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Introduction: Neoadjuvant radiotherapy (NART) is often used in the treatment of extremity soft tissue sarcomas (STS) including myxoid liposarcoma (MLS). Postoperative major wound complications (WC) are a well-recognised problem following NART. Aims: A review of the literature regarding the definition and incidence of WC following NART and surgery for STS and a retrospective review of a single surgeon series of 25 MLS. Methods: A literature search for papers focusing on MLS, NART and WC was performed, with 12 papers being reviewed. Retrospective data from a single surgeon series of 25 patients with MLS, treated with NART and surgery, were reviewed, focussing on WC. Results: The average rate of WC from the 12 papers included was 29·4% (20–47%), and the average rate of reoperation was 15·6% (7·3–24%). There were a range of definitions used for WC, most commonly O'Sullivan's definition. In the single surgeon series, two patients (8%) developed WC and were treated conservatively, and there were no reoperations within 120 days. Conclusion: This literature review identified that there was a lack of consistency between the definitions used for major WC. The single surgeon series of MLS showed WC that were lower when compared to the reviewed literature (8% versus 29·4%). [ABSTRACT FROM AUTHOR]

Background: The Dutch Committee for the Evaluation of Oncological Drugs evaluates the effectiveness of new oncological treatments. The committee compares survival endpoints to the so-called PASKWIL-2023 criteria for palliative treatments, which define if treatment effects are considered clinically relevant. A positive recommendation depends on whether the median overall survival (OS) is below or above 12 months in the comparator arm. If the former applies, an OS benefit of at least 12 weeks, and a hazard ratio (HR) smaller than 0.7 are required. If the latter applies, an OS or progression free survival (PFS) benefit of at least 16 weeks, and an HR smaller than 0.7 are required. Nonetheless, the median survival time may not be reached and the proportional hazards (PH) assumption, quantified by the HR, is likely violated for immuno-oncology (IO) therapies, deeming these criteria inappropriate. Methods: We conducted a systematic literature review to identify statistical methods used to represent the clinical effectiveness of IO therapies based on trial data. We searched MEDLINE and EMBASE databases from inception to August 31, 2022, limited to English papers. Methodological studies, randomized controlled trials, and discussion papers recognising key issues of survival data analysis of IO therapies were eligible for inclusion. Results: A total of 1,035 unique references were identified. After full paper screening, 17 publications were included in the review. Additionally, 43 papers were identified through 'snowballing'. We conclude that the current PASKWIL-2023 criteria are methodologically incorrect under non-PH. In that case, single summary statistics fail to capture the treatment effect and any measure should be interpreted in combination with the Kaplan-Meier curves. We recommend 'parameter-free' measures, such as the difference in restricted mean survival time, avoiding assumptions on the underlying survival. Conclusions: The HR is commonly used to assess treatment effectiveness, without investigating the validity of the PH assumption. This happens with the application of the PASKWIL-2023 criteria for palliative oncology treatments, which can only be valid under a PH setting. Under non-PH, alternative treatment effect measures are suggested. We propose a step-by-step approach supporting the choice of the most appropriate methods to quantify treatment effectiveness that can be used to redefine the PASKWIL-2023 criteria, or similar criteria in other clinical areas. [ABSTRACT FROM AUTHOR]

Background: This systematic review and meta-analysis investigated the relationship between somatic TP53 oncogenic variants and prognosis, specifically with overall survival (OS) and progression-free survival (PFS) in patients diagnosed with supratentorial glioblastoma. Methods: We included longitudinal studies and clinical trials involving a minimum of 40 adult participants diagnosed with supratentorial glioblastoma, wherein the status of TP53 variants was assessed. We conducted searches in multiple databases. We assessed bias risk using a modified version of the Quality in Prognosis Studies tool, and the certainty of evidence was evaluated following the principles of the GRADE approach. Results and conclusion: This study encompassed 23 papers involving 2,555 patients, out of which 716 had reported oncogenic variants. TP53 oncogenic variants were associated with a reduced likelihood of 1-year survival (OR 0.52, 95% CI 0.29–0.94). However, our analysis did not reveal any significant impact of TP53 variants on overall survival, progression-free survival, or 2-year survival. Therefore, this comprehensive analysis demonstrates that the presence of genetic variants in TP53 does not provide useful information for the prognosis of glioblastoma. Systematic review registration: https://www.crd.york.ac.uk/prospero/ , identifier CRD42021289496. [ABSTRACT FROM AUTHOR]

Background: Rectal cancer is a common cancer worldwide and lacks effective prognostic markers. The development of prognostic markers by computational pathology methods has attracted increasing attention. This paper aims to construct a prognostic signature from whole slide images for predicting progression-free survival (PFS) of rectal cancer through an unsupervised artificial intelligence algorithm. Methods: A total of 238 patients with rectal cancer from two datasets were collected for the development and validation of the prognostic signature. A tumor detection model was built by transfer learning. Then, on the basis of the tumor patches recognized by the tumor detection model, a convolutional autoencoder model was built for decoding the tumor patches into deep latent features. Next, on the basis of the deep latent features, the tumor patches were divided into different clusters. The cluster number and other hyperparameters were optimized by a nested cross-validation method. The percentage of each cluster from the patient's tumor patches, which is hereafter called PCF, was calculated for prognostic signature construction. The prognostic signature was constructed by Cox proportional hazard regression with L2 regularization. Finally, bioinformatic analysis was performed to explore the underlying biological mechanisms of the PCFs. Results: The accuracy of the tumor detection model in distinguishing tumor patches from non-tumor patches achieved 99.3%. The optimal cluster number was determined to be 9. Therfore, 9 PCFs were calculated to construct the prognostic signature. The prognostic signature achieved a concordance index of 0.701 in the validation cohort. The Kaplan-Meier survival curves showed the prognostic signature had good risk stratification ability. Through the bioinformatic analysis, several PCF-associated genes were identified. These genes were enriched in various gene ontology terms. Conclusion: The developed prognostic signature can effectively predict PFS in patients with rectal cancer and exploration of the underlying biological mechanisms may help to promote its clinical translation. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC), the primary liver cancer arising from hepatocytes, the predominant cell constituting the liver, accounts for ~90% of all liver cancers. HCC is characterized by activation of receptors on tumor cell surface which regulates tumor cell proliferation and spread to distant organs (metastasis). The class of drugs which predominantly inhibits these receptors are collectively known as tyrosine kinase inhibitors (TKIs). Among them sorafenib, lenvatinib, regorafenib, and cabozantinib have been approved either as the first or as the second line of treatment for advanced HCC. In general, ~30% of HCC patients respond to TKIs, and those that respond invariably develop resistance in ~6 months. This review paper addresses the potential molecular mechanisms by which resistance to TKIs develop and enumerates potential strategies to overcome them thereby providing prolonged survival benefit to HCC patients. Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and the development of effective treatment strategies remains a significant challenge in the management of advanced HCC patients. The emergence of tyrosine kinase inhibitors (TKIs) has been a significant advancement in the treatment of HCC, as these targeted therapies have shown promise in prolonging the survival of patients with advanced disease. Although immunotherapy is currently considered as the first line of treatment for advanced HCC patients, many such patients do not meet the clinical criteria to be eligible for immunotherapy, and in many parts of the world there is still lack of accessibility to immunotherapy. As such, TKIs still serve as the first line of treatment and play a major role in the treatment repertoire for advanced HCC patients. However, the development of resistance to these agents is a major obstacle that must be overcome. In this review, we explore the underlying mechanisms of resistance to TKIs in HCC, the clinical implications of this resistance, and the potential strategies to overcome or prevent the emergence of resistance. [ABSTRACT FROM AUTHOR]

