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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Mesenchymal-epithelial transition (MET) signaling pathway plays a role in the pathogenesis of selected patients with papillary renal cell carcinoma (PRCC). In the phase II PAPMET trial (ClinicalTrials.gov identifier: NCT02761057), cabozantinib significantly prolonged progression-free survival and improved objective response rate compared with sunitinib in patients with advanced PRCC. Here, we present the final overall survival (OS) analysis. In this multicenter, randomized phase II, open-label trial, 147 patients with advanced PRCC who have received up to one previous therapy (excluding vascular endothelial growth factor-directed agents) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib. Ultimately, savolitinib and crizotinib arms were closed because of futility. With a median follow-up of 17.5 months, the median OS was 21.5 months (95% CI, 12.0 to 28.1) with cabozantinib and 17.3 months (95% CI, 12.8 to 21.8) with sunitinib (hazard ratio, 0.83; 95% CI, 0.51 to 1.36; P = .46). The OS landmark estimates for cabozantinib and sunitinib were 50% versus 39% at 24 months and 32% versus 28% at 36 months. In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease.

The Response Evaluation in Solid Tumors (RECIST) 1.1 provides key guidance for performing imaging response assessment and defines image-based outcome metrics in oncology clinical trials, including progression free survival. In this framework, tumors identified on imaging are designated as either target lesions, non-target disease or new lesions and a structured categorical response is assigned at each imaging time point. While RECIST provides definitions for these categories, it specifically and objectively defines only the target disease. Predefined thresholds of size change provide unbiased metrics for determining objective response and disease progression of the target lesions. However, worsening of non-target disease or emergence of new lesions is given the same importance in determining disease progression despite these being qualitatively assessed and less rigorously defined. The subjective assessment of non-target and new disease contributes to reader variability, which can impact the quality of image interpretation and even the determination of progression free survival. The RECIST Working Group has made significant efforts in developing RECIST 1.1 beyond its initial publication, particularly in its application to targeted agents and immunotherapy. A review of the literature highlights that the Working Group has occasionally employed or adopted objective measures for assessing non-target and new lesions in their evaluation of RECIST-based outcome measures. Perhaps a prospective evaluation of these more objective definitions for non-target and new lesions within the framework of RECIST 1.1 might improve reader interpretation. Ideally, these changes could also better align with clinically meaningful outcome measures of patient survival or quality of life.

BackgroundImmune checkpoint inhibitor (ICI) therapies have become increasingly popular treatment options for patients with cancer, even for patients in non-metastatic settings. Survival and responses have been reported for individual tumor types, but little is known about these outcomes, collectively. We sought to provide an overview of overall survival (OS) and progression-free survival (PFS) in ICI drugs tested in registration trials.MethodsIn a cross-sectional analysis of US FDA oncology ICI drug approvals (2011-2023), we searched for supporting ICI registration trials. We characterized these trials, regarding differences in median OS and PFS between patients in intervention and control arm participants in ICI registration trials; percentage of patients who receive ICI crossover; and whether there is correlation between the percentage of crossover and differences in OS or PFS.ResultsFifty-six (54.4 %) approvals had trials that reported median OS for both intervention and control arms (median difference was 2.8 months; IQR: 2.2 to 5.0 months). Sixty-five (63.1 %) approvals had trials that reported PFS data for both arms (median of 0.9 months; IQR: -0.2 to 3.0 months). Subsequent therapy was common (median=18.9 %) and was significantly correlated with a higher difference in median OS in all studies with reported differences (R2 =0.15; p = 0.001).ConclusionICIs are increasingly used in the treatment of cancer, yet the median OS improvement is modest, and many ICIs have not been tested for OS benefit. OS is the outcome most meaningful for patients, and drug regulation should require better testing and reporting of these data.

BACKGROUND: In the phase 3 EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first-line platinum-based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. METHODS: Patients were enrolled regardless of programmed cell death-ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigators choice  single-agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression-free survival (PFS) and objective response rate (ORR). RESULTS: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow-up was 13.6 (6.0-25.3) versus 18.2 (6.0-38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0-not evaluable) and 9.4 (5.4-14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43-1.68). Median PFS (95% CI) was 4.0 (1.4-8.2) versus 3.7 (1.8-4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50-1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44-13.99). Incidence of treatment-emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. DISCUSSION: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6-month shorter median duration of follow-up versus the overall study population.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy (PRINCE, NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Sacituzumab govitecan (SG), a first-in-class anti-trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physicians choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study.Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression. Final efficacy secondary end point analyses and post hoc analyses of outcomes stratified by Trop-2 expression and human epidermal growth factor receptor 2 status are reported. Updated safety analyses are provided.In this final analysis, SG (n = 267) improved median progression-free survival (PFS; 4.8 v 1.7 months; hazard ratio (HR), 0.41 [95% CI, 0.33 to 0.52]) and median overall survival (OS; 11.8 v 6.9 months; HR, 0.51 [95% CI, 0.42 to 0.63]) over TPC (n = 262). SG improved PFS over TPC in each Trop-2 expression quartile (n = 168); a trend was observed for improved OS across quartiles. Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups.These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.

No study has unequivocally proven that chemotherapy prolongs overall survival (OS) in advanced esophageal cancer. We conducted a Phase III randomized study in first‐line advanced unresectable/metastatic esophageal/GEJ cancer. Patients aged 18–70 years, with performance status 0–2, were randomized to best supportive care (BSC) alone, or BSC with weekly paclitaxel 80 mg/m2. BSC comprised, as indicated, education, counselling, radiation, stenting, feeding tube placement, nutritional supplementation, medications like analgesics, and referral to a support group and palliative care. The primary endpoint was OS; secondary endpoints included progression free survival (PFS), response, toxicity, and QoL. Between May 2016–December 2020, we recruited 281 patients: 143 to chemotherapy and 138 to BSC. Histopathology was squamous in 269 (95.7%) patients. Median number of paclitaxel doses was 12 (IQR, 7–23). Median OS was 4.2 months (95% CI, 3.42–5.32) in BSC, and 9.2 months (95% CI, 8.02–10.48) in chemotherapy; HR, 0.49 (95% CI, 0.39–0.64); p <.001. As compared to BSC, chemotherapy increased response (2.9% to 39%), median PFS (2.1 to 4.2 months), 1‐year OS (11% to 32%), 2‐year OS (0 to 9%), median dysphagia‐free survival (2.9 to 14.8 months), and global and esophagus‐specific QoL, without significantly increasing all‐grade or grade ≥3 toxicities. Using ESMO clinical benefit scale and ASCO Value Framework, palliative chemotherapy scored as having "substantial value." Our study provides the first level 1 evidence that chemotherapy prolongs survival in advanced esophageal/GEJ carcinoma. BSC alone is no longer appropriate. Weekly paclitaxel is an attractive option, especially in LMICs with limited access to immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: While randomized controlled trials remain the reference standard for evaluating treatment efficacy, there is an increased interest in the use of external control arms (ECA), namely in oncology, using real-world data (RWD). Challenges related to measurement of real-world oncology endpoints, like progression-free survival (PFS), are one factor limiting the use and acceptance of ECAs as comparators to trial populations. Differences in how and when disease assessments occur in the real-world may introduce measurement error and limit the comparability of real-world PFS (rwPFS) to trial progression-free survival. While measurement error is a known challenge when conducting an externally-controlled trial with real-world data, there is limited literature describing key contributing factors, particularly in the context of multiple myeloma (MM). Methods: We distinguish between biases attributed to how endpoints are derived or ascertained (misclassification bias) and when outcomes are observed or assessed (surveillance bias). We further describe how misclassification of progression events (i.e., false positives, false negatives) and irregular assessment frequencies in multiple myeloma RWD can contribute to these biases, respectively. We conduct a simulation study to illustrate how these biases may behave, both individually and together. Results: We observe in simulation that certain types of measurement error may have more substantial impacts on comparability between mismeasured median PFS (mPFS) and true mPFS than others. For instance, when the observed progression events are misclassified as either false positives or false negatives, mismeasured mPFS may be biased towards earlier (mPFS bias = −6.4 months) or later times (mPFS bias = 13 months), respectively. However, when events are correctly classified but assessment frequencies are irregular, mismeasured mPFS is more similar to the true mPFS (mPFS bias = 0.67 months). Discussion: When misclassified progression events and irregular assessment times occur simultaneously, they may generate bias that is greater than the sum of their parts. Improved understanding of endpoint measurement error and how resulting biases manifest in RWD is important to the robust construction of ECAs in oncology and beyond. Simulations that quantify the impact of measurement error can help when planning for ECA studies and can contextualize results in the presence of endpoint measurement differences. [ABSTRACT FROM AUTHOR]

