Search Results (211)

The concept of “platinum sensitivity” has long guided prognostic assessment and treatment selection in recurrent ovarian cancer. However, the emergence of targeted agents, such as bevacizumab and poly (ADP-ribose) polymerase inhibitors, has complicated its clinical utility. In contrast, emerging evidence suggests that platinum sensitivity may also be applicable to recurrent endometrial cancer. As in ovarian cancer, a prolonged platinum-free interval (PFI) in recurrent endometrial cancer is associated with an improved efficacy of subsequent platinum-based chemotherapy. The PFI is linearly correlated with the response rate to platinum re-administration, progression-free survival, and overall survival. Patients are typically classified as having platinum-resistant or platinum-sensitive disease based on a PFI cutoff of 6 or 12 months. However, unlike in ovarian cancer—where the duration of response to second-line platinum-based chemotherapy rarely exceeds the prior PFI (~3%)—approximately 30% of patients with recurrent endometrial cancer exhibit a sustained response to platinum rechallenge that extends beyond their preceding PFI. Despite the incorporation of immune checkpoint inhibitors into the treatment landscape of endometrial cancer, the role of platinum sensitivity in clinical decision-making—particularly regarding treatment sequencing and drug selection—remains a critical and unresolved issue. Further research is warranted to elucidate the mechanisms underlying platinum resistance and to guide optimal therapeutic strategies. Full article

Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group, n = 651; Without-ICI group, n = 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96, p = 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes. Full article

Recent advances in technology and pharmacologic agents have significantly improved both local and systemic therapies, making the treatment of non-small cell lung cancer (NSCLC) more effective and less invasive. However, recurrence after radical resection remains a major clinical challenge. Among the various recurrence patterns, oligo-recurrence—particularly metachronous oligo-recurrence, characterized by a limited number of metastatic lesions appearing after a disease-free interval—has gained attention due to its potential for long-term survival and even cure through local therapy. Concurrently, systemic treatments have advanced with the development of molecularly targeted therapies and immune checkpoint inhibitors. Numerous studies have demonstrated their clinical efficacy, resulting in significant improvements in patient prognosis. Therefore, selecting an appropriate treatment strategy for recurrent NSCLC involves a broad spectrum of therapeutic options, including targeted therapies, immune checkpoint inhibitors, and conventional chemotherapy. Treatment decisions are particularly complex in cases of oligo-recurrence, where local therapy is feasible, making it challenging to choose the best approach from the available options. This narrative review summarizes current evidence from retrospective and ongoing prospective trials and discusses the clinical characteristics and treatment strategies for oligo-recurrent NSCLC. Full article

Background: A single measurement or a summary of a limited number of measurements of CA125 was considered in the prediction of clinical outcomes for patients with ovarian cancer. We aimed to identify the classes of patients with advanced ovarian cancer based on their CA125 trajectory and to investigate the heterogeneity of clinical outcomes among the patients in the different classes. Methods: CA125 trajectory classes were identified by latent-class mixed models based on values collected within 3 and 6 months post-treatment for 819 women with advanced ovarian cancer enrolled in a randomized trial. Results: Based on their CA125 values during the first 6 months of treatment, the patients with low CA125 levels at baseline that remained low during treatment had the best clinical outcome (a median survival of 83 months and a progression-free survival of 34 months). In contrast, the patients with high CA125 values at baseline with a modest decrease during treatment had the highest risk of death and progression (hazard ratio [95% confidence interval]: 4.83 [3.56, 6.54] for overall survival and 5.15 [3.87, 6.87] for progression-free survival). Conclusions: Longitudinal trajectories of CA125 may provide more direct information for the prognoses of patients with advanced ovarian cancer undergoing chemotherapy treatment. Full article

Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article

Backgroud: Ovarian cancer is the deadliest gynecologic malignancy, with most patients presenting with peritoneal dissemination at diagnosis. Complete cytoreduction and sensitivity to platinum-based systemic chemotherapy remain the most significant prognostic factors. However, even after optimal first-line management, over half of patients relapse due to residual microscopic disease. Intraperitoneal chemotherapy aims to target this component, with normothermic intraperitoneal chemotherapy long-term (NIPEC-LT) and hyperthermic intraperitoneal chemotherapy (HIPEC) being the most studied approaches. While NIPEC-LT has demonstrated improved survival in select trials, concerns regarding toxicity and catheter-related complications have limited its adoption as standard care. Conversely, HIPEC has shown survival benefits, particularly in patients undergoing interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy, leading to its inclusion in clinical guidelines. However, HIPEC is administered as a single intraoperative treatment, limiting its prolonged effect. Objectives and Method: This study investigates the combination of HIPEC and postoperative NIPEC-LT in the BICOV-1 trial, a prospective, non-randomized phase I study evaluating the feasibility, safety, and oncologic outcomes. The primary objective is to assess the treatment completion rates and morbidity. The secondary endpoints include disease-free survival (DFS), overall survival (OS), and quality-of-life measures. Combining HIPEC and NIPEC-LT is a rational approach, as both have shown independent benefits and do not overlap in toxicity. HIPEC-induced biological changes may enhance the effectiveness of subsequent intraperitoneal chemotherapy. This trial will provide essential data for future phase II/III studies assessing the role of intensified intraperitoneal treatment in ovarian cancer management. Full article

Background/Objectives: Anlotinib is a novel oral antiangiogenic tyrosine kinase inhibitor (TKI) approved as a third-line treatment for advanced non-small-cell lung cancer (NSCLC). However, its efficacy in combination with docetaxel remains incompletely understood. Given the need for effective second-line therapies after platinum-based chemotherapy, this systematic review aims to evaluate the therapeutic potential of anlotinib plus docetaxel in advanced NSCLC. Methods: The PubMed, WOS, Medline, and Scopus databases were screened for published articles up to 12 April 2024. We included RCTs comparing anlotinib plus docetaxel with docetaxel alone in advanced NSCLC after receiving platinum-based chemotherapy, reporting progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) as outcomes for both groups. Results: Our systematic review included three randomized controlled trials (RCTs) with a total of 151 patients in the anlotinib plus docetaxel group and 132 in the docetaxel-only group. Meta-analysis results demonstrated that the combination therapy significantly prolonged PFS (mean difference (MD) = 2.98, 95% confidence interval (CI), 1.95–4.00; p < 0.00001) and improved ORR (risk ratio (RR) = 3.04, 95% CI = 1.77–5.24; p < 0.00001). Additionally, the DCR was notably higher in the combination group (RR = 1.58, 95% CI = 1.34–1.87; p < 0.00001). Conclusions: Anlotinib plus docetaxel appears to be more effective as a second-line treatment of advanced NSCLC than docetaxel in prolonging PFS and increasing ORR and DCR. Full article

S-1 adjuvant chemotherapy (AC) is the standard treatment for pancreatic ductal adenocarcinoma (PDAC) after curative surgery in Japan. Our prior research suggested that a lower postoperative geriatric nutritional risk index (GNRI) predicts S-1 discontinuation due to adverse events (AEs). This study aimed to validate the GNRI as a predictor of S-1 non-completion using an independent cohort. Methods: This retrospective study analyzed 180 patients who underwent curative PDAC resection at Dokkyo Medical University from January 2010 to March 2023. Postoperative GNRI values were recorded as part of nutritional screening. Data on S-1 therapy completion and related clinical factors were analyzed statistically. Results: Patients were classified based on S-1 completion (N = 93) and non-completion (N = 48). GNRI values were significantly lower in the non-completion group. A GNRI threshold of 94.4, identified in a prior study, effectively distinguished patients at risk of discontinuation. Univariate analysis confirmed that a GNRI of ≥94.4 was a significant predictor of successful S-1 completion [hazard ratio (HR) for recurrence-free survival (RFS), 1.54; 95% confidence interval (CI) 1.04–2.28 and for overall survival (OS), 1.89; 95% CI 1.20–2.99]. Conclusions: This study validated previous findings, confirming that the postoperative GNRI reliably identifies patients at risk of S-1 non-completion due to AEs after PDAC surgery. The GNRI serves as a practical marker for optimizing patient care and enhancing AC efficacy. Full article