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment. Clinical Trial Registration: NCT05904886 (ClinicalTrials.gov) Plain Language Summary This research study is designed to test a new treatment combination for liver cancer, specifically for patients whose cancer cannot be removed with surgery or has spread. The treatment involves three medications: atezolizumab, bevacizumab and tiragolumab. Atezolizumab and bevacizumab are already used together as a standard treatment for liver cancer. Tiragolumab is designed to block the TIGIT receptor, which is normally involved in holding back the immune cells that would attack the tumor. Because tiragolumab may restore the immune response against the tumor, adding tiragolumab might make the treatment more effective. The study is being done worldwide and includes patients who have not received any previous systemic treatment for their advanced liver cancer. Patients participating in the study will be randomly placed into two groups. One group will receive the new combination of three medications, while the other group will receive the standard treatment of two medications plus a placebo (a treatment with no active ingredient). The main goal is to see if the new combination helps patients live longer and slows the cancer's growth compared with the standard treatment. Safety and how patients feel during the treatment are also important parts of the study. Tweetable Abstract IMbrave152/SKYSCRAPER-14: New Phase III trial tests atezolizumab, bevacizumab & tiragolumab in advanced HCC, aiming to revolutionize treatment outcomes. #HCCResearch #OncologyInnovation Article highlights Advanced hepatocellular carcinoma treatment Atezolizumab in combination with bevacizumab has become the standard first-line therapy for advanced hepatocellular carcinoma (HCC). The immunosuppressive hepatic tumor microenvironment may limit the clinical activity of this combination in patients with HCC. TIGIT, a protein often found at high levels within these immunosuppressive cells, is a potential therapeutic target to overcome this resistance. Tiragolumab is an agent that inhibits TIGIT, suggesting a possible improvement in clinical outcomes when combined with the existing therapy. IMbrave152/SKYSCRAPER-14 trial rationale The randomized Phase III trial (NCT05904886) is designed to compare the efficacy and safety of the addition of tiragolumab to the current atezolizumab and bevacizumab regimen for HCC. The trial is designed to confirm efficacy signals from the Phase Ib/II MORPHEUS-Liver study, testing the hypothesis that targeting TIGIT with tiragolumab can enhance treatment response. Study design & eligibility Approximately 650 participants with no prior systemic treatment will be assigned to receive either the triple combination of atezolizumab, bevacizumab and tiragolumab or the standard dual therapy plus placebo. Participants will be randomly divided into two groups with stratification based on geographic region, disease progression, α-fetoprotein levels and HCC etiology. Treatment & trial objectives Patients will be administered intravenous doses of the treatment every three weeks, with outcomes measured in terms of progression-free survival and overall survival. Secondary end points include safety, efficacy, pharmacokinetics, immunogenicity and quality-of-life assessments. Preliminary results & safety profile The MORPHEUS-Liver trial indicated improved outcomes with the addition of tiragolumab to the existing atezolizumab and bevacizumab treatment, suggesting a well-tolerated safety profile with manageable adverse events. Conclusions & implications for hepatocellular carcinoma treatment IMbrave152/SKYSCRAPER-14 aims to establish whether the addition of tiragolumab can redefine the standard of care for unresectable HCC. This trial's findings could significantly impact the therapeutic landscape for HCC, addressing a critical unmet medical need [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the head and neck (SCCHN) is among the ten most common cancers worldwide, with advanced SCCHN presenting with a 5-year survival of 34% in the case of nodal involvement and 8% in the case of metastatic disease. Disease-free survival at 2 years is 67% for stage II and 33% for stage III tumors, whereas 12–30% of patients undergo distant failures after curative treatment. Previous treatments often hinder the success of salvage surgery and/or reirradiation, while the standard of care for the majority of metastatic SCCHN remains palliative chemo- and immuno-therapy, with few patients eligible for locoregional treatments. The aim of this paper is to review the characteristics of recurrent SCCHN, based on different recurrence sites, and metastatic disease; we will also explore the possibilities not only of salvage surgery and reirradiation but also systemic therapy choices and locoregional treatment for metastatic SCCHN. [ABSTRACT FROM AUTHOR]

Background: Sinonasal tumors represent a rare and heterogeneous group of rhinologic neoplasms. Even with advancements in surgical approaches, mortality rates of patients with sinonasal adenocarcinoma (SNAC) have not significantly improved and persistently high rates of recurrence in certain patients with inverted papilloma (IP) are seen. The use of 5-fluorouracil (5-FU) has been successfully described as an adjuvant treatment of SNAC and in the prevention of IP recurrence. Objective: This review aims to present the current evidence on the management of SNAC and IP with topical 5-FU. Methods: A three-author independent literature review was conducted to identify research involving the use of topical 5-FU for the treatment of SNAC and IP. A total of nine papers on the treatment of SNAC and IP were collected. Results: The earliest study looking at the combination of adjuvant low-dose radiation and topical 5-FU for adenocarcinoma of the ethmoid sinus showed a 5-year survival rate of 100%. A follow-up study evaluating a similar protocol reported adjusted disease-free survival at 2, 5, and 10 years of 96%, 87%, and 74%, respectively. Similar results have been demonstrated for adjuvant 5-FU use following endoscopic resection and have even been described in the novel setting of transcutaneous 5-FU delivery following frontal trephination. Topical 5-FU has also been described in the treatment of aggressive IP. The largest case series described the use of 5-FU for eighteen cases and demonstrated only a single recurrence. Conclusion: The use of topical 5-FU currently represents an underutilized therapeutic modality within the treatment of rhinologic neoplasms. Available literature suggests that neoadjuvant use of topical 5-FU can improve survival and decrease recurrence for SNAC and IP. However, the small sample sizes prevent advocation for routine use in the general population and further research on 5-FU is necessary. [ABSTRACT FROM AUTHOR]

Plexiform neurofibroma (PF) is a rare benign variant belonging to a subtype of neurofibromatosis type 1 that forms bulging or deforming masses arising from the peripheral nerve sheath. These masses involve surrounding connective tissue or dermal layers, leading to multiple cutaneous changes and certain characteristic appearances. It is these appearances that aid in the diagnosis of PF. We have encountered two distinct patients diagnosed with this disorder. While one patient was clinically and pathologically confirmed for PF, the other had no characteristic cutaneous changes. The diagnosis was made with postoperative histopathology and confirmed with an immunohistochemical examination. There are various modalities in the management of PFs, with surgery being a mainstay in the treatment of disfiguring large PFs, especially in resource-restrained settings. In view of high recurrence rates, postoperative clinical follow-up is a must. This paper describes these patients' typical and atypical clinical presentation and subsequent management. [ABSTRACT FROM AUTHOR]

Digital twins are a relatively new form of digital modeling that has been gaining popularity in recent years. This is in large part due to their ability to update in real time to their physical counterparts and connect across multiple devices. As a result, much interest has been directed towards using digital twins in the healthcare industry. Recent advancements in smart wearable technologies have allowed for the utilization of human digital twins in healthcare. Human digital twins can be generated using biometric data from the patient gathered from wearables. These data can then be used to enhance patient care through a variety of means, such as simulated clinical trials, disease prediction, and monitoring treatment progression remotely. This revolutionary method of patient care is still in its infancy, and as such, there is limited research on using wearables to generate human digital twins for healthcare applications. This paper reviews the literature pertaining to human digital twins, including methods, applications, and challenges. The paper also presents a conceptual method for creating human body digital twins using wearable sensors. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of pre-emptive and prophylactic tyrosine kinase inhibitors (TKIs) after allogeneic hematopoietic stem cell transplantation (Allo-SCT) remains highly heterogeneous and very little is known about the use of third generation TKIs in this context. In this paper, we analyze the feasibility of maintenance with ponatinib administered after Allo-SCT to prevent cytologic relapse in a population of 48 patients with Philadelphia-positive acute lymphoblastic leukemia undergoing transplant while in complete cytologic remission. Although with the caution of the retrospective data, our analysis supports the feasibility of a ponatinib maintenance strategy after Allo-SCT, resulting in a low rate of discontinuation due to toxicity and a high probability of survival and relapse-free survival, particularly in the prophylactic group. In the majority of cases where a daily dose of 45 mg was started a dose reduction to 30–15 mg/day was required, which may be the appropriate dose to balance efficacy and tolerability. The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p = 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rank p = 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design: Meta-analysis and systematic evaluation. Data sources: The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies: Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results: A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39–3.15], P = 0.0004; HR = 1.79, 95% CI [1.40–2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58–3.11], P < 0.0001; HR = 1.66, 95% CI [1.07–2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65–1.13], P = 0.28). Conclusions: Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number: CRD42023445619. [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]