Purpose: This study compared the timing effects of immune checkpoint inhibitor (ICIs) administration on the efficacy and safety of concurrent chemoradiotherapy for cervical cancer. Methods: This study included patients with advanced cervical cancer who received concurrent chemoradiotherapy with ICIs. The patients were divided into early-application (n=51) and late-application groups (n=56) according to the ICI application timing. The primary objective was assessing progression-free survival (PFS) and its associated factors; secondary objectives included assessing objective remission rates (ORR) and treatment-related adverse events (TRAEs). Results: Before propensity score matching (PSM), the median PFS (mPFS) times were significantly different: 11.5 months (95% CI: 11.0–13.2) and 7.5 months (95% CI: 6.5–9.0) for the early and late groups, respectively (P<0.001). After PSM, the mPFS times remained significantly different: 11.5 months (95% CI: 11.0–13.8) and 6.5 months (95% CI: 6.1–9.0), respectively (P<0.001). The PSM tumor-response ORR in the early combination group (74.3%) was significantly greater than the 31.4% in the late combination group (P<0.001). After PSM, multivariate Cox analysis showed tumor diameter (P=0.004), distant organ metastasis (P=0.047), and timing of combination therapy (P<0.001) were independently associated factors affecting PFS. The most common TRAEs in the two groups of patients were neutropenia, nausea and vomiting, and fatigue, with no significant difference in incidence (P>0.050).All adverse reactions were resolved, and no adverse reaction-related deaths occurred. Conclusion: In patients with cervical cancer treated with concurrent chemoradiotherapy, earlier immunotherapy improves survival and is equivalent in safety to ICIs late application. [ABSTRACT FROM AUTHOR]

Objective: Radiological prediction of Ki-67 plays a crucial role in determining the clinical outcomes of meningioma patients. The aim of this review is to comprehensively review the literature to synthesize evidence on how accurate radiological prediction of the Ki-67 proliferation index is to determine the Ki-67 index's association with clinical outcomes of meningioma. Materials and methods: A narrative synthesis systematic review followed PRISMA guidelines. The literature was searched using database-specific, relevant keywords, text words, and MeSH terms (controlled vocabulary) such as "Meningioma," "ki-67," "Ki 67 proliferation index," "proliferation index," "Radiomics," and "clinical outcomes" on electronic databases PubMed, Web of Science, and Google Scholar from 2014 to April 2024. Results: Out of 218 publications identified initially, only 03 moderate-quality studies were included in this paper after methodological quality assessment using the Newcastle–Ottawa scale. Discussion: The evidence synthesis by systematic review emphasizes the importance of radiographic approaches in predicting the Ki-67 proliferation index and their consequences for prognosis and treatment results in meningioma patients. Various radiological techniques, such as pre-operative MRI with clinical and radiomic analysis and machine learning algorithms, show promise for accurately predicting Ki-67 status, with significant associations between radiological features and clinical outcomes such as recurrence, survival, and progression-free survival. The radiomics models were compared and found that Lasso with LDA radiomic models outperformed other radiomics models in terms of accuracy, sensitivity, specificity, and predictive power. Lasso with LDA model also showed significant improvements in performance when the clinical datasets of meningiomas patients were combined to predict ki-67 levels. However, the comparison to histological evaluation emphasizes the necessity for additional validation and standardization. While these approaches provide non-invasive and possibly time-saving alternatives, drawbacks such as inherent biases, methodological limits, and practical challenges with automated selection procedures highlight future research and development topics. [ABSTRACT FROM AUTHOR]

To explore the altered malignant behavior, prognosis and survival of glioblastoma in contact with Subventricular Zone (SVZ) and independent predictors on patients' overall survival. The records of 131 patients with supratentorial primary glioblastoma who underwent surgery at our hospital between 2012 and 2018 were reviewed retrospectively. The authors reviewed preoperative MRI images and divided patients into two groups: Glioblastoma not in contact with SVZ (G-SVZ) and glioblastoma in contact with SVZ (G + SVZ). They computed and compared the overall survival (OS) of these two groups using the Kaplan–Meier method. The correlation between G + SVZ and OS was investigated using the Cox Proportional Hazard Ratio Model. The median progression-free survival (PFS) of the patient was 10 months (Interquartile Range), and the median OS was 13 months. At six months and one year, the OS was 81 percent and 51.1 percent, respectively. Patients with G + SVZ and G-SVZ had a median OS of 12 months and 15 months, respectively (p = 0.0093). According to Cox Multivariate model, repeat surgery (p = 0.001), among other independent predictors, including age ≥60, Karnofsky Performance Score (KPS) < 70, and extent of resection (Subtotal/biopsy vs total resection), had the strongest associated decreased OS. G + SVZ independently correlated significantly with reduced patient survival (p = 0.014). Repeat surgery had the strongest association with decreased OS among the independent predictors of survival in patients with G + SVZ lesions. Prospective studies about molecular mechanisms are needed to explain why G + SVZ lesions are thought to be aggressive and associated with a poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Cortisol rhythm disruptions predict early mortality in renal, colorectal, lung, and metastatic breast cancer. In head and neck cancer (HNC), various cortisol indices are known to correlate with adverse psychological and biological (e.g., inflammatory) outcomes, but links to mortality have yet to be demonstrated. We hypothesize that the prognostic value of diurnal cortisol aberrations will hold in HNC. Prior work leads us to predict that flattened or elevated diurnal cortisol profiles will be associated with elevations of serum inflammatory and tumor-promoting cytokines in this population, and that these immune markers would themselves predict poor progression-free survival. Method: We prospectively recruited a pilot sample of HNC patients (N=40) at a multidisciplinary HNC clinic. Most patients presented with late-stage oral/oropharyngeal cancer, were older than 50, male, and subsequently received combined-modality (surgery and/or radiotherapy with or without chemotherapy) treatment with curative intent. Saliva was collected twice daily for six days to assess diurnal slope, mean, waking, and evening cortisol levels. Serum was assayed for an exploratory panel of inflammatory and tumor-promoting cytokines. Two years post study-entry, disease progression and survivorship status were abstracted from medical records. Bivariate correlations, linear regressions, and Cox Proportional Hazards models tested hypotheses. Results: Elevations of evening cortisol and diurnal mean levels were each associated with shorter progression-free survival (evening: Hazard Ratio [HR]=1.848, 95% Confidence Interval [CI]=1.057-3.230, p=.031; diurnal mean: HR=2.662, 95% CI=1.115-6.355, p=.027). Bivariate correlations revealed that higher levels of the serum inflammatory marker interferon (IFN)-γ were linked with elevated evening (r=.405, p=.014) and mean (r=.459, p=.004) cortisol. Higher expression of IFN-γ also predicted poorer progression-free survival (HR=4.671, 95% CI=1.409-15.484, p=.012). Discussion: Elevated evening and diurnal mean cortisol were both prognostic; suggesting cortisol secretion is both dysregulated and elevated among patients who subsequently experienced accelerated disease progression. These exploratory data from 40 HNC patients mirror relationships between cortisol and survival identified among patients with numerous other tumor types. This pilot study highlights the need for research on effects of cortisol rhythm disruption among HNC patients. Future research in larger samples should also examine the role of inflammatory and tumor-promoting factors–both systemically and within the tumor microenvironment–as potential mediators of cortisol rhythm disruption. [ABSTRACT FROM AUTHOR]

