Search Results (187)

Metastasis is the main cause of failure in anticancer therapies, and is frequently related to poor prognosis for patients. The true challenge in extending cancer patient life expectancy, eventually managing cancer as a chronic disease with periodic but controllable relapses, relies on the development of effective therapeutic strategies specifically targeting key mechanisms involved in the metastatic cascade. Traditional chemotherapy with alkylating agents, microtubule inhibitors, and antimetabolites has shown limited efficacy against metastatic cells, largely due to the emergence of chemoresistant populations that undergo epithelial-to-mesenchymal transition (EMT), promoting the colonization of distant organs and sustaining metastatic progression. This scenario has spurred significant efforts to identify small molecules and biologics capable of interfering with specific steps in the metastatic process. In this review, we provide an overview of recent advances involving small interfering RNAs (siRNAs) and microRNAs (miRNAs) in cancer therapy. Although most of these agents are still under investigation and have not yet been approved for clinical use, insights into their development stage offer valuable information to identify new targets in the ongoing fight against metastasis. Particular emphasis is placed on the role of chemical modifications applied to siRNAs, such as backbone, sugar, terminal, base, and conjugation changes, and how these factors influence their stability, immunogenicity, and targeting precision. By integrating these aspects into the discussion, this review provides a focused and up-to-date resource for researchers in medicinal chemistry, drug delivery, and pharmaceutical formulation, where molecular design plays a critical role in therapeutic success. Full article

Background: Conservative mastectomy with prepectoral breast reconstruction is becoming increasingly widespread and validated in recent years. Today, while aesthetic advantages and improvement in quality-of-life outcomes are widely acknowledged, oncological safety remains subject of debate. There is limited evidence on residual breast tissue after conservative mastectomy, and it still represents an unknown risk for local recurrence. The recent spread of this surgical technique precludes a standardized surgical approach in case of local recurrence of ipsilateral breast cancer, and the lack of evidence in the literature complicates the decision-making process. The objective of this study is to describe the surgical treatment of local relapses for breast cancer patients following conservative mastectomy and prepectoral implant-based reconstruction. Methods: Between January 2018 and May 2024 at a single institution, 648 consecutive patients underwent conservative mastectomy and prepectoral reconstruction as their primary treatment. We identified 12 patients with T1-2 breast cancer who subsequently had histologically confirmed ipsilateral breast cancer recurrence and a local wide excision or radical mastectomy were performed. Each clinical case was discussed in a multidisciplinary meeting to define the most appropriate surgical treatment. At time of diagnosis of recurrence, patients with lymph node metastasis or systemic involvement were excluded from the study. Results: Among 648 consecutive patients who underwent conservative mastectomy, 12 with histologically confirmed ipsilateral breast cancer recurrence were included. The mean interval to recurrence was 43 months (range 10–76 months) from the primary operation. Recurrence sites were as follows: upper outer quadrant in four patients (33.4%), upper inner quadrant in three (25.0%), lower inner quadrant in two (16.6%), lower outer quadrant in one (8.4%), and central quadrant with nipple involvement in two (16.6%). Of the 12 patients, 9 (75%) underwent wide local excision, including 2 who also received partial capsulectomy, while 3 (25%) required radical mastectomy with implant removal. Adjuvant radiation therapy was administered to 6 patients (50%)—5/6 (83.3%) in the excision group and 1/6 (16.7%) in the mastectomy group. No significant differences were observed in distant disease–free survival or overall survival between the two groups. Conclusions: Currently, surgical treatment of ipsilateral breast tumor recurrence following conservative mastectomy and prepectoral breast reconstruction is not reported in the literature, and this study represents the first instance where wide local excision is described. The management of ipsilateral recurrence should be discussed in multidisciplinary meetings and could be performed safely in selected cases, sparing the prosthesis and avoiding radical mastectomy. Full article