Background: The role of brain metastases (BM) surgery is of paramount importance for patients' progression-free and overall survival. "En-bloc" and "piecemeal" resection represent the main surgical techniques. Although en-bloc resection remains the best surgical option, it is not widely adopted or feasible as the first choice. We describe our point of view about the en-bloc surgical technique with an illustrative case and discuss its indications with pros and cons through a comprehensive literature review. Materials and methods: A Medline search up to December 2023 in the Embase and PubMed online electronic databases was made and PRISMA statement was followed. An illustrative case of "en-bloc" resection from our surgical series was also added as a technical note. Results: We describe tips and tricks of our surgical technique and added a surgical video from our series. The literature review disclosed 19 studies. Resulting data suggested that "en-bloc" resection, when feasible, provides lesser risk of leptomeningeal dissemination, local recurrence rates, intraoperative bleeding occurrence and perioperative complications; in addition, it preserves the normal anatomy. Conclusions: En-bloc resection is the gold standard technique for surgical treatment of brain metastases especially for patients with superficial lesions that are small in size and far from eloquent areas. [ABSTRACT FROM AUTHOR]

In oncology anti—PD1 / PDL1 therapy development for solid tumors, objective response rate (ORR) is commonly used clinical endpoint for early phase study decision making, while progression free survival (PFS) and overall survival (OS) are widely used for late phase study decision making. Developing predictive models to late phase outcomes such as median PFS (mPFS) and median OS (mOS) based on early phase clinical outcome ORR could inform late phase study design optimization and probability of success (POS) evaluation. In existing literature, there are ORR / mPFS / mOS association and surrogacy investigations with limited number of included clinical trials. In this paper, without establishing surrogacy, we attempt to predict late phase survival (mPFS and mOS) based on early efficacy ORR and optimize late phase trial design for anti—PD1 / PDL1 therapy development. In order to include adequate number of eligible clinical trials, we built a comprehensive quantitative clinical trial landscape database (QLD) by combining information from different sources such as clinicaltrial.gov, publications, company press releases for relevant indications and therapies. We developed a generalizable algorithm to systematically extract structured data for scientific accuracy and completeness. Finally, more than 150 late phase clinical trials were identified for ORR / mPFS (ORR / mOS) predictive model development while existing literature included at most 50 trials. A tree-based machine learning regression model has been derived to account for ORR / mPFS (ORR / mOS) relationship heterogeneity across tumor type, stage, line of therapy, treatment class and borrow strength simultaneously when homogeneity persists. The proposed method ensures that the predictive model is robust and have explicit structure for clinical interpretation. Through cross validation, the average predictive mean square error of the proposed model is competitive to random forest and extreme gradient boosting methods and outperforms commonly used additive or interaction linear regression models. An example application of the proposed ORR / mPFS (ORR / mOS) predictive model on late phase trial POS evaluation for anti—PD1 / PDL1 combination therapy was illustrated. [ABSTRACT FROM AUTHOR]

Background: The newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients. Methods: Literature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software. Results: Five studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p<0.001] for overall survival (OS) in patients with high PCI. Further subgroup analysis by the FIGO staging revealed that in stage III [HR: 2.61, 95%CI: (2.00, 3.40), p<0.001] and stage III-IV patients [HR: 2.69, 95%CI: (1.66, 4.36), p<0.001], a high PCI score was significantly associated with a worse prognosis. The PCI score had a greater impact on the OS of patients with higher stages. The combined hazard ratio was 1.89 [95%CI: (1.51, 2.36), p<0.001] for progression-free survival (PFS) in patients with high PCI. Conclusion: PCI may be used as a postoperative prognosis indicator in patients with advanced OC on primary debulking surgery. High PCI indicates a worse prognosis. However, further research is warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

The aim of this systematic review is to analyze epidemiology, clinical presentation, histopathological features, treatment and oncological outcomes in laryngeal mucoepidermoid cancer (MEC) in order to improve the knowledge on the management of such a rare malignant neoplasm. Specifically, authors highlight patients' and tumors' features about local, regional, and distant recurrence of disease. PRISMA 2020 guidelines were applied in this systematic literature review. A computerized search was performed using the Embase/Pubmed, Scopus, and Cochrane databases, for articles published from 1971 to December 2023. A descriptive and univariate analysis including selected papers with low or intermediate risk of bias was performed. Twenty‐seven papers (11 case series and 16 case reports) were included in this review. Fifty‐six patients were included in the analyses, with a mean age of 56.7 years; 84% of them were males. Most patients (86%) underwent a primary surgical approach. Clinical stage was reported as follows: early stage (26 patients) and locally advance and advanced stage (19 patients). Overall survival (OS) and disease‐free survival (DFS) at 2 years was 80% and 78%, respectively. The mean time to local recurrence was 18.7 months (range 8–36 months). The survival after recurrence is about 85% and 70% at 5 years, respectively. The mean time of lymph node recurrence was 14.7 months (range 7–19 months). Finally, the mean time of distant recurrence was 15 months (range 7–36 months) with a poor prognosis: all patients died due to the disease in a range of 0–7 months after metastasis evidence. Laryngeal MEC is a rare neoplasm of minor salivary glands in the larynx. No guidelines or indications about the management of this neoplasm are reported in the literature. The lower incidence of regional recurrence of the disease and the better OS and DFS underline how the prognosis of MEC is more favorable respect to other malignant histotypes. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper discusses the importance of addressing sarcopenia in patients with hepatocellular carcinoma (HCC). The aim is to analyze how sarcopenia affects treatment outcomes for HCC, including liver transplantation, surgical resection, locoregional treatments, and systemic therapies. Sarcopenia is prevalent among HCC patients and independently correlates with lower overall survival, recurrence-free survival, and progression-free survival across all treatment modalities. Sarcopenia also increases the rate and severity of adverse events, particularly in surgery and systemic therapies. This research highlights the need for evaluating sarcopenia before HCC treatment initiation to better predict patient prognosis and tailor treatment approaches accordingly. However, the impact of sarcopenia on HCC recurrence and spread beyond the liver remains poorly understood, indicating a need for further research in this area. Overall, this research sheds light on the significance of considering sarcopenia in HCC management and may prompt efforts to identify therapies that can address muscle loss in these patients, potentially improving treatment outcomes and patient care. Introduction: Hepatocellular carcinoma (HCC) represents a major global health concern, characterized by evolving etiological patterns and a range of treatment options. Among various prognostic factors, sarcopenia, characterized by loss of skeletal muscle mass, strength, and function, has emerged as a pivotal contributor to HCC outcomes. Focusing on liver transplantation, surgical resection, locoregional treatments, and systemic therapies, this review aims to analyze the impact of sarcopenia on HCC treatment outcomes, shedding light on an underexplored subject in the pursuit of more personalized management. Methods: A comprehensive literature review was conducted by searching peer-reviewed articles on sarcopenia and treatment outcomes in patients with HCC from inception up to October 2023. Results: Sarcopenia was found to be prevalent among HCC patients, exhibiting different occurrence, possibly attributable to diverse diagnostic criteria. Notably, despite variations in studies utilizing skeletal muscle indices, sarcopenia independently correlated with lower overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) across surgical (both transplantation and resection), locoregional, and systemic therapies, including tyrosine-kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs). Moreover, a link between sarcopenia and increased rate and severity of adverse events, particularly in surgery and TKIs recipients, and larger tumor size at diagnosis was observed. While baseline sarcopenia negatively influenced treatment outcomes, alterations in muscle mass post-treatment emerged as primary determinants of reduced OS. Conclusions: Sarcopenia, either present before or after HCC treatment, negatively correlates with response to it, across all etiologies and therapeutic strategies. Although only a few studies have evaluated the impact of supervised physical activity training on muscle mass and OS after HCC treatment, it is crucial to evaluate the presence of sarcopenia before treatment initiation, to better stratify patients' prognosis, thus performing a more tailored approach, and identify therapies able to restore muscle mass in HCC patients. Conversely, the impact of sarcopenia on HCC recurrence and extrahepatic spread remains inadequately explored. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer. [ABSTRACT FROM AUTHOR]

Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled t-test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test ( α = 0.05 ). Our analysis indicates that KIT mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, FLT3 mutation correlates with lower serum galectin-1 and -9 levels and TP53 mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both TP53 and PIK3CA mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a KIT or PIK3CA mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) tumors are among the most common malignancies in various age ranges. Low-grade glioma (LGG) can account for nearly 30% of pediatric CNS malignancies. Progression or recurrence after the first-line treatments is common among these patients. Therefore, more treatments are required. Bevacizumab as an anti-VEGF antibody has come into the spotlight recently and is especially used in relapse or recurrence settings. This review aims to study the safety and efficacy of bevacizumab for patients with recurrent LGG. Methods: This study was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Scopus, Web of Science, and Embase were comprehensively searched using the relevant key terms until 24th August 2023 to retrieve the studies that investigated clinical outcomes of bevacizumab in patients with recurrent LGG. All statistical analysis was performed by STATA v.17. Results: A total of 1306 papers were gathered, out of which 13 were incorporated in the meta-analysis. The pooled incidence rate of treatment according to the RANO scale was 70% (95% CI = 43–98%) for objective response rate, 26% (95% CI = 58–96%) for partial response, 21% (95% CI = 15–28%) for minor response, 14% (95% CI = 3–24%) for complete response, 48% (95% CI = 37–59%) for stable disease, and 8% (95% CI = 4–11%) for progressive disease. Furthermore, according to progressive survival after treatment, it was 4% (95% CI = −1 to 9%) for 6-month PFS, 41% (95% CI = 32–50%) for 2-year PFS, and 29% (95% CI = 22–35%) for 3-year PFS. Conclusion: According to the RANO scale and PFS, clinicians should be aware that Bevacizumab could be a favorable alternative therapy for recurrent LGG. Furthermore, bevacizumab exhibits minimal toxicity and high tolerability in recurrent LGG. [ABSTRACT FROM AUTHOR]

Data on gonadotoxicity of chemotherapies are essential to better counsel young females and males about the risk of infertility and to better indicate fertility preservation measures before cancer therapies. However, such data have not recently been reviewed for bone cancer. Therefore, a systematic literature search was conducted considering papers published since 2000. This study is part of the FertiTOX® project, which aims to improve the lack of data regarding gonadotoxicity of cancer therapies to enable more accurate counseling regarding fertility preservation. Only relapse-free women and men were included. Gonadotoxic therapy-induced suspected infertility was defined as very low anti-mullerian hormone, high gonadotropin concentration, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia. The quality of the individual studies was assessed using the Newcastle–Ottawa Scale (NOS). In total, 11 out of 831 studies were included in the review. Suspected infertility was found in 10/190 (5.1%, range 0%–66%) of female patients with osteosarcoma (six studies), in 24/46 (52.2%, range 46%–100%) of male patients with osteosarcoma (three studies), in 18/138 (13.0%, range 3%–18%) of female patients with Ewing's sarcoma (three studies), and in 34/38 (89.5%) of male patients with Ewing's sarcoma (one study). A risk calculation in relation to specific chemotherapies was not possible. Risk of suspected infertility tends to be higher in Ewing's sarcoma in which all patients received chemotherapies with alkylating agents. Two of the 11 included studies received a high NOS quality score, whereas the remaining nine studies received a low quality score, mainly because of the lack of a comparator group. Published data are too limited for precise estimation of the gonadotoxicity. However, data indicate clinically relevant risk for infertility, supporting counseling patients before chemotherapy about fertility preservation measures. [ABSTRACT FROM AUTHOR]

Patients with supp-SM grade 6 N0P1/N1P1 modifiers are at significantly increased risk of surgical morbidity, and could serve as a operability boundary in the selection of patients for microsurgical AVM resection. PROPHYLACTIC ANTI-REFLUX PROCEDURE IS NOT NECESSARY FOR PAEDIATRIC PATIENTS UNDERGOING LAPARO... ACH Fung, HM Hui, MKY Mok, PHY Chung and KKY Wong Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR B Aim: b Laparoscopic gastrostomy is a frequently performed procedure for children requiring long-term enteral tube nutrition. B Results: b Cancer detection rate for MRI fusion biopsy (45.3%, 53/117 patients) was higher than sTPBx (32.1%, 84/262 patients, I p i = 0.013). Patients with Supp-SM grade 6 and N0P0/N1P0 subtypes ("good 6") had comparable outcomes as Supp-SM grade 5 patients ( I p i = .51), while those with N0P1/N1P1 subtypes ("bad 6") had similar outcomes to grade 7 patients ( I p i = .59). [Extracted from the article]

BACKGROUND: How to improve efficacy and reduce side effects in treating recurrent esophageal cancer by applying the second course of radiotherapy alone and its combination with chemotherapy has been attracting broad research interest. OBJECTIVE: This review paper aims to systematically evaluate efficacy and side effects of applying the second course of anterograde radiotherapy alone and its combination with chemotherapy in treating recurrent esophageal cancer. METHODS: First, the relevant research papers are retrieved from PubMed, CNKI and Wanfang databases. Next, Redman 5.3 software is used to calculate the relative risk and 95% confidence interval to evaluate the efficacy and adverse reactions of applying the single-stage radiotherapy with and without combining single/multi dose chemotherapy to treat recurrent esophageal cancer. Then, a meta data analysis is applied to examine the effectiveness and side effects of radiation alone and re-course radiotherapy plus chemotherapy in treating esophageal cancer recurrence after the first radiotherapy. RESULTS: Fifteen papers are retrieved, which included 956 patients. Among them, 476 patients received radiotherapy combined with single drug/multi drug chemotherapy (observation) and others received only radiotherapy (control). Data analysis results show that the incidence of radiation induced lung injury and bone marrow suppression is high in the observation group. Subgroup analysis also shows the higher effective rate or one-year overall survival rate of patients treated with the second course radiotherapy combined with single drug chemotherapy. CONCLUSION: The meta-analysis result demonstrates that combining the second course of radiotherapy with single-drug chemotherapy has advantages in treating recurrent esophageal cancer with the manageable side effects. However, due to insufficient data, it is not possible to conduct the further subgroup analysis comparing the side effects of restorative radiation with the combined chemotherapy using between a single drug and multiple drugs. [ABSTRACT FROM AUTHOR]