Introduction: This meta-analysis was performed to evaluate the efficacy and safety of angiogenesis inhibitors (Ais) combined with poly ADP ribose polymerase inhibitors (PARPi) in the maintenance treatment of advanced ovarian cancer (OC). Materials and methods: A systematic search was conducted in four databases (Pubmed, Embase, Web of Science, and Cochrane) for articles published from the inception of the databases until January 15, 2024. The focus of the search was on articles investigating the combination of Ais with PARPi in the maintenance treatment of ovarian cancer. Meta-analyses were conducted to assess the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the risk of Grade ≥ 3 adverse events (Grade≥ 3 AEs). Results: Totally nine studies were included for meta-analysis. The overall pooled ORR of Ais combined with PARPi was 57% (95% CI, 35% to 77%). Subgroup analyses showed that the ORR for patients with platinum-resistant recurrent ovarian cancer, platinum-sensitive recurrent ovarian cancer and newly diagnosed advanced ovarian cancer were 30% (95% CI, 12% to 52%), 70% (95% CI, 61% to 78%) and 59% (95% CI, 55% to 63%), respectively. The median PFS was 5.8 months (95% CI, 5.3 to 7.1), 12.4 months (95% CI, 10.6 to 13.2) and 22.4 months (95% CI, 21.5 to 24.2), respectively. The median OS was 15.5 months (95% CI, 12.3 to 24.8), 40.8 months (95% CI, 33.4 to 45.2) and 56.3 months (95% CI, 49.0 to 62.0), respectively. The rate Grade≥ 3 TRAEs rate was found to be 0.22 (95% CI, 0.13 to 0.33). Conclusions: Our results confirmed that PARPi plus Ais was a feasible and safe option for the maintenance treatment of advanced ovarian cancer. The combination therapy should be recommended as the first-line maintenance treatment for patients with advanced ovarian cancer. PARPi plus Ais yielded more favorable oncological prognosis for patients with platinum-sensitive recurrent ovarian cancer, compared to patients with platinum-resistant recurrent ovarian cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42024543590 , identifier CRD42024543590. [ABSTRACT FROM AUTHOR]

Objective: Patients with multiple myeloma (MM) typically require multiple regimens and become harder to treat with each line of treatment. Furthermore, there is a lack of direct comparative clinical trial data to guide effective treatment sequencing. A novel model is described comparing alternative MM treatment sequences to optimize patient outcomes. Methods: The model compares treatment sequences and outcomes for adults with newly diagnosed transplant-eligible (TE) or transplant-ineligible (TIE) MM across four treatment lines (first-line [FL] to fourth-line [4L]). Inputs are derived from patient-level data from clinical trials and indirect treatment comparisons. We report a base case prediction using data representing clinical practice in Italy. Results: For FL TE, overall survival (OS) and progression-free survival (PFS) were greatest for FL regimens containing daratumumab; OS ranged from 11.80–18.10 years. PFS ranged from 4.82–13.42 years (FL) to 0.66–6.03 years (second-line [2L]), 0.81–1.76 years (third-line [3L]), and 0.69–0.72 years (4L). For FL TIE, OS rates were greater for treatment sequences with FL daratumumab vs. sequences with either 2L or no daratumumab (OS ranging from 5.95–10.61 years). PFS was greatest for FL daratumumab regimens in the TIE group, with PFS ranging from 2.12–7.48 years (FL), 0.53–4.73 years (2L), 0.63–1.17 years (3L), and 0.42 years (4L). Discussion: This novel model demonstrates that using the most effective treatment in FL optimizes treatment sequencing and clinical outcomes for patients. Conclusion: The optimal MM treatment sequences begin with daratumumab-containing regimens in FL and improve outcomes compared with alternative sequences. Plain language summary: Over the past few years, many new treatments have been approved for patients with multiple myeloma (MM) and these have improved outcomes like response rates and survival. However, although patients usually respond to treatment initially, over time they typically relapse and often need multiple lines of subsequent treatment. There are a lot of treatments to choose from, but no data to guide physicians on what the most effective sequence of those treatments should be in order to maximize outcomes for individual patients. This remains an important unmet clinical need. We therefore developed a novel model to compare treatment sequences and their associated outcomes across different lines of MM treatment, from first-line through fourth-line therapy. The model uses data from individual patients who took part in clinical trials of daratumumab, as well as some data from indirect comparisons between other MM treatments. When using data representing clinical practice in Italy, the model showed that patients have the best clinical outcomes (overall survival and progression-free survival) when the most effective treatment is used first. We found that the optimal MM treatment sequences begin with first-line regimens containing daratumumab, which improve outcomes compared with alternative sequences. The model highlights the importance of starting with the most effective regimens and planning the optimal treatment sequence for individual patients. [ABSTRACT FROM AUTHOR]

Purpose: The objective is to establish a radiomics nomogram (Rad‐nomogram) using dual‐phase enhanced computed tomography (DPE‐CT) for the prediction of progression‐free survival (PFS) in patients diagnosed with stage IV lung adenocarcinoma (ADC). Methods: From DPE‐CT scans, radiomic characteristics were retrieved from 133 patients diagnosed with stage IV lung ADC. Clinical data were analyzed using univariate and multivariate Cox regression analyses. The radiomics signature was combined with clinical features employing multivariate Cox analysis in order to develop a Rad‐nomogram. The predictive efficiency of the nomogram was evaluated using survival studies, such as Kaplan–Meier curves and Harrell's C‐index. The benefits and clinical utility of various models were compared using the net reclassification index (NRI), decision curve analysis (DCA), and integrated discrimination improvement (IDI). Results: In the test cohort, the C‐indexes for the clinical, artery, and vein phase CT models were 0.675, 0.691, and 0.678, respectively. The dual‐phase achieved a C‐index of 0.731, exceeding the CT model, while the developed nomogram reached a C‐index of 0.783. The Kaplan–Meier survival study classified patients into low‐risk and high‐risk groups related to PFS using the Rad‐nomogram (p < 0.05). The Rad‐nomogram demonstrated a greater net advantage when compared with clinical and Rad models, as indicated by positive values of the NRI and IDI (ranging from 11.6% to 52.6%, p < 0.05). Conclusion: The Rad‐nomogram, employing DPE‐CT scans, offers a promising approach to predict PFS in individuals diagnosed with stage IV lung ADC. [ABSTRACT FROM AUTHOR]

This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02–0.10), PR (0.15, 95%CI: 0.08–0.22), SD (0.16, 95%CI: 0.13–0.20), PD (0.50, 95%CI: 0.25–0.75), ORR (0.26, 95%CI: 0.11–0.41) and DCR (0.42, 95%CI: 0.13–0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3–5 AEs was significantly lower, rarely surpassing 0.10. For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Introduction: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy. Methods: We analyzed cfDNA before and 6–8 weeks after the start of treatment in 20 advanced HCC patients who started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, −124C>T and −146C>T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. Computerized tomography evaluation was performed at 6–8 weeks and 3–4 months to assess the efficacy. Results: Frequencies of TERT promoter, CTNNB1, and TP53 mutations in pretreatment cfDNA were 45%, 65%, and 65%, but 53%, 41%, and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression. Conclusion: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs. [ABSTRACT FROM AUTHOR]

Introduction: Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients. Materials and Methods: The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, microsatellite instability status, tumor locations, recurrence risk factors, preoperative carcinoembryonic antigen levels, and adjuvant treatments were systematically evaluated. Results: In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index of 25.1 kg/m2. In the patient group without risk factors, no statistically significant difference was detected in disease-free survival (DFS) rates between those who received treatment and those who did not (p = 0.546). DFS rates of patients with >1 risk factor were statistically significantly lower than those with a single risk factor (p = 0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p < 0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was significantly higher in the group receiving capecitabine (p = 0.01). Conclusion: The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity. [ABSTRACT FROM AUTHOR]

Background: It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC). Methods: This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups. Results: Patients were followed up ranged from 1.03 to 91.60 months, with a median follow-up time of 67.37 months. Kaplan–Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P < 0.001) and DFS (67.15% vs 77.76%, P < 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95% CI): 0.54 (0.41, 0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100 ml vs. 200 ml, P < 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P < 0.001). Similar results were found after PSM. Conclusion: In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates. [ABSTRACT FROM AUTHOR]