Background/Objectives: Primary central nervous system lymphoma (PCNSL) is a rare but aggressive tumor, primarily affecting elderly patients. Radiotherapy (RT) remains an important treatment option, particularly for patients who are ineligible for systemic chemotherapy. This study aims to identify prognostic factors and evaluate recurrence patterns in a real-world cohort of PCNSL patients treated with RT. Methods: We retrospectively analyzed 64 PCNSL patients treated with radiotherapy at our institution between 2000 and 2022. Clinical characteristics, treatment details, and outcomes were collected by chart review. Overall survival (OS) was analyzed using Kaplan–Meier and Cox regression methods. Recurrence patterns were assessed based on available post-treatment imaging. Results: Median patient age was 71 years (range: 31–83); 53.1% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2. Radiotherapy was used as first-line treatment in 62.5% of cases, primarily due to contraindications to chemotherapy. Median OS was 10 months from diagnosis. Age, poor performance status, seizures at presentation, absence of systemic therapy, incomplete radiotherapy, and <80% applied dose of planned radiotherapy were associated with inferior OS in our univariable analysis. Multivariable analysis confirmed age, systemic therapy, seizures, and radiotherapy dose <80% as independent predictors. Among twenty-nine patients with imaging follow-up, eight recurrences after RT were documented: six of those within, and two outside of the initially affected areas. All recurrences occurred within previously irradiated areas. Conclusions: This study confirms known negative prognostic factors in PCNSL and underscores the importance of systemic chemotherapy for curatively intended treatments aiming for prolonged survival. The recurrence patterns observed question the added benefit of whole-brain irradiation in preventing distant relapses. These findings support the need for prospective trials to optimize radiotherapy strategies while balancing efficacy and neurotoxicity. Full article

Background/Objectives: Definitive radiotherapy (RT) is a frequently employed salvage option in early-stage, endometrial cancer (EC) loco-regional recurrence patients. Local control (LC) and survival rates are highly variable in the literature. The aim of this review is to assess the impact of modern salvage radiotherapy (SRT) in this group of patients. Methods: A systematic review of the literature was performed, focusing on studies that included EC local recurrence patients receiving SRT after 2000 to reflect advances in radiotherapy techniques. Our report followed the principles as outlined in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Nine studies were included in our analysis with a total sample size of 648 patients. Conclusions: SRT offers excellent LC rates in this group of patients with minimal ≥ grade 3 toxicity. Salvage rates are limited by the presence of well-known risk factors for loco-regional relapses, with distant control being the primary mode of failure, resulting in lower survival rates. The decision to omit adjuvant RT should be weighed against the anticipated salvage outcomes in case of relapse. Full article

Sarcomas are very complex and clinically challenging mesenchymal tumors. Although the standard therapeutic approach has improved the 5-year survival rate, many patients experience local relapses and/or distant metastases. To improve patient outcome, new strategies need to be investigated. Immunotoxins (ITs) based on rRNA N-glycosylases (also named ribosome-inactivating proteins, RIPs) are promising tools for cancer therapy because, by combining rRNA-glycosylase’s high cytotoxicity with carrier selectivity, they can specifically eliminate target neoplastic cells. In the last few years, 3D models have been extensively used in cancer research, particularly for target-specific drug screening. This study aimed to evaluate the possibility of utilizing ribosome-inactivating protein (RIP)-containing ITs to selectively target TfR1-, EGFR1- and Her2-expressing sarcoma adherent cells (ACs), spheroids (SSs) and organoids (ORs). To compare Its’ efficacy and ability to induce apoptosis, we performed dose–response viability and caspase 3/7 activation assays on rhabdomyosarcoma and osteosarcoma ACs, SSs and ORs treated with Tf-IT, αEGFR1-IT and αHer2-IT. Our results indicate that, compared to the corresponding unconjugated RIPs, all ITs showed increased cytotoxicity in sarcoma ACs. Despite the increased complexity characterizing 3D models, the higher IC₅₀ differences between ITs and unconjugated RIPs were obtained in ORs, which appeared more resistant to the nonspecific killing of the RIPs than either the ACs or SSs, thus augmenting the therapeutic window between unconjugated and conjugated RIPs. IT induced a more delayed apoptosis in 3D compared to 2D models. Our results provide essential outcomes for the potential use of these RIP-based ITs as a therapeutic strategy to treat sarcoma. Full article