Lung cancer ranks as the second most prevalent cancer globally and is the primary contributor to neoplastic-related deaths. The approach to its treatment relies on both tumour staging and histological type determination. Data indicate that the prognosis of lung cancer is strongly linked to its clinical stage, underscoring the importance of early diagnosis in enhancing patient outcomes. Consequently, the choice of an appropriate diagnostic method holds significant importance in elevating both the early detection rate and prognosis of lung cancer. This paper aims to assess computer tomography features specific to the most common lung cancer types (adenocarcinoma, squamous cell carcinomas and small cell lung cancer). Data were collected retrospectively from CT scans of 58 patients pathologically diagnosed with lung cancer. The following CT features were evaluated and recorded for each case: location, margins, structure, lymph node involvement, cavitation, vascular bundle-thickening, bronchial obstruction, and pleural involvement. Squamous cell carcinoma (SQCC) and small cell lung cancer (SCLC) showed a higher incidence of central location, while adenocarcinoma (ADC) showed a significant predilection for a peripheral location. Internal cavitation was mostly observed in SQCC, and a solid structure was observed in almost all cases of ADC. These features can provide information about the prognosis of the patient, considering that NSCLCs are more frequent but tend to demonstrate positive results for targetable driver mutations, such as EGFR, thereby increasing the overall survival. In addition, SCLC presents with early distant spreads, which limits the opportunity to investigate the evolution of tumorigenesis and gene alterations at early stages but can have a rapidly positively response to chemotherapy. The location of the lung cancer exhibits distinct forecasts, with several studies suggesting that peripheral lung tumours offer a more favourable prognosis. Cavity formation appears correlate with a poorer prognosis. Histopathological analysis is the gold standard for diagnosing the type of lung cancer; however, using CT scanning for the purpose of a rough, but fast, preliminary diagnosis has the potential to shorten the waiting time for treatment by helping clinicians and patients to know more about the diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients' quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments. Methods: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire. Results: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL. Conclusion: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL. [ABSTRACT FROM AUTHOR]

Several novel drugs for multiple myeloma, including monoclonal and bispecific antibodies, immunomodulatory agents, and newer-generation proteasome inhibitors, have been introduced over the last decade. Based on the results of randomized clinical trials, the drugs have been incorporated into current treatment recommendations, with the most substantial changes observed in patients under the age of 75. However, new therapeutic options have been indirectly proposed for patients over 75, despite the lack of conclusive data from randomized prospective trials. This paper outlines the development of myeloma therapy and summarizes the current treatment recommendations for patients over 75 by systematically reviewing the most crucial studies involving this group of individuals, with a focus on evaluating treatment safety and efficacy. Melphalan-prednisone (MP), bortezomib plus MP (VMP), lenalidomide-dexamethasone (Rd), and bortezomib plus Rd (VRd) regimens have evolved over the past few years as therapies of choice for the first-line treatment of these patients. A breakthrough came with daratumumab, which increased response rates, extended median progression-free survival (PFS) and overall survival (OS) in the absence of significantly increased toxicity when added to the above regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Neo-adjuvant systemic (NAS) therapy for melanoma is leading the way in immunotherapy for oncology. There is both a strong biological rationale to support NAS therapy, as well as exciting results in terms of superior efficacy to the current standards of care. Simply giving pembrolizumab 3 doses prior to surgery and 14 after rather than all 17 courses as adjuvant therapy only, demonstrated a 23% improvement in event-free survival (EFS). Combination immunotherapy with ipilimumab and nivolumab seems even more potent with ~60% of patients achieving Major Pathologic Responses (MPR) vs. ~25–30% for single agent anti-PD-1. NAS therapy will allow for a tailored approach to the therapy of melanoma patients, which includes a potential safe de-escalation of the extent of surgery and discontinuation of systemic therapy for MPR patients. And early identification of non-responders who can be directed towards clinical trials with novel therapies. These developments are now splashing over to other solid tumors, but there is still a need to develop a bespoke panel of biomarkers to further improve upon the current treatments. NAS therapy will soon become the novel standard of care approach for macroscopic stage III melanoma. Melanoma treatment is leading the neo-adjuvant systemic (NAS) therapy field. It is hypothesized that having the entire tumor in situ, with all of the heterogeneous tumor antigens, allows the patient's immune system to have a broader response to the tumor in all its shapes and forms. This translates into a higher clinical efficacy. Another benefit of NAS therapy potentially includes identifying patients who have a favorable response, which could offer an opportunity for the de-escalation of the extent of surgery and the need for adjuvant radiotherapy and/or adjuvant systemic therapy, as well as tailoring the follow-up in terms of the frequency of visits and cross-sectional imaging. In this paper, we will review the rationale for NAS therapy in resectable metastatic melanoma and the results obtained so far, both for immunotherapy and for BRAF/MEKi therapy, and discuss the response assessment and interpretation, toxicity and surgical considerations. All the trials that have been reported up to now have been investigator-initiated phase I/II trials with either single-agent anti-PD-1, combination anti-CTLA-4 and anti-PD-1 or BRAF/MEK inhibition. The results have been good but are especially encouraging for immunotherapies, showing high durable recurrence-free survival rates. Combination immunotherapy seems superior, with a higher rate of pathologic responses, particularly in patients with a major pathologic response (MPR = pathologic complete response [pCR] + near-pCR [max 10% viable tumor cells]) of 60% vs. 25–30%. The SWOG S1801 trial has recently shown a 23% improvement in event-free survival (EFS) after 2 years for pembrolizumab when giving 3 doses as NAS therapy and 15 as adjuvant versus 18 as adjuvant only. The community is keen to see the first results (expected in 2024) of the phase 3 NADINA trial (NCT04949113), which randomized patients between surgery + adjuvant anti-PD-1 and two NAS therapy courses of a combination of ipilimumab + nivolumab, followed by surgery and a response-driven adjuvant regimen or follow-up. We are on the eve of neo-adjuvant systemic (NAS) therapy, particularly immunotherapy, becoming the novel standard of care for macroscopic stage III melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Percutaneous cryoablation (PCA) is a minimally invasive procedure that should be considered in comorbid patients with stage T1 renal tumours who are suboptimal candidates for partial nephrectomy (PN). However, there is a scarcity of scientific data regarding the efficacy of PCA. The aim of this meta-analysis was to compare PCA and PN in terms of complications, renal function and survival outcomes. According to this analysis, PCA is associated with fewer complications than PN. Moreover, in tumours up to 4 cm, it provides the same time without local recurrence. Therefore, PCA should be proposed to patients with cT1 renal tumours who are not fit for PN but want to undergo a radical treatment. Percutaneous cryoablation (PCA) can be an alternative to partial nephrectomy (PN) in selected patients with stage T1 renal tumours. Existing meta-analyses regarding ablative techniques compared both laparoscopic and PCA with PN. That is why we decided to perform a meta-analysis that focused solely on PCA. The aim of this study was to compare the complications and functional and oncological outcomes between PCA and PN. A systematic literature search was performed in January 2024. Data for dichotomous and continuous variables were expressed as pooled odds ratios (ORs) and mean differences (MDs), both with 95% confidence intervals (CIs). Effect measures for the local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were expressed as pooled hazard ratios with 95% CIs. Among 6487 patients included in the 14 selected papers, 1554 (23.9%) and 4924 (76.1%) underwent PCA and PN, respectively. Compared with the PN group, patients undergoing PCA had significantly lower overall and major postoperative complication rates. There was no difference in renal function between PCA and PN groups. When analysing collective data for cT1 renal carcinoma, PCA was associated with worse LRFS compared with PN. However, subgroup analysis revealed that in the case of PCA, LRFS was not decreased in patients with cT1a tumours. Moreover, patients undergoing robotic-assisted PN had improved LRFS compared with those undergoing PCA. No significant differences were observed between PCA and PN in terms of MFS and CSS. Finally, PCA was associated with worse OS than PN in both collective and subgroup analyses. In conclusion, PCA is associated with favourable postoperative complication rates relative to PN. Regarding LRFS, PCA is not worse than PN in cT1a tumours but has a substantially relevant disadvantage in cT1b tumours. Also, RAPN might be the only surgical modality that provides better LRFS than PCA. In cT1 tumours, PCA shows MFS and CSS comparable to PN. Lastly, PCA is associated with a shorter OS than PN. [ABSTRACT FROM AUTHOR]