Advanced gastroesophageal cancers are still associated with poor outcomes. We aim to study PD-1/PD-L1 inhibitors in phase III clinical trials that have compared them to chemotherapy in gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma. On March 28, 2024, we searched: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov. We only included randomized clinical trials for PD-1/PD-L1 inhibitors alone or with chemo vs chemotherapy in advanced gastric, GEJ, or esophageal adenocarcinoma. The primary endpoints were overall survival and progression-free survival. A subgroup analysis was conducted for the following variables: treatment line, type of intervention, age group, gender, ECOG Performance Status, combined positive scores (CPS), microsatellite instability (MSI) status, liver metastasis, and primary tumor location. Only 10 out of 8,942 articles were included, involving 6,782 patients. PD-1/PD-L1 inhibitors showed a significant improvement in the overall survival compared to chemotherapy alone (hazard ratio (HR): 0.86, 95% CI: 0.80–0.93; p = 0.0002). Combining PD-1/PD-L1 inhibitors with chemotherapy significantly improved overall and progression-free survival compared to monotherapy (combined therapy HR 0.80; p < 0.00001 vs. monotherapy HR 0.98; p = 0.77). CPS ≥1 had an HR of 0.78 (95% CI: 0.73–0.84; p < 0.00001), CPS ≥10 had an HR of 0.67 (95% CI: 0.59–0.76; p < 0.00001), and MSI-high status had an HR of 0.35 (95% CI: 0.24–0.52; p < 0.00001). Esophageal adenocarcinoma, reported in three trials, did not show significant improvement in the overall survival (HR 0.89; 95% CI: 0.69–1.14; p = 0.37). PD-1/PD-L1 inhibitors have significantly improved overall survival, and combining them with chemotherapy is more effective than monotherapy. Both CPS ≥10 and MSI-H showed an added benefit to overall survival and should be included in biomarker investigations. Clinical trials are needed for second-line treatments and esophageal adenocarcinoma. • Systematic review of PD-1 inhibitors vs chemotherapy in phase III trials: 10 studies, 6,782 patients. • Combining PD-1/PD-L1 inhibitors with chemotherapy improves overall and progression-free survival vs inhibitors alone. • CPS ≥ 10 and MSI-H showed added overall survival benefits; include them in biomarker studies. • Trials combining PD-1/PD-L1 inhibitors with chemo are needed for second-line treatment patients. • PD-1/PD-L1 inhibitors didn't improve OS in advanced esophageal adenocarcinoma; further trials needed. [ABSTRACT FROM AUTHOR]

In the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. BIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). 61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. Focal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. NCT02125175. • Focal boosting is a safe prostate radiotherapy technique with a low toxicity profile. • It can be used with moderately fractionated radiotherapy schedules (20 fractions). • High-risk localised prostate cancer patients achieve excellent long-term outcomes. • Patients with PET-avid pelvic lymph nodes were treated with prostate focal boost, pelvic node and nodal boost radiotherapy. [ABSTRACT FROM AUTHOR]

Aim: This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients. Methods: One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child–Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression‐free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy. Results: After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin–bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186–0.782), 2.220 (95% CI, 1.410–3.493), and 0.982 (95% CI, 0.966–0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176–0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215–0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed. Conclusion: Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy. [ABSTRACT FROM AUTHOR]

Background: Tisotumab vedotin (TV) holds promise for treating recurrence or metastatic cervical cancer (r/mCC), with recent FDA approval for second‐line use in recurrent or metastatic cases. Our research aims to evaluate TV's efficacy and safety in these patients, focusing on overall survival (OS) and progression‐free survival (PFS) outcomes. Methods: We searched five electronic databases in February 2024, retrieved articles, screened them based on inclusion and exclusion criteria, and assessed their quality. A meta‐analysis of the extracted data was performed and applied a random‐effects model for our analysis. Results: The search identified 86 articles, with six meeting the inclusion criteria. Meta‐analysis revealed 80.8% and 48.0% OS at 6 and 12 months, and a 29.9% PFS at 6 months. Combined treatment with carboplatin or pembrolizumab showed 33.0% PFS at 1 year and 15.1% at 2 years. The objective response rate (ORR) was 21.0%, reaching 43.3% with combined treatment. Confirmed disease control rate (CDCR) was 70.0% overall and in combination. The median duration of response (DOR) was 6.1 months, increasing to 9.5 months in combined treatment, with a consistent time to response (TTR) of 1.4 months. Adverse events included ocular issues (conjunctivitis 30.3%, dry eye 18.7%) and common side effects (nausea 38.4%, epistaxis 35.7%). Conclusion: This systematic review and meta‐analysis highlights the potential of TV as a treatment option for r/mCC patients. However, healthcare providers must communicate safety profiles and recommend prophylactic measures for optimal patient outcomes. Further studies, particularly assessing combination treatments, are needed to clarify TV's role in treatment algorithms and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this experiment is to explore the role of long intergenic noncoding RNA 261 (LINC00261) gene in the chemoresistance and clinical prognosis of epithelial ovarian cancer (EOC). Methods: We used matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry to detect the methylation levels of the LINC00261 promoter region in EOC patient specimens. The expression levels of LINC00261, miR‐545‐3p, and MT1M in EOC patients were evaluated by quantitative real‐time reverse transcriptase PCR (RT‐qPCR). Spearman's correlation analysis was used for relevance analyses and clinical prognosis was counted by Kaplan–Meier analysis. Stable overexpressed LINC00261 SKOV3 cells were established to test the influence of LINC00261 on proliferation, platinum sensitivity, migration, and invasion. Results: The promoter region methylation level of the LINC00261 was hypermethylated and LINC00261 was significantly downregulated in platinum‐resistant EOC tissues. The methylation level of LINC00261was significantly negative correlated with its RNA expression in EOC. Moreover, hypermethylation and lower expression of LINC00261 in EOC patients were related to shorter progression‐free survival (PFS) and overall survival (OS). Furthermore, Spearman's correlation analysis showed that the expression of miR‐545‐3p had a negative relevance with LINC00261. According to the website prediction, MT1M might be the downstream target gene of LINC00261. Expression of MT1M was negatively correlated with miR‐545‐3p and positively with LINC00261 in EOC tissues. And lower MT1M mRNA expression was correlated with chemotherapy resistance and worse prognosis. In vitro, overexpression of LINC00261 could inhibit cisplatin resistance, proliferation, and suppression of migration and invasion in SKOV3 cells. Conclusions: This research indicates that the aberrant hypermethylation and low expression of LINC00261 were associated with platinum resistance and adverse outcomes in EOC patients. [ABSTRACT FROM AUTHOR]

Introduction: Complete mesocolic excision (CME) is widely adopted for its assumed superior oncological outcome. However, it's unclear if all right-sided colon cancer patients benefit from CME. The aim of this systematic review is to investigate whether CME contributes to postoperative outcomes and to determine the surgical indications for CME. Material and methods: We searched eligible articles about CME versus non-CME procedures for right-sided colon cancer in the OVID Medline, Embase, and Cochrane CENTRAL databases, and a meta-analysis was conducted. Results: Twenty-two articles and seven abstracts involving 8088 patients were included in this study. Among them, 3803 underwent CME and 4285 non-CME procedures. The analysis showed that CME was favoured for three-year disease-free survival (DFS) and overall survival (OS), for local, systemic, and total recurrence, and for hospital stay durations. However, increased vascular injury and longer surgery time were observed in CME. Regarding the three-year OS, the superiority of CME was observed only in Stage III. Additionally, no significant differences were observed between CME and non-CME groups regarding overall complications, 30-day readmission rates, reoperation, or postoperative mortality rates. Conclusions: CME for right-sided colon cancer should be considered, particularly in Stage III patients, to contribute to improved oncological outcomes. However, careful attention must be paid to the increased risk of vascular injury. [ABSTRACT FROM AUTHOR]