Purpose: The aim of the present study is to analyze, for the first time, the results of a large prospective academic multicenter trial of partial breast irradiation (PBI) with exclusive photon intraoperative radiation therapy (ph-IORT) in early breast cancer patients, focusing on ipsilateral breast tumor recurrence. The secondary endpoints were (a) incidence of regional/distant recurrence, (b) survival, and (c) toxicity. Methods: From January 2013 to December 2022, patients with low-risk TARGIT-A criteria invasive breast cancer were included in a prospective academic multicenter study of exclusive PBI with ph-IORT during breast-conserving surgery, conducted in three university hospitals in Las Palmas (Hospital Universitario Insular, Hospital Universitario Materno-Infantil, and Hospital Universitario de Gran Canaria Dr. Negrín). Results: Three hundred and twelve patients were included in the study. The mean age at diagnosis was 62 years (46–88). All tumors were classified as luminal molecular profile. No patient received supplementary external beam radiotherapy. Four patients developed ipsilateral breast tumor recurrence (IBTR) at 19, 29, 43, and 62 months of follow-up. Seventeen patients died of intercurrent diseases, and there were only 2 breast cancer-related deaths at 68 and 95 months, respectively. With a median follow-up of 78 months (7–140), actuarial 5-year freedom from local relapse and cancer survival rates were 98.9% and 100%, respectively. No patient developed early or late grade-3 toxicity. Conclusions: Partial breast irradiation with ph-IORT is a feasible, safe, and useful treatment in early breast cancer patients after BCS. A longer follow-up is needed to confirm the present results. Full article

Background: While intratumoral microbiota have been identified in various cancers, their presence and clinical significance in lacrimal gland tumors remain largely unexplored. This study investigates the existence, composition, and potential clinical significance of intratumoral bacteria in lacrimal gland tumors. Methods: High-throughput 16S rDNA sequencing was performed on tumor DNA extracted from 89 paraffin-embedded tissues from patients with lacrimal gland tumors. Diversity analysis and LEfSe differential analysis were conducted to identify tumor-type-specific bacterial taxa. LASSO regression and the Cox proportional hazards models were used to analyze the relationship between intratumoral microbiota and prognosis. Results: Significant differences in the β diversity of intratumoral microbiota were observed across adenoid cystic carcinoma (ACC), carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA), and IgG4-related disease (IgG4-RD) patients. After FDR correction, Garicola, Prevotella, Polaribacter, and Helicobacter were notably enriched in the tumors of ACC, CXPA, PA, and IgG4-RD patients, respectively. Importantly, patients with malignant lacrimal gland tumors who experienced relapse, distant metastasis, or death had significantly higher α diversity within their tumors. Furthermore, specific genera, such as Roseburia and Alloprevotella, were particularly associated with poorer prognosis in patients with malignant lacrimal gland tumors. Conclusions: This study provides a comprehensive analysis of microbial profiles in lacrimal gland tumors, highlighting distinct microbial characteristics across tumor types. Our findings suggest that intratumoral bacterial diversity and specific genera may serve as potential prognostic markers for malignant lacrimal gland tumors. Full article