Background: Ovarian cancer, particularly in advanced stages, requires cytoreductive surgery followed by chemotherapy. A significant proportion of patients are elderly, yet older women are often treated with non-standard regimens despite a lack of consistent evidence linking age to prognosis. The aim of this study is to assess age-specific differences in treatment and survival outcomes for ovarian cancer in women aged 70 years or older. Methods: This retrospective study included ovarian cancer patients treated at the Hospital del Mar, Barcelona, between 2016 and 2022. Patients were stratified into two groups: <70 and ≥70 years. Clinical and pathological data were analyzed, and hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS) were calculated using Cox proportional hazards regression models. Multivariate analysis was performed to compare outcomes. Results: A total of 110 patients were included (73 <70 years, 37 ≥70 years). Among the older group, 80.5% were diagnosed at advanced stages (III–IV), compared to 63% in the younger group (p = 0.012). Patients aged ≥70 were more likely to undergo interval surgery (p = 0.053) and receive non-standard treatment (p = 0.023). Complete cytoreduction was achieved in 95.8% of younger patients versus 81.3% of older patients (p = 0.024). Age ≥70 did not significantly impact DFS (p = 0.091), but OS was significantly worse in the older group (44.4% vs. 67.2%, p = 0.014). Conclusions: Older women (≥70 years) with ovarian cancer are more likely to be diagnosed at advanced stages, receive non-standard treatment, and achieve suboptimal cytoreduction compared to younger patients. While DFS was similar across age groups, older age was associated with worse OS, highlighting the need for age-tailored treatment strategies. Full article

Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative for patients with extensive disease. Achieving complete cytoreduction is a critical prognostic factor for OS and progression-free survival (PFS). This study evaluated the prognostic value of two biomarkers—the neutrophil–lymphocyte ratio (NLR) and the cancer antigen-125 (CA-125) ELIMination rate constant K (KELIM)—in predicting survival outcomes and recurrence rates in patients with AOC undergoing NACT. Methods: A retrospective, single-center analysis was conducted on 78 patients with high-grade serous AOC (stages III–IV) treated with platinum-based NACT followed by IDS between January 2013 and December 2023. NLR was calculated from prechemotherapy complete blood counts, with a threshold of ≥3 indicating elevated levels. KELIM, a marker of tumor chemosensitivity, was derived from CA-125 kinetics during the first 100 days of chemotherapy, with a cutoff of ≥1 denoting a favorable outcome. Clinical outcomes, including PFS and OS were analyzed using Kaplan–Meier survival curves, log-rank tests, and Cox regression models. Results: Results demonstrated that elevated NLR (≥3) and low KELIM (<1) were associated with poorer PFS and OS. KELIM score was identified as a strong prognostic marker for both PFS and OS, while NLR demonstrated weak association. Complete cytoreduction was achieved in 69.2% of patients, significantly correlating with improved survival outcomes. Postoperative complications, assessed using the Clavien–Dindo classification, were observed in a small subset of patients, with a total median hospital stay of 8 days. Conclusions: This study highlights the potential of NLR and KELIM as prognostic tools in AOC, aiding in patient selection for radical surgical interventions and predicting chemosensitivity. Future multicenter studies with larger cohorts are needed to validate these results and further explore the clinical utility of these biomarkers in optimizing treatment strategies for AOC. Full article

Background: Advanced-stage ovarian cancer presents a significant therapeutic challenge, with primary cytoreductive surgery (PCS) followed by chemotherapy and neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS) as the two main treatment modalities. This study aims to compare the clinical outcomes, surgical complexity, and survival rates between these approaches and to assess the impact of molecular markers such as BRCA and HRD status. Methods: This retrospective, single-center observational study included 100 patients diagnosed with stage III-IV high-grade serous ovarian cancer. The patients were divided into two cohorts based on their treatment strategy: PCS followed by adjuvant chemotherapy or NACT followed by IDS. Clinical outcomes, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) were analyzed, along with the impact of genetic biomarkers. Results: No statistically significant differences were observed in OS and PFS between the two treatment approaches. Patients who underwent NACT followed by IDS had lower surgical complexity scores and reduced perioperative morbidity. The HRD-positive patients exhibited improved responses to PARP inhibitors, reinforcing the significance of molecular profiling in therapeutic decision-making. The KELIM scores demonstrated prognostic relevance, particularly in the patients receiving neoadjuvant chemotherapy. Conclusion: Both PCS and NACT-IDS are viable treatment options for advanced ovarian cancer, with similar survival outcomes. The choice between strategies should be tailored based on patient-specific factors, including tumor burden, performance status, and molecular profile. The integration of biomarkers such as BRCA mutations and HRD status into clinical practice can further refine treatment selection and improve personalized management strategies. Full article

Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response. Full article

Objective. To compare the survival outcomes of primary debulking surgery and platinum-based adjuvant chemotherapy versus interval debulking surgery after platinum-based neoadjuvant chemotherapy in patients with stage IVb endometrial cancer and peritoneal carcinosis. Methods. The online search included the following data sources: PubMed, Scopus, WOS, and the Cochrane Library from 1990 to 2024 (PROSPERO registration code: CRD42023438602). A total of 3230 studies were identified, with the inclusion of 16. Individual patient data on survival outcomes, disease distribution, and residual tumors, as well as details of neoadjuvant chemotherapy and adjuvant treatment, were extracted. Results. A total of 285 patients were included: 197 (69%) underwent primary debulking surgery and 88 (31%) underwent interval debulking surgery. The pooled analysis revealed a median progression-free survival in the primary debulking surgery group of 18.0 months compared to 12.0 months in the interval debulking surgery group (p = 0.028; log-rank test), and a median overall survival of 30.92 months versus 28.73 months (p = 0.400; log-rank test). Among the 134 patients with available information on the residual tumor after primary debulking surgery or interval debulking surgery, 110 (82%) had no macroscopic residual tumor (residual tumor = 0). The median progression-free survival was 18.9 months in the residual tumor = 0 group compared to 6.19 months in the residual tumor > 0 group (p < 0.001; log-rank test); the median overall survival was 40.6 months versus 21 months (p = 0.028; log-rank test). Conclusions. These results indicate that primary debulking surgery should be considered the preferred treatment approach for advanced endometrial cancer with carcinosis, especially in carefully selected patients where complete cytoreduction is achievable. Further prospective studies are warranted to confirm these results and to establish standardized criteria for patient selection, incorporating molecular-integrated risk profiles for endometrial cancer. Full article

The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25–10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care. Full article

Background/Objectives: Hyperthermic intraperitoneal chemotherapy (HIPEC) was revealed as a promising adjunct to cytoreductive surgery (CRS) in the treatment of advanced epithelial ovarian cancer (EOC). This review evaluated the impact HIPEC had on survival outcomes, recurrence patterns and safety in patients that underwent HIPEC in conjunction with interval and secondary CRS for advanced and recurrent ovarian cancer. Methods: A thorough search was conducted using PubMed, Scopus, Cochrane Library, and Google Scholar to identify relevant studies published until 1 January 2025. The studies were assessed for survival outcomes, recurrence patterns, safety, and quality of life. The risk of bias was evaluated using the ROB 2 tool for randomized and ROBINS-I for non-randomized articles. The results are presented narratively, highlighting key findings, comparing results and assessing inconsistencies and limitations. Results: HIPEC demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS), particularly in cases with optimal cytoreduction (CC-0/CC-1). The recurrence patterns showed a reduction in peritoneal dissemination with HIPEC, although extraperitoneal recurrences were reported in some cases. Most studies reported comparable morbidity rates between HIPEC and non-HIPEC groups, with acceptable safety profiles. The variability in the HIPEC protocols and the limited quality-of-life and cost-effectiveness data were noteworthy limitations. Conclusions: HIPEC, when performed during interval or secondary CRS, offers survival benefits and can modify recurrence patterns in advanced EOC, although challenges related to protocol standardization, patient selection, and long-term outcomes persist. Future research should focus on multicenter trials with uniform protocols, long follow-up periods and patient-centered outcomes to further validate the role of HIPEC in clinical practice. Full article