Introduction: Paraneoplastic neurological syndrome (PNS) is associated with small‐cell lung cancer (SCLC). However, the frequency and characteristics of PNS and the efficacy of anticancer treatment for these patients have not been investigated in the Japanese/Asian population previously. Therefore, we aimed to better understand PNS by evaluating real‐world data from patients with PNS complicated by SCLC. Methods: Patients diagnosed with Stage II–IV SCLC at a single center between August 2007 and April 2021 were retrospectively analyzed. The primary outcome was the incidence of PNS. The secondary outcomes were the change in performance status (PS) after treatment commencement and outcomes following anticancer treatment, including objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results: A total of 318 patients were evaluated; PNS was present in 2.8% (n = 9) of the overall population. All patients with PNS exhibited poor Eastern Cooperative Oncology Group PS (≥2); moreover, 78% of patients had a PS score of 3–4. An improvement in PS was observed in 56% (n = 5) of patients. Patients with PNS exhibited treatment efficacies similar to patients without PNS (ORR: 89% vs. 83%, p = 1.0; PFS: 7.6 vs. 5.7 months, p = 0.69; OS: not reached vs. 15.6 months, p = 0.23). Conclusions: A total of 2.8% of patients had SCLC complicated by PNS, with poor PS observed. However, anticancer therapy led to an improvement in PS and comparable ORR, as well as PFS and OS similar to those observed in patients without PNS. Thus, anticancer therapy should be considered in patients with PNS. [ABSTRACT FROM AUTHOR]

Background: Patients with non‐small‐cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor‐related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small‐cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first‐line chemoimmunotherapy and to assess its relationship with prognosis. Methods: We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first‐line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. Results: A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574–18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506–18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179–3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001–1.002; p < 0.001) were statistically significant for increased mortality risk in multivariate Cox regression analysis. Conclusions: In SCLC patients receiving first‐line chemoimmunotherapy, baseline ILA is a risk factor for CIP and is associated with poorer prognosis. [ABSTRACT FROM AUTHOR]

Background: Hippo‐avoidance prophylactic cranial irradiation (HA‐PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall‐off and compensate for setup errors. Most studies recommend a 5‐mm margin, while it could be optimized to a 2‐mm expansion. Here, we showed the details of optimized HA‐PCI for limited‐stage small cell lung cancer (LS‐SCLC). Methods: This cohort study reviewed patients with LS‐SCLC receiving optimized HA‐PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo‐related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test—Revised (HVLT‐R) scores in different time points was conducted. The Kaplan–Meier method was used to calculate the survival rates. Results: A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40–7.44) and 7.63 Gy (IQR: 7.14–8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric‐modulated arc therapy [VMAT]). The decline of HVLT‐R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow‐up of 52 months (95% CI: 47.2–56.7), the 2‐year overall survival and progression‐free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus. Conclusions: Optimized HA‐PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the most aggressive cancers with a poor prognosis. Global expression profiling was conducted on primary ESCC tissues with distant metastases. We investigated the identification of secretogranin V (SCG5) as a promising biomarker for the detection and assessment of ESCC. SCG5 transcription levels were evaluated in 21 ESCC cell lines. Small interfering RNA–mediated knockdown experiments validated SCG5's roles in cell invasion, proliferation, and migration. We utilized a mouse subcutaneous xenograft model to assess tumor growth. SCG5 expression was measured in 164 ESCC tissues by quantitative reverse transcription quantitative polymerase chain reaction, and its association with clinicopathological parameters was investigated. SCG5 protein levels were assessed in surgically resected tissues from 177 patients with ESCC using a tissue microarray. The mRNA expression levels of SCG5 varied widely in ESCC cell lines. The in vitro cell invasion, proliferation, and migration of ESCC cells were suppressed by the knockdown of SCG5. Mouse xenograft models revealed that tumor growth was reduced by small interfering RNA–mediated SCG5 knockdown. Analysis of clinical samples demonstrated that SCG5 mRNA was expressed in ESCC compared to adjacent normal esophageal tissues. High SCG5 mRNA expression was linked to significant decreases in overall and disease-specific survival. Furthermore, SCG5 protein expression was linked to a decrease in disease-specific survival and disease-free survival. The expression of the SCG5 was significantly associated with disease-specific survival, suggesting that SCG5 may play a significant role as a diagnostic and prognostic biomarker for ESCC. [ABSTRACT FROM AUTHOR]

Purpose: In Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [177Lu]Lu-DOTATATE therapeutic regimen. Methods: The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD_TOT was calculated as the mean between cycle 1 (GTD_1) and 4 (GTD_4) multiplied by 4. Patients were followed-up for median 32.8 (range 18–45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months. Results: The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5%. GTD_1 and GTD_TOT were statistically associated with PFS > / < 24 m (p = 0.026 and p = 0.03 respectively). The stratification of patients on GTD_1 lower or higher than the best cut-off value at 10.6 Gy provided significantly different median PFS of 21 months versus non reached, i.e. longer than 45.5 months (p = 0.004), with a hazard ratio of 8.6, (95% C.I.: [2 – 37]). Using GTD_TOT with the best cut-off at 43 Gy, the same PFS values were obtained as after cycle 1 (p = 0.035). At multivariate analysis, a decrease in GTD_1 and, with lower impact, a higher global tumour volume were significantly associated with PFS < 24 months. We calculated the Tumour Control Probability of obtaining PFS > 24 months as a function of GTD_1. Discussion: Several statistical analyses seem to confirm that simple tumour dosimetry with 2 SPECT/CT scans after the first administration allows to predict PFS values after 4 × 7.4 GBq administrations of 177Lu[Lu]-DOTATATE in G1-G2 GEP NETs. This result qualitatively confirms recent findings by a Belgian and a French study. However, dosimetric thresholds are different. This probably comes from different cohort baseline characteristics, since the median PFS in our study (42 m) was longer than in the other studies (28 m and 31 m). Conclusion: Tumour dosimetry after the first administration of [177Lu]Lu-DOTATATE offers an important prognostic value in the clinical decision-making process, especially for the future as alternative emitters or administration schedule may become available. [ABSTRACT FROM AUTHOR]

Background: Previously reported results from phase III KEYNOTE-048 demonstrated similar or improved overall survival (OS) with pembrolizumab or pembrolizumab-chemotherapy versus cetuximab-chemotherapy (EXTREME) in Japanese patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We report results in Japanese patients from KEYNOTE-048 after 5 years of follow-up. Methods: Patients with R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or EXTREME. Primary endpoints were OS and progression-free survival. Efficacy was evaluated in the programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, PD-L1 CPS ≥ 1, and total Japanese populations. Results: In Japan, 67 patients were enrolled (pembrolizumab, n = 23; pembrolizumab-chemotherapy, n = 25; EXTREME, n = 19). Median follow-up was 71.0 months (range, 61.2–81.5); data cutoff, February 21, 2022. 5-year OS rates with pembrolizumab versus EXTREME were 35.7% versus 12.5% (hazard ratio [HR] 0.38; 95% CI 0.13–1.05), 23.8% versus 12.5% (HR 0.70; 95% CI 0.34–1.45), and 30.4% versus 10.5% (HR 0.54; 95% CI 0.27–1.07) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. 5-year OS rates with pembrolizumab-chemotherapy versus EXTREME were 20.0% versus 14.3% (HR 0.79; 95% CI 0.27–2.33), 10.5% versus 14.3% (HR 1.18; 95% CI 0.56–2.48), and 8.0% versus 12.5% (HR 1.11; 95% CI 0.57–2.16) in the PD-L1 CPS ≥ 20, CPS ≥ 1, and total Japanese populations, respectively. Conclusion: After 5 years of follow-up, pembrolizumab and pembrolizumab-chemotherapy showed long-term clinical benefits; results further support these treatments as first-line options for Japanese patients with R/M HNSCC. Clinical trial registration: NCT02358031. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancer (BTC) comprises a heterogeneous group of malignancies with poor prognosis because of the limited treatment options. With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests have been widely introduced into daily clinical practice. Patients and methods: We performed a retrospective, multicenter, observation cohort study. The genomic and clinical data of 85 BTC patients, who underwent CGP testing from August 2021 to September 2023, were analyzed. Results: There were 62 (73%) cases in which treatment recommendations were raised during expert meetings, including 34 intrahepatic cholangiocarcinoma (ICC), 20 extrahepatic cholangiocarcinoma (ECC) and 8 gall bladder carcinoma (GBC). The drug accessibility rate of the BTC patients was 15.3% (13 cases): ten ICCs, two ECCs, and one GBC. Five ICC patients (three male and two female) with the FGFR2 fusion gene were treated with pemigatinib. Those patients who received a genomically matched therapy had significantly longer median overall survival than those patients who not received. (n = 13; not reached [95% CI not reached-not reached] vs n = 72; 8.6 months [95% CI 6.6–10.0]; hazard ratio 0.24 [95% CI 0.12–0.49], p = 0.013). The median observation period of pemigatinib treatment was 15.4 months (range 10.1–27.4). The responses were classified as PR in three patients, SD in one patient and PD in one patient. The median progression free survival is 9.0 months. No patient had grade 3/4 AEs requiring discontinuation of the treatment. Conclusion: The drug accessibility rate of ICC is high and pemigatinib is effective and well-tolerated in ICC patients harboring FGFR2 gene fusions. [ABSTRACT FROM AUTHOR]