Background/Objectives: Pancreatic cancer is a very aggressive disease with a poor prognosis, even when diagnosed at an early stage. This study aimed to validate and refine a radiomic-based [¹⁸F]FDG-PET model to predict distant relapse-free survival (DRFS) in patients with unresectable locally advanced pancreatic cancer (LAPC). Methods: A Cox regression model incorporating two radiomic features (RFs) and cancer stage (III vs. IV) was temporally validated using a larger cohort (215 patients treated between 2005–2022). Patients received concurrent chemoradiotherapy with capecitabine and hypo-fractionated Intensity Modulated Radiotherapy (IMRT). Data were split into training (145 patients, 2005–2017) and validation (70 patients, 2017–2022) groups. Seventy-eight RFs were extracted, harmonized, and analyzed using machine learning to develop refined models. Results: The model incorporating Statistical-Percentile10, Morphological-ComShift, and stage demonstrated moderate predictive accuracy (training: C-index = 0.632; validation: C-index = 0.590). When simplified to include only Statistical-Percentile10, performance improved slightly in the validation group (C-index = 0.601). Adding GLSZM3D-grayLevelVariance to Statistical-Percentile10, while excluding Morphological-ComShift, further enhanced accuracy (training: C-index = 0.654; validation: C-index = 0.623). Despite these refinements, all versions showed similar moderate ability to stratify patients into risk classes. Conclusions: [¹⁸F]FDG-PET radiomic features are robust predictors of DRFS after chemoradiotherapy in LAPC. Despite moderate performance, these models hold promise for patient risk stratification. Further validation with external cohorts is ongoing. Full article

Background: Implant-based breast reconstruction (IBBR) following conservative mastectomy is the most common approach for women undergoing breast cancer surgery. The aim of this study was to compare the oncological outcomes of conservative mastectomy combined with prepectoral IBBR to the subpectoral technique. Methods: The clinical and demographic data of consecutive breast cancer patients who underwent conservative mastectomy with either prepectoral or subpectoral IBBR between January 2018 and December 2023 were retrospectively analyzed. The primary outcome was the impact of conservative mastectomy with prepectoral IBBR on local recurrence-free survival (LRFS). Secondary outcomes included distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 842 women (with a median age of 46 years and a range of 20–79 years) were included in the study. Of these, 648 patients (77.0%) underwent prepectoral IBBR, while 194 (23.0%) received subpectoral IBBR. The median follow-up was 32 months (3–74). Locoregional relapse occurred in 19 patients (2.9%) in the prepectoral group and 14 (7.2%) in the subpectoral group. Distant metastases were observed in 21 (3.2%) patients in the prepectoral group and 11 (5.7%) in the subpectoral group. Deaths were reported in eight patients (1.2%) in the prepectoral group and five (2.6%) in the subpectoral group. There were no statistically significant differences between the two groups in terms of the LRFS, DDFS, and OS (p = 0.676; p = 0.994; p = 0.940, respectively). Conclusions: Our study indicates that conservative mastectomy combined with prepectoral IBBR produces similar results to those of the subpectoral approach, with no significant differences in LRFS, DDFS, and OS. Full article

Background/Objectives: According to Globocan, Romania has the highest incidence of nasopharyngeal cancer (NPC) in Europe. Our objective was to evaluate the survival data for a cohort of non-Asian patient population treated with curative intent at a tertiary cancer center in Romania. Methods: We retrospectively analyzed 161 patients with histologically proven, non-metastatic NPC treated at our institution between October 2014 and December 2021 with intensity modulated arc radiotherapy (IMRT) with or without neoadjuvant or concomitant chemotherapy according to the stage of the disease. Kaplan-Meier estimates of overall, disease-free, locoregional relapse free and distant metastasis free survival were calculated. The log-rank test was used to determine significant prognostic determinants of overall and disease-free survival. Results: The median age was 50 years (range 19–80), 88% had nonkeratinizing undifferentiated carcinoma. Epstein Barr virus status was not evaluated routinely. 42.2% of patients were stage III and 46% stage IVA disease. Induction chemotherapy was prescribed for 72.7% of patients and 89.4% received concurrent chemotherapy. After a median follow up of 44 months (range: 3.6, 104.7 months), the estimated 3 years overall, disease free, locoregional relapse free and distant metastasis free survival of the entire cohort were 82.6%, 73.3%, 83.2% and 86.3% respectively. On testing interactions, concomitant chemotherapy offered significant survival benefit (HR—0.287; 95% CI 0.137–0.603; p = 0.001) and cumulative Cisplatin dose of more than 100 mg/mp was statistically significant for survival (HR—0.350;95% CI 0.157–0.779; p = 0.01) Conclusions: This is the largest retrospective series of nasopharyngeal cancer from Romania reporting survival data. Despite the high percentage of advanced stage disease our data shows very good disease control. Compliance to optimal concomitant chemotherapy should represent a priority in clinical practice in a non-Asian patient population. Full article

