protocols for long-term outcome assessment. Full article

Mammary gland tumors in dogs are very common in clinical practice. Betulinic acid is currently a compound considered to have anticancer properties in human mammary tumors via nanoemulsions. In this study, betulinic acid nanoemulsions with a particle size of less than 300 nm were prepared. Biopsies were obtained from five female dogs with mammary tumors for histopathological analysis, confirming that two were tubular mammary carcinomas (MMTs, malignant) and three were complex mammary adenomas (BMTs, benign). The five female dogs were administered with a daily oral dose of nanoemulsion containing 5 mg/kg of betulinic acid for 30 days. Tumor size was measured every 7 days, and the response to treatment was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors) standards. In one of the females with MMTs treated with the nanoemulsion, the tumor size was reduced by approximately 38%, while in the BMT female dogs, the nanoemulsion reduced the tumor size by 25.3%. It was concluded that oral administration of betulinic acid nanoemulsions reduced the size of canine mammary tumors. Experimental studies are still needed to further evaluate this preparation. Full article

Background: A previous published Phase 2 trial using 2–4 doses of neoadjuvant cemiplimab in stage II–IV resectable cutaneous squamous cell carcinoma (CSCC) demonstrated that a complete pathological (pCR) rate of 51% and major pathological response (mPR) rate of 13% could be achieved with durable disease control. Methods: In this open-label, single-institution phase II trial (NCT05878288), patients with stage II–IV resectable CSCC received up to four doses of neoadjuvant cemiplimab prior to surgery. The primary endpoint of the study was to perform comprehensive molecular profiling. The focus of this report are the secondary clinical endpoints of pCR rate, mPR (defined as <10% viable tumour) rate, overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, immune-modified RECIST (imRECIST) and Immune PET Response Criteria in Solid Tumours (iPERCIST), disease-free survival (DFS), overall survival (OS), safety, and to describe changes in planned surgery. Results: Eleven patients were enrolled, with all proceeding with surgery. An ORR and pCR rate of 73% (8/11; 95% CI 0.39–0.93) was achieved, whilst 3/11 patients progressed on treatment. On pre-operative imaging, all 8/11 pCR patients demonstrated a partial response (RECIST 1.1), whilst 6/8 achieved a complete metabolic response and 2/8 a partial metabolic response (iPERCIST). Median follow-up was 10.2 (IQR 6.7–16.4) months. DFS was 91% (95% CI 0.57–1) and OS was 100% (95% CI 0.68–1), with one non-responder patient who developed recurrent locoregional and distant metastatic disease. There were no unexpected safety signals. Pathological features of response to neoadjuvant immunotherapy most commonly were granulomatous inflammation with keratin, fibrosis and inflammation. No cases with a dense inflammatory infiltrate were observed. Neoadjuvant immunotherapy did not impact the intra-operative planning and execution of surgery, but in the eight pCR cases, it reduced the extent of required surgery, whilst in the three non-responder cases, surgery was more extensive than originally planned. Conclusions: The DISCERN trial confirms that an excellent complete response rate can be achieved with four doses of neoadjuvant immunotherapy in stage II–IV CSCC. Proposed refinements to the pathological assessment of response and metabolic response criteria in CSCC for the neoadjuvant context are provided. Full article