Background: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. Methods: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. Results: Out of 104 patients who met the criteria, the median age was 58 years (range, 16–72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4–12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6–15.0) and 27.9 months (95% CI 21.6–34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. Conclusion: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials. [ABSTRACT FROM AUTHOR]

Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) has been associated with oncological outcome. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatic resection for PDAC. Patients who received NAT before undergoing PDAC resection at two institutions were reviewed. Tumour regression grading (TRG) was scored according to the College of American Pathologists (CAP) system. Interactions between chemotherapy, tumour and surgical factors with TRG were explored. 54 patients were identified, with 12 (22%) displaying a favourable response to NAT. The type of chemotherapy agent received, the number of cycles or a dose reduction during NAT course was not significantly different between the groups. The time from diagnosis to chemotherapy and time from end of chemotherapy to surgery were also similar between the groups. A favourable TRG was associated with greater disease-free survival median 33.2 months vs. 10.3 months; p = 0.0) but not overall survival (median 43.8 months vs. 32.3 months; p = 0.200), which may be due to small sample size. Chemotherapy factors were not significantly related to a favourable response to NAT. Future studies should seek to identify modifiable factors associated with a favourable TRG. [ABSTRACT FROM AUTHOR]

Introduction: Radiotherapy-related damage of normal tissue inevitably influences the treatment outcomes in the context of high-grade gliomas (HGGs) treatment. We reported the survival outcomes and toxicities of patients with HGG treated with helical tomotherapy (HT) and the prognostic factors were analyzed. Materials and methods: A total of 67 patients (29 had grade III and 38 had grade IV HGGs) who received HT between January 2016 and June 2020 were analyzed. Overall survival (OS) and progression-free survival (PFS) from the beginning of HT and OS from surgery were assessed, and toxicity and disease control were described briefly. Results: For patients with grade III HGGs, median OS (mOS) and median PFS (mPFS) from the beginning of HT were 68.933 and 62.967 months, respectively. For patients with grade IV HGGs, mOS and mPFS from the beginning of HT were 19.667 and 7.23 months, respectively. No grade ≥3 acute or late nonhematologic toxicities were observed. Multivariable Cox regression analysis showed that methylguanine methyltransferase (MGMT) methylated status, age, number of lesions, WHO grade, and monocyte count for PFS were significant. Age, monocyte count, and isocitrate dehydrogenase (IDH) status for OS. Conclusion: Treatment of HGGs with HT appears to be potentially effective and safe. HT is promising for glioblastomas (GBM), especially complex cases with infratentorial involvement or multiple lesions. This study highlighted the potential clinical significance of systemic inflammation indicators in predicting survival and disease progression. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high‐grade neuroendocrine carcinoma of the cervix (NECC). Methods: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2–IIA2 and IIIC1/2p high‐grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan–Meier methods were used for analysis. Results: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high‐grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02–86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0–18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34–16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02–19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20–22.53, P = 0.027). Kaplan–Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). Conclusion: Patients with mixed histologic types who undergo surgery for high‐grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high‐risk factors should be considered in clinical practice. Synopsis: Patients with surgically treated NECC who had mixed histologic types, underwent ovariectomy, and received adjuvant EP chemotherapy had a better prognosis. [ABSTRACT FROM AUTHOR]

Marginal mandibulectomy is indicated for oral cavity squamous cell carcinomas that involve floor of mouth, abut or minimally erode the mandible without gross invasion. Successful outcomes after Marginal mandibulectomy is predicated on accurate patient selection and appropriate adjuvant treatment based on specific host and tumor characteristics. To study the onclogical outcomes in terms of loco-regional recurrence free survival and disease specific survival of marginal mandibulectomy done for oral squamous cell carcinomas. Study Design—Retrospective study. Setting—The study was done from January 2018 to January 2021 at our tertiary care centre Madras Medical College, Chennai. Subjects—30 cases were included in our study who underwent Marginal Mandibulectomy for oral cavity SCC. Methods—The decision to perform a marginal mandibulectomy was taken based on preoperative clinical examination, contrast enhanced computed tomography (CECT) findings and intra-operative assessment under anesthesia. Disease-free survival, cause-specific survival, and local control rates were plotted using the Kaplan-Meier method. Oncologic outcomes in terms of Overall survival and Disease-specific survival at the end of 1 year and 3 years for the gingival, buccal, tongue, floor of mouth cancers were analyzed. Independent impacts including the site of tumor, T and N stage, microscopic bony invasion, grade of differentiation, adjuvant radiotherapy on the loco-regional control and cause-specific survival were evaluated using Kaplan meier method. Our study group was comprised of 20(66.67%) males and 10 (33.33%) females of mean age 54 years. None of them had prior radiotherapy to the head and neck region. A total of 7 (23.33%) marginal mandibulectomies were carried out for SCC in the gingival region, 11(36.67%) for buccal mucosa, 8(26.67%) for tongue, 2(6.67%) for floor of mouth SCC, 1(3.33%) involving lip, 1(3.33%) in Retromolar trigone. Clinically 2 (6.67%) patients had T1 cancer, 18 (54.54%) had T2, 6 (18.18%) had T3, 4(13.33%) had T4 tumor. Clinically Neck nodes were not palpable in 17 (56.67%) patients, 10 (33.33%) had N1 disease and 3 (10%) had N2 disease. T and N stage distributions for tongue/floor of mouth and gingival buccal complex cancers are summarized in the table and there were no statistically significant differences between the 2 groups. 19 (63.33%) had selective neck dissection (levels I–III), and 11 (36.67%) had comprehensive neck dissection. Well-differentiated tumors were encountered in 12 (40%) cases, moderately differentiated tumors in 16 (53.33%) cases, and poorly differentiated tumors in 2 (6.67%) cases. Bone was microscopically involved in 4 (13.33%) cases and mucosal margin of excision was less than 5 mm from the tumor in 2 (6.67%) cases. Cumulative hazard of local recurrence was not significantly affected by mandibular involvement. On histopathologic examination, positive nodes were seen in 6(20%) cases that included 3 (10%) with pN1 and the rest with pN2 disease. Adjuvant radiotherapy (56 to 64 Gy) was given to 13 (43.33%) patients. In carefully selected patients, marginal mandibulectomy in oral squamous cancer achieves good oncological outcome in terms of locoregional control and overall survival rates. [ABSTRACT FROM AUTHOR]