Background and Objectives: Mixed ductolobular carcinomas (mDLCs) are tumors that contain both ductal and lobular components. The clinicopathological characteristics and impacts on survival of the two components, which have distinct biological behaviors, are still not clearly understood. This study aimed to compare the clinicopathological characteristics, recurrence/metastasis patterns, and survival outcomes of mDLC and invasive lobular carcinoma (ILC), as well as to investigate the prognostic significance of both histopathologies. Materials and Methods: The outcomes of 132 patients who were followed and treated between 2010 and 2021 were analyzed. Patients were examined in two groups, ILC and mDLC. Chi-square tests were performed to compare the baseline clinicopathological characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan–Meier method and compared using the Cox proportional hazards model. Results: In this study, 80 (61%) patients had ILC histopathology, while 52 (39%) had mDLC histopathology. Differences between the groups were observed in median age (p = 0.038), N stage (p = 0.046), estrogen receptor (ER) status (p = 0.005), lymphovascular invasion (p = 0.007), median tumor diameter (p = 0.050), and frequency of distant metastasis (p = 0.029). The treatments, relapse patterns, and metastasis patterns were similar (p > 0.05). No differences in overall survival (OS) and disease-free survival (DFS) were observed. In the multivariate analysis, mDLC histopathology was identified as a poor prognostic factor (HR: 2.95, CI 95%: 1.10–7.88, p = 0.030). Histopathology (ILC vs. mDCL) was not identified as a prognostic factor in the Cox regression analysis for DFS. Conclusion: Although mDLC has poor clinicopathological features (younger age, more advanced N stage, more ER negativity, more lymphovascular invasion, and more frequency of metastases) and appears more aggressive than ILC, these changes do not affect survival in this study. However, mDLC histopathology seems to be associated with poor prognosis for OS. Full article

Background/Objectives: Colorectal cancer (CRC) is the third most common cancer in the US and the second leading cancer-associated mortality cause. Available CRC therapies achieve modest outcomes and fail to prevent its recurrence. Epidemiological studies indicated that the Mediterranean diet rich in olive oil reduced CRC incidence. This study aimed at the identification and assessment of active anti-CRC olive phenolics. Methods: The MTT, wound-healing and colony formation assays were used to discover and assess the in vitro anti-CRC activity of olive phenolics. A nude mouse xenografting model was used to assess the in vivo CRC progression and recurrence suppressive activity of OC in pure and crude forms. OC was isolated from olive oil using liquid–liquid extractions. Results: Screening of olive phenolics for in vitro antiproliferative activity against a diverse panel of CRC cell lines identified the extra-virgin olive oil (EVOO) S-(-)-oleocanthal (OC) as the most active hit. OC showed IC₅₀ values of 4.2, 9.8, 14.5, and 4.9 μM against HCT-116, COLO-320DM, WiDr, and SW48 CRC cells, respectively. The lysine methyltransferases SMYD2 and EZH2, along with the receptor tyrosine kinase c-MET proved aberrantly dysregulated in invasive and metastatic CRC. SMYD2 and c-MET were validated as OC molecular targets in multiple malignancies. Daily oral 10 mg/kg OC treatments over 15 days suppressed 72.5% of the KRAS mutant HCT-116-Luc cells tumors weight in male nude mice. Continued OC daily oral use after primary tumor surgical excision over an additional 40 days significantly suppressed the HCT-116-Luc locoregional tumor recurrence and totally prevented the distant tumor recurrence. The SMYD2-EZH2 expressions and c-MET activation were notably suppressed by OC treatments in vitro and in collected animal primary tumors. Conclusions: OC and olive phenolics are potential nutraceutical interventions useful for CRC control and the prevention of its relapse. Full article