Introduction: Molecular and genomic profiling in endometrial cancer is increasing popularity. L1 cell adhesion molecule (L1CAM) is frequently mutated in endometrial cancer. In this paper, we aim to evaluate the prognostic role of L1CAM in patients with stage I endometrial cancer. Methods: We performed a systematic review and meta-analysis searching in PubMed (MEDLINE), EMBASE, and Web of Science database to identify studies reporting the expression of L1CAM in endometrial cancer. The primary endpoint measure was to assess and evaluate the impact of L1CAM on survival outcomes. This study was performed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. Results: Five studies were included. The pooled results suggested that L1CAM expression influences survival outcomes in stage I endometrial cancer. High L1CAM expression correlated with worse disease-free survival (HR 4.11, 95% CI 1.02–16.59, p = 0.047) and overall survival (HR 3.62, 95% CI 1.32–9.31, p = 0.012). High L1CAM level was also associated with a more aggressive FIGO grade and with older age. Conclusion: This systematic review supported that L1CAM have a prognostic role in stage I endometrial cancer, thus providing a potential useful tool for tailoring the need of adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Decisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS). Methods: HRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P < 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum. Results: 168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8–5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1–5.9). Conclusions: Kd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact. [ABSTRACT FROM AUTHOR]

Chemoradiotherapy (CRT) followed by durvalumab is standard for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study assesses how CRT alters the T-cell receptor (TCR) repertoire in CD8 + PD-1 + T-cells and its impact on clinical outcomes. This prospective study, conducted from November 2019 to May 2021 at three institutions in Japan, evaluated the diversity of TCR repertoire (DE50) in PD-1 + CD8 + T-cells and CD8 + T-cell phenotypes in peripheral blood before and after CRT. Forty patients treated with CRT were included. The diversity and usage of TCR beta variable chains (TRBV) and 14 junctional chains (TRBJ) were significantly and positively correlated before and after CRT. Regarding the DE50, the progression-free survival (PFS) of patients with DE50High before CRT was significantly greater than that of those with DE50Low (NR vs. NR months, HR 0.17, p = 0.01). The diversity of TCR repertoire might more accurately predict the efficacy of CRT followed by durvalumab therapy. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) is a type of cancer that develops in the biliary tract. CCA accounts for 10% of primary hepatic cancers and is characterized by its aggressive nature and poor prognosis. This systematic review and meta-analysis aims to assess the prognostic value of the novel hepatic function assessment measure known as albumin-bilirubin (ALBI) grade in patients with CCA. Method: A comprehensive search was conducted on PubMed, Web of Science, Embase, and Scopus databases until August 11, 2023. Studies examining the prognostic impact of ALBI grade in patients with CCA were included. The prognostic effect was evaluated using hazard ratio (HR) with 95% confidence intervals (CI). The quality of the included studies was assessed using the Newcastle–Ottawa Scale (NOS). The final meta-analysis was performed using R version 4.3.1. Results: The final meta-analysis included 13 studies with 3,434 patients. In univariate analysis (HR = 1.90, 95% CI: 1.65–2.19, P < 0.01) and multivariate analysis (HR = 1.88, 95% CI: 1.41–2.52, P < 0.01), higher ALBI grade was associated with lower overall survival (OS) in patients with intrahepatic CCA (ICCA). Higher ALBI grade was also correlated with decreased recurrence-free survival (RFS), with an HR of 1.63 (95% CI: 1.36–1.97, P < 0.01). Subgroup analysis of different ALBI grade comparisons showed consistent findings with our pooled data. Conclusion: A high ALBI grade indicates poor OS and RFS in patients with CCA especially intrahepatic type. ALBI should be considered a reliable and clinically useful prognostic indicator. Registration: PROSPERO ID: CRD42022379877 [ABSTRACT FROM AUTHOR]

Background: There is still no consensus regarding the correlation between TLS and the prognosis of lung cancer patients. This meta-analysis aimed to investigate the association between TLS and prognosis in patients with lung cancer. In addition, the prognostic value of TLS for the efficacy of immunotherapy was also studied. Methods: We systematically searched the PubMed, Embase, Cochrane Library, and Web of Science databases from database inception to November 1, 2023. The hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), progression-free survival (PFS) and disease-specific survival (DSS) were extracted and merged with STATA 14.0. The study protocol was registered with PROSPERO (CRD42024502483). Results: A total of 17 studies comprising 4291 patients were included in this meta-analysis. The pooled results revealed that high TLS/TLS + patients had better OS (HR = 0.66, 95% CI: 0.50–0.88), DFS (HR = 0.46, 95% CI: 0.33–0.64), DSS (HR = 0.48, 95% CI: 0.39–0.60) and RFS (HR = 0.43, 95% CI: 0.33–0.57). High TLS/TLS + patients tended to have longer PFS than low TLS/TLS + patients (HR = 0.68, 95% CI: 0.35–1.35). Interestingly, in the Asia subgroup, the association between TLS and survival was especially significant, whereas there was no significant difference in Europe. In addition, in patients who received neoadjuvant chemoimmunotherapy, high TLS/TLS + was associated with prolonged DFS (HR = 0.21, 95%CI: 0.05–0.93). Conclusion: High TLS/TLS + was associated with improved survival and an improved response to neoadjuvant chemoimmunotherapy in lung cancer patients, suggesting that TLS may be a prognostic biomarker and may also be a promising predictive marker for the response to neoadjuvant chemoimmunotherapy. However, additional original studies are needed to further confirm these findings. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were utilized to simulate MPLC and IPM, with various sequenced panels constructed through gene subsampling. Two clonal interpretation approaches primarily applied in clinical practice, MoleA (based on shared mutation comparison) and MoleB (based on probability calculation), were subsequently evaluated. ROC analysis highlighted MoleB's superior performance, especially with the NCCNplus panel (AUC = 0.950 ± 0.002) and pancancer MoleA (AUC = 0.792 ± 0.004). In two independent cohorts (WES cohort, N = 42 and non-WES cohort, N = 94), NGS-based methodologies effectively stratified disease-free survival, with NCCNplus MoleB further predicting prognosis. Phylogenetic analysis further revealed evolutionary distinctions between MPLC and IPM, establishing an optimized NGS-based framework for differentiating multiple lung cancers. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most prevalent malignancy in women. Potential therapeutic targets for BC are of great significance. In our previous study, we found that prenylated rab acceptor 1 domain family member 2 (PRAF2) is an oncogene in BC. However, the exact mechanism of PRAF2 in BC cancer promotion is still not fully understood. Methods: Pan-cancer analysis of PRAF2 was performed in the TIMER, Kaplan‒Meier, UALCAN and GEPIA databases.The prognostic value of PRAF2 in BC was investigated in the GEPIA database. The influence of PRAF2 on immune infiltration in BC was analyzed in the TISIDE and TIMER databases. Finally, we validated the expression of PRAF2 in our institutional samples. After downregulating PRAF2 in two BC cell lines, we tested cell proliferation by CCK-8 and Wound healing assays. Results: PRAF2 was highly expressed in various cancers, including BC, and in most BC cell lines. Higher expression of PRAF2 indicated poorer overall survival (OS) but not disease-free survival (DFS). Higher expression of PRAF2 is an independent prognostic factor in BC.PRAF2 is more highly expressed in BC than in the corresponding normal tissues. Downregulation of PRAF2 in BC can significantly inhibit viability and migration. Conclusions: PRAF2 is highly expressed in various cancers, including BC. The expression of PRAF2 is related to Liquid–Liquid Phase Separation in BC. Finally, PRAF2 is upregulated in BC based on our institutional data. Downregulation of PRAF2 significantly inhibits cellular viability、migration in BC. PRAF2 may be a potential biomarker and therapeutic target for BC. [ABSTRACT FROM AUTHOR]