Patients with advanced tumors enrolled in phase I trials display strong treatment expectations and few therapeutic alternatives. When oligoacquired resistance (OAR; ≤3 lesions of disease progression) occurs, local ablative stereotactic radiation therapy (SRT) could allow disease control and continuing the experimental systemic treatment. Data from patients enrolled in phase I trials evaluating systemic treatments, who experienced OAR while on the phase I systemic therapy and subsequently received SRT between January 2014 and April 2023, were retrospectively analyzed. Progression-free survival (PFS)1 (trial entry to OAR), PFS2 (SRT to first subsequent relapse), time to next systemic treatment (TTNT), and overall survival (OS) were assessed. First subsequent patterns of relapse after SRT were distinguished as OAR2, which could be locally rechallenged, or systemic acquired resistance (SAR; >3 lesions of disease progression). When available, correlations between molecular profile and pathway enrichments of OAR and SAR were explored. Forty-two patients with 52 oligoprogressive lesions were analyzed. The median follow-up was 24 months. SRT allowed a median PFS2 of 7.1 months and a median TTNT of 12.8 months. PFS2 included 49% OAR2 and 51% SAR. Median time to first subsequent relapse (9.6 vs 3.5 months; P =.014) and TTNT (22.4 vs 7.6 months; P <.001) were longer for OAR2 compared with that for SAR. No severe toxicities were reported. A PFS1 of <6 months and de novo oligoprogressive lesions were associated with the presence of SAR. More diverse enriched gene pathways were observed for SAR compared with that for OAR2. In patients enrolled in phase I trials, OAR managed with SRT may increase time on investigational systemic treatments. Predictive factors reflecting tumor aggressiveness and clonal heterogeneity could help deciphering OAR2 from SAR and maximize SRT output in the oligoprogressive setting. [ABSTRACT FROM AUTHOR]

We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer. Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity. Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P =.83). There was no significant difference (P =.17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P =.17). In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates. [ABSTRACT FROM AUTHOR]

This phase 1 study aimed to assess the safety and feasibility of SABR therapy delivery to all sites of polymetastatic disease (>10 metastases). A 3 + 3 study design was used with 5 dose levels from 6 Gy (6 Gy × 1) to 30 Gy (6 Gy weekly × 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity or more than 3 grade 3 toxicities within 6 weeks of treatment. The primary endpoint was the maximal tolerated dose, defined as the dose level where ≥2/6 of patients experienced DLT. Secondary endpoints included quality of life (Functional Assessment of Cancer Therapy – General and European Quality of Life 5 Dimension 5 Level) at 6 weeks posttreatment, progression-free survival, and overall survival. Thirteen patients were accrued: 12 Gy (n = 3), 18 Gy (n = 3), 24 Gy (n = 4), and 30 Gy (n = 3), and 207 lesions were treated. Nine patients (69%) had acute toxicity: grade 1 (n = 6, 46%), grade 2 (n = 2, 15%; n = 1 pneumonitis and n = 1 fatigue), and grade 3 (n = 1, 7.7% neutropenia). There were no grade 4 or 5 toxicities. Mean ± SD quality of life (Functional Assessment of Cancer Therapy – General and European Quality of Life 5 Dimension 5 Level health state) was 80.4 ± 21.9 and 77.4 ± 20.9 at baseline versus 76.4 ± 21.8 and 68.0 ± 24.2 at 6-week follow-up, respectively (p =.009 and p =.055, respectively). With a median follow-up of 8.7 months posttreatment (IQR, 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month progression-free survival were 3.6 months and 11.3%, respectively. The median and 12-month overall survival were 13.8 months and 62%, respectively. In this phase 1 trial, SABR therapy for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly × 5). DLT was not observed. [ABSTRACT FROM AUTHOR]

This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). Chemotherapy-naïve patients with resectable ESCC (stage IB-III, Union for International Cancer Control, International Cancer Control seventh edition) were eligible for the study. All patients received 3 cycles of docetaxel, cisplatin, and 5-FU (DCF) therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every 3 weeks). Remarkable response was defined as a reduction in the tumor to T1, metastatic lymph nodes <1 cm on the short axis, and downstaging to stage IA after 3 cycles of DCF therapy. Remarkable responders then underwent dCRT, which included 2 courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1 to 4, repeated every 4 weeks, along with 50.4 Gy of concurrent radiation therapy. The primary endpoint was 1-year progression-free survival in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival. Of the 92 patients registered, 90 were analyzed. A remarkable response to 3 courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range, 1-85 months), the 1-year progression-free survival was 89.8% (95% confidence interval [CI], 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and esophagectomy-free survival rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after 2 courses of DCF therapy was significantly associated with OS (P =.0049). In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with 3 courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection. [ABSTRACT FROM AUTHOR]

Metaplastic breast cancer (MBC) is a rare and heterogeneous breast cancer subtype, and there are critical gaps in our understanding of its long-term outcomes. This retrospective cohort study aimed to address these gaps by scrutinizing the pathologic and clinical aspects of MBC to enhance clinical decision-making and refine patient care strategies. This registry-based retrospective cohort study included women aged ≥21 years diagnosed with MBC or matrix-producing carcinoma. The data were obtained from January 2001 to August 2020 from the Joint Breast Cancer Registry of Singapore Health Services, which included 23,935 patients. Demographic and clinicopathologic characteristics, neoadjuvant chemotherapy responses, and survival outcomes were analyzed. Statistical assessments involved univariate and multivariate Cox proportional hazards models and Kaplan-Meier survival analyses. This study enrolled 170 patients; 87.1% had non-metastatic disease, and 12.9% had metastatic disease. The age of patients at diagnosis ranged from 46 to 65 years (median, 56 years). The cohort's predominant characteristics were triple negative breast cancer (64%), advanced clinical stage (77.6%), node negativity (67.6%), and grade 3 disease (74.1%). In patients receiving neoadjuvant chemotherapy with curative intent treatment (17.6%), neoadjuvant chemotherapy yielded a pathologic complete response of 19.2% and a disease progression rate of 46.2%. Multivariate analysis showed that adjuvant radiation therapy significantly improved overall survival and disease-free survival, with hazard ratios of 0.29 (95% CI, 0.13-0.62; P <.005) and 0.23 (95% CI, 0.10-0.50; P <.005), respectively. Clinical T3 and T4 stages and nodal involvement were associated with poor outcomes. Stable disease after neoadjuvant chemotherapy was associated with poor overall survival and disease-free survival. This study sheds light on the complex landscape of MBC and emphasizes the pivotal role of adjuvant radiation therapy in enhancing patient outcomes. Despite advancements, challenges persist that warrant continued research to refine neoadjuvant chemotherapy strategies and delve into the nuanced factors that influence treatment responses. [ABSTRACT FROM AUTHOR]

Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT). In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET-positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT. A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival were 96.8% (95% CI, 91.6%-98.8%) in the IFRT group and 95.4% (95% CI, 89.9%-97.9%; HR, 1.40; 95% CI, 0.44-4.42) in the ISRT group. The pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P =.03). For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the clinical benefit and safety of the triple combination of stereotactic body radiotherapy (SBRT), lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors with the dual combination of SBRT and lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC). Patients with uHCC who received SBRT in combination with lenvatinib and PD-1 inhibitors or SBRT in combination with lenvatinib alone as first-line treatment from October 2018 to July 2022 were reviewed in this study. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were intrahepatic PFS, extrahepatic PFS, and objective remission rate. In addition, safety profiles were assessed by analyzing treatment-related adverse events between the two groups to assess safety profiles. In total, 214 patients with uHCC who received combination therapy were included in this retrospective study. Among them, 146 patients received triple combination therapy of SBRT, lenvatinib, and PD-1 inhibitors (SBRT-L-P group), and 68 patients received dual therapy of SBRT and lenvatinib (SBRT-L group). The median OS times of the 2 groups were 31.2 months and 17.4 months, respectively (P <.001). The median PFS time was significantly longer in the SBRT-L-P group than in the SBRT-L group (15.6 months vs 8.8 months, P <.001). Additionally, the median intrahepatic PFS (17.5 vs 9.9 months, P <.001) and extrahepatic PFS (20.9 vs 11.6 months, P <.001) were significantly longer in the SBRT-L-P group than in the SBRT-L group. The objective remission rate in the SBRT-L-P group was higher than in the SBRT-L group (63.0 vs 39.7%, P =.002). The incidence and severity of treatment-related adverse events in the SBRT-L-P group were comparable to those in the SBRT-L group. The use of both lenvatinib and PD-1 inhibitors with SBRT in patients with uHCC was associated with improved overall survival compared with lenvatinib and SBRT alone with a manageable safety profile. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL. Methods: In this study, we retrospectively investigated the clinicopathological characteristics, outcome, and prognostic impact of negative CD117 expression (CD117−) in 169 APL patients treated with all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO) containing regimen. Results: The median follow‐up period was 63.0 months. CD117− was detected in 13 APL patients (7.7%). No significant differences were found in baseline characteristics between CD117+ and CD117− subgroups. However, compared to CD117+ APL, the incidence of early death (ED) was significantly higher in CD117− APL (p = 0.023). By multivariate analysis, CD117‐ was an independent adverse prognostic factor for overall survival (OS) and progression‐free survival (PFS) (p = 0.022 and p = 0.014, respectively). Conclusions: To sum up, CD117− is associated with greater risk of ED and has the statistical power to predict inferior OS and PFS, this marker may be considered to build prognostic scores for risk‐adapted therapeutic strategies in APL management. [ABSTRACT FROM AUTHOR]