Objectives: In this single-center retrospective study, we aimed to verify the extent of duodenal follicular lymphoma (DFL) and investigate the role and clinical significance of video capsule endoscopy (VCE) in the treatment process. Methods: We analyzed the clinical and imaging data of 40 patients diagnosed with DFL. Results: Imaging workup and bone marrow biopsies revealed DFL only in the gastrointestinal tract (stage I) in 22 patients and in local lymph nodes (stage II₁), distant lymph nodes (stage II₂), pancreas (stage II₂E_pancreas), and extranodal regions (stage IV) in 1, 3, 1, and 13 patients, respectively. Fifteen of the 23 patients with localized (stages I and II₁) DFL underwent VCE for comprehensive small bowel evaluation, which revealed lesion extension beyond the duodenum in 10 patients (66.7%). A watch-and-wait strategy was implemented for one patient and systemic chemotherapy was administered to the remaining nine. Of the eight patients without VCE, seven and one received radiotherapy and observation, respectively. Nine of the 23 patients (39.1%) received systemic treatment based on positive VCE results. Only one of the 17 patients with advanced-stage DFL (stages II₂ and IV) accepted radiotherapy; 16 underwent systemic chemotherapy. During follow-up (median, 48.4 months), two relapse events occurred in the advanced stage, with no lymphoma-associated deaths. DFL tends to be indolent and has favorable outcomes. Conclusions: Proactive VCE for diagnosing DFL is recommended to determine small bowel involvement, which may influence subsequent treatment decisions. Full article

Tumor dormancy plays a pivotal role in cancer relapse. Dormant tumor cells have been identified in distant sites, even in early-stage tumors, and are associated with worse outcomes. This review explores the current understanding of the molecular and cellular mechanisms behind tumor dormancy, including the role of the immune system and the microenvironment. Targeting dormant tumor cells could be a therapeutic strategy to offer long-term remission and potentially cure cancer. Unfortunately, the translation of this knowledge in clinical practice is lacking. We assess the feasibility of detecting and measuring dormant tumor cells in clinical practice, and give an overview of potential therapeutic targets, both in terms of maintaining tumor cells in a dormant state, and in terms of eradicating this tumor population. Full article

Background: Cervical cancer is the most important cancer type found in women throughout the world. Numerous research studies are being performed to investigate the effectiveness of different strategies for the imaging and treatment of locally advanced cervical cancer, which are showing favorable outcomes. Brachytherapy is characterized by the application of very high radiation doses to target tumor cells with the least exposure to normal tissues. Methods: In the present case study, we report a 43-year-old female patient suffering from cervical cancer belonging to urban origin, with no personal pathological history, who presented herself to the gynecology department of the Bihor County Emergency Clinical hospital with vaginal bleeding. The histopathological examination of the cervix showed squamous cell carcinoma. The treatment was performed with neoadjuvant chemotherapy and concurrent chemoradiotherapy. Results: According to the clinical and histopathological examination, a diagnosis of non-keratinizing squamous carcinoma of the uterine cervix at FIGO stage III C1 was established. Radio-chemotherapy was performed, as well as periodic imaging assessments with a CT of the chest, pelvis, and abdomen, without local and distant relapse. FDG PET imaging was performed for the management and follow-up of cervical cancer by retrieving the SUVmax value. Conclusions: The post-therapeutic complications are represented by the vaginal stenosis installed 6 months after the end of the radiotherapeutic treatment. Full article