Background: In the past, numerous investigations have delved into the influence of p27 (p27kip) on the prognosis and clinicopathological characteristics of colorectal cancer (CRC), yielding conclusions that are not universally statistically significant, thus rendering the discourse rather contentious. Methods: We collected available articles published before August 2024 and extracted data to analyze the association between the expression of p27 and the prognosis and clinicopathological features of CRC. In addition, we used Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham's Cancer Data Analysis Portal (UALCAN), and the Human Protein Atlas (HPA) to validate our results. Results: Through an extensive examination of four prominent databases, a total of 21 original articles encompassing a cohort of 3,378 patients were identified. The findings indicated that a low expression of p27 could lead to shorter overall survival (OS) [hazard ratio (HR) = 0.44, 95% confidence interval (95%CI) = 0.31–0.61, Z = 4.89, p = 0.000] and disease-free survival (DFS) (HR = 0.40, 95%CI = 0.28–0.59, Z = 4.75, p = 0.000). In addition, a low expression of p27 predisposed tumors to the right colon [odds ratio (OR) = 0.61, 95%CI = 0.46–0.82, Z = 3.32, p = 0.001] and limited tumor differentiation (OR = 0.56, 95%CI = 0.41–0.77, Z = 3.62, p = 0.000), but had no effect on TNM staging (OR = 0.80, 95%CI = 0.52–1.22, Z = 1.05, p = 0.295), lymph node metastasis (OR = 0.90, 95%CI = 0.25–3.28, Z = 0.16, p = 0.876), and tumor size (OR = 0.94, 95%CI = 0.54–1.65, Z = 0.21, p = 0.835). The results from GEPIA and UALCAN showed that p27 had no effect on TNM staging, lymph node metastasis, DFS, and OS; moreover, there was no expression difference between tumor tissues and normal tissues. The findings from the HPA indicated that there was lower expression of p27 in tumor tissues compared with normal tissues. Conclusion: Although inconsistent results were reached with the bioinformatics analysis from this meta-analysis, it was confirmed that a low expression of p27 can adversely affect the prognosis of patients with CRC and make a meaningful impact on a part of the clinicopathological features in the meta-analysis with abundant data. In the future, predicting the prognosis of patients with CRC and guiding treatment might emerge as a significant objective. [ABSTRACT FROM AUTHOR]

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion: This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles. [ABSTRACT FROM AUTHOR]

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion: Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival, and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion, and histologic compact type. Postoperative carbohydrate antigen 19-9, tumor necrosis, LVI, and close/positive margin were associated with poor OS. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion: The prognosis of cHCC-CCA is notably poor when combined with LVI. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis. [ABSTRACT FROM AUTHOR]

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.7–NR, median follow-up 50 months). The secondary endpoint, biochemical PFS, was 48.6 months (95% CI: 39.9–NR) and coincided with or preceded SLiM-CRAB in eight patients. For additional secondary objectives, the overall response rate was 93% with 31% achieving complete response (CR) and 45% very good partial response (VGPR) or better. CR correlated strongly with the absence of SLiM-CRAB and biochemical progression. MRD-negativity (10-5 sensitivity) predicted a 5-year biochemical PFS of 100% versus 40% in MRD-positive patients (p = 0.051), demonstrating that deep responses significantly improve time to progression. Exploratory single-cell RNA sequencing linked tumor MHC class I expression to proteasome inhibitor response, and a lower proportion of GZMB+ T cells within clonally expanded CD8+ T cells associated with suboptimal outcomes. Depth of response (CR/VGPR, MRD-) links to better outcomes, while biochemical progression predicts end-organ damage. Higher MHC-I on tumors and greater GZMB+ T cells in clonally expanded CD8+ T cells are tied to improved outcomes. [ABSTRACT FROM AUTHOR]

PET/CT targeting prostate-specific membrane antigen (PSMA) is commonly used in patients with prostate cancer. PSMA has been found in other solid tumours, including primary brain tumours. The aim of this study was to evaluate the usefulness of [68Ga]Ga-PSMA-11 PET/CT for preoperative diagnosis and 2-year prognosis. We prospectively screened patients with suspected glioma tumour. The PET/CT qualitative and quantitative results were compared to the histopathological examination. We compared glioblastoma (GBM) diagnostic data or between high-grade (HGG) and low-grade (LGG) gliomas. Overall (OS) and progression free survival (PFS) were analysed. Forty-four patients met the inclusion criteria. Twenty of them had positive and twenty-four negative scans. The sensitivity, specificity, positive predictive value, and negative predictive value for HGG diagnosis were 71.4 (95% confidence interval – 51.3–86.8), 100.0 (79.4–100.0), 100.0 (83.1–100.0), and 66.7 (44.7–84.4), respectively. For differentiation between GBM vs non-GBM tumours, the best parameter was the tumour-to-background ratio, with the area under the receiver operating characteristic curve 0.81 (0.66–0.96; 42.2) (95% CI; cut-off). Patients with positive PET/CT scans had similar PFS and OS to patients with HGG. PSMA accumulation negatively affected the PFS and OS of patients with diagnosed GBM. [68Ga]Ga-PSMA-11 PET/CT showed optimistic diagnostic results and may be prognostic a factor. Registration at www.clinicaltrials.gov 09/06/2023 with number NCT05896449. [ABSTRACT FROM AUTHOR]

Objective: Assess the contribution of early tumor growth dynamics modeling to predict clinical outcomes in non-small cell lung cancer patients receiving immunotherapy, alongside standard RECIST 1.1 criteria. Methods: Our retrospective studies used data from 861 patients with advanced NSCLC enrolled in three randomized Phase III trials evaluating immunotherapy plus chemotherapy were analyzed. Tumor size measurements up to two follow-up time points were used to fit a novel Gompertz model and estimate growth rate (GR) and kinetic parameters representing depth of response (A), speed of response (B), and long-term modulation (M). Correlations between these early tumor growth parameters and clinical outcomes such as progression-free survival (PFS) and time to response (TTR) were assessed. Descriptive and discriminative analyses were performed to delineate tumor growth dynamics across various response profiles based on RECIST 1.1 criteria. Results: The novel Gompertz model accurately described early tumor growth kinetics in 861 non-small cell lung cancer patients treated with immunotherapy. Lower growth rate (GR) and model parameter M were associated with longer progression-free survival (PFS) (HR=0.897 and 7.47x10^-7, respectively). Higher GR and parameter A correlated with shorter time to response (HR=0.575 and 0.696, respectively). Responders had significantly lower A (p=1.51e-53) and higher GR (p=0.4e-12) than non-responders. Non-durable stable disease patients had higher GR (p=0.0001) and parameter B (p=0.0002) compared to late responders. Early tumor growth parameters showed potential for predicting long-term outcomes and treatment response patterns. [ABSTRACT FROM AUTHOR]

Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free survival and correlates with treatment response. We also identify genetic variants and transcriptomic pathways associated with progression risk, highlighting links to tumor growth and immune response. This radiogenomic study in pLGGs provides a framework for the identification of high-risk patients who may benefit from targeted therapies. Understanding the molecular and pathological features of paediatric low-grade glioma (pLGG) is crucial to develop targeted therapies. Here, the authors perform a radiogenomic analysis of pLGGs combining treatment-naïve multiparametric MRI and RNA sequencing, enabling prognostication based on immune profiles as well as prediction of treatment response. [ABSTRACT FROM AUTHOR]