Introduction: Current molecular research has shown the several oncogenic pathways that give rise to the peripheral T‐cell lymphoma, not otherwise defined (PTCL, NOS) subtypes, which alter prognosis and might have predictive value. This study was conducted to assess the immunohistochemistry (IHC) algorithm by Amador et al for the subtyping of PTCL, NOS and determine its applicability in relation to the clinicopathological profile. Methods: This study included 43 patients with PTCL, NOS diagnosis. Following the use of IHC for the transcription factors GATA3, TBX21, CCR4, and CXCR3, two pathologists subtyped the samples. Comprehensive clinicopathological correlation was carried out. Results: Applying the algorithm of Amador et al., cases were classified into GATA3 (20), TBX21 (15), and unclassified (8) subtypes. No significant association with clinical parameters of subtypes or CD4/ CD8 positivity was observed. Although a higher proportion of cases in the TBX21 subgroup showed a polymorphic population compared with the GATA3 subgroup, which had a monomorphic population, no significant p‐value (0.111) was observed. Two Lennert lymphomas were classified into the GATA3 subgroup. Multivariate analysis showed no significant difference in overall survival (p‐value = 0.105) and progression‐free survival (p‐value = 0.0509) between IHC‐defined subtypes; trends indicate that overall survival and progression‐free survival are worse in the GATA3 subgroup. Conclusion: Although the algorithm is reproducible, a proportion of cases remains unclassifiable and may require additional investigation and gene expression profiling. The GATA3 subgroup was found to have a monomorphic population with a poor overall prognosis and thus requires a larger sample size for validation. [ABSTRACT FROM AUTHOR]

PURPOSE: The National Cancer Institute-Children's Oncology Group Pediatric Molecular Analysis for Therapy Choice trial assigned patients age 1-21 years with relapsed or refractory solid tumors, lymphomas, and histiocytic disorders to phase II treatment arms of molecularly targeted therapies on the basis of genetic alterations detected in their tumor. Patients with tumors that harbored prespecified genomic alterations in the cyclinD-CDK4/6-INK4a-Rb pathway with intact Rb expression were assigned and treated with the cdk4/6 inhibitor palbociclib. METHODS: Patients received palbociclib orally once daily for 21 days of 28-day cycles until disease progression, intolerable toxicity, or up to 2 years. The primary end point was objective response rate; secondary end points included safety/tolerability and progression-free survival. RESULTS: Twenty-three patients (median age, 15 years; range, 8-21) were enrolled; 20 received protocol therapy and were evaluable for toxicity and response. Of the evaluable patients, the most common diagnoses were osteosarcoma (n = 9) and rhabdomyosarcoma (n = 6). A single actionable gene amplification was found in 19 tumors (CDK4 , n = 11, CDK6 , n = 2, CCND3 , n = 6), with one tumor harboring two amplifications (CDK4 and CCND2). Hematologic toxicities were the most common treatment-related events. No objective responses were seen. Two patients with tumors harboring CDK4 amplifications (neuroblastoma and sarcoma) had best response of stable disease for six and three cycles. Six-month progression was 10% (95% CI, 1.7 to 27.2). CONCLUSION: The CDK4/6 inhibitor palbociclib at 75 mg/m2 orally daily was tolerable in this heavily pretreated cohort. No objective responses were observed in this histology-agnostic biomarker-selected population with treatment-refractory solid tumors, demonstrating that pathway alteration alone is insufficient in pediatric cancers to generate a response to palbociclib monotherapy. [ABSTRACT FROM AUTHOR]

PURPOSE: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. MATERIALS AND METHODS: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. RESULTS: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P =.17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P =.0004 and 21.7 v 6.4 months, log rank P =.04, respectively). CONCLUSION: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS. [ABSTRACT FROM AUTHOR]

PURPOSE: Cisplatin-based combination chemotherapy (CHT) is standard of care in metastatic urothelial cancer (mUC); however, no predictive molecular biomarkers are available for clinical use. The aim of this study was to investigate the impact of molecular subtypes in relation to treatment response and survival in patients with mUC treated with first-line CHT. PATIENTS AND METHODS: Molecular subtype classification according to the Lund Taxonomy (LundTax) was performed by tumor transcriptomic profiling and immunostaining in a retrospective cohort. Molecular subtypes were investigated in relation to the primary end point overall response rate (ORR) and secondary end points progression-free survival (PFS) and overall survival (OS). Differential gene expression and association to treatment response were explored. RESULTS: Ninety-five patients with mUC were classified into urothelial-like (Uro, 43%), genomically unstable (GU, 26%), basal squamous-like (Ba/Sq, 20%), mesenchymal-like (Mes-like, 8%), and small cell neuroendocrine-like (Sc/NE, 3%) subtypes. Patients with Mes-like tumors had lower ORR (14%) compared with Uro (70%), GU (77%), Ba/Sq (75%), and Sc/NE (67%; odds ratio, 0.06 [95% CI, 0.01 to 0.54], P =.012). Furthermore, patients with Mes-like tumors had significantly shorter PFS (hazard ratio [HR], 5.18 [95% CI, 2.28 to 11.76], P <.001) and OS (HR, 3.19 [95% CI, 1.45 to 7.03], P =.004). Patients with Uro and GU showed the longest survival. In responders, an enrichment of downregulated stromal- and immune-related genes was seen. Downregulation of interferon-induced transmembrane protein 2 was associated with increased ORR and improved OS. CONCLUSION: This study identifies different CHT responses by LundTax molecular subtypes in patients with mUC, where the Mes-like subtype was associated with lower response rate and shorter survival. Molecular subtypes correlate with treatment response and survival in metastatic urothelial cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored. MATERIALS AND METHODS: We obtained 79 samples of metastatic peritoneal tumor deposits from patients diagnosed with HGAA and performed whole-exome sequencing, RNA sequencing, and immunoprofiling before and after HIPEC. Tumor biopsies were subjected to immunogenomic profiling to detect mutational signatures and immune populations associated with oncologic outcomes. RESULTS: Fifteen patients with HGAA-PMs were included in the study. The median progression-free survival (PFS) was 6.7 months (2.7-25.3) and the median overall survival was 11.4 months (4.7-42). Mucin-associated genes (MUC16 , MUC3A , and MUC5AC) and titin (TTN) had the highest mutation frequencies. Mutational signatures such as single-base substitution 29 and doublet-base substitution 11 were present in >50% of single-base and double-base mutations. Higher PD-L1 coexpression on CD8+ T cells demonstrated a higher PFS both intratumorally (P =.019) and at the margin (P =.025). CONCLUSION: HIPEC-associated mutational signatures were identified in HGAA-PMs. Elevated PD-L1+ cytotoxic T-cell populations after HIPEC had better PFS, offering valuable insights for prognostication in the context of HIPEC treatment. [ABSTRACT FROM AUTHOR]