Purpose: In-vivo proton magnetic resonance spectroscopy (MRS) is a non-invasive method of analyzing choline metabolism that has been used to predict breast cancer prognosis. A strong choline peak may be a surrogate for aggressive tumor biology but its clinical relevance is unclear. The present study assessed whether total choline (tCho), as measured by proton MRS, can predict late recurrence in patients with hormone receptor (HR)-positive, HER2-negative early breast cancer. Methods: The study cohort included 261 HR+/HER2- breast cancer patients who underwent diagnostic single-voxel proton MRS (3.0T scanner) prior to first-line surgery from March 2011 to July 2014. The relationships between tCho compound peak integral (tChoi) values and others prognostic factor were analyzed, as were the effects of tChoi on 10-year disease-free survival (DFS) and overall survival (OS). The clinical significance of tChoi was also analyzed using Harrell's C-index. Results: Mean tChoi in HR+/HER2- study group was 15.47 and we set the cut-off for tChoi at 15 for survival analysis. 10-year DFS differed significantly between tChoi <15 and ≥15 (p = 0.017), with differences differing significantly for late (5–10 years; p = 0.02) but not early (0–5 years; p = 0.323) recurrence. Cox regression analysis showed that tChoi was significantly predictive of 10-year DFS (p = 0.046, OR 2.69) and tended to be predictive of late recurrence (HR 4.36, p = 0.066). Harrell's C-index showed that the Ki-67 index (AUC = 0.597) and lymphovascular invasion (AUC = 0.545) were also predictive of survival, with the addition of normalized tChoi improving the AUC to 0.622 (p = 0.014), indicating better predictive power. Conclusion: tChoi determined by in vivo MRS was predictive of prognosis in patients with HR+/HER2- early breast cancer. This parameter may serve as a valuable, non-invasive tool to predict prognosis when combined with other known prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy that occurs in women. Due to the pain caused by the disease itself and the adverse reactions in the treatment process, breast cancer patients are prone to anxiety, depression, fear of recurrence, and other negative emotions, which seriously affect the quality of life. As a systematic stress reduction therapy, mindfulness-based stress reduction is widely applied to the treatment of breast cancer patients and has been found by a growing number of studies to relieve stress, regulate mood, and improve the state. However, due to the absence of recent research and uniform outcome measures, previous studies have failed to fully explain the role of mindfulness-based stress reduction in improving the quality of life in breast cancer patients. Objective: We conducted a systematic review and meta-analysis to evaluate and compare the effects of mindfulness-based stress reduction therapy and standard care on the quality of life and psychological status of breast cancer patients. Methods: We searched PubMed, Web of Science, Embase, China's National Knowledge Infrastructure and the Cochrane Central Registry of Controlled Trials up to July 2023 to identify candidate randomized clinical trials addressing the values of mindfulness-based stress reduction in breast cancer patients. Results: A total of 1644 patients participated in 11 randomized controlled trials. The results of the meta-analysis showed that mindfulness-based stress reduction therapy can significantly reduce negative emotions such as perceived stress (MD = -1.46, 95%CI = -2.53 to -0.38, p = 0.03), depression (MD = -1.84, 95%CI = -3.99 to -0.30, p = 0.0004), anxiety (MD = -2.81, 95%CI = -5.31 to -0.32, p = 0.002), and fear of recurrence (MD = -1.27, 95%CI = -3.44 to 0.90, p = 0.0004). Mindfulness-based stress reduction therapy also has certain advantages in improving the coping ability (MD = 1.26, 95%CI = -3.23 to5.76, p = 0.03) and the emotional state (MD = -7.73, 95%CI = -27.34 to 11.88, p = 0.0007) of patients with breast cancer. Conclusion: Our analyses support that, compared with standard care, mindfulness-based stress reduction therapy can significantly improve patients' coping ability, reduce adverse emotions and improve patients' emotional states. [ABSTRACT FROM AUTHOR]

Sequential, multiple assignment, randomized trial (SMART) designs are appropriate for comparing adaptive treatment interventions, in which intermediate outcomes (called tailoring variables) guide subsequent treatment decisions for individual patients. Within a SMART design, patients may be re-randomized to subsequent treatments following the outcomes of their intermediate assessments. In this paper, we provide an overview of statistical considerations necessary to design and implement a two-stage SMART design with a binary tailoring variable and a survival final endpoint. A chronic lymphocytic leukemia trial with a final endpoint of progression-free survival is used as an example for the simulations to assess how design parameters, including, choice of randomization ratios for each stage of randomization, and response rates of the tailoring variable affect the statistical power. We assess the choice of weights from restricted re-randomization on data analyses and appropriate hazard rate assumptions. Specifically, for a given first-stage therapy and prior to the tailoring variable assessment, we assume equal hazard rates for all patients randomized to a treatment arm. After the tailoring variable assessment, individual hazard rates are assumed for each intervention path. Simulation studies demonstrate that the response rate of the binary tailoring variable impacts power as it directly impacts the distribution of patients. We also confirm that when the first stage randomization is 1:1, it is not necessary to consider the first stage randomization ratio when applying the weights. We provide an R-shiny application for obtaining power for a given sample size for SMART designs. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC). Methods: We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively). Results: The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54–0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21–0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20–0.76), and OS (HR: 0.63, 95% CI: 0.57–0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39–0.69), radiotherapy (HR: 0.63, 95% CI: 0.56–0.71) in NRCTs. Conclusions: LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden. [ABSTRACT FROM AUTHOR]

Background: Few real-world studies exist regarding the clinical value of local consolidative therapy (LCT) for oligo-residual disease (ORD) in NSCLC patients treated with immune checkpoint inhibitors. Therefore, we retrospectively evaluated whether LCT could improve the prognosis of NSCL patients with ORD after effective first-line PD-1/PD-L1 inhibitors treatment. Methods: A total of 132 patients with metastatic NSCLC who had received first-line PD-1/PD-L1inhibitors-based systemic treatment and developed ORD (defined as residual tumors limited to three organs and five lesions) were included. The LCT group consisted of 41 patients received LCTs for oligo-residual lesions before treatment failure, and the remaining 91 patients, who did not receive local therapies, constituted the non-LCT group. The progression-free survival (PFS) and overall survival (OS) of the two groups were analyzed. Results: With a median follow-up of 12.0 months, 86 patients developed progressive disease and 42 patients died. Compared with the non-LCT group, LCT group exhibited significant longer progression-free survival (PFS) (median 11.0 vs. 7.0 months, P=0.017) and overall survival (OS) (median 26.0 vs. 17.0 months, P=0.003). Multivariable analysis demonstrated that LCT was an independent predictor of prolonged PFS (HR=0.606, 95% CI=0.370–0.964, P=0.035) and OS (HR=0.467, 95% CI=0.229–0.949, P=0.035). Subgroup analysis revealed that the dominant population considerably benefited from LCT in terms of PFS and OS included patients with 1-2 residual tumor sites (mPFS: 11.0 vs. 7.0 months, P=0.013; mOS: 23.0 vs. 17.0 months, P=0.018) and those with high PD-L1 expression (mPFS: 13.0 vs. 7.0 months, P=0.018; mOS: 34.0 vs. 16.0 months, P=0.030). In addition, the All-LCT group had significantly longer PFS (mPFS 16.0 vs. 7.0, P=0.002) and OS (mOS 28.0 vs. 17.0, P= 0.002) than did the non-LCT group. However, patients who received LCT to only some of their lesions had not experienced improvements in PFS (P=0.546) or OS (P=0.198). Conclusion: LCT may provide extra survival benefits among patients with oligo-residual NSCLC after effective first-line PD-1/PD-L1 inhibitors treatment, particularly in those patients with one or two residual lesions, high PD-L1 expression, or who had received LCT for all lesions. LCT may be a novel treatment option for this specific population. [ABSTRACT FROM AUTHOR]